Integrated analysis identifies GABRB3 as a biomarker in prostate cancer.

BACKGROUND: Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer. METHODS: We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer. RESULTS: After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer. CONCLUSION: Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted.

Relapsing polychondritis with isolated tracheobronchial involvement complicated with Sjogren's syndrome: A case report.

BACKGROUND: Relapsing polychondritis (RP) is a rare, long-term, and potentially life-threatening disease characterised by recurrent paroxysmal inflammation that can involve and destroy the cartilage of the external ear, nose, larynx, and trachea. CASE SUMMARY: We here report a case of RP involving solely the tracheobronchial cartilage ring (and not the auricular. nasal or articular cartilage) complicated by Sjögren's syndrome in a 47-year-old female whose delayed diagnosis caused a sharp decline in pulmonary function. After corticosteroid treatment, her pulmonary function improved. CONCLUSION: In such cases, our experience suggested that 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and fiberoptic bronchoscopy should be used to diagnose airway chondritis as relapsing polychondritis in the early phase of disease.

Complete mitochondrial genome sequence and mutations of the Glioma model inbred C57BL/6 mice strain.

In the present work we undertook the complete mitochondrial genome sequencing of an important glioma model inbred rat strain for the first time. The total length of the mitogenome was 16,308 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region (D-loop region). The mutation events were also reported.

Computational study of estrogen receptor-alpha antagonist with three-dimensional quantitative structure-activity relationship, support vector regression, and linear regression methods.

Human estrogen receptor (ER) isoforms, ERα and ERß, have long been an important focus in the field of biology. To better understand the structural features associated with the binding of ERα ligands to ERα and modulate their function, several QSAR models, including CoMFA, CoMSIA, SVR, and LR methods, have been employed to predict the inhibitory activity of 68 raloxifene derivatives. In the SVR and LR modeling, 11 descriptors were selected through feature ranking and sequential feature addition/deletion to generate equations to predict the inhibitory activity toward ERα. Among four descriptors that constantly appear in various generated equations, two agree with CoMFA and CoMSIA steric fields and another two can be correlated to a calculated electrostatic potential of ERα.

3,5-Diaryl-1H-pyrazole as a molecular scaffold for the synthesis of apoptosis-inducing agents.

The scaffold of 3,5-diaryl-1H-pyrazole was selected as a molecular template to synthesize novel growth-inhibitory agents in the present study. Our findings suggested that analogs bearing electron-withdrawing groups on one ring while electron-donating groups on another reveal significant activities. In particular, 26 bearing a 1,1'-biphenyl moiety displayed the most potent activity against OVCA, SW620, H460 and AGS cells with GI(50) values of 0.67, 0.89, 0.73 and 0.79 microM, respectively. The mechanistic study revealed that 26-mediated apoptosis-inducing effect on OVCA cells was, in part, attributed to the inhibition of protein kinase B/Akt activity, accompanied by the mitochondrial apoptotic pathway through the activation of caspase-9, caspase-3, as well as the cleavage of protein poly(ADP-ribose) polymerase (PARP) and DNA fragmentation. Further structure-activity relationship study employed by Comparative Molecular Field Analysis (CoMFA) was carried out with q(2) and R(2) values of 0.671 and 0.846, respectively.