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Introduction: Amygdalin (AMG) is a plant-based agent that has many therapeutic applications. Metabolism of this herbal remedy may cause cytotoxicity in cells. Objective: In this study, the role of rhodanese (RH) enzyme against the cyanide of amygdalin has been investigated in human and mouse cell lines in vitro. MethodS: We analyzed the cytotoxicity, morphologic changes, apoptotic effects, and gene expression alterations resulting from treatment with AMG and AMG combined with RH (AMG-RH) in mouse fibroblasts (L929) and human dermal fibroblasts (HDF) cell lines. ResultS: The lowest half-maximal inhibitory concentration (IC50) values were 87.95±3.63 mg/ml and 80.82±2.13 mg/ml at 72 h in both cell lines. Cell viability of both cell lines was significantly decreased after AMG treatment; however, it increased following treatment with AMG-RH for 24, 48, and 72 h. Morphological changes were observed in both cell lines after AMG treatment for 72 h. AMG-RH combination did not cause any significant morphological alterations in either cell line. Conclusion: The apoptosis rates were increased in both cell lines treated with AMG and decreased in AMG-RH treatment for 72 h. BAX, CASP-3, BCL-2, and TST genes were upregulated after treatment with AMG for 72 h in both cell lines. BCL-2 and TST genes were upregulated, while BAX and CASP3 were downregulated after treatment with AMG-RH for 72 h. The findings of this study indicate the IC50 dose of AMG could cause cytotoxicity in HDF and L929 cell lines. Furthermore, it was found that the RH enzyme could decrease AMG cytotoxicity and might have a protective role against AMG.

The breakdown of self-tolerance of the immune response can lead to autoimmune conditions in which chronic inflammation induces tissue damage. Systemic lupus erythematosus (SLE) is a debilitating multisystemic autoimmune disorder with a high prevalence in women of childbearing age; however, SLE incidence, prevalence, and severity are strongly influenced by ethnicity. Although the mystery of autoimmune diseases remains unsolved, disturbance in the proportion and function of B cell subsets has a major role in SLE's pathogenesis. Additionally, colocalizing hyperactive T helper cell subgroups within inflammatory niches are indispensable. Despite significant advances in standard treatments, nonspecific immunosuppression, the risk of serious infections, and resistance to conventional therapies in some cases have raised the urgent need for new treatment strategies. Without the need to suppress the immune system, mesenchymal stem cells (MSCs), as ''smart" immune modulators, are able to control cellular and humoral auto-aggression responses by participating in precursor cell development. In lupus, due to autologous MSCs disorder, the ability of allogenic engrafted MSCs in tissue regeneration and resetting immune homeostasis with the provision of a new immunocyte repertoire has been considered simultaneously. In Brief The bone marrow mesenchymal stem cells (BM-MSCs) lineage plays a critical role in maintaining the hematopoietic stem-cell microstructure and modulating immunocytes. The impairment of BM-MSCs and their niche partially contribute to the pathogenesis of SLE-like diseases. Allogenic MSC transplantation can reconstruct BM microstructure, possibly contributing to the recovery of immunocyte phenotype restoration of immune homeostasis. In terms of future prospects of MSCs, artificially gained by ex vivo isolation and culture adaptation, the wide variety of potential mediators and mechanisms might be linked to the promotion of the immunomodulatory function of MSCs.

Objectives Acute renal injury (AKI) is a major limiting factor for cisplatin administration. Recent evidence suggests the potential contribution of mesenchymal stem cells (MSCs) to rehabilitation from several disorders via both direct and indirect routes. Thus, the present study aimed, for the first time, to explore and compare the reno-protective potential of human dental pulp-derived stem cells (hDPSCs) vs. hDPSC-conditioned medium (hDPSC-CM) in recovery of impaired kidney tissues in a rat animal model of cisplatin-induced AKI. Methods AKI was induced via cisplatin injection (n=36). One day after, 24 rats were treated with either hDPSCs or hDPSC-CM (n=12). An extra set of rats (n=12) served as sham group. On days 2 or 7 (n=6), rats were humanly sacrificed for further analysis. Renal injury was explored via measuring serum creatinine and BUN. Renal level of oxidative stress was assessed by determining malondialdehyde, and enzymatic activities of superoxide dismutase and catalase. Renal histopathological changes were scored for comparison among different experimental groups. Results A single dose of cisplatin resulted in considerable renal dysfunction and oxidative stress. Treatment with hDPSCs or hDPSC-CM resulted in significantly restored renal function, reduced level of oxidative stress, and improved histopathological manifestations. Furthermore, as compared to hDPSC-CM, administration of hDPSCs led to superior results in AKI-induced animals. Conclusions The current study described the first comparative evidence of reno-protective potential of hDPSCs and their CM against cisplatin-induced nephrotoxicity in an AKI rat model, proposing them as useful adjunctive therapy in AKI. Yet, future explorations are still needed.

Lupus is known as a systemic immune-mediated disorder. Like other diseases in this category, its cause and definitive treatment remain unknown. Gold standard therapies, which mainly include immunosuppressive agents, have been able to have therapeutic effects on patients. However, a significant percentage of cases still do not respond to this kind of treatment, resulting in death from complications. Recently, a new source of non-hematopoietic cells, mesenchymal stem/stromal cells (MSCs), with the potency to re-establishment immune homeostasis and tissue regeneration, has been wildly used in both primary and clinical research. One of the remarkable features of MSCs is their anti-inflammatory and immunosuppressive properties and stimulating tissue differentiation programs. Under the influence of background signals, MSCs migrate to inflammatory bioactive substances and then regulate overactive immune responses to restore immune tolerance. MSCs have shown a two-way interaction with most immunocytes, which plays a significant role in resolving sterile inflammation. Restricting the entry of inflamed cells into the site of inflammation and re-educated infiltrated cells to achieve a tolerant phenotype have been reported as mechanisms of MSCs in tissue repair. Stimulation of the endogenous and tissue-dwelling stem cells in addition to releasing immunomodulatory agents, suggests MSCs transplantation as a potential modality in the treatment of future immune-mediated disorders.

Background: Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models. Objective: This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control. Methods: MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times. Results: Our data showed that treatment of HepG2 cells with high concentration (400μg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (p Conclusion: The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.

Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial. In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1× PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis. we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group. These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.

Background: Radiotherapy is thecrucial treatment for most malignancies, however; it has short and long-term side effects. The occurrence of secondary cancer following radiation-induced genomic instability in stem cells is an important long-term side effect of radiation therapy. The radiation response of human mesenchymal stromal cells (hMSCs) is critical in cancer patients who are treated with radiotherapy for hMSCs lifetime proliferative potential. Evaluation of genomic instability in human mesenchymal stem cells at different radiation doses and times, and examining the relative expression of some effective genes, have been the objectives of this study. Methods: After extraction, characterization, and expansion of hMSCs, they were irradiated for 0, 0.5, 2, and 6 Grays. Nuclear alterations were evaluated at 2, 10, and 15 days after irradiation using the cytokinesis-block micronucleus assay. As well as TP53, Bax, Bcl2, and KRAS gene expressions were analyzed 48 hours post-irradiation for genomic response evaluation. Results: The mean incidence of micronucleus, nucleoplasmic bridges, and nuclear buds incidences were 4.8±1.6, 47.6±6, and 18±2.6, respectively, 48 hours after the fourth passage in the non-irradiated (control) group for one thousand binucleated cells. Micronuclei incidences in 0.5, 2, and 6 grays radiation groups were 14.3±4.9, 32.3±6.5 and 55±9.1 respectively in 48 hours after irradiation and 12.6±1.5, 19±5.5, and 22.3±5.2, respectively ten days post-irradiations. Conclusion: Low levels of nuclear alterations as genomic instability markers were seen in various cell generations of control groups, which must be considered for cell therapy and regenerative medicine applications. In the irradiated groups, chromosomal aberration increased significantly with the dose, 2days post-irradiation due to a disproportionate increase in the Bax/Bcl2 ratio and high expression of the KRAS gene. significant nuclear alterations were seen in the tenth to fifteenth generations of irradiated hMSCs due to radiation-induced genomic instability which may persuade secondary malignancies in the following years after the radiotherapy treatment of patients.

Objectives: The present study was designed to evaluate the association of transporters associated with antigen processing (TAP2) polymorphisms TAP2-379Ile > Val (rs1800454), TAP2-665Thr > Ala (rs241447) and TAP2-565Ala > Thr (rs2228396) as a candidate gene with susceptibility to the Systemic Lupus Erythematosus (SLE). Methods: To analyze these three polymorphic variants, 88 patients with SLE and 100 healthy controls from northeastern Iran were enrolled from May 2018 to July 2019. Genomic DNA polymorphisms were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. Data were analyzed by SPSS software. Results: In this cross-sectional study, there was a stratification between patients and controls. The distribution of the frequency of Ala73 (41.5%) allele at TAP2/665 and Ile 19 (10.8%) allele at TAP2/379 was higher in patients. Additionally, the Ala/Ala 13(14.8%) and Ala/Thr 49(55.7%) genotypes distributions at 665 positions were higher in SLE patients compared to the controls. Furthermore, frequencies of TAP2*H allele significantly increased in SLE patients 10(5.71%) (P=0.01). Frequency of TAP2*A allele in the control group was 120(60%) (p=0.06) due to the dominant genetic model. This allele has a protective effect against SLE. There was no relationship between TAP2*D, TAP2*E, TAP2*F and TAP2*G alleles with the outbreak of SLE. Conclusions: Our data indicated that genetic variants in TAP2 gene may be associated with SLE disease. A correlation between Ala allele at TAP2/665 and Ile allele at TAP2/379 polymorphisms and pathogenesis of SLE was observed.

Stem cell-based treatments have emerged as potentially effective approaches to delay the progression of amyotrophic lateral sclerosis (ALS). This study was designed as a single-center, prospective, and open-label study without a placebo control group to assess the safety and efficacy of concurrent intrathecal (IT) and intravenous (IV) administration of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS. Autologous BM-MSCs were isolated and expanded under standard conditions. Fifteen patients were neurologically examined before BM-MSCs transplantation (1 × 10 6 cells/kg BW) to evaluate the rate of pre-treatment disease progression. To assess the safety and efficacy, patients were examined at 1, 3, and 6 months following the treatment with BM-MSCs. Adverse reactions were assessed, and the clinical outcome was determined by the evaluation of the ALS functional rating scale-revised (ALSFRS-R) and forced vital capacity (FVC). No serious adverse reaction was observed after combined IT and IV administration of BM-MSCs. The mean ALSFRS-R and FVC values remained stable during the first 3 months of the treatment. However, a significant reduction in ALSFRS-R and FVC levels was observed in these patients 6 months after BM-MSCs administration. Our study revealed that the concurrent IT and IV application of BM-MSCs in patients with ALS is a safe procedure. Furthermore, our data indicate a temporary delay in the progression of ALS after a single combined IT and IV administration of BM-MSCs. Further studies are required to explore if the repeated applications of BM-MSCs could prolong survival and delay the progression of ALS.

The Covid-19 disease has recently become one of the biggest challenges globally, and there is still no specific medication. Findings showed the immune system in severe Covid-19 patients loses regulatory control of pro-inflammatory cytokines, especially IL-6 production, called the “Cytokine storm” process. This process can cause injury to vital organs, including lungs, kidneys, liver, and ultimately death if not inhibited. While many treatments have been proposed to reduce cytokine storm, but the safety and effectiveness of each of them are still in doubt. Mesenchymal stem cells (MSCs) are multipotent cells with self-renewal potential capable of suppressing overactive immune responses and leading to tissue restoration and repair. These immuno-modulatory properties of MSCs and their derivatives (like exosomes) can improve the condition of Covid-19 patients with serious infectious symptoms caused by adaptive immune system dysfunction. Many clinical trials have been conducted in this field using various MSCs around the world. Some of these have been published and summarized in the present article, while many have not yet been completed. Based on these available data, MSCs can reduce inflammatory cytokines, increase oxygen saturation, regenerate lung tissue and improve clinical symptoms in Covid-19 patients. The review article aims to collect available clinical data in more detail and investigate the role of MSCs in reducing cytokine storms as well as improving clinical parameters of Covid-19 patients for use in future clinical studies.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1× cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells. These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

The proliferation and differentiation of stem cells into Germ-Like Cells (GLCs) is mediated by several growth factors and specific genes, of which some are related to long non-coding RNAs (lncRNAs). We have developed a modified differentiation process and identified a panel of GermlncRNAs related to GLCs.Human Wharton Jelly Mesenchymal Stem Cells were treated with 25 ng/ml Bone Morphogenetic Protein (BMP)-4 and 10After 21 days of induction, the HWJ-MSCs derived germ-like cells were formed. Also, qPCR and immunocytochemistry showed that the pluripotent Oct4 marker was expressed in the undifferentiated HWJ-MSCs, but its expression gradually decreased in the differentiated cells. C-kit was expressed on days 7, 14, and 21 of differentiation. Both GLC markers of Stella and Vasa genes/proteins were present only in differentiated cells. Of the 44 lncRNA genes array, 36 of them showed an increase and eight genes showed a decrease.Our study showed that BMP4 and RA are effective in inducing HWJ-MSCs differentiation into GLCs. In addition, our study for the first time showed changes in the lncRNAs expression during the differentiation of HWJ-MSCs into GLCs by using BMP4 and RA.

Autoreactive inflammatory CD4+ T cells, such as T helper (Th)1 and Th17 subtypes, have been found to associate with the pathogenesis of autoimmune disorders. On the other hand, CD4+ Foxp3+ T regulatory (Treg) cells are crucial for the immune tolerance and have a critical role in the suppression of the excessive immune and inflammatory response promoted by these Th cells. In contrast, dendritic cells (DCs) and macrophages are immune cells that through their inflammatory functions promote autoreactive T‐cell responses in autoimmune conditions. In recent years, there has been increasing attention to exploring effective immunomodulatory or anti‐inflammatory agents from the herbal collection of traditional medicine. Berberine, an isoquinoline alkaloid, is one of the main active ingredients extracted from medicinal herbs and has been shown to exert various biological and pharmacological effects that are suggested to be mainly attributed to its anti‐inflammatory and immunomodulatory properties. Several lines of experimental study have recently investigated the therapeutic potential of berberine for treating autoimmune conditions in animal models of human autoimmune diseases. Here, we aimed to seek mechanisms underlying immunomodulatory and anti‐inflammatory effects of berberine on autoreactive inflammatory responses in autoimmune conditions. Reported data reveal that berberine can directly suppress functions and differentiation of pro‐inflammatory Th1 and Th17 cells, and indirectly decrease Th cell‐mediated inflammation through modulating or suppressing other cells assisting autoreactive inflammation, such as Tregs, DCs and macrophages.

From ancient times, medicinal plants have been usually utilized to treat many disorders, but today, interest in these herbs is again aroused, because of their fewer side effects and low-cost. In traditional medicine, for many diseases, various medicinal herbs have been suggested so far. Drimia maritime, also named squill, is an important medicinal plant for the treatment of many diseases, especially respiratory diseases. In the current evidence-based study, we conducted a review of the general characteristics, ingredients, administration form, and side effects of squill in traditional medicine. For this purpose, traditional Persian medicine literatures and electronic databases were examined including PubMed, Scopus, and Google Scholar. Many compounds are isolated from D.maritima, including scillaren, scillirubroside, scillarenin, and bufadienolide glycosides. Oxymel is the most commonly used form of squill for various diseases, especially respiratory diseases. Besides, squill has been used in the treatment of cardiovascular, digestive, and dermatological disorders, it is also used against various cancer cells for its antioxidant and cytotoxic properties. Moreover, there is relatively reliable evidence of its benefits for bacterial and helminthic infections, rheumatism, edema, gout, abortion induction, healing of wounds and urine induction. It seems that supplementary studies are required to explore the bioactive agents and their effective mechanisms.

Background: The relationship between SLE and traditional risk factors for cardiovascular events was evaluated. Methods: The data regarding sixty patients with SLE and 30 healthy controls (age and sex matched) were gathered using SLEDAI forms. Venous blood (10mL) from all the participants was examined for hs-CRP, homocysteine, VCAM1, CBC, anti-DNA antibody, C3, C4, low-density lipoprotein (LDL), cholesterol, FBS and triglyceride. : The IMT of carotid arteries was determined bilaterally by ultrasound. Other measurements included insulin levels via Elisa (Linco/Millipore Corp) and the HOMA-IR index for insulin resistance. Results: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively. Results: The mean age (in years) in the test and control groups was 28.8±10.3 (18-52) and 33.8±9.13 (18-48), respectively. : The average IMT in the test group was directly related to serum levels of VCAM1 (p Conclusion:: Our findings did not show an increase in the prevalence of atherosclerosis in patients with SLE. There was no association between IMT and insulin resistance. However, the former was associated with FPG, total cholesterol, LDL, TG, homocystein and VCAM1.

BackgroundAcute respiratory distress syndrome (ARDS) is the devasting complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, Mesenchymal Stem Cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and efficacy of three injections of Umbilical Cord-derived MSCs (UC-MSCs) in mild-moderate COVID-19-induced ARDS patients.MethodsTwenty confirmed COVID-19 patients with mild to moderate ARDS degree (using the WHO guideline for ARDS classification) entered the study and were randomly divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × \({10}^{6}\) cells/kg BW per injection) every other day. Respiratory markers, CRP levels and some serum cytokines were assessed four times (days of 0,5,10 and 17) during the 17 days follow-up period.ResultsDuring the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P

Background Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild–moderate COVID-19-induced ARDS patients. Methods Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × $${10}^{6}$$ 10 6 cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. Results During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P Conclusion Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).

Cancer of the prostate is an indicated type that is often recorded as a kind of cancer in men and the second critical cause of mortality through cancer cases. Many pharmacological investigations have shown that numerous herbal substances possess anticancer action. Amygdalin (AMD) has antitumour capabilities and works as an antioxidant, antibacterial, anti-inflammatory, and immune-regulating characteristics. The anticancer effects of amygdalin and its metabolizing enzymes, rhodanese (RHD) and betaglucosidase (BGD), were examined in vivo, as well as their antitumour processes. Novel, effective combination agents are necessary to increase existing cancer treatment rates. This research was aimed at determining the anticarcinogenic impact of amygdalin (AMD) in vivo. This research was aimed at determining the RHD and BGD on the anticarcinogenic impact of AMD in vivo. Subcutaneously, PC3 prostate cancer cell lines were implanted into nude mice. Mice were treated every day with 0.5 ml of 50 mg/ml (AMD), AMD+ (RHD 0.1 mg/ml), AMD+(BGD 0.1 mg/ml), and doxorubicin (DOX 50 mg/ml). Mice were normalized for negative control with untreated mice. In in vivo, morphopathological alterations in the tumour tissue were analyzed by histopathological staining methods. After 35 days of therapy, tumour growth and size inhibition were evident, indicating a function for the metabolic enzymes BGD and RHD in regulating AMD’s anticancer effect in vivo. We concluded the critical role of metabolic enzymes BGD and RHD in elevating the antigrowth of PC3 cancer cell lines in Balb/c nude mice treated with AMD.

The stem cell-based therapy has emerged as a promising therapeutic strategy for treating cardiovascular ischemic diseases (CVIDs), such as myocardial infarction (MI). However, some important functional shortcomings of stem cell transplantation, such as immune rejection, tumorigenicity and infusional toxicity, have overshadowed stem cell therapy in the setting of cardiovascular diseases (CVDs). Accumulating evidence suggests that the therapeutic effects of transplanted stem cells are predominately mediated by secreting paracrine factors, importantly, microRNAs (miRs) present in the secreted exosomes. Therefore, novel cell-free therapy based on the stem cell-secreted exosomal miRs can be considered as a safe and effective alternative tool to stem cell therapy for the treatment of CVDs. Stem cell-derived miRs have recently been found to transfer, via exosomes, from a transplanted stem cell into a recipient cardiac cell, where they regulate various cellular process, such as proliferation, apoptosis, stress responses, as well as differentiation and angiogenesis. The present review aimed to summarize cardioprotective exosomal miRs secreted by transplanted stem cells from various sources, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and cardiac stem/progenitor cells, which showed beneficial modulatory effects on the myocardial infracted heart. In summary, stem cell-exosomal miRs, including miR-19a, mirR-21, miR-21-5p, miR-21-a5p, miR-22 miR-24, miR-26a, miR-29, miR-125b-5p, miR-126, miR-201, miR-210, and miR-294, have been shown to have cardioprotective effects by enhancing cardiomyocyte survival and function and attenuating cardiac fibrosis. Additionally, MCS-exosomal miRs, including miR-126, miR-210, miR-21, miR-23a-3p and miR-130a-3p, are found to exert cardioprotective effects through induction of angiogenesis in ischemic heart after MI.

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive as well as an inflammatory peripheral vascular disease with unknown etiology. Recent evidence has supported the immunopathogenesis of the disease, however, the factors contributing to the altered immune function and vascular tissue inflammation are still unclear. This review was intended to collate the more current knowledge on the regulatory molecules involved in TAO from an immunoreactive perspective. The homeostasis of the immune system as well as a variety of progenitor cell populations appear to be affected during TAO and these alterations are associated with intrinsic signaling defects that are directing to an improved understanding of the crosstalk between angiogenesis and the immune system, as well as the potential of new co-targeting strategies applying both immunotherapy and angiogenic therapy.

Background Different genetic variants in hormone‐regulating pathways have been identified to influence the risk of breast cancer. This study aimed to evaluate the association of CYP19A1 rs10046 and rs700519 polymorphisms with the risk, clinicopathological factors and prognosis of breast cancer. Methods In a case‐control study, rs10046 and rs700519 polymorphisms were genotyped using ARMS‐PCR and high‐resolution melting (HRM), respectively, in a total of 702 females. Statistical analysis and evaluation of haplotypes and linkage disequilibrium were performed using SPSS v16, PHASE and 2LD. Results Although no association of rs700519 with breast cancer was observed, rs10046 in different genetic models as well as C‐C/C‐T and C‐C/C‐C diplotypes, revealed the association with the risk of breast cancer (p, This study aimed to evaluate the association of CYP19A1 rs10046 and rs700519 polymorphisms with the risk, clinicopathological factors and prognosis of breast cancer. Our findings help to enrich the literature about the genetic basis of breast cancer. rs10046 and rs700519 may have a diagnostic and prognostic role, respectively. ​

Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.

Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models.This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control.MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times.Our data showed that treatment of HepG2 cells with high concentration (400μg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (p0.05 and p0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200μg/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose- and time-dependent, which could promote its anticancer properties.The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy.

Gut microbiota has essential roles in the prevention and progression of multiple sclerosis (MS). The association between the gut microbiota and the central nervous system (CNS) or immune system response of MS patients has been documented in many studies. The composition of the gut microbiota could lead to sensitization or resistance against promotion and development of MS disease. Probiotics are the major part of gut microflorapopulation and could be substituted with tolerogenic probiotics that protect the CNS against autoimmune responses. Tolerogenic probiotics with anti-inflammatory and immuno-modulatory properties have effects on intestinal flora and can reestablish regulatory mucosal and systemic immune responses. Probiotics are able to prevent and restore excessive activation of inflammatory responses, especially autoreactive T cells and inflammatory cytokines. Tolerogenic probiotics, through induction of regulatory T cells and increase of anti-inflammatory cytokines, play a crucial role in controlling inflammation and maintaining tolerance and hemostasis. Therefore, probiotics can be considered as a preventive or therapeutic tool in MS. In the present review, we focus on the immunoregulatory effects of tolerogenic probiotics on the severity of disease, as well as Th1, Th2, and Treg populations in different experimental and human studies of MS.

Background Breast cancer is the most common known malignancy in women and it is therefore very important to prevent and treat this cancer. In this experimental study, the anti-breast cancer effect of Urginea matrima was investigated. Method Breast cancer cell lines [MCF-7 and MDA-MB231] and L929 normal cells [as a control group] were cultivated in DMEM medium. Bulb aqueous and hydroalcoholic extracts [70:30] were prepared through maceration method. The cultured cells were treated with different concentrations [6, 3, 1.5, 0.75, 0.375, 0.187 and 0.093 μg/mL] of U.maritima extracts for 24, 48 and 72 h. Toxicity of the extracts on cells were examined using MTT test. The Annexin V-FITC Apoptosis Detection Kit was used to evaluate apoptosis and necrosis. Flow cytometry technique was employed to evaluate the cell cycle and the cell migration was evaluated by Scratch method. Data were analyzed by GraphPad Prism and SPSS software and P Result Results showed that both extracts of U.maritima in the concentration of 1.5 and 3 μg/ ml at 24,48 and 72h presented cytotoxicity effect on MCF7 cell line . Also, both extracts in the concentration of 3 μg/ ml at 24 and 72h, and in the concentration of 6 μg/ ml at 72h showed cytotoxicity effect significantly on MDA-MB231 cells. In addition, the plant extracts at the dosage of 3 and 6 μg/ ml induced an accumulation of G0/G1 cells, as well as reduce in S and G2/M phases in MCF-7 and MDA-MB231 cells. Moreover, the aqueous and hydroalcoholic of U.maritima extracts at three concentrations [ 1.5, 3 and 6 μg/ ml ] in 24h inhibited the cell migration by 60% up to 70% respectively. In addition, the content of phenolic compounds in both extracts [aqueous and hydroalcoholic] was 7 mg and 10 mg gallic acid equivalent per gram of the crude extract, respectively. Conclusion Our results suggest that U.maritima extracts has significant anti-cancer activity against breast cancer cells due to cell cycle arrest and induction of apoptosis pathway.

Introduction This study aimed to determine the safety and efficacy of treatment with autologous bone marrow mesenchymal stem cell (BMMSCs) compared with the routine treatment in children with autism spectrum disorder (ASD). Methods In this ethically approved randomized controlled trial, 32 ASD children aged 5-15 years were randomly assigned to receive either autologous BMMSC plus rehabilitation therapy and risperidone (intervention group) or rehabilitation therapy and risperidone (control group). Autologous BMMSCs were intrathecally injected in the intervention group twice in 4 weeks. Patients were assessed using childhood autism rating scale (CARS), Gilliam autism rating scale-second edition (GARS-II), and clinical global impression (CGI) at the baseline, as well as 6 and 12 months after intervention. Results Overall, 32 patients in two groups of intervention (n = 14) and control (n = 18) completed the study, of which 27 (84.4%) were male. Mean age was 9.50 ± 2.14 years. The improvements in CARS total score, GARS-II autism index, and CGI global improvement showed no significant differences between the groups over 12 months. However, the main effect for time*group interaction was significant regarding the CGI-severity of illness, showing a significantly more pronounced improvement in the intervention group (F = 6.719; P = .002). Discussion Intrathecal injection of autologous BMMSCs seems to be safe and feasible, but has limited clinical efficacy in treatment of children with ASD.