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.

Effect of Aerobic Exercise Training and Deconditioning on Oxidative Capacity and Muscle Mitochondrial Enzyme Machinery in Young and Elderly Individuals.

Mitochondrial dysfunction is thought to be involved in age-related loss of muscle mass and function (sarcopenia). Since the degree of physical activity is vital for skeletal muscle mitochondrial function and content, the aim of this study was to investigate the effect of 6 weeks of aerobic exercise training and 8 weeks of deconditioning on functional parameters of aerobic capacity and markers of muscle mitochondrial function in elderly compared to young individuals. In 11 healthy, elderly (80 ± 4 years old) and 10 healthy, young (24 ± 3 years old) volunteers, aerobic training improved maximal oxygen consumption rate by 13%, maximal workload by 34%, endurance capacity by 2.4-fold and exercise economy by 12% in the elderly to the same extent as in young individuals. This evidence was accompanied by a similar training-induced increase in muscle citrate synthase (CS) (31%) and mitochondrial complex I-IV activities (51-163%) in elderly and young individuals. After 8 weeks of deconditioning, endurance capacity (-20%), and enzyme activity of CS (-18%) and complex I (-40%), III (-25%), and IV (-26%) decreased in the elderly to a larger extent than in young individuals. In conclusion, we found that elderly have a physiological normal ability to improve aerobic capacity and mitochondrial function with aerobic training compared to young individuals, but had a faster decline in endurance performance and muscle mitochondrial enzyme activity after deconditioning, suggesting an age-related issue in maintaining oxidative metabolism.

Preserved Capacity for Adaptations in Strength and Muscle Regulatory Factors in Elderly in Response to Resistance Exercise Training and Deconditioning.

Aging is related to an inevitable loss of muscle mass and strength. The mechanisms behind age-related loss of muscle tissue are not fully understood but may, among other things, be induced by age-related differences in myogenic regulatory factors. Resistance exercise training and deconditioning offers a model to investigate differences in myogenic regulatory factors that may be important for age-related loss of muscle mass and strength. Nine elderly (82 ± 7 years old) and nine young, healthy persons (22 ± 2 years old) participated in the study. Exercise consisted of six weeks of resistance training of the quadriceps muscle followed by eight weeks of deconditioning. Muscle biopsy samples before and after training and during the deconditioning period were analyzed for MyoD, myogenin, insulin-like growth-factor I receptor, activin receptor IIB, smad2, porin, and citrate synthase. Muscle strength improved with resistance training by 78% (95.0 ± 22.0 kg) in the elderly to a similar extent as in the young participants (83.5%; 178.2 ± 44.2 kg) and returned to baseline in both groups after eight weeks of deconditioning. No difference was seen in expression of muscle regulatory factors between elderly and young in response to exercise training and deconditioning. In conclusion, the capacity to gain muscle strength with resistance exercise training in elderly was not impaired, highlighting this as a potent tool to combat age-related loss of muscle function, possibly due to preserved regulation of myogenic factors in elderly compared with young muscle.

Estimating deaths from foodborne disease in the UK for 11 key pathogens.

OBJECTIVE: To estimate the number of deaths from foodborne disease in the UK from 11 key pathogens. DESIGN: Four different models were developed using data from a range of sources. These included enhanced surveillance, outbreaks, death certificates and hospital episode statistics data. For each model, median estimates were produced with 95% credible intervals (CrI). The results from the different models were compared. RESULTS: The estimates for foodborne deaths for each pathogen from the different models were consistent, with CrIs largely overlapping. Based on the preferred model for each pathogen, foodborne norovirus is estimated to cause 56 deaths per year (95% CrI 32 to 92), foodborne Salmonella 33 deaths (95% CrI 7 to 159), foodborne Listeria monocytogenes 26 deaths (95% CrI 24 to 28), foodborne Clostridium perfringens 25 deaths (95% CrI 1 to 163) and foodborne Campylobacter 21 deaths (95% CrI 8 to 47). The considerable overlap in the CrIs means it is not possible to make any firm conclusions on ranking. Most of these deaths occur in those aged over 75 years. Foodborne deaths from Shigella, Cryptosporidium, Giardia, adenovirus, astrovirus and rotavirus are all rare. CONCLUSIONS: We estimate that there are 180 deaths per year in the UK (95% CrI 113 to 359) caused by foodborne disease based on these 11 pathogens. While this is a small fraction of the estimated 2.4 million cases of foodborne illness per year it still illustrates the potential severity of these illnesses demonstrating the importance in continuing efforts to reduce these infections.

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.

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.

Analysis of detection enhancement using microcantilevers with long-slit-based sensors.

The present work analyzes theoretically and verifies the advantage of utilizing rectangular microcantilevers with long-slits in microsensing applications. The deflection profile of these microcantilevers is compared with that of typical rectangular microcantilevers under the action of dynamic disturbances. Various force-loading conditions are considered. The theory of linear elasticity for thin beams is used to obtain the deflection-related quantities. The disturbance in these quantities is obtained based on wave propagation and beam vibration theories. It is found that detections of rectangular microcantilevers with long-slits based on maximum slit opening length can be more than 100 times the deflections of typical rectangular microcantilevers. Moreover, the disturbance (noise effect) in the detection quantities of the microcantilever with long-slits is found to be always smaller than that of typical microcantilevers, regardless of the wavelength, force amplitude, and the frequency of the dynamic disturbance. Eventually, the detection quantities of the microcantilever with long-slits are found to be almost unaffected by dynamic disturbances, as long as the wavelengths of these disturbances are larger than 3.5 times the microcantilever width. Finally, the present work recommends implementation of microcantilevers with long-slits as microsensors in robust applications, including real analyte environments and out of laboratory testing.

Analysis of deflection enhancement using epsilon assembly microcantilevers based sensors.

The present work analyzes theoretically and verifies the advantage of utilizing ɛ-microcantilever assemblies in microsensing applications. The deflection profile of these innovative ɛ-assembly microcantilevers is compared with that of the rectangular microcantilever and modified triangular microcantlever. Various force-loading conditions are considered. The theorem of linear elasticity for thin beams is used to obtain the deflections. The obtained defections are validated against an accurate numerical solution utilizing finite element method with maximum deviation less than 10 percent. It is found that the ɛ-assembly produces larger deflections than the rectangular microcantilever under the same base surface stress and same extension length. In addition, the ɛ-microcantilever assembly is found to produce larger deflection than the modified triangular microcantilever. This deflection enhancement is found to increase as the ɛ-assembly's free length decreases for various types of force loading conditions. Consequently, the ɛ-microcantilever is shown to be superior in microsensing applications as it provides favorable high detection capability with a reduced susceptibility to external noises. Finally, this work paves a way for experimentally testing the ɛ-assembly to show whether detective potential of microsensors can be increased.

[A method for creating fuzzy neural-network models using the MATLAB package for biomedical applications].

Problems of MATLAB-based simulation of hybrid neural networks for data classification in biomedical applications are considered. The neural-network structure is used as a defuzzifier. Graphic interfaces for constructing fuzzy neural-network models are suggested. Methods for merging models constructed using different MATLAB packages and an algorithm for constructing a fuzzy neural-network model are suggested. The algorithm includes both modules for tuning membership functions of the fuzzy system fuzzifier, and modules for tuning the parameters of the defuzzifier implemented as a two-layer neural-network structure of the perceptron type.

The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis.

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon-Lefèvre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early-onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p.V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 micro moles/mg/min vs. 1,678.7 +/- SD 527.2 micro moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS.