Introduction Diabetes and coronavirus disease 2019 (COVID-19) are interrelated. The presence of hyperglycemia per se during COVID-19 infection regardless of diabetes status has been associated with poor prognosis and increased risk of mortality. Objectives The main aim of the current study was to assess the association between admission hyperglycemia and COVID-19 outcomes. Methods This is a retrospective cohort study including 315 patients, mainly employed in the facility, who presented to the emergency department or were admitted with confirmed COVID-19 infection from April 2020 to August 2021. Results The mean age of the studied cohort was 40.2±12.5 years, where 59.68% were males and 37.7% were symptomatic. Older age, male gender, history of diabetes and hypertension, and elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH) levels were associated with a significantly increased risk of developing cytokine release syndrome (CRS). Admission hyperglycemia was significantly associated with poor outcomes. The time to negativity was 9.30±0.1 days for asymptomatic patients; however, it increased significantly according to clinical presentation, presence of comorbidities, and severe outcomes, in patients with cytokine release syndrome. Conclusions Admission hyperglycemia was associated with an increased risk of progression to critical condition in patients hospitalized with COVID-19 independent of the history of diabetes. Therefore, it should not be overlooked but instead should be detected and appropriately treated to improve outcomes. In addition, post-COVID-19 care should be individualized, where severe cases require almost double the time needed by mild cases to convert to negative.

Background: In this work, a low-dose rate (100mGy/min of whole body gamma irradiation fractionated (0.5, 1, and 2Gy) was used to study the effects of cumulative doses on the expression of target genes implicated in the intestinal inflammatory process in high fat diet (HFD) wistar rats. Material and Methods: Total RNA was extracted and the expression of target genes was measured in the four intestinal segments (duodenum, jejunum, ileum and colon) of HFD Wistar rats. Results: Our in-vivo results in the four intestinal segments (duodenum, jejunum, ileum, and colon) demonstrated that gamma irradiation exposure in HFD rats amplified the low-grade inflammatory state already induced by HFD. This phenomenon occurs through the induction of pro-inflammatory cytokines mainly the tumor necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6) or via overexpression/increasing of anti-inflammatory response involved interleukin 10 (IL-10) and the growth factor beta (TGF beta) overall the bowel segments. Results suggested that whole body gamma irradiation might have dual roles, first, engraving the inflammatory state already initiated by HFD, and second, an over expressed anti-inflammatory response via anti-inflammatory cytokines mainly IL-10 and TGF beta. Conclusion: The current study clearly demonstrated the important role of the gut in HFD rats during fractionated whole body irradiation (FWBGI) and indicated that TGF beta and IL-10 may be the target in whole body radiotherapy as a mechanism to recompense for the imbalance between pro-inflammatory and anti-inflammatory cytokines.

Carotenoids, a group of phytochemicals, are naturally found in the Plant kingdom, particularly in fruits, vegetables, and algae. There are more than 600 types of carotenoids, some of which are thought to prevent disease, mainly through their antioxidant properties. Carotenoids exhibit several biological and pharmaceutical benefits, such as anti-inflammatory, anti-cancer, and immunity booster properties, particularly as some carotenoids can be converted into vitamin A in the body. However, humans cannot synthesize carotenoids and need to obtain them from their diets or via supplementation. The emerging zoonotic virus severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19), originated in bats, and was transmitted to humans. COVID-19 continues to cause devastating international health problems worldwide. Therefore, natural preventive therapeutic strategies from bioactive compounds, such as carotenoids, should be appraised for strengthening physiological functions against emerging viruses. This review summarizes the most important carotenoids for human health and enhancing immunity, and their potential role in COVID-19 and its related symptoms. In conclusion, promising roles of carotenoids as treatments against emerging disease and related symptoms are highlighted, most of which have been heavily premeditated in studies conducted on several viral infections, including COVID-19. Further in vitro and in vivo research is required before carotenoids can be considered as potent drugs against such emerging diseases.

Polyphenols are a large family of more than 10,000 naturally occurring compounds, which exert countless pharmacological, biological and physiological benefits for human health including several chronic diseases such as cancer, diabetes, cardiovascular, and neurological diseases. Their role in traditional medicine, such as the use of a wide range of remedial herbs (thyme, oregano, rosemary, sage, mint, basil), has been well and long known for treating common respiratory problems and cold infections. This review reports on the most highlighted polyphenolic compounds present in up to date literature and their specific antiviral perceptive properties that might enhance the body immunity facing COVID-19, and other viral infectious diseases. In fact, several studies and clinical trials increasingly proved the role of polyphenols in controlling numerous human pathogens including SARS and MERS, which are quite similar to COVID-19 through the enhancement of host immune response against viral infections by different biological mechanisms. Thus, polyphenols ought to be considered as a potential and valuable source for designing new drugs that could be used effectively in the combat against COVID-19 and other rigorous diseases.

Wistar rats were whole body irradiated with a single dose of 2 Gy post administration with 10 or 100 mg/kg of resveratrol (RSV) intraperitoneally for 30 days. Rats’ livers were dissected and processed to analyze immune response profiles of Th1, Th2, Th9, Th17, and Th22 by flow cytometry. In addition, peripheral blood samples were collected and circulating endothelial cells (CECs) were counted as an indicator for endothelial damage. Results demonstrated that resveratrol at 100 mg/kg enhanced liver immunological response influenced by irradiation by inducing Th2 immune response that was revealed by an increase in IL-10 secretion to more than 5,000 pmol/ml post irradiation. Results also indicated that RSV, at a dose of 100 mg/kg, decreased levels of the main pro-inflammatory cytokines such as INF-γ, IL-22, IL-17A, and GM-CSF post irradiation. In addition, the same RSV was bound to upregulate the expression of IL-10 mRNA in isolated Kupffer cells (KCs) and their secretion of IL-10 post irradiation. The result demonstrated that KCs were the central source of this anti-inflammatory response mediated mainly by IL10. These results, proposed for the first time, clearly states that RSV promotes IL-10 mediated immune resolution by Kupffer cells and not by hepatocytes. This implies that KCs have a crucial role in radiotherapy. Additionally, this study showed that RSV had an anti-apoptotic effect through re-increasing the number of CECs, which is implicated in irradiation damage. Result of the current work discloses novel findings about the potential of RSV as a radio-protector agent of a natural origin and suggests novel roles of KCs as a pharmacological target during radiation exposure.

HFD animals were exposed to a low rate of different fractionated whole body gamma irradiation doses (0.5, 1 and 2 Gy, three fractions per week for two consecutive months) and the expression of certain genes involved in type 2 diabetes mellitus (T2DM) in livers and brains of HFD Wistar rats was investigated. Additionally, levels of diabetes-related proteins encoded by the studied genes were analyzed. Results indicated that mRNA level of incretin glucagon like peptite-1 receptor (GLP-1R) was augmented in livers and brains exposed to 1 and 2 Gy doses. Moreover, the mitochondrial uncoupling proteins 2 and 3 (UCP2/3) expressions in animals fed on HFD compared to those fed on normal chow diet were significantly increased at all applied doses. GLP-1R and UCP3 protein levels were up regulated in livers. Total protein content increased at 0.5 and 1 Gy gamma irradiation exposure and returned to its normal level at 2 Gy dose. Results could be an indicator of type 2 diabetes delayed development during irradiation exposure and support the importance of GLP-1R as a target gene in radiotherapy against T2DM and its chronic complications. A new hypothesis of brain-liver and intestine interface is speculated by which an increase in the hepatic GLP-1R is influenced by the effect of fractionated whole body gamma irradiation.

In this work, the effects of irradiation and high fat diet (HFD) intake have been examined in Wistar rat livers. HFD Wistar rats were exposed three times per week for 2 months to three different doses (0.5, 1, and 2 Gy) of a fractionated whole body gamma irradiation (FWBGI). Hepatic mRNA of these rats was evaluated for five cytokines, TNFα, IL1β, IL6, CRP and IL10. In addition, some critical protein levels were evaluated.

Purpose: The effects of a low rate (100 mGy/min) fractionated whole body gamma irradiation (FWBGI) at different doses were assessed using a real-time PCR technique on the expression of some target genes implicated in the development of type 2 diabetes mellitus in high-fat diet (HFD) Wistar rats. Method: HFD Wistar rats were exposed to different doses (12, 24 and 48 Gy) divided into 24 fractions (three times a week for two months), thus, the daily doses were 0.5, 1, 2 Gy, respectively. Total RNA was extracted and the expression of target genes was measured in the four intestinal segments (duodenum, jejunum, ileum and colon). Results: The pre-diabetic state already induced by HFD was found to be improved by irradiation exposure. This irradiation effect occurs mainly via altered anti-diabetic gene expressions (mRNA and protein levels) of the incretin glucagon-like peptide-1 (GLP-1) overall bowel segments except the colon which has its own specific response to irradiation exposure by the induction of the insulin receptor substrate 4 (IRS-4) and the uncoupling protein 3 (UCP3). Conclusions: Results could be of great importance suggesting for the first time, a protective role for FWBGI on HFD animal models by increasing GLP-1 and UCP3 levels.

An HPLC system equipped with a fluorescent and UV detection was deployed to determine the concentrations of 16 different polycyclic aromatic hydrocarbons (PAHs) in bran and endosperm of wheat grains before and after gamma irradiation treatments. Wheat grains were subjected to 0, 5, 10 and 15 kGy doses of gamma irradiation and concentrations of PAHs extracted from control and treated tissues were determined. Results demonstrate that accumulation of PAHs was significantly higher in wheat bran (293.1 µg × kg−1) than that observed in endosperms (61.4 µg × kg−1). This indicates that PAHs traceability and contamination via an atmospheric exposure is likely compared with other possible sources of a soil origin for instance. The effect of gamma irradiation dose was more effective on grain endosperm with a reduction percentage of about 92% (15 kGy) for ∑16 EPA PAHs. PAHs reduction in both tissues of studied wheat grains increased along with the applied dose of gamma irradiation.

A qualitative characterization of 16 polycyclic aromatic hydrocarbons (PAHs) in pea seeds before and post gamma irradiation has been carried out using gas chromatography-mass spectrometry (GC-MS). Seeds were exposed to gamma irradiation at 1, 5, 10 and 15 kGy doses. PAHs were extracted and their concentrations were correlated with the peak height, at each dose and compared to control samples. PAHs peaks decreased with the increase of gamma irradiation dose. Total bacterial and total fungal counts decreased from 2.43 and 1.66 log10 cfu g-1, respectively (non-irradiated), to <1 log10 cfu g-1 after gamma irradiation. The results indicate the potential utilization of gamma irradiation for PAHs and microbial inactivation from pea seeds.

Gamma irradiation effects on seven carcinogenic polycyclic aromatic hydrocarbons (PAHs) were investigated. 0, 1, 5, 10, and 15 kGy of gamma irradiation doses were used in wheat grain treatments. PAHs were extracted and their concentrations at each doses were determined using HPLC equipped with fluorescence analysis. Results demonstrate a reverse relationship between PAHs concentrations and gamma irradiation doses. PAHs concentrations decreased when the gamma irradiation dose increased. The total of PAHs concentration decreased by 35% at 1 kGy while the reduction exceeded 70% for doses higher than 5 kGy. PAHs reduction in irradiated grain samples versus irradiation dose was linear/exponential depending on the structure of PAHs compounds. Results could be of great importance when gamma irradiation is used for the elimination of PAHs from wheat grains.

Food contamination may contribute to serious human health problems. In this work, the effect of γ-irradiation 0, 5, 10, and 15 kGy doses on the removal of polycyclic aromatic hydrocarbons from wheat kernels was investigated. Additionally, variations in the contents of 16 congeners on bacterial load and other chemical parameters were studied. Polycyclic aromatic hydrocarbons concentrations were determined by high-performance liquid chromatography followed by fluorescence detection. The effects of γ-irradiation on the concentrations varied for each congener, with the highest irradiation dose being the most effective. Benzo[a]pyrene was reduced by ∼50%, and the total concentration of all congeners decreased dramatically from 154 to 21 µg.kg−1 upon 15 kGy irradiation at a dose rate of 8.49 kGy h−1. The total bacterial load was reduced from 2.4 to < 1 log10 cfu g−1, while wheat chemical properties were not affected.

BACKGROUND:We previously showed that blood serum induced cytochrome P450 1A1 (CYP1A1) monooxygenase expression in vitro. OBJECTIVE:Our purpose was (i) to identify the molecular mechanism involved and (ii) to characterize the inducer compound(s) in serum involved at least in part. METHODS:Serum was fractionated on hydrophobic columns. PPARα involvement was demonstrated by gene reporter assays, DNA mutagenesis and EMSA. Gene expression was evaluated by qRT-PCR. Serum samples were analyzed using HS-SPME-GC-MS. RESULTS:The inductive effect of serum did not depend on the AhR pathway and was enhanced by cotransfection of PPARα cDNA. Mutations in the PPAR response elements of the CYP1A1 gene promoter suppressed this effect. One of the PPRE sites appeared highly specific for human PPARα, an unreported PPRE property. A link was found between CYP1A1 inducibility and serum hydrophobic compounds. Characterization of sera showed that hexanal, a metabolite produced by peroxidation of linoleic acid, was involved in CYP1A1 induction by serum, possibly along with other serum entities. CONCLUSION:We demonstrate that serum induces CYP1A1 via the PPARα pathway and that hexanal is one of the serum inducers. The two PPRE sites within the CYP1A1 promoter are functional and one of them is specific for PPARα.

We demonstrate that intestinal inflammation caused by high-fat diet is increased by the environmental contaminant benzo[a]pyrene. Our in vivo results indicate that a high-fat diet (HFD) induces a pre-diabetic state in mice compared with animals fed normal chow. HFD increased IL-1betamRNA concentration in the jejunum, colon, and liver, and TNFalpha was increased in the colon and strongly increased in the liver. HFD also increased the expression of other genes related to type 2 diabetes, such as the uncoupling protein UCP2, throughout the bowel and liver, but not in the colon. The treatment of HFD with BaP enhanced the expression of IL-1beta in the liver and TNFalpha throughout the bowel and in the liver. Adding BaP to the diet also caused a significant decrease in the expression of the incretin glucagon-like peptide 1, which plays an important role in insulin secretion. Our results suggest that intestinal inflammation may be involved in the onset of type 2 diabetes and that chronic exposure to environmental polycyclic aromatic hydrocarbons can increase the risk of type 2 diabetes by inducing pro-inflammatory cytokine production.

In this work we demonstrate that Caco-2 cell treatment with WY-14643 (a potent PPARalpha agonist) causes an increase in AhR expression. Luciferase assays and directed mutagenesis experiments showed that induction mainly occurred at transcriptional level and involved a PPRE site located within the AhR promoter. These results were further confirmed by the use of PPARalpha knockout mice in which AhR induction by WY14643 was abrogated. In addition to CYP1 regulation, AhR has been described as being involved in inflammation, so we also studied the effect of AhR regulation by PPARalpha on the expression of some inflammation target genes. 3-Methylcholanthrene (a potent AhR agonist) increased the expression (mRNA) of the major inflammatory targets IL-1beta and MMP9. WY-14643 co-treatment abrogated the 3-methylcholanthrene pro-inflammatory effect. Hence the anti-inflammatory effect of PPARalpha overrides the pro-inflammatory effect of AhR.