Cannabinoids in neuroinflammatory disorders: Focusing on multiple sclerosis, Parkinsons, and Alzheimers diseases.

The medicinal properties of cannabis and cannabinoid-derivative are entirely investigated and known. In addition, the identification of psychotropic plant cannabinoids has led to more studies regarding the cannabinoid system and its therapeutic features in the treatment and management of clinical symptoms of neuroinflammatory disorders, such as multiple sclerosis (MS), Parkinsons disease (PD), and Alzheimers disease (AD). In fact, cannabinoid agonists are able to control and regulate inflammatory responses. In contrast to the cannabinoid receptor type 1 (CB1) and its unwanted adverse effects, the cannabinoid receptor type 2 (CB2) and its ligands hold promise for new and effective therapeutic approaches. So far, some successes have been achieved in this field. This review will discuss an outline of the endocannabinoid system's involvement in neuroinflammatory disorders. Moreover, the pharmacological efficacy of different natural and synthetic preparations of phytocannabinoids acting on cannabinoid receptors, particularly in MS, PD, and AD, will be updated. Also, the reasons for targeting CB2 for neurodegeneration will be explained.

Concomitant Expression of IL-6 and TGF-ß Cytokines and their Receptors in Peripheral Blood of Patients with Multiple Sclerosis: The Effects of INFß Drugs.

BACKGROUND: Concomitant signals from IL-6 and TGF-ß have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). OBJECTIVES: To evaluate the simultaneous IL-6 and TGF-ß gene and their receptor protein expression in patients with Relapsing-Remitting (RR)-MS. MATERIALS AND METHODS: IL-6 and TGF-ß mRNA and their receptor expression on the surface of CD4+T cells were evaluated using real-time PCR (RT-PCR) and flow cytometry, respectively. RESULTS: The IL-6 mRNA expression in patients with RRMS was significantly higher than in the controls (p= 0.019). When patients who did not receive any other treatment were compared with the controls, the significant difference was substantial (p=0.006). The TGF-ß mRNA expression in patients was lower than in the controls (p = 0.03). However, in patients receiving IFNß, it increased compared with the other patients (p= 0.036). There was no difference in cytokine receptor expression between patients and the control group. CONCLUSION: Our data conclude an increase and decrease in mRNA expression levels of IL-6 and TGF-ß in patients with RRMS, respectively. Moreover, there were no significant differences in receptor expression of either cytokines. Based on our data the balance of TGF and IL-6 appears to have a positive impact on the disease control.

The Reasons for Higher Mortality Rate in Opium Addicted Patients with COVID-19: A Narrative Review.

The outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused COVID-19 has developed into an unexampled worldwide pandemic. The most important cause of death in patients with COVID-19 is Acute Respiratory Distress Syndrome (ARDS). Opium is widely used for its analgesic features in control of acute and chronic pain related to different diseases. Opium consumption is increased over the last three decades and leads to adverse effects on the respiratory system; opium also affects the lungs' functions and respiration. The contemplative issue is the higher mortality rate due to SARS-CoV-2 infection in opium addicts' patients. Studies have shown that despite the decrease in proinflammatory cytokines production in opium addicts, there are at least 4 reasons for this increase in mortality rate: downregulation of IFNs expression, development of pulmonary edema, increase thrombotic factors, increase the expression of Angiotensin-converting enzyme 2 (ACE2). Therefore, identifying the causes of mortality and approved therapies for the treatment of COVID-19 patients who use opium for any reason is an important unmet need to reduce SARS-CoV-2 infection-related mortality. This review study demonstrated the effects of opium on immune responses and the reasons for the higher mortality rate in opium addicts' patients with COVID-19.

Induced Pluripotent Stem Cell Meets Severe Combined Immunodeficiency.

Severe combined immunodeficiency (SCID) is classified as a primary immunodeficiency, which is characterized by impaired T-lymphocytes differentiation. IL2RG, IL7Ralpha, JAK3, ADA, RAG1/RAG2, and DCLE1C (Artemis) are the most defective genes in SCID. The most recent SCID therapies are based on gene therapy (GT) of hematopoietic stem cells (HSC), which are faced with many challenges. The new studies in the field of stem cells have made great progress in overcoming the challenges ahead. In 2006, Yamanaka et al. achieved "reprogramming" technology by introducing four transcription factors known as Yamanaka factors, which generate induced pluripotent stem cells (iPSC) from somatic cells. It is possible to apply iPSC-derived HSC for transplantation in patients with abnormality or loss of function in specific cells or damaged tissue, such as T-cells and NK-cells in the context of SCID. The iPSC-based HSC transplantation in SCID and other hereditary disorders needs gene correction before transplantation. Furthermore, iPSC technology has been introduced as a promising tool in cellular-molecular disease modeling and drug discovery. In this article, we review iPSC-based GT and modeling for SCID disease and novel approaches of iPSC application in SCID.

Therapeutic plasma exchange may adjust IL-6 and TGF-ß signals in relapsed MS patients peripheral blood.

OBJECTIVE: Effects of therapeutic plasma exchange (TPE) on immune cells and their cytokine production in MS, are unknown. Since interleukine-6 and tumor growth factor-ß have critical roles in MS immunopathogenesis, the impacts of TPE on the expression of these cytokines and their receptors on the surface of CD4+ T lymphocytes, were investigated. METHODS: Blood cells were obtained from 30 Relapsing-Remitting (RR) MS patients, before and after a complete TPE course. Cytokines mRNA and their receptor expression on the CD4+ T cells surface were assessed using real-time PCR and flowcytometry, respectively. RESULTS: TPE reduced symptom severity (P = .01) and the relief was higher in males than in females (P = .039). TPE also increased TGF-ß mRNA and decreased IL-6 receptor expressing cells frequency (P = .009 and P = .028, respectively). Moreover, the frequency of CD4+IL6R+ T cells was positively correlated with disease severity (P = .001). CONCLUSION: TPE impacts simultaneously on the TGF-ß mRNA and IL-6 receptor expression, and this may be a mechanism of improvement in MS relapse symptoms induced by the TPE.

A serologic study on Toxoplasma gondii infection in slaughtered sheep and goats in Qazvin Province, Iran.

BACKGROUND: Toxoplasma gondii is a common protozoan parasite among all mammals, in particular small ruminants, worldwide. Traditional husbandry can be a major risk factor for infection of sheep and goats with this parasite. OBJECTIVES: The present study aimed to determine the current status of the prevalence for T. gondii in livestock of Qazvin Province. METHODS: In this cross-sectional study, the sera of 455 sheep and 375 goats were examined to detect anti-Toxoplasma IgG antibodies by using in-house indirect ELISA. RESULTS: Overall, 33.62% (153/455) of sheep and 36.41% (130/375) of goats were positive for anti-Toxoplasma IgG antibodies with no statistically significant difference. The prevalence rate of T. gondii among the sheep of Qazvin County was significantly higher than in Abyek and Abhar counties (p < 0.001). CONCLUSIONS: The results of the present study indicate that the prevalence of T. gondii in sheep and goats of the study area is high. Therefore, the meat of the animals reared in this area can be a potential source of human infections by this parasite.

Role of Chicoric Acid and 13-Cis Retinoic Acid in Mycobacterium tuberculosis Infection Control by Human U937 Macrophage.

Mycobacterium tuberculosis (Mtb) survives and proliferates within the main cells of the innate immune system, macrophages. The goal of our study was to investigate the immunostimulatory effects of 13-cis retinoic acid (RA) and chicoric acid (CA) in human U937 macrophages against H37Ra Mtb infection by evaluating its potential role in the cell surface expression of HLA-DR, CD14 molecules as well as nitric oxide (NO) production and prevention of the Mtb growth within macrophages. In this study, we investigated the effects of 13-cis RA and CA on Mtb-infected macrophages using flowcytometry and Griess methods, respectively. Moreover, inhibitory effect of 13-cis RA and CA on Mtb growth within macrophages were assessed using colony-forming unit. 13-Cis RA and CA enhanced the cell surface expression of HLA-DR and CD14 molecules on U937 macrophages and prevented the growth of Mtb within macrophages. In addition, 13-cis RA and CA, have increased NO generation compared to untreated control macrophages, significantly (p < 0.001). Both drugs have a significant inhibitory effect on Mtb growth but CA at the highest concentration was more potent than 13-cis RA (p < 0.05). The results of our study showed that infected U937 macrophages treated with 13-cis RA and CA represented significant increases in NO production, CD14 and HLA-DR expression and also prevents intracellular survival of Mtb. Therefore, 13-cis RA and CA may have a significant therapeutic approach in the control of Mtb infection.

Investigation of CTLA-4-318C/T gene polymorphism in cases with type 1 diabetes of Azerbaijan, Northwest Iran.

This study analyzed the association of CTLA-4-318C/T gene polymorphism with susceptibility, clinical course and laboratory findings of Type 1 diabetes (T1D). One hundred and fifty-three T1D patients and 189 healthy controls entered this study. CTLA-4-318C/T genotyping was performed by tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of -318C/T gene polymorphism were similar in patients and controls. However, younger age, earlier age at onset, higher HbA1c levels, higher frequency of Glutamic acid decarboxylase antibodies (GADA) and Insulinoma Associated-2 Autoantibodies (IA-2A) were observed in T1D patient carriers of CT genotype. The current study demonstrates that although CTLA-4-318C/T polymorphism was not linked with a higher genetic risk for T1D, the presence of a CT genotype was associated with a younger age of onset, poor control of HbA1c level and positive anti-GAD or IA-2 serum autoantibodies in Iranian Azeri population.

Detection of IL-20R1 and IL-20R2 mRNA in C57BL/6 mice astroglial cells and brain cortex following LPS stimulation.

BACKGROUND: Astrocytes, which comprise ~90% of overall brain mass, are involved in brain immunity. These cells represent the non-professional class of CNS-resident APCs and may promote or inhibit CNS inflammation depending on the cytokines they secrete. IL-10 family of cytokines and their receptors, IL-20R1 and IL-20R2, may have a role in shifting astrocytes to a neuroprotective or neurodegenerative function. OBJECTIVE: To address the expression of IL-20R1 and IL-20R2 cytokine receptors in astrocytes and brain cortex of C57BL/6 mice. METHODS: We investigated the expression of IL-20R1 and IL-20R2 in C57BL/6 mice astroglial cells and brain cortex in response to lipopolysaccharide (LPS), using reverse-transcription polymerase chain reaction (RT-PCR) method. RESULTS: Astrocytes were able to express IL-20R1 and IL-20R2 mRNA not only in response to LPS stimulation but also in the absence of LPS. Furthermore, we found the expression of IL-20R1 and IL-20R2 mRNA in the cortex of adult C57BL/6 mice. CONCLUSIONS: IL-20R1 and IL-20R2 are constitutively express in the brain. Since most neuropathological processes involve astrocytes and inflammatory cytokines, these findings have important implications for future therapeutic strategies.