COVID-19 and Risk of Acute Ischemic Stroke and Acute Lung Injury in Patients With Type II Diabetes Mellitus: The Anti-inflammatory Role of Metformin

Background: Coronavirus disease 19 (COVID-19) is regarded as an independent risk factor for acute ischemic stroke (AIS) due to the induction of endothelial dysfunction, coagulopathy, cytokine storm, and plaque instability. Method: In this retrospective cohort study, a total of 42 COVID-19 patients with type 2 diabetes mellitus (T2DM) who presented with AIS within 1 week of displaying COVID-19 symptoms were recruited. According to the current anti-DM pharmacotherapy, patients were divided into two groups: a Metformin group of T2DM patients with COVID-19 and AIS on metformin therapy (850 mg, 3 times daily (n = 22), and a Non-metformin group of T2DM patients with COVID-19 and AIS under another anti-DM pharmacotherapy like glibenclamide and pioglitazone (n = 20). Anthropometric, biochemical, and radiological data were evaluated. Results: Ferritin serum level was lower in metformin-treated patients compared to non-metformin treated patients (365.93 ± 17.41 vs. 475.92 ± 22.78 ng/mL, p = 0.0001). CRP, LDH, and D-dimer serum levels were also lowered in metformin-treated patients compared to non-metformin treated patients (p = 0.0001). In addition, lung CT scan scores of COVID-19 patients was 30.62 ± 10.64 for metformin and 36.31 ± 5.03 for non-metformin treated patients. Conclusion: Metformin therapy in T2DM patients was linked to a lower risk of AIS during COVID-19. Further studies are needed to observe the link between AIS in COVID-19 diabetic patients and metformin therapy.NC-M acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017). This work was supported by Taif University Researchers Supporting Program (project number: TURSP-2020/93), Taif University, Saudi Arabia

COVID-19 in relation to hyperglycemia and diabetes mellitus

Coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), may lead to extrapulmonary manifestations like diabetes mellitus (DM) and hyperglycemia, both predicting a poor prognosis and an increased risk of death. SARS-CoV-2 infects the pancreas through angiotensin-converting enzyme 2 (ACE2), where it is highly expressed compared to other organs, leading to pancreatic damage with subsequent impairment of insulin secretion and development of hyperglycemia even in non-DM patients. Thus, this review aims to provide an overview of the potential link between COVID-19 and hyperglycemia as a risk factor for DM development in relation to DM pharmacotherapy. For that, a systematic search was done in the database of MEDLINE through Scopus, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), and Wanfang Data. Data obtained underline that SARS-CoV-2 infection in DM patients is more severe and associated with poor clinical outcomes due to preexistence of comorbidities and inflammation disorders. SARS-CoV-2 infection impairs glucose homeostasis and metabolism in DM and non-DM patients due to cytokine storm (CS) development, downregulation of ACE2, and direct injury of pancreatic beta-cells. Therefore, the potent anti-inflammatory effect of diabetic pharmacotherapies such as metformin, pioglitazone, sodium-glucose co-transporter-2 inhibitors (SGLT2Is), and dipeptidyl peptidase-4 (DPP4) inhibitors may mitigate COVID-19 severity. In addition, some antidiabetic agents and also insulin may reduce SARS-CoV-2 infectivity and severity through the modulation of the ACE2 receptor expression. The findings presented here illustrate that insulin therapy might seem as more appropriate than other anti-DM pharmacotherapies in the management of COVID-19 patients with DM due to low risk of uncontrolled hyperglycemia and diabetic ketoacidosis (DKA). From these findings, we could not give the final conclusion about the efficacy of diabetic pharmacotherapy in COVID-19; thus, clinical trial and prospective studies are warranted to confirm this finding and concern

A Survey Comparing the Management of Diabetes, Hypoglycaemia and Hyperglycaemia by Type 1 and Type 2 Insulin Users

Aim: The opinions and attitudes of type 1 (T1) and type 2 (T2) insulin users toward their diagnosis, management, treatment and complications as a result of their diabetes were sought. Methods: A bottom-up survey design consisting of 66 open and closed questions was used to determine both positive and negative experiences of patients currently using insulin by injection only. Results: 707 insulin users (71% T1 and 29% T2) predominately from the UK completed the questionnaire. A comparison between T1 and T2 insulin users found that exercise, diet, BG testing and excursions from normoglycaemia were the most common source of difficulty amongst these insulin dependent patients. The majority of T1 participants were found to use a basal bolus insulin regimen (Lantus/Levemir and a short-acting insulin such as Novorapid®, Humalog® or Actrapid® but only 34% of T2 insulin users used a similar system with 35% using biphasic insulin aspart 30 (Novomix®) which may have due to lesser hypoglycaemic events. Conclusions: The results from this survey which focus on the common needs of insulin users show that careful follow-up after diagnosis, frequent testing and education about calorie turnover from intake and exercise are required for both T1 patients but more so for T2 patients whose needs become similar to those of T1 patients once they begin to inject insulin

Natural Products Modulating Angiotensin Converting Enzyme 2 (ACE2) as Potential COVID-19 Therapies

The 2019 coronavirus disease (COVID-19) is a potentially fatal multisystemic infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Currently, viable therapeutic options that are cost effective, safe and readily available are desired, but lacking. Nevertheless, the pandemic is noticeably of lesser burden in African and Asian regions, where the use of traditional herbs predominates, with such relationship warranting a closer look at ethnomedicine. From a molecular viewpoint, the interaction of SARS-CoV-2 with angiotensin converting enzyme 2 (ACE2) is the crucial first phase of COVID-19 pathogenesis. Here, we review plants with medicinal properties which may be implicated in mitigation of viral invasion either via direct or indirect modulation of ACE2 activity to ameliorate COVID-19. Selected ethnomedicinal plants containing bioactive compounds which may prevent and mitigate the fusion and entry of the SARS-CoV-2 by modulating ACE2-associated up and downstream events are highlighted. Through further experimentation, these plants could be supported for ethnobotanical use and the phytomedicinal ligands could be potentially developed into single or combined preventive therapeutics for COVID-19. This will benefit researchers actively looking for solutions from plant bioresources and help lessen the burden of COVID-19 across the globe.We appreciate the support and resource provided by staff and postgraduate members of the Center for Advanced Medical Research and Training (CAMRET), Usmanu Danfodiyo University, Sokoto, Nigeria. DU acknowledges the postgraduate scholarship awarded to him (CAMRET/ 2019/MSc/SCH003) by CAMRET. NC-M. acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/ 28076/2017). The work was also supported by Taif University Researchers Supporting Program (Project number: TURSP-2020/93), Taif University, Saudi Arabia

Hesperetin and Capecitabine Abate 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis in Wistar Rats via Suppressing Oxidative Stress and Enhancing Antioxidant, Anti-Inflammatory and Apoptotic Actions

Colon cancer is a major cause of cancer-related death, with significantly increasing rates of incidence worldwide. The current study was designed to evaluate the anti-carcinogenic effects of hesperetin (HES) alone and in combination with capecitabine (CAP) on 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. The rats were given DMH at 20 mg/kg body weight (b.w.)/week for 12 weeks and were orally treated with HES (25 mg/kg b.w.) and/or CAP (200 mg/kg b.w.) every other day for 8 weeks. The DMH-administered rats exhibited colon-mucosal hyperplastic polyps, the formation of new glandular units and cancerous epithelial cells. These histological changes were associated with the significant upregulation of colon Ki67 expression and the elevation of the tumor marker, carcinoembryonic antigen (CEA), in the sera. The treatment of the DMH-administered rats with HES and/or CAP prevented these histological cancerous changes concomitantly with the decrease in colon-Ki67 expression and serum-CEA levels. The results also indicated that the treatments with HES and/or CAP showed a significant reduction in the serum levels of lipid peroxides, an elevation in the serum levels of reduced glutathione, and the enhancement of the activities of colon-tissue superoxide dismutase, glutathione reductase and glutathione-S-transferase. Additionally, the results showed an increase in the mRNA expressions of the anti-inflammatory cytokine, IL-4, as well as the proapoptotic protein, p53, in the colon tissues of the DMH-administered rats treated with HES and/or CAP. The TGF-β1 decreased significantly in the DMH-administered rats and this effect was counteracted by the treatments with HES and/or CAP. Based on these findings, it can be suggested that both HES and CAP, singly or in combination, have the potential to exert chemopreventive effects against DMH-induced colon carcinogenesis via the suppression of oxidative stress, the stimulation of the antioxidant defense system, the attenuation of inflammatory effects, the reduction in cell proliferation and the enhancement of apoptosis

The Effects of Bacterial Lipopolysaccharide (LPS) on Turkey Poults: Assessment of Biochemical Parameters and Histopathological Changes

A lipopolysaccharide (LPS) is a large molecule and an outer membrane glycolipid found in Gram-negative bacteria, including Escherichia coli (E. coli). These molecules (LPS) target acute inflammatory responses and significant physiological changes. Importantly, E. coli is considered one of the most important bacterial causes of avian colibacillosis that affect domestic turkey industry. However, little information is available about the potential influence of LPS on the biochemical parameters and histopathological changes in turkey poults. Therefore, this study aimed to evaluate the influence of bacterial lipopolysaccharide (LPS) molecules on serum biomarkers and histopathological changes in turkey poults. The birds were randomly divided into five groups, as follows: group I did not receive any inoculation; group II was inoculated with sterile saline; and groups III, IV, and V were inoculated intraperitoneally with LPS at 0.01, 0.1, and 1 mg/kg of body weight (BW), respectively. The biochemical parameters and the histopathology of different organs were examined in all birds one day post-inoculation. Our results revealed hypolipidemia, hypoglycemia, a significant decrease in uric acid, and a significant increase in serum activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and creatine kinase (CK), as well as cardiac troponin T concentrations in treated groups. Moreover, there was a significant increase in α1-, β-, and γ-globulin concentrations and a decrease in albumin and α2-globulin concentrations in group V. However, a significant increase in α2- and γ-globulin levels and a decrease in albumin levels were detected in groups III and IV. In addition, significant decreases in the albumin/globulin ratio were recorded in all LPS-treated groups. Hepatocellular and cardiac muscle necrosis, slight renal changes, and massive pulmonary inflammatory reactions were recorded. This study provides valuable information about serum biomarkers, protein fractions, and histopathological changes in turkey poults treated with LPS for further investigations of pathophysiological mechanisms in avian medicine along with biomedical research

Effects of royal jelly supplementation on regulatory T cells in children with SLE

Background and objective: To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). Methods: This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks. Results: The percentages of CD4+ CD25+high FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+ regulatory T cells) were significantly increased after RJ treatment when compared with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased after RJ therapy when compared with baseline values and the control group. Conclusion: This is the first human study on the effect of RJ supplementation in children with SLE. Our results showed improvements with 3-month RJ treatment with regard to the clinical severity score and laboratory markers for the disease. At this stage, it is a single study with a small number of patients, and a great deal of additional wide-scale randomized controlled studies are needed to critically validate the efficacy of RJ in SLE

Serological Investigation and Epidemiological Analysis of Bovine Leptospirosis in Egypt

Bovine leptospirosis is a bacterial zoonotic disease of worldwide distribution. Little information is available regarding the occurrence of the disease in the Nile Delta provinces, Egypt. The present study investigated the seroprevalence of leptospirosis among cattle from Dakahlia province, Northern Egypt, and identified the individual variables factors associated with infection. To this end, a total of 600 serum samples from cattle of small stakeholders with various clinical manifestations possibly associated with leptospirosis were collected from different localities across Dakahlia province, Egypt. Sera were examined serologically via ELISA to investigate the occurrence of the disease among animals. Chi-square test and multivariable logistic regression analyses were applied to determine the association between hypothesized risk factors and the disease. Interestingly, our findings showed that 39.33% of the examined sera were positive for Leptospira antibodies, with significant differences among different localities. In addition, statistical analysis showed significant differences among age groups. Notably, the highest prevalence rate (22%) was observed in those aged between 3 and 5 years (p < 0.0001), whereas the lowest prevalence (2.66%) was reported in cattle <1 year old (p < 0.0001). Moreover, females had a significantly higher prevalence rate (35.33%) than males (4%) (p < 0.0001). Furthermore, our results showed significant differences in the occurrence of infection and reported clinical signs (p < 0.0001). Multivariable logistic regression identified repeated breeder and drop milk yield as the best predictors for prediction of ELISA results and linear discriminant analysis (LDA) model showed that overall classification accuracy of ELISA result using clinical signs and demographic data as predictors was 70.7%. The current study concluded a relative high prevalence of leptospirosis among cows bred in movable herds and households in the studied area and that age, repeated breeder and drop milk yield can be considered major risk factors associated with infection