Non-alcoholic fatty liver disease (NAFLD) embraces several forms of liver disorders involving fat disposition in hepatocytes ranging from simple steatosis to the severe stage, namely, non-alcoholic steatohepatitis (NASH). Recently, several experimental in vivo animal models for NAFLD/NASH have been established. However, no reproducible experimental animal model displays the full spectrum of pathophysiological, histological, molecular, and clinical features associated with human NAFLD/NASH progression. Although methionine-choline-deficient (MCD) diet and high-fat diet (HFD) models can mimic histological and metabolic abnormalities of human disease, respectively, the molecular signaling pathways are extremely important for understanding the pathogenesis of the disease. This review aimed to assess the differences in gene expression patterns and NAFLD/NASH progression pathways among the most common dietary animal models, i.e., HFD- and MCD diet-fed animals. Studies showed that the HFD and MCD diet could induce either up- or downregulation of the expression of genes and proteins that are involved in lipid metabolism, inflammation, oxidative stress, and fibrogenesis pathways. Interestingly, the MCD diet model could spontaneously develop liver fibrosis within two to four weeks and has significant effects on the expression of genes that encode proteins and enzymes involved in the liver fibrogenesis pathway. However, such effects in the HFD model were found to occur after 24 weeks with insulin resistance but appear to cause less severe fibrosis. In conclusion, assessing the abnormal gene expression patterns caused by different diet types provides valuable information regarding the molecular mechanisms of NAFLD/NASH and predicts the clinical progression of the disease. However, expression profiling studies concerning genetic variants involved in the development and progression of NAFLD/NASH should be conducted.

Background: Several instruments are currently used to assess Coronavirus Disease 2019 (COVID-19) -induced psychological distress, including the 22-item Impact of Event Scale-Revised (IES-R). The IES-R is a self-administered scale used to assess post-traumatic stress disorder (PTSD). The current study aimed to examine the construct validity of the IES-R, based on the Rasch model, with COVID-19-related data, as well as to test the multilevel construct validity of the IES-R within and among countries during the pandemic crisis. Methods: A multi-country web-based cross-sectional survey was conducted utilizing the 22-item IES-R. A total of 1020 participants enrolled in our survey, of whom 999 were included in the analyses. Data were analyzed using Rasch modeling and multilevel confirmatory factor analysis (MCFA). Results: The Rasch modeling results of the IES-R demonstrated that the IES-R is a satisfactory instrument with the five-point Likert scale, asserting that its 22 items are significant contributors to assessing PTSD as a unidimensional construct covered by the items of the IES-R. The MCFA confirmed that the 22-item IES-R, with its three factors, including intrusion, avoidance, and hyperarousal, demonstrates adequate construct validity at the within- and among-country levels. However, the results of the Akaike information criterion (AIC) model determined that the 16-item IES-R is better than the 22-item IES-R. Conclusion: The results suggested that the 22-item IES-R is a reliable screening instrument for measuring PTSD related to the COVID-19 pandemic, and can be utilized to provide timely psychological health support, when needed, based on the screening results.

The COVID-19 pandemic, on a global scale, has prompted multifaceted challenges, including a notable psychological toll on the general population. This study uses mixed-method approach for a nuanced exploration of these experiences. Using a phenomenological strategy, qualitative responses from 999 participants were analyzed regarding their pandemic-induced anxiety and the influence of quarantine measures on their lives. Quantitative measures, including the revised Impact of Event Scale (IES-R), patient health questionnaire-9 (PHQ-9), the seven-item generalized anxiety disorder assessment (GAD-7), and Insomnia Severity Index (ISI), were used to quantify trauma, depression, anxiety, and insomnia attributed to COVID-19. Partial least squares structural equation modeling (PLS-SEM) was utilized for quantitative data analysis. The anxiety-related responses were mainly clustered into four themes: life threats, support shortage, economic consequences, and disruptions to family and social life. Subthemes that addressed the perceived effects encapsulated disruptions to academic and professional lives, familial and social relationships, psychopathological stress, and movement limitations. The findings from quantitative analysis revealed the significant associations between COVID-19-related trauma and symptoms of anxiety, depression, and insomnia, as indicated by coefficients exceeding 0.10 (all z-values > 1.96; p-values < 0.05). In conclusion, the findings underscore COVID-19’s role in escalating anxiety, influenced by various factors, and its disruptive effects on daily life due to quarantine measures. The strong associations between the pandemic and the symptoms of depression, anxiety, and insomnia underscore the urgency of comprehensive psychological and public health interventions to alleviate these impacts.

Apoptosis Induction, Cell Cycle Arrest and in Vitro Anticancer Activity of Gonothalamin in a Cancer Cell Lines Goniothalamin;HeLa cervical cancer cell line;fluorescence microscopy;cellular DNA content;apoptosis; Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.

Background: Ceratonia siliquapods (carob) have been nominated to control the high blood glucose of diabetics. In Yemen, however, its antihyperglycemic activity has not been yet assessed. Thus, this study evaluated thein vitroinhibitory effect of the methanolic extract of carob pods against α-amylase and α-glucosidase and thein vivoglycemic effect of such extract in streptozotocin-nicotinamide induced diabetic rats.Methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric reducing antioxidant power assay (FRAP) were applied to evaluate the antioxidant activity of carob.In vitrocytotoxicity of carob was conducted on human hepatocytes (WRL68) and rat pancreatic β-cells (RIN-5F). Acute oral toxicity of carob was conducted on a total of 18 male and 18 femaleSprague-Dawley(SD) rats, which were subdivided into three groups (n = 6), namely: high and low dose carob-treated (CS5000 and CS2000, respectively) as well as the normal control (NC) receiving a single oral dose of 5,000 mg kg⁻¹carob, 2,000 mg kg⁻¹carob and 5 mL kg⁻¹distilled water for 14 days, respectively. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine and urea were assessed. Livers and kidneys were harvested for histopathology.In vitroinhibitory effect against α-amylase and α-glucosidase was evaluated.In vivoglycemic activity was conducted on 24 male SD rats which were previously intraperitoneally injected with 55 mg kg⁻¹streptozotocin (STZ) followed by 210 mg kg⁻¹nicotinamide to induce type 2 diabetes mellitus. An extra non-injected group (n = 6) was added as a normal control (NC). The injected-rats were divided into four groups (n = 6), namely: diabetic control (D0), 5 mg kg⁻¹glibenclamide-treated diabetic (GD), 500 mg kg⁻¹carob-treated diabetic (CS500) and 1,000 mg kg⁻¹carob-treated diabetic (CS1000). All groups received a single oral daily dose of their treatment for 4 weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance test, biochemistry, insulin and hemostatic model assessment were assessed. Pancreases was harvested for histopathology.Results: Carob demonstrated a FRAP value of 3191.67 ± 54.34 µmoL Fe⁺⁺and IC₅₀of DPPH of 11.23 ± 0.47 µg mL⁻¹.In vitro,carob was non-toxic on hepatocytes and pancreatic β-cells. In acute oral toxicity, liver and kidney functions and their histological sections showed no abnormalities. Carob exerted anin vitroinhibitory effect against α-amylase and α-glucosidase with IC₅₀of 92.99 ± 0.22 and 97.13 ± 4.11 µg mL⁻¹, respectively. In diabetic induced rats, FBG of CS1000 was significantly less than diabetic control. Histological pancreatic sections of CS1000 showed less destruction of β-cells than CS500 and diabetic control.Conclusion: Carob pod did not cause acute systemic toxicity and showedin vitroantioxidant effects. On the other hand, inhibiting α-amylase and α-glucosidase was evident. Interestingly, a high dose of carob exhibits anin vivoantihyperglycemic activity and warrants further in-depth study to identify the potential carob extract composition.

Background: Several natural products have been reported to elicit beneficial effects against neurodegenerative disorders due to their vitamin E contents. However, the neuroprotective efficacy of palm oil or its tocotrienol-rich fraction (TRF) from the pre-clinical cell and animal studies have not been systematically reviewed. Methods: The protocol for this systematic review was registered in “PROSPERO” (CRD42019150408). This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Medical Subject Heading (MeSH) descriptors of PubMed with Boolean operators were used to construct keywords, including (“Palm Oil”[Mesh]) AND “Nervous System”[Mesh], (“Palm Oil”[Mesh]) AND “Neurodegenerative Diseases”[Mesh], (“Palm Oil”[Mesh]) AND “Brain”[Mesh], and (“Palm Oil”[Mesh]) AND “Cognition”[Mesh], to retrieve the pertinent records from PubMed, Scopus, Web of Science and ScienceDirect from 1990 to 2019, while bibliographies, ProQuest and Google Scholar were searched to ensure a comprehensive identification of relevant articles. Two independent investigators were involved at every stage of the systematic review, while discrepancies were resolved through discussion with a third investigator. Results: All of the 18 included studies in this review (10 animal and eight cell studies) showed that palm oil and TRF enhanced the cognitive performance of healthy animals. In diabetes-induced rats, TRF and α-tocotrienol enhanced cognitive function and exerted antioxidant, anti-apoptotic and anti-inflammatory activities, while in a transgenic Alzheimer’s disease (AD) animal model, TRF enhanced the cognitive function and reduced the deposition of β-amyloid by altering the expression of several genes related to AD and neuroprotection. In cell studies, simultaneous treatment with α-tocotrienols and neurotoxins improved the redox status in neuronal cells better than γ- and δ-tocotrienols. Both pre-treatment and post-treatment with α-tocotrienol relative to oxidative insults were able to enhance the survival of neuronal cells via increased antioxidant responses. Conclusions: Palm oil and its TRF enhanced the cognitive functions of healthy animals, while TRF and α-tocotrienol enhanced the cognitive performance with attenuation of oxidative stress, neuroinflammation and apoptosis in diabetes-induced or transgenic AD animal models. In cell studies, TRF and α-tocotrienol exerted prophylactic neuroprotective effects, while α-tocotrienol exerted therapeutic neuroprotective effects that were superior to those of γ- and δ-tocotrienol isomers.