Taoli Liu

Objective: To evaluate the effect of modified fasting therapy on blood pressure in dysglycemic adults and to examine the mediating role of weight loss and modifying effects of age, sex, and baseline glycemic status. Methods: This retrospective cohort study included 833 dysglycemic adults who underwent modified fasting therapy. Blood pressure, body weight, and laboratory parameters were measured before and after the intervention. Linear mixed models were used to estimate the effect of fasting on systolic blood pressure (SBP) and diastolic blood pressure (DBP), with adjustment for age, sex, baseline body mass index (BMI), glycosylated hemoglobin (HbA1c), and baseline blood pressure. Mediation analyses were performed using “MEMORE macro” and “wsMed” package to examine the mediating role of weight loss. Interaction terms were included to test effect modification by age, sex, and baseline HbA1c. Results: Fasting therapy significantly reduced SBP (−7.73 mmHg, 95% CI: −8.64 to −6.82, p < 0.001) and DBP (−4.76 mmHg, 95% CI: −5.39 to −4.12, p < 0.001). Mediation analyses revealed that weight loss did not significantly mediate the blood pressure-lowering effect for either SBP (indirect effect: −0.22, p = 0.588) or DBP (indirect effect: 0.09, p = 0.636). The fasting effect was significantly modified by age, sex, and baseline HbA1c, with greater reductions observed in younger patients, males, and those with higher HbA1c levels. Conclusions: Modified fasting therapy significantly reduces blood pressure in dysglycemic adults independent of weight loss. Age, sex, and baseline HbA1c modify the response, suggesting that personalized approaches may optimize the benefits of fasting-based interventions.

Objective: Bladder cancer (BC) is a highly prevalent malignant tumor. The traditional Chinese medicine formula Guo Lou Qu Mai Wan (GLQMW), when used in conjunction with chemotherapy, has been shown to reduce adverse reactions and prolong survival time, although its specific mechanisms remain unclear. This study aims to investigate whether GLQMW exerts its therapeutic effects on bladder cancer by modulating the tumor immune microenvironment. Methods: To elucidate the molecular mechanisms of GLQMW, we employed bioinformatics analysis, systems pharmacology, and molecular docking to explore the prognostic value of GLQMW-related target genes for BC and to establish a prognostic prediction model. We analyzed the relationship between GLQMW-related target genes and immune cell infiltration, as well as the compositional differences of immune cell subpopulations across different risk groups. Molecular docking was used to screen for pachymic acid (PA) as the main anticancer active compound, and CCK8 and western blot were used to determine the target of PA as the active compound. Result: In our immune infiltration analysis, the expression levels of five genes (MAPK12, MAN1B1, EGFR, FABP6, and ZAP70) were found to be associated with immune cells. Moreover, a higher presence of naïve B cells, plasma cells, CD8+ T cells, and Tregs was observed in the low-risk group, indicating that GLQMW can significantly impact the immune microenvironment by targeting these five model genes, thereby exerting therapeutic effects. In the single-cell data analysis, our results demonstrated that the percentage of CD8 T+ cells and plasma cells in tumor tissue was significantly lower than that in adjacent non-tumor tissue. In addition, through drug similarity analysis and molecular docking, we identified PA as a potential anti-tumor compound. Furthermore, PA was validated in vitro to upregulate FABP6 and downregulate EGFR expression and suppress the bladder cancer progression in vivo . Conclusions: PA, the active ingredient of GLQMW, can inhibit BC by inhibiting EGFR and upregulating FABP6.

Welcome to ProBiologists | ProBiologists International Open Access Journals

Background: Ginsenoside Rc has been known for its promising protective effects against myocardial injury, including inflammation, apoptosis, oxidative stress, and related pathways. However, the underlying molecular mechanisms behind these effects still need to be explored. The purpose of this study was to explore the therapeutic effect of Ginsenoside Rc on acute myocardial infarction (MI) and the molecular mechanism behind it. Methods: MI mouse model and oxygen-glucose deprivation (OGD) cardiomyocyte injury model were established and Ginsenoside Rc was treated. Troponin I3 (TNNI3)/C-reactive protein (CRP) expression was altered by plasmid transfection or lentiviral vector injection. Myocardial histopathological changes were evaluated by hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling (TUNEL) staining. The changes in inflammatory cytokines in cells and tissues were evaluated by enzyme-linked immunosorbent assay (ELISA). Commercial kits were used for the assessment of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH). Western blot was used to analyze cleaved caspase-3 protein expression in cells and tissues. The apoptosis rate of cardiomyocytes was measured by flow cytometry. The interaction between TNNI3 and CRP was detected by co-immunoprecipitation (CO-IP) assay. Results: TNNI3/CRP expression was abnormally high in MI, and Ginsenoside Rc decreased their relative expression (p < 0.05). Ginsenoside Rc administration reduced inflammation and apoptosis in MI mice and OGD-injured cardiomyocytes (p < 0.05). Ginsenoside Rc administration or TNNI3 knockdown improved the myocardial tissue injury in MI mice (p < 0.05). The therapeutic effect of Ginsenoside Rc on myocardial injury in MI mice was weakened by overexpressing TNNI3 (p < 0.05). Similarly, its therapeutic effect on OGD cardiomyocyte injury was also weakened by enhancing TNNI3 and CRP (p < 0.05). TNNI3 and CRP also interacted in cardiomyocytes. Conclusions: Ginsenoside Rc improves MI-induced cardiomyocyte apoptosis and inflammation by inhibiting the TNNI3/CRP axis. The study shows that Ginsenoside Rc can serve as a potential drug for the future treatment of MI.

Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells. Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial–mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5. Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, β-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins. Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells’ proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC.