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Streptococcus mutans is a main organism of tooth infections including tooth decay and periodontitis. The aim of this study was to assess the influence of sucrose and starch on biofilm formation and proteome profile of S. mutans ATCC 35668 strain. The biofilm formation was assessed by microtiter plating method. Changes in bacterial proteins after exposure to sucrose and starch carbohydrates were analyzed using matrix‐assisted laser desorption/ionization mass spectrometry. The biofilm formation of S. mutans was increased to 391.76% in 1% sucrose concentration, 165.76% in 1% starch, and 264.27% in the 0.5% sucrose plus 0.5% starch in comparison to biofilm formation in the media without sugars. The abundance of glutamines, adenylate kinase, and 50S ribosomal protein L29 was increased under exposure to sucrose. Upregulation of lactate utilization protein C, 5‐hydroxybenzimidazole synthase BzaA, and 50S ribosomal protein L16 was formed under starch exposure. Ribosome‐recycling factor, peptide chain release factor 1, and peptide methionine sulfoxide reductase MsrB were upregulated under exposure to sucrose in combination with starch. The results demonstrated that the carbohydrates increase microbial pathogenicity. In addition, sucrose and starch carbohydrates can induce biofilm formation of S. mutans via various mechanisms such as changes in the expression of special proteins. [ABSTRACT FROM AUTHOR]

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre‐eclampsia are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid‐derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications. [ABSTRACT FROM AUTHOR]

Purpose: The authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients. Methods: Mono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted. Results: Well‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention. Conclusions: S‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance. [ABSTRACT FROM AUTHOR]

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody‐dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed. [ABSTRACT FROM AUTHOR]

Hematopoietic stem cells (HSCs) transplantation is considered a suitable treatment for malignant or nonmalignant hematological diseases. This study aims to investigate the HSCs homing factors in bone marrow (BM) donors of acute lymphoblastic leukemia (ALL) patients following granulocyte colony‐stimulating factor (G‐CSF) injection, as well as the G‐CSF effects on BM transplantation quality in these patients. To mobilize HSCs into peripheral blood, G‐CSF was used for ALL patient's BM donors. For HSCs counting, CD34+ cells were evaluated in analogous and autologous donors using flow cytometry. The expression of stem cell homing factors in CD34+ cells and peripheral blood mononuclear cells (PBMCs) were investigated using a real‐time polymerase chain reaction. Finally, hematological factors after BM transplantation in ALL patients were assessed. According to our results, after G‐CSF injection, the level of CD34+ HSCs was statistically increased. Besides, autologous donors showed a higher level of CD34+ cells compared to analogous donors before and after G‐CSF injection. Additionally, a higher number of CD34+ HSCs was achieved in the autologous samples following G‐CSF injection. Furthermore, after G‐CSF injection, the expression of matrix metalloproteinase (MMP)‐2, MMP‐9 was increased; while, stromal cell‐derived factor 1, intercellular adhesion molecule‐1, and vascular cell adhesion molecule‐1 expression were decreased. Moreover, the expression of C‐X‐C chemokine receptor type 4, lymphocyte function‐associated antigen 1, and very late antigen‐4 in CD34+ cells and PBMCs were decreased. BM transplantation on Day 90 also caused an increased level of white blood cells, red blood cells, and platelets as compared to the first day; however, no statistical differences were observed in hemoglobin level. In conclusion, G‐CSF by altering the expression of HSCs homing factors in ALL donors improves BM transplantation quality in ALL patients. [ABSTRACT FROM AUTHOR]

Exosomes derived from solid tumour cells are involved in immune suppression, angiogenesis and metastasis; however, the role of leukaemia‐derived exosomes has less been investigated. Hence, changes in immune response‐related genes and human T cells apoptosis co‐incubated with exosomes isolated from patients' pre‐B cell acute lymphoblastic leukaemia were evaluated in this in vitro study. Vein blood sample was obtained from each newly diagnosed acute lymphoblastic leukaemia (ALL) patient prior any therapy. ALL serum exosomes were isolated by ultrafiltration and characterized using Western blotting and transmission electron microscopy. Exosomes were then co‐incubated with T lymphocytes and the gene expressions, as well as functions of human T cells were quantified by qRT‐PCR. Apoptosis and caspase‐3 and caspase‐9 protein expression were also evaluated by flowcytometry and Western blotting analysis, respectively. Exosomes isolated from ALL patients affected T lymphocytes and elevated the apoptosis. Moreover, these exosomes altered the T cells profile into regulatory type by increasing the expression of FOXP3 and Tregs‐related cytokines, including TGF‐B and IL‐10. The expression level of Th17‐related transcription factors (RoRγt) and interleukins (IL‐17 and IL‐23) decreased after this treatment. According to our findings, exosomes derived from ALL patients' sera carry immunosuppressive molecules, indicating the possible effect of exosomes as liquid biomarkers for cancer staging. [ABSTRACT FROM AUTHOR]

Background and aims: Evaluation of learners is considered as one of the most important principles in education, especially in the clinical fields. Continuous assessment can be used to provide appropriate feedback to students about their strengths and weaknesses. In this regard, this study is aimed to design a system of continuous assessment of medical residents (SCMARs). Methods: This study was performed using a combination of qualitative methods, including focus group discussion, expert panel, and Delphi technique. The study population consisted of all the stakeholders involved in the evaluation process of medical residents in Imam Reza Hospital Complex (IRHC) in Iran. This study was conducted in three phases, including identification of subthemes and indicators, production of a primary framework for the SCMAR, and agreement on the subthemes of the SCMAR. The nominal group technique was used for generating priority information. Data analysis was performed during the agreement review stage with the Excel software version 2016. Results: The finalized SCMAR consisted of 10 main themes and 38 subthemes. The themes included objectives, evaluators, areas, and indicators of evaluation, evaluation periods, evaluation requirements, data collection, data sources, point assignment and data analysis methods, reporting, and feedback dissemination methods. Five areas of evaluation and 11 indicators of evaluation were proposed. Conclusion: A comprehensive assessment system that continuously evaluates the performance of Medical Residents can be used as a stimulus to improve the quality of educational processes. The present study was aimed to address this need by designing a framework for such a system. [ABSTRACT FROM AUTHOR]

In recent years, stem cells have known as a helpful biological tool for the accurate diagnosis, treatment and recognition of diseases. Using stem cells as biomarkers have presented high potential in the early detection of many diseases. Another advancement in stem cell technology includes stem cell derived organoids model that could be a promising platform for diagnosis and modeling different diseases. Furthermore, therapeutic capabilities of stem cell therapy have increased hope in the face of different disability managements. All of these technologies are also widely used in reproductive related diseases especially in today's world that many couples encounter infertility problems. However, with the aid of numerous improvements in the treatment of infertility, over 80% of couples who dreamed of having children could now have children. Due to the fact that infertility has many negative effects on personal and social lives of young couples, many researchers have focused on the treatment of male and female reproductive system abnormalities with different types of stem cells, including embryonic stem cells, bone marrow mesenchymal stem cells (MSCs), and umbilical cord‐derived MSCs. Also, design and formation of reproductive system organoids provide a fascinating window into disease modeling, drug screening, personalized therapy, and regeneration medicine. Utilizing these techniques to study, model and treat the infertility‐related diseases has drawn attention of many scientists. This review explains different applications of stem cells in generating reproductive system organoids and stem cell‐based therapies for male and female infertility related diseases treatment. [ABSTRACT FROM AUTHOR]

Innate and adaptive immune systems have a crucial role in initiating and progressing some pregnancy disorders such as preeclampsia (PE), which is one of the pregnancy‐specific disorders that could result in neonatal and maternal morbidity and mortality. The dysregulation of the spiral artery and inadequate trophoblast invasion lead to PE symptoms through producing various inflammatory cytokines and anti‐angiogenic factors from the placenta. T lymphocytes play a special role in the epithelium and stroma of the human endometrium. CD4+ T helper (Th) cells, Th1/Th2, and Th17/T regulatory (Treg) balance mainly contribute to the establishment of a pregnancy‐favorable environment. This review examined the dysregulation of some cytokines produced from T cells, the dysregulation of the transcription factors of Th cells, the expression of chemokine receptors on T cells, as well as the effects of some factors including vitamin D on the activity of T cells, and finally, the dysregulation of various miRNAs related to T cells, which could cause PE. [ABSTRACT FROM AUTHOR]

The kidney is one of the main targets attacked by viruses in patients with a coronavirus infection. Until now, SARS‐CoV‐2 has been identified as the seventh member of the coronavirus family capable of infecting humans. In the past two decades, humankind has experienced outbreaks triggered by two other extremely infective members of the coronavirus family; the MERS‐CoV and the SARS‐CoV. According to several investigations, SARS‐CoV causes proteinuria and renal impairment or failure. The SARS‐CoV was identified in the distal convoluted tubules of the kidney of infected patients. Also, renal dysfunction was observed in numerous cases of MERS‐CoV infection. And recently, during the 2019‐nCoV pandemic, it was found that the novel coronavirus not only induces acute respiratory distress syndrome (ARDS) but also can induce damages in various organs including the liver, heart, and kidney. The kidney tissue and its cells are targeted massively by the coronaviruses due to the abundant presence of ACE2 and Dpp4 receptors on kidney cells. These receptors are characterized as the main route of coronavirus entry to the victim cells. Renal failure due to massive viral invasion can lead to undesirable complications and enhanced mortality rate, thus more attention should be paid to the pathology of coronaviruses in the kidney. Here, we have provided the most recent knowledge on the coronaviruses (SARS, MERS, and COVID19) pathology and the mechanisms of their impact on the kidney tissue and functions. [ABSTRACT FROM AUTHOR]

Aging is a biological process caused by the accumulation of senescent cells with a permanent proliferative arrest. To the influence of aging on human life expectancy, there is essential for new biomarkers which possibly will assistance in recognizing age‐associated pathologies. Exosomes, which are cell‐secreted nanovesicles, make available a new biomarker detection and therapeutic approach for the transfer of different molecules with high capacity. Recently, non‐coding RNAs (ncRNA) which are contained in exosomes have developed as important molecules regulating the complexity of aging and relevant human diseases. The discovery of ncRNA provided perceptions into an innovative regulatory platform that could interfere with cellular senescence. The non‐coding transcriptome includes a different of RNA species, spanning from short ncRNAs (<200 nucleotides) to long ncRNAs, that are >200 bp long. Upgraded evidence displays that targeting ncRNAs possibly will influence senescence pathways. In this article, we will address ncRNAs that participated in age‐related and cellular senescence diseases. Growing conception of ncRNAs in the aging process possibly will be responsible for new understandings into the improvement of age‐related diseases and elongated life span. [ABSTRACT FROM AUTHOR]

One of the most common diseases in the present era is cancer. The common treatment methods used to control cancer include surgery, chemotherapy, and radiotherapy. Despite progress in the treatment of cancers, there still is no definite therapeutic approach. Among the currently proposed strategies, immunotherapy is a new approach that can provide better outcomes compared with existing therapies. Employing natural killer (NK) cells is one of the means of immunotherapy. As innate lymphocytes, NK cells are capable of rapidly responding to cancer cells without being sensitized or restricted to the cognate antigen in advance, as compared to T cells that are tumor antigen‐specific. Latest insights into the biology of NK cells have clarified the underlying molecular mechanisms of NK cell maturation and differentiation, as well as controlling their effector functions through the investigation of the ligands and receptors engaged in recognizing cancer cells by NK cells. Elucidating the fact that NK cells recognize cancer cells could similarly show the mechanism through which cancer cells possibly avoid NK cell‐dependent immune surveillance. Additionally, the expectations for novel immunotherapies by targeting NK cells have increased through the latest clinical outcomes of T–cell‐targeted cancer immunotherapy. For this emerging method, researchers are still attempting to develop protocols for conferring the best proliferation and expansion medium, activation pathways, utilization dosage, transferring methods, as well as reducing possible side effects in cancer therapy. This study reviews the NK cells, their proliferation and expansion methods, and their recent applications in cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Umbilical cord Wharton's jelly‐derived mesenchymal stem cells (WJ‐MSCs) have recently gained considerable attention in the field of regenerative medicine. Their high proliferation rate, differentiation ability into various cell lineages, easy collection procedure, immuno‐privileged status, nontumorigenic properties along with minor ethical issues make them an ideal approach for tissue repair. Besides, the number of WJ‐MSCs in the umbilical cord samples is high as compared to other sources. Because of these properties, WJ‐MSCs have rapidly advanced into clinical trials for the treatment of a wide range of disorders. Therefore, this paper summarized the current preclinical and clinical studies performed to investigate the regenerative potential of WJ‐MSCs in neural, myocardial, skin, liver, kidney, cartilage, bone, muscle, and other tissue injuries. [ABSTRACT FROM AUTHOR]

There is an interconnected network between S1P/sphingosine‐1‐phosphate receptor 1 (S1PR1), IL‐6/glycoprotein 130 (GP130), and signal transducer and activator of transcription 3 (STAT3) signaling pathways in the tumor microenvironment, which leads to cancer progression. S1P/S1PR1 and IL‐6/GP130 signaling pathways phosphorylate and activate STAT3, and it then induces the expression of S1PR1 and interleukin‐6 (IL‐6) in a positive feedback loop leading to cancer progression. We hypothesized that blockade of this amplification loop can suppress the growth and development of cancer cells. Therefore, we silenced STAT3 upstream molecules including the S1PR1 and GP130 molecules in cancer cells using small interfering RNA (siRNA)‐loaded alginate‐conjugated trimethyl chitosan (ATMC) nanoparticles (NPs). The generated NPs had competent properties including the appropriate size, zeta potential, polydispersity index, morphology, high uptake of siRNA, high rate of capacity, high stability, and low toxicity. We evaluated the effects of siRNA loaded ATMC NPs on tumor hallmarks of three murine‐derived cancer cell lines, including 4T1 (breast cancer), B16‐F10 (melanoma), and CT26 (colon cancer). The results confirmed the tumor‐suppressive effects of combinational targeting of S1PR1 and GP130. Moreover, combination therapy could potently suppress tumor growth as assessed by the chick chorioallantoic membrane assay. In this study, we targeted this positive feedback loop for the first time and applied this novel combination therapy, which provides a promising approach for cancer treatment. The development of a potent nanocarrier system with ATMC for this combination was also another aspect of this study, which should be further investigated in cancer animal models in further studies. [ABSTRACT FROM AUTHOR]

Cancer, even currently, is one of the main reasons for mortality and morbidity, worldwide. In recent years, a great deal of effort has been made to find efficient therapeutic strategies for cancer, however, particularly with regards to side effects and the possibility of complete remission. Berberine (BBR) is a nature‐driven phytochemical component originated from different plant groups such as Berberis vulgaris, Berberis aquifolium, and Berberis aristata. BBR is a well‐known nutraceutical because of its wide range of pharmacological activities including anti‐inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide. In addition, it exhibits inhibitory effects on multiple types of cancers. In this review, we have elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion. [ABSTRACT FROM AUTHOR]

Exosomes, as small vesicles, are released by tumor cells and tumor microenvironment (cells and function as key intercellular mediators and effects on different processes including tumorigenesis, angiogenesis, drug resistance, and evasion from immune system. These functions are due to exosomes' biomolecules which make them as efficient markers in early diagnosis of the disease. Also, exosomes have been recently applied in vaccination. The potential role of exosomes in immune response toward leukemic cells makes them efficient immunotherapeutic agents treating leukemia. Furthermore, variations in exosomes contents make them beneficial to be used in treating different diseases. This review introduces the role of exosomes in the development of hematological malignancies and evaluates their functional role in the treatment of these malignancies. [ABSTRACT FROM AUTHOR]

As an evolutionarily conserved pathway, Hippo signaling pathway impacts different pathology and physiology processes such as wound healing, tissue repair/size and regeneration. When some components of Hippo signaling dysregulated, it affects cancer cells proliferation. Moreover, the relation Hippo pathway with other signaling including Wnt, TGFβ, Notch, and EGFR signaling leaves effect on the proliferation of cancer cells. Utilizing a number of therapeutic approaches, such as siRNAs and long noncoding RNA (lncRNA) to prevent cancer cells through the targeting of Hippo pathways, can provide new insights into cancer target therapy. The purpose of present review, first of all, is to demonstrate the importance of Hippo signaling and its relation with other signaling pathways in cancer. It also tries to demonstrate targeting Hippo signaling progress in cancer therapy. [ABSTRACT FROM AUTHOR]

Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity; each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/β‐catenin, transforming growth factor‐β, and mitogen‐activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy; most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor‐κ B, phosphoinositide‐3‐kinase/Akt, and extracellular‐signal‐regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) usually happens former to the age of 40 and affects the female physiological state premenopausal period. In this condition, ovaries stop working long before the expected menopausal time. Of diagnostic symptoms of the disease, one can mention amenorrhea and hypoestrogenism. The cause of POF in most cases is idiopathic; however, cancer therapy may also cause POF. Commonly utilized therapies such as hormone therapy, in‐vitro activation, and regenerative medicine are the most well‐known treatments for POF. Hence, these therapies may be associated with some complications. The aim of the present study is to discuss the beneficial effects of tissue engineering for fertility rehabilitation in patients with POF as a newly emerging therapy. [ABSTRACT FROM AUTHOR]

As critical mediators in biological processes, microRNAs (miRNAs) which are small and endogenous noncoding RNAs have been associated with disease progression, cell proliferation, and development. Pre‐eclampsia (PE), a pregnancy‐related disorder with no early markers or symptoms is recognized as the main reason for fetal and maternal mortality and morbidity in the initial steps or even during pregnancy, worldwide. Clinical symptoms usually appear in the third trimester of the pregnancy. Although numerous research have unraveled several aspects of placenta development abnormalities associated with abnormal trophoblastic invasion and angiogenesis modification, many questions about the PE pathogenesis remains unanswered. A large number of studies have shown the important role of miRNAs as potential biomarkers in the PE prognosis and diagnosis. Here, the latest investigations about the PE and placental miRNAs expression, as well as, the crucial role of miRNA molecules including miR‐210 and miR‐155 which are deregulated in patients with PE, will be argued. [ABSTRACT FROM AUTHOR]

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano‐sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell‐to‐cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole‐cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders. [ABSTRACT FROM AUTHOR]

Summary: Dendritic cell (DC) ‐based cancer immunotherapy is one of the most important anti‐cancer immunotherapies, and has been associated with variable efficiencies in different cancer types. It is well‐known that tumor microenvironment plays a key role in the efficacy of various immunotherapies such as DC vaccine. Accordingly, the expression of programmed death ligand 1 (PD‐L1) on DCs, which interacts with PD‐1 on T cells, leads to inhibition of anti‐tumor responses following presentation of tumor antigens by DCs to T cells. Therefore, we hypothesized that down‐regulation of PD‐L1 in DCs in association with silencing of PD‐1 on T cells may lead to the enhancement of T‐cell priming by DCs to have efficient anti‐tumor T‐cell responses. In this study, we silenced the expression of PD‐L1 in DCs and programmed cell death protein 1 (PD‐1) in T cells by small interfering RNA (siRNA) ‐loaded chitosan–dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T‐cell functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size 77·5 nm and zeta potential of 14·3) that were associated with efficient cellular uptake and target gene silencing. Moreover, PD‐L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD‐L1‐negative DCs to PD‐1‐silenced T cells led to induction of potent T‐cell responses. Our findings imply that PD‐L1‐silenced DCs can be considered as a potent immunotherapeutic approach in combination with PD‐1‐siRNA loaded NPs, however; further in vivo investigation is required in animal models. [ABSTRACT FROM AUTHOR]

miR‐143 is a tumor suppressor miRNA which its downregulation is frequently reported in colorectal cancer (CRC). This miRNA is a negative regulator of K‐RAS, c‐MYC, BCL‐2, and MMP‐9 genes which are engaged in tumor growth and metastasis. In the present study, miR‐143 restoration was performed by transfection of the pCMV‐miR‐143 vector into the SW‐480 CRC cells. Subsequently, alterations in proliferative and migratory potential of the cells were investigated by the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) and wound‐healing assays, respectively. Moreover, to detect apoptosis incidence in the transfected cells, 4',6‐diamidino‐2‐phenylindole (DAPI) staining was used. Furthermore, mRNA levels of c‐MYC, K‐RAS, MMP‐9, and BCL‐2, as potential targets of miR‐143, were assessed by quantitative Real‐Time PCR (qRT‐PCR). Also the expression levels of c‐MYC, K‐RAS, and MMP‐9 proteins were investigated by the western blot analysis. Finally, the ratio of BAX to BCL‐2 expression, as a potential marker of the response to apoptosis stimuli, was compared between the control and test groups. Furthermore, the trypan blue test was performed to determine the cell viability in cell suspension. According to the results, a decreased viability and migratory potential was observed for the miR‐143 receiving cells. The DAPI staining also confirmed the occurrence of apoptosis. Moreover, BCL‐2, K‐RAS, MMP‐9, and c‐MYC mRNAs were significantly downregulated in the miR‐143 grafted cells. The BAX/BCL‐2 ratio also indicated a notable increase in the cells with miR‐143 overexpression. In brief, miR‐143 replacement could be considered as an effective strategy for the management of CRC and attenuating its invasive features. [ABSTRACT FROM AUTHOR]

Renal transplantation is the best therapeutic approach for end stage renal dysfunction patients. There are direct relationships between proportions of Treg cells, Treg/Th17 cells ratio and secreted immunosuppressive cytokines with increased survival rate of the transplanted organ. The aim of this study was the measurement of Treg and Th17 cells frequency and their secreted cytokines. Ninety renal‐transplanted patients were divided in three groups based on times after transplantation (1–6 month, 6–36 month, and more than 3 years). Treg and Th17 cells frequency, expression level of their transcription factors and cytokines, and their secreted cytokines level were measured in these groups. Higher expression level of Interleukin (IL)‐10 and FoxP3 mRNA were observed in patients who had longer posttransplantation time. In contrast, lower mRNA expressions of IL‐6, IL‐17, IL‐23, and TGF‐β were observed in this group. Receptor γt showed no significant changes in studied groups. In addition IL‐10 level was increased and IL‐6, IL‐17, IL‐23, and TGF‐β level were decreased in patients who had longer posttransplantation time. Treg cells frequency was raised in mentioned group whereas no remarkable changes were observed in Th17 cell frequency. The present study declared that in stable renal transplantation, over time, the percentage of Treg cells and Treg/Th17 ration is increased. This increase in ratio induces a change in cytokine profile, resulting in an increased immunosuppressive cytokines such as IL‐10 leading to increase in the survival rate of the transplanted organ. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is a one of the most common obstetrical complications. Since, the successful pregnancy occurs in T helper 2 (Th2)‐dominant situation and since, Th1 type immunity is related to pregnancy failure, we investigated the effects of cyclosporine on Th1 and Th2 cells in RPL women. Totally, 76 RPL patients (38 women as treated group and 38 as control group) were included in this study. Flow cytometry was utilized to analyze the frequency of Th1 and Th2 in blood samples. Also, real‐time polymerase chain reaction was carried out to assess the messenger RNA (mRNA) expression of transcription factors and enzyme‐linked immunosorbent assay was used to evaluate Th1 and Th2 related cytokines. Significant decrease in Th1 frequency (p = 0.0004), Th1/Th2 ratio (p < 0.0001), T‐bet mRNA expression (p < 0.0001), interferon‐γ (p = 0.0007), and tumor necrosis factor α (p = 0.0002) secretion level were observed in cyclosporine group. Moreover, significant increase in Th2 frequency (p < 0.0001), mRNA expression of GATA binding protein 3 (p = 0.0001), and interleukin 10 secretion level (p = 0.0027) was also evident in treated group. At the end of the investigation, 31 (81.5%) patients in cyclosporine‐treated group had successful childbirth when compared with 16 (42.1%) women in control group (p = 0.0001). Given this, cyclosporine treatment for RPL patients with elevated Th1/Th2 ratio can result in improved pregnancy outcome. [ABSTRACT FROM AUTHOR]

Hemoderivative materials are used to treat different diseases. These derivatives include platelet‐rich plasma, serum, platelet gel, and platelet lysate (PL). Among them, PL contains more growth factors than the others and its production is inexpensive and easy. PL is one of the proper sources of platelet release factors. It is used in cells growth and proliferation and is a good alternative to fetal bovine serum. In recent years, the clinical use of PL has gained more appeal by scientists. PL is a solution saturated by growth factors, proteins, cytokines, and chemokines and is administered to treat different diseases such as wound healing, bone regeneration, alopecia, oral mucositis, radicular pain, osteoarthritis, and ocular diseases. In addition, it can be used in cell culture for cell therapy and tissue transplantation purposes. Platelet‐derived growth factor, fibroblast growth factor, insulin‐like growth factor, transforming growth factor β, and vascular endothelial growth factor are key PL growth factors playing a major role in cell proliferation, wound healing, and angiogenesis. In this paper, we scrutinized recent advances in using PL and PL‐derived growth factors to treat diseases and in regenerative medicine, and the ability to replace PL with other hemoderivative materials. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a disorder affecting 2–10% of pregnancies and has a major role for perinatal and maternal mortality and morbidity. PE can be occurred by initiation of new hypertension combined with proteinuria after 20 weeks gestation, as well as various reasons such as inflammatory cytokines, poor trophoblast invasion can be related with PE disease. Environmental factors can cause epigenetic changes including DNA methylation, microRNAs (miRNAs), and histone modification that may be related to different diseases such as PE. Abnormal DNA methylation during placentation is the most important epigenetic factor correlated with PE. Moreover, changes in histone modification like acetylation and also the effect of overregulation or low regulation of miRNAs or long noncoding RNAs on variety signaling pathways can be resulted in PE. The aim of this review is to describe of studies about epigenetic changes in PE and its therapeutic strategies. [ABSTRACT FROM AUTHOR]

The liver has remarkable regeneration potency that restores liver mass and sustains body hemostasis. Liver regeneration through signaling pathways following resection or moderate damages are well studied. Various cell signaling, growth factors, cytokines, receptors, and cell types implicated in liver regeneration undergo controlled hypertrophy and proliferation. Some aspects of liver regeneration have been discovered and many investigations have been carried out to identify its mechanisms. However, for optimizing liver regeneration more should be understood about mechanisms that control the growth of hepatocytes and other liver cell types in adults. The current paper deals with the possible applicability of liver regeneration signaling pathways as a target for therapeutic approaches and preventing various liver damages. Furthermore, the latest findings of spectrum‐specific signaling pathway mechanisms that underlie liver regeneration are briefly described. [ABSTRACT FROM AUTHOR]

Mitogen‐activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal‐regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is a member of the evolutionary phosphatidylinositol kinase‐related kinases (PIKKs). mTOR plays a pivotal role in the regulation of diverse aspects of cellular physiology such as body metabolism, cell growth, protein synthesis, cell size, autophagy, and cell differentiation. Immunologically, mTOR has a fundamental part in controlling and shaping diverse functions of innate and adaptive immune cells, in particular, T‐cell subsets differentiation, survival, and metabolic reprogramming to ultimately regulate the fate of diverse immune cell types. Researchers report that rapamycin, a selective mTOR inhibitor, and immunosuppressive agent, has surprising immunostimulatory effects on inducing both quantitative and qualitative aspects of virus‐specific memory CD8+ T‐cells differentiation and homeostasis in a T‐cell‐intrinsic manner. The mTOR signaling pathway also plays a critical role in dictating the outcome of regulatory T cells (Treg), T helper 17 (Th17) cells, and natural killer (NK) cells proliferation and maturation, as well as the effector functions and cytotoxic properties of NK cells. Manipulation of mTOR activity is a critical therapeutic approach for pharmacological agents that seek to inhibit mTOR. This approach should enhance specific memory CD8 + T‐cells responses and induce fully functional effector properties of NK cells to provoke their antitumor and antiviral activities. [ABSTRACT FROM AUTHOR]

Clustered regularly interspaced short palindromic repeats/CRISPR‐associated nuclease 9 (CRISPR‐Cas9) is an RNA‐guided gene editing tool which offers several advantageous characteristics in comparison with the conventional methods (e.g., zinc finger nucleases and transcription activator‐like effector nucleases) such as cost‐effectiveness, flexibility, and being easy‐to‐use. Despite some limitations such as efficient delivery and safety, CRISPR‐Cas9 is still the most convenient tool for gene editing purposes. Due to the potential capability of the CRISPR‐Cas9 system in genome editing and correction of casual mutations, it can be considered as a possible therapeutic system in the treatment of disorders associated with the genome mutations and in particular cancer treatment. In this review, we will discuss CRISPR‐Cas‐based gene editing along with its classifications and mechanism of action. Furthermore, the therapeutic application of the CRISPR‐Cas9 system in mutational disorders, delivery systems, as well as its advantages and limitations with a special emphasis on cancer treatment will be discussed. [ABSTRACT FROM AUTHOR]

Background: Despite at the beginning known as a benign disease, endometriosis is defined as a risk factor for developing ovarian carcinoma. The effect of endometriosis on ovarian malignancy is known but its role in granulosa cell tumor is still unclear. Methods and Materials: In this study, serum samples were collected from patients with endometriosis and divided into whole and steroid‐depleted groups. Desertification was performed according to the charcoal–dextran protocol and sera were added to the culture media of granulosa cells retrieved from tubal or male factor infertile women. Quantitative real‐time polymerase chain reaction and flow cytometry were performed to determine the expression level of inflammatory and apoptotic genes and apoptosis level of granulosa cells. The total concentration of lipid was measured using gas chromatography method in the granulosa cells. Results: Results revealed that the expression of AKT and NF‐κB/RelA gene was significantly higher in the granulosa cells treated with steroid‐depleted serum obtained from patients with distrificated endometriosis (DE) compared with the control group (9.39‐ and 7.9‐folds, respectively; p < 0.0001). In the DE group, the declined pattern of expression was observed for the genes related to apoptosis. The synthesis of saturated fatty acids was significantly decreased; however, unsaturated fatty acids showed increased levels in the DE group. Conclusion: The effect of steroids on endometriosis is contradictory. The level of cortisol and sex hormones could be affected by endometriosis, causing alterations of the disease progression. Reduced level of steroid hormones in patients with endometriosis may be considered as a critical risk factor for granulosa cell tumor. [ABSTRACT FROM AUTHOR]

A 60‐year‐old man was referred to hospital for loss of consciousness. Her late‐onset Wilson disease was diagnosed with elevated serum bilirubin, hepatic copper concentration, and urinary copper excretion. Zinc sulfate administration decreased the majority of clinical symptoms. [ABSTRACT FROM AUTHOR]

Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side‐effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long‐standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell‐based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell‐based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell‐based strategy in osteoporosis. Stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell‐based therapy for osteoporosis has suggested substantial attention over the years, no clinical trial has been published in humans. The cell studies on the basis of osteoporosis are primarily attentive on osteoclastic activity and bone resorption procedures; at that point on osteoblastogenesis, and in recent times on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell‐based strategy in osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Recurrent miscarriage (RM) has a multifactorial etiology mainly due to chromosomal abnormalities and immunological factors. Treating RM has remained to be a challenging issue and the role of intravenous immunoglobulin (IVIG) in treating RM is still controversial. Materials and Methods: This study aimed to evaluate the changes in natural killer (NK) cells' frequency and cytotoxicity in patients with RM who received the IVIG therapy. A total of 78 women with a history of three or more recurrent miscarriages were included and their peripheral blood was drawn in case of positive pregnancy test. On the same date, 400 mg/kg of IVIG was administrated intravenously in 38 women and it continued every four weeks through weeks 30–32 of gestation. The remaining 40 patients with RM were included to be the untreated control group. Then, the effects of IVIG on NK cell frequency, cytotoxic activity, and the expression of inhibitory and activating receptors in the patients with RM, pre and posttreatment were assessed. Results: NK cells percentage and cytotoxicity were significantly reduced in the IVIG‐treated patients after 32 weeks of gestation (p < 0.0001). Expression levels of inhibitory receptors was increased, however, the expression levels of activating receptors were significantly decreased after the IVIG therapy. Pregnancy outcome after the treatment was significantly higher (86.8%) in the IVIG‐treated patients than controls (45%; p = 0.0006). Conclusion: Our results suggested that women with RM may benefit from IVIG as a therapeutic approach and the frequency and functional status of peripheral NK cells may serve as a valuable predictive factor of therapy response. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) is a phenomenon in which epithelial cells lose their cell‐to‐cell connection and are detached from the base membrane. EMT is fundamental for many biological processes such as embryonic development and neurogenesis. It also plays a significant role in cancer progression and metastasis. EMT regulation occurs through a sophisticated network of transcription regulations that include many signaling pathways. The exact mechanism of cancer gene regulation has not been understood yet. However, it is interesting to study the role of microRNAs and epigenetics mechanism in the cancer development. In this review, the transcription regulation of EMT and the analysis of possible overlap between microRNAs and their targets which are involved in the cancer development are scrutinized. In nature, MT participates in many physiological and pathological processes including embryonic development, organogenesis, wound healing, and cancer metastasis. Many aspects regulate EMT including: transcription factors, gene expression patterns, and signaling pathway crosstalk. MicroRNAs as noncoding genes play a distinct role in the progression or suppression of EMT. [ABSTRACT FROM AUTHOR]

Problem: Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17 (Th17)/regulatory T (Treg) cells is thought to play considerable roles in preeclampsia (PE). To investigate the probable effects of the adaptive immune system in the pathophysiology of PE, we analyzed the dynamic changes of Th17/Treg cells, cytokines profile, and transcription pattern of Th17/Treg‐related genes and microRNAs (miRNAs) in 50 women suffering from PE in comparison with 50 healthy pregnant women. Methods: Expressions of cytokines, specific transcription factors, and related miRNAs were measured by real‐time polymerase chain reaction (PCR). Enzyme‐linked immunosorbent assay (ELISA) was used to test the interleukin (IL)‐17, IL‐23, IL‐6, and IL‐10 and transforming growth factor β in serum and supernatant of peripheral blood mononuclear cells (PBMCs). The frequency of Th17 and Treg cells were determined by flow cytometry. Results: PE patients exhibited a decreased number of Treg cells (p = 0.006), while Th17 cells were increased (p = 0.004). Forkhead box P3 and IL‐10 mRNA expressions were reduced (p = 0.0001 and 0.0028, respectively), while expressions of retinoic acid receptor‐related orphan nuclear receptor γt, IL‐17, IL‐23, and IL‐6 were enhanced (p < 0.0001, 0.0018, 0.0014, and 0.027, respectively). ELISA results also showed increased levels of IL‐6, IL‐17, and IL‐23 (p = 0.022, 0.0005, 0.0081, respectively), and decreased levels of IL‐10 in the supernatant of PBMCs of PE patients compared with control group (p = 0.0011). There was significant upregulation of miR‐106b and miR‐326 (p = 0.0048 and 0.028, respectively) in PE patients in comparison with the control group. Conclusions: These findings suggest that imbalance of Th17/Treg cells, regulated possibly via microRNAs, may be involved in the pathogenesis of PE, emphasizing on the importance of these cells in feto‐maternal immune cross‐talk. Inappropriate activation of the immune system, particularly the imbalance of T‐helper type 17/regulatory T cells is thought to play considerable roles in preeclampsia. [ABSTRACT FROM AUTHOR]

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet's disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real‐time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme‐linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)‐10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL‐17, IL‐23, and retinoic acid‐related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17‐associated cytokines in the supernatant was found to be elevated in BD patients. T‐cell‐associated miRNA expression levels, miR‐25, miR‐106b, miR‐326, and miR‐93 were significantly upregulated, while miR‐146a and miR‐155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) is a multifactorial disorder of women in reproductive age, which in some cases is caused by immunologic abnormalities. In this study, we aimed to evaluate cellular and molecular components of the immune system like different T‐cell subsets and their regulating microRNAs (miRNAs) in RPL women and control group. Fifty RPL and 50 healthy subjects were recruited. Subsets of T cells, including regulatory T (Treg) cells, helper T (Th) 17 cells, exhausted T cells, exhausted Treg cells were evaluated by flow cytometry. Transcription factors of T cells and related miRNA profile were quantified using real‐time polymerase chain reaction (RT‐PCR). Assessment showed that Treg and exhausted T cells, were decreased in RPL patients (p = 0.009 and 0.02, respectively), while an increase was observed in Th17 and exhausted Treg frequency (p = 0.013 and 0.0037, respectively). Messenger RNA expression level of T‐bet and IRF4 was upregulated in RPL patients (p = 0.011 and 0.0001, respectively), while Th2‐ and Treg‐related transcription factors, GATA3 and GITR, were downregulated in these patients compared with the healthy subjects (p = 0.0008 and <0.000, respectively). Treg‐associated miRNAs, the miR‐106b‐25–93 cluster, showed a higher rate in RPL patients (P = 0.007, 0.001, and 0.029, respectively), however, we observed no significant difference in the expression level of Th17‐associated miRNA, mir‐326. According to the results, we concluded that unbalanced immune responses and deregulated function of T‐cell subsets may lead to reproduction‐related failure like a miscarriage. Therefore, evaluation of immune cells and related miRNA profile may serve as prognostic biomarker for the treatment of RPL patients. Balanced immune responses are required for a successful pregnancy therefore lack of suppressor mechanisms and increased inflammatory parameters may negatively affect the pregnancy. [ABSTRACT FROM AUTHOR]

Evading immune destruction is a hallmark of cancer. Myeloid‐derived suppressor cells (MDSCs), a heterogeneous population of myeloid immune cells, are thought to foster the establishment of an immunosuppressive tumor microenvironment, but it remains unclear how. This study aims to determine the levels of circulating MDSCs and their subpopulations and test their immunosuppressive functions in patients with breast cancer (BC). We analyzed the fractions of MDSCs in freshly isolated peripheral blood mononuclear cells of patients with BC and healthy donors using flow cytometry. Circulating MDSCs were further phenotyped using fluorescently labeled antihuman monoclonal antibodies. Coculture experiments revealed the effects of MDSCs on CD3+ T cell response. Moreover, we correlated circulating MDSC levels with clinicopathological features of patients with BC. We show that the fraction of HLA‐DR – CD33 + MDSCs in peripheral blood is about 10‐fold higher in patients with BC than in healthy control individuals. The levels of all MDSC subpopulations, including monocytic and granulocytic MDSCs, are significantly elevated. Coculture experiments of purified HLA‐DR – CD33 + MDSCs and CD3 + T cells demonstrate that T cell proliferation is more effectively inhibited by BC patient‐derived MDSCs than by healthy control MDSCs. Moreover, increased circulating MDSC levels robustly associate with advanced BC stage and positive lymph node status. By being more abundant and more effective T cell suppressors, BC patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Our findings pave the way to develop novel diagnostic and immunotherapeutic strategies, aimed at detecting and inhibiting MDSCs in patients with BC. Myeloid‐derived suppressor cells (MDSCs) are thought to foster the establishment of an immunosuppressive tumor microenvironment. By being more abundant and more effective T cell suppressors, breast cancer patient‐derived circulating MDSCs exert a dual immunosuppressive effect. Moreover, increased circulating MDSC levels robustly associate with advanced breast cancer stage and positive lymph node status. [ABSTRACT FROM AUTHOR]

The cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV‐CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC‐mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer. Investigating the mechanisms by which cancer cells acquire the capability to avoid cell death upon exposure to antineoplastic agents is of great significance, currently being a hot topic in cancer research. In this study, we review the recent and growing body of evidence that supports the contribution of cancer stem cells to multidrug resistance in ovarian cancer. [ABSTRACT FROM AUTHOR]