Berberine protects against sepsis-related acute lung injury in rats via PPAR-γ signaling pathway upregulation and improvement at the cellular level: Functional, biochemical, and immunohistochemistry study.

This study aimed to assess the prophylactic effects of Berberine on experimentally induced lung sepsis and examine its effects on selected cytokines, genes, and protein expression besides the histopathological evaluation. Berberine significantly reduced the wet/dry lung ratio, the broncho-alveolar lavage fluid (BALF) protein, cells, neutrophils percentage, and cytokines levels. In addition, pretreatment with Berberine decreased the myeloperoxidase (MPO) and malondialdehyde (MDA) levels and decreased gene expression of nuclear factor kappa B (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and the intracellular adhesion molecule 1 (ICAM-1) by RT-qPCR analysis, revealing Berberine's antioxidant and anti-inflammatory mode of action. Western blot analysis revealed increased peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in the Berberine pretreated group compared to the cecal ligation and puncture (CLP) group, in which the histopathological examination evidenced this improvement. In conclusion, Berberine improved lung sepsis via its PPAR-γ mediated antioxidant and anti-inflammatory effects.

Evaluating the potential impact of sodium-glucose cotransporter-2 inhibitor "canagliflozin" on the hepatic damage triggered by hypertension in rats.

Hypertension (HTN) is a prevalent chronic disease. HTN and liver disease association is extensively noted. Thus, finding a medication that can alleviate HTN and its accompanying liver insult would be promising. This study investigated the potential impacts of canagliflozin "sodium-glucose cotransporter-2 inhibitor" on the liver of the Nω-nitro-L-arginine methyl ester (L-NAME)-induced HTN rat model. Twenty-four adult male rats were divided into four groups; negative control group, canagliflozin group, L-NAME group: 50 mg/kg of L-NAME was injected daily for 5 weeks and L-NAME + canagliflozin group: 1 week after L-NAME injection both L-NAME + canagliflozin (40 mg/kg) were given concomitantly daily for further 4 weeks. Liver functions, serum lipid profile, hepatic oxidative/nitrative stress biomarkers, gene expression of lipogenic enzymes, B-cell lymphoma 2 (Bcl2), and DNA fragmentation, were measured. Besides, hepatic histology and immunohistochemistry of nuclear factor kappa B (NF-κB) and endothelial nitric oxide synthase (eNOS) were assessed. Canagliflozin improved hepatic lipogenesis via the downregulation of fatty acid synthase (FAS) and transcriptional regulatory element binding protein 1c (SREBP1c) genes leading to an improved serum lipid profile. Further, canagliflozin modified the eNOS/inducible nitric oxide synthase (iNOS) pathway and decreased the NF-κB immunoreactivity besides restoring the oxidants-antioxidants balance; increased reduced glutathione concomitant with declined malondialdehyde. This improvement of the liver was mirrored by the significant restoration of liver architecture and confirmed by the preserved liver DNA content and upregulation of the antiapoptotic Bcl2 mRNA level and attenuation of the alanine transaminase, aspartate aminotransferase. In conclusion, canagliflozin is a promising anti-hypertensive and hepatic-supportive medication. RESEARCH HIGHLIGHTS: Canagliflozin's antioxidant, anti-inflammatory, anti-lipogenic, and antiapoptotic characteristics mitigate remote liver compromise caused by hypertension. Canagliflozin can be exploited as a hepatoprotective and antihypertensive medication.

Vitamin D and vitamin B12 profiles in children with primary nocturnal enuresis, an analytical cross-sectional study.

PURPOSE: To outline the prevalence of vitamin D and vitamin B12 deficiencies in enuretic children. METHODS: An analytical descriptive study was conducted on enuretic children who were followed up at the outpatient clinic for nocturnal enuresis at the Children's Hospital, Cairo University. Sociodemographic and clinical data were recorded. The levels of vitamin D and vitamin B12 were assessed and correlated with the severity of enuresis. RESULTS: Two hundred and eighty-eight children were enrolled. Insufficiency of Vitamin D predominated (n = 139; 48.3%). Vitamin D deficiency was present in 31.3%, n = 90 and it was normal in 20.5%, n = 59). Vitamin B12 deficiency was observed in 25% of the studied children, n = 72). The one-sample Wilcoxon signed-rank test was significant for both vitamins (P value =0.001). Vitamin D showed a stronger inverse correlation with the number of enuresis episodes per day than vitamin B12 (-0.680 vs. -0.219 respectively). A cut-off of 13.7 ng/ml for vitamin D was detected, below which the child was predicted to have failed dry nights. Using multivariate logistic regression, higher vitamin D levels and behavioural treatment coexistence were significant protective factors for the absence of dry nights. CONCLUSION: Low levels of vitamin D and B12 were detected in children with primary nocturnal enuresis, which could be considered a burden on the clinical severity of enuresis.

What is already known on this topic?Children with Primary Nocturnal Enuresis may have vitamin D and vitamin B₁₂ abnormalities as deficienciesWhat does this study add?Vitamin D insufficiency may be the most prevalent vitamin D abnormality in children with primary nocturnal enuresis. Vitamin D insufficiency may be more common in children with severe enuresis than vitamin B₁₂ deficiency.How might this study affect research, practice, or policy?This study may invite further research to examine the possible use of vitamin D and vitamin B12 as potential adjuvant therapies for children with Primary Nocturnal Enuresis.

SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats.

Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA's potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

Prognostic significance of the genetic variant of lymphotoxin alpha (p.Thr60Asn) in egyptian patients with advanced hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide in terms of mortality, and susceptibility is attributed to genetic, lifestyle, and environmental factors. Lymphotoxin alpha (LTA) has a crucial role in communicating the lymphocytes with stromal cells and provoking cytotoxic effects on the cancer cells. There are no reports on the contribution of the LTA (c.179 C>A; p.Thr60Asn; rs1041981) gene polymorphism to HCC susceptibility. The main aim of this study is to investigate the association of LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant with the HCC risk in the Egyptian population. METHODS: This case-control study included 317 participants (111 HCC patients, and 206 healthy controls). The LTA (c.179 C>A; p.Thr60Asn; rs1041981) polymorphism was assessed by tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique. RESULTS: The frequencies of the dominant and recessive models (CA + AA; AA) of the LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant were statistically significant among HCC patients in comparison to controls (p = 0.01; p = 0.007; respectively). The A-allele of LTA (c.179 C>A; p.Thr60Asn; rs1041981) variant was statistically significant in HCC patients in comparison to controls (p ˂ 0.001). CONCLUSION: The LTA (c.179 C>A; p.Thr60Asn; rs1041981) polymorphism was independently associated with an increased risk for hepatocellular carcinoma in the Egyptian population.

Protective effect of grape seed extract against chronic physical stress-induced zona fasciculata injury in male rats: Functional, immunohistochemical and electron microscopic study.

In the present study, we investigated the antioxidant effect of grape seed extract (GSE) against chronic immobilization stress-induced zona fasciculata injury in Wistar male rats. Thirty male rats were divided into three groups: Non-stress group: rats were not subjected to stress protocol and received distilled water orally for 30 days. Stress group: rats received distilled water orally for 15 consecutive days before the induction of chronic immobilization stress experiment (repeated stress for 15 consecutive days), distilled water was continued along with the constant stress experiment. GSE-stress group: rats treated with oral GSE (300 mg/kg), administered orally for 15 consecutive days before the induction of chronic immobilization stress experiment (repeated stress for 15 consecutive days), GSE was continued along with the stress exposure. Chronic stress was induced by placing each animal in a restrainer for 2 h daily for 15 consecutive days in both Stress and GSE-stress groups. The serum corticosterone and adrenal cortex malondialdehyde (MDA) levels were measured as indices of stress. Immunohistochemistry of the inducible nitric oxide synthase (iNOS) as a nitrosative stress marker beside the adrenal cortex's ultrastructure, particularly zona fasciculata, was assessed. Chronic restraint stress significantly elevated the serum corticosterone and adrenal cortex MDA levels, while oral administration of GSE reduced the serum corticosterone level, adrenal cortex MDA levels, and iNOS immunoreactivity in zona fasciculata. Besides, adrenocortical ultrastructure significantly improved. These results suggested that GSE enhanced the antioxidant defense against reactive oxygen species produced under chronic stress conditions, protecting the adrenal cortex. RESEARCH HIGHLIGHTS: This research highlighted the significant protective effects of grape seed extract administration on the histological findings, both in light and electron microscopic studies, as well as the biochemical and functional parameters in cases of stress-induced adrenal cortex injury in rats.

Effect of nebivolol on altered skeletal and cardiac muscles induced by dyslipidemia in rats: impact on oxidative and inflammatory machineries.

AIM: High cholesterol diet is greatly linked to deleterious health consequences. In this work we tried to explore direct effects of high cholesterol diet on striated (skeletal and cardiac) muscle tissues and the mechanisms by which nebivolol could improve such harmful effects. METHODS: The study included 24 healthy adult male albino rats weighing 200-220 grams that were assigned into four groups: control group, control drug group, high cholesterol diet fed groups; one untreated the other was treated with nebivolol. RESULTS: In the cholesterol fed group, we found decreased blood HDL and NO with elevated total cholesterol, triglycerides, myoglobin, CK, LDH, ALP, in addition to elevated muscle tissue levels of HIF-1, NF-kB, MDA, and decreased expression of both eNOS, reduced GSH. Wire hanging test time was shorter in the high cholesterol group than control group rats, which was confirmed histologically by increased striated muscle fibre thickness and cytochrome area %. Nebivolol treatment ameliorated the effects of high cholesterol diet. CONCLUSION: High cholesterol diet caused myopathic changes in rat striated muscle tissues mostly due to oxidative stress associated with enhanced NF-kB and HIF-1 expression. Nebivolol appears beneficial in the management of hypercholesterolaemia-induced striated muscle injury.

High-fat diet augments ovariectomy-induced bone resorption in rats / Dieta rica en grasas aumenta la resorción ósea inducida por ovariectomía en ratas

Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.

Las complicaciones de la menopausia, como las enfermedades cardiovasculares y óseas, representan un importante problema de salud pública. Intentamos determinar si una dieta alta en grasas (HFD) puede aumentar la resorción ósea inducida por ovariectomía en un modelo de menopausia en ratas, a través de la regulación positiva de los biomarcadores inflamatorios y la dislipidemia. Las ratas fueron ovariectomizadas y alimentadas con una comida estándar de laboratorio (grupo modelo) o fueron ovariectomizadas y alimentadas con un HFD durante 15 semanas antes de ser sacrificadas. La ovariectomía aumentó significativamente (p <0,05) el peso corporal, dislipidemia, resistencia a la insulina, citocinas proinflamatorias, factor de necrosis tumoral a (TNF-α) e interleucina-6 (IL-6), y el biomarcador de resorción ósea, factor nuclear-kB (NF-kB), que se aumentaron alimentando animales con un HFD. Esto se confirmó a través del estudio inmunohistoquímico, donde la ovariectomía indujo la expresión de la proteína p65 / NF-kB en secciones de hueso de tibia del grupo modelo, que fueron aumentadas por HFD. HFD aumenta la resorción ósea inducida por ovariectomía a través del aumento de biomarcadores inflamatorios y NF-kB en ratas.

Interrelation of liver vascularity to non-alcoholic fatty liver through a comparative study of the vasodilator effect of carvedilol or nicorandil in rats.

AIM: An experimental study of the effect of two vasodilators, carvedilol (B blocker with alpha-antagonist) and nicorandil (NO donor) on nonalcoholic fatty liver (NAFLD) induced by hypercholesterolemia and fatty diet in rats through studying the possible anti-inflammatory and antioxidant mechanisms. MAIN METHODS: The rats were divided into 4 groups (6 rats each): The first (negative control group). The second, third and fourth groups were fed with cholesterol and fat- enriched diet for one month that stopped and continued on the standard diet for another month without treatment in the second group but treated with carvedilol and nicorandil in the third and fourth group respectively. KEY FINDINGS: They revealed that both improved NAFLD especially nicorandil treated proved by the reduction of liver enzymes (AST, ALT), the fatty infiltration determined histologically and biochemically (decrease liver triglycerides). This may be due to either being antioxidants (reduced malondialdehyde and elevated reduced glutathione) or anti-inflammatory (decreased of TNF-α) together with the reduction of insulin resistance and adiponectin elevation or gene expression (increased liver NF-κB and decreased eNOS expression) and finally maybe by their obvious effect on improvements of lipid parameters. SIGNIFICANCE: Carvedilol and nicorandil improved NAFLD through the interrelationship between inflammatory cytokines, antioxidants and insulin resistance.