This study aimed to analyze the ameliorative effect of Crataegus aronia against type 2 diabetes mellitus (type 2-DM). Type 2-DM rats were treated with the extract and the changes in serum parameters (glucose, insulin, HbA1c and lipids) and hepatic parameters (oxidative stress, inflammation and mRNA levels of GLUT-2 and gluconeogenesis enzymes) were compared to those of control and untreated type 2-DM rats. Also, levels of hepatic insulin receptors 1A (IR-1A) were measured immunohistochemically and compared between groups. In type 2-DM rats, C. aronia significantly improved the oral glucose tolerance test (OGTT), lowered plasma glucose, serum lipid levels and the hepatic glycogen content. Also, it significantly lowered the levels of hepatic lipid peroxidation, tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) and enhanced the level of reduced glutathione (GSH) and increased superoxide dismutase (SOD) activity. C. aronia enhanced hepatic mRNA expression of the insulin receptor A isoform (IR-A) and glucose 6-phosphatase (G6Pase), and lowered glucose transporter-2 (GLUT-2) and glycerol kinase (GK) mRNA expression. In conclusion, C. aronia ameliorates T2DM by inhibiting hepatic glucose output.

Resveratrol (RES) has the ability to ameliorate nonalcoholic fatty liver disease (NAFLD) and the mechanism remains unclear. Hence, using high-fat diet (HFD) obese rat model, we investigated the effect of a low dose of RES (20 mg/kg) on the hepatic sterol regulatory element-binding protein (SREBPs) - lipogenesis pathway, enzymes involved in β-oxidation and activity of pancreatic lipase. Four groups of rats (n = 8) of control (12% of calories as fat) and HFD (40% of calories as fat) were administered orally with either normal saline as a vehicle or RES as a concomitant treatment for 8 weeks on a daily basis. Then, various biochemical, histological, and molecular experiments were carried out. RES prevented the development and progression of NAFLD and significantly improved insulin sensitivity through (1) inhibiting the proteolytic cleavage of SREBPs-1 and SREBPs-2 without affecting their precursor mRNA or protein levels, (2) inhibiting free fatty acid β-oxidation and generation of reactive oxygen species through significant inhibition of CPT-1 and UCP-2, and (3) decreasing activity of pancreatic lipase in vivo and in vitro. In conclusion, our findings are the first in the literature to show new mechanisms of the hepatoprotective effect of RES against HFD induced NAFLD in rats.

Background/Aims To assess the safety and efficacy of argon laser photocoagulation as a new modality for the treatment of presumed trematode-induced granulomatous anterior uveitis (PTGAU) in children.

To analyze astigmatic changes after intrastromal corneal ring segments (ICRSs) implantation accompanied by corneal collagen cross-linking (CXL) in keratoconic eyes using the Alpins vectorial method.

Background: Asthmatic smokers are a distinct phenotype of asthma. There is a lack of specific information about the treatment of asthma in smokers. The purpose of this study was to compare the effects of inhaled corticosteroid (ICS) on asthmatic smokers and non-smokers. Results: The present observational, cross-sectional study was conducted at the Chest Department in Assiut University Hospital, during the period from August 2018 to January 2020. Hundred and seventeen asthmatic patients (42 smokers, 30 ex-smokers, and 45 non-smokers) were assessed using an asthma control questionnaire (ACQ), spirometry, sputum cytology, and serum periostin and eotaxin-2 to compare between a patient on inhaled corticosteroid for at least 3 months and patients who do not receive any form of corticosteroid. Asthmatic smokers had poor response to ICS and had insignificant improvement as regard all parameters. However, asthmatic exsmokers had a partial response to ICS. They had higher post-bronchodilator FEV1 in comparison to those who did not receive ICS. Asthmatic non-smokers on ICS showed the best response as they were well controlled as regard ACQ. Moreover, they had higher post-bronchodilator FEV1/FVC, post-bronchodilator FEV1, and post-bronchodilator FEF25-75, and lower sputum eosinophils and neutrophils. Conclusion: Smoking adversely affects the course and response to ICS therapy in asthma. Trial registration: Interrelation between bronchial asthma and smoking: ClinicalTrials.gov ID: NCT03207620. Registered 27 June 2017.

Sepsis-associated acute lung injury (ALI) is a critical condition characterized by severe inflammatory response and mitochondrial dysfunction. Coenzyme Q10 (CoQ10) and aescin (AES) are well-known for their anti-inflammatory activities. However, their effects on lipopolysaccharide (LPS)-induced lung injury have not been explored yet. Here, we asked whether combined pretreatment with CoQ10 and AES synergistically prevents LPS-induced lung injury. Fifty male rats were randomized into 5 groups: (1) control; (2) LPS-treated, rats received a single i.p. injection of LPS (8 mg/kg); (3) CoQ10-pretreated, (4) AES-pretreated, or (5) combined-pretreated; animals received CoQ10 (100 mg/kg), AES (5 mg/kg), or both orally for 7 days before LPS injection. Combined CoQ10 and AES pretreatment significantly reduced lung injury markers; 52.42% reduction in serum C-reactive protein (CRP), 53.69% in alkaline phosphatase (ALKP) and 60.26% in lactate dehydrogenase (LDH) activities versus 44.58, 37.38, and 48.6% in CoQ10 and 33.81, 34.43, and 39.29% in AES-pretreated groups, respectively. Meanwhile, combination therapy significantly reduced interleukin (IL)-1β and tumor necrosis factor (TNF)-α expressions compared to monotherapy (p < 0.05). Additionally, combination therapy prevented LPS-induced histological and mitochondrial abnormalities greater than separate drugs. Western blotting indicated that combination therapy significantly suppressed nucleotide-binding oligomerization domain (NOD)-like receptors-3 (NLRP-3) inflammasome compared to separate drugs (p < 0.05). Further, combination therapy significantly decreased the expression of signaling cascades, p38 mitogen-activated protein kinases (p38 MAPK), nuclear factor kappa B (NF-κB)-p65, and extracellular-regulated kinases 1/2 (ERK1/2) versus monotherapy (p < 0.05). Interestingly, combined pretreatment significantly downregulated high mobility group box-1 (HMGB1) by 72.93%, and toll-like receptor 4 (TLR4) by -0.93-fold versus 61.92%, -0.83-fold in CoQ10 and 38.67%, -0.70-fold in AES pretreatment, respectively. Our results showed for the first time that the enhanced anti-inflammatory effect of combined CoQ10 and AES pretreatment prevented LPS-induced ALI via suppression of NLRP-3 inflammasome through regulation of HMGB1/TLR4 signaling pathway and mitochondrial stabilization.

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia. The disease became a global health issue due to development of resistance to commonly used drugs. Since many plant-derived products have been used to treat many parasitic infestations, we aimed to assess the therapeutic utility of Artemisia annua (A. annua) for giardiasis. We showed that NO production was significantly reduced whereas serum levels of IL-6, IFN-γ, and TNF-α were elevated in infected hamsters compared to uninfected ones. Additionally, infection resulted in increased numbers of intraepithelial lymphocytes and reduced villi heights, goblet cell numbers, and muscularis externa thickness. We also showed that inducible NO synthase (iNOS) and caspase-3 were elevated in the intestine of infected animals. However, treatment with A. annua significantly reduced the intestinal trophozoite counts and IEL numbers, serum IL-6, IFN-γ, and TNF-α, while increasing NO and restoring villi heights, GC numbers, and ME thickness. Moreover, A. annua treatment resulted in lower levels of caspase-3, which indicates a protective effect from apoptotic cell death. Interestingly, A. annua therapeutic effects are comparable to metronidazole. In conclusion, our results show that A. annua extract is effective in alleviating infection-induced intestinal inflammation and pathological effects, which implies its potential therapeutic utility in controlling giardiasis.

Aim: Ulcerative colitis (UC) is a common intestinal problem characterized by the diffusion of colon inflammation and immunity dysregulation. Nifuroxazide, a potent STAT-3 inhibitor, exhibits diverse pharmacological properties. The present study aimed to elucidate a novel anti-colitis mechanism of nifuroxazide against the acetic acid-induced UC model.

Methods: Rats were grouped into control (received vehicle), UC (2 ml of 5% acetic acid by intrarectal infusion), UC plus sulfasalazine (100 mg/kg/day, P.O.), UC plus nifuroxazide (25 mg/kg/day, P.O.), and UC plus nifuroxazide (50 mg/kg/day, P.O.) and lasted for 6 days.

Results: The present study revealed that nifuroxazide significantly reduced UC measures, hematological changes, and histological alteration. In addition, treatment with nifuroxazide significantly down-regulated serum CRP as well as the colonic expressions of MPO, IL-6, TNF-α, TLR-4, NF-κB-p65, JAK1, STAT-3, DKK1 in a dose-dependent manner. Besides, our results showed that the colonic Wnt expression was up-regulated with nifuroxazide treatment. In a dose-dependent manner, nifuroxazide markedly alleviated acetic acid-induced cellular infiltration and improved ulcer healing by increasing intestinal epithelial cell regeneration.

Significance: Our results collectively indicate that nifuroxazide is an effective anti-colitis agent through regulation of colon inflammation and proliferation via modulation IL-6/STAT-3/Wnt signaling pathway.

Keywords: Epithelial cell proliferation; IL-6/STAT-3/Wnt; Nifuroxazide; STAT-3 inhibitor; Ulcerative colitis.