Molecular docking targeting autophagy pathway mediate abrogation of NASH by specific functional foods: update review.

Autophagy is a very well-conserved self-digestive mechanism that transports unwanted or disposable cytoplasmic debris to lysosomes for destruction, including misfolded proteins and damaged organelles. Advanced liver illnesses can develop from the prevalent clinical condition known as non-alcoholic steatohepatitis (NASH). There is no effective treatment, is still unclear. Therefore, in order to create novel therapeutics, it is necessary to comprehend the pathogenic pathways causing disease onset and progression. Natural components from medicinal plants are currently the subject of a larger number of studies since they provide fresh promise for NASH. This review provided an overview of the aetiology of NASH, in addition the role of natural products as alternative or complementary therapeutic agent for management of NASH via autophagy induction. It was concluded that, alternative and complementary supplement of natural functional food as Arabica coffee that rich with chlorogenic acid targeting autophagy mechanism mediate amelioration effect of NASH.

Endostatin and Cystatin C as Potential Biomarkers for Early Prediction of Preeclampsia.

Preeclampsia (PE) is characterized by new onset hypertension and proteinuria. Undoubtedly, some individuals do not fit precisely into this description, and it could be challenging to spot newly developed PE in females who already have hypertension or renal illness. Monitoring the disease's progression enables the optimization of delivery time while minimizing premature births. The current study explores the diagnostic benefits of serum endostatin and cystatin C in addition to serum and urinary magnesium (Mg) and fractional excretion magnesium (FEMg) for early prediction of PE. The population sample included 82 pregnant women divided into 3 groups: normal pregnancy group served as a control (n = 26), nonpreeclampsia (NPE, n = 34) group included pregnant women with one or more risk factors but did not progress to PE, and pregnant women who developed preeclampsia (PE, n = 22) group. Blood samples were withdrawn at two sampling times: at 12th to 16th and 24th to 26th weeks of gestation. Compared to normal pregnancy, results (X̅ ± SD) indicated a significant increase in serum endostatin in NPE at the first sample (10.78 ± 3.63 ng/mL) and the second sample (28.03 ± 3.79 ng/mL), while cystatin C was at the first sample (0.68 ± 0.06 mg/dL) and the second sample (0.71 ± 0.07 mg/dL). In the PE group, the serum endostatin was 18.86 ± 4.37 ng/mL at the first sampling time and 53.56 ± 9.76 ng/mL for the second sample. Serum cystatin C was also elevated in PE with X̅ ± SD equivalent to 0.73 ± 0.08 and 0.89 ± 0.08 mg/dL at the first and second samples, respectively. On the other hand, serum and urinary Mg in addition to FEMg levels did not significantly differ across the groups under study. Receiver operating characteristic (ROC) curve analysis proved that both endostatin and cystatin C could be good indicators for PE. The findings imply that measuring endostatin and cystatin C at early pregnancy and before progression to PE may be effective in detecting the likelihood of PE. Endostatin could be more precise and sensitive in assessing the probability of PE than cystatin C; however, coupling of the two parameters may be promising.

Evaluation of miRNA-7, miRNA-10 and miRNA-21 as diagnostic non-invasive biomarkers of hepatocellular carcinoma.

Aim of the study: Liver cancer (hepatocellular carcinoma - HCC) remains a serious health challenge; it is the fourth leading cause of death worldwide. Egypt ranks fifteenth worldwide and the third in Africa in terms of HCC burden. The present study aimed to assess some microRNAs (miRNAs) including miRNA-7, miRNA-10, and miRNA-21, serum markers such as cluster of differentiation-14 (CD-14) and transforming growth factor b1 (TGF-b1), and other biochemical parameters as non-invasive tools for HCC diagnosis. Material and methods: The study included 100 participants divided into five groups: group I (20 normal subjects as a healthy group), group II (20 participants with chronic HCV infection but non-cirrhotic), group III (20 volunteers with chronic HCV infection and compensated cirrhosis), group IV (20 patients with chronic HCV infection and decompensated cirrhosis), and group V (20 participants with HCC). Levels of miR-7, miR-10, and miR-21 were evaluated using qRT-PCR. Serum ALT, AST, total bilirubin, total protein, albumin, PT, INR, and platelet count were determined. FIB-4 and APRI test levels were also calculated. CD-14 and TGF-ß1 serum levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits. Results: The expression levels of miR-21 followed by miR-10 showed high sensitivity and specificity in predicting HCC. Serum CD-14 and TGF-b1 levels were significantly increased in all patient groups. Conclusions: From the study, it is concluded that the expression level of miR-21 has the highest sensitivity and specificity, followed by miR-10, which has high sensitivity and low specificity as non-invasive markers for HCC detection, while miR-7 exhibits high sensitivity and reasonable specificity in fibrosis detection.

Pomegranate Peel Extract Sensitizes Hepatocellular Carcinoma Cells to Ionizing Radiation, Induces Apoptosis and Inhibits MAPK, JAK/STAT3, ß-Catenin/NOTCH, and SOCS3 Signaling.

Tumor resistance is typically blamed for the failure of radiotherapy and chemotherapy to treat cancer in clinic patients. To improve the cytotoxicity of tumor cells using radiation in conjunction with specific tumor-selective cytotoxic drugs is crucial. Pomegranate has received overwhelmingly positive feedback as a highly nutritious food for enhancing health and treating a variety of ailments. In the present study, we aimed to examine the effects as well as mechanism of action of pomegranate peel extract (PPE) and/or γ-radiation (6-Gy) on hepatocellular carcinoma (HCC) cell lines HepG2. The findings of this study showed that PPE treatment of HepG2 cells considerably slowed the proliferation of cancer cells, and its combination with γ-irradiation potentiated this action. As a key player in tumor proliferation, and inflammatory cascade induction, the down-regulation of STAT3 following treatment of irradiated and non-irradiated HepG2 cells with PPE as recorded in the present work resulted in reduction of tumor growth, via modulating inflammatory response manifested by (down-regulation of TLR4 expression and NFKB level), suppressing survival markers expressed by reduction of JAK, NOTCH1, ß-catenin, SOCS3, and enhancing apoptosis (induction of tumor PPAR-γ and caspase-3) followed by changes in redox tone (expressed by increase in Nrf-2, SOD and catalase activities, and decrease in MDA concentration). In conclusion, PPE might possess a considerable therapeutic potential against HCC in addition to its capability to enhance response of HepG2 cells to gamma radiation.

Nattokinase attenuates bisphenol A or gamma irradiation-mediated hepatic and neural toxicity by activation of Nrf2 and suppression of inflammatory mediators in rats.

Nattokinase (NK), a protease enzyme produced by Bacillus subtilis, has various biological effects such as lipid-lowering activity, antihypertensive, antiplatelet/anticoagulant, and neuroprotective effects. Exposure to environmental toxicants such as bisphenol A (BPA) or γ-radiation (IR) causes multi-organ toxicity through several mechanisms such as impairment of oxidative status, signaling pathways, and hepatic and neuronal functions as well as disruption of the inflammatory responses. Therefore, this study is designed to evaluate the ameliorative effect of NK against BPA- or IR-induced liver and brain damage in rats. Serum ammonia level and liver function tests were measured in addition to brain oxidative stress markers, amyloid-beta, tau protein, and neuroinflammatory mediators. Moreover, relative quantification of brain nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) genes, as well as apoptotic markers in brain tissue, was carried out in addition to histopathological examination. The results showed that NK improved liver functions, impaired oxidative status, the cholinergic deficits, and minified the misfolded proteins aggregates. Furthermore, NK alleviated the neuroinflammation via modulating NF-κB/Nrf2/HO-1 pathway and glial cell activation in addition to their antiapoptotic effect. Collectively, the current results revealed the protective effect of NK against hepatic and neurotoxicity derived from BPA or IR.

Pre-micro RNA polymorphism detection in small versus large vessel disease in stroke Egyptian patients.

Stroke is the main cause of adult disability and is responsible for around 11% of deaths all over the world. Ischemic stroke encompasses about 80-85% of total stroke cases. Several studies have shown the relation between microRNAs polymorphism and ischemic stroke. The aim of the study was to evaluate the influence of three common single nucleotide polymorphisms in pre-miRNAs (hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913 and hsa-miR-499/rs3746444) on individual susceptibility to the risk of ischemic stroke subtypes in Egyptian population with 117 ischemic stroke patients. Results showed that hsa-miR-146a/rs2910164 was significantly associated with the risk of small vessel disease stroke in Egyptian population with no significant association between hsa-miR-196a2/rs11614913 and hsa-miR-499/rs3746444 with the risk of ischemic stroke. Therefore, it can be concluded that miR-146a/rs2910164 polymorphism is involved in the vulnerability to small vessel disease ischemic stroke risk in Egyptian population.

Amphora algae with low-level ionizing radiation exposure ameliorate D-galactosamine-induced inflammatory impairment in rat kidney.

d-Galactosamine (d-GalN) is a well-known toxin that causes many metabolic and morphological abnormalities resulting in advanced renal failure and liver damage. Occupational exposure to low-level ionizing radiation (<1 Gy) was shown to enhance cell protection via attenuating an established inflammatory process. The present study was therefore aimed to investigate the protective impact of Amphora coffaeiformis extract and low dose gamma radiation against d-GalN induced renal damage in rats. Forty-eight adult male Swiss albino rats were distributed equally into eight groups. The measurements included antioxidants activities (superoxide dismutase, catalase and glutathione peroxidase) as well as lipid peroxidation level in kidney tissue. Also, kidney function tests and inflammatory markers (tumor necrosis factor alpha and nuclear factor kappa-light-chain-enhancer of activated B cells) were measured. Additionally, relative quantification of kidney nuclear factor erythroid 2-related factor 2 (Nrf-2) gene was estimated. Histopathological examination was also performed in kidney tissue. The results revealed decreases in antioxidant activities and downregulation of Nrf-2 expression accompanied by increases in lipid peroxidation level, kidney function tests and inflammatory markers in d-GaIN group. The treatment with Amphora algal extract and low dose gamma radiation ameliorated the previous measurements which were harmony with histopathological findings. In conclusion, A coffaeiformis extract and low dose gamma radiation provided marked functional and histological effects in the treating acute renal damage induced by d-GalN in rats.