Objective: To investigate the potential protective effect of Shexiang Tongxin dropping pills (STDP) on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease (CMVD). Methods: A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery. The effect of STDP (21.6 mg/kg) on cardiac function was evaluated using echocardiography, hematoxylin-eosin staining, and Evans blue staining. The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production, endothelial nitric oxide synthase expression, structural variety of tight junctions (TJs), and the expression of zonula occludens-1 (ZO-1), claudin-5, occludin, and vascular endothelial (VE)-cadherin proteins. The mechanisms of STDP (50 and 100 ng/mL) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2 (S1PR2), Ras Homolog family member A (RhoA), and Rho-associated coiled-coil-containing protein kinase (ROCK) proteins and the distribution of ZO-1, VE-cadherin, and F-actin proteins in an oxygen and glucose deprivation/reoxygenation model. Results: The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions (all P < .05). STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1, occludin, claudin-5, and VE-cadherin in vivo (all P < .05). The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro, leading to the regulation of endothelial cell TJs, adhesion junctions, and cytoskeletal morphology. Conclusion STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

N-glycosides comprise a broad range of compounds, some of which have demonstrated a variety of bioactivities, such as antiviral, antitumor, and antibacterial activities. Serving as essential building blocks for DNA and RNA, nucleosides are a particularly important subclass of N-glycosides. Accordingly, natural N-glycosides and their analogs have garnered great interests of both organic and pharmaceutical chemists, who have developed numerous synthetic methods for the preparation of N-glycosides. By reviewing the natural N-glycosides published between 1980 and 2023, this article summarizes current strategies for synthesizing N-glycosides, aiming to provide support for the development and research of N-glycosides.

Platelet to lymphocyte ratio (PLR) is a prognostic marker in human hepatocellular carcinoma (HCC) however, its utility in canine HCC has not been explored. The aim of the study was to determine if PLR could predict survival outcomes in 42 dogs with HCC. PLR was not a significant predictive factor (p = 0.15) but lymphopenia alone was significantly correlated with a reduced probability of survival (p = 0.024). Further studies are needed to evaluate if peripheral lymphocyte count mirrors that of the tumor microenvironment in canine HCC.

During the development of therapeutic microRNAs (miRNAs or miRs), it is essential to define their pharmacological actions. Rather, miRNA research and therapy mainly use miRNA mimics synthesized in vitro. After experimental screening of unique recombinant miRNAs produced in vivo, three lead antiproliferative miRNAs against human NSCLC cells, miR-22-3p, miR-9-5p, and miR-218-5p, were revealed to target folate metabolism by bioinformatic analyses. Recombinant miR-22-3p, miR-9-5p, and miR-218-5p were shown to regulate key folate metabolic enzymes to inhibit folate metabolism and subsequently alter amino acid metabolome in NSCLC A549 and H1975 cells. Isotope tracing studies further confirmed the disruption of one-carbon transfer from serine to folate metabolites by all three miRNAs, inhibition of glucose uptake by miR-22-3p, and reduction of serine biosynthesis from glucose by miR-9-5p and -218-5p in NSCLC cells. With greater activities to interrupt NSCLC cell respiration, glycolysis, and colony formation than miR-9-5p and -218-5p, recombinant miR-22-3p was effective to reduce tumor growth in two NSCLC patient-derived xenograft mouse models without causing any toxicity. These results establish a common antifolate mechanism and differential actions on glucose uptake and metabolism for three lead anticancer miRNAs as well as antitumor efficacy for miR-22-3p nanomedicine, which shall provide insight into developing antimetabolite RNA therapies.

Background: and Purpose The optimal management of patients with acute basilar artery occlusion (BAO) is uncertain. We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) compared to medical management (MM) for acute BAO through a meta-analysis of randomized controlled trials (RCTs). Methods: We performed a systematic review and meta-analysis of RCTs of patients with acute BAO. We analyzed the pooled effect of EVT compared to MM on the primary outcome (modified Rankin Scale [mRS] of 0–3 at 3 months), secondary outcome (mRS 0–2 at 3 months), symptomatic intracranial hemorrhage (sICH), and 3-month mortality rates. For each study, effect sizes were computed as odds ratios (ORs) with random effects and Mantel-Haenszel weighting. Results: Four RCTs met inclusion criteria including 988 patients. There were higher odds of mRS of 0-3 at 90 days in the EVT versus MM group (45.1% vs. 29.1%, OR 1.99, 95% confidence interval [CI] 1.04–3.80; P=0.04). Patients receiving EVT had a higher sICH compared to MM (5.4% vs. 0.8%, OR 7.89, 95% CI 4.10–15.19; P<0.01). Mortality was lower in the EVT group (35.5% vs. 45.1%, OR 0.64, 95% CI 0.42–0.99; P=0.05). In an analysis of two trials with BAO patients and National Institutes of Health Stroke Scale (NIHSS) <10, there was no difference in 90-day outcomes between EVT versus MM. Conclusion In this systematic review and meta-analysis, EVT was associated with favorable outcome and decreased mortality in patients with BAO up to 24 hours from stroke symptoms compared to MM. The treatment effect in BAO patients with NIHSS <10 was less certain. Further studies are of interest to evaluate the efficacy of EVT in basilar occlusion patients with milder symptoms.

Background: and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. Methods: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. Results: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). Conclusion In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.