Neuroprotective and cognitive enhancing effects of herbecetin against thioacetamide induced hepatic encephalopathy in rats via upregulation of AMPK and SIRT1 signaling pathways.

Acute liver injury, there is a risky neurological condition known as hepatic encephalopathy (HE). Herbacetin is a glycosylated flavonoid with many pharmacological characteristics. The purpose of this study was to assess the ability of herbacetin to protect against the cognitive deficits associated with thioacetamide (TAA) rat model and delineate the underlying behavioral and pharmacological mechanisms. Rats were pretreated with herbacetin (20 and 40 mg/kg) for 30days. On 30th day, the rats were injected with TAA (i.p. 350 mg/kg) in a single dose. In addition to a histpathological studies, ultra-structural architecture of the brain, liver functions, oxidative stress biomarkers, and behavioral tests were evaluated. Compared to the TAA-intoxicated group, herbacetin improved the locomotor and cognitive deficits, serum hepatotoxicity indices and ammonia levels. Herbacetin reduced brain levels of malodialdeyde, glutamine synthetase (GS), tumor necrosis factor- alpha (TNF-α), interleukin 1 B (IL-1ß), annexin v, and increased brain GSH, Sirtuin 1 (SIRT1), and AMP-activated kinase (AMPK) expression levels. Also, herbacetin improve the histopathological changes and ultra- structure of brain tissue via attenuating the number of inflammatory and apoptotic cells. Herbacetin treatment significantly reduced the toxicity caused by TAA. These findings suggest that herbacetin might be taken into account as a possible neuroprotective and cognitive enhancing agent due to its ability to reduce oxidative stress, inflammation and apoptosis associated with TAA.

Involvement of INF-γ functional single nucleotide polymorphism +874 T/A (rs2430561) in breast cancer risk.

According Global Cancer Statistics 2020 GLOBOCAN estimates female breast cancer was found as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), and the fourth leading cause (6.9%) of cancer death among women worldwide. Identification of new diagnostic marker sharply characterize the tumor feature is intensive need. The present work was performed to investigate the involvement of the INF-γ + 874 T/A gene polymorphism in different breast cancer prognostic factors. Polymorphism detection analysis was performed on 163 subjects from breast cancer patients, 79 with inflamed cells of breast patients and 144 controls. The gene polymorphism was detected using the amplification refractory mutation system- polymerase chain reaction method (ARMS-PCR). The distribution of INF-γ T + 874A gene polymorphism shows strong significant association between INF-γ + 874 T/A genotypes TT in BC patients (ORTT: 6.41 [95% CI = 2.72-15.1] P < 0.0001) as well as strong significant association regarding T allele (ORT: 1.99 [95% CI = 1.43-2.76] P < 0.0001) when compared to the healthy control. In ICB group the strong association was noted with INF-γ + 874 T/A genotypes AT genotype (ORAT: 2.28 [95% CI = 1.22-4.29] P = 0.007). From the different histological BC hormonal markers the human epidermal growth factor receptor 2 (HER2) was showing significant association in INF-γ + 874 T/A genotypes TT (P = 0.03) and recessive model (TT versus AA + AT P = 0.03). Concerning different BC prognostic models, the poor prognostic one of luminal B, (ER+ve PR+ve Her2+ve) show significant association in the host INF-γ + 874 T/A genotype (TT, P = 0.03) and recessive model (TT versus AA + AT P = 0.02) when compared to the good prognostic hormonal status luminal A model, (ER+ve PR+ve Her2-ve). It seems that this is the first study that interested in correlate the INF-γ + 874 T/A gene polymorphisms in Egyptian BC patients. T allele, TT genotype and recessive model of the INF-γ + 874 T/A gene variants were documented as risk factors for BC pathogenesis. It may be used as practical biomarker to guide the BC carcinogenesis and risk process.

Adipocytokines in Patients with Chronic Kidney Disease Stage 5.

BACKGROUND: Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD). METHODS: 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR). RESULTS: Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients. CONCLUSIONS: The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.