SARS-CoV-2 outbreak: role of viral proteins and genomic diversity in virus infection and COVID-19 progression.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications.

Phenotypical changes of hematopoietic stem and progenitor cells in COVID-19 patients: Correlation with disease status.

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a crucial role in the context of viral infections and their associated diseases. The link between HSCs and HPCs and disease status in COVID-19 patients is largely unknown. This study aimed to monitor the kinetics and contributions of HSCs and HPCs in severe and non-severe COVID-19 patients and to evaluate their diagnostic performance in differentiating between healthy and COVID-19 patients as well as severe and non-severe cases. Peripheral blood (PB) samples were collected from 48 COVID-19 patients, 16 recovered, and 27 healthy controls and subjected to deep flow cytometric analysis to determine HSCs and progenitor cells. Their diagnostic value and correlation with C-reactive protein (CRP), D-dimer, and ferritin levels were determined. The percentages of HSCs and common myeloid progenitors (CMPs) declined significantly, while the percentage of multipotent progenitors (MPPs) increased significantly in COVID-19 patients. There were no significant differences in the percentages of megakaryocyte-erythroid progenitors (MEPs) and granulocyte-macrophage progenitors (GMPs) between all groups. Severe COVID-19 patients had a significantly low percentage of HSCs, CMPs, and GMPs compared to non-severe cases. Contrarily, the levels of CRP, D-dimer, and ferritin increased significantly in severe COVID-19 patients. MPPs and CMPs showed excellent diagnostic performance in distinguishing COVID-19 patients from healthy controls and severe from non-severe COVID-19 patients, respectively. Collectively, our study indicated that hematopoietic stem and progenitor cells are significantly altered by COVID-19 and could be used as therapeutic targets and diagnostic biomarkers for severe COVID-19.

Protective effect of dexamethasone against paraquat-triggered toxicity in A549 cells through inhibiting inflammation, apoptosis and TGF-ß1/Smad3 pathway.

Dexamethasone is a glucocorticoid that is used for the treatment of interstitial pneumonia and pulmonary fibrosis as it possesses anti-inflammatory and anti-fibrosis properties. In the current study, A549 cells were exposed to paraquat, dexamethasone, or both of them, to investigate the potential effect of dexamethasone against paraquat-triggered poisoning in A549 cells. The inflammatory response was evaluated by measuring tumor necrosis factor-α, interleukin-1ß, and interleukin-6 while the degree of fibrosis was assessed by detecting collagen I and fibronectin using enzyme-linked immunosorbent assay. Western blotting was used to assess the protein expression of apoptotic proteins as well as transforming growth factor-ß1, Smad 3 and phospho-Smad 3. DNA ladder assay was performed to estimate DNA damage in different groups of the alveolar epithelial cells. Dexamethasone protected against paraquat-induced inflammatory response as shown by the significantly reduced levels of the pro-inflammatory cytokines and it also alleviated paraquat-provoked fibrosis as it substantially diminished collagen I and fibronectin levels. Moreover, dexamethasone remarkably decreased the relative expression levels of transforming growth factor-ß1 and phospho-Smad3 that were upregulated upon PQ treatment. Dexamethasone also protected against paraquat-induced genotoxicity and apoptosis. In conclusion, dexamethasone may protect against paraquat-induced inflammation, fibrosis, genotoxicity, and apoptosis via modulating TGF-ß1/Smad 3 signaling pathway.

Effect of resveratrol on the inflammatory status and oxidative stress in thymus gland and spleen of sulfoxaflor-treated rats.

Resveratrol (Res), a polyphenolic compound that exerts mitigating consequences against various insults due to its antioxidant, anti-inflammatory, and immunomodulatory properties. Sulfoxaflor (SFX), a neonicotinoid insecticide, has been used worldwide and leading to deleterious effects on the environment and public health. The current study aimed to investigate the protective effect of Res on the inflammatory response and oxidative stress induced by SFX in the thymus and spleen of rats. Thirty-six Sprague Dawley rats were divided randomly into six groups; control group, SFX treated groups (24.8 mg/kg or 79.4 mg/kg/day), Res (alone) treated group (20 mg/kg/day), Res + SFX treated groups (20 mg /kg Res + 24.8 mg/kg SFX or 20 mg/kg Res + 79.4 mg/kg SFX) orally for 28 days. Res treatment reversed the significantly elevated white blood cells' count and the reduced count of red blood corpuscles, platelets as well as hemoglobin content of SFX treated rats. Biochemically, Res administration inhibited the remarkably increased serum levels of the inflammatory cytokines as well as thymic and splenic levels of malondialdehyde following SFX treatment. Res treatment ameliorated the conspicuously reduced antioxidant enzymes' activities due to SFX supplementation. The immunomodulatory effect of Res treatment was detected by suppressing the upregulation of the cluster of differentiation (CD)11b and CD3 gene expressions. Histopathological alterations attributed to SFX administration were ameliorated by Res treatment. In conclusion, Res can be used as a protective agent to counteract SFX toxic effects on lymphatic organs through alleviation of the antioxidant defense mechanism and modulation of the inflammatory response.

Protective effects of Egyptian cloudy apple juice and apple peel extract on lipid peroxidation, antioxidant enzymes and inflammatory status in diabetic rat pancreas.

BACKGROUND: Apples possess rich content of varied polyphenolic compounds showing a variety of biological activities that may ascribe to worthy effects against some chronic diseases. The present study was designed to assess the protective effects of the cloudy apple juice (CAJ) and apple peel extract (APE) of Egyptian Anna apple on the complications in experimental diabetes. MATERIALS AND METHODS: Four groups were studied. Diabetes was induced by a single dose of streptozotocin (STZ) to only three groups of albino Wistar rats. Two of the diabetic groups received either CAJ or APE for 21 days. At the end of the study, lipid profile parameters were measured in serum while lipid peroxidation (LPO) level, antioxidant enzyme activities and inflammatory markers were evaluated in pancreas tissue samples. The gas chromatography-mass spectrometry (GC-MS) analysis of phenolic compounds found in CAJ and APE was carried out. Moreover, total phenolic content of CAJ and APE were measured. RESULTS: The significant increase of blood glucose level, serum total cholesterol (TC), triglycerides (TG), low- density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein (VLDL) levels, in addition to tissue malondialdehyde (MDA), nuclear factor kappa B (NF-kB), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8) levels, but a significant decrease in high-density lipoprotein cholesterol (HDL-C), and the activity of pancreatic antioxidant enzymes were the remarkably parameters observed in diabetic control rats. Dissimilarly, oral supplementation of 15 ml/kg CAJ and 1 g/kg APE for 21 days resulted in a significant decrease in fasting blood glucose, serum TC, TG, LDL-C, VLDL-C and tissue MDA, NF-kB, TNF-α, IL-6, IL-8 levels coupled with a significant elevation of HDL-C and antioxidant enzymes' activity when compared with diabetic control animals. CONCLUSIONS: The results indicate that Egyptian CAJ and APE supplementation may have protective effects against deleterious complications of diabetes mellitus.

Memory T Cells Discrepancies in COVID-19 Patients.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Protective effect of Moringa oleifera Lam. leaf extract against oxidative stress, inflammation, depression, and apoptosis in a mouse model of hepatic encephalopathy.

The present study aimed to assess the antioxidative, anti-inflammatory, antiapoptotic, and anti-depression impacts of Moringa oleifera Lam. leaf ethanolic extract (MOLE) in the hippocampus and cerebral cortex of CCl4-induced hepatic encephalopathy mouse model. High-performance liquid chromatography was used to detect marker compounds: rutin and ß-sitosterol. Animals were divided into four groups: vehicle group, CCl4-treated group, MOLE-treated group, and (CCl4 + MOLE) group treated with MOLE for 14 days before CCl4-induced neurotoxicity. MOLE decreased alanine aminotransferase, aspartate aminotransferase, corticosterone, and ammonia levels in serum and improved the antioxidant status of CCl4-treated mice in the hippocampus and cerebral cortex. It reduced the expression of toll-like receptor 4 (TLR4), TLR2, myeloid differentiation primary response 88 (MYD88), and nuclear factor-kappa B (NF-κB) genes and the protein levels of the pro-inflammatory cytokines. MOLE also attenuated apoptosis, as revealed by the reduced expression of caspase3, and prevented histological deterioration. Furthermore, MOLE attenuated CCl4-induced anxiety and depression-like behavioral changes. Collectively, MOLE modulates neuroinflammation, oxidative stress, TLR4/2-MyD88/NF-κB signaling, and apoptosis in the hippocampus and cerebral cortex of the hepatic encephalopathy experimental model.

Neuroprotective effects of pomegranate (Punica granatum L.) juice and seed extract in paraquat-induced mouse model of Parkinson's disease.

BACKGROUND: Paraquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans. The consumption of phytochemical-rich plants can reduce the risk of chronic illnesses such as inflammation and neurodegenerative diseases. The present study aimed to investigate the protective effects of pomegranate seed extract (PSE) and juice (PJ) against PQ-induced neurotoxicity in mice. METHODS: Mice were assigned into 4 groups; three groups received PQ (10 mg/kg, i.p.) twice a week for 3 weeks. Two of the PQ-induced groups pretreated with either PSE or PJ. Detection of phytochemicals, total phenolics, and total flavonoids in PSE and PJ was performed. Tyrosine hydroxylase (TH) level was measured in the substantia nigra (SN) by Western blotting technique. Striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were detected using high-performance liquid chromatography (HPLC). The levels of adenosine triphosphate (ATP), malondialdehyde (MDA), and the activity of the antioxidant enzymes were estimated in the striatum by colorimetric analysis. Striatal pro-inflammatory and anti-inflammatory markers using enzyme-linked immunosorbent assay (ELISA) as well as DNA fragmentation degree by qualitative DNA fragmentation assay, were evaluated. Real-time polymerase chain reaction (qPCR) assay was performed for the detection of nuclear factor kappa B (NF-кB) gene expression. Moreover, Western blotting analysis was used for the estimation of the cluster of differentiation 11b (CD11b), transforming growth factor ß (TGF-ß), and glial cell-derived neurotrophic factor (GDNF) levels in the striatum. RESULTS: Pretreatment with PSE or PJ increased the levels of TH in the SN as well as DA and its metabolite in the striatum that were reduced by PQ injection. PSE and PJ preadministration improved the PQ-induced oxidative stress via a significant reduction of the MDA level and the augmentation of antioxidant enzyme activities. PSE and PJ also significantly downregulated the striatal NF-кB gene expression, reduced the PQ-enhanced apoptosis, decreased the levels of; pro-inflammatory cytokines, CD11b, and TGF-ß coupled with a significant increase of; interleukin-10 (IL-10), GDNF, and ATP levels as compared with PQ-treated mice. CONCLUSIONS: The current study indicated that PSE and PJ consumption may exhibit protective effects against PQ-induced neurotoxicity in mice.

Impact of post-laparoscopic sleeve gastrectomy weight loss on C-reactive protein, lipid profile and CA-125 in morbidly obese women.

INTRODUCTION: Obesity increases production of adipose tissue-derived proteins, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Also there are elevated levels of C-reactive protein (CRP) and IL-6, CD8, and CD4, indicating chronic subclinical inflammation. Since obesity represents a serious risk factor in several metabolic diseases, identifying the status of carbohydrate antigen-125 (CA-125) would further link obesity and tumors. AIM: To examine the effect of weight loss by laparoscopic sleeve gastrectomy (LSG) on plasma CRP, lipid profiles and CA-125 level in morbidly obese patients. MATERIAL AND METHODS: This prospective study was conducted in the Surgery Department, Fayoum University Hospital, between August 2013 and September 2015. To assess the effect of excess weight loss following this operation CRP, lipid profile and CA-125 were measured before and 12 months after the LSG operation for weight loss. The study included 30 cases of morbidly obese patients: 30 (100%) females aged 23-55 years who were considered clinically obese with a mean body mass index of 42.71 ±4.3 (38-46) kg/m(2) and mean age of 40.3 ±8.5 (23-55) years. The National Institute of Health (NIH) inclusion criteria for bariatric surgery were used. RESULTS: A mean weight loss of 29.30% decreased plasma CRP, triglycerides, total cholesterol and low-density lipoprotein cholesterol (HDL cholesterol), CA-125 level and increased high-density lipoprotein cholesterol (HDL cholesterol) The percentage weight loss was significantly associated with changes in plasma CRP, triglycerides, total cholesterol, total HDL cholesterol and CA-125. CONCLUSIONS: Weight loss by LSG improves inflammation, dyslipidemia and CA-125 level.

Peripheral blood lymphocyte subsets (CD4+, CD8+ T cells), leptin level and weight loss after laparoscopic greater curvature plication in morbidly obese patients.

INTRODUCTION: The aim of the study was to detect the effect of laparoscopic greater curvature plication (LGCP) on peripheral blood lymphocyte subsets (helper and cytotoxic T lymphocytes - CD4+ and CD8+ T cells respectively), leptin level and weight loss in morbidly obese patients. MATERIAL AND METHODS: Morbidly obese patients (n = 20, age range: 25-50 years, body mass index (BMI) range: 37-45 kg/m(2)) who underwent LGCP were enrolled in a prospective study to determine the percentages of their peripheral blood T cells (CD4+ and CD8+) before and 4 months postoperatively using flow cytometry. Also, the level of their leptin before and 4 months postoperatively was established using enzyme-linked immunosorbent assay (ELISA). The data are expressed as the percentage of total lymphocytes ± the standard error of the mean. RESULTS: A decrease in the BMI and loss of weight (31.20 ±1.2%) were confirmed 4 months postoperatively since BMI was 44.71 ±4.3 (range: 37-45) kg/m(2) preoperatively, and decreased to 31.80 ±1.1 (range: 24-33) kg/m(2) after surgery. The mean percentage of CD4+ and CD8+ T lymphocytes significantly decreased postoperatively (38.2 ±1.5 before and 29.3 ±2.6 after operation for CD4+, 17.3 ±1.8 preoperatively and 9.5 ±1.7 postoperatively for CD8+, p < 0.05). The mean leptin level was 43.01 ±22.01 preoperatively while postoperatively it was 24.8 ±11.1 (p < 0.05), so the leptin level substantially decreased compared to its preoperative values. CONCLUSIONS: This study found that weight loss after LGCP in morbidly obese patients led to decreases in levels of leptin and circulating immune cells compared to their preoperative values.