Future Science OA最新文献

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.

Aim: The primary objective of this study is to investigate the impact of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its functional receptor, fibroblast growth factor-inducible 14 (Fn14), on the process of vascular smooth muscle cell (VSMC) senescence.

Methods: Rat arterial VSMCs were cultured with angiotensin II to establish a model of premature senescence. The effects of TWEAK and Fn14 on senescent VSMCs were evaluated. Additionally, the role of p38 phosphorylation pathway in the effect of TWEAK on VSMCs senescence was assessed.

Results: Expressions of TWEAK and Fn14 were significantly elevated in senescent VSMCs. TWEAK activated the p38 phosphorylation pathway and promoted the SA-β-gal staining and P53 expression.

Conclusion: These preliminary findings suggest that the TWEAK/Fn14 axis may play a crucial role in promoting VSMC senescence.

Introduction: Alzheimer's disease is a developing public health concern in aging communities that affects a sizable section of the global population. The risk of Alzheimer's disease increases with age; it affects one-third of males and two-thirds of women^. This research attempts to assess the effect of nano-selenium and thymoquinone on Nrf2 gene expression levels in Alzheimer's disease (AD).

Methods: There were five identical groups of 50 albino male rats: a control group that was healthy; an AD positive control group; an AD group that received nano-selenium (5 mg/kg); an AD group that received thymoquinone (2 mg/kg); and an AD group that received both. The duration of treatment was 4 weeks. The levels of Nrf2 in brain tissues were evaluated using real-time PCR.

Results: Nrf2 mean expression levels in the nano-selenium-treated rats, the thymoquinone-treated rats, and the rats that were given both treatments all increased significantly compared to AD rats with no treatment.

Conclusions: This study showed that nano-selenium and thymoquinone elevated Nrf2 gene expression levels in AD.

Background: Including racial and ethnic minorities in clinical trials is essential for advancing health equity. Despite progress, trials often do not mirror patient population demographics.

Methods: The National Library of Medicine's Clinical Trials database was queried for phase III trials of lung, colorectal, breast, and prostate cancers. A reference population was identified from the Surveillance, Epidemiology, and End Result (SEER) database, covering 48% of the US population.

Results: Among 181 trials, race and ethnicity data were included in 86.7% and 60.2% of trials, respectively, with improving reporting over time. Participants were predominantly White (76.3%), followed by Asian/Pacific Islander (14.1%), Black/African American (4.5%), and American Indian/Alaska Native (0.6%). Hispanic/Latino constituted 6.4% of participants. The proportion of non-White groups increased from 19.4% in trials started before 2011 to 26.2% after 2015. Compared with SEER data, the percentages were lower for Asian/Pacific Islander across all cancers, Black/African American in breast and prostate cancers, American Indian or Alaska Native in colorectal, breast, and prostate cancers in US solely trials.

Conclusions: Reporting and enrollment of racial and ethnic minorities in trials remain inadequate but improving. To enhance diversity, real-world data are warranted to identify recruitment goals by better assessing the geographic distribution within the patient population.

Background: Shoulder dystocia, a challenging condition for obstetricians, poses significant risks to both maternal and neonatal health, including maternal postpartum hemorrhage, neonatal hypoxia, and brachial plexus injury. Despite being unpredictable and unpreventable, effective management can mitigate these risks. Miscommunication and poor leadership are responsible for 72% of medical errors, which further highlights the importance of robust leadership skills in obstetric emergencies.

Research design and methods: A qualitative study involving 20 participants through structured interviews assessed preferred leadership styles in managing shoulder dystocia.

Results: Findings revealed that 55% of participants favored quantum leadership. Other preferences included laissez-faire by one anesthesiologist and democratic by two midwives. However, all participants acknowledged the efficacy of the seven quantum leadership skills in managing shoulder dystocia. Discussion emphasized that traditional leadership styles are less effective compared to quantum leadership in managing the complexities of shoulder dystocia. The quantum Ob-Wheel, consisting of 12 milestones, integrates these seven interdependent skills to guide the management process.

Conclusions: Despite the limited sample size of this study, it is worth noting that, given the unpredictable nature of shoulder dystocia, clinicians should be prepared for its occurrence during any birth, with quantum leadership providing a strategic advantage in such scenarios.

Introduction: CHA2DS2-VASc and CHA2DS2-VA scores are often used to demonstrate thromboembolic risk in nonvalvular atrial fibrillation. Elevated whole blood viscosity is an independent risk factor for ischemic stroke.

Objective: This study aimed to ascertain the correlation between whole blood viscosity and CHA2DS2-VASc/CHA2DS2-VA scores.

Methods: This study was performed retrospectively in a tertiary cardiac facility, encompassing 150 patients.

Results: The study's results demonstrate that whole blood viscosity, concerning both high shear rate and low shear rate variables, are statistically significant in forecasting the likelihood of elevated CHA2DS2-VA and CHA2DS2-VASc scores. (AUC: 0.690, 0.693; p: <0.001; 0.647, 0.665; p: <0.05).

Conclusion: Whole blood viscosity had a substantial correlation with the CHA2DS2-VASc/CHA2DS2-VA scores in patients with atrial fibrillation and may be used to evaluate thromboembolism risk, akin to these scores.

Purpose: Intracameral phenylephrine 1.0%/ketorolac 0.3% (OMIDRIA^®) is used during cataract surgery to prevent intraoperative miosis and reduce postoperative pain. Although studied in beagles, no human data exist showing the duration ketorolac remains in the eye postoperatively. A clinical trial measuring ketorolac concentrations in aqueous/vitreous samples necessitated the development of a validation process for acquiring these measurements. Due to limited human aqueous/vitreous humor sample availability, a bioanalytical method was developed and validated to quantify ketorolac levels using human plasma as a surrogate matrix.

Methods: The developed process involves extracting ketorolac and its internal standard (ketorolac-d5) from plasma as a surrogate for aqueous and vitreous humor using a protein precipitation sample preparation technique, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.

Results: The validated method can be successfully applied for quantitation of ketorolac over a concentration range of 2.5 ng/mL to 5000 ng/mL. The method met the acceptance criteria with respect to selectivity, specificity, precision, accuracy, linearity, dilution integrity, and stability.

Conclusions: The validated method can use plasma as a surrogate matrix for quantitation of ketorolac in aqueous and vitreous humor, thereby eliminating the need to procure human vitreous and aqueous samples for validation prior to initiation of a clinical trial.