The effect of vitamin D, magnesium and zinc supplements on interferon signaling pathways and their relationship to control SARS-CoV-2 infection

The concern of today’s communities is to find a way to prevent or treat COVID-19 and reduce its symptoms in the patients. However, the genetic mutations and more resistant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge; the designed vaccines and adjuvant therapies would potentially control the symptoms and severity of COVID-19. The most important complication of this viral infection is acute respiratory distress syndrome, which occurs due to the infiltration of leukocytes into the alveoli and the raised cytokine storm. Interferons, as a cytokine family in the host, play an important role in the immune-related antiviral defense and have been considered in the treatment protocols of COVID-19. In addition, it has been indicated that some nutrients, including vitamin D, magnesium and zinc are essential in the modulation of the immune system and interferon (IFN) signaling pathway. Several recent studies have investigated the treatment effect of vitamin D on COVID-19 and reported the association between optimal levels of this vitamin and reduced disease risk. In the present study, the synergistic action of vitamin D, magnesium and zinc in IFN signaling is discussed as a treatment option for COVID-19 involvement

A Comprehensive Review on the Metabolic Cooperation Role of Nuclear Factor E2-Related Factor 2 and Fibroblast Growth Factor 21 against Homeostasis Changes in Diabetes

Objective: Type 1 and type 2 diabetes are associated with metabolic disorders including hyperglycemia, hyperlipidemia, and inflammation, leading to the production of reactive oxygen species and nitrogen activators. In these cases, some of the body’s innate factors are activated to cope with these dangerous situations. The purpose of the review is to explain the collaboration between the nuclear factor E2-related factor 2 (NRF2) and fibroblast growth factor 21 (FGF21) in homeostasis and body metabolism with a focus on diabetes. Materials and methods: This review is based on searching the PubMed database, SCOPUS, Elsevier and citation lists of relevant publications. Subject heading and key words used include diabetes, oxidative stress, inflammation, NRF2, and FGF21. Only articles in English were included. Results: NRF2 and FGF21 are two attractive biomarkers for the diagnosis of specific metabolic disorders and therapeutic targets, which have been implicated as therapeutic targets for the management of diabetic complications. The combination of both factors leads to the regulation of antioxidant and anti-inflammatory responses and metabolic pathways. Conclusions: Given most studies of NRF2- and FGF21-based therapeutic interventions in animal models and the possibility of not achieving the same results in humans, further clinical studies are needed to determine the efficacy of NRF2 and FGF21 in treatment of patients with diabetes

Effects of Pomegranate Juice with and without Aerobic Training on Glycemic Control and Lipid Profile in Women with Type 2 Diabetes

Background and Aim: Type 2 diabetes is a common metabolic disease, which is associated with obesity and inactivity. Plant-based dietary patterns are recommended for the treatment of type 2 diabetes. On the other hand, the effect of aerobic training on the improvement of type 2 diabetes is also highly emphasized. The purpose of this study was to investigate the effects of 2-months of pomegranate juice consumption with and without aerobic training on the levels of HbA1c, fasting blood glucose (FBG), lipid profile in women with type 2 diabetes. Methods: In this study, 58 women with type 2 diabetes who were referred to Tehran Lorzadeh clinic were randomly divided into four groups: control, pomegranate juice, aerobic training, combined pomegranate juice with aerobic training. The aerobic training plan consisted of 2-months and three times per week (training time from 20 minutes to 45 minutes). Three days before and after this interventional study, serum levels of FBG, total cholesterol (TC), triacylglyceride (TG), and low-density lipoprotein (LDL) were measured by colorimetric methods. Results: Results showed that combined pomegranate extract consumption with aerobic exercise training significantly decreased the levels of FBG, HbA1c, and TG in women with type 2 diabetes compared to the control group after the intervention (P<0.01), while TC, LDL-c, and BMI remained unchanged. There was no statistically significant difference in the levels of TC, TG, HbA1c, and FBG in pomegranate extract or aerobic training groups compared to the control group after intervention. Conclusion: The results of this study indicate that combined pomegranate juice with aerobic training has beneficial effects on type 2 diabetes and could be recommended in their therapeutic program. *Corresponding Author: Fariba Mohammadi Tahroodi; Email: [email protected] Please cite this article as: Vaziri Javid R, Safizadeh F, Rastegary M, Nabi Afjadi M, Khonakdar-Tarsi A, Zare Z, Zarpou S, Mohammadi Tahroodi F. Effects of Pomegranate Juice with and without Aerobic Training on Glycemic Control and Lipid Profile in Women with Type 2 Diabetes. Arch Med Lab Sci. 2020;6.1-6 (e17). https://doi.org/10.22037/amls.v6.3038

Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide

Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients. Securigera Securidaca (S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes

Association of MicroRNA-146a with Type 1 and 2 Diabetes and their Related Complications

Most medical investigations have found a reduced blood level of miR-146a in type 2 diabetes (T2D) patients, suggesting an important role for miR-146a (microRNA-146a) in the etiology of diabetes mellitus (DM) and its consequences. Furthermore, injection of miR-146a mimic has been confirmed to alleviate diabetes mellitus in diabetic animal models. In this line, deregulation of miR-146a expression has been linked to the progression of nephropathy, neuropathy, wound healing, olfactory dysfunction, cardiovascular disorders, and retinopathy in diabetic patients. In this review, besides a comprehensive review of the function of miR-146a in DM, we discussed new findings on type 1 (T1MD) and type 2 (T2DM) diabetes mellitus, highlighting the discrepancies between clinical and preclinical investigations and elucidating the biological pathways regulated through miR-146a in DM-affected tissues

Design of an Epitope Candidate Vaccine Against Iha Protein in Escherichia Coli: an in Silico Approach: An Epitope Candidate Vaccine Against Escherichia Coli

Introduction: Iron-regulated outer membrane virulence protein (IrgA) involved in the initial step of iron uptake by binding ferric- iron chelation siderophore that allows the bacterium to extract iron from the environment. IrgA homologue adhesion (Iha) revealed as a novel adherence conferring molecule. In this study, homology modeling, fold recognition and Ab-initio approaches along with their combination were invoked to determine the tertiary structure of Iha. Material and Methods: Specific bioinformatics methods were used to forecast their immunological, biochemical and functional properties. Results: The results showed that IrgA constitutes beta barrel structures. The immunological, biochemical and functional analyzes led us to pick a region of every antigen with the highest immunogenic properties. Comparison of antigenicity scores for selected regions and the whole proteins showed that the antigenicity of the selected regions is considerably higher than the whole antigen. Conclusion: Our strategy for prediction of the 3D structure and epitopes could be deemed as an amenable approach for efficient vaccine design. These approaches used could provide the basis for future functional studies to design and development of a suitable vaccine. In this regard, a region includes residues 200-340, covering a part of barrel, was chosen as vaccine candidate against Iha protein in Escherichia Coli

Unveiling the potential effects of resveratrol in lung cancer treatment: Mechanisms and nanoparticle-based drug delivery strategies

Lung cancer ranks among the most prevalent forms of cancer and remains a significant factor in cancer-related mortality across the world. It poses significant challenges to healthcare systems and society as a whole due to its high incidence, mortality rates, and late-stage diagnosis. Resveratrol (RV), a natural compound found in various plants, has shown potential as a nanomedicine for lung cancer treatment. RV has varied effects on cancer cells, including promoting apoptosis by increasing pro-apoptotic proteins (Bax and Bak) and decreasing anti-apoptotic proteins (Bcl-2). It also hinders cell proliferation by influencing important signaling pathways (MAPK, mTOR, PI3K/Akt, and Wnt/β-catenin) that govern cancer progression. In addition, RV acts as a potent antioxidant, diminishing oxidative stress and safeguarding cells against DNA damage. However, using RV alone in cancer treatment has drawbacks, such as low bioavailability, lack of targeting ability, and susceptibility to degradation. In contrast, nanoparticle-based delivery systems address these limitations and hold promise for improving treatment outcomes in lung cancer; nanoparticle formulations of RV offer advantages such as improved drug delivery, increased stability, controlled release, and targeted delivery to lung cancer cells. This article will provide an overview of lung cancer, explore the potential of RV as a therapeutic agent, discuss the benefits and challenges of nanoparticle-based drug delivery, and highlight the promise of RV nanoparticles for cancer treatment, including lung cancer. By optimizing these systems for clinical application, future studies aim to enhance overall treatment outcomes and improve the prognosis for lung cancer patients

A cellular and molecular biology-based update for ivermectin against COVID-19: is it effective or non-effective?

Despite community vaccination against coronavirus disease 2019 (COVID-19) and reduced mortality, there are still challenges in treatment options for the disease. Due to the continuous mutation of SARS-CoV-2 virus and the emergence of new strains, diversity in the use of existing antiviral drugs to combat the epidemic has become a crucial therapeutic chance. As a broad-spectrum antiparasitic and antiviral drug, ivermectin has traditionally been used to treat many types of disease, including DNA and RNA viral infections. Even so, based on currently available data, it is still controversial that ivermectin can be used as one of the effective antiviral agents to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or not. The aim of this study was to provide comprehensive information on ivermectin, including its safety and efficacy, as well as its adverse effects in the treatment of COVID-19

The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways

Abstract Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML. Video Abstrac

Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients’ susceptibility to COVID-19 to the possible caution of future global diabetes tsunami

According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as β cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications