Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming.Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria.Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1–61.10), ACE2 rs2285666 CT + TT 9.9 (3.2–30.9), both p < 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p < 0.001).Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.

It is still a matter of debate as to whether in vitro mesenchymal stem cell (MSC)-derived hepatocytes may efficiently repopulate a host liver to provide adequate functional substitution. The aim of this study is to assess the efficacy and consistency of in vitro hepatic differentiation from Wharton jelly-derived MSCs, and to validate their therapeutic potential in experimentally induced liver fibrosis compared with nondifferentiated MSCs. Forty adult male albino rats were divided into 4 main groups: (I) normal control group; (II) carbon tetrachloride (CCl4)-treated group (injected CCl4 solution twice a week for 8 wk); (III) MSC-treated group (a single intravenous dose of MSCs from human umbilical cord at the fourth week of induction of fibrosis); and (IV) hepatocyte-like stem cells (HLCs)-treated group (a single intravenous dose of MSCs after in vitro conversion to hepatocyte at the fourth week of induction of fibrosis). Portal blood flow velocity and resistance, serum alanine transaminase, aspartate transaminase, albumin, and total bilirubin were measured. Liver homogenate was prepared for malondialdehyde, superoxide dismutase (SOD), nitric oxide (measured as nitrites), and TGFβ (transforming growth factor beta) assessment. Assessment of human cells homing into liver rat and their function was performed using immunohistochemistry for detection of human hepatocytes and α-fetoprotein antigens. Significant elevation of serum alanine transaminase, aspartate transaminase, and bilirubin, liver malondialdehyde, nitrites, TGFβ, fibrotic score, and significant reduction in serum albumin, liver SOD, and portal flow velocity in the CCl4-treated group were found when compared with normal rats. All these parameters significantly reversed in MSC-treated and hepatocyte-treated groups when compared with the CCl4-treated group. The MSC-treated group shows statistically better results in most liver function and oxidation parameters when compared with the HLC-treated group. Human MSCs can differentiate in vitro into functional HLCs. Transplantation of both MSCs and HLCs was feasible and effective in a liver fibrosis rat model. However, MSCs were better in regaining liver function. Future studies should address strategies to improve long-term implantation of MSCs and HLCs in the host liver.

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Introduction: Metabolic Syndrome (MetS) can be induced by ingestion of large amounts of fructose as a con sequence of oxidative stress and dyslipidemia. aim: We investi gated the possible protective effects of melatonin administration on MetS induced in fructose-fed rats with special focus on the role of renal aquaporin-3 (AQP-3). materials and methods: Thirty rats were randomly divided into three groups; control, fructose, and fructose plus melatonin. MetS was induced by fructose rich diet and melatonin was injected at a dose of 5 mg/kg dissolved in 1% ethanol in normal saline. After the end of the 6-week experimental period, body weight and fat accretion were assessed. Invasive blood pressure and vascular reactivity were evaluated. Serum lipid profile, glucose, insulin levels, insulin resistance, malondialdehyde (MDA) and uric acid were measured, also underwent renal AQP-3 immunohistochemistry.

Schizophrenia remains one of the most chronic and highly disabling mental disorders. Lumateperone is a recent FDA-approved atypical antipsychotic drug for the treatment of schizophrenia. However, the internal FDA pathologist raised concerns regarding pigment deposition associated with degeneration in different tissue in animal studies with lumateperone treatment. The adrenal gland may be implicated in lumateperone side effects, and quercetin may have the ability to fulfill this treatment gap. To prove this hypothesis, 40 male guinea pigs were used and divided into four groups; control, quercetin-treated, lumateperone-treated, and quercetin/lumateperone cotreated orally for 28 consecutive days. Behavioral forced swim (FST) and open field (OF) tests were done at the end of treatment. Retro-orbital blood samples were taken to assess hormones: adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone acetate (DHEA), and aldosterone, along with an assessment of oxidative stress parameters: malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Adrenal glands were extracted for histopathological assessment with H&E, Mallory trichome staining, immunostaining, and electron microscopy studies. Lumateperone-treated group showed a significant reduction in the activity in FST and OF with histopathological deterioration in adrenal secretory function and structure and increased expression of interleukin-6 (IL-6), CASPASE-3, collagen deposition, and decreased proliferating cell nuclear antigen (PCNA). Cytoplasmic vacuolation, pyknosis of the nuclei, increase in the lysosome, lipofuscin pigment, and cellular infiltration with diminishing in the number of secretory granules could all be observed in lumateperone-treated group. Coadministration of quercetin and lumateperone showed improvement of the previously deteriorated parameters. Quercetin had a prophylactic effect against lumateperone depressive-like effect on animal behavior and its possible adrenal damage.Graphical AbstractConceptual framework for the proposed mechanism of action of coadministration of quercetin and lumateperone.