The role of polybrominated diphenyl ethers in the induction of cancer: a systematic review of insight into their mechanisms.

Environmental pollution caused by persistent organic pollutants (POPs) has increased the challenge for the scientific communities. Polybrominated diphenyl ethers (PBDEs), classified as POPs, are widely applied in various materials as brominated flame retardants (BFRs). Because of the nature of these chemical compounds including toxicity, stability, and capability to bioaccumulate and biomagnify, PBDEs have posed a great challenge and risk to human health and wildlife. Therefore, the side effects of exposure to PBDEs as ubiquitous pollutants in the environment on cancer progression were investigated using a systematic review (SR) survey. To achieve this goal, forty studies were considered after defining the search terms and inclusion criteria, and/or exclusion criteria; the eligible records were collected from the international bibliographic databases. Based on the findings of the reviewed records, environmental exposure to the BFRs including PBDEs has a positive association with different mechanisms that induce cancer progression. However, the findings of the reviewed studies were not totally consistent with the mode of action and side effects are yet to be fully elucidated. Several articles have reported that BFRs can be carcinogenic and induce epithelial to mesenchymal transition via different mechanisms. The main mode of action involved in the environmental exposure to BFRs and the risk of cancer progression is endoplasmic reticulum and oxidative stress (OS). Generally, the imbalance of antioxidant mechanisms, reactive nitrogen species (RNSs) and reactive oxygen species (ROSs), during damage in cells, and stress caused OS, which increases tumorigenesis via multiple mechanisms, such as DNA damage, inflammation, and angiogenesis.

The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease-modifying therapies.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56bright NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56dim NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway. AIM: We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes. MATERIALS AND METHODS: The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease-modifying therapies on the number of NK and NKT subtypes. RESULTS: Expansion of CD56bright NK cells, reduction in the CD56dim cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease-modifying therapies. CONCLUSION: Expansion of CD56bright NK cells or reduction in the CD56dim cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow.

Sudden cardiac death in COVID-19 patients, a report of three cases.

The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1-6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.

Association between air pollution and Multiple Sclerosis: A systematic review.

Air pollution is a major public health threat. The present study is the first systematic review (SR) to determine the association of exposure to air pollution and Multiple Sclerosis (MS) Progression. A Literature search was carried out using relevant keywords within several international databases. A comprehensive literature search was carried out systematically and yielded 24 eligible studies concerning the relationship of exposure to air pollution including criteria air pollutants such as particulate matter, NOx and SOx, CO2, traffic noise, etc. and MS disease. The results of the included studies reveal that there was a significant relationship between exposure to air pollution and MS development and progression. Although the effect of air pollution in the pathogenesis of MS is notfully known, according to the results of the included studies exposure to polluted air can stimulate several mechanisms that act as risk factors for developing MS and for having disease relapses or neurological disability. The major potential mechanism is Dysimmune inflammatory responses subsequent oxidative stress (OS), which leads to neuroinflammation and breakdown of the normal balance between immunity and self-tolerance. Air pollutants induce and sustain chemical reactions that produce reactive oxygen species (ROSs) and nitrogen reactive species (RNSs) which can initiate inflammatory cascades via the redox-sensitive mitogen-activated protein kinase (MAPK) and NF-κB that recruit and activate neutrophils, monocytes, and dendritic cells that stimulate the adaptive immune responses such as Th1 and Th17 inflammatory responses. The uncontrolled inflammatory responses following these events cause cell death and the release of self-antigens capable of stimulating the production of auto-aggressive T-cells via enhancing antigen presentation and facilitate entry of these cells to the central nervous system. Thus, oxidative stress is the culprit in the systemic inflammation and immune imbalance development and progression, powerful risk factors in MS.

Immune and bioinformatics identification of T cell and B cell epitopes in the protein structure of SARS-CoV-2: A systematic review.

The beginning of 2020 was marked as the emergence of a COVID-19 outbreak caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, there is no vaccine or approved treatment for this infectious virus so the invention of an efficient vaccine is certainly a high priority. Some studies have employed several techniques to facilitate the combination of the immunoinformatics approach and comparative genomic approach in order to determine the potential peptides for designing the T-cell epitope-based peptide vaccine using the 2019-nCoV envelope protein as a target. Via screening the bioimmunoinformatic SARS-CoV2 derived B-cell and T-cell epitopes within the basic immunogenic of SARS-CoV2 proteins, we presented a set of inferred B-cell and T-cell epitopes from the spike (S) and nucleocapsid (N) proteins with high antigenicity and without allergenic property or toxic effects. Our findings provide a screened set of epitopes that can be introduced as potential targets for developing peptide vaccines against the SARS-CoV-2 virus.

Oral chitin treatment improved demyelination in murine autoimmune encephalomyelitis model by inhibition of inflammatory responses.

This study aimed to determine whether chitin microparticles (CMP), glucosamine-based polymers, have an anti-inflammatory response in a murine model of autoimmune encephalomyelitis. Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by immunization with myelin antigens emulsified in complete Freund adjuvant. A standard clinical and histological method (Luxol Fast Blue staining) was used to validate the model and document the impact of CMP treatment. ELISA was used to determine the production of spleen cell cytokines and serum levels of anti-chitin antibodies. Flowcytometry was used to determine the percentage of regulatory lymphocytes. The relative expression of the breast regression protein 39 (BRP-39) gene was examined through real time-PCR amplification. Clinical signs were significantly improved in mice given CMP compared with untreated mice. Histological analysis of the spinal cord revealed that treatment significantly reduced demyelination. The levels of interferon-γ, interleukin-17, and tumor necrosis factor-α were also reduced; conversely, no significant change was detected in interleukin-10 level and regulatory T cell count. The CMP-fed mice showed lower BRP-39 expression compared with the control group. It was ultimately determined that CMP modulates immune responses which could indirectly alter the pathology of an injured central nervous system. The data suggests that CMP may be used as an effective and cheap oral therapeutic agent for multiple sclerosis.

Co-administration of chitin micro-particle and Leishmania antigen proposed a new immune adjuvant against experimental leishmaniasis.

AIMS: We investigated the protective effect of chitin micro-particle (CMP) as an adjuvant against Leishmania infection in BALB/c mice. METHODS: Mice were immunized subcutaneously with soluble Leishmania antigen (SLA) plus CMP (100 µg SLA + 100 µg CMP/100 µL) as the test group. Three weeks after the last immunization, test and control groups were infected by Leishmania major (L major). Eight weeks post-infection, evaluation of parasites load in lymph nodes was performed using limiting dilution assay. Then, the spleen cell cytokine response (TNF-α, IFN-γ, IL-4, IL-10, IL-17 and IL-27) to SLA among vaccinated and nonvaccinated groups was investigated using ELISA. Serum levels of IgG1 and IgG2a were measured as well. RESULTS: The SLA plus CMP group demonstrated the protection. The responses included reduced lesion formation and lower parasite load. Also, in comparison with control group higher levels of IFN-γ and, IL-10 in the culture of spleen cells, and lower levels of IgG1 in sera were seen in SLA plus CMP group. CONCLUSION: The data supported the possibility of using CMP as a suitable adjuvant in Leishmania vaccination.

Chitin Micro Particles Regulate Splenocytes Immune Response in Experimental Autoimmune Encephalomyelitis.

Contrasting studies are reported on the induction of IL-10 and IFN-γ via chitin microparticles (CMPs) during immune stimulation. Our previous studies have shown marked protection among CMP treated Leishmania-infected mice via regulated IL-10/IFN-γ response, at the present study, once more, examined the inconsistent responses regarding the immunologic response of CMPS. To verify whether CMPs could indeed up-regulate IL-10/IFN-γ axis, isolated spleen cells from the myelin oligodendrocyte glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) mice were cultured in the presence of MOG peptide and/or CMPs. The effects of CMPs on IL-10, IFN-γ and IL-17 production were evaluated by Enzyme-linked Immunosorbent Assay (ELISA). Moreover, GATA binding protein 3 (Gata3), T-box transcription factor TBX21 (Tbx21), and RAR-related orphan receptor gamma (RORγT) expressions (real-time PCR) were investigated. MOG alone stimulated the production of IFN-γ (p≤0.004) but not, IL-10 (p≤0.140). MOG/chitin stimulation resulted in a significant increase in IFN-γ and IL-10 levels, respectively; (p≤0.004 and p≤0.003) rather than MOG. Additionally, the expression of Tbx21 (p≤0.001), but not Gata3 (p≤0.08), was increased in the MOG/chitin-treated spleen cells. All in all, CMP supports Gata3 independent IL-10 production and promotes Tbx21 dependent IFN-γ induction. These results, alongside our previous data, indicate that CMPs has particular adjuvant effects.