Notes

Sequence involving diversity, capabilities, as well as interactions from the candica group in initialized gunge underneath savoury hydrocarbon tension.
journal and presentation at scientific conferences. Medicinal plants have been important sources for the development of many effective drugs currently available in orthodox medicine. Botanically derived medicines have played a major role in human societies throughout history. Plants components used in traditional medicine gained much attention by many toxinologists as a tool for designing potent antidotes against snake envenoming. Our systematic review will provide a synthesis of the literature on the efficacy of these medicinal plants. We will also appraise the prospects of African medicinal plants with pharmacologically demonstrated activity against snakebite and envenoming.The aristolochic acids (AAs), derived from Aristolochia and Asarum species used widely in herbal medicines, are closely associated with liver cancer. The major AA derivatives are aristolochic acid I (AAI) and II (AAII), which can bind DNA covalently to form AA-DNA adducts after metabolic activation in vivo. Among all these AA-DNA adducts, 7-(deoxyadenosine-N6-yl) aristolactam I (dA-AL-I) is the most abundant and persistent DNA lesion in patients. However, the direct evidence indicating AA exposure in human liver cancer is still missing. Here, we analyzed dA-AL-I adduct, the direct biomarker of AAI exposure, by ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-TQ/MS) in 209 liver cancer patients. Also, DNA samples from mice treated with/without AAI were used as positive and negative controls. dA-AL-I adduct was present in 110 of 209 (52.6%) patients, indicating that these patients were exposed to AAI prior to their clinical investigations and also had a worse prognosis. Rosuvastatin The relative high AA exposure rate and worse prognosis in our cohort of patients emphasize the significance to increase public awareness to avoid the use of herbal medicine containing AAs or their derivatives.A new and valid method was developed for the quantitative voltammetric analysis of midodrine hydrochloride (MID) in pharmaceutical tablets (Midodrine) and biological samples. The method is based on electro-oxidation of MID supported by both disposable pencil electrode (PE) and glassy carbon electrode (GCE). The analysis was carried out using cyclic voltammetry, differential pulse voltammetry (DPV), and square wave voltammetry (SWV) techniques. The proposed analytical method was validated according to ICH guidelines. MID was successively assayed at concentration ranges of 1.15-6.55 and 0.58-3.05 μg mL-1 at PE. Also, MID was successively assayed at concentration ranges of 1.15-5.28 and 2.86-27.6 μg mL-1 at GCE for DPV and SWV methods, respectively. The proposed method was successfully used for the analysis of MID in its dosage form and human urine with good recoveries of 99.66 ± 0.33, 99.8 ± 0.45 at PE and 99.8 ± 0.25, 98.7 ± 1.27 at GCE for the DPV and SWV methods, respectively. The suggested method could be applied to the studied drug in the quality control lab as well as in its pharmacokinetic studies.Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50 mg/kg/BW orally daily for 4 weeks; the GA3 group received 55 mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-admxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.Contemporary exposure to PM2.5 has been reported to disrupt spermatogenesis. However, the subsequent toxicological responses and the mechanisms of male reproductive damage in offspring induced by maternal exposure to PM2.5 remain largely unknown. For the first time, this study aimed to explore the apoptotic response in spermatogenesis of male offspring following maternal exposure to PM2.5 and its mechanisms. The C57BL/6 mice with vaginal plugs were randomly divided into four groups. Mice in the PM2.5 groups were intratracheally exposed to PM2.5 (4.8 mg/kg body weight, 43.2 mg/kg body weight) during pregnancy (every 3 days, six times in total). The mice in the membrane control group were treated similarly to the PM2.5 groups, applying only PM2.5 sampling membrane, while mice in the control group were kept untreated. The results showed that maternal exposure to PM2.5 during pregnancy resulted in structural lesions of the testis, reduced numbers of primary spermatocytes and spermatids, decreased sperm count and quality, shortened diameter of seminiferous tubules, and reduced testosterone and ABP in the offspring testes. Furthermore, cell apoptosis was increased and protein expression of IRE-1/P-JNK/cleaved caspase-12/cleaved caspase-3 was activated. These findings suggested that maternal exposure to PM2.5 may affect spermatogenesis by increasing apoptosis through activation of UPR-mediated JNK apoptotic pathway in offspring testicles and by reducing testosterone secretion.Acrylamide is a well-known neurotoxicant and carcinogen. Apart from industrial exposure, acrylamide is also found in different food products. The present study deals with in vivo experiment to test the protective effect of rutin against acrylamide induced toxicity in rats. The study was carried out on female rats with exposure of acrylamide at the dose of 38.27 mg/kg body weight, orally for 10 days followed by the therapy of rutin (05, 10, 20 and 40 mg/kg orally), for three consecutive days. All animals were sacrificed after 24 h of last treatment and various biochemical parameters in blood and tissue were investigated. Histopathology of liver, kidney and brain was also done. On administration of acrylamide for 10 days, neurotoxicity was observed in terms of decreased acetylcholinesterase activity and oxidative stress was observed in terms of increased lipid peroxidation, declined level of reduced glutathione, antioxidant enzymes (superoxide dismutase and catalase) in liver, kidney and brain. Acrylamide exposure increased the activities of serum transaminases, lipid profile, bilirubin, urea, uric acid and creatinine in serum indicating damage. Our experimental results conclude that rutin showed remarkable protection against oxidative DNA damage induced by acrylamide, which may be due to its antioxidant potential.Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by reduced insulin sensitivity and dysfunction of β-cells. Although the increasing prevalence of diabetes worldwide is largely attributed to genetic predisposition or lifestyle factors (insufficient physical activity), and caloric intake. Environmental factors, exposure to xenobiotics and heavy metals have also been reported to be causative factors of T2DM. At this juncture, we, through our work unveil a plausible link between Pb2+ exposure and diabetes mellitus, and delineated a comprehensive understanding of the potential mechanisms of Pb2+-induced β-cells dysfunction. In our in vivo observations, we found that Pb2+ exposure strongly reduced glucose-stimulated insulin secretion and diminished functional pancreatic β-cell mass. Mechanistically, we found that Pb2+ downregulates intracellular cAMP level via hyper-activating Ca2+/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C and thereby reduces glucose-stimulated insulin secretion. Further, we report that Pb2+ inhibited mitochondrial adenosine triphosphate production and also identified Pb2+ as a negative regulator of β-cell proliferation via Ca2+/calmodulin-dependent protein kinase kinases-pAMPK-pRaptor axis. Together, our findings strongly reinforce Pb2+ to hijack the physiological role of calcium ions, by mimicking Ca2+ within pancreatic β-cell and thereby stands as a diabetogenic xenobiotic.
Fine particulate matter (PM
) is a ubiquitous air pollutant, and it has been reported to be closely associated with lung inflammatory injury. In this study, the potential molecular mechanisms underlying PM
-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated.

Ambient PM
particulates from Suzhou, China, were collected and re-suspended in ultrapure water. Cellular damages, characterized by oxidative stress, mitochondrial injury, and inflammatory cytokine production, were determined in 24h PM
-treated BEAS-2B cells with or without 3-methyladenine (3-MA; autophagy inhibitor) pretreatment. Biomarkers related to oxidative damage, inflammatory injury and autophagy signaling pathways were also measured.

Uptake of PM
in BEAS-2B cells induced cellular oxidative damage, mitochondrial injury, and inflammatory responses as indicated by a significant decrease in GSH/GSSG ratio, increased MDA content, dilated mitochondria with loss and rupture of crista, and production e a critical contributor to defective mitophagy and cellular inflammatory response.Neratinib is a pan-HER tyrosine kinase inhibitor newly approved by FDA in 2017 to treat HER2-positive breast cancer, but the phase III trial of neratinib showed that 96% of the patients taking neratinib experienced diarrhea. So far very few mechanistic studies explore neratinib-induced gastrointestinal (GI) toxicity. Hereby, we performed toxicity studies in mice to characterize the potential mechanism underlying this adverse effect. C57BL/6 J mice were separated into three groups A, B, C. Group A received vehicle; group B was orally dosed with 100 mg/kg neratinib once daily for 18 days. Group C was dosed with 100 mg/kg neratinib for 12 days and switched to vehicle for 6 days. Intestine and liver were collected for further analysis. Human intestine-derived cells were treated with neratinib in vitro. Our results showed that 12 days treatment of neratinib caused persistent histological damage in mouse GI tract. Both gene expression and activity of Cyp3a11, the major enzyme metabolizing neratinib in mice was reduced in small intestine. The gene expression of proinflammatory cytokines increased throughout the GI tract. Such damages were not recovered after 6 days without neratinib treatment. In addition, in vitro data showed that neratinib was potent in killing human intestine-derived cell lines. Based on such findings, we hypothesized that neratinib downregulates intestinal CYP3A enzyme to cause excessive drug disposition, eventually leading to gut injury.Ayurvedic formulations are widely used and perceived as safer medicine and subjected to be self-prescribed. However, recent reports have demonstrated adulterating these drugs with toxic quantities of heavy metals. To study the magnitude of the problem in Indian-manufactured Ayurvedic medications, we randomly collected common over-the-counter Ayurvedic preparations from the licensed Ayurvedic shops in the local markets of Chandigarh in 2017. The samples were analyzed to identify and quantify eight metal ions, including mercury, arsenic, lead, cadmium, zinc, iron, copper, and chromium, using inductively coupled plasma mass spectrometry in Postgraduate Institute of Medical Education and Research, Chandigarh. The permissible limit set by the Food and Agriculture Organization/World Health Organization (FAO/WHO) for herbal medicines was followed to define the high metal concentrations. Out of 43 Ayurvedic preparations, 42 were analyzed. Heavy metals were detected in all formulations. The median (range) concentrations (in μg/g or mg/kg) of the metals were quantified as follows- mercury, 13.
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