The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19.

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.

MIR96 Has Good Potential to Differentiate Human Bone Marrow-Derived Mesenchymal Stem Cells into Photoreceptor-Like Cells.

OBJECTIVES: MicroRNAs play an important role in the development and function of neuron cells. Among these, the miRNA known as MIR96 is abundantly expressed in mammalian retina and significantly affects differentiation, maturation, and survival of human photoreceptor cells. In this study, a mimic to miRNA-96 was transfected into human bone marrowderived mesenchymal stem cells to explore the biological functions of MIR96 at differentiation processing. MATERIALS AND METHODS: A mimic to miRNA-96 and a competitive control were transfected into human bone marrow-derived mesenchymal stem cells using Lipofectamine. After 24 and 48 hours, we evaluated changes in expression levels of genes associated with neural progenitor and photoreceptor differentiation (OTX2, NRL, protein kinase C, SLC1A1, and recoverin) by real-time polymerase chain reaction. In addition, we measured expression of mRNA and protein of the CRX gene (neuroretinal progenitor cell marker) and the RHO gene (terminal differentiation marker) using real-time polymerase chain reaction and immunocytochemistry, respectively. RESULTS: Real-time polymerase chain reaction results showed increased levels of RHO and recoverin mRNA after 24 hours in transfected cells. In addition, mRNA levels of OTX2, CRX, NRL, RHO, recoverin, and protein kinase C increased after 48 hours in transfected cells. Immunocytochemistry results confirmed these findings by demonstrating RHO and CRX at both 24 and 48 hours in transfected cells. CONCLUSIONS: Control of the expression of MIR96 can be a good strategy to promote cell differentiation and can be used in cell therapy for retinal degeneration. Our results showed that human bone marrow-derived mesenchymal stem cells can differentiate into photoreceptor cells after transfection with MIR96. These results support therapeutic use of MIR96 in retinal degeneration and suggest human bone marrowderived mesenchymal stem cells as a promising tool for interventions.

The Role of Rosavin in the Pathophysiology of Bone Metabolism.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Emerging roles of HOTAIR lncRNA in the pathogenesis and prognosis of cardiovascular diseases.

Highlights HOTAIR, a long noncoding RNA, plays a role in the regulation of proteins involved in the pathogenesis of cardiovascular disease. Furthermore, it has been identified as a biomarker of this type of disease. Several factors and cells contribute to atherosclerosis, a progressive disease. However, the prognosis of HOTAIR in this disease varies depending on the path in which it plays a role. For this condition, there is no single prognosis to consider.

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant attention in the neuroscience and oncological community regarding its neuroimmunomodulatory and oncogenic functions. This review of the literature summarizes and updates contemporary knowledge about PGRN, its associated receptors and signalling pathway involvement in GBM pathogenesis, indicating possible cellular and molecular mechanisms with potential diagnostic, prognostic and therapeutic targets in order to yield successful individual therapeutic strategies. After a review of the literature, we found that there are possible PGRN-targeted therapeutic approaches for implementation in GBM treatment algorithms both in preclinical and future clinical studies. Furthermore, PGRN-targeted therapies exerted their highest efficacy in combination with other established chemotherapeutic agents, such as temozolomide. The results of the analysis suggested that the possible implementation of routine determinations of PGRN and its associated receptors in tumour tissue and biofluids could serve as a diagnostic and prognostic biomarker of GBM. Furthermore, promising preclinical applications of PGRN-related findings should be investigated in clinical studies in order to create new diagnostic and therapeutic algorithms for GBM treatment.

lncRNA TUG1 as potential novel biomarker for prognosis of cardiovascular diseases.

Globally, cardiovascular diseases (CVDs) are among the leading causes of death. In light of the high prevalence and mortality of CVDs, it is imperative to understand the molecules involved in CVD pathogenesis and the signaling pathways that they initiate. This may facilitate the development of more precise and expedient diagnostic techniques, the identification of more effective prognostic molecules and the identification of potential therapeutic targets. Numerous studies have examined the role of lncRNAs, such as TUG1, in CVD pathogenesis in recent years. According to this review article, TUG1 can be considered a biomarker for predicting the prognosis of CVD.

Considering that cardiovascular diseases (CVDs) are very common and can be fatal, we must have a method for assessing heart health and its probability of worsening in order to prevent and treat these diseases. In order to accomplish this, it is possible to look for biomarkers in bodily fluids that are indicative of CVD. The purpose of this article is to examine a molecule called TUG1, which is found in varying levels in patients suffering from CVD. There is an impact of TUG1 on the growth, death and inflammation response of heart cells. The potential application of TUG1 as a biomarker to predict the severity and progression of heart disease is therefore not surprising.

The Role of Progranulin (PGRN) in the Pathogenesis of Ischemic Stroke.

Stroke is a life-threatening medical condition and is a leading cause of disability. Cerebral ischemia is characterized by a distinct inflammatory response starting with the production of various cytokines and other inflammation-related agents. Progranulin (PGRN), a multifunctional protein, is critical in diverse physiological reactions, such as cell proliferation, inflammation, wound healing, and nervous system development. A mature PGRN is anti-inflammatory, while granulin, its derivative, conversely induces pro-inflammatory cytokine expression. PGRN is significantly involved in the brain tissue and its damage, for example, improving mood and cognitive disorders caused by cerebral ischemia. It may also have protective effects against nerve and spinal cord injuries by inhibiting neuroinflammatory response and apoptosis or it may be related to the proliferation, accumulation, differentiation, and activation of microglia. PGRN is a neurotrophic factor in the central nervous system. It may increase post-stroke neurogenesis of the subventricular zone (SVZ), which is particularly important in improving long-term brain function following cerebral ischemia. The neurogenesis enhanced via PGRN in the ischemic brain SVZ may be attributed to the induction of PI3K/AKT and MAPK/ERK signaling routes. PGRN can also promote the proliferation of neural stem/progenitor cells through PI3K/AKT signaling pathway. PGRN increases hippocampal neurogenesis, reducing anxiety and impaired spatial learning post-cerebral ischemia. PGRN alleviates cerebral ischemia/reperfusion injury by reducing endoplasmic reticulum stress and suppressing the NF-κB signaling pathway. PGRN can be introduced as a potent neuroprotective agent capable of improving post-ischemia neuronal actions, mainly by reducing and elevating the inflammatory and anti-inflammatory cytokines. Expression, storage, cleavage, and function of progranulin (PGRN) in the pathogenesis of ischemic stroke.

Late side effects of cancer treatment in childhood cancer survivors.

INTRODUCTION: Childhood cancers are usually treated with chemotherapy and radiation. Therefore, understanding the late side effects of such treatments is important to improve the quality of life in childhood cancer survivors. The present study aimed to investigate the late complications of treatments in childhood cancer survivors. METHODS: This study is a retrospective descriptive study. A total number of 93 cases were enrolled in this study. These cases had a history of childhood cancer documented in their medical records at the Shafa Hospital, Ahvaz, Iran. The age range was 5.9-21.3 years and included 62 males and 31 female patients. RESULTS: Many of the patients at this hospital with childhood cancer had experienced chemotherapy side effects as well as late effects of cancer therapy. Hypothyroidism is a late complication of therapy in thoracic cancers and head/neck tumors with relative frequencies of 23.1% and 12.5%, respectively. Scoliosis was observed in the patients undergoing the ABVD + COPP and 8/1 regimens with relative frequencies of 4% and 50%, respectively. Lower growth percentiles were also late side effects of cancer therapy. The highest relative frequency of growth retardation was observed in the <5 age group (46.7%). Restrictive lung changes had an overall relative frequency of 6.5% in male patients with all types of tumors. Sensorineural hearing loss was observed in patients with leukemia and Hodgkin lymphoma with relative frequencies of 8.7% and 24.0, respectively. CONCLUSION: The occurrence of most side effects could be decreased through early diagnosis, dose adjustment of some drugs, and preventative measures.

Long non-coding RNA signatures and related signaling pathway in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy caused by clonal proliferation of T-cell pre-cursors arising from the thymus. Although the optimized chemotherapy regimen could improve the outcome of such patients, some challenges such as higher risk for induction failure, early relapse and isolated central nervous system (CNS) relapse occurring in T-ALL patients are of great significance, leading to increased mortality rates. Long non-coding RNA (lncRNA) is a key component involved in cell signaling through a variety of mechanisms in regulating gene expression. Oncogenes and tumor suppressors are no exception and their expression can be affected by lncRNAs. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. In addition, accumulating researches in samples from T-ALL patients as well as pre-clinical studies in mice suggest that the expression profile of lncRNAs in T-ALL could be aberrant, resulting in deregulation of target genes and downstream signaling pathways. These lncRNAs may be determinants of proliferation, apoptosis, and drug resistance observed in T-ALL. Thus, lncRNAs can be a good tool to develop novel strategies against cancer cells in the treatment of relapsed and refractory T-ALL. They can also act as promoting biomarkers in assessing T-ALL and differentiating between patients with poor prognosis and good prognosis.

Association of human papillomavirus with breast cancer: a new perspective on an old debate.

Breast cancer is a common cancer in the female population. Despite remarkable progress in the treatment of this cancer, its exact etiology is still unknown. Since the first evidence of an association between breast cancer and human papillomavirus (HPV) was provided in 1992, numerous studies have explored this subject but have reached contradictory results. In this review, the authors examine the existing evidence and hypotheses regarding the pathways whereby HPV infection can reach breast cells and the mediators linking HPV oncoproteins to breast cancer pathogenesis. Furthermore, the authors discuss contradictory findings regarding the association of HPV with breast cancer. Showing the link between HPV infection and increased genomic instability, reduced apoptosis, immune system dysfunction and progression of metastasis, the reviewed findings highlight the importance of active presence or history of HPV infection as a prognostic factor for breast tumor development.

Breast cancer is a common cancer in the female population. Although the exact cause of this cancer is still unknown, it has several major risk factors including family history, hormonal problems and age. It has been suggested that various viral infections, including human papillomavirus, can increase the likelihood of developing breast cancer. This review discusses the evidence regarding the association of human papillomavirus with breast cancer.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Association between extract of Euphorbia szovitsii and expression level of microRNAs in MDA-MB-231 cell line.

BACKGROUND: The miRNAs have been shown to be involved in breast cancer. The aim of the present research was to evaluate the impacts of extract from Euphorbia szovitsii Fisch & C.A. Mey on the expression level of microRNAs in triple-negative breast cancer (MDA-MB-231) cell line. METHODS AND RESULT: The alterations in the expression level of miRNAs in MDA-MB-231 cell line exposed to the extract of E. szovitsii were determined exploiting qRT-PCR technique. The expression of MDA-MB-231 cell microRNAs including miR-15, miR-16, miR-21, miR-29, miR-34a, miR-146b, miR-151, miR-155, miR-181b, miR-221, miR-222, and Let-7 was evaluated at 24 and 48 h after treatment with the E. szovitsii extract. The treatment of MDA-MB-231 cells with E. szovitsii caused a significant elevation in the expression of miR-155, miR-146b (P < 0.05), miR-16, miR-21, miR-151 (P < 0.01), and miR-34a (P < 0.001) after 24 h, and also miR-155, Let-7 (P < 0.05), miR-15, miR-29, miR-151 (P < 0. 01), miR-146b and miR-34a (P<0.001) after 48 h. CONCLUSIONS: The qRT-PCR findings at 24 and 48 h after treatment revealed that the MDA-MB-231 cell line in the presence of E. szovitsii extract showed an alteration in the expression profile of miRNAs implicated in the induction of cell proliferation, apoptosis and migration. These results may be helpful in determining the anticancer activity of E. szovitsii in MDA-MB-231 cell line.

Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer.

Breast cancer constitute a common type of oncological disease with a highlighted mortality rate. In recent years, researchers have introduced progranulin (PGRN) as an novel potential biomarker and associated its function with higher risk factor for development of breast cancer. The present review article collects evidence on the association of PGRN with clinicopathological features and drug resistance in the patients with breast cancer. The results of this study suggested the use of routine determination of PGRN in the clinic as a reliable biomarker for screening people at high risk or as early indication of breast cancer. Targeting PGRN and its associated signaling pathways and receptors, such as sortilin (SORT1), could also cover a novel therapeutic strategy in the breast cancer.

The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial.

In this study, the therapeutic efficacy of quercetin in combination with remdesivir and favipiravir, were evaluated in severe hospitalized COVID-19 patients. Our main objective was to assess the ability of quercetin for preventing the progression of the disease into critical phase, and reducing the levels of inflammatory markers related to SARS-Cov-2 pathogenesis. Through an open-label clinical trial, 60 severe cases were randomly divided into control and intervention groups. During a 7-day period, patients in the control group received antivirals, i.e., remdesivir or favipiravir, while the intervention group was treated with 1000 mg of quercetin daily in addition to the antiviral drugs. According to the results, taking quercetin was significantly associated with partial earlier discharge and reduced serum levels of ALP, q-CRP, and LDH in the intervention group. Furthermore, although the values were in normal range, the statistical outputs showed significant increase in hemoglobin level and respiratory rate in patients who were taking quercetin. Based on our observations, quercetin is safe and effective in lowering the serum levels of ALP, q-CRP, and LDH as critical markers involved in COVID-19 severity. However, according to the non-significant borderline results in comparing the mortality, the ICU-admission rate, and the duration of ICU-admission, further studies can be helpful to compensate the limitations of our study and clarify the therapeutic potential of quercetin in COVID-19 treatments.

Radiographic Features of the Maxillofacial Anomalies in Beta-Thalassemia Major: With New View.

BACKGROUND: Beta- thalassemia major causes the basic skeletal changes due to ineffective erythropoiesis in suffering patients. The aim of the study was to determine the frequency of maxillo-facial anomalies and the hemoglobin and ferritin levels in patients with beta-thalassemia major compared to the healthy control group. METHODS: The present study was performed on 72 beta- thalassemia major patients and 70 healthy control group in Ahvaz, Southwest Iran, from Jan 2014 to Mar 2015. Panoramic radiographs were taken using a standard procedure. The frequency of abnormalities including enlargement of bone marrow spaces, small maxillary sinuses, thickness of inferior mandibular cortex, prominent antegonial notch, absence of inferior alveolar canal and thin lamina dura, were determined by two Oral and Maxillofacial Radiologist. We also paid to identification of the relationship between abnormalities frequency and hemoglobin and ferritin levels during previous 6 months in thalassemia patients. RESULTS: The mean age of case and control groups was 18.6±7.25 and 17 ± 6. 55 yr, respectively. The frequency of abnormalities in the case and control groups was as follows, enlargement of bone marrow spaces [69 (95.8%) vs 3 (4.3%)], small maxillary sinuses [45 (62.5%) vs 1(1.4%)], reduced thickness of inferior mandibular cortex [21(29.2%) vs 6 (8.6%)], prominent antegonial notch [10 (13.9%) vs 2 (2.9%)], absence of inferior alveolar canal [68(94.4%) vs 41(58.6%)] and thin lamina dura [40 (55.6%) vs 5 (7.1%)]. CONCLUSION: The all above mentioned abnormalities in patients with beta-thalassemia major was higher than the control group. Moreover, the frequency of maxillo-facial abnormalities decreased by increasing hemoglobin and decreasing ferritin.

miRNA-223 as a regulator of inflammation and NLRP3 inflammasome, the main fragments in the puzzle of immunopathogenesis of different inflammatory diseases and COVID-19.

Millions of people around the world are involved with COVID-19 due to infection with SARS-CoV-2. Virological features of SARS-CoV-2, including its genomic sequence, have been identified but the mechanisms governing COVID-19 immunopathogenesis have remained uncertain. miR-223 is a hematopoietic cell-derived miRNA that is implicated in regulating monocyte-macrophage differentiation, neutrophil recruitment, and pro-inflammatory responses. The miR-223 controls inflammation by targeting a variety of factors, including TRAF6, IKKα, HSP-70, FOXO1, TLR4, PI3K/AKT, PARP-1, HDAC2, ITGB3, CXCL2, CCL3, IL-6, IFN-I, STMN1, IL-1ß, IL-18, Caspase-1, NF-κB, and NLRP3. The key role of miR-223 in regulating the inflammatory process and its antioxidant and antiviral role can suggest this miRNA as a potential regulatory factor in the process of COVID-19 immunopathogenesis.

Genetic variants and risk of thyroid cancer among Iranian patients.

The definition of an exclusive panel of genetic markers is of high importance to initially detect among this review population. Therefore, we gave a summary of each main genetic marker among Iranian patients with thyroid cancer for the first time which were classified based on their cellular function. Due to the results, a significant relationship was found between SNP in codons 194, 280, and 399 (XRCC1), Allele 3434Thr (XRCC7), GC or CC genotype 31, G/C (Survivin), 399G>A (XRCC1), Tru9I (vitamin D receptor), G-D haplotype (MDM2), TT genotype, -656 G/T (IL-18), TAGTT haplotype (IL-18), G allele in +49 A>G (CTLA-4), +7146 G/A (PD-1.3), +7785 C/T (PD-1.5), rs1143770 (let7a-2), rs4938723 (pri-mir-34b/c) genes, and thyroid cancers. Moreover, SNP in 677C-->T (MTHFR), GG genotype Asp1312Gly (thyroglobulin), 2259C>T (Rad52), R188H, (XRCC2), T241M (XRCC3) had higher risks of thyroid cancer and lower risks were observed in -16 Ins-Pro (p53), rs3742330 (DICER1). At last, the protective effects were explored in 127 CC genotype (IL-18), rs6877842 (DROSHA). Conduct further studies on the types of DNA repair gene polymorphisms with a larger number in the thyroid cancer using modern methods such as SNP array so that these genes could be used as a biomarker in prediction, diagnosis, and treatment of thyroid cancer. This review presents for the first time a summary of important genetic markers in Iranian patients with thyroid cancer.

Polymorphisms in genes involved in breast cancer among Iranian patients.

This review gives a summary of the important genetic polymorphisms in breast cancer with a focus on people in Iran. Several single nucleotide polymorphisms were considered as breast cancer susceptibility polymorphisms within genes (STK15, ERRs, ESR1, p53, SEP15, AURKA, SHBG, SRC, FAS, VEGF, XRCC1, GST, NFκB1, XPC, XRCC3, sirtuin-3, NKG2D). Cytosine-adenine repeat (IGF-I), rs3877899, G-2548A, GGC (eRF3a/GSPT1), IVS2nt-124A/G have shown an increased risk of breast cancers and a decreased risk has been observed in 4G/5G (PAI-1), rs6505162, tri-nucleotide (GCG TGFBR1). We observed that the signaling pathways and antioxidant related genes are the main molecular processes associated with breast cancer progression. Further studies on types of polymorphisms in breast cancer could validate the prognostic value of biomarkers.

Genetic polymorphisms associated with polycystic ovary syndrome among Iranian women.

Polycystic ovary syndrome (PCOS) involves abnormalities in ovarian, reproductive, and metabolic systems. Genetic polymorphisms associated with individual differences and variations might be related to complex disorders with unknown causes, including PCOS. Several leading genetic markers with known cellular functions have been identified among Iranian women presenting with PCOS. In particular, the existing evidence shows a significant relationship between PCOS and the following genetic polymorphisms: rs2275913 (interleukin-17A), rs9927163 (interleukin-32), Pro12Ala (peroxisome proliferator-activated receptor-γ), rs17173608 (chemerin), rs2236242 (vaspin), ApaI (vitamin D receptor), and rs7895833 (sirtuin 1). In addition, a higher risk of PCOS is associated with the rs2910164 (microRNA 146a), rs2241766 (adiponectin), -34 T/C (cytochrome 17), and rs1800682 (Fas) polymorphisms. Furthermore, protective effects against PCOS have been reported for the A4223C polymorphism of adenosine deaminase 1. Overall, the available data indicate that Iranian women with PCOS have a higher prevalence of polymorphisms in inflammation- and metabolism-related genes, but not in insulin-related genes. More extensive studies are needed to identify the ethnicity-related genetic associations in PCOS.