Graphical abstract Collectively, p53-dependent lincRNA-p21 expression downregulated miR-17-5p, whichconsequently protecting against AS progression via SIRT7 elevation.The use of Δ9-tetrahydrocannabinol (THC) and Δ9-tetrahydrocannabinol-valine-hemisuccinate (THC-VHS; NB1111) has recently been investigated in the management of intraocular pressure (IOP). The current study was undertaken to develop an optimized THC-VHS-loaded nanoemulsion formulation (NE; THC-VHS-NE) that could improve the drug load and duration of activity. THC-VHS-NE formulation was prepared by homogenization followed by ultrasonication. Sesame oil, Tween®80, and Poloxamer®188 were used as the oil, surfactant, and cosurfactant, respectively. Stability of the optimized THC-VHS-NE formulation was observed at 4 °C. The IOP lowering effect of the lead formulations, commercial timolol, and latanoprost ophthalmic solutions, as well as an emulsion in Tocrisolve™ (THC-VHS-TOC), was studied in New Zealand White rabbits following topical administration. The effect of surfactant concentration and sterilization process on IOP-lowering activity was also studied. THC-VHS-NE formulations (0.5, 1.0, and 2.0% w/v) showed dose dependent duration of action. The 1.0%w/v THC-VHS-NE formulation was selected for further evaluation because of its desirable physical and chemical characteristics. THC-VHS-NE formulation prepared with 2% w/v Tween®80 exhibited a higher drop in IOP than the 0.75 and 4.0% w/v of Tween®80 containing formulations. The IOP-lowering duration was, however, similar for the formulations with 0.75 and 2.0% Tween®80, while that with 4.0% Tween®80 was shorter. THC-VHS-NE formulation produced a greater drop in IOP (p less then 0.05) and a longer duration of activity compared to THC-VHS-TOC, latanoprost, and timolol. The formulation could be sterilized by filtration without impacting product attributes. Overall, the optimized THC-VHS-NE formulation demonstrated a significantly better IOP reduction profile in the test model compared to the commercial ophthalmic solutions evaluated.Human T cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), as the most common neurological emersion related to HTLV-1, is a debilitating and lifelong treating disease with no definitive treatment.  https://www.selleckchem.com/TGF-beta.html  Furthermore, it has been determined that dietary compositions (inflammatory and anti-inflammatory) and some micronutrients (such as vitamin D and selenium) have an effect on inflammatory and immune processes and with this background; the study was done to compare the nutritional status between age- and sex-matched with infected and non-infected HTLV-1. In a multi-center setting, 70 healthy controls (HCs), 35 asymptomatic carriers (ACs), and 35 HAM/TSP patients were recruited in the HTLV-1 Foundation, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. Nutritional status including anthropometric indices, dietary (micro- and macronutrient) intake, and serum vitamin D, vitamin B12, zinc, and selenium were measured. In anthropometric indices, mean waist cically, the considerable difference was found only in the selenium concentration (p = 0.001). The study showed that there were differences in dietary intake (including energy, macronutrients, and fatty acids), WC, and selenium serum levels between HAM/TSP patients and HTLV-1 carriers, suggesting that nutritional statues influence the inflammatory immune response in HTLV-1 infection.The prevalence of diabetes in sub-Saharan Africa (SSA) is growing rapidly, and a steadily increasing number of adults are estimated to be living with type 2 diabetes mellitus (T2DM). Insulin therapy is the treatment of choice in patients who present with severe hyperglycaemia and in most of those who do not achieve target goals on oral hypoglycaemic agents. Initiating treatment with the appropriate type of insulin based on the meal patterns and lifestyle of the individual patient is a strategy that is more likely than others to improve glycaemic control and adherence. African cuisine typically has a high carbohydrate load. Given these predominantly carbohydrate-rich food habits, it is essential to modify this dietary pattern whilst at the same time ensuring that insulin therapy is initiated, titrated and maintained in a timely manner, as needed to suit the patient's habits. To date, there are no published clinical guidelines to guide practitioners and patients on tailoring insulin to match the high carbohydrate content in African cuisine. To address this gap, we have reviewed current insulin therapy practices and propose a patient-centric guide to insulin therapy based on African cuisine. A literature search was conducted for studies published in English up to November 2019 that focused on the choice of insulin and its dosing in relation to African foods. All articles extracted were reviewed by an expert group. The recommendation of the expert group was that basal-bolus and premix insulin regimens are best suited to manage post-meal glycaemia in African cuisine. The timing and constituents of the meal, portion sizes, glycaemic load and glycaemic index of meals should be considered when choosing the type of insulin and insulin regimen. Assessment of individual preferences and comorbidities should be prioritised and form an integral part of diabetes management.
  Imeglimin is a novel oral antidiabetic drug used to treat type 2 diabetes, targeting the mitochondrial bioenergetics. Imeglimin is mainly excreted unchanged by the kidneys and is a substrate of organic cation transporters, which are expressed in the kidney and the liver.
 
  The aim of this study was to assess the effect of hepatic impairment on the pharmacokinetics of imeglimin.
 
  An open-label, single-dose, parallel-group study was carried out in seven subjects with normal hepatic function and seven subjects with moderate hepatic impairment who received a single dose of imeglimin 1000mg. Blood and urine samples were collected up to 48h after imeglimin administration. Pharmacokinetics were determined using non-compartmental methods.
 
  Imeglimin maximum observed plasma concentration (C
  ) and area under the plasma concentration-time curve (AUC) in subjects with moderate hepatic impairment was 1.3-fold (90% confidence interval [CI] 1.05-1.60) and 1.5-fold (90% CI 1.19-1.82) higher than in subjects with normal hepatic function, but was not considered as clinically meaningful.