PUBCHEM.COMPOUND:3559

The study investigates the role of glutamatergic neurotransmission mediated by NMDA receptors in the inferior colliculus (IC) on haloperidol-induced catalepsy in rats. The results show that microinjections of glutamate NMDA receptor antagonists, MK-801 and AP7, into the IC prior to systemic injections of haloperidol significantly reduced the catalepsy. Conversely, microinjection of the NMDA receptor agonist N-methyl-d-aspartate (NMDA) increased the catalepsy. This suggests that glutamate-mediated mechanisms in the IC influence haloperidol-induced catalepsy and participate in the regulation of motor activity.


UMLS:C0813872


UMLS:C3536824


UMLS:C0511168


UMLS:C0870602

The study performed a molecular analysis of the androgen receptor (AR) and SRD5A2 genes in 29 patients with 46,XY DSD. Six patients from four unrelated families were found to have mutations in the SRD5A2 gene. Five patients had a p.R246Q missense mutation, four of whom were homozygous and one was compound heterozygous. Another patient had a heterozygous p.G196S missense mutation. No AR gene mutation was detected. The study suggests that the p.R246Q mutation is common among patients with an SRD5A2 gene defect in the Northern states of India. A novel deletion in exon 1 of the SRD5A2 gene was also identified in a patient with severe hypospadias.


UMLS:C0030705


UMLS:C5680052

The study investigates the early changes in the glomerulus during proteinuria using puromycin aminonucleoside nephrosis (PAN) rats. The researchers studied the expression of podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2. By day 2, some foot process effacement was observed, but no proteinuria. The amount of nephrin was reduced in both diseased and normal areas. By day 4, foot process effacement was complete and proteinuria appeared along with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. The study suggests that altered nephrin expression precedes significant pathology in PAN glomeruli, and the novel proteins dendrin and plekhh2 may also play roles in PAN.


PR:000011365


PR:000006350


UMLS:C3495974


UMLS:C2198619

The study reports a case of a 4-year-old child with growth failure and normal serum concentrations of GH-binding protein (GHBP), but clinical evidence of GH insensitivity. The child had elevated serum GH concentrations, abnormally low serum IGF-I and IGFBP-3 concentrations. DNA analysis revealed compound heterozygosity for mutations of GHR, including a previously reported R211H mutation and a novel duplication of a nucleotide in exon 9 (899dupC), which resulted in a frameshift and a premature stop codon. Treatment with recombinant DNA-derived IGF-I resulted in growth acceleration. The study concludes that mutations affecting the intracellular domain of the GHR can result in GH insensitivity and IGF deficiency, despite normal serum concentrations of GHBP.


UMLS:C2198619


UniProtKB:A0A0S7L586


UMLS:C5696658


UMLS:C2006131

The study establishes a rat model of thoracic aortic aneurysm (TAA) by using calcium chloride (CaCl(2)) to induce arterial injury. The study found that the expression of MMP-2, MMP-9, ADAM10 and ADAM17 was significantly elevated in the pathogenesis of vascular remodeling. These proteins were found to be involved in the formation of TAA, with features of media degeneration such as regional disruption, fragmentation of elastic fiber, and increased collagen deposition.


UMLS:C1566416

ADAM (a disintegrin and metalloproteinase)


MESH:D020782


UMLS:C1956541


UMLS:C3845271

The study aimed to find a link between the susceptibility to migraines and the 12-nucleotide insertion/deletion (indel) polymorphism in the promoter region of the alpha(2B)-adrenergic receptor gene (ADRA2B) in the Chinese Han population. The study included 368 migraine cases and 517 controls. The results showed no association between the indel polymorphism and migraines, neither at the allele nor at the genotype level.


UMLS:C3272453


NCBIGene:100399144

The study investigated the association of a 32 base-pair deletion (Δ32) in the C-C chemokine receptor 5 (CCR5) gene with disease susceptibility and severity in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and lupus nephritis (LN). The study found no significant difference in genotype frequencies between patients and healthy controls, and no significant association between the CCR5 Δ32 deletion and disease severity in RA, SLE, or LN. The study concludes that the CCR5 Δ32 deletion does not seem to be a disease susceptibility genotype for RA, SLE, or LN.


NCIT:C94634


NCBIGene:3362

The study investigates the association of the serotonin 6 (5-HT6) receptor gene (HTR6) with methamphetamine (METH)-induced psychosis in a Japanese population. The research used five tagging SNPs and conducted a genetic association analysis of case-control samples. The results showed that the SNP rs6693503 was associated with METH-induced psychosis patients. The study suggests that HTR6 may play a significant role in the pathophysiology of METH-induced psychosis in the Japanese population.


UMLS:C1527094


PUBCHEM.COMPOUND:91826472


UMLS:C1511518

The study investigates the association of DNA polymorphisms within steroid synthesis genes (CYP11B2, CYP11B1) and the postoperative resolution of hypertension in Chinese patients undergoing adrenalectomy for aldosterone-producing adenomas (APA). The study found that certain polymorphisms and haplotypes within these genes were associated with persistent postoperative hypertension. Other factors such as duration of hypertension, family history of hypertension, and elevated systolic blood pressure were also predictors of persistent postoperative hypertension.


UMLS:C3498511


UMLS:C0455527


UMLS:C0455405


HP:0004421


UMLS:C4312845

The study investigates the role of a single nucleotide polymorphism (SNP) in the fibrinogen gamma (FGG) gene in peripheral arterial disease (PAD). The study included 891 patients with PAD and 777 control subjects. The FGG genotype frequencies were not significantly different between PAD patients and control subjects. The FGG 10034 T variant was not significantly associated with the presence of PAD. The study concludes that the FGG 10034 T gene variant does not contribute to the genetic susceptibility to PAD.


UMLS:C1851196


UMLS:C4312845


PUBCHEM.COMPOUND:60953

The paper reviews the safety and efficacy of capecitabine, an oral prodrug of 5-fluorouracil (5-FU), which has been used for over 40 years in the treatment of various solid tumors. The study focuses on the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. The drug has shown promising results in treating colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most common side effects reported are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. The paper concludes that capecitabine has a well-established safety profile and can be safely administered to patients with advanced age, hepatic and renal dysfunctions.


PUBCHEM.COMPOUND:60953


PUBCHEM.COMPOUND:60953

Patients with advanced age, hepatic and renal dysfunctions


PUBCHEM.COMPOUND:163297077

The study investigates the association between three functional polymorphisms in the promoter region of the dopamine D4 receptor (DRD4) gene and schizophrenia, depression, and heroin addiction. The results suggest that the -120-bp duplication polymorphism of DRD4 is associated with schizophrenia and that the -521 C/T polymorphism is associated with heroin addiction.


UMLS:C0035158


NCBIGene:1815


UMLS:C4699132

The study identifies a new gene mutation, c.2554+1G>T, as the cause of aceruloplasminemia, a rare neurodegenerative disease associated with iron accumulation in the brain and liver. This mutation results in defective cellular iron export, leading to iron overload. The study also found that iron chelation therapy with deferasirox effectively reduced iron levels in the liver but not in the brain.


MONDO:0011426


PUBCHEM.COMPOUND:214348


PUBCHEM.COMPOUND:6918289

Summary not provided or could not be parsed.


PUBCHEM.COMPOUND:6918289


PUBCHEM.COMPOUND:6918289

Tumor microvessel density and VEGF expression


UMLS:C0008059

The study reports a fatal case of a premature male neonate diagnosed with Keratitis-ichthyosis-deafness (KID) syndrome, a rare congenital ectodermal disorder. The child exhibited symptoms such as hearing impairment, ichthyosiform erythroderma, palmoplantar keratoderma, alopecia, and a thick vernix caseosa-like covering of the scalp. The child's condition was further complicated by intraventricular and intracerebral haemorrhage, septicaemia, meningitis, and severe respiratory failure, leading to his death at 13 weeks postnatally. Genetic analysis revealed a novel heterozygous de novo mutation in the Cx26 gene (c.263C>T; p.Ala88Val) causing the KID syndrome.


UMLS:C4266380


UMLS:C0008059

Intraventricular and intracerebral haemorrhage


UMLS:C0008059


NCBIGene:57152

The study investigates the role of SLURP1 gene mutation in T-cell activation in a Taiwanese family with Mal de Meleda (MDM), a skin condition. The mutation in the SLURP1 gene, specifically a G to A substitution at nucleotide 256, results in a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. This mutation was found to impair T-cell activation, which could be restored by the addition of recombinant human SLURP-1 protein. This suggests that the presence of wild-type SLURP-1 is essential for normal T-cell activation.


UMLS:C4763489

Glycine to arginine substitution at amino acid 86 (G86R)


UMLS:C2609412

Glycine to arginine substitution at amino acid 86 (G86R)


UMLS:C1699394


UMLS:C0043210

The paper discusses a case of a 76-year-old woman who experienced loss of consciousness due to hyperkalemia-induced bradycardia. The hyperkalemia was caused by the combination of spironolactone and ramipril, medications she was taking. After the correction of her serum potassium level, her normal sinus rhythm was restored. The paper emphasizes the need for clinicians to be aware of the risk of hyperkalemia, especially in elderly patients taking ACE/ARB in combination with potassium sparing agents and who have mild renal disturbance.


UMLS:C0268022


UMLS:C5177978


UMLS:C0871685


UMLS:C5425061

The study reveals that approximately 30% of alleles causing genetic disorders generate premature termination codons (PTCs), which are usually associated with severe phenotypes. However, the bypassing of the deleterious stop codon can lead to a mild disease outcome. The study identifies a mechanism that results in the mild to asymptomatic phenotype observed in cystic fibrosis patients homozygous for the E831X mutation in the CFTR gene. This mechanism involves splicing at NAGNAG tandem splice sites, which results in the insertion or deletion of three nucleotides. This finding is significant for genetic counseling and deciding appropriate therapeutic strategies.


NCIT:C167282


UniProtKB:A0A023FHK2


UMLS:C0460067


UMLS:C5142907

Methicillin-sensitive Staphylococcus aureus (MSSA)

The paper reports a case of a 54-year-old male with methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and suspected MSSA meningitis. The patient was initially treated with vancomycin, levofloxacin, and piperacillin/tazobactam, which was later narrowed to nafcillin. However, due to acute renal failure and relapsing bacteremia, nafcillin was discontinued and high-dose daptomycin was initiated. The penetration of daptomycin into the cerebrospinal fluid (CSF) was higher than in previous reports, suggesting it may be an alternative treatment for MSSA bacteremia in patients who cannot tolerate standard therapy.


UMLS:C0030705


PUBCHEM.COMPOUND:16134395


UMLS:C0015576

The study investigates a rare hereditary disease, primary glucocorticoid resistance, which causes partial insensitivity to glucocorticoid action due to genetic alterations of the glucocorticoid receptor (GR). A family with eight affected individuals across three generations was found to be prone to cortisol resistance, bilateral adrenal hyperplasia, arterial hypertension, and hypokalemia. The family's condition was linked to the first heterozygous nonsense mutation p.R469[R,X] in the GR. This mutation leads to a truncated GR lacking hormone and DNA binding capacity. The mutated GR transcript is selectively degraded, leading to GR haploinsufficiency, which in turn leads to hypertension due to elevated cortisol. The study suggests that GR haploinsufficiency may be a novel genetic cause of subclinical hypercortisolism, bilateral adrenal hyperplasia, and mineralocorticoid-independent hypertension.


UMLS:C5420633


NCIT:C132237


NCBIGene:1558

The study aimed to develop a method for screening mutations of CYP2C8, a gene involved in the cytochrome P450 epoxygenase pathway, using denaturing high performance liquid chromatography (DHPLC). DNA samples from 200 subjects, including hypertensive patients and healthy controls, were screened for SNPs in CYP2C8. Six variants were detected, two of which were new. Differences in variant frequencies were observed between the controls and hypertensive patients. The controls had a significantly higher prevalence of C35322C compared to the patients. The study suggests that being homozygous for C35322C could be a protective factor for hypertension.


NCBIGene:1558


NCBIGene:1621

The study investigates the association of the dopamine β-hydroxylase (DBH) -1021T allele and Alzheimer's disease (AD). The DBH gene is responsible for the conversion of dopamine to noradrenaline, a process that is disrupted in AD. The study found that the presence of the -1021T allele was associated with an increased risk of AD, particularly in men under 75 years old. Additionally, an interaction was found between the DBH -1021T allele and the -889TT genotype of the IL1A gene, which could contribute to the onset of AD through misregulation of inflammation in the brain.


NCBIGene:1621


NCBIGene:78987

The study investigates the role of CRELD1 gene mutations in patients with atrioventricular septal defects (AVSDs). The study included 133 patients with AVSD and 200 healthy controls. Two novel mutations in the CRELD1 gene were identified in patients with AVSD. One mutation was a C-to-G transition at nucleotide 857 in exon 8, resulting in a substitution of alanine for proline at amino acid 286. The other mutation was a c.973G>A transition in exon 9, resulting in a substitution of lysine for glutamic acid at amino acid 325. These findings suggest that CRELD1 is likely an AVSD-susceptibility gene and its mutations may increase the risk of developing a heart defect.


UMLS:C1135968


UMLS:C5142643


UMLS:C0805998

The study demonstrates the feasibility of detecting EGFR mutations in plasma DNA samples from lung cancer patients using mass spectrometry genotyping and ME-PCR. The EGFR mutation status in plasma DNA was found to be identical to the primary tumor in 61% of patients. The presence of EGFR mutation in plasma and/or tumor tissue was correlated with overall survival for patients treated with erlotinib, indicating that a positive EGFR result in plasma DNA has a high predictive value for tumor EGFR status and for favorable clinical course on EGFR-targeted therapy.


UMLS:C5555657


UMLS:C5389385


UMLS:C4700954

EGFR mutation in plasma and/or tumor tissue


NCBIGene:1234

The study investigates the relationship between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics. The researchers used hierarchical phylogenetic models (HPMs) to test for differences in dynamics across host populations. The study found that the HPM provides more efficient estimation of evolutionary parameters such as nucleotide substitution rates and d(N)/d(S) rate ratios. The study suggests an association between nucleotide substitution rate and disease progression, but the role of CCR5 genotype remains unclear. The delayed onset of AIDS symptoms appears to be associated with lower viral replication rates rather than with differences in selection on amino acid fixation.


UMLS:C0556037

differences in dynamics across host populations


UMLS:C3872672


UMLS:C0740831


UMLS:C0796451

The study investigates the association of the T704C polymorphism of the angiotensinogen (AGT) gene with hypertrophic cardiomyopathy (HCM) in a South Indian population. The study included 150 HCM patients and 165 healthy controls. The results showed a significant association of the T allele of the AGT gene with sporadic hypertrophic cardiomyopathy (SHCM), but not with familial hypertrophic cardiomyopathy (FHCM).


UMLS:C0422392

The study presents a new method for detecting mutations in the COL3A1 gene, which causes Ehlers-Danlos syndrome, vascular type (vEDS). The method uses high-resolution melting curve analysis (hrMCA) and small amplicon genotyping (SAG) from genomic DNA, which is simpler, faster, cheaper, and more sensitive than the traditional method that requires a skin biopsy. The method successfully detected all known COL3A1 mutations in validation samples and identified five new mutations. It also differentiates mutations before sequencing using SAG. This method will improve understanding of the genotype-phenotype correlation in COL3A1, leading to better diagnosis and treatment.


UMLS:C3669233


UMLS:C1511879


UMLS:C5160547


NCBIGene:35197

The study identifies Brain Tumor (Brat) as a significant differentiation factor and target of Pumilio (Pum) and Nanos (Nos) regulation in Drosophila ovarian germline stem cells (GSCs). Brat, excluded from GSCs by Pum-Nos, works with Pum in cystoblasts (CBs) to repress distinct targets, including the Mad and dMyc mRNAs. This regulation reduces cellular responsiveness to Dpp signaling, forcing the cell to become refractory to the self-renewal signal. Mathematical modeling shows bistability of cell fate in the Brat-mediated system, explaining how autoregulation of GSC number can arise from Brat coupling extracellular Dpp regulation to intracellular interpretation.


UMLS:C1256951


NCBIGene:35197


UMLS:C5700359

The study reports a novel mutation in the apolipoprotein E (apoE) gene, named apoE Osaka, in a patient with lipoprotein glomerulopathy (LPG) and dyslipidemia. The patient, a 45-year-old man, showed characteristic signs of LPG, including thrombus-like deposits in dilated glomerular capillaries. Despite having mild dyslipidemia, his serum apoE level was normal. The apoE Osaka mutation involves a nucleotide substitution of G to C at codon 158 of exon 4, resulting in an amino acid substitution of arginine for proline at position 158 of apoE. This mutation may cause a conformational change in the apoE protein, affecting its interaction with abnormal apoE-containing lipoproteins and endothelial cells of glomerular capillaries. The exact mechanism of LPG related to apoE Osaka remains unclear.


UMLS:C5700359


UMLS:C0003595


NCBIGene:2979

The research paper investigates the role of GUCA1B gene mutations in inherited retinal diseases, specifically autosomal dominant cone dystrophy and cone rod dystrophy. The study included 24 unrelated patients with these conditions from European and North-American origins. Three different sequence variants were identified, but all were previously reported in healthy subjects. The study concludes that the GUCA1B gene is a minor cause for retinal degenerations in Europeans or North-Americans.


NCBIGene:2979


UMLS:C4520816

Sequence variants c.-17T>C, c.171T>C, c.465G>T


GTOPDB:5874

The study investigates the association between chronic immune thrombocytopenia (ITP) and the frequency of the single-nucleotide polymorphism rs763780 (7488T/C) in the IL-17F gene. The study found that patients with chronic ITP had a significantly lower frequency of the IL-17F 7488CC genotype and the number of IL-17F 7488C alleles compared to the control group. Additionally, patients with the IL-17F 7488TT genotype showed a severe thrombocytopenic state at diagnosis than those with the IL-17F 7488TC genotype. These findings suggest that the IL-17F 7488 T allele is significantly associated with the development of chronic ITP.


GTOPDB:5874


UMLS:C3890210

significantly associated with the development of


UMLS:C0796451

The study investigates the impact of the G1359A polymorphism of the cannabinoid receptor gene (CNR1) on weight loss and adipocytokines in obese patients following a lifestyle modification involving a Mediterranean hypocaloric diet and exercise. The study found that both the wild type group (G1359G) and the mutant type group (G1359A or A1359A) experienced decreases in weight, body mass index, fat mass, waist circumference, and systolic blood pressure. However, the mutant type group also showed a decrease in resistin, leptin, and interleukin-6 levels after the dietary treatment.


UMLS:C0796451


UMLS:C5197815


UMLS:C1863955

The study investigates the frequency of the XRCC1 Arg399Gln gene polymorphism in patients with systemic lupus erythematosus (SLE) in the Polish population. The results suggest that the XRCC1 Arg399Gln polymorphism may increase the risk of SLE incidence and the occurrence of some SLE manifestations. The study also found a significant contribution of the Gln/Gln or Arg/Gln versus Arg/Arg genotype to the presence of either the malar rash or photosensitivity manifestations of SLE.


UMLS:C1863955


NCBIGene:224

The study reports on two patients with Sjögren-Larsson syndrome (SLS), a disorder characterized by skin, mental, and motor symptoms, caused by mutations in the ALDH3A2 gene. The researchers found that these patients had large contiguous gene deletions in the ALDH3A2 locus. One patient had a 352-kb deletion involving ALDH3A2 and four other genes, while the other had a 1.44-Mb deletion and a missense mutation. The study suggests that large gene deletions may account for up to 5% of the mutant alleles in SLS.


UMLS:C0150905


UMLS:C0457503


UMLS:C0085756

The study investigates the genetic basis of systemic lupus erythematosus (SLE) in African American women, focusing on the major histocompatibility complex (MHC) on chromosome 6p21. The study found four independent signals in the MHC region associated with risk of SLE in African American women. The most strongly associated single nucleotide polymorphism (SNP) with SLE was rs9271366 near the HLA-DRB1 gene. Three other SNPs, rs204890, rs2071349, and rs2844580, were also associated with SLE independent of rs9271366. The study also confirmed two SNPs found in a genome-wide association study (GWAS) of European ancestry women, indicating shared genetic risk factors for SLE among African Americans, Europeans, and Chinese.


UMLS:C1257905

European ancestry women, Chinese subjects


NCBIGene:1602

The study found that the DACH1 gene, located at chromosome 13q21, is deleted in glioblastoma multiformes. This gene is a tumor suppressor and its loss or reduction in function contributes to tumorigenesis. Forced expression of DACH1 resulted in decreased cell proliferation of glioma cell lines. The study also found that DACH1 suppresses the growth of tumor cells and regulates bFGF-mediated tumor-initiating activity of glioma cells.


NCBIGene:1602


NCBITaxon:31643

The study investigates the relationship between serum lipid and factors that predict the efficacy of PEG-IFN/RB therapy in chronic Hepatitis C Virus (HCV) genotype 1b infection. The study found that both the amino acid 70 substitution in the core region of the HCV and the rs8099917 SNP near the IL28B gene were independent factors in determining serum apolipoprotein B-100 and low-density lipoprotein cholesterol levels. Higher levels of these lipids were associated with the Arg70 variant and the rs8099917 TT responder genotype. The study suggests that these lipids could be markers of impaired cellular lipoprotein pathways or host endogenous interferon response to HCV in chronic HCV infection.


UMLS:C1527094


UMLS:C5239128


UMLS:C4554543


PR:000004145


NCBIGene:5080

The study investigated the PAX6 gene mutations in patients with different clinical phenotypes including Aniridia (AN), coloboma of iris and choroid, or anterior segment malformations. Two novel mutations were identified: a heterozygous splicing-site mutation (c.357-3C>G) in the AN group, and a missense mutation (c.643T>C) in the anterior segment malformation group. A large deletion was also detected in one sporadic patient from the AN group. No mutation or deletion was found in the group with coloboma of iris and choroid. The findings suggest that different mutations might cause different ocular phenotypes.


NCBIGene:5080


UMLS:C0152035

The study identified a new mutation in the fibrillin-1 gene (FBN1) in a Chinese family with Marfan syndrome. The mutation, a heterozygous c.3703T>C change in exon 29 of FBN1, resulted in the substitution of serine by proline at codon 1235 (p.S1235P). This mutation was found in two family members with the syndrome but not in unaffected family members or in 170 healthy Chinese individuals. The mutation is likely to cause a conformation change in the calcium binding epidermal growth factor-like#15 domain, which is highly conserved among mammalian species.


NCBIGene:2200


UMLS:C2045655


UniProtKB:A0A090L7E8

Calcium binding epidermal growth factor-like#15 domain


UMLS:C0796451

The study investigates the association between the polymorphism rs2234671 in the CXCR1 gene and chronic periodontitis in a Brazilian population. The CXCR1 gene is a receptor for interleukin 8 (IL-8), which plays a significant role in the inflammatory response. The polymorphism rs2234671 was previously associated with decreased lung cancer risk. However, the study found no association between this polymorphism and susceptibility to chronic periodontitis.


NCBIGene:3577


UMLS:C1721046


UMLS:C0796451


NCBIGene:4280

Chronic lymphocytic leukemia/small lymphocytic lymphoma

The study found that mice with a deficiency in TNFR-associated factor 2 (TRAF2) in B lymphocytes are predisposed to chronic lymphocytic leukemia/small lymphocytic lymphoma. This deficiency results in an expanded marginal zone B cell population and increased expression of TRAF3, X-linked inhibitor of apoptosis, and Bcl-X(L). The absence of TRAF2 also makes B cells independent of B cell activating factor for survival, suggesting that TRAF2 deficiency cooperates with BCL-2 in promoting chronic lymphocytic leukemia/small lymphocytic lymphoma in mice.


UMLS:C0302813


PR:000007142

The study investigates the effects of EPO/EPOR on primary bone marrow-derived CFUe-like progenitors. The research identified 160 EPO/EPOR target transcripts that were significantly modulated. The study also discovered a unique set of EPO-regulated survival factors and cell cycle mediators. The research found that EPO regulation of signal transduction factors was complex. The study identified Tnfr-sf13c as a novel positive regulator of proerythroblast formation.


PR:000007142


UMLS:C4742174


UMLS:C0528094


UMLS:C1262147

The paper discusses a case of Scleroderma renal crisis (SRC), a rare but severe complication of systemic sclerosis (SSc), induced by the use of tacrolimus and corticosteroids. The study aims to highlight the risk associated with the use of tacrolimus in patients with SSc.


UMLS:C3540725


PUBCHEM.COMPOUND:445643


MONDO:0019737


NCBIGene:3586

The study investigates the association of variations in genes involved in immune response, including IL10, and the risk of recurrence after surgery for localized prostate cancer. The study found that the minor allele (A) in IL10 rs1800872, which produces less interleukin-10 (IL-10), was associated with a higher risk of recurrence, while the minor allele (G) in rs1800896, which produces more IL-10, was associated with a lower risk of recurrence. Variations in IL10, CRP, GSTP1, IL1B, and NOS2 were associated with prostate cancer recurrence independent of pathologic prognostic factors.


NCBIGene:2950

Variations in IL10, CRP, GSTP1, IL1B, and NOS2


PR:000011382

The study investigates the role of neuronal pentraxin 1 (NP1), a protein, in hypoxic-ischemic (HI) neuronal injury. The research used wild-type and NP1 knockout mouse hippocampal cultures and found that NP1 is induced in primary hippocampal neurons following oxygen glucose deprivation (OGD). This induction leads to increased interactions of NP1 with Bad and Bax proteins, facilitating their mitochondrial translocation and dissipation of mitochondrial membrane potential. This process precedes the increased mitochondrial release of cytochrome C into the cytosol, activation of caspase-3 and OGD time-dependent cell death. In contrast, in NP1-KO neurons, there was no translocation of Bad and Bax, and no evidence of loss of mitochondrial membrane potential, increased Cyt C release and caspase-3 activation following OGD, resulting in significantly reduced neuronal death. The findings suggest NP1 as a potential therapeutic target against HI brain injury in neonates.


PR:000011382


PR:000011382

Mitochondrial membrane potential (ΔΨ(m))


UMLS:C4469152


UMLS:C0040724

Summary not provided or could not be parsed.


UMLS:C0563648


UMLS:C1283034


NCBIGene:2542128


PUBCHEM.COMPOUND:11949636

The study investigates the use of Bortezomib and Dexamethasone as salvage therapy for patients with relapsed/refractory multiple myeloma who have previously undergone autologous stem cell transplantation or conventional chemotherapy. The results show that 55% of the patients achieved at least a partial response, with a median time to progression, progression-free survival, and overall survival of 8.9, 8.7, and 22 months, respectively. The most common adverse event was peripheral neuropathy, which led to treatment discontinuation in 6% of the patients.


PUBCHEM.COMPOUND:11949636


MONDO:0005244

led to discontinuation of treatment in 6% of patients


UMLS:C1170010

The study investigates the cytogenetic action of Ifosfamide (IFO), an antineoplasmic agent, and sodium 2-sulfanylethanesulfonate (Mesna) on rabbit lymphocytes. IFO has a side effect of intense urotoxic action, which necessitates the co-administration with Mesna to minimize this effect. The study found that Mesna, when used in conjunction with IFO, reduces the frequency of sister chromatid exchanges (SCEs). Additionally, high concentrations of Mesna alone significantly reduce the proliferation rate index (PRI) compared to IFO at the same concentration. Mesna significantly reduces IFO's genotoxicity and acts in an inhibitory fashion on the cytostatic action of the drug when administered in high concentrations.


UMLS:C1170010


PUBCHEM.COMPOUND:23662354


UMLS:C0030705

The study investigates the prevalence and predictors of levodopa-induced dyskinesia in multiethnic Malaysian patients with Parkinson's disease. The study found that 44% of the patients developed dyskinesia after a median of 3 years of levodopa therapy. The significant predictors of dyskinesia were found to be the duration of levodopa therapy, the total daily levodopa dose, and the age of onset of the disease.


UMLS:C0444921


UMLS:C2348070


UMLS:C5238863


NCBIGene:100124785

The paper reports a novel disease gene, LYRM7/MZM1L, associated with a severe mitochondrial encephalopathy. A homozygous mutation (c.73G>A) in this gene was identified in a baby patient with early onset, severe encephalopathy, lactic acidosis, and profound, isolated complex III (cIII) deficiency in skeletal muscle. This mutation predicts a drastic change in a highly conserved amino-acid residue (p.Asp25Asn). The mutation was further studied in a yeast strain, where it caused a temperature-sensitive respiratory growth defect, decreased oxygen consumption, impaired maturation/stabilization of the Rieske Fe-S protein, and reduced complex III activity and amount.


UMLS:C5542292


NCBIGene:9646

The study reveals that two components of the RNA polymerase II associated factor complex, Ctr9 and Rtf1, are crucial during mammalian preimplantation development. Ctr9-deficient embryos fail to correctly specify lineages at the blastocyst stage, with some lineage-specific factors being markedly reduced and others being inappropriately expressed. Several imprinted genes are also aberrantly expressed, although allele-specific DNA methylation is not altered. The study also documents a loss of histone H3 lysine 36 trimethylation (H3K36me3) in Ctr9-deficient embryos, indicating that the PAF1 complex is required for mammalian development, likely through regulation of H3K36me3.


UMLS:C3686817


UMLS:C3686817

Histone H3 lysine 36 trimethylation (H3K36me3)


UniProtKB:A0A5J4Y2K7


UMLS:C0747045

The study investigates the effects of oral galactose treatment on cognitive deficits in a rat model of sporadic Alzheimer's disease (sAD). The research found that one month of oral galactose treatment, initiated immediately after the administration of streptozotocin (a compound used to induce the Alzheimer's disease model), successfully prevented the development of cognitive deficits. This beneficial effect was independent of the rat's age and the dose of galactose, ranging from 100 to 300 mg/kg/day. The study suggests that oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in Alzheimer's disease.


UMLS:C0747045


UMLS:C0920381

The paper discusses a case of a 54-year-old woman who developed Takotsubo syndrome (TS), also known as broken heart syndrome, after taking the drug Zolmitriptan for persistent migraines. TS is characterized by left ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes suggestive of an acute coronary syndrome. The woman's coronary angiogram showed normal coronary arteries but reduced left ventricular ejection fraction with wall motion abnormalities consistent with TS. This is the first reported case of TS associated with Zolmitriptan.


PUBCHEM.COMPOUND:60857


UMLS:C0030705


UMLS:C4737984


PUBCHEM.COMPOUND:134694162

Hippocampal long-term potentiation (LTP)


PUBCHEM.COMPOUND:134694162


PUBCHEM.COMPOUND:2733556

The study investigates the protective effects of Cultured mycelium Cordyceps sinensis (CMCS) on liver sinusoidal endothelial cells (LSECs) in mice with acute liver injury. The liver injury was induced by injecting the mice with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). The results showed that CMCS significantly improved liver function, reduced inflammation, and improved peroxidative injury in the liver. It also decreased the activities of matrix metalloproteinase-2 and 9 (MMP-2/9) in liver tissue, improved the integration of scaffold structure, and decreased the protein expression of VCAM-1 and ICAM-1. The protective mechanism of CMCS was associated with the down-regulation of MMP-2/9 activities and inhibition of peroxidation in the injured liver.


PUBCHEM.COMPOUND:2733556


UMLS:C4017159

The study investigates the association between the -930A>G polymorphism of the CYBA gene and coronary artery disease (CAD). The CYBA gene encodes p22phox, a critical component of vascular NADPH oxidases, which are the main source of reactive oxygen species (ROS) in the vasculature. ROS are involved in the pathogenesis of atherosclerosis and CAD. The study found that the -930G allele carrier state was a risk factor for CAD. Furthermore, a synergistic effect of the -930G allele with overweight/obesity and cigarette smoking was found. The risk of CAD was significantly higher in overweight/obesity individuals and smokers carrying the -930G allele.


UMLS:C0683223


UMLS:C2219945


PUBCHEM.COMPOUND:5743

The study investigates the effects of bovine lactoferrin (LF), an iron-binding glycoprotein, on dexamethasone-induced hypertension in rats. The results show that chronic administration of LF significantly reduces blood pressure and reactive oxygen species production, and improves antioxidant capacity in dexamethasone-induced hypertension. This suggests that LF's antihypertensive action may be due to its role in inhibiting oxidative stress.


UMLS:C0022942


UMLS:C0850110

The study analyzed data from 11,529 patients who underwent cardiac surgery involving cardiopulmonary bypass between 2004 and 2010. The research found that 0.9% of these patients developed postoperative convulsive seizures, with the median time of occurrence being 7-8 hours after surgery. Factors that independently predicted the occurrence of these seizures included age, female sex, redo cardiac surgery, calcification of the ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp, and the use of tranexamic acid. Notably, tranexamic acid was a strong predictor of seizures. Patients who experienced seizures had higher in-hospital mortality rates and longer hospital stays. The study suggests that the administration of tranexamic acid, especially in doses exceeding 80 mg.kg(-1), should be carefully considered due to the risk of postoperative seizures.


PUBCHEM.COMPOUND:5526


UMLS:C0311334


NCBIGene:50490

The study investigates the role of the isoform NOX4 in endothelial cells (ECs) in contributing to vascular endothelial growth factor (VEGF)-induced angiogenesis and intravitreal neovascularization (IVNV). The study found that NOX4 was the most prevalent isoform of NADPH oxidase in vascular ECs and its expression increased in retinal lysates at a time point when IVNV developed. The study also found that VEGF-activated NOX4 led to an interaction between VEGF-activated VEGFR2 and NOX4 that mediated EC proliferation via activation of STAT3. The results suggest that NOX4 may regulate VEGFR2-mediated IVNV through activated STAT3.


UMLS:C0388176


GO:0038190


UMLS:C1752857

Interaction between VEGF-activated VEGFR2 and NOX4


NCBIGene:50490


UMLS:C0105770

The study investigates the role of β-catenin, a component of Wnt signaling, in the development of anorectal malformations (ARMs). The researchers manipulated the β-catenin gene in endodermal epithelia and found that both loss and gain of function mutants displayed abnormal clefts and reduced cell proliferation. The gain of function mutants also showed reduced apoptosis and increased expression of bone morphogenetic protein (Bmp) genes. An additional mutation for a Bmp receptor gene partially restored elongation. The results suggest that some ARM phenotypes in the β-catenin gain of function mutants were caused by abnormal Bmp signaling.


REACT:R-HSA-2394007


UMLS:C4526838


UMLS:C0920381

The paper reports a case of a 76-year-old man with Waldenström macroglobulinaemia who developed necrotising fasciitis after being treated with a combination of bortezomib, high-dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, the patient died 23 hours after the onset of the infection. The authors suggest that physicians should be aware of the potential for fatal bacterial infections in elderly patients treated with bortezomib and high-dose dexamethasone, and call for further investigation.


UMLS:C0031831


UMLS:C0085973


NCBIGene:4280

The study investigates the effects of ginsenosides (Re, Rg1, and Rb1) on opioid-induced hyperalgesia (OIH) in mice. OIH was induced in mice through the administration of morphine for 7 days. During withdrawal, the mice were given Re, Rg1, or Rb1. The ginsenoside Re was found to inhibit OIH, while Rg1 and Rb1 did not have the same effect. In fact, Rg1 seemed to aggravate OIH.


PUBCHEM.COMPOUND:58774156


PUBCHEM.COMPOUND:3086007


PUBCHEM.COMPOUND:441923


UMLS:C0772037

The study demonstrates that field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) can be used to predict the effects of multichannel blockers on QT interval, a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The study found that IKr and IKs blockers prolonged FPD, while Ca(2+) channel blockers shortened it. Multichannel blockers like Amiodarone, Paroxetine, Terfenadine, and Citalopram also prolonged FPD in a concentration-dependent manner. The study also found that this assay can help detect early afterdepolarization (EAD) for drugs with Torsade de Pointes (TdP) potential.


NCBITaxon:1581408


UMLS:C2193820


UniProtKB:A7LNJ2

The study reveals that CSF-1 plays a significant role in IL-3-mediated hematopoiesis, particularly in the generation of CD11c+ macrophages. CSF-1 enhances IL-3-driven CD11c+ cell expansion and reduces basophil and mast cell generation from bone marrow. The CD11c+ cells produced by IL-3 or IL-3/CSF-1 are competent in cellular maturation and endocytosis, and they produce high levels of IL-10, IL-1, IL-6, and TNFα in response to LPS. These cells resemble macrophages in morphology and are relatively poor T cell stimulators.


UniProtKB:A7LNJ2


UMLS:C4737575


PUBCHEM.COMPOUND:245005

The study investigates the role of calcium (Ca2+) in aconitine poisoning. Aconitine, a diterpenoid alkaloid derived from aconitum plants, was found to cause Ca2+ overload, leading to accelerated heart rhythm and arrhythmia in rats. This overload also resulted in myocardial injury and reduced viability of neonatal rat ventricular myocytes (NRVMs). Furthermore, aconitine was found to stimulate apoptosis, or cell death, in a time-dependent manner. This was linked to the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic protein BCL-2. The study suggests that aconitine promotes Ca2+ overload and apoptosis via the phosphorylation of P38 mitogen-activated protein kinase (MAPK).


UMLS:C1827667


PUBCHEM.COMPOUND:245005


PUBCHEM.COMPOUND:245005

P38 mitogen-activated protein kinase (MAPK)


PUBCHEM.COMPOUND:4091

The study found that chronic pre-treatment with metformin, a medication, can reduce cardiac dysfunction and suppress inflammatory responses following a myocardial infarction (heart attack). This is possibly due to the inhibition of toll-like receptor 4 (TLR4) activities. The study also found that lower doses of metformin (25 and 50mg/kg) were more effective than a higher dose (100mg/kg).


PUBCHEM.COMPOUND:4091


PUBCHEM.COMPOUND:24850574

The study investigates the effects of Garcinielliptone FC (GFC), a compound isolated from the seed extract of Platonia insignis Mart, on seizures in mice. The results showed that GFC increased the latency to first seizure and reduced the mortality rate of the mice. It also influenced the levels of certain amino acids in the hippocampus of the mice, suggesting that it may have anticonvulsant properties.


PUBCHEM.COMPOUND:24850574


UMLS:C3810656

The study identifies a new genetic disorder caused by a mutation in the THRA gene, which encodes the thyroid hormone receptor α1 (TRα1). This mutation leads to a severe skeletal dysplasia in children, characterized by high serum T3:T4 ratio, intellectual deficit, and constipation. The study uses Thra1(PV/+) mice as a disease model, which exhibit similar symptoms. Despite treatment with T4, the skeletal abnormalities in the mice did not improve, indicating a resistance to thyroid hormone. Prolonged T4 treatment, however, increased bone stiffness and strength, suggesting potential long-term detrimental effects. The study concludes that TRα1 plays a crucial role in skeletal development and that patients with different THRA mutations may respond variably to T4 treatment.


MESH:D008821


UMLS:C4535841


PUBCHEM.COMPOUND:3028194

The study found that the absence of PKC-alpha can reduce the effects of lithium-induced nephrogenic diabetes insipidus (NDI). Lithium, an antipsychotic, causes NDI in about 40% of patients. This is due to lithium disrupting the cAMP pathway and reducing the expression of urea transporter (UT-A1) and water channel (AQP2) in the inner medulla. However, in mice without PKC-alpha, there was no change in urine output or concentration after lithium treatment. Furthermore, the expression of AQP2 and UT-A1 was preserved in these mice, preventing the development of severe polyuria associated with lithium therapy.


PUBCHEM.COMPOUND:3028194


UMLS:C0030705

experienced prolonged neuromuscular block after administration of

The study reports a case of prolonged neuromuscular block after administration of suxamethonium, leading to the discovery of a new BCHE variant (c.695T>A, p.Val204Asp). This mutation disrupts the catalytic triad and results in a "silent" phenotype. The patient's plasma butyrylcholinesterase showed low activity, consistent with a heterozygous atypical silent genotype. The mutation also disrupts hydrogen bonding between Gln223 and Glu441, leading to a disruption of the catalytic triad functionality. The enzyme volume is increased, suggesting a pre-denaturation state.


UMLS:C1142182

The study investigates the impact of sepsis on leucine resistance in skeletal muscle, hypothesizing that it is linked to a down-regulation of amino acid transporters or an impairment in the formation of the Leucine-sensitive mTOR-Ragulator complex. The results show that sepsis in adult male rats decreases protein synthesis in the gastrocnemius muscle, associated with a reduction in mTOR activation. Sepsis also alters the content of certain amino acid transporters, but these changes are not associated with the development of leucine resistance. Instead, the inability of leucine to fully activate mTOR and muscle protein synthesis may be partially explained by the leucine-stimulated binding of raptor with RagC and the recruitment of mTOR/raptor to the endosome-lysosomal compartment.


UMLS:C1142182


PUBCHEM.COMPOUND:6106


UMLS:C1656431

The study investigates the host cytokine response to Respiratory syncytial virus (RSV) infection and the impact of neutralizing an RSV-inducible cytokine. The study found that RSV infection in the lung epithelium induces a network of immune factors, including newly identified RSV-inducible cytokines such as leukemia inhibitory factor (LIF), migration inhibitory factor (MIF), stem cell factor (SCF), CCL27, CXCL12 and stem cell growth factor beta (SCGF-β). The study also found that the expression of LIF protects the lung from injury during RSV infection.


UMLS:C0375023


UMLS:C1453954


UMLS:C0911651

The study found that the androgen receptor (AR) in female mice has a protective effect against diet-induced atherosclerosis, obesity, and dyslipidemia. Female mice without AR (ARKO) showed increased atherosclerosis, body weight, body fat percentage, and hepatic triglyceride levels, and reduced insulin sensitivity when fed a high-fat diet. These differences were not observed in mice that had their ovaries removed before puberty, suggesting that ovarian androgens mediated via the AR have a protective effect. The AR agonist dihydrotestosterone reduced atherosclerosis, subcutaneous fat mass, and cholesterol levels in ovariectomized mice, and regulated the expression of hepatic genes crucial for lipid homeostasis.


UMLS:C0332074


UMLS:C0002845


PUBCHEM.COMPOUND:160230


NCBIGene:2950

The study investigated the association of 18 polymorphisms in 16 genes with disease-free survival (DFS), overall survival (OS), and toxicity in rectal cancer patients treated with 5-fluorouracil (5-FU)-based chemoradiation. The study found that the GSTP1-Ile105Val (rs1695) polymorphism was significantly associated with DFS and OS. The IL8-251A/A genotype (rs4073) was associated with a lower risk of toxicities in one treatment arm, while the VEGFR2 H472Q Q/Q genotype (rs1870377) was associated with a higher risk of upper gastrointestinal tract mucositis in one treatment arm but a lower risk in another.


NCBIGene:2950


NCBITaxon:1761325


PUBCHEM.COMPOUND:10246418


UniProtKB:A0A0S7IBD0

The study investigates the role of Sag/Rbx2 E3 ligase in cellular senescence and immortalization of mouse embryonic fibroblasts. The findings suggest that Sag is necessary for proper cell proliferation and Kras(G12D)-induced immortalization. Inactivation of Sag by genetic deletion suppresses cell proliferation by inducing senescence, which is associated with accumulation of p16, but not p53. This senescence can be largely rescued by simultaneous deletion of Cdkn2a, the p16 encoding gene. Furthermore, Kras(G12D)-induced immortalization can also be abrogated by Sag deletion via senescence induction. The study concludes that Sag is a Kras(G12D)-cooperating oncogene required for Kras(G12D)-induced immortalization and transformation, and targeting SAG-SCF E3 ligase may have therapeutic value for senescence-based cancer treatment.


UniProtKB:A0A0S7IBD0


UMLS:C3669233


UniProtKB:A0A2L2T1L6


UMLS:C0299809

The study investigates the activation of P-21-activated kinases (PAKs), specifically PAK2, in pancreatic acinar cells by gastrointestinal hormones, neurotransmitters, and growth factors. The findings reveal that PAK2 is activated by certain pancreatic growth factors, secretagogues, and post-receptor stimulants, but not by agents that only mobilize cellular calcium or increase cyclic AMP. The activation of PAK2 by CCK, a gastrointestinal hormone, showed novel features and was partially reduced by PKC- or Src-inhibition. The study suggests that PAK2 plays a significant role in signaling cascades activated by various pancreatic stimuli and could be a potential target for therapies in certain pancreatic disorders like pancreatitis.


UMLS:C0299809


UMLS:C2917328


PUBCHEM.COMPOUND:36462

The study investigates the role of OCT4A, a gene associated with stem cell renewal, in embryonal carcinoma cells treated with etoposide, a chemotherapy drug. The researchers found that etoposide treatment led to an increase in OCT4A and p21Cip1, a gene involved in cell cycle regulation and senescence. Silencing OCT4A suppressed p21Cip1, altered cell cycle regulation, and suppressed terminal senescence. The study also found that OCT4A induction following DNA damage in PA-1 cells performs a cell stress function by moderating the expression of p21Cip1, which alongside AMPK helps to regulate autophagy. Persistent DNA damage, leading to exhaustion of autophagy, was identified as the cause of terminal cellular senescence.


UMLS:C0012860


UMLS:C0936225

The paper discusses the harmful effects of early-life exposure to inorganic arsenic (iAs), particularly in relation to the development of cancer in adulthood. The research focuses on identifying the molecular mechanisms that link early-life iAs exposure to latent diseases. The paper suggests that epigenetic reprogramming, the development of cancer stem cells, and immunomodulation are potential mechanisms through which early-life iAs exposure can lead to latent carcinogenic effects. The paper calls for future research to include animal studies and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.


UMLS:C5392223


GO:0141044


UMLS:C3511617


UMLS:C0597010


UMLS:C4067589

Summary not provided or could not be parsed.


UMLS:C4067589


UMLS:C1611999


UMLS:C4746538

The study identified single-nucleotide polymorphisms (SNPs) that increase the risk of prostate cancer (PCa). The researchers found that 80 of the 48 GWAS index risk SNPs and 3,917 linked SNPs were located in androgen receptor-binding sites (ARBSs). One of these, rs11891426:T>G, is located in an intron of the melanophilin gene (MLPH) and is within a novel putative auxiliary AR-binding motif. The T→G exchange reduced the transcriptional activity of the ARBS. The expression of MLPH in primary prostate tumors was significantly lower in those with the G allele compared to the T allele and correlated significantly with AR protein. Higher melanophilin levels in prostate tissue of patients with a favorable PCa risk profile suggest a tumor-suppressive effect.


PUBCHEM.COMPOUND:121494112


UMLS:C2699841


PR:000010456


UMLS:C0001282

The study investigates the role of PPARα in human liver by analyzing whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. The results show that PPARα activation upregulates 617 genes and downregulates 665 genes, many of which are involved in lipid metabolism, xenobiotic metabolism, or the unfolded protein response. PPARα activation also suppresses immunity/inflammation-related genes, which could be therapeutically relevant for non-alcoholic fatty liver disease. The study also identifies several new potential target genes of PPARα.


UMLS:C0001282


UMLS:C4307884

The study investigates the role of Centrosomal protein 55 (CEP55) in epithelial ovarian carcinoma (EOC). The research found that CEP55 was significantly upregulated in ovarian cancer cell lines and lesions compared to normal cells and noncancerous ovarian tissues. High levels of CEP55 were associated with clinical stage, lymph node metastasis, intraperitoneal metastasis, tumor recurrence, differentiation grade, residual tumor size, ascites see tumor cells, and serum CA153 level. Patients with high CEP55 protein expression had shorter overall survival and disease-free survival. The study suggests that CEP55 could be a prognostic marker and therapeutic target for EOC.


UMLS:C4307884


UMLS:C0417781

The study investigates the genomic profiles of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Whole exome sequencing was performed on 12 GEP-NETs from patients in a phase II study for pazopanib. The number of somatic mutations varied widely, with eight showing mutations of more than one cancer-related gene. TP53 was recurrently mutated in three cases. Three GEP-NET patients with TP53 mutations showed a durable response, while one with a BRAF V600E mutation showed progression after pazopanib treatment. The BRAF V600E mutation was found in an independent cohort of 44 GEP-NETs. The study concludes that the BRAF V600E mutation may result in resistance to pazopanib but could be a potentially actionable mutation in metastatic GEP-NETs patients.


NCBIGene:7157


NCIT:C153163


PR:000016039

The study investigates the role of transgelin, an actin-binding protein, in colorectal cancer (CRC) cells. The research found that manipulating the levels of transgelin in CRC cells led to changes in metastatic potential. Overexpression of transgelin in RKO cells resulted in increased invasiveness, growth, and lung metastases. Conversely, reducing transgelin expression in HCT116 cells decreased metastases. The overexpression of transgelin also altered the levels of approximately 250 other transcripts, particularly those affecting the function of actin or other cytoskeletal proteins. The study concludes that higher transgelin expression promotes metastasis.


PR:000016039


NCBIGene:3426

The study investigated the association between Complement factor I (CFI) genetic polymorphisms and Vogt-Koyanagi-Harada (VKH) syndrome. No significant association was found between CFI-rs7356506 polymorphisms and VKH syndrome. However, patients with recurrent VKH syndrome and those with VKH syndrome with complicated cataract had lower frequencies of the G allele and GG homozygosity in CFI-rs7356506 compared to the controls. No significant association was detected for CFI-rs7356506 polymorphisms with patients with VKH syndrome in steroid-sensitive statuses.


NCBIGene:3426


NCBIGene:3426

no significant association with patients with VKH syndrome in


UMLS:C0002723

The study investigates the role of Serum amyloid A (SAA), a protein predominantly secreted by hepatocytes, in liver injury and fibrogenesis. The research found that SAA activates several kinases and enhances NF-κB-dependent luciferase activity in hepatic stellate cells (HSCs), the main fibrogenic cell type of the liver. SAA also induces the transcription of MCP-1, RANTES and MMP9 in an NF-κB- and JNK-dependent manner. Blocking NF-κB revealed cytotoxic effects of SAA in HSCs, including signs of apoptosis. SAA also induced HSC proliferation, which depended on JNK, Erk and Akt activity. In primary hepatocytes, SAA activated MAP kinases but did not induce significant cell death after NF-κB inhibition. In two models of hepatic fibrogenesis, hepatic mRNA levels of SAA1 and SAA3 were strongly increased. The findings suggest that SAA may modulate fibrogenic responses in the liver by inducing inflammation, proliferation and cell death in HSCs.


UMLS:C0002723


NCBIGene:835209

The study reveals that the leucine-rich repeat receptor-like kinase (LRR-RLK) MOL1 is essential for cambium homeostasis in Arabidopsis thaliana. MOL1 operates in a domain distinct from the CLE41/PXY signaling module and acts in opposition to it. Altering the domain or level of MOL1 expression disrupts cambium organization. MOL1 and PXY cannot replace each other when their expression domains are interchanged. MOL1, unlike PXY, can rescue CLV1 deficiency in the shoot apical meristem. MOL1 represses genes associated with stress-related ethylene and jasmonic acid hormone signaling pathways, which play a role in coordinating lateral growth of the Arabidopsis stem.


NCBIGene:835209


NCBIGene:835209

genes associated with stress-related ethylene and jasmonic acid hormone signaling pathways


UMLS:C1956422

The study identifies the presence of cancer stem cells (CSC) in adenoid cystic carcinoma (ACC), a type of cancer. These CSCs are CD133-positive and express NOTCH1 and SOX10. They can form spheroids and initiate tumors in mice. The study also found that the knockdown of NOTCH1, SOX10, and their common effector FABP7 negatively affected each other, inhibited spheroid formation, and induced cell death, indicating their crucial roles in CSC maintenance. The study also found that a γ-secretase inhibitor, DAPT, selectively depleted CD133(+) cells, suppressed N1ICD and SKP2, induced p27Kip1, inhibited ACC growth in vivo, and sensitized CD133(+) cells to radiation. This suggests new opportunities for targeted ACC therapies.


NCBIGene:2173


PUBCHEM.COMPOUND:5311272


UniProtKB:A0A6J8AMW6

The study investigates the relationship between circulating FASN (fatty acid synthase), an enzyme highly expressed in the human placenta, with blood pressure, maternal metabolism, and newborn parameters in healthy pregnant women. The study found that higher circulating FASN was associated with lower systolic blood pressure, a more favorable metabolic phenotype, and lower placental and birth weight. The study suggests a physiological role of placental FASN in human pregnancy and its potential influence on the pregnant mother's insulin sensitivity and blood pressure.


UniProtKB:A0A6J8AMW6


UMLS:C0032050


UMLS:C1527348

The study investigates the role of peroxisome proliferator-activated receptor α (PPARα) in the heart's adaptation to hypoxia. The findings suggest that hypoxia decreases PPARα expression, fatty acid oxidation, and mitochondrial uncoupling protein 3 (UCP3) levels, while increasing glycolysis, which helps maintain normal ATP concentrations and ejection fractions. However, a high-fat diet increases cardiac PPARα expression, fatty acid oxidation, and UCP3 levels, and decreases glycolysis. This prevents hypoxia from altering the high PPARα expression or reversing the metabolic changes caused by the high-fat diet, resulting in a significant decrease in ATP concentrations and contractile function.


UMLS:C5441638


PUBCHEM.COMPOUND:5460033

down-regulates expression of cell surface molecules

The study investigates the impact of cisplatin, a cancer therapy drug, on dendritic cells (DCs) and their functionality. The research found that cisplatin-treated DCs down-regulated the expression of certain cell surface molecules and up-regulated endocytic capacity. When stimulated with toll-like receptor (TLR) agonists, these DCs produced more IL-10, leading to the induction of tolerogenic DCs. This effect was dependent on IL-10 production. The study also found that DCs treated with cisplatin and lipopolysaccharide (LPS) contributed to Th2-type T cell immunity and increased a unique T cell population, IL-10-producing Tr1 cells, without altering the Foxp3+ regulatory T cell population. This suggests that cisplatin induces immune-suppressive tolerogenic DCs in TLR agonist-induced inflammatory conditions via abundant IL-10 production, skewing Th cell differentiation towards Th2 and Tr1 cells, potentially allowing cancer cells to evade the immune system.


UMLS:C0011306


UMLS:C0011306

Cisplatin and LPS treated Dendritic cells


PUBCHEM.COMPOUND:5460033


PUBCHEM.COMPOUND:5460033

may provide an opportunity to evade the immune system


PUBCHEM.COMPOUND:216239

The study investigates the impact of sorafenib, a kinase inhibitor used against various solid tumours, on the redox metabolism of cancer cells. The research found that sorafenib induces the expression of genes in the metallothionein-1 (MT1) family in hepatocellular carcinoma (HCC) cells. This effect was not observed with other clinically-approved kinase inhibitors. The study also found that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and this was associated with reduced overall survival. Therefore, MT1 could be a potential biomarker for exploring the impact of sorafenib on the redox metabolism of cancer cells.


PUBCHEM.COMPOUND:216239


UMLS:C1137274


UMLS:C3658249

The study shows that overexpression of the mitotic checkpoint protein Mad2 along with Kras(G12D) or Her2 in the mammary glands of adult mice leads to a delay in tumor onset due to mitotic checkpoint overactivation, error-prone mitosis, mitotic arrest, and cell death. However, Mad2 expression continues and increases karyotype complexity in Kras tumors. When faced with oncogene withdrawal, Mad2-positive tumors have a higher chance of developing persistent subclones that avoid remission and continue to grow.


UMLS:C3658249


CHEBI:30879


PUBCHEM.COMPOUND:5281633

The study found that Gartanin, a natural xanthone of mangosteen, suppresses proliferation, migration and colony formation in T98G glioma cells. It leads to cell cycle arrest in the G1 phase and induces autophagy in these cells. The anti-proliferation effect of gartanin is likely due to cell cycle arrest modulated by autophagy, regulated by the PI3K/Akt/mTOR signalling pathway. The anti-migration effect is likely due to the suppression of MMP-2/-9 activity, which is involved in the MAPK signalling pathway.


PUBCHEM.COMPOUND:5281633


UMLS:C3537120

Histone deacetylase inhibitor depsipeptide

The study found that combining the histone deacetylase inhibitor depsipeptide with the anticancer drug 5-fluorouracil (5-FU) increased the antitumor activity in human colon cancer cells. The combination treatment resulted in a 3-4 fold increase in activated caspase-3/7, a key player in apoptosis, and upregulated genes related to cell death and the apoptotic process. The treatment also significantly increased the expression of major histocompatibility complex (MHC) class II genes, which are involved in antigen processing and presentation. This is the first study to report that the combination of 5-FU and depsipeptide induces apoptosis in human colon cancer cells in conjunction with the induction of MHC class II gene expression.


UMLS:C0393027


GTOPDB:4968

The study investigates the role of CD4+IFN-γ+IL-10+ T cells during primary and secondary malaria infections. The research found that these cells, produced during primary infection, have limited memory potential and do not stably express IL-10. They are also lost from the memory population post-infection and exhibit signs of cellular exhaustion. During secondary infection, these cells fail to proliferate. However, CD4+YFP+GFP- T cell-derived cells expand rapidly and upregulate IL-10 expression during secondary infection. These cells are the major producers of an accelerated IL-10 response during secondary malaria infection. The study concludes that IL-10 has stronger regulatory effects on innate and CD4+ T cell responses during primary and secondary infections, respectively.


UMLS:C5420769


HP:0005407


UMLS:C1120088


CHEBI:30879

The study investigates the relationship between alcohol consumption and prostate cancer incidence and progression. The research was conducted on 23,868 men with prostate cancer and 23,051 controls from 25 studies within the international PRACTICAL Consortium. The study found little evidence that genetic variants in alcohol metabolising genes were associated with prostate cancer diagnosis. However, four variants in two genes were associated with prostate cancer mortality. The study suggests that alcohol consumption may not affect prostate cancer incidence, but it may influence disease progression.


UMLS:C2010873

Genetic variants in alcohol-metabolising genes


NCBIGene:283665


NCBIGene:219


UMLS:C5441638

The study investigates the impact of a high-fat diet on adiponectin expression, an adipocyte-derived adipokine with antidiabetic, anti-inflammatory, and antiatherogenic activity. The research found that a high-fat diet, whether normal or high in vitamin A, resulted in reduced adiponectin expression. This reduction was associated with an increase in aldehyde dehydrogenase A1 (ALDH1A1) and retinoic acid receptor signaling in white adipose tissue (WAT). The study concludes that the reduction in adiponectin expression under high-fat dietary conditions is dependent on increased ALDH1A1 expression, increased retinoic acid response element-mediated signaling, and retinoic acid receptor ligand-dependent reduction of adiponectin expression.


UMLS:C5441638


UniProtKB:A0A2U9NKJ8


UNII:VGN2HJC1Q3


NCBIGene:55300

The study found that the type II phosphatidylinositol 4-kinase (PI4KII) enzymes, specifically PI4KIIβ, play a role in suppressing invadopodia formation and invasive cellular behavior. Depletion of PI4KIIβ led to actin remodeling and induced the formation of invadopodia containing membrane type I matrix metalloproteinase (MT1-MMP). This depletion also affected trans-Golgi network pools of PI(4)P and post-TGN traffic, causing increased MT1-MMP trafficking to invasive structures at the plasma membrane. The study suggests that PI4KIIβ may be a clinically significant suppressor of invasion, as loss of the PI4K2B allele and underexpression of PI4KIIβ mRNA are associated with human cancers.


NCBIGene:5251

The study investigated the PHEX gene mutations in patients with hypophosphatemic rickets. 43 patients from 18 unrelated families and 250 healthy controls were enrolled. 17 different PHEX gene mutations were detected, 7 of which were novel and 6 were de novo. The novel mutations included 3 missense mutations, 2 deletion mutations, and 2 alternative splicing mutations. The serum levels of FGF23 varied widely among the patients and showed no significant difference when compared with the healthy controls. The findings provide new insight into the spectrum of PHEX mutations and potential evidence of a critical domain in PHEX protein.


NCBIGene:5251


MONDO:0009431


UMLS:C1564917

The study investigates the role of protein arginine methyltransferase 5 (PRMT5) in the inflammation, cell proliferation, migration, and invasion of fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) patients. The research found that PRMT5 was increased in synovial tissues and FLSs from RA patients and was up-regulated by IL-1β and TNF-α stimulation. Inhibiting PRMT5 reduced IL-6 and IL-8 production, and the proliferation, migration, and invasion of RA FLSs. The study suggests that targeting PRMT5 could be a promising therapy for RA.


UMLS:C1564917


UMLS:C4045661


PUBCHEM.COMPOUND:72093

The study investigates the effects of repeated Otilonium bromide (OB) treatment on neurotransmitter changes in the colon of rats subjected to wrap restraint stress (WRS), a psychosocial stressor that reproduces the main signs and symptoms of irritable bowel syndrome (IBS). The results show that OB counteracts most of the neurotransmitter changes caused by WRS, including preventing the decrease in SP-, NK1r-, nNOS-, VIP-, and S100β-immunoreactivity (IR) and the increase in CGRP-, and CRF1r-IR. However, OB does not affect the increase in CRF2r-IR neurons observed in WRS rats and does not interfere with the mild mucosal inflammation due to WRS. OB also reduces the number of spontaneous abdominal contractions in treated rats.


PUBCHEM.COMPOUND:72093


NCBIGene:189429

The study identifies RAB-28 as a novel ciliary GTPase associated with the BBSome and intraflagellar transport. The research used the nematode C. elegans to identify new cilium-associated genes. The study found that RAB-28 is exclusively expressed in ciliated neurons where it associates with IFT trains. The study also found that overexpression of predicted GDP or GTP locked variants of RAB-28 perturbs cilium and sensory pore morphogenesis and function.


NCBIGene:189429


UMLS:C0157221

cilium and sensory pore morphogenesis and function


MONDO:0018943

The study investigates the role of Voltage-Dependent Anion Channel 1 (VDAC1) in the apoptosis of mitochondrial dysfunction in Desminopathy, a disease caused by mutations in the desmin gene. The researchers constructed a desminopathy rat model and found that VDAC1 was accumulated in the desmin highly stained area of muscle fibers in both desminopathy patients and the rat model. Apoptosis-related proteins such as bax and ATF2 were also involved in desminopathy, but not bcl-2, bcl-xl or HK2. The study suggests a correlation between VDAC1 and desmin, and apoptosis-related proteins in desminopathy.


UniProtKB:A0A0S7L8Q4

participates in the apoptosis of mitochondrial dysfunction in


PR:000002193


UniProtKB:A0A0S7L8Q4


NCBIGene:571

The study investigates the role of Bach1, a transcriptional repressor, in pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. The researchers used small interfering RNA (siRNA) to knock down Bach1 and found that this significantly reduced Bach1 mRNA and protein levels. This also increased the expression of antioxidant factors and reduced the expression of fibrosis-related cytokines. The study found that the use of Bach1 siRNA attenuated the inflammatory infiltration of alveolar and interstitial cells and the destruction of lung structure in mice with BLM-induced PF. These findings suggest that Bach1 siRNA could be a potential therapeutic strategy for PF.


UMLS:C1956353


PUBCHEM.COMPOUND:702

The study investigates the effects of long-term exposure to ethanol on MCF-7, a human breast cancer cell line. It was found that short-term exposure to ethanol upregulated the stem cell related proteins Oct4 and Nanog, but they were reduced after exposure at 25 mM. Long-term exposure to 25 mM ethanol upregulated these proteins, as well as the malignancy marker Ceacam6. DNA microarray analysis showed upregulated expression of certain malignancy related genes and numerous microRNAs involved in oncogenesis and/or malignancy. Long-term 25 mM ethanol also induced a 5.6-fold upregulation of anchorage-independent growth, an indicator of malignant-like features. The results suggest alcohol's potential involvement in malignant progression of breast cancer.


PUBCHEM.COMPOUND:702


UniProtKB:A0A0S7IU77

The study reveals that CenpH, a component of the kinetochore inner plate, plays a crucial role in the G2/M transition in meiotic mouse oocytes. The absence of CenpH leads to a decrease in cyclin B1 levels, which in turn affects the activation of maturation-promoting factor (MPF), severely compromising meiotic resumption. CenpH protects cyclin B1 from destruction by competing with the action of APC/CCdh1. The impaired G2/M transition due to CenpH depletion can be rescued by the expression of exogenous cyclin B1. Interestingly, blocking CenpH does not affect spindle organization and meiotic cell cycle progression after germinal vesicle breakdown.


UniProtKB:A0A0S7IU77


UMLS:C0235425


UMLS:C0385333


UniProtKB:A0A0S7IU77

Spindle organization and meiotic cell cycle progression


UMLS:C0380190

The study investigates the role of the Type I Interferon receptor (IFNAR) in the development of virus-induced autoimmune diabetes in rats. The researchers used CRISPR-Cas9 genome editing to create IFNAR1 subunit-deficient rats and found that the deficiency significantly delayed the onset and frequency of diabetes and reduced the intensity of insulitis after treatment with a viral mimetic. The occurrence of Kilham rat virus-induced diabetes was also reduced in IFNAR1-deficient animals. These findings suggest that alterations in innate immunity can influence the course of autoimmune diabetes.


MESH:D011917


UMLS:C5690801


UMLS:C3172492

Esophageal squamous cell carcinoma (ESCC)

The study aimed to determine the consistency between PIK3CA mutations found in endoscopic biopsy specimens and surgically resected specimens of esophageal squamous cell carcinoma (ESCC). The study found a high concordance rate of 98.3% between the two types of specimens. The study suggests that endoscopic biopsy specimens can be used to detect PIK3CA mutations in patients with ESCC.


UMLS:C0184980


UMLS:C5389394


RXCUI:199857

The study found that lipopolysaccharides (LPS) from Spirulina, a type of bacteria, can inhibit tumor growth. This is achieved by altering the cytokine milieu from interleukin-17/interleukin-23 to interferon-γ. Unlike LPS from E. coli, Spirulina LPS has low toxicity and barely induces the production of IL-6 and IL-23 in mice. The antitumor effects of Spirulina LPS were observed in a hepatoma model and were found to be dependent on the Toll-like receptor 4 (TLR4). The study also found that Spirulina LPS can inhibit the spontaneous development of mammary tumors. These findings suggest that Spirulina LPS could be used as an immunomodulator for cancer immunotherapy.


RXCUI:199857


NCBIGene:4751

The study investigates the role of NEK2, a microtubule-associated protein, in hepatocellular carcinoma (HCC). The research found that NEK2 is overexpressed in HCC cells and tissues, and its overexpression is significantly correlated with poor prognosis, tumor nodule number, and recurrence in HCC patients. The study also found a positive correlation between NEK2 expression and the expression of phospho-AKT and MMP-2. These findings suggest that NEK2 could serve as a prognostic biomarker for HCC and its overexpression may contribute to the invasion and metastasis of HCC.


NCIT:C146952


NCIT:C177693


UMLS:C4280008

The study found that ADAM12, a metalloprotease-disintegrin, is upregulated in human breast cancers and is a predictor of chemoresistance in estrogen receptor-negative tumors. ADAM12 promotes the cancer stem cell (CSC) phenotype in claudin-low breast cancer cells. High ADAM12 levels were associated with elevated expression of CSC markers and an increased ability to form mammospheres. Knockdown of ADAM12 reduced cell migration and invasion, decreased resistance to anoikis, compromised mammosphere formation, and reduced tumorigenesis in mice. The study also found that ADAM12 modulates the Epidermal Growth Factor Receptor (EGFR) pathway.


UMLS:C4280008


UMLS:C2350567


NCBIGene:522795

The study investigates the role of TIEG1 in ischemic heart disease. The absence of TIEG1 in cardiomyocytes was found to prevent apoptosis and promote higher proliferation, stimulating the proliferation of endothelial cells both in vitro and in vivo. This resulted in improved cardiac function and less scar formation in TIEG1 knockout mice. The study also observed altered expression of Pten, Akt, Bcl-2/Bax, and VEGF. The findings suggest that the absence of TIEG1 plays a cardioprotective role in ischemic heart disease by promoting changes in Pten/Akt signaling.


NCBIGene:522795


NCBIGene:5326

The study investigates the role of pleomorphic adenoma gene like-2 (PLAGL2) in colorectal adenocarcinoma (CRC). It was found that PLAGL2 expression was higher in CRC tissues compared to benign tissues. The overexpression of PLAGL2 protein was found to enhance cell scratch wound-healing and transwell ability, and it also upregulated mesenchymal marker proteins, N-cadherin and vimentin, while downregulating the epithelial marker E-cadherin. PLAGL2 was also found to activate the Wnt/β‑catenin signaling pathway. More CRC cell metastasis to the lungs was observed when PLAGL2 overexpressing cells were injected into rats, suggesting that PLAGL2 might be a key molecule regulating epithelial-mesenchymal transition (EMT) involved in the Wnt/β‑catenin signaling pathway.


NCIT:C146952

cell scratch wound-healing and transwell ability


NCBIGene:5326


NCIT:C153406


EFO:0009444

The study investigates the role of Insulin-like growth factor-1 receptor (IGF-1R) in hypoxia-induced apoptosis. The research used mouse embryonic fibroblasts with either disrupted or overexpressed IGF-1R. The results showed that hypoxia increased apoptosis, reactive oxygen species (ROS) production, and autophagy. Cells with overexpressed IGF-1R had lower apoptosis and ROS production, and higher autophagy levels. Inhibition of autophagy led to increased ROS production and apoptosis. The study suggests that IGF-1R may enhance cell survival under hypoxic conditions by promoting autophagy and reducing ROS production, through the PI3K/Akt/mTOR signaling pathway.


UniProtKB:A0A1W5KKG5


GO:0006914


PUBCHEM.COMPOUND:60823

The study investigates the protective effects of atorvastatin against contrast-induced nephropathy (CIN), a type of acute renal failure caused by the injection of iodinated radiographic contrast medium. The research used a rat model and human embryonic proximal tubule (HK2) cells to test the effects of atorvastatin. The results showed that atorvastatin reduced apoptosis and deterioration of renal function, and it achieved this by upregulating the expression of heat shock protein (Hsp27).


PUBCHEM.COMPOUND:60823


PUBCHEM.COMPOUND:3220

The study investigates the effect of emodin, a naturally occurring anthraquinone, on fatty acid synthase (FASN) and its role in colon cancer. FASN is a key enzyme for fatty acid synthesis and is highly expressed in colon carcinoma. Emodin was found to inhibit the proliferation of HCT116 cells, a human colon cancer cell line, and downregulate the protein expression of FASN. This was due to protein degradation caused by increased protein ubiquitination. Emodin also inhibited FASN enzymatic activity and reduced intracellular free fatty acid levels. It enhanced antiproliferation and apoptosis in a dose- and time-dependent manner. The combined treatment of emodin and cerulenin, a commercial FASN inhibitor, had an additive effect. The final product of the FASN reaction, palmitate, rescued emodin-induced viability and apoptosis. Emodin also altered FASN-involved signaling pathways. These results suggest that emodin-regulated cell growth and apoptosis are mediated by inhibiting FASN, providing a molecular basis for colon cancer therapy.


PUBCHEM.COMPOUND:3220


PUBCHEM.COMPOUND:3220

Phosphatidylinositol 3-kinase/Akt and mitogen‑activated protein kinases/extracellular signal-regulated kinases 1/2


PUBCHEM.COMPOUND:5282054


NCBIGene:41673

The study investigates the role of Liver kinase B1 (LKB1) in angiogenesis and tumor growth. The researchers created mice with a specific deletion of LKB1 in endothelial cells. These mice showed increased levels of vascular endothelial growth factor (VEGF), increased vascular permeability, and faster tumor growth. The study suggests that LKB1 regulates angiogenesis and tumor growth by modulating the expression of VEGF.


NCBIGene:41673

Vascular endothelial growth factor (VEGF)


UniProtKB:D0VXD5

Vascular endothelial growth factor (VEGF)

endothelial cell angiogenesis and tumor growth


NCBIGene:41673


NCBIGene:4609

The study investigates the relationship between the oncogenic transcription factor MYC and B-cell receptor (BCR) signaling in pre-malignant B cells. The research used the Eμ-myc mouse model, where Myc is overexpressed specifically in B cells. The findings show that both basal and stimulated BCR signaling were increased in precancerous B lymphocytes from Eμ-myc mice compared with wild-type littermates. B cells overexpressing Myc displayed higher levels of activated CD79α, Btk, Plcγ2, and Erk1/2. These cells maintained elevated BCR signaling despite treatment with ibrutinib, a Bruton's tyrosine kinase inhibitor. The study also found that PI3K/Akt pathway signaling was increased in Eμ-myc B cells. The results suggest that precancerous B cells have already acquired enhanced survival and growth capabilities before transformation, and that elevated MYC levels confer resistance to pharmacologic inhibitors of BCR signaling.


UMLS:C1837337


NCBIGene:80177


NCIT:C153406


UMLS:C3280472

pharmacologic inhibitors of BCR signaling


UniProtKB:A0A8B9SYM6

The study investigates the role of the leukemia inhibitory factor (LIF) receptor in the process of blastocyst implantation in the uterus. The researchers created a line of mice with a specific deletion of the LIF receptor in the uterine luminal epithelium. The female mice from this line were infertile and despite repeated matings, did not become pregnant. The unimplanted blastocysts from these mice, when transferred to normal mice, implanted normally, indicating that the issue was with uterine receptivity and not the competency of the embryo. The absence of the LIF receptor resulted in the failure of STAT3 to move to the luminal epithelium nuclei and a reduction in the expression of the LIF regulated gene Msx1, which regulates uterine receptivity. This suggests that the LIF receptor is essential for successful embryo implantation.


MESH:D008821


UBERON:0000358


UMLS:C0520941


NCBIGene:6278

promotes invasion, aggregation and survival of

The study investigates the role of Psoriasin (S100A7), a small calcium binding protein, in pancreatic cancer progression. The research found that higher levels of Psoriasin were associated with local invasion in pancreatic cancers. Overexpression of Psoriasin led to increased growth, migration, and invasion of pancreatic cancer cells, which was linked to the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. Psoriasin also promoted aggregation and survival of pancreatic cancer cells when they lost anchorage. Therefore, Psoriasin could be a potential therapeutic target for pancreatic cancer.


NCBIGene:6278

Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9)


NCBIGene:6278


UMLS:C5454591

The study investigates the role of mutations T71N and A190T in the neuronal calcium sensor (NCS) hippocalcin, which are identified as the genetic cause of primary isolated dystonia (DYT2 dystonia). The research shows that these mutations do not affect the stability, calcium-binding affinity or translocation to cellular membranes of hippocalcin. However, they do affect the protein's ability to oligomerise and cause an increased calcium influx in KCl-depolarised cells, suggesting a central role for perturbed calcium signalling in DYT2 dystonia.


UMLS:C5454591

do not affect stability, calcium-binding affinity or translocation to cellular membranes


UMLS:C5454591


GO:0019722


UMLS:C3509741

The study investigates the impact of a common variant in the gene encoding a component of the sulfonylurea receptor (ABCC8 p.A1369S) on cardiometabolic traits, type 2 diabetes, and coronary heart disease. The variant was found to be associated with a significantly lower risk of type 2 diabetes and coronary heart disease, despite being associated with increased BMI. This suggests that long-term sulfonylurea therapy may reduce the risk of coronary heart disease, despite its known association with increased weight.


UMLS:C3509741


UMLS:C0454057


PUBCHEM.COMPOUND:12589400

The study investigates the impact of a TSPO ligand, etifoxine, on brain injury and inflammation in two mouse models of intracerebral hemorrhage (ICH). The results show that etifoxine significantly reduced neurodeficits and perihematomal brain edema after ICH induction. The protective effect of etifoxine was associated with reduced leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α. The study concludes that the TSPO ligand etifoxine attenuates brain injury and inflammation after ICH, suggesting TSPO as a potential therapeutic target for ICH.


PUBCHEM.COMPOUND:135413553

neurodeficits and perihematomal brain edema


PUBCHEM.COMPOUND:135413553

leukocyte infiltration into the brain and microglial production of IL-6 and TNF-α


PUBCHEM.COMPOUND:135413553


PUBCHEM.COMPOUND:22833602

The study investigates the role of prostaglandin A2 (PGA2) in modulating vascular endothelial function. The findings reveal that PGA2 enhances the endothelial cell barrier and protects against dysfunction caused by thrombin and lipopolysaccharide (LPS). The study identifies EP4 as a novel PGA2 receptor that mediates these protective effects by activating various targets at cell adhesions and cytoskeleton. PGA2 also suppresses LPS-induced inflammatory signaling by inhibiting the NFκB pathway. In vivo, PGA2 was found to be protective in two models of acute lung injury. These protective effects were absent in mice with endothelial-specific EP4 knockout, suggesting a critical role for the PGA2-EP4 axis in vascular endothelial cell protection.


PUBCHEM.COMPOUND:22833602


UMLS:C2936367


PUBCHEM.COMPOUND:16130139

The study investigates the impact of a specific mutation (c.474delA) in the caveolin-1 gene, found in a family with heritable pulmonary arterial hypertension (PAH). The mutation alters the final 20 amino acids of the caveolin-1 protein, which leads to an increase in fibroblast proliferation due to hyperphosphorylation of Smad1/5/8. The mutation also impairs the antiproliferative function of caveolin-1. Inhibition of type I TGFβ receptors ALK1/2/3/6, which are responsible for phosphorylation of Smad1/5/8, reduced the hyperproliferation seen in c.474delA fibroblasts. This suggests that augmented Smad signaling and fibroblast hyperproliferation are contributing factors in the pathogenesis of PAH in patients with this mutation.


PUBCHEM.COMPOUND:16130139


UMLS:C0010116


UMLS:C1435231

The study investigates the role of ubiquitin carboxyl-terminal esterase L1 (UCHL1) in pediatric high-grade gliomas, a type of aggressive brain tumor in children. The researchers found that depleting UCHL1 in glioma cells resulted in decreased cell proliferation and invasion, and a reduced ability to grow in soft agar and form spheres. This was associated with a 70% reduction in Wnt signaling. The study also identified 306 differentially expressed genes in UCHL1 knockdowns, including known cancer-related genes and potential novel genes. The findings suggest that UCHL1 may promote cell invasion, transformation, and self-renewal properties in pediatric high-grade gliomas, potentially acting as an oncogene.


UMLS:C0235425


UMLS:C1741727


UMLS:C1435231


MESH:D000074085

Summary not provided or could not be parsed.


UMLS:C4053825


PUBCHEM.COMPOUND:16133832


PUBCHEM.COMPOUND:156013414


UMLS:C1396874

The study compared 71 erysipelas patients with 55 healthy individuals to understand the relationship between erysipelas predisposition and serum cytokine levels, and the presence of single polymorphism mutations (SNPs) in CAT, SOD1, and SOD2. The study found that female patients had a higher predisposition to erysipelas, while male patients were more likely to have a facial localization of the infection. Certain alleles of SOD1, SOD2, and CAT were linked to erysipelas predisposition and the localization of the infection. Serum levels of certain cytokines were associated with symptoms, predisposition, and recurrence of erysipelas. Variations of certain cytokines were associated with the SOD2 and CAT SNPs.


UMLS:C4746438


UMLS:C0150904


UMLS:C4737127


UMLS:C5161706

Symptoms, predisposition, and recurrence of erysipelas


UMLS:C0731793

The study investigates the role of the calcium sensing receptor (CaSR) in diabetic cardiomyopathy (DCM), a major complication in diabetes patients. The researchers found that high glucose levels decrease the expression of CaSR and other proteins involved in energy metabolism, leading to a disruption in the structure and function of mitochondria and cell gap junctions. This results in reduced ATP synthesis and increased ATP leakage. However, stimulation of CaSR can significantly attenuate these effects, suggesting that CaSR could be a potential therapeutic target for DCM.


UMLS:C0731793


PR:000005058


UniProtKB:A0A812ERD0

The study reports two hemizygous mutations in the OGT gene in individuals with X-linked intellectual disability (XLID) and dysmorphic features. These mutations are a missense mutation (p.Arg284Pro) and a mutation leading to a splicing defect (c.463-6T>G). Both mutations are found in the tetratricopeptide repeats of OGT, which are essential for substrate recognition. The mutations result in slightly reduced levels of OGT protein and reduced levels of its opposing enzyme O-GlcNAcase in patient-derived fibroblasts. However, global O-GlcNAc levels appear to be unaffected. The study suggests that mutant cells attempt to maintain global O-GlcNAcylation by down-regulating O-GlcNAcase expression. The c.463-6T>G mutation leads to aberrant mRNA splicing, but no stable truncated protein was detected in the corresponding patient-derived fibroblasts. The p.Arg284Pro mutation was prone to unfolding and exhibited reduced glycosylation activity against a complex array of glycosylation substrates and proteolytic processing of the transcription factor host cell factor 1, which is also encoded by an XLID-associated gene. The study concludes that defects in O-GlcNAc homeostasis and host cell factor 1 proteolysis may play roles in mediation of XLID in individuals with OGT mutations.


UMLS:C4478313


UMLS:C0892938


UniProtKB:A0A836AU84

The study reveals that the endosomal sorting complex required for transport (ESCRT)-III, which mediates membrane fission during cytokinesis, undergoes dynamic subunit turnover. This turnover is regulated by the ATPase VPS4, which is necessary for the assembly of functional ESCRT-III structures. The study also found that the Vps2/Vps24 subunits of ESCRT-III form filaments with Snf7 and inhibit further polymerization, but this inhibition is alleviated by the addition of Vps4 and ATP. The continuous remodelling of ESCRT-III by subunit turnover may facilitate shape adaptations to variable membrane geometries, which has implications for various cellular processes.


UniProtKB:A0A8J5QEG5


NCBIGene:108604717


UniProtKB:A0A836AU84


NCBIGene:421644

The study identifies the opioid receptor μ1 (OPRM1) as a key regulator of resistance to the chemotherapy drug L-asparaginase in pediatric acute lymphoblastic leukemia (ALL). The researchers found that OPRM1 is expressed in all leukemic cells tested and its specific knockdown confers resistance to L-asparaginase. Methadone, an agonist of OPRM1, enhances the sensitivity of leukemic cells to L-asparaginase treatment, but not in OPRM1-depleted cells. This suggests that OPRM1 loss promotes leukemic cell survival likely through downregulation of the OPRM1-mediated apoptotic pathway. The study concludes that OPRM1 could be a functional biomarker for defining high-risk subpopulations and for the detection of evolving resistant clones.


PUBCHEM.COMPOUND:4095


NCBIGene:421644


MESH:D000074085

The study investigates the role of angiotensin II subtype receptor 1a (AT1a) in the formation of liver metastasis in colorectal cancer (CRC). The research used a model of liver metastasis developed by injecting mouse colon cancer into AT1a knockout mice and wild-type mice. The results showed that liver weight and metastatic rate were significantly lower in AT1a knockout mice. The study also found that the formation of liver metastasis correlated with collagen deposition in the metastatic area, which was dependent on AT1a signaling. The results suggest that resident hepatic macrophages induce liver metastasis formation by inducing TGF-β1 through AT1a signaling.


NCBIGene:59238961


UMLS:C5233078


PUBCHEM.COMPOUND:172198


NCBIGene:9229592

The study investigates the role of the oncoprotein gankyrin in hepatocellular carcinomas (HCC), a type of liver cancer often caused by chronic inflammation. The research found that gankyrin upregulates the expression of vascular endothelial growth factor in tumor cells and activates the STAT3 protein, which is involved in cell growth and division. This activation is achieved through gankyrin's interaction with SHP-1 protein, primarily found in non-parenchymal liver cells. The absence of gankyrin in these cells led to reduced STAT3 activity, lower production of interleukin (IL)-6, and decreased expression of cancer stem cell markers, thereby reducing the tumorigenic potential. The study also found that chronic inflammation increases gankyrin expression in the human liver and that high gankyrin levels in the tumor microenvironment are associated with poorer outcomes in patients treated with sorafenib for HCC. Therefore, gankyrin could be a potential target for HCC treatment and prevention strategies.


NCBIGene:9229592


UMLS:C0021376


REACT:R-BTA-3371353


UMLS:C3532504


UMLS:C1955888


UMLS:C0015193


UMLS:C0796451

The study investigates the association of a specific gene polymorphism (rs368698783) in the Aγ-globin gene with β-thalassemia, a blood disorder. The polymorphism is found to be linked with high production of fetal hemoglobin (HbF) in β-thalassemia patients, which is associated with milder or asymptomatic disease. The polymorphism is also associated with the Gγ-globin-XmnI polymorphism and both are linked with the β039-globin gene, but not with the β+IVSI-110-globin gene. The study suggests that this genetic combination has been selected within the population of β0-thalassemia patients due to its functional association with high HbF.


UMLS:C0796451


MONDO:0007736


UMLS:C2350438


NCBIGene:23299

The study investigates the role of BICD2 gene mutations in spinal muscular atrophy. The researchers found that these mutations hyperactivate the motility of the dynein-dynactin complex, which could lead to an imbalance in microtubule motility in neurons. This hyperactivity was also found to decrease neurite growth in rat hippocampal neurons, suggesting a potential mechanism for the development of spinal muscular atrophy.


NCBIGene:23299


NCBIGene:178156


PUBCHEM.COMPOUND:91976823

The study presents an inducible mouse model of podocin-mutation-related nephrotic syndrome. The model was created using a tamoxifen-inducible Cre recombinase, which allows the study of the effects of the mutation in postnatal life. The mice developed proteinuria within the first week of induction, which peaked after 4-5 weeks, and then developed progressive renal failure. The number of podocytes per glomerulus gradually diminished and severe tubulointerstitial fibrosis was present at later disease stages. The model is a valuable tool to test the efficacy of novel pharmacological interventions aimed to improve podocyte function and viability and attenuate proteinuria, glomerulosclerosis and progressive renal failure.


UMLS:C1328818


UMLS:C1831759


NCBIGene:383

The study investigates the role of arginase1 (ARG1) in the development of airway hyperresponsiveness and lung inflammation in female mice with ovalbumin-induced allergic asthma. The results show that the deletion of ARG1 does not influence the development of airway hyperresponsiveness but does reduce the expression of several genes related to arginine transport, TH2-type cytokines, chemokines, TH1-type cytokine, goblet cell markers, and OVA-specific IgE. The study also found an increase in pulmonary IL-10 protein content, but no effect on IL-4, IL-5, IL-13, TNFα and IFNγ content, and lung histopathology.


NCBIGene:383


NCBIGene:383

IL-4, IL-5, IL-13, TNFα and IFNγ content


PUBCHEM.COMPOUND:159278

The study investigates the effects of Salidroside (Sal), a compound from Rhodiola rosea, on renal interstitial fibrosis. The research used both in vivo and in vitro models, including mice with induced renal interstitial fibrosis and human proximal tubular epithelial cells. The results showed that Sal treatment improved kidney function, reduced the deposition of extracellular matrix components, and decreased the release of inflammatory cytokines. It also suppressed epithelial-mesenchymal transition and inhibited the TLR4/NF-κB and MAPK signaling pathways. These findings suggest that Sal could be a potential treatment for renal fibrosis.


PUBCHEM.COMPOUND:159278


PUBCHEM.COMPOUND:159278

Inflammatory cytokines (IL-1β, IL-6, TNF-α)


UMLS:C0672987

The study found that the chemokine receptor CCR7 is elevated in knee osteoarthritis (OA) patients. Using a murine model of OA, the researchers found that deficiency of CCR7 led to a delay in the development of joint damage and functional deficits. The CCR7-deficient mice showed a reduction in locomotor activities and were protected from early cartilage degeneration and subchondral bone changes. These findings suggest that CCR7 plays a role in the early development of functional deficits and subchondral bone changes in OA.


NCBIGene:1236


MONDO:0005178

The paper reviews recent and ongoing trials for pain management in osteoarthritis (OA). It identifies three categories of therapies: biological therapies, small molecules, and cryoneurolysis. The most promising strategy is the blockade of nerve growth factor with antibodies, specifically tanuzemab and fasinumab. Other interventions being tested include cytokine inhibition, selective opioid receptor agonists, zoledronate, and intra-articular capsaicin. Cryoneurolytic strategies that target peripheral nerves are also being considered, but their long-term effects need further study. The challenge lies in identifying which patients will benefit most from specific approaches.


UMLS:C0027752


UMLS:C0005527


MONDO:0008143

The study focuses on the mechanisms and mediators contributing to the pain associated with Osteoarthritis (OA), a common form of arthritis. The pain from OA is often resistant to traditional analgesics and there are no disease-modifying therapies available. The study suggests that both peripheral and central mechanisms contribute to OA pain. Mediators such as nerve growth factor, chemokines, cytokines, and inflammatory cells can contribute to sensitization. Structural alterations in joint innervation and nerve damage also occur in OA. The study suggests that understanding these mechanisms could lead to the identification of new targets for intervention.


UMLS:C1371833


UMLS:C0243042


UMLS:C0021516


EFO:0005413