Background
Alopecia areata (AA) is an organ‐specific autoimmune disease characterized by T‐cell infiltrates and cytokine production. T‐helper 17 (Th17) cells are crucially involved in the ...pathogenesis of autoimmune diseases.
Objectives
Our aim was to assess the association of Th17 with AA. We examined interleukin (IL)‐17, IL‐21, IL‐22, IL‐6, and tumor necrosis factor‐alpha (TNF‐α) levels in the serum of patients with AA and studied their association with clinical type and severity of AA.
Subjects and methods
The serum concentrations of IL‐17, IL‐21, IL‐22, IL‐6, and TNF‐α were measured in 47 patients with AA and 40 healthy controls. The clinical type of AA was determined, and the severity of hair loss was assessed in accordance with the Alopecia Areata Investigational Assessment Guideline criteria.
Results
The serum concentrations of IL‐17, IL‐21, IL‐22, IL‐6, and TNF‐α were significantly higher in patients with AA as compared with healthy controls (mean: IL‐17 33.23 ± 11.58 vs. 4.62 ± 1.88 pg/ml; P = 0.000, IL‐21 62.10 ± 6.11 vs. 48.38 ± 3.31 pg/ml; P = 0.000, IL‐22 19.27 ± 3.36 vs. 7.09 ± 1.62 pg/ml; P = 0.000, IL‐6 17.18 ± 3.08 vs. 4.59 ± 1.66 pg/ml; P = 0.000, TNF‐α 19.94 ± 3.59 vs. 9.95 ± 2.42 pg/ml; P = 0.000, respectively). There were significant positive correlations between serum IL‐17, TNF‐α, and disease severity. There was also significant positive correlation between serum IL‐22 and duration of AA.
Conclusion
Our results showed high serum levels of Th17 cytokines among patients with AA that may suggest a functional role of these cytokines in the pathogenesis of this important skin disease. It could also provide the rationale for new treatment strategies in AA.
Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin ...against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks. The control rats were injected with the vehicle for the same period. The metformin-treated group received 200 mg/kg metformin daily for 10 weeks, beginning week 1, and received TAA injections with dosage and timing similar to those of the model group. All rats were culled at week 10. It was observed that TAA induced substantial renal injury, as demonstrated by significant kidney tissue damage and fibrosis, as well as augmented blood and kidney tissue levels of urea, creatinine, inflammation, oxidative stress, dyslipidemia, tissue inhibitor of metalloproteinases-1 (TIMP-1), and hypertension. TAA nephrotoxicity substantially inhibited the renal expression of phosphorylated AMPK. All these markers were significantly protected by metformin administration. In addition, a link between kidney fibrosis and these parameters was observed. Thus, metformin provides profound protection against TAA-induced kidney damage and fibrosis associated with the augmentation of the tissue protective enzyme AMPK and inhibition of oxidative stress, inflammation, the profibrogenic gene TIMP-1, dyslipidemia, and hypertension for a period of 10 weeks in rats.
Acetaminophen (also called paracetamol, or APAP) causes acute kidney injury after accidental or intentional ingestion of a toxic dose of the drug. We tested whether the antioxidant and ...anti-inflammatory agent, quercetin (QUR) given alone can protect against acute nephrotoxicity induced by APAP overdose in a rat model of APAP-induced acute kidney injury. Rats were either given a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Kidneys were examined by light microscopy after staining with hematoxylin and eosin (H&E) and collected blood samples were assayed for biomarkers of oxidative stress, inflammation, and kidney injury. H&E stained sections of kidney from the model group of rats (APAP) showed substantial damage to the kidney architecture as demonstrated by widening of Bowman’s space, tubular dilatation, vacuolization of tubular epithelium, and congested dilated blood vessels, which were partially protected by QUR. In addition, APAP significantly (p<0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6), which were significantly (p<0.05) reduced by QUR. These results indicate that quercetin partially protects against APAP-induced acute kidney injury in rats, which is associated with the inhibition of biomarkers of oxidative stress and inflammation and kidney injury.
This study was conducted to study the expression of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, interleukin-6 (IL-6), and other inflammatory markers among obese children ...with/and without diabetes mellitus.
One hundred obese children with diabetes in addition to 100 age- and sex-matched obese children without diabetes, and 100 age- and sex-matched apparently healthy children were included in the study. Expressions of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, IL-6, tumor necrosis factor-α (TNF-α), and high sensitive-CRP (hsCRP) were measured for all included study populations.
Study results showed that the expressions of both microRNA-29a and microRNA-122, serum levels of IL-6, TNF-α, and hsCRP were significantly higher among obese children with diabetes in comparison to both obese children without diabetes and healthy children. In contrast, serum sestrin level was significantly low among obese children with diabetes in comparison to the other study populations. Expressions of both microRNA-29a and microRNA-122 were correlated with waist circumference, BMI, total cholesterol, triglycerides, LDL-cholesterol, HbA
, c-peptide, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP, and TNF-α among obese children with diabetes. However, serum sestrin-2 level was correlated inversely with these parameters. Higher expressions of both microRNA-29a and microRNA-122 among obese children either with or without diabetes mellitus (DM) can suggest their roles in the development of obesity among children.
The study results can hypothesize that down-regulation of these micro-RNAs may solve this health problem with its sequelae, a hypothesis that needs more studies.
Environmental pollution is a highly challenging global health concern, affecting the natural ecosystem and human health. The obesity risk is allied to diverse factors, including genetics, behaviour, ...food, and socio-cultural conditions, however, literature is lacking in exploring the effect of environmental pollution on obesity and the causal pathways are not fully understood. Therefore, this study aimed to investigate the effect of environmental pollutants particulate matter PM2.5 μm, PM10 μm, Nitrogen Dioxide (NO2), and ground level Ozone (O3) on obesity.
This study recorded data on air pollutants and obesity using the electronic platforms Pub Med, Web of Science, Scopus, and Google Scholar. The keywords included for the literature search were based on a combination of two main aspects, which were used to represent exposure (air pollutants), and outcome (obesity). Initially, 324 articles and reports were identified, and after revising the abstracts and full articles, 12 studies were selected for a detailed analysis and discussion. The Odds Ratio (OR) and 95 % confidence intervals (CIs) were extracted to investigate the impact between air pollutants and obesity. The Cochrane chi-squared test (Chi2), fixed-effects design was used when I2 < 50 % and P > 0.05; otherwise, a random-effects model was adopted.
Environmental pollutants, particulate matter PM2.5 (OR = 1.18; 95 % CI: 1.10–1.25p < 0.01), PM10 (OR = 1.11; 95 % CI: 1.02–1.20; p < 0.01), Nitrogen Dioxide NO2 (OR = 1.14; 95 % CI: 1.02–1.28; p = 0.03), ground-level Ozone O3 (OR = 1.01; 95 % CI: 1.00–1.01; p = 0.01) were significantly and positively associated with obesity.
Environmental pollution could be a risk factor for obesity. The potential mechanisms involved in the pathogenesis of this relationship are oxidative stress, inflammation, hormonal disruption, and adipose tissue function alteration. Addressing this multifaceted issue requires collaboration between public health officials, policymakers, and the public at large. Moreover, raising public awareness is a crucial step towards mitigating the impact of environmental pollution on obesity.
Background and Objective
Diabetic nephropathy (DN) is the most common cause of end stage renal failure or even death among patients with type 2 diabetes mellitus. Genetic predisposition is widely ...studied among these patients to identify manageable aspects of the disease pathogenesis. This study was carried out to test the association of engulfment and cell motility 1 (ELMO1) gene polymorphism with DN among Egyptians. ELMO1 is required for phagocytosis of apoptotic cells and cell motility.
Methods
This case‐control study was conducted on type 2 diabetic patients who attended Suez Canal University Hospital, Egypt, between November 2016 and October 2017. Peripheral blood was collected from 200 diabetic patients (without nephropathy), 200 patients with DN, and 100 healthy controls for DNA extraction. The single nucleotide polymorphism of ELMO1 (rs741301) was genotyped using real‐time polymerase chain reaction and the allele discrimination technique.
Results
GG genotype was significantly associated with DN (odds ratio OR = 2.7; 95% confidence interval CI: 1.4‐5.3) (P = .016). The OR for the high‐risk allele (G) was 1.9 with 95% CI from 1.5 to 2.9 (P < .001).
Conclusion
ELMO1 gene (rs741301) polymorphism is a candidate variant in the predisposition to DN.
This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and ...gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = −0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.
Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in ...vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.
Imidacloprid (IMI) is a commonly used new-generation pesticide that has numerous harmful effects on non-targeted organisms, including animals. This study analysed both the adverse effects on the ...pancreas following oral consumption of imidacloprid neonicotinoids (45 mg/kg daily for 30 days) and the potential protective effects of lycopene (LYC) administration (10 mg/kg/day for 30 days) with IMI exposure in male Sprague–Dawley rats. The apoptotic, pyroptotic, inflammatory, oxidative stress, and endoplasmic reticulum stress biomarkers were evaluated, along with the histopathological alterations. Upon IMI administration, noticeable changes were observed in pancreatic histopathology. Additionally, elevated oxidative/endoplasmic reticulum-associated stress biomarkers, inflammatory, pyroptotic, and apoptotic biomarkers were also observed following IMI administration. LYC effectively reversed these alterations by reducing oxidative stress markers (e.g., MDA) and enhancing antioxidant enzymes (SOD, CAT). It downregulated ER stress markers (IRE1α, XBP1, CHOP), decreased pro-inflammatory cytokines (TNF-α, IL-1β), and suppressed pyroptotic (NLRP3, caspase-1) along with apoptotic markers (Bax, cleaved caspase-3). It also improved the histopathological and ultrastructure alterations brought on by IMI toxicity.
Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) ...axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (
< 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects.
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