Dietary polyphenols and the risk of metabolic syndrome: a systematic review and meta-analysis.

BACKGROUND: Accumulating evidence has suggested that dietary polyphenols may be protective against metabolic syndrome (MetS); however, the available evidence is contradictory. The aim of this meta-analysis was to assess the association between dietary intake of polyphenols and the odds of MetS. METHODS: The PubMed and Scopus databases were systematically searched to obtain eligible studies. The risk of MetS for the highest versus the lowest intakes of total, subclasses and individual polyphenols were examined by pooling odds ratios (OR) and 95% confidence intervals (95%CI) using the random effects model. RESULTS: A total of 14 studies (6 cohort and 8 cross-sectional studies) involving a total of 50,366 participants with 10,879 cases of MetS were included. When various polyphenol compounds were pooled, they were significantly related to a 22% decreased odds of MetS (([5 studies]; OR: 0.78; 95%CI: 0.72-0.85). Higher intakes of total flavonoids (([9 studies]; OR: 0.78; 95%CI: 0.72-0.85), flavan-3-ols (([2 studies]; OR: 0.64; 95%CI: 0.43-0.94), isoflavones (([3 studies]; OR: 0.84; 95%CI: 0.75-0.93), stilbenes (([4 studies]; OR: 0.86; 95%CI: 0.76-0.97), flavones (([2 studies]; OR: 0.79; 95%CI: 0.71-0.89), and quercetin (([2 studies]; OR: 0.63; 95%CI: 0.43-0.93) were also significantly associated with a decreased risk of MetS. The associations were not modified by the age of the participants. No association was found for total polyphenols, phenolic acids, lignans, anthocyanins, and flavonols. CONCLUSION: The results of this meta-analysis supported that higher polyphenol intake can lower the risk of MetS.

Potential Role of Nrf2, HER2, and ALDH in Cancer Stem Cells: A Narrative Review.

Cancer is one of the main causes of death among humans, second only to cardiovascular diseases. In recent years, numerous studies have been conducted on the pathophysiology of cancer, and it has been established that this disease is developed by a group of stem cells known as cancer stem cells (CSCs). Thus, cancer is considered a stem cell disease; however, there is no comprehensive consensus about the characteristics of these cells. Several different signaling pathways including Notch, Hedgehog, transforming growth factor-ß (TGF-ß), and WNT/ß-catenin pathways cause the self-renewal of CSCs. CSCs change their metabolic pathways in order to access easy energy. Therefore, one of the key objectives of researchers in cancer treatment is to destroy CSCs. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an essential role in the protection of CSCs from reactive oxygen species (ROS) and chemotherapeutic agents by regulating antioxidants and detoxification enzymes. Human epidermal growth factor receptor 2 (HER2) is a member of the tyrosine kinase receptor family, which contributes to the protection of cancer cells against treatment and implicated in the invasion, epithelial-mesenchymal transition (EMT), and tumorigenesis. Aldehyde dehydrogenases (ALDHs) are highly active in CSCs and protect the cells against damage caused by active aldehydes through the regulation of aldehyde metabolism. On the other hand, ALDHs promote the formation and maintenance of tumor cells and lead to drug resistance in tumors through the activation of various signaling pathways, such as the ALDH1A1/HIF-1α/VEGF axis and Wnt/ß-catenin, as well as changing the intracellular pH value. Given the growing body of information in this field, in the present narrative review, we attempted to shed light on the function of Nrf2, HER2, and ALDH in CSCs.

Tumor-derived lncRNAs: Behind-the-scenes mediators that modulate the immune system and play a role in cancer pathogenesis.

Having been involved in complex cellular regulatory networks and cell-to-cell communications, non-coding RNAs (lncRNAs) have become functional carriers that transmit information between cells and tissues, modulate tumor microenvironments, encourage angiogenesis and invasion, and make tumor cells more resistant to drugs. Immune cells' exosomal lncRNAs may be introduced into tumor cells to influence the tumor's course and the treatment's effectiveness. Research has focused on determining if non-coding RNAs affect many target genes to mediate regulating recipient cells. The tumor microenvironment's immune and cancer cells are influenced by lncRNAs, which may impact a treatment's efficacy. The lncRNA-mediated interaction between cancer cells and immune cells invading the tumor microenvironment has been the subject of numerous recent studies. On the other hand, tumor-derived lncRNAs' control over the immune system has not gotten much attention and is still a relatively new area of study. Tumor-derived lncRNAs are recognized to contribute to tumor immunity, while the exact mechanism is unclear.

Methanol extract of Iraqi Kurdistan Region Daphne mucronata as a potent source of antioxidant, antimicrobial, and anticancer agents for the synthesis of novel and bioactive polyvinylpyrrolidone nanofibers.

In this study, aqueous, ethanol, methanol, and hexane extracts from Iraqi Kurdistan Region Daphne mucronata were prepared due to the numerous applications and development of nanofibers in biological and medical fields, including food packaging, enzyme stabilization, and wound dressing. In the initial evaluation of the extracts, the antioxidant properties against DPPH, antimicrobial properties against 3-gram-positive bacterial species, 3-gram negative bacterial species, 3-common bacterial species between aquatic and human, and 3-fungal species, and anticancer properties against breast cancer cells were performed. The results proved that the methanol extract has the highest antimicrobial, antifungal, antioxidant, and anticancer properties. After identifying the compounds of prepared methanol extract using GC/MS, polyvinylpyrrolidone nanofibers containing methanol extract of Daphne mucronata were prepared. The structure and characteristics of prepared nanofibers were confirmed and determined using FTIR, TGA, BET, SEM, flexural strength, compressive strength, and hydrophilicity. Synthesized polyvinylpyrrolidone nanofibers containing methanol extract of D. mucronata were subjected to antimicrobial properties on the strains studied in methanol extract of D. mucronata. The antimicrobial properties of synthesized polyvinylpyrrolidone nanofibers containing methanol extract of D. mucronata were compared. The results showed that synthesized polyvinylpyrrolidone nanofibers containing methanol extract of D. mucronata have the potential to introduction bioactive natural synthesis nanoparticles.

Double-edged sword role of miRNA-633 and miRNA-181 in human cancers.

Understanding the function and mode of operation of microRNAs (miRNAs) in cancer is of growing interest. The short non-coding RNAs known as miRNAs, which target mRNA in multicellular organisms, are described as controlling essential cellular processes. The miR-181 family and miR-633 are well-known miRNAs that play a key role in the development and metastasis of tumor cells. They may facilitate either tumor-suppressive or oncogenic function in malignant cells, according to mounting evidence. Metastatic cells that are closely linked to cancer cell migration, invasion, and angiogenesis can be identified by abnormal levels of miR-181 and miR-633. Numerous studies have demonstrated their capacity to control drug resistance, cell growth, apoptosis, and the epithelial-mesenchymal transition (EMT) and metastasis process. Interestingly, the levels of miR-181 and miR-633 and their potential target genes in the basic cellular process can vary depending on the type of cancer cells and their gene expression profile. Such miRNAs' interactions with other non-coding RNAs such as long non-coding RNAs and circular RNAs can influence tumor behaviors. Herein, we concentrated on the multifaceted roles of miR-181 and miR-633 and potential targets in human tumorigenesis, ranging from cell growth and metastasis to drug resistance.

Unraveling the impact of 27-hydroxycholesterol in autoimmune diseases: Exploring promising therapeutic approaches.

The role of 27-hydroxycholesterol (27-OHC) in autoimmune diseases has become a subject of intense research in recent years. This oxysterol, derived from cholesterol, has been identified as a significant player in modulating immune responses and inflammation. Its involvement in autoimmune pathogenesis has drawn attention to its potential as a therapeutic target for managing autoimmune disorders effectively. 27-OHC, an oxysterol derived from cholesterol, has emerged as a key player in modulating immune responses and inflammatory processes. It exerts its effects through various mechanisms, including activation of nuclear receptors, interaction with immune cells, and modulation of neuroinflammation. Additionally, 27-OHC has been implicated in the dysregulation of lipid metabolism, neurotoxicity, and blood-brain barrier (BBB) disruption. Understanding the intricate interplay between 27-OHC and autoimmune diseases, particularly neurodegenerative disorders, holds promise for developing targeted therapeutic strategies. Additionally, emerging evidence suggests that 27-OHC may interact with specific receptors and transcription factors, thus influencing gene expression and cellular processes in autoimmune disorders. Understanding the intricate mechanisms by which 27-OHC influences immune dysregulation and tissue damage in autoimmune diseases is crucial for developing targeted therapeutic interventions. Further investigations into the molecular pathways and signaling networks involving 27-OHC are warranted to unravel its full potential as a therapeutic target in autoimmune diseases, thereby offering new avenues for disease intervention and management.

The pathological role of C-X-C chemokine receptor type 4 (CXCR4) in colorectal cancer (CRC) progression; special focus on molecular mechanisms and possible therapeutics.

Colorectal cancer (CRC) is comprised of transformed cells and non-malignant cells including cancer-associated fibroblasts (CAF), endothelial vasculature cells, and tumor-infiltrating cells. These nonmalignant cells, as well as soluble factors (e.g., cytokines), and the extracellular matrix (ECM), form the tumor microenvironment (TME). In general, the cancer cells and their surrounding TME can crosstalk by direct cell-to-cell contact and via soluble factors, such as cytokines (e.g., chemokines). TME not only promotes cancer progression through growth-promoting cytokines but also provides resistance to chemotherapy. Understanding the mechanisms of tumor growth and progression and the roles of chemokines in CRC will likely suggest new therapeutic targets. In this line, a plethora of reports has evidenced the critical role of chemokine receptor type 4 (CXCR4)/C-X-C motif chemokine ligand 12 (CXCL12 or SDF-1) axis in CRC pathogenesis. In the current review, we take a glimpse into the role of the CXCR4/CXCL12 axis in CRC growth, metastasis, angiogenesis, drug resistance, and immune escape. Also, a summary of recent reports concerning targeting CXCR4/CXCL12 axis for CRC management and therapy has been delivered.

Tumor-associated Macrophages (TAMs) in Cancer Resistance; Modulation by Natural Products.

Tumor-associated macrophages (TAMs) play a pivotal role in the progression and resistance of tumors to different anticancer drugs. TAMs can modulate the tumor microenvironment (TME) in favor of immune system exhaustion. The interactions of TAMs with TME can affect the function of cytotoxic CD8+ T lymphocytes (CTLs) and natural killer (NK) cells. Furthermore, TAMs can induce cancer cell proliferation by releasing some growth factors, such as transforming growth factor (TGF)-ß. TAMs have several positive cross-talks with other immune suppressive cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), cancerassociated fibroblasts (CAFs), and cancer cells, leading to the release of growth factors, the proliferation of cancer cells and tumor growth. These interactions also can induce invasion and migration of cancer cells, angiogenesis, and metastasis. The inhibition of TAMs is an intriguing strategy for overcoming tumor resistance and suppression of cancer cells. Some natural-derived agents such as melatonin, curcumin, resveratrol, apigenin, and other flavonoids have shown the ability to modulate TME, including TAMs. These adjuvants may be able to boost antitumor immunity through the modulation of TAMs. This review explains the modulatory effects of some well-known naturally derived agents on the activity of TAMs. The modulation of TAMs by these agents may be useful in suppressing tumor growth and invasion.

Investigating the effect of pregabalin on postoperative pain in non-emergency craniotomy.

BACKGROUND: Surgical procedures performed in the suboccipital and subtemporal regions are associated with severe pain. The present study was designed to determine pregabalin's effect on postoperative pain in elective craniotomy. METHOD: This double-blind prospective randomized clinical trial was conducted on 50 patients aged 20-60 with ASA classifications I and II. The patients who qualified for elective craniotomies were split into intervention (two capsules =300 mg pregabalin) and control groups (two capsule starch). Patients were also assessed at recovery, 2, 6, 12, and 24 h after surgery for their pain and level of sedation. Data were analyzed by SPSS software version 23, and a P-value ≤ 0.05 was considered significant. RESULTS: The mean pain score in the intervention group was lower than the control group at recovery (p = 0.224), 2 h (p = 0.001), 6 h (p = 0.011), and 12 h (p = 0.032) after surgery. The methadone consumption in the control group was significantly higher than the intervention group (p < 0.05). There was no significant difference between the two groups regarding the level of sedation (p > 0.05). The mean heart rate at induction (p = 0.01), 15 min (p = 0.01), 30 min (p = 0.025), recovery (p = 0.031), and 2 h (p = 0.021) after surgery and the MAP at recovery, 2 h, and 6 h after surgery was significantly lower than the control group (p = 0.029), (p = 0.013), and (p = 0.038), respectively. CONCLUSION: Our investigation demonstrated the effectiveness of pregabalin two hours before surgery on decreasing postoperative pain and analgesic consumption without disturbance in neurological examinations and any specific adverse effects.

The functions and molecular mechanisms of Tribbles homolog 3 (TRIB3) implicated in the pathophysiology of cancer.

Currently, cancer ranks as the second leading cause of death worldwide, and at the same time, the burden of cancer continues to increase. The underlying molecular pathways involved in the initiation and development of cancer are the subject of considerable research worldwide. Further understanding of these pathways may lead to new cancer treatments. Growing data suggest that Tribble's homolog 3 (TRIB3) is essential in oncogenesis in many types of cancer. The mammalian tribbles family's proteins regulate various cellular and physiological functions, such as the cell cycle, stress response, signal transduction, propagation, development, differentiation, immunity, inflammatory processes, and metabolism. To exert their activities, Tribbles proteins must alter key signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/AKT pathways. Recent evidence supports that TRIB3 dysregulation has been linked to various diseases, including tumor development and chemoresistance. It has been speculated that TRIB3 may either promote or inhibit the onset and development of cancer. However, it is still unclear how TRIB3 performs this dual function in cancer. In this review, we present and discuss the most recent data on the role of TRIB3 in cancer pathophysiology and chemoresistance. Furthermore, we describe in detail the molecular mechanism TRIB3 regulates in cancer.

Detection of abemaciclib, an anti-breast cancer agent, using a new electrochemical DNA biosensor.

Detection of DNA molecules and possible chemotherapy-induced changes in its structure has been the goal of researchers using rapid, sensitive and inexpensive approaches. Therefore, the aim of this study was to fabricate a new electrochemical DNA biosensor using pencil graphite electrodes modified with polypyrrole/Ce doped hexagonal nickel oxide nanodisks or PP/Ce-doped H-NiO-ND composites for determination of Abemaciclib (AMC) and ds-DNA molecules. The DNA biosensor was prepared by immobilizing ds-DNA on the surface of PP/Ce-doped H-NiO-ND/PGE. Differential pulse voltammetry (DPV) was used to electrochemically detect AMC. The results elucidate the extremely high sensitivity of the ds-DNA/PP/Ce-doped H-NiO-ND/PGE biosensor to AMC, with a narrow detection limit of 2.7 nM and a lengthy linear range of 0.01-600.0 µM. The admirable performance of as-fabricated biosensor could be related to the active reaction sites and the unique electrochemical response related to the nanocomposites by enhancing ds-DNA stabilization and accelerating electron transfer on the surface of electrode.

Application of novel Fe3O4/Zn-metal organic framework magnetic nanostructures as an antimicrobial agent and magnetic nanocatalyst in the synthesis of heterocyclic compounds.

Using the microwave-assisted method, novel Fe3O4/Zn-metal organic framework magnetic nanostructures were synthesized. The crystallinity, thermal stability, adsorption/desorption isotherms, morphology/size distribution, and magnetic hysteresis of synthesized Fe3O4/Zn-metal organic framework magnetic nanostructures were characterized by XRD patterns, TGA curve, BET adsorption/desorption technique, SEM image, and VSM curve, respectively. After confirming the Fe3O4/Zn-metal organic framework magnetic nanostructures, its antimicrobial properties against Gram-positive bacterial, Gram-negative bacterial, and fungal strains based on minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungicidal concentration (MFC) values were studied. The MIC values in antimicrobial activity for Gram-positive and Gram-negative bacterial strains, between 16-128 µg/ml, and for fungal strain, 128 µg/ml were observed. The results showed that the high specific surface area of Fe3O4/Zn-metal organic framework magnetic nanostructures caused the antimicrobial power of nanoparticles to be high, and the observed antimicrobial effects were higher than some known commercial antimicrobial drugs. Another advantage of the specific surface area of Fe3O4/Zn-metal organic framework magnetic nanostructures was its high catalytic properties in the three-component reaction of isatin, malononitrile, and dimedone. New spiro [indoline-pyranopyrimidines] derivatives were synthesized with high efficiency. The catalytic activity results of Fe3O4/Zn-metal organic framework magnetic nanostructures showed that, in addition to recyclability, derivatives could be synthesized in less time than previously reported methods. The results of investigating the catalytic activity of Fe3O4/Zn-metal organic framework magnetic nanostructures showed that the spiro [indoline-pyranopyrimidines] derivatives were synthesized in the time range of 10-20 min with an efficiency of over 85%. As a final result, it can be concluded that the microwave synthesis method improves the unique properties of magnetic nanostructures, especially its specific surface area, and has increased its efficiency.

Functions and therapeutic interventions of non-coding RNAs associated with TLR signaling pathway in atherosclerosis.

Nowadays, emerging data demonstrate that the toll-like receptor (TLR) signaling pathway plays an important role in the progression of inflammatory atherosclerosis. Indeed, dysregulated TLR signaling pathway could be a cornerstone of inflammation and atherosclerosis, which contributes to the development of cardiovascular diseases. It is interesting to note that this pathway is heavily controlled by several mechanisms, such as epigenetic factors in which the role of non-coding RNAs (ncRNAs), particularly microRNAs and long noncoding RNAs as well as circular RNAs in the pathogenesis of atherosclerosis has been well studied. Recent years have seen a significant surge in the amount of research exploring the interplay between ncRNAs and TLR signaling pathway downstream targets in the development of atherosclerosis; however, there is still considerable room for improvement in this field. The current study was designed to review underlying mechanisms of TLR signaling pathway and ncRNA interactions to shed light on therapeutic implications in patients with atherosclerosis.

Modulatory role of dietary curcumin and resveratrol on growth performance, serum immunity responses, mucus enzymes activity, antioxidant capacity and serum and mucus biochemicals in the common carp, Cyprinus carpio exposed to abamectin.

In this study, we investigate the potentials of dietary curcumin and resveratrol on blood biochemistry, immune responses and resistance to the toxicity of the pesticide, abamectin. 540 common carps (30.78 ± 0.17 g) were randomly distributed into 18 tanks (30 fish per tank), as six experimental groups (T1: non-supplemented and on-exposed fish, T2: 300 mg/kg curcumin, T3: 300 mg/kg resveratrol, T4: 12.5% LC50 of abamectin, T5: 300 mg/kg curcumin +12.5% LC50 of abamectin, T6: 300 mg/kg resveratrol + 12.5% LC50 of abamectin). Use of 300 mg/kg resveratrol in the diet of non-abamectin exposed fish improved the growth performance (P < 0.05), while such effects were not observed for curcumin (P > 0.05). There were no differences in the final weight (FW), feed conversion ratio (FCR) and weight gain (WG) between control and fish of the treatments, resveratrol + abamectin and curcumin + abamectin (P < 0.05). The immune components in blood [lysozyme, complement activity, Total immunoglobulin (total Ig), protease, myeloperoxidase (MPO), nitro-blue-tetrazolium (NBT), peroxidase, albumin] and mucus [acid phosphatase (ACP), alkaline phosphatase (ALP), esterase, antiprotease)] and antioxidant enzymes [(superoxide dismutase (SOD), glutathione peroxidase (GPx)] exhibited various change patterns compared to the control group, however, these components were almost all higher in fish supplemented with curcumin and resveratrol in an abamectin-free medium than in control and other groups (P < 0.05). In most cases, the levels of immune and antioxidant components in the control did not show significant difference with the treatments, resveratrol + abamectin and curcumin + abamectin (P > 0.05). Abamectin induced oxidative stress in fish, as the malondialdehyde (MDA) levels significantly increased in the exposed fish compared to non-exposed groups (P < 0.05). It appears that neither curcumin nor resveratrol were as effective in preventing oxidative stress, because MDA levels were higher in exposed fish (abamectin, curcumin + abamectin, resveratrol + abamectin) than in control and non-exposed individuals (P < 0.05). Curcumin and resveratrol also showed protective effects on liver, since the levels of liver metabolic enzymes [aspartate transaminase (AST), ALP, lactate dehydrogenase (LDH)] were lower in the supplemented fish in a abamectin-free medium than in control (P < 0.05). Curcumin and resveratrol also mitigated the stress responses in the exposed fish, as cortisol and glucose levels showed significant decreases in the supplemented fish (P < 0.05). In conclusion, this study revealed that abamectin can depress the growth and immunity in the common carp. Although, both resveratrol and curcumin were mitigated the toxic effects of abamectin, it seems that resveratrol be more effective than curcumin.

Cytotoxicity evaluation of environmentally friendly synthesis Copper/Zinc bimetallic nanoparticles on MCF-7 cancer cells.

Bimetallic nanoparticles offer unique chemical, physical and optical properties that are not available for monometallic nanoparticles. Bimetallic nanoparticles play a major role in various therapeutic, industrial and energy fields. Recently, nanoparticles of Copper/Zinc bimetallic nanoparticles have attracted attention in various fields, especially medicine. In this study, bimetallic CuO/ZnO nanostructures were biosynthesized using plant extracts. The plant-mediated synthesis nanoparticles were characterized by Transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), Field Emission Scanning Electron Microscopy (FESEM) and Energy-Dispersive Spectroscopy (EDAX). The cytotoxicity of plant-mediated synthesis bimetallic nanoparticles and the synergistic effects of these nanoparticles in combination with the anticancer drug doxorubicin on MCF-7 cancer cells were evaluated by MTT assay.

Application of extracellular vesicles derived from mesenchymal stem cells as potential therapeutic tools in autoimmune and rheumatic diseases.

Mesenchymal stem cells (MSCs) have been proven to have superior potential to be used astherapeutic candidates in various disorders. Nevertheless, the clinical application of these cells have been restricted because of their tumorigenic properties. Increasing evidence has established that the valuable impacts of MSCs are mainly attributable to the paracrine factors including extracellular vesicles (EVs). EVs are nanosized double-layer phospholipid membrane vesicles contain various proteins, lipids and miRNAs which mediate cell-to-cell communications. Due to their inferior immunogenicity and tumorigenicity, as well as easier management, EVs have drawn attention as potential cell-free replacement therapy to MSCs. For that reason, herein, we reviewed the recent findings of researches on different MSC-EVs and their effectiveness in the treatment of several autoimmune and rheumatic diseases including multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis, osteoporosis, and systemic lupus erythematosus as well as Sjogren's syndrome, systemic sclerosis and other autoimmune diseases.

CXC chemokine ligand 16: a Swiss army knife chemokine in cancer.

Today, cancer is one of the leading causes of death worldwide. Lately, cytokine and chemokine imbalances have gained attention amongst different involved pathways in cancer development and attracted much consideration in cancer research. CXCL16, as a member of the CXC subgroup of chemokines, has been attributed to be responsible for immune cell infiltration into the tumour microenvironment. The aberrant expression of CXCL16 has been observed in various cancers. This chemokine has been shown to play a conflicting role in tumour development through inducing pro-inflammatory conditions. The infiltration of various immune and non-immune cells such as lymphocytes, cancer-associated fibroblasts and myeloid-derived suppressor cells by CXCL16 into the tumour microenvironment has complicated the tumour fate. Given this diverse role of CXCL16 in cancer, a better understanding of its function might build-up our knowledge about tumour biology. Hence, this study aimed to review the impact of CXCL16 in cancer and explored its therapeutic application. Consideration of these findings might provide opportunities to achieve novel approaches in cancer treatment and its prognosis.

The effects of oxygen-ozone therapy on regulatory T-cell responses in multiple sclerosis patients.

Multiple sclerosis (MS) is a common degenerative disorder of the central nervous system. The decreased frequency and dysfunction of Treg cells cause inflammation and disease progression. Ozone autohemotherapy can be used as a potential therapeutic approach to regulate the immune system responses and inflammation in MS. For this purpose, 20 relapsing-remitting multiple sclerosis patients were under treatment with ozone twice weekly for 6 months. The frequency of Treg cell, the expression levels of the Treg cell-related factors (FoxP3, IL-10, TGF-ß, miR-17, miR-27, and miR-146A), and the secretion levels of IL-10 and TGF-ß were assessed. We found a significant increase in the number of Treg cells, expression levels of FoxP3, miRNAs (miR-17 and miR-27), IL-10, and TGF-ß factors in patients after oxygen-ozone (O2 -O3 ) therapy compared to before treatment. In contrast, oxygen-ozone therapy notably decreased the expression level of miR-146a in treated patients. Interestingly, the secretion levels of both IL-10 and TGF-ß cytokines were considerably increased in both serum and supernatant of cultured peripheral blood mononuclear cells in posttreatment condition compared to pretreatment condition. According to results, oxygen-ozone therapy raised the frequency of Treg cell and its relevant factors in treated MS patients. Oxygen-ozone therapy would contribute to improving the MS patients by elevating the Treg cell responses.