Human ACE-2, MCP1 and micro-RNA 146 as Novel Markers for COVID- 19 Affection and Severity.

BACKGROUND & AIMS: Coronavirus disease - 2019 (COVID-19) is a major pandemic that causes high morbidity and mortality rates. AIM OF THIS STUDY: to detect the relations between many risk factors, ACE-2, MCP-1, Micro RNA 146 gene expression, and COVID-19 infection and disease severity. METHODS: This study was carried out on 165 cases of COVID-19 and 138 controls. ACE2 and MCP1 levels were measured in COVID-19 cases and control by ELISA and micro-RNA-146 expression by PCR. RESULTS: We found an increased blood level of ACE2 and MCP1 in COVID- 19 patients than in healthy persons and a significant down-regulation of micro-RNA 146 gene expression in cases than in controls. There was a significant correlation between increased blood level of ACE2, regulation of micro-RNA 146 gene expression and severity of lung affection, a significant correlation was found between increased blood level of MCP1 and thrombosis in COVID-19 patients. Neurological complications were significantly correlated with more viral load, more ACE2 blood level, and down regulation of micro RNA146 expression. CONCLUSION: High viral load, increased blood level of ACE2, and down-regulation of micro-RNA 146 expression are associated with more severe lung injury and the presence of neurologic complications like convulsions and coma in COVID-19 Egyptian patients.

Association of rs1544410 and rs7975232 Polymorphisms and Serum Vitamin D Levels with Psoriasis Susceptibility and Severity: A Case-Control Study in Egyptian Patients.

Background: Vitamin D is a regulatory factor for skin immune functions through vitamin D receptor, which is expressed on many immune cells. Vitamin D receptor is located on chromosome 12q 13.11 and has many single nucleotide polymorphisms. Some of them were hypothesized to be associated with psoriasis. Psoriasis is a genetic disease that is greatly affected by environmental factors. Methods: A total of 135 psoriasis patients and 114 healthy controls were recruited. Both had a measurement of serum vitamin D and two vitamin D receptor variants:, rs1544410: G > A (HGVS:NC_000012.12:g.47846052) and rs7975232: C > A (HGVS: NC_000012.12:g.47845054). We assessed the relationship between vitamin deficiency as well as the two gene polymorphisms with psoriasis susceptibility and severity. Results: Serum vitamin D levels were not significantly different between cases and controls. However, a significant association between vitamin D levels and severity was observed. We attributed this to our finding that rs7975232 was more significantly polymorphic among cases than controls, while rs1544410 polymorphism did not show a significant difference among the 2 groups. Conclusion: We did not find a significant difference in serum vitamin D levels between cases and controls. Yet, psoriasis severity was significantly associated with serum vitamin D levels. We attributed this to other findings that the vitamin D receptor rs7975232 gene is polymorphic in psoriasis patients. At the same time, rs1544410 was not significantly more polymorphic in psoriasis patients. Both genes' polymorphisms were associated with severe psoriasis.

Pro-Neurotensin as a Potential Novel Diagnostic Biomarker for Detection of Nonalcoholic Fatty Liver Disease.

Background and Aims: Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case-control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases. Methods: Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs-122 and pro-neurotensin. Results: Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108. Conclusion: The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH.

Covid-19: Urgent Call to Action.

Novel Corona Virus 2019 (COVID-19) is a new virus spread rapidly all over the world. It has specific respiratory or gastrointestinal tract symptoms. Its reported complications include respiratory distress, systemic inflammatory response syndrome, and septic shock. Due to heavy cytokines released by the virus; corticosteroids (40-120 mg / day) were given to severe cases to reduce pneumonia. It's a difficult task to control the spread of SARS-CoV-2, and to invent proper vaccines and treatments. In this review, the existing understanding of fatal, pandemic human coronavirus SARS-Cov2 (COVID-19), with special reference to its diagnosis, origin, transmission, and different approaches to develop its therapeutics, will be discussed.

Vitamin E inhibits cyclosporin A-induced CTGF and TIMP-1 expression by repressing ROS-mediated activation of TGF-ß/Smad signaling pathway in rat liver.

Cyclosporin A (CsA) is the most common immunosuppressive drug used in organ transplantation. However, the clinical use of CsA is often limited by several side effects including hepatotoxicity. In the present study, it was found that administration of CsA causes a rapid activation of TGF-ß/Smad signaling cascade and subsequent expression of the profibrotic genes connective tissue growth factor (CTGF) and tissue inhibitors of matrix metallproteinases-1 (TIMP-1) in rat liver. In addition, Smad phosphorylation and subsequent CTGF and TIMP-1 expression were markedly reduced in the presence of neutralizing monoclonal TGFß1-3 antibody. Furthermore, CsA administration significantly increased the serum levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as lipid peroxidation in hepatic tissues. Moreover, significant reduction in the hepatic content of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) was observed in CsA-alone-treated animals. Histopathological changes were also observed in CsA-alone-treated rats. Pretreatment of animals with Vitamin E (Vit E) before CsA administration significantly reduced TGF-ß level as well as Smad phosphorylation and subsequent CTGF and TIMP-1 expression. Furthermore, administration of PEG-SOD clearly attenuated TGF-ß/Smad signaling induced by CsA. Moreover, concomitant administration of Vit E along with CsA significantly ameliorated the histopathological changes and improved liver function as well as the antioxidant capacity. Finally, this study shows that the immunosuppressive efficiency of CsA was not altered in the presence of Vit E. These data may support the concept of using antioxidant therapy as a valuable approach for the prevention of CsA-induced tissue fibrosis.

Levels of soluble advanced glycation end product-receptors and other soluble serum markers as indicators of diabetic neuropathy in the foot.

OBJECTIVE: Advanced glycation end products (AGEs) and the interaction with their receptors (RAGE) play an important role in the pathogenesis of diabetic foot (DF) associated with diabetic neuropathy. Our study examined the association between asymmetric dimethyl arginine (ADMA), fructosamine, nitric oxide (NO), and soluble (s) RAGE levels in serum of diabetic patients with and without neuropathy. METHODS: Circulating levels of ADMA, fructosamine, NO, and sRAGE, estimated either chemically or by enzyme-linked immunosorbent assay, were examined in 60 type 2 diabetes mellitus (T2DM) overweight/obese (body mass index, 30.5 ± 1.5 kg/m²) male patients and 20 age-matched (55 ± 3 years) obese healthy subjects as control group. The T2DM subjects were categorized as patients without DF (n = 30), and the remaining were patients with DF associated with neuropathy. RESULTS: First sRAGE levels were significantly increased in T2DM patients without DF in comparison to healthy controls (1656.6 [1198.8-2065.4] vs 1111.7 [909-1605.3] pg/mL, respectively; P < 0.05). However, in the DF group (1049.6 [783.7-1221.8] pg/mL), its level decreased significantly in comparison to both groups (P < 0.05). However, ADMA and fructosamine were significantly higher in diabetic patients with DF than both T2DM without DF and healthy controls. Moreover, NO was significantly lower in DF than in diabetic patients without DF and controls (5 ± 0.4 and 8 ± 0.4 vs 42 ± 2.5 µmol/L, respectively; P < 0.05). Finally, sRAGE levels were significantly correlated with ADMA, fructosamine, and NO. CONCLUSIONS: Soluble forms of the receptor for advanced glycation end product could be an endogenous protection factor against occurrence of DF, hence may be of therapeutic value in the treatment of DF.