No abstract

No abstract

Chloroquine (CQ) and hydroxychloroquine, are promising anti-inflammatory drugs for the treatment of Diabetes mellitus (DM) to prevent associated complications. therefore, this study evaluated the anti-inflammatory effects of CQ-free and CQ-incorporated polylactic acid nanoparticles (NPs) in the peripheral blood mononuclear cells (PBMCs) of patients with type 1 Diabetes mellitus (T1DM). In total, 25 normoglycemic individuals and 25 patients with T1DM aged 10-16 years were selected and glycemic controls evaluated. After cell viability assessed by MTT assay, T1DM PBMCs were subjected to a CQ concentration of 10 µM in three different conditions: not treated (NT), treated with CQ, and treated with CQ NPs. The cells were incubated for 48 h, and the mRNA expressions of cytokines IL1B, IFNG, TNFA, IL12, and IL10 were determined by relative quantification through real-time PCR at 24 h intervals. IL1B expression decreased in CQ and CQ NP-treated cells after 48 h (p < 0.001) and 24 h (p < 0.05) of treatment, respectively. IFNG and IL12 expressions significantly decreased (p < 0.001) in cells treated with CQ and CQ NPs at 24 and 48 h compared to NT. TNFA and IL10 expressions significantly decreased after 48 h (p < 0.001) and 24 h (p < 0.002), respectively, by both CQ and CQ NPs treatment. Despite being a preliminary in vitro study, CQ has anti-inflammatory activity in the primary cells of T1DM patients and could represent an alternative and adjuvant anti-inflammatory therapy to prevent diabetes complications. Diabetes mellitus (DM) is a serious health concern worldwide and patients with diabetes develop health problems due to complications, leading to the need for increased medical attention, a reduced quality of life, and premature death 1,2. According to the International Diabetes Federation, more than 463 million people had diabetes in 2019, which is projected to reach 700 million in 2045. Therefore, continuous medical monitoring is necessary to reduce the risk of complications 2. Type 1 DM (T1DM) occurs primarily in childhood with over 100,000 children and adolescents diagnosed each year. It is a chronic autoimmune disease characterized by hyperglycemia due to the destruction of pancreatic β cells, leading to an absolute deficiency of insulin 1,3. In the long run, inadequate glycemic control leads to the formation of advanced glycation end products (AGEs), which in turn cause changes to synthesis and damage to tissue structure and function. In addition, AGEs activate the signaling cascade that causes an intense inflammatory response with the production of reactive oxygen species in nerve and endothelial cells, causing microvascular (nephropathy, neuropathy, and retinopathy) and macrovascular (coronary disease, cerebrovascular disease, and peripheral arterial disease) lesions 4,5. Generally speaking, this event occurs when damage-associated molecular pattern proteins, AGEs, high mobility group box-1 proteins, heat shock proteins, and growth-specific protein 6 bind to toll-like receptors (TLRs) 2 and 4 on the β-cell membra...

Associations between vitamin D deficiency and metabolic syndrome (MS) have been reported; however, the underlying biological mechanisms remain controversial. The aim of this study was to investigate the associations of CYP2R1 and VDR variants with MS and MS components in non-diabetic Brazilian adolescents. This cross-sectional study included 174 adolescents who were classified as overweight/obese. Three CYP2R1 variants and four VDR variants were identified by allelic discrimination. The CYP2R1 polymorphisms, rs12794714 (GG genotype) (odds ratio [OR] = 3.54, 95% confidence interval [CI] = 1.24–10.14, p = 0.023) and rs10741657 (recessive model—GG genotype) (OR = 3.90, 95%CI = 1.18–12.92, p = 0.026) were significantly associated with an increased risk of MS and hyperglycemia, respectively. The AG + GG genotype (dominant model) of the rs2060793 CYP2R1 polymorphism was associated with hyperglycemia protection (OR = 0.28, 95%CI = 0.08–0.92, p = 0.037). Furthermore, the CC genotype (recessive model) of the rs7975232 VDR polymorphism was significantly associated with a risk of hypertension (OR = 5.91, 95%CI = 1.91–18.32, p = 0.002). In conclusion, the CYP2R1 rs12794714 polymorphism could be considered a possible new molecular marker for predicting the risk of MS; CYP2R1 rs10741657 polymorphism and VDR rs7975232 polymorphism are associated with an increased risk of diabetes and hypertension in adolescents with overweight/obesity.

In the present study, we aimed to evaluate the therapeutic effect of Passiflora edulis fruit peel aqueous (AFA) extract as an adjuvant to insulin to confer nephroprotection against streptozotocin-induced diabetes. Male Wistar rats were divided into four groups based on treatment received for 60 days: diabetic (DB), control (CTL), insulin (INS), and insulin + AFA extract (INS + AFA). mRNA and protein expression levels of podocyte (nephrin, podocin, and WT1) and tubular (megalin) proteins were measured in kidney tissue specimens and urine. Biochemical parameters and kidney histopathology were also examined. Herein, the INS + AFA group showed superior glycemic control, which resulted in the reduction of urinary albumin/creatinine ratio, maintenance of baseline levels of Nphs1, Nphs2, Wt1, and Lrp2 mRNA expression, prevention of protein loss from the kidney tissue into the urinary space, along with the maintenance of glomerular basement membrane thickness, hyalinization, glomerular and tubulointerstitial fibrosis at values approximating those of the CTL group and significantly lower than those in the DB group. Therefore, these results suggest that, as an anti-diabetic agent, the AFA extract adjuvant to insulin could reduce and potentially prevent diabetic kidney disease.

Plants have long been used in traditional medicine to treat illnesses. Nevertheless, their chemical diversity requires studies to establish the extract dosage and its safe use. Pseudobombax parvifolium, an endemic species of the Brazilian Caatinga biome, is commonly used in folk medicine, due to its anti-inflammatory properties related to cellular oxidative stress; however, its biological properties have scarcely been studied. In this study, we chemically characterized the P. parvifolium hydroalcoholic bark extract (EBHE) and evaluated its cytotoxic, mutagenic, and preclinical aspects, as well as its antioxidant effect. Our phytochemical analysis revealed a significative total polyphenol content and identified loliolide for the first time in this species. Cytotoxicity, mutagenicity, and acute oral and repeated dose indicated no toxic effects on cell culture, Drosophila melanogaster, and Wistar rat exposure to different EBHE concentrations, respectively. Furthermore, we observed a significant decrease in lipid peroxidation and a mild hypoglycemic and hypolipidemic effect with repeated oral dosing of EBHE. Although there were no significant changes in glutathione content, we did observe a significant increase in superoxide dismutase at a dose of 400 mg/kg and in glutathione peroxidase at doses of 100, 200, and 400 mg/kg. These findings suggest that EBHE has potential as a source of bioactive molecules, and it can be used safely in traditional medicine and in the development of herbal medicines for application in the public health system.

Background Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease that requires treatment with hydroxychloroquine and glucocorticoids. Glucocorticoids are responsible for adverse effects such as increased weight, which can modify the severity and chronicity of autoimmune pathologies. Aim To summarize scientific evidence regarding the impact of overweight and obesity on disease activity and remission in SLE. Methods The protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) and published in the International Prospective Register of Systematic Reviews database (PROSPERO—CRD42021268217). PubMed, Scopus, Embase, and Google Scholar will be searched for observational studies including adult patients with SLE who were overweight and obese or not, that included disease activity or remission as outcomes. The search is planned for May 2023. Three independent authors will select the eligible articles and extract their data. Subsequently, three authors will independently extract data from each included study using an extraction form created by the researchers. Methodological quality analyses will be performed using the modified Newcastle-Ottawa scale. The results will be presented as a narrative synthesis according to the synthesis without a meta-analysis reporting guideline (SWiM). Meta-analysis will be conducted where appropriate using random-effects models. Expected results This review will identify the impact of overweight and obesity on the clinical features of SLE, helping clinicians manage disease activity and remission, both important to optimize disease outcomes and patient quality of life.