Intraperitoneal injection of mesenchymal stem cells-conditioned media (MSCS-CM) treated monocyte can potentially alleviate motor defects in experimental autoimmune encephalomyelitis female mice; An original experimental study.

INTRODUCTION: Multiple sclerosis (MS), as a destructive pathology of myelin in central nervous system (CNS), causes physical and mental complications. Experimental autoimmune encephalomyelitis (EAE) is laboratory model of MS widely used for CNS-associated inflammatory researches. Cell therapy using macrophage M2 (MPM2) is a cell type with anti-inflammatory characteristics for all inflammatory-based neuropathies. This experimental study investigated the probable therapeutic anti-inflammatory effects of intraperitoneal (IP) injection of MPM2 on alleviation of motor defect in EAE-affected animals. MATERIALS AND METHODS: 24 C57/BL6 female mice were divided into four groups of EAE, EAE + Dexa, EAE + PBS, and EAE + MP2. EAE was induced through deep cervical injection of spinal homogenate of guinea pigs. MPM2 cells were harvested from bone marrow and injected (106cells/ml) in three days of 10, 13 and 16 post-immunizations (p.i). Clinical score (CS), anti-inflammatory cytokines (IL-4, IL-10), pro-inflammatory gene expression (TNF-α, IL-1ß) and histopathological investigations (HE, Nissl and Luxol Fast Blue) were considered. Data were analyzed using SPSS software (v.19) and p < 0.05 was considered significant level. RESULTS: During EAE induction, the mean animal weight was decreased (p < 0.05); besides, following MPM2 injection, the weight gain was applied (p < 0.05) in EAE + MPM2 groups than control. Increased (p < 0.05) levels of CS was found during EAE induction in days 17-28 in EAE animals; besides, CS was decreased (p < 0.05) in EAE + MPM2 group than EAE animals. Also, in days 25-28 of experiment, the CS was decreased (p < 0.05) in EAE + MPM2 than EAE + Dexa. Histopathological assessments revealed low density of cell nuclei in corpus callosum, microscopically. LFB staining also showed considerable decrease in white matter density of corpus callosum in EAE group. Acceleration of white matter density was found in EAE + MPM2 group following cell therapy procedure. Genes expression of TNF-α, IL-1ß along with IL-4 and IL-10 were decreased (p < 0.05) in EAE + MPM2 group. CONCLUSION: IP injection of MPM2 to EAE-affected female mice can potentially reduce the CNS inflammation, neuronal death and myelin destruction. MPM2 cell therapy can improve animal motor defects.

Revolutionizing cancer treatment: the power of bi- and tri-specific T-cell engagers in oncolytic virotherapy.

Bi- or tri-specific T cell engagers (BiTE or TriTE) are recombinant bispecific proteins designed to stimulate T-cell immunity directly, bypassing antigen presentation by antigen-presenting cells (APCs). However, these molecules suffer from limitations such as short biological half-life and poor residence time in the tumor microenvironment (TME). Fortunately, these challenges can be overcome when combined with OVs. Various strategies have been developed, such as encoding secretory BiTEs within OV vectors, resulting in improved targeting and activation of T cells, secretion of key cytokines, and bystander killing of tumor cells. Additionally, oncolytic viruses armed with BiTEs have shown promising outcomes in enhancing major histocompatibility complex I antigen (MHC-I) presentation, T-cell proliferation, activation, and cytotoxicity against tumor cells. These combined approaches address tumor heterogeneity, drug delivery, and T-cell infiltration, offering a comprehensive and effective solution. This review article aims to provide a comprehensive overview of Bi- or TriTEs and OVs as promising therapeutic approaches in the field of cancer treatment. We summarize the cutting-edge advancements in oncolytic virotherapy immune-related genetic engineering, focusing on the innovative combination of BiTE or TriTE with OVs.

MiR-320a upregulation contributes to the effectiveness of pemetrexed by inhibiting the growth and invasion of human lung cancer cell line (Calu-6).

BACKGROUND: Lung cancer is a common and deadly disease. Chemotherapy is the most common treatment, which inhibits cancer cell growth. Pemetrexed (PMX) is often used with other drugs. Environmental stress can affect regulatory non-coding RNAs such as MicroRNAs that modify gene expression. This study investigates the effect of PMX on the hsa-miR-320a-3p expression in the Calu-6 lung cancer cell line. METHODS AND RESULT: Calu-6 cells were cultured in an incubator with 37 °C, 5% CO2, and 98% humidity. The MTT test was performed to determine the concentration of PMX required to inhibit 50% of cell growth. To examine growth inhibition and apoptosis, release of lactate dehydrogenase (LDH), cell assays and caspase 3 and 7 enzyme activity were used. Finally, molecular studies were conducted to compare the expression of hsa-miR-320a-3p and genes including VDAC1, DHFR, STAT3, BAX and BCL2 before and after therapy. RESULTS: According to a study, it has been observed that PMX therapy significantly increases LDH release after 24 h. The study found that PMX's IC50 on Calu-6 is 8.870 µM. In addition, the treated sample showed higher expression of hsa-miR-320a-3p and BAX, while the expression of VDAC1, STAT3, DHFR and BCL2 decreased compared to the control sample. CONCLUSION: According to the findings of the current research, hsa-miR-320a-3p seems to have the potential to play an important role in the development of novel approaches to the treatment of lung cancer.

Caffeine and naloxone treated mesenchymal stem cells improve symptoms and reduce inflammation in a mouse model of ulcerative colitis.

BACKGROUND AND OBJECTIVE: Ulcerative colitis (UC) causes ulcers in the colon and rectum, leading to abdominal pain, diarrhea, and rectal bleeding, and if left untreated, can lead to serious complications. The therapeutic effects of mesenchymal stem cells (MSCs) on experimental models of UC have been proven. Since the microenvironment around these cells is crucial in maintaining cell proliferation, differentiation, metabolism, and overall function, this study aims to evaluation the role of caffeine and naloxone as a new microenvironment for MSCs in reducing inflammation and improving symptoms in an experimental model of UC. MATERIAL AND METHOD: A group of 40 outbred NMRI mice were studied and divided randomly into four equal groups (N = 10 each group). UC was induced in all groups using acetic acid. The first group (control) was treated with phosphate buffer saline (PBS), the second group with MSCs-Caffeine, the third with MSCs-Naloxone, and the fourth with Mesalazine. The disease activity index (DAI), tissue damage, myeloperoxidase (MPO) activity, nitric oxide (NO) levels, and the production of IL-1, IL-6, and TNF-α cytokines were evaluated. RESULT: Our research demonstrated that all treatments were effective in improving the symptoms and reducing inflammatory markers in mice with colitis. Among the two MSCs treatments, the MSCs-Caffeine was found to be the most potent in reducing the levels of NO, IL-1, IL-6, tissue damage (P < 0.001) and as well as TNF-α (P < 0.0001) in compared to the control group. CONCLUSION: MSCs treated with caffeine and naloxone can enhance the immunoregulatory potential of these. As a result, treated MSCs can lead to improved clinical signs and reduced inflammatory parameters in mice with UC, making this approach a useful way for controlling and treating the disease. However, additional research is needed to access the mechanism behind the stronger immune system regulatory effects of treated MSCs in UC treatment.

Anti-inflammatory activity of peiminine in acetic acid-induced ulcerative colitis model.

Ulcerative colitis is a chronic inflammatory disorder of the intestinal mucosa and a prevalent gastrointestinal condition in developed countries. Peiminine, derived from the Fritillaria imperialis plant, exhibits remarkable anti-inflammatory and anti-cancer properties. This study aims to investigate the anti-inflammatory effects of peiminine in an experimental model of ulcerative colitis. Ulcerative colitis was induced intra-rectally in all groups, except the negative control, using 100 µl of 4% acetic acid. Peiminine treatment was initiated after ulcerative colitis induction and symptom manifestation. After the final injection, mice were sacrificed on day 15 for assessment. Various parameters were evaluated, including disease activity index, myeloperoxidase activity, nitric oxide levels, production and expression of IL-1, IL-6, TNF-α cytokines, and expression of IL-1ß, IL-6, TNF-α, iNOS, and COX2 genes. Microscopic pathological evaluation was performed on colon tissue. Peiminine treatment resulted in reduced levels of NO, MPO, IL-1ß, IL-6, and TNF-α. Furthermore, the expression of IL-1ß, IL-6, TNF-α genes, iNOS, and COX2 genes was decreased in response to peiminine treatment in these mice. This study demonstrates the effectiveness of peiminine in alleviating inflammatory manifestations and mitigating intestinal tissue damage in an experimental model of ulcerative colitis, probably by anti-inflammatory procedure. Peiminine holds potential as a therapeutic adjunct for the management of ulcerative colitis.

Exosomes from Adipose Tissue-derived Mesenchymal Stem Cells Induce Regulatory T Cells in COVID-19 Patients.

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into  Tregs from patients with COVID-19. Exosomes were isolated from adipose tissue-derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo. The frequency of CD4+CD25+CD127-  Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-ß1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo-treated PBMCs. The concentration of IL-10 increased significantly after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-ß was significantly higher in the supernatant of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL). MSC-Exo has the potential to raise anti-inflammatory responses by induction of  Tregs, potentiating its therapeutic effects in COVID-19.

Antibiofilm effect of melittin alone and in combination with conventional antibiotics toward strong biofilm of MDR-MRSA and -Pseudomonas aeruginosa.

Introduction: Multidrug-resistant (MDR) pathogens are being recognized as a critical threat to human health if they can form biofilm and, in this sense, biofilm-forming MDR-methicillin resistant Staphylococcus aureus (MRSA) and -Pseudomonas aeruginosa strains are a worse concern. Hence, a growing body of documents has introduced antimicrobial peptides (AMPs) as a substitute candidate for conventional antimicrobial agents against drug-resistant and biofilm-associated infections. We evaluated melittin's antibacterial and antibiofilm activity alone and/or in combination with gentamicin, ciprofloxacin, rifampin, and vancomycin on biofilm-forming MDR-P. aeruginosa and MDR-MRSA strains. Methods: Antibacterial tests [antibiogram, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC)], anti-biofilm tests [minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC)], as well as synergistic antibiofilm activity of melittin and antibiotics, were performed. Besides, the influence of melittin alone on the biofilm encoding genes and the cytotoxicity and hemolytic effects of melittin were examined. Results: MIC, MBC, MBIC, and MBEC indices for melittin were in the range of 0.625-5, 1.25-10, 2.5-20, and 10-40 µg/ml, respectively. The findings found that the combination of melittin AMP with antibiotics was synergistic and fractional biofilm inhibitory concentration index (FBICi) for most tested concentrations was <0.5, resulting in a significant reduction in melittin, gentamicin, ciprofloxacin, vancomycin, and rifampin concentrations by 2-256.4, 2-128, 2-16, 4-64 and 4-8 folds, respectively. This phenomenon reduced the toxicity of melittin, whereby its synergist concentration required for biofilm inhibition did not show cytotoxicity and hemolytic activity. Our findings found that melittin decreased the expression of icaA in S. aureus and LasR in P. aeruginosa genes from 0.1 to 4.11 fold for icaA, and 0.11 to 3.7 fold for LasR, respectively. Conclusion: Overall, the results obtained from our study show that melittin alone is effective against the strong biofilm of MDR pathogens and also offers sound synergistic effects with antibiotics without toxicity. Hence, combining melittin and antibiotics can be a potential candidate for further evaluation of in vivo infections by MDR pathogens.

Potential therapeutic applications of extracellular vesicles in the immunopathogenesis of COVID-19.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which has emerged as a global health crisis. Recently, more than 50 different types of potential COVID-19 vaccines have been developed to elicit a strong immune response against SARS-CoV-2. However, genetic mutations give rise to the new variants of SARS-CoV-2 which is highly associated with the reduced effectiveness of COVID-19 vaccines. There is still no efficient antiviral agent to specifically target the SARS-CoV-2 infection and treatment of COVID-19. Therefore, understanding the molecular mechanisms underlying the pathogenesis of SARS-CoV-2 may contribute to discovering a novel potential therapeutic approach to the management of COVID-19. Recently, extracellular vesicle (EV)-based therapeutic strategies have received great attention on account of their potential benefits in the administration of viral diseases. EVs are extracellular vesicles containing specific biomolecules which play an important role in cell-to-cell communications. It has been revealed that EVs are involved in the pathogenesis of different inflammatory diseases such as cancer and viral infections. EVs are released from virus-infected cells which could mediate the interaction of infected and uninfected host cells. Hence, these extracellular nanoparticles have been considered a novel approach for drug delivery to mediate the treatment of a wide range of diseases including, COVID-19. EVs are considered a cell-free therapeutic strategy that could ameliorate the cytokine storm and its complications in COVID-19 patients. Furthermore, EV-based cargo delivery such as immunomodulatory agents in combination with antiviral drugs may have therapeutic benefits in patients with SARS-CoV-2 infection. In this review, we will highlight the potential of EVs as a therapeutic candidate in the diagnosis and treatment of COVID-19. Also, we will discuss the future perspectives regarding the beneficial effects of Evs in the development of COVID-19 vaccines.

Design of a multi-epitope-based vaccine consisted of immunodominant epitopes of structural proteins of SARS-CoV-2 using immunoinformatics approach.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown rapid global spread and has resulted in a significant death toll worldwide. In this study, we aimed to design a multi-epitope vaccine against SARS-CoV-2 based on structural proteins S, M, N, and E. We identified B- and T-cell epitopes and then the antigenicity, toxicity, allergenicity, and similarity of predicted epitopes were analyzed. T-cell epitopes were docked with corresponding HLA alleles. Consequently, the selected T- and B-cell epitopes were included in the final construct. All selected epitopes were connected with different linkers and flagellin and pan-HLA DR binding epitopes (PADRE) as an adjuvant were used in the vaccine construct. Furthermore, molecular docking was used to evaluate the complex between the final vaccine construct and two alleles, HLA-A*02:01 and HLA-DRB1*01:01. Finally, codons were optimized for in silico cloning into pET28a(+) vector using SnapGene. The final vaccine construct comprised 11 CTL, HTL, and B-cell epitopes corresponding to 394 amino acid residues. In silico evaluation showed that the designed vaccine might potentially promote an immune response. Further in vivo preclinical and clinical testing is required to determine the safety and efficacy of the designed vaccine.

The effect of bergamot (KoksalGarry) supplementation on lipid profiles: A systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis were conducted to evaluate the impact of bergamot (KoksalGarry) and its nutraceutical compounds on lipid profiles. PubMed, Web of Knowledge, Scopus, and Google Scholar searched for relevant articles. Trials investigating the effect of oral bergamot supplementation on serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in adults were included. The mean differences and standard deviations were pooled using a random-effects model. Fourteen trials were included in this systematic review and meta-analysis. Bergamot supplementation significantly decreased serum levels of TC (weighted mean difference (WMD): -63.60 mg/dL; 95% CI: -78.03 to -49.18; p < .001), TG (WMD: -74.72 mg/dL; 95% CI: -83.58 to -65.87; p < .001), LDL-C (WMD: -55.43 mg/dL; 95% CI: -67.26 to -43.60; p < .001), and increased HDL-C (WMD: 5.78 mg/dL; 95% CI: 3.27 to 8.28; p < .001), respectively. Our systematic review of the effects of nutraceuticals containing bergamot on lipid markers showed inconsistent results. The results showed that bergamot supplementation might improve lipid profiles. The findings for nutraceutical compounds containing bergamot were inconsistent. However, the clinical efficacy of bergamot on lipid profiles needs to be further established through higher-quality studies.

Comprehensive Assessment of Multiple Sclerosis: From Immunotherapy and Immunopathogenesis to Predictive Biomarkers.

Background & Objective: Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies for MS, the disease progresses and relapses through several immunological pathways. New medicines aimed at remyelination and neurodegeneration are being developed; however, they need stronger evidence before being introduced into routine clinical care. The purpose of this study was a thorough assessment of MS immunopathology and predictive biomarkers. Methods: Immunotherapy, immunopathogenesis, and prognostic biomarkers were all parts of the search method. Only publications in English were considered for inclusion in the study. For that purpose, we went through the current state of knowledge around MS immunopathology and related biomarkers. Immunology, as well as the identification of increased inflammation as an important component of neurodegeneration, shaped our understanding of this disease aetiology. The relevant sources examined covered the years 2015-2021. Conclusion: We found biomarkers in the cerebrospinal fluid and blood that might be used for the prediction and diagnosis of MS, as well as for measuring treatment response and adverse effects. Many variables, including the role of some infectious organisms and the impact of environmental and social factors, might contribute to the immunological dysfunctions seen in MS. Patients with MS may benefit from better therapy options if a better understanding of MS biomarkers and immune response mechanisms would be obtained.

Lactobacilli and Bifidobacterium as anti-atherosclerotic agents.

Atherosclerosis is the thickening or hardening of the arteries which is caused by a buildup of atheromatous plaque in the inner lining of an artery. Hypercholesterolemia, inflammation, oxidative stress, and trimethylamine N-oxide (TMAO) are important risk factors for atherosclerosis. Therefore, this study aimed to review the anti-atherosclerotic effects of Lactobacilli and Bifidobacterium via improving lipid profile and reducing the effects of oxidative stress, inflammation, and TMAO. To prepare the present review, several databases such as Scopus, PubMed, and Google Scholar were searched, and relevant articles from 1990 until 2022 were selected and reviewed. The present review showed that Lactobacilli and Bifidobacterium reduce the risk of atherosclerosis in both in vitro and in vivo studies by breaking down or altering cholesterol metabolism with the help of their by-products and by reducing inflammation and oxidative stress and TMAO. Consumption of Lactobacilli and Bifidobacterium can be useful in prevention of atherosclerosis.

COVID-19 vaccine acceptance among pregnant women worldwide: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has led to the death of many people worldwide. The World Health Organization (WHO) has declared vaccine resistance as one of the greatest health threats in the world even before the COVID-19 epidemic. The aim of this study was to evaluate the acceptance of COVID-19 vaccine in pregnant women. METHOD: We performed this systematic review and meta-analysis in accordance with the PRISMA guidelines. We applied the standard search strategy to the PubMed/Medline, Web of Science (ISI), Scopus, Science Direct, Cochrane Library, EMBASE, and EBSCO databases, and the Google Scholar search engine. Heterogeneity between studies was relatively high and therefore meta-analyses were performed based on random effects model with 95% CI using STATA version 16. RESULTS: In 16 articles with a sample size of 19219 pregnant women, the acceptance of COVID-19 vaccine was estimated 53.46% (95%CI: 47.64%-59.24%). Subgroup analysis was performed based on continent (p = 0.796), data collection method (p = 0.450) and meta-regression based on the month of the study (P<0.001), and only meta-regression was significant based on the month of the study. The effect of some variables such as graviad (OR = 1.02 [95%CI: 0.90-1.16]), maternal age was (OR = 1.02 [95%CI: 0.93-1.11]) and history of influenza vaccination (OR = 0.87 [95%CI: 0.71-1.06]) on COVID-19 vaccine acceptance was evaluated, which was not significant. CONCLUSION: The prevalence of COVID-19 vaccine acceptance in pregnant women was 53.46%, which was much lower than the general COVID-19 vaccination. Therefore, necessary interventions should be taken to increase the acceptance of the vaccine, address safety concerns and educate about it.

Stem cells as an ideal carrier for gene therapy: A new approach to the treatment of hepatitis C virus.

BACKGROUND AND AIM: Various chemical drugs have been approved for the treatment of patients with hepatitis C, but most of these treatments are costly, and also have an inadequate response and many side effects. Also, there is no effective vaccine for hepatitis C due to its high genetic diversity. In recent decades, clinical trials have grown dramatically regarding the benefits of stem cell therapy as a modulator of immune system responses and anti-inflammatory drugs. The most promising point in stem cell therapy and similar therapies is that patients with chronic pain and severe injuries are offered drug-free treatment or surgery. In the present study, we examine the various dimensions of the use of stem cells with the approach of gene therapy carriers as a new treatment method in the treatment of Hepatitis C. METHODS: Search terms were including gene carrier, stem cell therapy, gene therapy, liver disorders, hepatitis C virus. At first, 1000 article titles related to the mentioned keywords for different diseases were found. After removing duplicate titles and items that did not match the scope of the research, articles that met the criteria for entering the research and had usable information were selected. All abstracts of selected articles were studied by researchers. In the initial review, articles related to the title were identified and categorized based on the type of challenge. CONCLUSION: Gene therapy, either directly and in vivo or indirectly and in vitro, requires carriers (vectors) to transfer the gene. These carriers are divided into two groups, viral and non-viral. In indirect gene therapy, living cells are isolated from a person's body and genetically modified. Stem cells have the properties to transfer the desired genes to the patient's body, including the ability to proliferate for a long time and differentiate into the tissue cells in which they are located.

Melatonin as a complementary and prophylactic agent against COVID-19 in high-risk populations: A narrative review of recent findings from clinical and preclinical studies.

The coronavirus disease 2019 (COVID-19) pandemic has been going on around the world for more than a year and has cost a lot, as well as affected the quality of life of many. The psychological stress like delirium and sleep disturbances caused by the COVID-19 has affected many people in direct or indirect way by the disease. Insomnia and sleep deprivation have a negative effect on the immune system as well as disorders of the hormonal system, including the production and secretion of melatonin, known as the sleep hormone. Melatonin is a known anti-inflammatory and antioxidant agent in addition to its role in regulating circadian rhythms. In this review, we investigated the relationship between the effect of psychological stress caused by COVID-19 on patients, their families, health care workers, and occupations as well as how melatonin might act as a prophylactic agent with sedative effects and sleep enhancement potential. Search terms "melatonin" and "COVID-19" were manually searched on PubMed or other electronic database and relevant articles were included. Based on the review of scholarly articles, it can be inferred that melatonin, as an endogenous hormone controlling and regulating sleep and wakefulness in various researches, has a good potential due to its antioxidant and anti-inflammatory with minimal side effects. These beneficial effects highlight the impact of melatonin as an adjuvant and a potential alternative for the better management of SARS-CoV-2 infection in high-risk populations.

Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses.

BACKGROUND: Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. MAIN BODY: CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. CONCLUSION: Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.

NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement.

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1ß in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1ß, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1ß cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

An evaluation of the effects of Pistacia atlantica gum hydro-alcoholic extract on the phagocytosis ability of macrophages and atherosclerosis development in hypercholesteremic rats.

BACKGROUND: Atherosclerosis is an inflammatory disease that various factors affect the onset and its progression, including free radicals, hypertension, diabetes, genetic changes, hypercholesterolemia, and even some microorganisms such as herpes viruses and chlamydia. Therefore, compounds that can be effective in any of the above cases may be considered as a useful therapeutic agent in the process of atherosclerosis. The aim of the present study was to evaluate the effects of Pistacia atlantica gum hydro-alcoholic extract on macrophage phagocytosis ability and development of atherosclerosis in hypercholesterolemic rats. METHODS: The statistical population of the present study consisted of 25 rats that were randomly divided into 5 groups (one control group under standard diet, 4 treatment groups under high-fat diet). After consumption of high-fat food for 45 days, the treatment groups orally received 100, 200, and 400 mg/kg of Pistacia atlantica gum hydro-alcoholic extract for 30 days. Then, peritoneal macrophages were isolated and blood samples were collected to measure the level of nitroblue tetrazolium (NBT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG). P ˂ 0.05 was considered significant in all evaluations. RESULTS: The level of cholesterol (503.66 ± 17.15), TG (436.66 ± 16.80), LDL-C (343.66 ± 11.59), HDL-C (54.33 ± 7.02), and NBT (0.64 ± 0.02) decreased in the treatment groups. Besides, exactly in a concentration-dependent manner, plant extract significantly reduced the level of respiratory potential level in macrophages. CONCLUSION: Hydro-alcoholic extract of Pistacia atlantica gum could effectively decrease hypercholesterolemia and increase phagocytic ability of macrophages. Therefore, it can be suggested for more investigation as a blockage of atherosclerosis.

Combination therapy with CAR T cells and oncolytic viruses: a new era in cancer immunotherapy.

Chimeric antigen receptor (CAR) T-cell therapy is an encouraging and fast-growing platform used for the treatment of various types of tumors in human body. Despite the recent success of CAR T-cell therapy in hematologic malignancies, especially in B-cell lymphoma and acute lymphoblastic leukemia, the application of this treatment approach in solid tumors faced several obstacles resulted from the heterogeneous expression of antigens as well as the induction of immunosuppressive tumor microenvironment. Oncolytic virotherapy (OV) is a new cancer treatment modality by the use of competent or genetically engineered viruses to replicate in tumor cells selectively. OVs represent potential candidates to synergize the current setbacks of CAR T-cell application in solid tumors and then and overcome them. As well, the application of OVs gives researches the ability to engineer the virus with payloads in the way that it selectively deliver a specific therapeutic agents in tumor milieu to reinforce the cytotoxic activity of CAR T cells. Herein, we made a comprehensive review on the outcomes resulted from the combination of CAR T-cell immunotherapy and oncolytic virotherapy for the treatment of solid cancers. In the current study, we also provided brief details on some challenges that remained in this field and attempted to shed a little light on the future perspectives.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.