Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer.

PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes. PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS). CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.

Phase II, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial Investigating the Efficacy of Mebendazole in the Management of Symptomatic COVID-19 Patients.

The outbreak of the COVID-19 pandemic has spread throughout the world, affecting almost all nations and territories. The current double-blind, randomized, placebo-controlled, phase II clinical trial sought to evaluate the clinical efficacy and safety of mebendazole as an adjuvant therapy for outpatients with COVID-19. The patients were recruited and divided into two groups: a Mebendazole-treated group and placebo group. The mebendazole and placebo groups were matched for age, sex, and complete blood count (CBC) with differential and liver and kidney function tests at baseline. On the third day, the C-reactive protein (CRP) levels were lower (2.03 ± 1.45 vs. 5.45 ± 3.95, p < 0.001) and the cycle threshold (CT) levels were higher (27.21 ± 3.81 vs. 24.40 ± 3.09, p = 0.046) significantly in the mebendazole group than in the placebo group on the third day. Furthermore, CRP decreased and CT dramatically increased on day three compared to the baseline day in the mebendazole group (p < 0.001 and p = 0.008, respectively). There was a significant inverse correlation between lymphocytes and CT levels in the mebendazole group (r = -0.491, p = 0.039) but not in the placebo group (r = 0.051, p = 0.888). Mebendazole therapy increased innate immunity and returned inflammation to normal levels in COVID-19 outpatients faster than it did in the placebo group in this clinical trial. Our findings add to the growing body of research on the clinical and microbiological benefits of repurposing antiparasitic therapy, specifically mebendazole, for SARS-CoV-2 infection and other viral infections.

Fungal-Mediated Silver Nanoparticle and Biochar Synergy against Colorectal Cancer Cells and Pathogenic Bacteria.

BACKGROUND: Silver nanoparticles (AgNPs) are attractive substrates for new medicinal treatments. Biochar is pyrolyzed biomass. Its porous architecture allows it to hold and gather minuscule particles, through which nanoparticles can accumulate in its porous structure. This study examined AgNPs' antibacterial and anticancer properties alone and combined with biochar. METHODS: The fungus Emericella dentata was responsible for biosynthesis of AgNPs. The characterization of AgNPs using STEM images and a Zetasizer was carried out. Accordingly, the antibacterial and antiproliferation activity of AgNPs and biochar was studied using MIC and MTT assays, respectively. To evaluate the antiangiogenic and anti-inflammatory effects of AgNPs with biochar, VEGF and cytokines including TNF alpha, IL-6 and IL-beta were tested using an ELISA assay. RESULTS: The size of the AgNPs ranged from 10 to 80 nm, with more than 70% of them being smaller than 40 nm. The combination of AgNPs and biochar enhanced the antibacterial activity against all tested bacteria. Furthermore, this combination showed antiproliferative properties against HT29 cancer cells with high selectivity to fibroblasts at low concentrations. AgNPs with biochar significantly reduced VEGF and proinflammatory cytokine expression levels. CONCLUSIONS: Biochar and AgNPs may be novel treatments for bacteria and colorectal cancer cells, according to the current findings.

Prognostic performance of combined use of high-sensitivity troponin T and creatine kinase MB isoenzyme in high cardiovascular risk patients with end-stage renal disease.

BACKGROUND: The principal goal of this study was to determine the importance of high-sensitivity troponin T (hs-TnT) and creatine kinase MB isoenzyme (CK-MB) in predicting cardiovascular events in asymptomatic end-stage renal disease (ESRD) patients. METHODS: This study included 110 participants; 54 ESRD patients undergoing hemodialysis and 56 healthy control participants. Biochemical parameters and cardiac markers were estimated. Comparative utilities were assessed through logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: We found that 96.3% of ESRD patients had an elevated level of hs-TnT (mean, 0.049 ± 0.0324 µg/L) compared to healthy participants. Among patients with ESRD, hs-TnT showed significant correlations with the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (HDL-C) (P = 0.042, r = 0.278) and total cholesterol/HDL-C (P = 0.044, r = 0.276) ratios. CK-MB (odds ratio [OR], 1.138; P = 0.04) and hs-TnT (OR, 2.153; P = 0.017) predicted cardiovascular events on logistic regression analysis, and the prediction was improved by the model that combined two cardiac markers. The diagnostic performance of hs-TnT and CK-MB alone and the combination of the two biomarkers was assessed by the area under the ROC curve (AUC). The highest AUC was produced by the combination of hs-TnT and CK-MB markers (0.920) compared to hs-TnT or CK-MB alone. CONCLUSION: In asymptomatic patients with ESRD, hs-TnT appeared to be an important predictor for cardiovascular mortality, and its diagnostic accuracy improved with CK-MB. This study provides new insights into the predictive value of multiple biomarkers for identifying cardiovascular events in ESRD patients on hemodialysis.