Aloe vera gel confers therapeutic effect by reducing pyroptosis in ethanol-induced gastric ulcer rat model: Role of NLRP3/GSDMD signaling pathway.

BACKGROUND: Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. METHODS: An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. RESULTS: The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. CONCLUSIONS: Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Monitoring the immune response of macrophages in tuberculous granuloma through the expression of CD68, iNOS and HLA-DR in naturally infected beef cattle.

Bovine tuberculosis still represents a universal threat that creates a wider range of public and animal health impacts. One of the most important steps in the pathogenesis of this disease and granuloma formation is the phagocytosis of tuberculous bacilli by macrophages. Mycobacteria replicate in macrophages, which are crucial to the pathophysiology of mycobacterial infections; however, scarce information is available about the dynamics of the granuloma-stage immunological response. Therefore, immunohistochemistry was used in this work to evaluate the expression of CD68, iNOS, and HLA-DR in different stages of TB granulomas from naturally infected cattle with tuberculosis. Two thousand, one hundred and fifty slaughtered beef cattle were examined during the period from September 2020 to March 2022. Sixty of them showed gross tuberculous pulmonary lesions and samples were collected from all of them for histopathological examination, Ziehl-Neelsen (ZN) staining, and bacteriological culturing. Selected samples that yielded a positive result for ZN and mycobacterial culturing were subjected to an immunohistochemical study of CD68, iNOS, and HLA-DR expression by macrophages according to granuloma stages. Immunohistochemical analysis revealed that the immunolabeling of CD68+, iNOS+, and HLA-DR+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P < 0.003, P < 0.002, and P < 0.002, respectively). The distribution of immunolabeled macrophages was similar for the three markers, with immunolabeled macrophages distributed throughout early-stage granulomas (I, II), and surrounding the necrotic core in late-stage granulomas (III, IV). Our results suggest a polarization to the pro-inflammatory environment and increased expression of CD68+, iNOS+, and HLA-DR+ macrophages in the early stages of granulomas (I, II), which may play a protective role in the immune response of naturally infected beef cattle with tuberculosis.

Novel therapeutic regimens for urethane-induced early lung cancer in rats: Combined cisplatin nanoparticles with vitamin-D3.

Lung cancer remains incurable; therefore, novel therapeutical approaches are of great demand. This study was designed to investigate the effectiveness of cisplatin nanoparticles combined with vitamin-D3 on urethane-induced early lung cancer in rats and to clarify the underlying signaling mechanisms. Early lung cancer was induced in male Wistar rats by urethane. Rats were divided into six groups: I-control, II-cancer untreated, III-cancer + free cisplatin, IV-cancer + cisplatin nanoparticles, V-cancer + free cisplatin + vitamin-D3 , VI-cancer + cisplatin nanoparticles + vitamin-D3 . Inflammation, proliferation, and apoptosis were evaluated together with the levels of tumor marker CK-19 along with histological assessment. Treatment of lung cancer with either free or nanoparticles of cisplatin alone demonstrated significant suppression in the expression of inflammatory, anti-apoptotic and tumor markers compared to rats with lung cancer. Moreover, vitamin-D3 supplementation with either cisplatin forms lead to a further decrease of all markers, markedly with cisplatin nanoparticles. The present study shows the synergistic effect of cisplatin-nanoparticles combined with vitamin-D3 as a new therapy regimen against lung cancer. Further studies with larger sample sizes and longer duration are needed to confirm these results.

Validation of the Diagnostic and Prognostic Values of ADAMTS5 and FSTL1 in Osteoarthritis Rat Model.

OBJECTIVE: Osteoarthritis (OA) is a global public health problem and a leading cause of morbidity and disability. Due to lack of sensitive and specific tools for early OA diagnosis and predicting prognosis, the availability of new reliable and sensitive biomarkers is a widely appreciated need to identify patients at risk for incident disease or disease progression. Accordingly, our study was conducted to validate the usefulness of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and follistatin-like protein 1 (FSTL1) to achieve this goal. DESIGN: Fifty-four male Wistar rats were randomized into 3 groups; 24 rats were subjected to medial meniscal tear (MMT) surgery on the right knee joint (OA group), 24 rats were subjected to sham surgery (sham group), and 6 healthy rats (negative control group). Six animals from each group were sacrificed every 2 weeks. At each time point, the right knee joint of each animal was visualized radiologically, a blood sample was collected, and cartilage tissues were isolated for histopathological and western blot analysis. RESULTS: We found that the expression levels of ADAMTS5 and FSTL1 significantly increased with OA progression, especially at weeks 4, 6, and 8 after surgery. Notably, the serum levels of ADAMTS5 and FSTL1 showed significant positive correlations with each other and with the studied inflammatory markers. CONCLUSIONS: Our findings suggest that ADAMTS5 and FSTL1 can serve as important and informative serological markers of disease activity in OA. However, further research is needed to validate their use for improving the diagnosis and prognosis of OA in humans.

Comparative study on dynamic and immunopathology of four intermediate-plus infectious bursal disease (IBD) vaccines in commercial broiler chickens.

INTRODUCTION: The selection of the right IBD control strategy is primarily based on the choice of the appropriate vaccine strain. High maternal IBD-specific antibodies (Abs) compete with the efficacy IBD vaccine, which necessitates the application of intermediate-plus vaccine strain. METHODS: A comparative experimental study was designed for evaluation of four different commercially available intermediate-plus IBD vaccines in commercial broilers before complete weaning of IBD-specific maternal Abs. RESULTS: As determined by IBD- specific quantitative real-time polymerase chain reaction, three tested vaccine strains (228E, Winterfield H2512, and Winterfield 2512) were able to establish in the bursal tissues as early as six hours (hrs) post-vaccination (PV). Both the 228E and the Winterfield H2512 strains vaccinated groups had the highest viral load and replication rate in the bursal tissues at 24, 36, 48 and 72 hrs PV. Earlier seroconversion, 7-14 days PV, was observed in the case of Winterfield H2512, 228E, and Winterfield 2512 vaccinated birds compared to the Lukert vaccinated birds. The 228E strain was more virulent and induces the highest lesion score with severe degrees of lymphocyte depletion and necrosis which persisted up to 28 days PV. CONCLUSION: Overall, the different intermediate-plus IBD strains possess variable early kinetics in the bursal tissues and eliciting antibody (Ab) responses differently withdifferent degrees of bursal lesions. The assessment of the intrabursal vaccine load together with humoral immunity and bursal damage lesion score are fundamental parameters in the evaluation of the intermediate-plus IBD vaccines.

Effect of a high fat, high sucrose diet on the promotion of non-alcoholic fatty liver disease in male rats: the ameliorative role of three natural compounds.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease with a complex pathophysiology. The clinical features of NAFLD include obesity, insulin resistance (IR) and dyslipidemia. Consumption of a diet high in saturated fats and sucrose is an important factor in the increasing occurrence of these metabolic disorders, primarily NAFLD and IR. We sought to assess the role of a high-fat, high-sucrose (HFS) diet in the promotion of NAFLD and to evaluate the effects of quercetin (Q), berberine (BB) and o-coumaric acid (CA) on modulation of these disorders. METHODS: Fifty male rats were divided into 2 main groups as follows: group 1 comprised 10 rats fed a standard diet (SD), and group 2 comprised 40 rats fed an HFS diet for 6 weeks and then subdivided equally into 4 groups; one of these groups served as the HFS diet and each of the other three groups received daily supplementation with either Q, CA or BB for 6 weeks. RESULTS: In the present study, several metabolic disorders were induced in our laboratory animal model, as evidenced by histological and biochemical changes. These alterations included serum and hepatic dyslipidemia (i.e., increased triglyceride, total cholesterol and low-density lipoprotein levels and decreased high-density lipoprotein levels), alterations in metabolic enzyme activities (lipase, glycerol-3-phosphate dehydrogenase, and glucose-6-phosphate dehydrogenase), histological changes in the liver (micro- and macrovesicular steatosis) and the downregulation of peroxisome proliferator-activated receptor γ (PPARγ) in adipose tissue and the liver. Daily oral supplementation with Q, CA or BB for 6 weeks after NAFLD induction had a hypolipidemic action and modulated metabolic markers. CONCLUSION: We showed that an HFS diet is able to promote NAFLD, and our results suggest that CA and BB are promising complementary supplements that can ameliorate the metabolic disorders associated with an HFS diet; however, Q requires further investigation.

Aluminum-induced neurotoxicity and oxidative damage in rabbits: protective effect of melatonin.

OBJECTIVE: The present study was aimed to investigate: (1) the neurotoxic oxidative damage of orally administered aluminum chloride (AlCl3) in rabbits (Biochemical and morphopathological studies). (2) The effect of melatonin as an antioxidant and free radical scavenger on oxidative neuropathic changes. METHODS: Thirty-five male rabbits were divided into 4 groups (A, B, C [10 animals each] and D [5 animals]). Group A received AlCl3 (20 mg/l via drinking water for 3 months). Group B received AlCl3 for 3 months then administered with melatonin (10 mg/kg b.w. sc daily for 15 days). Group C received AlCl3 plus melatonin for 3 months. Group D received the solvent and served as control. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) as lipid peroxides as well as superoxide dismutase (SOD) as an antioxidant enzyme were measured. Aluminum residue in the brain tissue was measured spectrophotometerically. The morphopathological changes were also examined by light and electron microscopes. RESULTS: MDA and 4-HAD were significantly increased in group A versus those of controls while significantly decreased in groups B and C compared with those of A group. SOD run in an opposite manner. Aluminum concentration was significantly increased in groups A, B and C when compared with group D while it significantly decreased in groups B and C when compared with that of group A. The neuropathlogical examination in the animals of group A revealed atrophy and apoptosis of the neurons in cerebral cortex and hippocampus. This was associated with neurofibrillary degeneration as well as argyrophilic inclusion. Schwan cell degeneration and nerve fiber demylination were also encountered. The elaboration of lipid peroxidation products, inhibition of antioxidant enzymes and the morphopathological changes were minimized in the Al/Mel treated groups and markedly improved in Al+Mel treated group CONCLUSION: Chronic aluminum exposure in rabbits had dramatic encephalopathic morphopathological lesions. It enhances the lipid peroxidation production and inhibits the SOD enzyme. Melatonin had a good prophylactic effect as an antioxidant in aluminum encephalopathy.