Future Science OA最新文献

Objective: Transcriptome and proteome analyses may yield inconsistent predictions regarding tumor prognosis. The clinical and pathological significance of ASPM expression in lung adenocarcinoma (LUAD) remains unclear. This study investigates the expression and prognostic value of ASPM, focusing on its role in chemotherapy outcomes.

Methods: We analyzed the prognostic relevance of ASPM using bioinformatics, immunohistochemical staining of LUAD tissue microarrays, and proteomics data. Further, in vitro experiments were conducted to evaluate the effects of ASPM overexpression on cell proliferation and sensitivity to cisplatin.

Results: Bioinformatics analysis revealed that ASPM's prognostic significance differed between transcriptomic and proteomic datasets. Immunohistochemistry showed that high ASPM expression predicted improved overall survival only in LUAD patients undergoing chemotherapy, not in those without. Proteomics analysis identified ASPM-related signatures enriched in cell cycle and mitosis pathways. In vitro, ASPM overexpression promoted tumor cell proliferation and enhanced cisplatin-induced cytotoxicity.

Conclusion: ASPM exhibits a dual role in LUAD prognosis, acting as a marker for improved chemotherapy outcomes while promoting tumor proliferation. These findings underscore ASPM's potential as a therapeutic target and predictive marker for personalized treatment in LUAD.

Protein kinases are vital drug targets, yet designing selective inhibitors is challenging, compounded by resistance and kinome complexity. This review explores Quantitative Structure-Activity Relationship (QSAR) modeling for kinase drug discovery, focusing on integrating traditional QSAR with machine learning (ML)-CNNs, RNNs-and structural data. Methods include structural databases, docking, and deep learning QSAR. Key findings show ML-integrated QSAR significantly improves selective inhibitor design for CDKs, JAKs, PIM kinases. The IDG-DREAM challenge exemplifies ML's potential for accurate kinase-inhibitor interaction prediction, outperforming traditional methods and enabling inhibitors with enhanced selectivity, efficacy, and resistance mitigation. QSAR combined with advanced computation and experimental data accelerates kinase drug discovery, offering transformative precision medicine potential. This review highlights deep learning-enhanced QSAR's novelty in automating feature extraction and capturing complex relationships, surpassing traditional QSAR, while emphasizing interpretability and experimental validation for clinical translation.

Background: Currently, the pathogenesis of depression remains poorly understood, leading to many patients receiving ineffective treatment. Resveratrol has demonstrated beneficial effects in the prevention and treatment of depression. However, it remains unknown whether resveratrol administration can counteract depression-like behaviors by regulating the SIRT1/NF-κB signaling pathway.

Methodology/principal findings: Male C57BL/6 mice were randomly assigned to a control group, a depression group, and a resveratrol group. The depression model was established using chronic unpredictable mild stress (CUMS) for 5 weeks. Behavioral tests were conducted to assess depressive-like behaviors. The expression levels of SIRT1 and NF-κB in the hippocampus of mice and BV2 microglial cells were measured. After 5 weeks of modeling, the results indicated that mice in the depression group exhibited significant depressive-like behaviors and inhibited activation of the SIRT1/NF-κB signaling pathway. In contrast, resveratrol administration effectively reversed these changes. Results from in vitro experiments showed that LPS stimulation increased microglial activity and downregulated the SIRT1/NF-κB signaling pathway in microglia; however, resveratrol treatment mitigated these effects.

Conclusions/significance: Our findings suggested that resveratrol can alleviate CUMS-induced depression-like behaviors via the activation of the Sirt1/NF-κB pathway in microglia.

Migraine is a common condition that can cause intense headaches, often on one side of the head, along with symptoms like nausea and sensitivity to light and sound. These headaches can be triggered by various factors, including stress, changes in hormones, sleep disturbances, diet, and even gut health. Migraines are more frequent in women, particularly those under 45, and this may be linked to hormones. After age 45, this difference between men and women becomes less noticeable. Women tend to experience migraines that are more severe and last longer than men, with menstrual migraines affecting about 22% of women during nearly half of their menstrual cycles, and 7.6% of women with migraines. Treatments for migraines include medications, lifestyle changes, and alternative therapies, all of which aim to address the different ways migraines can affect people. This review explores these aspects in detail.

Introduction: Microdissection testicular sperm extraction (micro-TESE) is the preferred sperm retrieval method, although success rates vary based on factors such as age and hormone levels. We evaluate sperm retrieval outcomes in first-time and repeated micro-TESE, identifying predictors of success to guide clinical management.

Material and methods: Retrospective study analyzed 152 men with nonobstructive azoospermia (NOA) who underwent micro-TESE between 2020 and 2022. Patients were grouped based on sperm retrieval outcomes, and clinical, demographic and hormonal factors were assessed. Comparisons were made between first-time and repeat micro-TESE cases.

Results: Sperm retrieval rate was higher for first-time TESE cases (64.6%) than repeated TESE cases (28.8%, p < 0.01). Repeated TESE cases were older, had higher smoking rates, and exhibited significantly elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, with lower total testosterone (p < 0.01). In repeated TESE cases, no significant differences in age, smoking status or hormone levels were found between successful and failed attempts.

Conclusion: First-time micro-TESE users had a significantly higher sperm retrieval rate than those undergoing repeated attempts. Repeated TESE was associated with older age, higher smoking rates and adverse hormonal profiles. Larger studies are needed to validate these findings and optimize patient selection for repeated micro-TESE.

Background: Low-intensity extracorporeal shockwave therapy (Li-ESWT) is proposed for the treatment of erectile dysfunction (ED).

Materials and methods: Randomized controlled trials (RCTs) that compared Li-ESWT with sham therapy in patients with vasculogenic ED were included. The International Index of Erectile Function - Erectile Function (IIEF-EF) domain score, increase in the Erection Hardness Score (EHS), and improvement in Sexual Encounter Profile (SEP) 2 and SEP-3 were assessed.

Results: This meta-analysis of 12 RCTs, including 882 men with vasculogenic ED, demonstrated a statistically significant improvement in IIEF-EF score (an improvement from baseline as well as MCID) and EHS (patients with EHS ≥ 3) following LI-ESWT compared to sham therapy.

Conclusion: The results support the role of Li-ESWT as a potential treatment for ED.

Background: The COVID-19 pandemic led to a surge in published medical literature, making it essential for physicians to critically assess and identify credible, peer-reviewed information.

Aim: This study aimed to evaluate the attitudes and knowledge of physicians and trainees regarding medical literature reading.

Methods: A cross-sectional study was conducted among 156 participants (mean age = 30.65 years) at LAU Medical Center-Rizk Hospital, including medical students, research fellows, residents, and attending physicians. Participation was anonymous. Descriptive statistics, chi-square tests, and Spearman's rank correlation were used for data analysis.

Results: Among the 156 participants (42% male, 57% female), attending physicians reported a higher average of weekly reading hours (2.95 hours) compared to medical students (2.10 hours). A weak positive correlation was found between age and reading time (Spearman's rho = 0.30, p < 0.05). Gender did not influence reading behaviors, as similar trends were observed across male and female participants. Additionally, no significant effect of clinical experience on reading time was noted.

Conclusion: This study highlights variations in reading practices among physicians and trainees. Further research is needed to explore influencing factors and address study limitations.

Aim: This study aimed to investigate the association between CA9 expression and the immune infiltration and prognosis of CC.

Materials & methods: The GSE9750 dataset in the GEO database, the UALCAN database, and the cBioPortal of cervical squamous cell carcinoma study were used for bioinformatic analysis, followed by validation via immunohistochemistry in clinical samples.

Results: Compared to normal controls, CC samples showed 1175 significantly downregulated and 698 significantly upregulated genes, respectively. Specifically, CA9 was identified among the up-regulated genes, with verification by analysis of TCGA data. The overexpression of CA9 in CC was further confirmed in clinical samples. The protein-protein interaction network results revealed that CA9 was closely associated with 12 genes, which were widely involved in cancer-related processes such as cell proliferation, migration, and metabolism. CA9 was associated with tumor histological subtypes, hypoxia scores, low immune infiltration, poor survival rate, and specific microorganisms.

Conclusion: Our study indicated that CA9 was upregulated in CC and closely related to tumor immune microenvironment, thereby becoming an important prognostic factor for CC. This study highlights CA9 as a potential diagnostic and therapeutic target for the disease.

Aim: To compare several laboratory results, including liver function, lipid metabolism (HDL), pulmonary function, and hematological parameters among COVID-19 recovered patients who were divided into two groups (asymptomatic/mild vs. moderate/severe).

Method: The sample consisted of patients matched by age and gender. These patients were divided into two groups. The first group consisted of mild or mild cases, and the second group included moderate and severe cases, classified based on their need for oxygen. Blood samples were collected from all participants, and analyses for complete blood count, liver function markers, kidney function markers, and lipid profiles were conducted at the Health Center of Jordan University of Science and Technology and King Abdullah University laboratories.

Results: The analysis revealed Significant differences were noted in ALT (p = 0.002), DBC (p = 0.005), HDL (p = 0.035), Notably, the Forced Vital Capacity (FVC) showed a significant difference (F = 6.292, p = 0.012). The FEV1/FVC ratio was also highly significant (F = 45.054, p = 0.000).

Conclusion: In this descriptive cohort study, the results indicating that specific biomarkers, such as elevated WBC and liver enzymes, are significantly associated with severe post-COVID outcomes. These findings highlight the systemic impact of the disease in severe cases, affecting multiple or one organ.