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Tarp Simpson posted an update 4 days, 12 hours ago
Background Patients with systemic lupus erythematosus (SLE) show increased serum levels of tumor necrosis factor (TNF)/TNF receptor (R) superfamily member, e.g. BAFF (B lymphocyte stimulator). Belimumab, a monoclonal antibody against soluble BAFF, is used for treatment of SLE. Although B cells are the main target, a BAFF-dependent T-cell activation pathway also plays a role. High levels of anti-DNA antibodies and low complement at baseline are known predictors of response to Belimumab. Objectives To explore the association of circulating lymphocytes and serum levels of B- cell related TNF/TNFR superfamily members with response to Belimumab in SLE patients. Methods Twenty-one SLE patients received Belimumab. Clinical evaluation and laboratory tests were performed at baseline, at 6 and 12 months. TNF super-family members (BAFF, APRIL, sBCMA, sCD40L, sTACI, TWEAK) were tested by high-sensitivity ELISA in all patients, and lymphocyte immunophenotyping was performed by flow cytometry in ten subjects. SLE-disease aat baseline. Baseline APRIL levels also showed an association, although the overall model fit was weaker. Conclusion In our real-life cohort, baseline serum levels of BAFF were the best predictor of response to Belimumab, confirming post-hoc results of the BLISS study and suggesting the utility of this particular biomarker for the identification of patients who are more likely to respond.Ivermectin (IVM) and moxidectin (MOX) are used extensively as parasiticides in veterinary medicine. Based on in vitro data, IVM has recently been proposed for the prevention and treatment of COVID-19 infection, a condition for which obesity is a major risk factor. In patients, IVM dosage is based on total body weight and there are no recommendations to adjust dosage in obese patients. The objective of this study was to establish, in a canine model, the influence of obesity on the clearance and steady-state volume of distribution of IVM, MOX, and a third analog, eprinomectin (EPR). An experimental model of obesity in dogs was based on a high calorie diet. IVM, MOX, and EPR were administered intravenously, in combination, to a single group of dogs in two circumstances, during a control period and when body weight had been increased by 50%. In obese dogs, clearance, expressed in absolute values (L/day), was not modified for MOX but was reduced for IVM and EPR, compared to the initial control state. However, when scaled by body weight (L/day/kg), plasma clearance was reduced by 55, 42, and 63%, for IVM, MOX and EPR, respectively. In contrast, the steady-state volume of distribution was markedly increased, in absolute values (L), by obesity. For IVM and MOX, this obese dog model suggests that the maintenance doses in the obese subject should be based on lean body weight rather than total weight. On the other hand, the loading dose, when required, should be based on the total body weight of the obese subject.Objective Hydroxytyrosol (HT), a polyphenol of olive plant is well known for its antioxidant, anti-inflammatory and anti-atherogenic properties. The aim of this systematic search is to highlight the scientific evidence evaluating molecular efficiency of HT in halting the progression of intimal hyperplasia (IH), which is a clinical condition arises from endothelial inflammation. Methods A systematic search was performed through PubMed, Web of Science and Scopus, based on pre-set keywords which are Hydroxytyrosol OR 3,4-dihydroxyphenylethanol, AND Intimal hyperplasia OR Neointimal hyperplasia OR Endothelial OR Smooth muscles. Eighteen in vitro and three in vitro and in vivo studies were selected based on a pre-set inclusion and exclusion criteria. Results Based on evidence gathered, HT was found to upregulate PI3K/AKT/mTOR pathways and supresses inflammatory factors and mediators such as IL-1β, IL-6, E-selectin, P-selectin, VCAM-1, and ICAM-1 in endothelial vascularization and functioning. Two studies revealed HT disrupted vascular smooth muscle cells (SMC) cell cycle by dephosphorylating ERK1/2 and AKT pathways. Therefore, HT was proven to promote endothelization and inhibit vascular SMCs migration thus hampering IH development. However, none of these studies described the effect of HT collectively in both vascular endothelial cells (EC) and SMCs in IH ex vivo model. Conclusions Evidence from this concise review provides an insight on HT regulation of molecular pathways in reendothelization and inhibition of VSMCs migration. Henceforth, we propose effect of HT on IH prevention could be further elucidated through in vivo and ex vivo model.Post-stroke depression (PSD) is one of the most common stroke complications, which seriously affects stroke’s therapeutic effect and brings great pain for patients. The pathological mechanism of PSD has not been revealed. Jiedu Tongluo granules (JDTLG) is an effective traditional Chinese medicine for PSD treatment which is widely used in clinical treatment. JDTLG has a significant therapeutic effect against PSD, but the mechanism is still unclear. The PSD rat model was established by carotid artery embolization combined with chronic sleep deprivation followed by treating with JDTLG. Neurobehavioral and neurofunctional experiments were engaged in studying the neural function of rats. check details Histomorphology, proteomics, and western blotting researches were performed to investigate the potential molecular mechanisms related to JDTLG therapy. Oral treatment of JDTLG could significantly improve the symptoms of neurological deficit and depression symptoms of PSD rats. Proteomic analysis identified several processes that may involve the regulation of JDTLG on the PSD animal model, including energy metabolism, nervous system, and N-methyl-D-aspartate receptor (NMDAR)/brain-derived neurotrophic factor (BDNF) signal pathway. Our results showed that JDTLG could reduce glutamate (Glu) level and increase gamma-aminobutyric acid (GABA) level via regulating the NMDAR/BDNF pathway, which may play a vital role in the occurrence and development of PSD.Morchella conica (M. conica) Pers. is one of six wild edible mushrooms that are widely used by Asian and European countries for their nutritional value. The present study assessed the anti-diabetic potential of M. conica methanolic extract (100 mg/kg body weight) on streptozotocin (STZ)-induced diabetic mice. STZ was used in a single dose of 65 mg/kg to establish diabetic models. Body weights, water/food intake and fasting blood glucose levels were measured. Histopathological analysis of the pancreas and liver were performed to evaluate STZ-induced tissue injuries. In addition, in vitro assays such as α-amylase and protein tyrosine phosphatase 1B (PTP1B) inhibitory, antiglycation, antioxidant and cytotoxicity were performed. The in vitro study indicated potent PTP1B inhibitory potential of M. conica with an IC50 value of 26.5 μg/ml as compared to the positive control, oleanolic acid (IC50 36.2 μg/ml). In vivo investigation showed a gradual decrease in blood sugar level in M. conica-treated mice (132 mg/dl) at a concentration of 100 mg/kg as compared to diabetic mice (346 mg/dl).