Prostate cancer: Novel genetic and immunologic biomarkers.

Prostate cancer (PCa) is considered one of the most prevalent male malignancies worldwide with a global burden estimated to increase over the next two decades. Due to significant mortality and debilitation of survival, early diagnosis has been described as key. Unfortunately, current diagnostic serum-based strategies have low specificity and sensitivity. Histologic examination is invasive and not useful for treatment and monitoring purposes. Hence, a plethora of studies have been conducted to identify and validate an efficient noninvasive approach in the diagnosis, staging, and prognosis of PCa. These investigations may be categorized as genetic (non-coding biomarkers and gene markers), immunologic (immune cells, interleukins, cytokines, antibodies, and auto-antibodies), and heterogenous (PSA-related markers, PHI-related indices, and urinary biomarkers) subgroups. This review examines current approaches and potential strategies using biomarker panels in PCa.

Omics-based novel strategies in the diagnosis of endometriosis.

Endometriosis, an enigmatic and chronic disorder, is considered a debilitating condition despite being benign. Globally, this gynecologic disorder affects up to 10% of females of reproductive age, impacting almost 190 million individuals. A variety of genetic and environmental factors are involved in endometriosis development, hence the pathophysiology and etiology of endometriosis remain unclear. The uncertainty of the etiology of the disease and its complexity along with nonspecific symptoms have led to misdiagnosis or lack of diagnosis of affected people. Biopsy and laparoscopy are referred to as the gold standard for endometriosis diagnosis. However, the invasiveness of the procedure, the unnecessary operation in disease-free women, and the dependence of the reliability of diagnosis on experience in this area are considered the most significant limitations. Therefore, continuous studies have attempted to offer a noninvasive and reliable approach. The recent advances in modern technologies have led to the generation of large-scale biological data sets, known as -omics data, resulting in the proceeding of the -omics century in biomedical sciences. Thereby, the present study critically reviews novel and noninvasive biomarkers that are based on -omics approaches from 2020 onward. The findings reveal that biomarkers identified based on genomics, epigenomics, transcriptomics, proteomics, and metabolomics are potentially able to diagnose endometriosis, predict prognosis, and stage patients, and potentially, in the near future, a multi-panel of these biomarkers will generate clinical benefits.

The constructive and destructive impact of autophagy on both genders' reproducibility, a comprehensive review.

Reproduction is characterized by a series of massive renovations at molecular, cellular, and tissue levels. Recent studies have strongly tended to reveal the involvement of basic molecular pathways such as autophagy, a highly conserved eukaryotic cellular recycling, during reproductive processes. This review comprehensively describes the current knowledge, updated to September 2022, of autophagy contribution during reproductive processes in males including spermatogenesis, sperm motility and viability, and male sex hormones and females including germ cells and oocytes viability, ovulation, implantation, fertilization, and female sex hormones. Furthermore, the consequences of disruption in autophagic flux on the reproductive disorders including oligospermia, azoospermia, asthenozoospermia, teratozoospermia, globozoospermia, premature ovarian insufficiency, polycystic ovarian syndrome, endometriosis, and other disorders related to infertility are discussed as well.Abbreviations: AKT/protein kinase B: AKT serine/threonine kinase; AMPK: AMP-activated protein kinase; ATG: autophagy related; E2: estrogen; EDs: endocrine disruptors; ER: endoplasmic reticulum; FSH: follicle stimulating hormone; FOX: forkhead box; GCs: granulosa cells; HIF: hypoxia inducible factor; IVF: in vitro fertilization; IVM: in vitro maturation; LCs: Leydig cells; LDs: lipid droplets; LH: luteinizing hormone; LRWD1: leucine rich repeats and WD repeat domain containing 1; MAP1LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; NFKB/NF-kB: nuclear factor kappa B; P4: progesterone; PCOS: polycystic ovarian syndrome; PDLIM1: PDZ and LIM domain 1; PI3K: phosphoinositide 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns3K: class III phosphatidylinositol 3-kinase; POI: premature ovarian insufficiency; ROS: reactive oxygen species; SCs: Sertoli cells; SQSTM1/p62: sequestosome 1; TSGA10: testis specific 10; TST: testosterone; VCP: vasolin containing protein.

Non-invasive diagnosis of endometriosis: Immunologic and genetic markers.

Endometriosis, a benign gynecologic and chronic inflammatory disease, is defined by the presence of endometrial tissue outside the uterus characterized mainly by pelvic pain and infertility. Because endometriosis affects approximately 10% of females, it represents a significant socioeconomic burden worldwide having tremendous impact on daily quality of life. Accurate and prompt diagnosis is crucial for the management of this debilitating disorder. Unfortunately, diagnosis is typically delayed to lack of specific symptoms and readily accessible biomarkers. Although histopathologic examination remains the current gold standard, this approach is highly invasive and not applicable for early screening. Recent work has focused on the identification of reliable biomarkers including immunologic, ie, immune cells, antibodies and cytokines, as well as genetic and biochemical markers, ie, microRNAs, lncRNAs, circulating and mitochondrial nucleic acids, along with some hormones, glycoproteins and signaling molecules. Confirmatory research studies are, however, needed to more fully establish these markers in the diagnosis, progression and staging of these endometrial lesions.

Clinical significance of IL-37 serum level and polymorphism in patients with endometrial cancer.

Endometrial cancer (EC) is recognized as the second most common type of cancer among women. Interleukin-37 (IL-37) is a recently discovered member of the IL-1 cytokine family characterized by its anti-inflammatory properties, which are believed to have both anti-tumour and tumorigenic effects. However, the precise role of IL-37 in the development of EC remains largely unknown. In the current study, we aimed to explore genotype and allele frequencies of the IL-37 gene (rs4241122) and measure IL-37 protein levels in patients with EC, with a view to determining the clinical significance in these patients. A total of 105 patients with confirmed EC and 105 healthy controls, aged 31-73, participated in the study. IL-37 serum levels were investigated using an ELISA method, while the frequency of genotypes and alleles of the IL-37 gene was determined using the ARMS-PCR method. The findings demonstrate a significant increase in IL-37 serum levels in EC patients compared to controls (p<0.0001). Moreover, higher levels of IL-37 were strongly associated with unfavourable indices, such as EC grade III, poorly differentiated tumours, and regional spread of tumour cells (p<0.05). However, genotyping of the IL-37 gene revealed no significant difference between the two groups, and there was no association between IL-37 genotype and IL-37 protein level or clinicopathological characteristics (p>0.05). The results of this study suggest that elevated serum levels of may contribute to tumour progression, probably through its immune suppressive activity. Clinically, IL-37 may serve as a promising factor and/or therapeutic target for EC management, although, further studies are warranted.

Comparison of nutritional supplements for glycemic control in type 2 diabetes: A systematic review and network meta-analysis of randomized trials.

AIMS: Direct and indirect evidence were combined in this systematic-review and network meta-analysis (NMA) to assess and compare the effect of nutritional supplements on glycemic control, and rank the supplements accordingly. METHODS: PubMed, Scopus, and Web of Science were searched up to April 2021. We included randomized controlled trials that investigated the effect of vitamins D, C, and E, magnesium, zinc, calcium, selenium, and omega-3 on at least one glycemic marker, including glycated hemoglobin (HbA1c), fasting blood sugar (FBS), homeostasis model assessment-estimated insulin resistance (HOMA-IR), HOMA-B, and insulin, in adults with type 2 diabetes. To estimate effectiveness of supplements, a random-effects NMA in the Bayesian framework was applied. To assess risk of bias, Cochrane Collaboration Tool was used. RESULTS: Analysis of 178 studies indicated that zinc, vitamin D, omega-3, vitamin C, and vitamin E were effective in reducing HbA1c with low certainty. For reduction of FBS, zinc, vitamin D, and vitamin C, and for HOMA-IR, vitamin D were effective with low certainty. None of the supplements were effective in the reduction of insulin and HOMA-B with low certainty. After excluding poor-quality studies, only vitamin D was significantly effective in reducing all of the markers. Consistently, when the analysis was restricted to studies with a duration of ≥12-weeks, vitamin D reduced HbA1c, FBS, and HOMA-IR. CONCLUSIONS: Vitamin D supplementation was more effective compared to other supplements in improving HbA1c, FBS, and HOMA-IR, albeit with low certainty of evidence. This result was confirmed by low-risk of bias studies. REGISTRATION: CRD42021240691.

Design of a new multi-epitope peptide vaccine for non-small cell Lung cancer via vaccinology methods: an in silico study.

Lung cancer is the most common type of tumor worldwide. Non-small-cell lung carcinoma (NSCLC) is considered any epithelial cell-related lung cancer, which includes more than 85% of all lung cancer cases. NSCLC is less responsive to chemotherapy than SCLC. Therefore, the need for other treatments has become more pronounced and immunotherapy has gained increasing attention as a promising therapy in recent years. The current study aimed to design a multi-epitope peptide vaccine targeting main cancer/testis antigens of SP17, AKAP4, and PTTG1, which have a major function in tumor cell proliferation invasion. The protein vaccine was constructed using the rigorous immunoinformatics analysis and investigation of several immune system parameters, considering B cell epitopes and CD4 and CD8 induced epitopes as the most important cells to respond to cancer cells. Inverse translation and optimization of codons were performed to have the designed protein's cloning as well as expression potential in E.coli. Physicochemical, antigenic, and allergenic features were assessed to confirm the safety and immunogenicity of the vaccine. The secondary and tertiary structures were predicted. Finally, intrinsic disorder and 3D model refinement and validation were performed to eliminate structural problems. The designed construct had a stable structure that could be an antigen and stimulate the immune system and not be an allergen. The built model 3D structure was valid and stable. Further investigations are needed to approve the safety and immunogenic property of this new vaccine for NSCLC before it can be used in patients.

Gastrointestinal disorder biomarkers.

Gastrointestinal (GI) disorders refer to gastrointestinal tract conditions, ranging from dyspepsia to inflammatory bowel diseases (IBDs) and malignant tumors. Biomarkers, which are assessable indicators of the presence or severity of the disorders, are indispensable agents to diagnose GI conditions. Diagnostic biomarkers, including serological biomarkers, antibodies, immunological biomarkers, fecal biomarkers, and genetic biomarkers (Non-encoding RNAs), are investigated and categorized in this review. Furthermore, we have discussed the essential biological functions and diagnostic roles and the advantages and disadvantages of these biomarkers, besides novel genetic biomarkers such as miRNA-146a and their role in GI diseases.

Medicinal plant compounds as promising inhibitors of coronavirus (COVID-19) main protease: an in silico study.

The novel Coronavirus (COVID-19) has spread rapidly across the globe and has involved more than 215 countries and territories. Due to a lack of effective therapy or vaccine, urgent and concerted efforts are needed to identify therapeutic targets and medications. COVID-19 main protease represents a major target for drug treatment to inhibit viral function. The present study sought to evaluate medicinal plant compounds as potential inhibitors of the COVID-19 main protease using molecular docking and molecular dynamic analysis. The PDB files of COVID-19 main protease and some medicinal plant compounds were retrieved from the Protein Data Bank (http://www.rcsb.org) and Pubchem server, respectively. The Gromacs software was used for simulation studies, and molecular docking analysis was done using Autodock 4.2. The COVID-19 main protease simulation, compared with some phytochemicals docked to the COVID-19 main protease, were analyzed. Glabridin, catechin, and fisetin had the greatest tendency to interact with the COVID-19 main protease by hydrogen and hydrophobic interactions. Docking of these phytochemicals to COVID-19 main protease led to an increase in the radius of gyration (Rg), decrease in the Root mean square fluctuation (RMSF), and induced variation in COVID-19 main protease secondary structure. The high tendency interaction of glabridin, catechin, and fisetin to COVID-19 main protease induced conformational changes on this enzyme. These interactions can lead to enzyme inhibition. This simulated study indicates that these phytochemicals may be considered as potent inhibitors of the viral protease; however, more investigations are required to explore their potential medicinal use.Communicated by Ramaswamy H. Sarma.

Effects of Urtica dioica on Metabolic Profiles in Type 2 Diabetes: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: Several studies have investigated the effect of Urtica dioica (UD) consumption on metabolic profiles in patients with type 2 diabetes mellitus (T2DM); however, the findings are inconsistent. This systematic review and meta-analysis of clinical trials were performed to summarize the evidence of the effects of UD consumption on metabolic profiles in patients with T2DM. METHODS: Eligible studies were retrieved from searches of PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Google Scholar databases until December 2019. Cochran (Q) and I-square statistics were used to examine heterogeneity across included clinical trials. Data were pooled using a fixed-effect or random-effects model and expressed as weighted mean difference (WMD) and 95% confidence interval (CI). RESULTS: Among 1485 citations, thirteen clinical trials were found to be eligible for the current metaanalysis. UD consumption significantly decreased levels of fasting blood glucose (FBG) (WMD = - 17.17 mg/dl, 95% CI: -26.60, -7.73, I2 = 93.2%), hemoglobin A1c (HbA1c) (WMD = -0.93, 95% CI: - 1.66, -0.17, I2 = 75.0%), C-reactive protein (CRP) (WMD = -1.09 mg/dl, 95% CI: -1.64, -0.53, I2 = 0.0%), triglycerides (WMD = -26.94 mg/dl, 95 % CI = [-52.07, -1.82], P = 0.03, I2 = 90.0%), systolic blood pressure (SBP) (WMD = -5.03 mmHg, 95% CI = -8.15, -1.91, I2 = 0.0%) in comparison to the control groups. UD consumption did not significantly change serum levels of insulin (WMD = 1.07 µU/ml, 95% CI: -1.59, 3.73, I2 = 63.5%), total-cholesterol (WMD = -6.39 mg/dl, 95% CI: -13.84, 1.05, I2 = 0.0%), LDL-cholesterol (LDL-C) (WMD = -1.30 mg/dl, 95% CI: -9.95, 7.35, I2 = 66.1%), HDL-cholesterol (HDL-C) (WMD = 6.95 mg/dl, 95% CI: -0.14, 14.03, I2 = 95.4%), body max index (BMI) (WMD = -0.16 kg/m2, 95% CI: -1.77, 1.44, I2 = 0.0%), and diastolic blood pressure (DBP) (WMD = -1.35 mmHg, 95% CI: -2.86, 0.17, I2= 0.0%) among patients with T2DM. CONCLUSION: UD consumption may result in an improvement in levels of FBS, HbA1c, CRP, triglycerides, and SBP, but did not affect levels of insulin, total-, LDL-, and HDL-cholesterol, BMI, and DBP in patients with T2DM.

Antioxidant ameliorative effect of caffeic acid on the ectopic endometrial cells separated from patients with endometriosis.

OBJECTIVE: Considering the role of oxidative stress in the development and progression of endometriosis, the ameliorative effect of caffeic acid treatment on ectopic, eutopic endometrial cells enzyme activities was investigated. We also determined the underlying cellular mechanisms. MATERIALS AND METHODS: Ectopic endometrial specimens were collected from women with confirmed cases of endometriosis (n = 10) and eutopic specimens from (n = 10) controls. Following endometrial cell isolation and culture, eutopic and ectopic endometrial cells were treated with caffeic acid. Then, reactive oxygen species (ROS) level, NAD(P)H quinone oxidoreductase 1 (NQO1), and Heme oxygenase 1 (HO-1) enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf-2) gene expression were measured. RESULTS: In ectopic endometrial cells, caffeic acid caused a significant elevation in Nrf-2 gene expression level, NQO1, and HO-1 enzyme activities. In addition, reduced ROS level was observed in caffeic acid-treated ectopic endometrial cells in comparison with the control. On the contrary, we did not observe any significant changes in caffeic acid-treated eutopic endometrial ones. CONCLUSION: Caffeic acid can protect the endometrial cells against oxidative stress and might be able to prevent the progression of endometriosis and its related complications, such as pain and infertility.

Effects of Diacerein Intake on Cardiometabolic Profiles in Type 2 Diabetics: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: A systematic review and meta-analysis of clinical trials were undertaken to evaluate the effect of diacerein intake on cardiometabolic profiles in patients with type 2 diabetes mellitus (T2DM). METHODS: Electronic databases such as PubMed, EMBASE, Scopus, Web of Science, Google Scholar, and Cochrane Central Register of Controlled Trials were searched from inception to 31 July 2019. Statistical heterogeneity was evaluated using Cochran's Q test and I-square (I2) statistic. Data were pooled using random-effects models and weighted mean difference (WMD). RESULTS: From 1,733 citations, seven clinical trials were eligible for inclusion and meta-analysis. A significant reduction in hemoglobin A1c (HbA1c) (WMD -0.73; 95%CI -1.25 to -0.21; P= 0.006; I2= 72.2%) and body mass index (BMI) (WMD -0.55; 95%CI -1.03 to -0.07; P= 0.026; I2= 9.5%) was identified. However, no significant effect of diacerein intake was identified on fasting blood sugar (FBS) (WMD -9.00; 95%CI -22.57 to 4.57; P= 0.194; I2= 60.5%), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD 0.39; 95%CI -0.95 to 1.73; P= 0.569; I2= 2.2%), body weight (WMD - 0.54; 95%CI -1.10 to 0.02; P= 0.059), triglycerides (WMD -0.56; 95%CI -24.16 to 23.03; P= 0.963; I2= 0.0%), total-cholesterol (WMD -0.21; 95%CI -12.19 to 11.78; P= 0.973; I2= 0.0%), HDL-cholesterol (WMD -0.96; 95%CI -2.85 to 0.93; P= 0.321; I2= 0.0%), and LDL-cholesterol levels (WMD -0.09; 95%CI -8.43 to 8.25; P= 0.983; I2= 37.8%). CONCLUSION: Diacerein intake may reduce HbA1c and BMI; however, no evidence of the effect was observed for FBS, HOMA-IR, body weight, triglycerides, total cholesterol, HDL-cholesterol or LDLcholesterol.

Ameliorative Effects of Quercetin and Metformin and Their Combination Against Experimental Endometriosis in Rats.

Endometriosis, as the leading cause of infertility, is attributed to oxidative stress, inflammation, and autophagy dysregulation. This study was conducted to evaluate the effect of quercetin and metformin, alone or in combination, on the ectopic and eutopic endometrial tissues in a rat model of endometriosis. We divided 60 female rats into 6 groups, including SH, Endo, Endo + Oil, Endo + Q, Endo + M, and Endo + Q + M. The last five groups underwent a surgery, so that we could induce endometriosis, and after 4 weeks, daily treatment began, lasting for a month. Subsequently, the size and histoarchitecture of the endometrial implants, serum levels of 17ß-estradiol, progesterone and tumor necrosis factor (TNF)-α, and markers of oxidative stress and autophagy were assessed utilizing ELISA and gene expression analysis. Our results shed light to the fact that serum TNF-α and 17ß-estradiol levels significantly increased in endometriosis rats. Moreover, NADPH: quinone oxidoreductase (NQO1) enzyme activity and gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and autophagy markers significantly decreased; meanwhile, mammalian target of rapamycin (mTOR) gene expression increased in the ectopic endometrial tissues, as compared with eutopic ones. Surprisingly, our results demonstrated that the treatment in which we applied the combination of quercetin and metformin significantly reversed these changes and had a pronounced effect on the endometrial implant size and gene expression levels of mTOR and autophagy markers in ectopic endometrium. The findings of the present study suggest that quercetin, metformin, and their combination were of potential therapeutic effects on the rat model of endometriosis.

The effect of cinnamon supplementation on lipid profiles in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials.

OBJECTIVE: The present systematic review and meta-analysis was performed to evaluate the effect of cinnamon supplementation on blood lipid profiles in patients with type 2 diabetes. METHODS: A systematic search (with no language restrictions) was performed in PubMed, Embase, Scopus, Web of Science, and Cochrane Library to identify relevant clinical trials up to 8th March 2020. Weighted mean differences (WMDs) and 95 % confidence intervals (CI) were pooled based on the random-effects model. Heterogeneity, publication bias, and sensitivity analyses were performed based on standard methods. RESULTS: Sixteen studies, involving 1025 participants, were included in the meta-analysis. This study found a significant decrease in triglycerides (TG) (WMD: -26.27 mg/dl, 95 % CI: [-38.93, -13.61], P < 0.001), total cholesterol (TC) (WMD: -13.93 mg/dl, 95 % CI: [-25.64, -2.22], P = 0.020), and low-density lipoprotein cholesterol (LDL-C) levels (WMD: -6.13 mg/dl, 95 % CI: [-10.72, -1.53], P = 0.009), while no change was observed on high-density lipoprotein cholesterol (HDL) concentration (WMD: 0.64 mg/dl, 95 % CI: [-0.18, 1.46], P = 0.128), in patients with type 2 diabetes. The reduction in TG, TC, and LDL-C was greater in; Eastern compared to Western countries, and studies with a duration of < 2 compared to ≥ 2 months. The increase in HDL was greater in; participants with a BMI ≥ 30 compared to <30, Western compared to Eastern countries, and intervention durations of ≥ 2 compared to < 2 months. CONCLUSIONS: Cinnamon supplementation significantly decreased serum TG, TC, and LDL-C concentrations, but did not change HDL-C levels, in patients with type 2 diabetes.

Effect of cinnamon supplementation on blood pressure and anthropometric parameters in patients with type 2 diabetes: A systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: The present systematic review and meta-analysis was conducted to investigate the effect of cinnamon supplementation on blood pressure and anthropometric indices in patients with type 2 diabetes. METHODS: PubMed, Embase, Scopus, Web of Science and Cochrane Library were systematically searched to find relevant records up to 22 August 2019. Standard mean difference (SMD) and 95% confidence interval (CI) were used to evaluate the effect of cinnamon supplementation on the outcomes of this study. In the case of heterogeneity, fixed and random effect models were used. The obtained data were analyzed by Stata 13. After excluding irrelevant records, 9 eligible articles were included. RESULTS: This meta-analysis found a significant reduction in systolic blood pressure (SBP) (SMD: -0.532, 95% CI: [-1.032, -0.033], P = 0.037) and diastolic blood pressure (DBP) (SMD: -0.681, 95% CI: [-1.297, -0.065], P = 0.030) of patients with type 2 diabetes following cinnamon supplementation. Based on the results of the present study, cinnamon supplementation had no significant effect on the body weight (BW) (SMD: -0.309, 95% CI: [-0.793, 0.175], P = 0.211), body mass index (BMI) (SMD: -0.550, 95% CI: [-1.244, 0.144], P = 0.120). and waist circumference (WC) (SMD: -0.235, 95% CI: [-0.518, 0.047], P = 0.103). CONCLUSIONS: Cinnamon supplementation significantly decreased SBP and DBP of patients with type 2 diabetes. Although cinnamon intake caused changes in anthropometric parameters, the observed changes were not statistically significant.

Combination Effect of Caffeine and Caffeic Acid Treatment on the Oxidant Status of Ectopic Endometrial Cells Separated from Patients with Endometriosis.

BACKGROUND: Endometriosis is a common gynecological disease in which oxidative stress is a potential factor. Caffeine and caffeic acid are present in various foods and beverages with anti-oxidant, anti-inflammatory, and anti-carcinogenic properties. In this study, we aimed to investigate the ameliorative effects of caffeine, caffeic acid, and caffeine+caffeic acid treatments on oxidative stress in ectopic endometrial cells taken from patients and eutopic ones from women without endometriosis. METHODS: In this experimental study, eutopic and ectopic endometrial cells were obtained from biopsies of women free of disease (n=10) and patients with endometriosis (n=10) who referred to Shiraz reference hospitals (2017-2018). Both eutopic and ectopic endometrial cells were divided into four groups: Treated with caffeine, with caffeic acid, with caffeine+caffeic acid, and the control. Also, antioxidant enzyme activities and the levels of glutathione (GSH) and malondialdehyde (MDA) were determined in each group. The data were analyzed using independent sample t test and one-way ANOVA followed by Tukey post-hoc test. RESULTS: Caffeic acid, but not caffeine treatment demonstrated a decrease in MDA level (P<0.001) as well as an increase in GSH level (P<0.001) and antioxidant enzyme activities in ectopic endometrial cells. Also, the treatment of the cells with caffeine+caffeic acid caused similar effects as those ectopic cells treated with caffeic acid. CONCLUSION: According to the findings of the present study, caffeic acid reduced oxidative stress which may alleviate the complications associated with endometriosis. However, more investigations are needed for evaluating the efficiency and safety of caffeic acid.