The relationship between aflatoxin B1 with the induction of extrinsic/intrinsic pathways of apoptosis and the protective role of taraxasterol in TM3 leydig cell line.

Aflatoxins B1 (AFB1) a dangerous type of aflatoxin, poses a serious threat to human health. Meanwhile, Taraxasterol, a bioactive compound in dandelion, exhibits strong anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to investigate the impact of AFB1 on the intrinsic and extrinsic pathways of apoptosis, as well as evaluate the protective role of taraxasterol in the TM3 Leydig cell line. Cell viability was evaluated using an MTT assay, measuring the effects of 3.6 µM AFB1 and varying concentrations of taraxasterol. Expression levels of Caspase 3,8, and 9 were analyzed with RT-qPCR, and flow cytometry was used to assess cell cycle progression and apoptotic alterations. The findings of this study demonstrated that exposure to 3.6 µM of AFB1 resulted in an upregulation of Caspase 3 and Caspase 9 expression, indicating an activation of apoptotic pathways in TM3 cells. Additionally, the analysis of apoptosis revealed a significant increase in cellular apoptosis at this AFB1 concentration. However, when TM3 cells were exposed to 5 µM of taraxasterol, a downregulation of Caspase 3 and Caspase 9 expression was observed, suggesting a protective effect against apoptosis. Moreover, the apoptotic rate in TM3 cells was reduced in the presence of 5 µM of taraxasterol. Consequently, this study highlights the potential of taraxasterol as a protective agent against AFB1-induced apoptosis and suggest its potential application in regulating cell survival and apoptosis-related processes. Further investigations are necessary to elucidate the underlying mechanisms and evaluate the clinical implications of taraxasterol in the context of fertility disorders and other conditions associated with AFB1 exposure.

Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies.

OBJECTIVES: We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2' and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images. RESULTS: The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2', and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2', p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05). DISCUSSION: Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2' or QSM.

Hyaluronic acid optimises therapeutic effects of hydrogen peroxide-induced oxidative stress on breast cancer.

Distinguishing the multiple effects of reactive oxygen species (ROS) on cancer cells is important to understand their role in tumour biology. On one side, ROS can be oncogenic by promoting hypoxic conditions, genomic instability and tumorigenesis. Conversely, elevated levels of ROS-induced oxidative stress can induce cancer cell death. This is evidenced by the conflicting results of research using antioxidant therapy, which in some cases promoted tumour growth and metastasis. However, some antioxidative or ROS-mediated oxidative therapies have also yielded beneficial effects. To better define the effects of oxidative stress, in vitro experiments were conducted on 4T1 and splenic mononuclear cells (MNCs) under hypoxic and normoxic conditions. Furthermore, hydrogen peroxide (H2 O2 ; 10-1,000 µM) was used as an ROS source alone or in combination with hyaluronic acid (HA), which is frequently used as drug delivery vehicle. Our result indicated that the treatment of cancer cells with H2 O2 + HA was significantly more effective than H2 O2 alone. In addition, treatment with H2 O2 + HA led to increased apoptosis, decreased proliferation, and multiphase cell cycle arrest in 4T1 cells in a dose-dependent manner under normoxic or hypoxic conditions. As a result, migratory tendency and the messenger RNA levels of vascular endothelial growth factor, matrix metalloproteinase-2 (MMP-2), and MMP-9 were significantly decreased in 4T1 cells. Of note, HA treatment combined with 100-1,000 µM H2 O2 caused more damage to MNCs as compared to treatment with lower concentrations (10-50 µM). Based on these results, we propose to administer high-dose H2 O2 + HA (100-1000 µM) for intratumoural injection and low doses for systemic administration. Intratumoural route could have toxic and inhibitory effects not only on the tumour but also on residential myeloid cells defending it, whereas systemic treatment could stimulate peripheral immune responses against the tumour. More in vivo research is required to confirm this hypothesis.

Mutations in SARS-CoV-2; Consequences in structure, function, and pathogenicity of the virus.

The third pandemic of coronavirus infection, called COVID-19 disease, began recently in China. The newly discovered coronavirus, entitled SARS-CoV-2, is the seventh member of the human coronaviruses. The main pathogenesis of SARS-CoV-2 infection is severe pneumonia, RNAaemia, accompanied by glass turbidity, and acute cardiac injury. It possesses a single-stranded positive-sense RNA genome which is 60-140 nm in diameter, and has a size of 26-32 kbp. Viral pathogenesis is accomplished with spike glycoprotein through the employment of a membrane-bound aminopeptidase, called the ACE2, as its primary cell receptor. It has been confirmed that various factors such as different national rules for quarantine and various races or genetic backgrounds might influence the mortality and infection rate of COVID-19 in the geographic areas. In addition to various known and unknown factors and host genetic susceptibility, mutations and genetic variabilities of the virus itself have a critical impact on variable clinical features of COVID-19. Although the SARS-CoV-2 genome is more stable than SARS-CoV or MERS-CoV, it has a relatively high dynamic mutation rate with respect to other RNA viruses. It's noteworthy that, some mutations can be founder mutations and show specific geographic patterns. Undoubtedly, these mutations can drive viral genetic variability, and because of genotype-phenotype correlation, resulting in a virus with more/lower/no decrease in natural pathogenic fitness or on the other scenario, facilitating their rapid antigenic shifting to escape the host immunity and also inventing a drug resistance virus, so converting it to a more infectious or deadly virus. Overall, the detection of all mutations in SARS-CoV-2 and their relations with pathological changes is nearly impossible, mostly due to asymptomatic subjects. In this review paper, the reported mutations of the SARS-CoV-2 and related variations in virus structure and pathogenicity in different geographic areas and genotypes are widely investigated. Many studies need to be repeated in other regions/locations for other people to confirm the findings. Such studies could benefit patient-specific therapy, according to genotyping patterns of SARS-CoV-2 distribution.

Measurement of oxidized albumin: An opportunity for diagnoses or treatment of COVID-19.

Human serum albumin (HSA) as the most abundant protein in human blood plasma, can be a good indicator for evaluating severity of some diseases in the clinic. HSA can be find in two forms: reduced albumin (human mercaptalbumin (HMA)) and oxidized albumin (human non-mercaptalbumin (HNA)). The rate of oxidized albumin to total albumin can be enhanced in multiple diseases. Increase in HNA level have been demonstrated in liver, diabetes plus fatigue and coronary artery diseases. In liver patients, this enhancement can reach to 50-200 percent which can then lead to bacterial/viral infections and eventually death in severe conditions. Due to the induction of cytokine storm, we can say that the level of HNA in serum of coronavirus disease 2019 (COVID-19) patients may be a positive predictor of mortality, especially in patients with underlying diseases such as cardiovascular disease (CVD), diabetes, aging and other inflammatory diseases. We suggest that checking oxidized albumin in COVID-19 patients may provide new therapeutic and diagnostic opportunities to better combat COVID-19.

Therapeutic Effects of Exosomal miRNA-4731-5p from Adipose Tissue-Derived Stem Cells on Human Glioblastoma Cells.

BACKGROUND AND AIM: Several microRNAs (miRNAs) are differentially expressed and serve as tumor suppressors in glioblastoma (GBM). The present study aimed to elucidate the function of exosomal microRNA-4731-5p (miR-4731-5p) from adipose tissue-derived mesenchymal stem cells (AD-MSCs) in the activity of human GBM cell lines. METHOD: First, GBM-related miRNAs, their expression, and potential target genes and cytokines of miR-4731-5p were identified using bioinformatic datasets. Subsequently, purified AD-MSCs were transfected with a miRNA-4731-5p expression plasmid, and exosomes were isolated and characterized. Next, the transfection process was confirmed and the 50% inhibitory concentration (IC50) of the overexpressed exosomal miRNA-4731-5p was inhibited for cancer cells. The probable anticancer action of exosomal miRNA-4731-5p on U-87 and U-251 GBM cell lines was verified by flow cytometry, DAPI staining, cell cycle, real-time PCR, and wound healing assays. RESULTS: A concentration of 50 ng/mL of miRNA-4731-5p-transfected exosomes was the safe dose for anticancer settings. The results showed that the exosomal miR-4731-5p exerted an inhibitory effect on the cell cycle and migration and induced apoptosis in GBM cell lines by regulating the phosphoinositide-3-kinase-AKT (PI3K-AKT) and nuclear factor-kB (NF-kB) signaling pathways. CONCLUSION: This study reveals that the expression of exosomal miRNA-4731-5p has favorable antitumor properties for the treatment of GBM cell lines and may be a fundamental therapeutic option for this type of brain tumor.

The influence of indole propionic acid on molecular markers of steroidogenesis, ER stress, and apoptosis in rat granulosa cells exposed to high glucose conditions.

Hyperglycemia is known as one of the main causes of infertility in human societies. Indole propionic acid (IPA) is produced by intestinal microbiota and has antioxidant and anti-inflammatory properties. This study aims to investigate the effects of IPA on molecular indices of steroidogenesis, ER stress, and apoptosis induced by high glucose (HG) in granulosa cells. Primary GCs, isolated from ovarian follicles of Rats were cultured in 5 mM (control) and 30 mM (HG) of glucose and in the presence of 10 and 20 µM of IPA for 24 h. The cell viability was assessed by MTT. The gene expression of P450SCC, 3ßHSD, CYP19A, BAX, BCL2, and STAR was evaluated by Real-Time PCR. Protein expression of ATF6, PERK, GRP78, and CHOP determined by western blot. Progesterone, estradiol, IL-1ß, and TNF-α were measured by ELISA. HG decreased the viability, and expression of P450SCC, 3ßHSD, CYP19A, BCL2, STAR, and increased BAX. 10 and 20 µM of IPA increased cell viability, expression of P450SCC, 3ßHSD, CYP19A, BCL2 and STAR and decreased BAX compared to the HG group. The expression of ATF6, PERK, GRP78, and CHOP proteins increased by HG and IPA decreased the expression of these proteins compared to the HG group. Also, HG decreased progesterone and estradiol levels and increased IL-1ß and TNF-α. IPA significantly increased progesterone and estradiol and decreased IL-1ß and TNF-α compared to the HG group. IPA can improve the side effects of HG in GCs of rats, as responsible cells for fertility, by improving steroidogenesis, regulation of ER-stress pathway, suppression of inflammation, and apoptosis.

The potential application of encapsulated exosomes: A new approach to increase exosomes therapeutic efficacy.

Cell therapy is one of the methods that have shown promising results in treating diseases in recent decades. However, the use of different types of cells comes with limitations. The application of immune cells in cell therapy can lead to cytokine storms and inappropriate responses to self-antigens. Also, the use of stem cells has the potential to create tumors. Also, cells may not migrate to the injury site after intravenous injection. Therefore, using exosomes from different cells as therapeutic candidates were proposed. Due to their small size and favorable characteristics, such as biocompatibility and immunocompatibility, the easy storage and isolation, exosomes have attracted much attention. They are used in treating many diseases, including cardiovascular diseases, orthopedic diseases, autoimmune diseases, and cancer. However, the results of various studies have shown that the therapeutic efficiency of exosomes (Exo) can be increased by loading different drugs and microRNAs inside them (encapsulated exosomes). Therefore, analyzing studies investigating encapsulated exosomes' therapeutic ability is critical. In this study, we have examined the studies related to the use of encapsulated exosomes in treating diseases such as cancer and infectious diseases and their use in regenerative medicine. Compared to intact exosomes, the results show that the application of encapsulated exosomes has a higher therapeutic ability. Therefore it is suggested to use this method depending on the treatment type to increase the treatment's efficiency.

Recent progress in the manipulation of biochemical and biophysical cues for engineering functional tissues.

Tissue engineering (TE) is currently considered a cutting-edge discipline that offers the potential for developing treatments for health conditions that negatively affect the quality of life. This interdisciplinary field typically involves the combination of cells, scaffolds, and appropriate induction factors for the regeneration and repair of damaged tissue. Cell fate decisions, such as survival, proliferation, or differentiation, critically depend on various biochemical and biophysical factors provided by the extracellular environment during developmental, physiological, and pathological processes. Therefore, understanding the mechanisms of action of these factors is critical to accurately mimic the complex architecture of the extracellular environment of living tissues and improve the efficiency of TE approaches. In this review, we recapitulate the effects that biochemical and biophysical induction factors have on various aspects of cell fate. While the role of biochemical factors, such as growth factors, small molecules, extracellular matrix (ECM) components, and cytokines, has been extensively studied in the context of TE applications, it is only recently that we have begun to understand the effects of biophysical signals such as surface topography, mechanical, and electrical signals. These biophysical cues could provide a more robust set of stimuli to manipulate cell signaling pathways during the formation of the engineered tissue. Furthermore, the simultaneous application of different types of signals appears to elicit synergistic responses that are likely to improve functional outcomes, which could help translate results into successful clinical therapies in the future.

Cancer-associated mesenchymal stem/stromal cells: role in progression and potential targets for therapeutic approaches.

Malignancies contain a relatively small number of Mesenchymal stem/stromal cells (MSCs), constituting a crucial tumor microenvironment (TME) component. These cells comprise approximately 0.01-5% of the total TME cell population. MSC differentiation potential and their interaction with the tumor environment enable these cells to affect tumor cells' growth, immune evasion, metastasis, drug resistance, and angiogenesis. This type of MSC, known as cancer-associated mesenchymal stem/stromal cells (CA-MSCs (interacts with tumor/non-tumor cells in the TME and affects their function by producing cytokines, chemokines, and various growth factors to facilitate tumor cell migration, survival, proliferation, and tumor progression. Considering that the effect of different cells on each other in the TME is a multi-faceted relationship, it is essential to discover the role of these relationships for targeting in tumor therapy. Due to the immunomodulatory role and the tissue repair characteristic of MSCs, these cells can help tumor growth from different aspects. CA-MSCs indirectly suppress antitumor immune response through several mechanisms, including decreasing dendritic cells (DCs) antigen presentation potential, disrupting natural killer (NK) cell differentiation, inducing immunoinhibitory subsets like tumor-associated macrophages (TAMs) and Treg cells, and immune checkpoint expression to reduce effector T cell antitumor responses. Therefore, if these cells can be targeted for treatment so that their population decreases, we can hope for the treatment and improvement of the tumor conditions. Also, various studies show that CA-MSCs in the TME can affect other vital aspects of a tumor, including cell proliferation, drug resistance, angiogenesis, and tumor cell invasion and metastasis. In this review article, we will discuss in detail some of the mechanisms by which CA-MSCs suppress the innate and adaptive immune systems and other mechanisms related to tumor progression.

New insights on circular RNAs and their potential applications as biomarkers, therapeutic agents, and preventive vaccines in viral infections: with a glance at SARS-CoV-2.

The occurrence of viral infections and approaches to handling them are very challenging and require prompt diagnosis and timely treatment. Recently, genomic medicine approaches have come up with the discovery of the competing endogenous RNA (ceRNA) network, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) on the basis of gene silencing. CircRNAs, as a group of non-encoded RNAs, make a loop-like structure by back-splicing through 3' and 5' ends. They are stable, abundant, specific, and highly conserved and can be quickly generated at large scales in vitro. CircRNAs have the potential to contribute in several cellular processes in a way that some serve as microRNA sponges, cellular transporters, protein-binding RNAs, transcriptional regulators, and immune system modulators. CircRNAs can even play an important role in modulating antiviral immune responses. In the present review, circRNAs' biogenesis, function, and biomarker and therapeutic potential as well as their prospective applications as vaccines against viral infections such as SARS-CoV-2 are explained. By considering their unique properties, their potential to be used as novel vaccines, biomarkers, and a therapeutic approach appears possible.

In vitro and in vivo Evidence on Intra-tumor Injection of Allogeneic Serum for Immunotherapy in a Mouse Model of Colon Cancer.

It is believed that preformed antibodies are responsible for blood transfusion reactions and transplant rejections. In order to remove a tumor, the tissue must be rejected. On the basis of transfusion reaction and transplantation immunology, we hypothesized that allogeneic serum can inhibit tumor growth when injected intra-tumor. Initially, an in vitro cytotoxicity test was conducted using the C57BL/6 serum (intact or decomplemented) in combination with the BALB/c-originating CT26 cell line.  The CT26 cell line was used to establish a mouse model of colon cancer. When the tumor was palpable, C57BL/6 serum was injected intra-tumor. In addition to tumor size, hypoxia, metastatic capacity, angiogenesis, and metabolic and inflammatory status, we evaluated matrix metalloproteinase-2 (MMP)-2 and 9, vascular endothelial growth factor (VEGF)-A, Cluster of Designation (CD) 31, CD38 and interleukine (IL)-10. An in vitro experiment showed that heat-inactivated C57BL/6 serum had significantly lower cytotoxic effects on BALB/c-derived CT26 cells than intact C57BL/6 serum or BALB/c serum. In vivo experiments revealed that tumor size, HIF-1α, MMP-2, and MMP-9 levels were significantly lower in the experimental group than in the control group. In contrast to control animals, allogeneic serum treatment led to marked reductions in CD31, VEGF-1, CD38, and IL-10 levels. A new approach to serum or plasma therapy and allogeneic vaccines for cancer is intra-tumor injection of allogeneic serum. In light of the ease and availability of allogeneic immunotherapies, allogeneic serum and plasma therapy could potentially be used as an alternative monotherapy or in combination with other therapies.

Synthesis of Artemether-Loaded Albumin Nanoparticles and Measurement of Their Anti-Cancer Effects.

Colorectal cancer is the third most common cancer in the world. Due to the side effects of common treatments such as chemotherapy and radiotherapy, the use of herbal medicines has received much attention. Artemether (ARM) is an herbal medicine derived from artemisinin, which has many anti-tumor properties. However, factors such as low solubility and short half-life have limited the use of artemether in clinical practice. In this study, we aimed to reduce these limitations by encapsulating artemether in human serum albumin (HSA). The hydrodynamic diameter and the zeta potential value of ARM-ALB nanoparticles (NPs) were 171.3 ± 5.88 nm and -19.1 ± 0.82 mV, respectively. Comparison of the effect of free and encapsulated artemether on CT 26 cell line showed that the use of artemether in capsulated form can reduce the effective concentration of the drug. Additionally, in vivo studies have also shown that albumin-artemether nanoparticles can control tumor growth by increasing the production of cytokine IFN-γ and decreasing the production of IL4. Therefore, ARM-ALB nanoparticles have greater anti-tumor effects than free artemether.

New Paradigm in Cell Therapy Using Sperm Head to Restore Brain Function and Structure in Animal Model of Alzheimer's Disease: Support for Boosting Constructive Inflammation vs. Anti-Inflammatory Approach.

Alzheimer's is characterized by accumulation of amyloid-ß (Aß) associated with insufficient clearance of toxicants from the brain establishing a chronic inflammation and other abnormalities in the brain. Inflammatory microglia and astrocytes along with abnormal lymphatics associated with insufficient clearance of Aß and other toxicants from the brain establish a chronic inflammation. This causes abnormal choroid plexus, leukocyte trafficking, and hypoxic condition along with high levels of regulatory T cells (Tregs). There is no consensus among researchers regarding decreasing or increasing Tregs to achieve therapeutic effects. Different opposing studies tried to suppress or boost inflammation to treat AD. Based on reproductive immunology, sperm induces constructive inflammatory response and seminal-vesicle-fluid (SVF) suppresses inflammation leading to uterus remodeling. It prompted us to compare therapeutic efficiency of inflammatory or anti-inflammatory approaches in AD model based on reproductive immunology. To do so, SVF, sperm, or sperm head (from Wistar rat) was administered via intra-cerebro-ventricular route to Sprague Dawley rat AD model. Behavioral and histological examination were made and treatment groups were compared with control AD model and normal groups. Therapeutic efficacy was in the order of sperm head>sperm>SVF. Sperm head returned learning memory, Aß, lymphatics, neural growth factors, choroid plexus function, Iba-1/GFAP, MHC II/CD86/CD40, CD38/IL-10, and hypoxia levels back to normal level. However, SVF just partially ameliorated the disease. Immunologic properties of sperm/sperm head to elicit constructive inflammation can be extended to organs other than reproductive. This nature-based approach overcomes genetic difference as an important obstacle and limitation in cell therapy, and is expected to be safe or with least side effects.

The Association between Proportion HLA-BW4 or HLA-BW6 May Causes Immunity Failure in COVID-19.

No Abstract.

A Rapid Qualitative Review of Sarcoidosis: Clinical Manifestations, Immunopathogenesis, Diagnosis and Treatment.

Sarcoidosis is a worldwide inflammatory disorder of unknown etiology that is characterized by the formation of non-caseating immune granulomas in involved organs,most commonly in the lungs and eyes. Although clinical manifestations of sarcoidosis depend on the organs involved, the most common symptoms include fatigue, fever, weight loss, eye pain, dyspnea, and chest pain. Sarcoidosis usually undergoes spontaneous regression, yet its chronic form progressively threatens the involved organs through the induction of fibrotic damage. Despite decades of medical research, the etiology of sarcoidosis still remains unclear. Nevertheless, a combination of contributors, including genetic factors, environmental exposures, and microbial agents, is believed to trigger the inflammatory state observed in this disease. Furthermore, a highly polarized Th1 and Th17 response with diminished immunomodulatory mechanisms constitute the most significant immunological event associated with this disorder. Indeed, sarcoid granulomas, which consist of highly activated antigen-presenting cells (APCs) and lymphocytes, maintain a robust specialized niche to facilitate antigen presentation and exaggerated immune responses. Both the unknown etiology and multisystem nature of the disease have hampered the development of specific therapeutics and definitive diagnostic assays for sarcoidosis. Consequently, its diagnosis and treatment still represent a challenging task for clinicians. In this article, we aim to summarize contemporary findings of sarcoidosis and its etiology, pathogenesis, and treatment.

Understanding the pivotal roles of ACE2 in SARS-CoV-2 infection: from structure/function to therapeutic implication.

In December 2019, a novel respiratory tract infection, from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in China that rapidly spread around the world. This virus possesses spike (S) glycoproteins on the surface of mature virions, like other members of coronaviridae. The S glycoprotein is a crucial viral protein for binding, fusion, and entry into the target cells. Binding the receptor-binding domain (RBD) of S protein to angiotensin-converting enzyme 2 (ACE 2), a cell-surface receptor, mediates virus entry into cells; thus, understanding the basics of ACE2 and S protein, their interactions, and ACE2 targeting could be a potent priority for inhibition of virus infection. This review presents current knowledge of the SARS-CoV-2 basics and entry mechanism, structure and organ distribution of ACE2, and also its function in SARS-CoV-2 entry and pathogenesis. Furthermore, it highlights ACE2 targeting by recombinant ACE2 (rACE2), ACE2 activators, ACE inhibitor, and angiotensin II (Ang II) receptor blocker to control the SARS-CoV-2 infection.

Aflatoxin G1 exposure altered the expression of BDNF and GFAP, histopathological of brain tissue, and oxidative stress factors in male rats.

Background and purpose: Aflatoxins are highly toxic compounds that can cause acute and chronic toxicity in humans and animals. This study aimed to evaluate the expression of BDNF and GFAP, histopathological changes, and oxidative stress factors in brain tissue exposed to aflatoxin G1 (AFG1) in male rats. Experimental approach: Twenty-eight male Wistar rats were used. Animals were randomly divided into 4 groups of 7 each. The control group received 0.2 mL of corn oil and the treatment groups were exposed to AFG1 (2 mg/kg) intra-peritoneally for 15, 28, and 45 days. The tissue was used for histopathological studies, and the level of TAC, SOD, and MDA, and the expression of BDNF and GFAP genes were evaluated. Findings/Results: Real-time PCR results showed that AFG1 increased GFAP expression and decreased BDNF expression in AFG1-treated groups compared to the control group. The tissue level of TAC and SOD over time in the groups receiving AFG1 significantly decreased and the tissue level of MDA increased compared to the control group. Histopathological results showed that AFG1 can cause cell necrosis, a reduction of the normal cells number in the hippocampal region of CA1, cerebral edema, shrinkage of nerve cells, formation of space around neuroglia, and diffusion of gliosis in the cerebral cortex after 45 days. Conclusion and implication: AFG1, by causing pathological complications in cortical tissue, was able to affect the exacerbation of nerve tissue damage and thus pave the way for future neurological diseases.

Physiological and Immunological Causes of the Susceptibility of Chronic Inflammatory Patients to COVID-19 Infection: Focus on Diabetes.

The coronavirus disease 2019 (COVID-19) pandemic has recently emerged, which was then spread rapidly in more than 190 countries worldwide so far. According to the World Health Organization, 3,232,062 global cases of COVID-19 were confirmed on April 30th with a mortality rate of 3.4%. Notably, the symptoms are almost similar to those of flu such as fever, cough, and fatigue. Unfortunately, the global rates of morbidity and mortality caused by this disease are more and still increasing on a daily basis. The rates for patients suffering from inflammatory diseases like diabetes, is even further, due to their susceptibility to the pathogenesis of COVID-19. In this review, we attempted to focus on diabetes to clarify the physiological and immunological characteristics of diabetics before and after the infection with COVID-19. We hope these conceptions could provide a better understanding of the mechanisms involved in COVID-19 susceptibility and increase the awareness of risk to motivate behavior changes in vulnerable people for enhancing the prevention. Up to now, the important role of immune responses, especially the innate ones, in the development of the worst signs in COVID-19 infection have been confirmed. Therefore, to better control patients with COVID-19, it is recommended to consider a history of chronic inflammatory diseases as well as the way of controlling immune response in these patients.