The Immune Response and Effectiveness of COVID-19 Therapies.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly pathogenic with relatively high mortality and morbidity. In addition to pneumonia, acute respiratory distress syndrome, and microembolic disorder, a high proportion of patients with SARS-CoV-2 develop lymphopenia and cytokine storm disorder. This review explores the underlying mechanisms behind the pathogenesis of SARS-CoV-2, especially the immune mechanisms, which could be potentially used as therapeutic targets for the management of COVID-19.

The potential therapeutic effects of curcumin on pregnancy complications: Novel insights into reproductive medicine.

Pregnancy complications including preeclampsia, preterm birth, intrauterine growth restriction, and gestational diabetes are the main adverse reproductive outcomes. Excessive inflammation and oxidative stress play crucial roles in the pathogenesis of pregnancy disorders. Curcumin, the main polyphenolic compound derived from Curcuma longa, is mainly known by its anti-inflammatory and antioxidant properties. There are in vitro and in vivo reports revealing the preventive and ameliorating effects of curcumin against pregnancy complications. Here, we aimed to seek mechanisms underlying the modulatory effects of curcumin on dysregulated inflammatory and oxidative responses in various pregnancy complications.

Unfolded protein response-mediated modulation of mesenchymal stem cells.

The endoplasmic reticulum (ER) receives unfolded proteins predestined for the secretory pathway or to be incorporated as transmembrane proteins. The ER has to accommodate the proper folding and glycosylation of these proteins and also to properly incorporate transmembrane proteins. However, under various circumstances, the proteins shuttling through the ER can be misfolded and undergo aggregation, which causes activation of the unfolded protein response (UPR). The UPR is mediated through three primary pathways: activating transcription factor-6, inositol-requiring enzyme-1 (IRE1), and PKR-like endoplasmic reticulum kinase, which up-regulate ER folding chaperones and temporarily suppress protein translation. The UPR can be both cytoprotective and/or cytotoxic depending on the duration of UPR activation and the type of host cell. Proteostasis controls stem cell function, while stress responses affect stem cell identity and differentiation. The present review aimed to explore and discuss the effects of the UPR pathways on mesenchymal stem cells.

The molecular mechanisms of curcumin's inhibitory effects on cancer stem cells.

Curcumin is a dietary polyphenol and a bioactive phytochemical that possesses anti-inflammatory, antioxidant, anticancer, and chemopreventive properties, which make it capable of affecting multiple sites along the stem cell pathways to induce apoptosis in these cells. Curcumin's function is through suppression of cytokine release, especially the secretion of interleukins. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types, leading to the development of tumors. Cancer stem cells (CSC) are capable of sustaining tumor formation and differentiation, and are normally characterized by self-renewal mechanisms. Furthermore, these cells might be responsible for tumor relapse and resistance to therapy. Several studies have focused on the mechanisms of curcumin action in manipulating transcription factors, signaling pathways, CSC markers, microRNAs related to CSCs functions and apoptosis induction in various human cancer cells. In the present review, we aimed to summarize the reported molecular mechanisms of curcumin's effects on CSCs.

Curcumin as a potential modulator of M1 and M2 macrophages: new insights in atherosclerosis therapy.

Accumulation of macrophages within the artery wall is an eminent feature of atherosclerotic plaques. Macrophages are influenced by various plaque microenvironmental stimuli, such as oxidized lipids, cytokines, and senescent erythrocytes, and thereby polarize into two main phenotypes called proinflammatory M1 and anti-inflammatory M2 macrophages. In the hemorrhagic zones of atheroma, upon exposure to iron, sequestration of iron by M1 macrophages results in an uncontrolled proinflammatory phenotype impairing wound healing, while M2 macrophages phagocytose both apoptotic cells and senescent erythrocytes. M1 macrophages are prominent phenotype in the unstable plaques, in which plaque shoulder contains macrophages mainly present markers of M1 phenotype, whereas the fibrous cap encompassing the necrotic lipid core content macrophages expressed markers of both M1 and M2 subtypes. The abovementioned findings suggest macrophage modulation as a potent approach for atherosclerosis therapy. Curcumin is a polyphenol dietary derived from turmeric with numerous pharmacological activities. Recent in vitro and in vivo studies have indicated that curcumin exerted lipid-lowering effects, and also can modulate function of different macrophage subsets in various macrophage-involved diseases. The current review aimed to present role of macrophage subtypes in atherosclerosis development and progression, and to understand effect of curcumin on macrophage polarization and foam cell formation in the atherosclerosis lesions. Overall, we would address important targets for macrophage modulation in atherosclerotic plaques.

Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades?

Curcumin is a dietary polyphenol from turmeric with numerous pharmacological activities. Novel animal and human studies indicate that curcumin can affect different immune cells, such as various T lymphocyte subsets, macrophages, dendritic cells, B lymphocytes and natural killer cells, which results in decreasing severity of various diseases with immunological etiology. The present review provides a comprehensive overview of the effects of curcumin on different immune cells and immune system-related diseases.

The novel role of pyrvinium in cancer therapy.

Pyrvinium pamoate (PP) is a quinoline-derived cyanine dye which was officially approved by FDA for its anthelmintic properties and therapeutic function against animal-like protists such as Cryptosporidium parvum and Plasmodium falciparum in the 1950s. In the last 10 years, several studies have shown the novel activity of pyrvinium in tumor therapy. Some investigations have indicated that pyrvinium could delay or inhibit tumor cell proliferation in cancer models including colon, breast, lung and prostate cancer, and some hematological malignancies. In this review, we discuss multiple critical signaling pathways and mechanisms underlying the anticancer effects of PP. In details, pyrvinium acts through the following main mechanisms: (i) energy and autophagy depletion; and (ii) inhibition of Akt and Wnt-ß-catenin-dependent pathways. Interestingly, pyrvinium has also shown potent anti-cancer stem cell activity. The overwhelming insights into the mechanism of anticancer properties of PP can help establishing novel and future anti-tumor treatment strategies.

Altered Expression of MicroRNAs in Rheumatoid Arthritis.

Rheumatoid arthritis is one of the most common types of inflammatory joint diseases. Women, smokers, and people with positive family history are more susceptible to this disease. Diagnostic criteria include at least one swollen joint that has not been caused by other diseases. MicroRNAs are non-coding RNAs that are evolutionarily conserved and have a length of 18-25 nucleotides. MicroRNAs control gene expression at the post-transcriptional level via promoting mRNA degradation or translational repression. Recognition of alterations in microRNA status and their respective targets, may offer an opportunity to better identify the pathways that are involved in the etiopathogenesis of autoimmune diseases. It has been suggested that microRNAs may serve as potential biomarkers for both diagnosis and prognosis of autoimmune diseases. Here, we review the available evidence on the deregulations of microRNA expression in rheumatoid arthritis. More precisely, this review focuses on the microRNA involved in T cell regulation and gives perspectives on the use of this microRNA as biomarkers of diagnosis, prognosis, or intervention efficacy. J. Cell. Biochem. 119: 478-487, 2018. © 2017 Wiley Periodicals, Inc.

Application of fluorescence lifetime imaging microscopy of DNA binding dyes to assess radiation-induced chromatin compaction changes.

In recent years several approaches have been developed to address the chromatin status and its changes in eukaryotic cells under different conditions-but only few are applicable in living cells. Fluorescence lifetime imaging microscopy (FLIM) is a functional tool that can be used for the inspection of the molecular environment of fluorophores in living cells. Here, we present the use of single organic minor groove DNA binder dyes in FLIM for measuring chromatin changes following modulation of chromatin structure in living cells. Treatment with histone deacetylase inhibitors led to an increased fluorescence lifetime indicating global chromatin decompaction, whereas hyperosmolarity decreased the lifetime of the used dyes, thus reflecting the expected compaction. In addition, we demonstrate that time domain FLIM data based on single photon counting should be optimized using pile-up and counting loss correction, which affect the readout even at moderate average detector count rates in inhomogeneous samples. Using these corrections and utilizing Hoechst 34580 as chromatin compaction probe, we measured a pan nuclear increase in the lifetime following irradiation with X-rays in living NIH/3T3 cells thus providing a method to measure radiation-induced chromatin decompaction.

Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA).

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as three or more consecutive abortions before the 20th week of gestation. There is increasing evidence to support an immunological mechanism for the occurrence of RSA. The purpose of our study was to examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, recurrent spontaneous abortion. MATERIALS AND METHODS: This is a case-control study. We recruited 200 patients with RSA (case group) using established diagnostic criteria and 200, normal individuals (control group) at the fertility and infertility center in Yazd city and Isfahan city during 2012 to 2013. We screened the I50V variant in IL-4R in patients and controls by PCR-RFLF method, and we performed an association analysis between I50V variant and RSA.the data was analyzed by spss 16 software using Chi-square test. RESULTS: No differences in the genotype and allele frequencies of the I50V SNPs were identified between patients with RSA and healthy controls. CONCLUSIONS: The frequency of SNP in IL-4 receptor (I50V) in patients with recurrent spontaneous abortion did not differ significantly compared with the control group. Analysis of IL4R SNP haplotypes or complex alleles suggested no dominant protection in patients with RSA.

Genetically Engineered Exosomes as a Potential Regulator of Th1 Cells Response in Rheumatoid Arthritis.

Background: Rheumatoid arthritis is a long-lasting inflammatory disease that usually involves joints, but it can also affect other organs, including the skin and lungs. In this case, it is important to maintain a balance between beneficial pro-inflammatory activity and harmful overactivation of the T helper cells (Th). We strive to investigate in this study the possibilities for the effect of mesenchymal stem cells (MSCs)-derived exosomes containing miR-146a/miR-155 on the lymphocyte population and function. Methods: Exosomes were isolated from overexpressed miR-146a/miR-155 MSCs for the purpose of this analysis. Splenocytes were isolated from collagen-induced arthritis (CIA) and control mice. It was important to consider the expressions of certain predominant autoimmune-response genes, including T-bet and interferon-γ (IFNγ), by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. It turned out to be a significant consideration with p < 0.05. Results: The results are expressed in percentages with respect to miR-146a/AntimiR-155 transduced MSC-derived exosomes treatment, which significantly decreased the mRNA expression level of IFNγ in healthy mice (p < 0.05). miR-146a transduced MSC-derived exosomes treatment significantly reduced the mRNA expression level of IFNγ in CIA mice (p < 0.05). It should be noted that the secretion of the pro-inflammatory factor IFNγ in CIA mice was inhibited in almost all groups (p < 0.05). Conclusion: Many research groups have mainly focused on strategies for reducing pro-inflammatory cytokines. This approach was recently suggested and investigated in our research team and suggested that manipulation of MSCs-derived exosomes could minimize pro-inflammatory cytokine production to strike a balance among Th subsets. These approaches tend to appear to achieve better results in the regulation of the immune system by the use of engineered exosomes derived from MSCs. By providing accurate information the reasonably practicable use of exosomes for cell-free therapy can be established.

Immunomodulatory Therapeutic Effects of Curcumin on M1/M2 Macrophage Polarization in Inflammatory Diseases.

BACKGROUND: Due to their plasticity, macrophages exert critical effects on both promoting and suppressing inflammatory processes. Pathologic inflammatory conditions are frequently correlated with dynamic alterations in macrophage activation, with classically activated M1 cells associated with the promotion and maintenance of inflammation and M2 cells being linked to the resolution or smouldering of chronic inflammation. Inflammation deputes a common feature of various chronic diseases and the direct involvement in the insurgence and development of these conditions. Macrophages participate in an autoregulatory loop characterizing the inflammatory process, as they produce a wide range of biologically active mediators that exert either deleterious or beneficial effects during the inflammation. Therefore, balancing the favorable ratios of M1/M2 macrophages can help ameliorate the inflammatory landscape of pathologic conditions. Curcumin is a component of turmeric with many pharmacological properties. OBJECTIVE: Recent results from both in-vivo and in-vitro studies have indicated that curcumin can affect polarization and/or functions of macrophage subsets in the context of inflammation-related diseases. There is no comprehensive review of the impact of curcumin on cytokines involved in macrophage polarization in the context of inflammatory diseases. The present review will cover some efforts to explore the underlying molecular mechanisms by which curcumin modulates the macrophage polarization in distant pathological inflammatory conditions, such as cancer, autoimmunity, renal inflammation, stroke, atherosclerosis, and macrophage-driven pathogenesis. RESULTS: The accumulation of the findings from in vitro and in vivo experimental studies suggests that curcumin beneficially influences M1 and M2 macrophages in a variety of inflammatory diseases with unfavorable macrophage activation. CONCLUSION: Curcumin not only enhances anti-tumor immunity (via shifting M polarization towards M1 phenotype and/or up-regulation of M1 markers expression) but ameliorates inflammatory diseases, including autoimmune diseases (experimental autoimmune myocarditis and Behcet's disease), nephropathy, chronic serum sickness, stroke, and atherosclerosis.

Severity of COVID-19 in pregnant women: a review on the potential role of regulatory T cells.

As a physiological condition, pregnancy may cause temporary alterations in the hematological, cardiopulmonary, and immune responses, affecting the maternal susceptibility to viral infections. Pregnant women are vulnerable to infection with the influenza A virus, hepatitis E virus, MERS CoV, and SARS CoV. The agent of Coronavirus disease (COVID-19) is the SARS coronavirus (SARS CoV-2), which affects the cells upon binding to the angiotensin-converting enzyme-2 (ACE2). However, ACE2 expression is elevated in the placental tissue. However, surprisingly, COVID-19 infection in pregnant women tends to have a lower severity and mortality. Therefore, it is interesting to find the immunological mechanisms related to the severity of COVID-19 in pregnancy. Regulatory T cells (Tregs) are a subset of CD4+T cells that may play a central role in maintaining maternal tolerance by regulating immune responses. Pregnancy-induced Tregs are developed to control immune responses against paternal antigens expressed by the semi-allograft fetus. The role of uncontrolled immune responses in COVID-19 pathogenesis has already been identified. This review provides insight into whether pregnancy-induced regulatory T-cell functions could influence the severity of COVID-19 infection during pregnancy.

Negatively-charged Liposome Nanoparticles Can Prevent Dyslipidemia and Atherosclerosis Progression in the Rabbit Model.

BACKGROUND AND AIM: Negatively charged nanoliposomes have a strong attraction towards plasma lipoprotein particles and can thereby regulate lipid metabolism. Here, the impact of such nanoliposomes on dyslipidaemia and progression of atherosclerosis was investigated in a rabbit model. METHODS: Two sets of negatively-charged nanoliposome formulations including [Hydrogenated Soy Phosphatidylcholine (HSPC)/1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)] and [1,2- Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC)/1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPG)/Cholesterol] were evaluated. Rabbits fed a high-cholesterol diet were randomly divided into 3 groups (n=5/group) intravenously administrated with HSPC/DSPG formulation (DSPG group; 100 mmol/kg), DMPC/DMPG formulation (DMPG group; 100 mmol/kg), or the normal saline (control group; 0.9% NaCl) over a 4-week period. The atherosclerotic lesions of the aortic arch wall were studied using haematoxylin and eosin staining. RESULTS: Both DSPG and DMPG nanoliposome formulations showed a nano-sized range in diameter with a negatively-charged surface and a polydispersity index of <0.1. After 4 weeks administration, the nanoliposome formulations decreased triglycerides (-62±3% [DSPG group] and -58±2% [DMPG group]), total cholesterol (-58±9% [DSPG group] and -37±5% [DMPG group]), and lowdensity lipoprotein cholesterol (-64±6% [DSPG group] and -53±10% [DMPG group]) levels, and increased high-density lipoprotein cholesterol (+67±28% [DSPG group] and +35±19% [DMPG group]) levels compared with the controls. The nanoliposomes showed a significant decrease in the severity of atherosclerotic lesions: mean values of the intima to media ratio in DMPG (0.96±0.1 fold) and DSPG (0.54±0.02 fold) groups were found to be significantly lower than that in the control (1.2±0.2 fold) group (p<0.05). CONCLUSION: Anionic nanoliposomes containing [HSPC/DSPG] and [DMPC/DMPG] correct dyslipidaemia and inhibit the progression of atherosclerosis.

Evaluation of Th17 and Treg cytokines in patients with unexplained recurrent pregnancy loss.

Background and Aim: The Th17/Treg balance in peripheral blood and reproductive tissues may have a role in the etiology of unexplained recurrent pregnancy loss (URPL). In this study, we evaluated the major cytokine of Treg cells transforming growth factor-beta (TGF-ß), and their specific transcription factor Forkhead box P3 (FOXP3), as well as the most highlighted cytokine of Th17 cells (interleukin [IL]-17A) in both URPL patients and healthy women. Methods: Samples were extracted from the peripheral blood, endocervix, endometrium, and vagina of 14 patients with URPL and 12 normal non-pregnant women as a control (normal) group. Quantitative reverse transcription polymerase chain reaction was used to determine gene expression. Enzyme-linked immunosorbent assay was used to determine the levels of cytokines in the serum and cervicovaginal fluid. Results: We found that in the URPL group, FOXP3 gene expression was considerably higher in peripheral blood than in the normal group (P=0.043). TGF-ß levels in the cervicovaginal fluid were different in the URPL and normal groups (P=0.015). In comparison to the control group, women with URPL had significantly greater IL-17 gene expression in the peripheral blood (P=0.01). Conclusion: Lower TGF-ß levels in the cervicovaginal fluid of patients compared to controls may be related with increased IL-17 and FOXP3 mRNA levels in patients with URPL. Dysregulation of local immune responses in reproductive tissues may represent dysregulation of systemic regulatory immunological responses in the pathogenesis of URPL. Relevance for Patients: Dysregulation of immune responses may play a role in the pathogenesis of URPL at least in some patients with URPL. We conclude that the breakdown of tolerance in the local immune responses is more critical than the breakdown of tolerance in systemic tolerance in the pathogenesis of URPL. Therefore, modulating immune responses in the endometrium and decidua may be the focus of future therapeutic approaches in URPL. The impact of seminal plasma on the expansion of Tregs may provide a novel therapeutic intervention that has already been used in assisted reproductive technologies. Therefore, we suggest that transvaginal TGF-ß in women with URPL may induce maternal tolerance which leads to the successful pregnancy.

The therapeutic potential of regulatory T cells in reducing cardiovascular complications in patients with severe COVID-19.

The SARS coronavirus 2 (SARS CoV-2) causes Coronavirus Disease (COVID-19), is an emerging viral infection. SARS CoV-2 infects target cells by attaching to Angiotensin-Converting Enzyme (ACE2). SARS CoV-2 could cause cardiac damage in patients with severe COVID-19, as ACE2 is expressed in cardiac cells, including cardiomyocytes, pericytes, and fibroblasts, and coronavirus could directly infect these cells. Cardiovascular disorders are the most frequent comorbidity found in COVID-19 patients. Immune cells such as monocytes, macrophages, and T cells may produce inflammatory cytokines and chemokines that contribute to COVID-19 pathogenesis if their functions are uncontrolled. This causes a cytokine storm in COVID-19 patients, which has been associated with cardiac damage. Tregs are a subset of immune cells that regulate immune and inflammatory responses. Tregs suppress inflammation and improve cardiovascular function through a variety of mechanisms. This is an exciting research area to explore the cellular, molecular, and immunological mechanisms related to reducing risks of cardiovascular complications in severe COVID-19. This review evaluated whether Tregs can affect COVID-19-related cardiovascular complications, as well as the mechanisms through which Tregs act.

Evaluation of the Effects of 1,25VitD3 on Inflammatory Responses and IL-25 Expression.

VitD3 may contribute to a successful pregnancy through modulation of immune responses, so VitD3 deficiency may have a role in the immunopathogenesis of unexplained recurrent spontaneous abortion (URSA). However, the mechanisms of immunomodulatory actions of VitD3 in decreasing the risk of recurrent spontaneous abortion have not been understood well. Objective: The purpose of this research was to investigate the influence of 1,25VitD3 on IL-25 and related cytokines of Th17 cells including IL-17A, IL-6, and IL-23 in peripheral blood mononuclear cells of healthy women as a control group and women with unexplained recurrent spontaneous abortion. Method: Isolation of peripheral blood mononuclear cells (PBMCs) was performed from peripheral blood of the subjects of the studied groups (20 women with URSA as a case group, and 20 control women). The effects of 1,25VitD3 (50 nM, for 24 h) on the studied parameters were evaluated and were compared to the positive and negative controls in vitro. Flow cytometry analysis was used to determine the percentages of regulatory T cells and Th17 cells. For gene expression measurement and cytokines assay, real-time PCR and ELISA were carried out. Results: The proportion of Th17 cells in women with URSA was considerably higher than in the control group. IL-25 mRNA and protein levels in cultured PBMCs from women with URSA were lower than the controls. 1,25VitD3 increased IL-25 expressions at both the protein and mRNA levels in PBMCs from women with URSA relative to the control group. Additionally, 1,25VitD3 treatment not only significantly decreased the percentage of Th17 cells frequency but also reduced expressions of IL-6, IL-17A, and IL-23 in PBMCs from women with URSA. Conclusion: 1,25VitD3 may diminish inflammatory responses cells via downregulation of IL-25 expression. It could be an interesting subject for future researches in the field of the immunopathology of URSA to identify molecular pathways in URSA treatment.

Impact of PCSK9 Immunization on Glycemic Indices in Diabetic Rats.

METHODS: To prepare the anti-PCSK9 vaccine, a peptide construct called Immunogenic Fused PCSK9-Tetanus (IFPT) was linked to the surface of nanoliposome carriers. Healthy rats received four subcutaneous injections of the vaccine at biweekly intervals. Two weeks after the last vaccination, anti-PCSK9 antibody titers, PCSK9 targeting, and inhibition of PCSK9-low-density lipoprotein receptor (LDLR) interaction were evaluated. After verification of antibody generation, the immunized rats were intraperitoneally treated with a single dose (45 mg/kg) of streptozotocin (STZ) to induce diabetes mellitus. The levels of fasting blood glucose (FBG) were measured, and the oral glucose tolerance test (OGTT) as well as the insulin tolerance test (ITT) were carried out to assess glycemic status. At the end of the study, the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol concentrations were assayed. Histopathology examination of the liver and pancreas was also performed using the hematoxylin-eosin staining method. RESULTS: The prepared nanoliposomal vaccine could strongly induce anti-PCSK9 antibodies in the vaccinated rats. Within one week following the STZ injection, the FBG level was lower in the vaccinated group vs. diabetic control group (49% (-171.7 ± 35 mg/dL, p < 0.001)). In the OGTT, the injected rats showed improved glucose tolerance as reflected by the reduction of blood glucose levels over 180 min, compared with the diabetic controls. Moreover, the ITT demonstrated that, after the insulin injection, blood glucose concentration declined by 49.3% in the vaccinated group vs. diabetic control group. Expectedly, the vaccinated rats exhibited lower (-26.65%, p = 0.03) plasma LDL-C levels compared with the diabetic controls. Histopathology examination of pancreas tissue demonstrated that the pancreatic islets of the vaccinated rats had a slight decline in the population of ß-cells and few α-cells. Normal liver histology was also observed in the vaccinated rats. CONCLUSION: PCSK9 inhibition through the liposomal IFPT vaccine can improve the glucose and insulin tolerance impairments as well as the lipid profile in diabetes.

Adoptive transfer of Tregs: A novel strategy for cell-based immunotherapy in spontaneous abortion: Lessons from experimental models.

Since half of the genes are inherited from the paternal side, the maternal immune system has to tolerate the presence of foreign paternal antigens. Regulatory T cells facilitate the development and maintenance of peripheral tissue tolerance of the fetus during pregnancy. Reduction in regulatory T cells is associated with complications of pregnancy, including spontaneous abortion. Recent studies in mouse models have shown that the adoptive transfer of Tregs can prevent spontaneous abortion in mouse models through improving maternal tolerance. Thus, adoptive cell therapy using autologous Tregs could potentially be a novel therapeutic approach for cell-based immunotherapy in women with unexplained spontaneous abortion. Besides, strategies for activating and expanding antigen-specific Tregs ex vivo and in vivo based on pharmacological agents can pave the foundation for an approach incorporating immunotherapy and pharmacotherapy. This review aims to elaborate on the current understanding of the therapeutic potential of the adoptive transfer of Tregs in the treatment of spontaneous abortion disease.

Experimental and theoretical studies of Palladium-hydrazide complexes' interaction with DNA and BSA, in vitro cytotoxicity activity and plasmid cleavage ability.

New palladium complexes with general formula trans-[Pd(L)2(OAc)2] (1,2), (L = Benzhydrazide and 2-Furoic hydrazide) have been synthesized and characterized with various methods including elemental analysis, FT-IR, 1HNMR and mass spectroscopy. Afterward their interactions with bovine serum albumin and calf thymus deoxyribonucleic acid have been investigated by UV-vis absorption, fluorescence emission and circular dichroism spectroscopy. Also, site-selective replacement experiments with site probes have been carried out. Analysis of fluorescence spectrum indicated static quenching mechanism. Spectroscopic measurements for DNA binding showed the groove binding to DNA for both complexes. Furthermore, cytotoxicity studies of complexes and cis-platin have been done against colon carcinoma (CT26) and breast cancer (4T1) cell lines. Evaluation of complexes (1) and (2) on induction of apoptosis in CT26 cells has been done. Finally, plasmid cleavage ability of (1) and (2) was investigated by gel electrophoresis that indicate the more activity of (1) than (2).