Uric acid to HDL ratio: A marker for predicting incidence of metabolic syndrome in patients with type II diabetes.

BACKGROUND AND AIM: Metabolic syndrome (MetS) refers to existence of a set of risk factors for developing cardiovascular disease and diabetes. Recently, uric acid to HDL ratio has attracted attention in predicting development of diabetes and incidence of metabolic syndrome in diabetic individuals. This study was performed to investigate UHR in patients with type II diabetes as a predicting factor for metabolic syndrome. METHODS AND RESULTS: This descriptive-analytical study examined 300 patients with type II diabetes referring to diabetes clinic of Ali-Ibn Abi-Talib hospital, Rafsanjan city in 2021, selected through convenient sampling. Data were collected by a research-made checklist (including demographic, clinical and laboratory parameters) and analyzed by SPSS 24 and chi-square, Fisher exact test, independent paired t-test, one-way analysis of variance (ANOVA), Mann-Whitney U, and receiver operating characteristic (ROC). The findings revealed that 74.33 % (95 % CI: 69 to 79.18 %) of the patients had metabolic syndrome. Further, patients with metabolic syndrome demonstrated a significantly higher mean UHR ratio and triglyceride levels compared to their counterparts without the syndrome (p = 0.002 and p < 0.001, respectively). The ROC analysis identified a UHR threshold of 8.118 % with a sensitivity of 70.32 % and specificity of 55.08 % for diagnosing metabolic syndrome development in type II diabetes (AUC: 0.621, P = 0.001, 95%CI: 0.549-0.694). CONCLUSION: The results of the present study revealed that the prevalence of metabolic syndrome was high in diabetic patients. UHR showed good sensitivity in the diagnosis of metabolic syndrome in type II diabetes. Thus, regular monitoring of laboratory tests is recommended in patients with diabetes.

The effect of laughter yoga and music intervention on depression, anxiety, and stress in the Rafsanjan-Iran aged: a randomized clinical trial study.

OBJECTIVES: This study aimed to compare the effects of laughter yoga and music intervention on depression, anxiety, and stress in aged individuals referred to Rafsanjan health centers. METHOD: In this 3-arm randomized clinical trial, 91 depressed aged participants aged 60-75 years, referred to Rafsanjan health centers, were randomly assigned to intervention and control groups. The study followed a parallel group design with an allocation ratio of 1:1. The laughter yoga intervention was conducted twice a week for eight weeks, and music intervention consisted of 30-min sessions twice a week for eight weeks. The control group received no intervention ('No treatment' concurrent control). Assessments for depressive symptoms (primary outcome), anxiety, and stress were conducted at baseline, post-intervention, and one month after the intervention. RESULTS: A total of 84 patients were analyzed in three groups included the laughter yoga intervention (n = 31), music intervention (n = 25), or control group (n = 28). Repeated measures ANOVA revealed a significant decrease in depressive and anxiety symptoms (p < 0.001) from pre-test to post-test and one-month follow-ups. The greatest impact of the intervention programs on stress was observed immediately after the intervention, but stress increased one month after the intervention programs (p = 0.125). CONCLUSION: Both laughter yoga and music interventions proved effective in improving depression, anxiety, and stress in aged individuals. However, laughter yoga intervention demonstrated a superior effect and better acceptance among elders.

Effect of Topical Hemp (Cannabis sativa L.) Seed Oil on Knee Osteoarthritis: A Randomized Double-Blind Controlled Trial.

PURPOSE, AND DESIGN: Knee osteoarthritis (OA) is one of the most common and debilitating diseases, especially in the elderly. Hemp seed oil is a plant product that has been used as a food or drug since ancient times because of its anti-inflammatory and analgesic properties. METHODS: A double-blind, active, placebo-controlled trial was done to assess the efficacy of hemp seed oil on knee OA. Ninety patients were randomly allocated to three groups; hemp seed oil, diclofenac gel, and placebo via a blocked randomization method, and were asked to apply the topical treatment daily for 2 months. The study participant underwent assessments before, and four and 8 weeks after the intervention. Evaluation included measurements of the heel-to-thigh distance, utilization of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and application of visual analog scale (VAS). Data analysis was performed using SPSS.24 and the significance level was considered as p < .05. RESULTS: All parameters, except heel-to-thigh distance, improved significantly in the hemp seed oil group compared to placebo group. Improvements in VAS and WOMAC parameters were not different comparing the hemp seed oil and diclofenac gel groups. Heel-to-thigh distance decreased significantly within all groups during the study. There were no significant differences in improvements in heel-to-thigh distance comparing the three groups. CONCLUSION, AND CLINICAL IMPLICATIONS: Hemp seed oil led to greater improvements in VAS pain score and WOMAC parameters, but not knee flexion range, compared to placebo. There were no differences in measured outcomes comparing hemp seed oil and diclofenac gel.

Postpartum depression and its correlates: a cross-sectional study in southeast Iran.

BACKGROUND: Postpartum depression has a negative impact on both infants and women. This study aimed to determine the correlates of postpartum depression in women in southern Iran. METHODS: This cross-sectional study was performed on 186 mothers who had recently given birth to a baby. Data were collected using the demographic form, Quality of Prenatal Care Questionnaire, Edinburgh Postnatal Depression Scale (EPDS), Depression, Anxiety and Stress Scale-21 items (DASS-21) 3 days after delivery and EPDS and DASS-21 6 months after childbirth. RESULTS: Postpartum depression (PPD) was 24.2% and 3.2% 3 days and 6 months after delivery, respectively. Anxiety, Prenatal Care Quality and educational level predicted 34.0% of the variance of PPD 3 days after delivery (R2 = 34.0%). Anxiety, type of delivery, and stress predicted 24% of the variance of PPD 6 months after delivery (R2 = 24.0%). CONCLUSIONS: With an increase in stress and anxiety and a reduction in the quality of prenatal care, the risk of postpartum depression increases. Therefore, attention to the quality of prenatal care and postpartum stress and anxiety should be carefully evaluated to prevent PPD. Psychological support and interventions are recommended to promote the mental health of women before and after childbirth.

Assessing the expression of immunosuppressive cytokines in the newly diagnosed systemic lupus Erythematosus patients: a focus on B cells.

BACKGROUND: The immunosuppressive effects of regulatory B-cells (Bregs) and their immunosuppressive cytokines on immune responses in autoimmune disorders, mainly systemic lupus erythematosus (SLE), have been recently established. Therefore, the purpose of this article has been the exploration of the expressions of cytokines produced by B cells in newly diagnosed SLE patients. RESULTS: The findings demonstrated that the gene expression of IL-10, TGF-ß, IL-35, PD-L1, and FasL was significantly up-regulated in SLE patients compared to healthy subjects (P < 0.05). Additionally, the results revealed that serum levels of IL-10, TGF-ß, IL-35, PD-L1 were remarkably increased in patients with SLE compared to healthy subjects (P < 0.0001). However, serum levels of IL-10 and TGF-ß decreased significantly with increasing SLEDAI score in studied patients (P < 0.05). CONCLUSION: It was concluded that the release of anti-inflammatory cytokines, particularly IL-10 and TGF-ß, might inhibit immune responses and autoreactive immune cells in a compensatory manner in SLE patients with mild to moderate disease activity.

The role and function of long non-coding RNAs in osteoarthritis.

Osteoarthiritis (OA) is the most prevalent disease of articulating joints in human that frequently results in joint pain, movement limitations, inflammation, and progressive degradation of articular cartilage. The etiology of OA is not completely clear and there is no full treatment for this disease. Molecular investigations have revealed the involvement of non-coding RNAs such as Long non-coding RNAs (lncRNAs) in OA pathogenesis. LncRNAs play roles in multiple cellular and biological processes. Moreover, numerous lncRNAs are differentially expressed in human OA cartilage. In this review, we underlie the increasing evidence for the critical role of lncRNAs in OA pathogenesis reviewing the latest researches.

Correlation of Dietary Intake and Helicobacter pylori Infection with Multiple Sclerosis, a Case-Control Study in Rafsanjan, Iran, 2017-18.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Some environmental factors, such as Helicobacter pylori infection (HPI), are likely to be considered a protective factor in MS. Dietary intake may provide exposure to or have protective effects for MS. The present study aimed to determine the relationship between serum anti-H. pylori IgG antibody (HPIA) level and dietary intake in patients with MS referred to the MS Clinic in Rafsanjan city, Iran. METHODS: The present case-control study was conducted on 97 patients with MS and 95 controls. The two groups had no significant difference in age and gender (p > 0.05). HPIA was checked, and the food frequency questionnaire was completed in both groups to measure nutritional intake. All data were analyzed by the SPSS 20 software using independent t-test, Chi-Square, Mann-Whitney U test, and correlation. RESULTS: The median serum HPIA level was significantly lower in MS cases than in controls. Furthermore, the median consumption of glutamic acid, arginine, serine, aspartic acid, alanine, proline, and caffeine was significantly lower in MS cases than in controls. A significant positive correlation was found between the levels of linoleic acid, lactose, Ca, molybdenum, galactose, leucine, and valine, and the level of HPIA in controls. CONCLUSION: Our study results demonstrated that some dietary nutrients had correlations with MS and HPI. Therefore, professionals from multiple disciplines must find which foods contain these dietary nutrients in future studies.

Perceived Social Stigma in Patients with Multiple Sclerosis: A Study from Iran.

OBJECTIVES: Social Stigma is potentially a major problem in multiple sclerosis patients which strongly affects the quality of life. The aim of this study was to determine the prevalence of perceived stigma in patients with MS in a sample of Iranian population. METHODS: This cross-sectional study was performed on 305 MS patients who were referred to Iranian Multiple Sclerosis Society in 2014. The main variables were perceived stigma, age, sex, marital status, educational level, occupation, duration of the disease, type of symptoms, disability expanded status scale, family history and economic status. Social stigma was measured through a 20-item questionnaire which was developed by authors and the reliability was assessed in a pilot study. RESULTS: The frequency of perceived stigma was significantly associated with occupation, disease duration, and visibility of symptoms, level of disability and the economic condition. There were no significant relationships between perceived stigma and age, sex, marital status, level of education and family history. About 44 percent of patients preferred to hide their disease from others and 52.6 percent believed that this disease would stigmatize them in society. Nearly, half of patients preferred not to mention their disease in job interviews. CONCLUSION: Recognition of the impacts of perceived stigma on various aspects of the patients' lives are necessary to find appropriate strategies to deal with stigma and its consequences. Training programs can improve the patients' skills for coping with stigma. Furthermore, programs aimed to upgrade public knowledge and reduce the negative attitudes toward the disease should be promoted.

Interventional heart catheterization to close atrial septal defect, patent ductus arteriosus, ventricular septal defect in a 3.5-year-old girl; a case report study.

The aim of this study was to introduce an interventional heart catheterization to close patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrial septal defect (ASD), and pulmonary hypertension without complications from open heart surgery and a 3-day hospitalization period. PDA, VSD, and ASD are among the most common abnormalities associated with various complications. This case is a 3.5-year-old girl with frequent lung infections and Failure to thrive. Treatment in the first stage aims to close the PDA using Amplatzer ADO II type AGA, size 5-6 mm and ASD using Amplatzer Septal Occluder size 15 mm. The patient was discharged the next day. Six months later, a successful interventional closure of the VSD was performed using Lifetech Symmetric Amplatzer membranous size 12 mm and patient was discharged 2 days after. All these defects were corrected without open heart surgery and the need for long-term Intensive care unitsadmission.

Relationship between metabolic syndrome and depression: A study based on Rafsanjan Youth Cohort Study.

BACKGROUND: Depressed people are susceptible to metabolic syndrome ression and metabolic syndrome in the Rafsanjan Youth Cohort Study in 2021. METHODS: In this cross-sectional study, the data of 3005 young people aged 15-35 under the coverage of urban and rural health centers was investigated in the enrollment stage of the Rafsanjan Youth Cohort Study as a part of the prospective epidemiological research studies in IrAN (PERSIAN). Data was collected using face-to-face interview and electronic questionnaires of the Rafsanjan Youth Cohort Study. RESULTS: Age of the youth was 25.78 ± 6.06 years, 56 % (n = 1682) were female. The prevalence of metabolic syndrome (MetS) was 7.7 % (95 % CI: 6.8 %-8.8 %) and the prevalence of depression was 11.1 % (95 % CI: 10.0 %-12.3 %). Depression did not have a significant impact on the odds ratio of developing MetS in young people (P = 0.604). The odds ratio (OR) of MetS increases by 1.057 times with increasing age (95 % CI for OR: 1.020-1.094). This OR is also 1.715 times higher in married young people than in unmarried Youth (95 % CI for OR: 1.715-2.692) and 0.196 times lower in young people with medium and high MET index than in young people with low MET index (95 % CI for OR: 0.048-0.811). LIMITATIONS: Inability to determine a causal relationship between MetS and depression. CONCLUSION: Due to the growing trend of components of MetS among the young population, this issue needs to be addressed in future policies and planning for prevention and control as a health priority.

Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis.

BACKGROUND: Interleukin-17 (IL-17) family plays a role in the pathogenesis of knee osteoarthritis (KOA) by contributing to the inflammatory and destructive processes in the affected joint. This study aimed to measure levels of IL-17 A and IL-25 (IL-17E) in serum of KOA patients and determine their roles in the disease severity of patients. METHODS: In this, 34 patients with KOA and 30 age and sex-matched healthy subjects (HS) were enrolled. Patients were categorized based on their Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS), and Body Mass Index (BMI) scores. The enzyme-linked immunosorbent assay (ELISA) technique was employed to measure serum levels of IL-17 A and IL-25. RESULTS: Level of IL-25 was significantly higher (P < 0.0001) in the KOA subjects than HS. IL-17 A level was significantly higher in KOA cases with WOMAC < 40 (P < 0.0001) in comparison to HS. IL-25 level was significantly higher in the KOA cases with WOMAC < 40 (P < 0.0001) and with WOMAC ≥ 40 (P < 0.0001) compared to HS. IL-17 A concentration was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) compared to HS. IL-25 level was significantly higher in the KOA cases with VAS < 5 (P < 0.0001) and with VAS ≥ 5 (P < 0.0001) in comparison to HS. KOA patients with BMI ≥ 30 had significantly higher IL-17 A and IL-25 concentration in comparison to HS. CONCLUSIONS: The serum level of IL-25 in KOA patients is increased probably due to negative controlling feedback on inflammatory responses, which can be associated with obesity and disease activity.

Mucinous non neoplastic cyst of the pancreas: a case report.

The aim of this study was to introduce a patient with mucinous nonneoplastic cyst (MNNC) at an unusual age. MNNCs of the pancreas are uncommon primary tumors, which affect middle-aged women in their fifth decade of life and have significant malignant potential. Therefore, it is important to accurately diagnose and remove them. This case is a 28-year-old woman patient who presented with a pain in the right and upper abdomen from 3 months ago and worsened at night. A cystic lesion was observed near the upper bridge of the left kidney in abdominal ultrasonography. Contrast-enhanced abdominal computed tomography (CT) scan showed a cystic lesion in the trunk and umbilical cord of the pancreas. The patient underwent surgery and the mass was removed and the MNNC was diagnosed.

General and central obesity prevalence in young adult: a study based on the Rafsanjan youth cohort study.

Growing prevalence of obesity among youth would have adverse consequences and increased risk of developing chronic diseases at older ages. This study explored the prevalence of obesity and its association with relevant risk factors in the Rafsanjan youth cohort population. This cross-sectional study was done on 3006 individuals from the 15-35-year-old population included in the Rafsanjan youth cohort study. The data were extracted from the youth cohort databases, which had been collected through in-person interview and standard questionnaires. Definition of general obesity was considered as body mass index ≤ 30 and that of central obesity as waist to hip ratio (WHR) ≥ 0.9 for men and ≥ 0.85 for women. Multivariate stepwise proportional odds model and multivariable stepwise logistic regression models were done to explore the factors associated with general obesity and central obesity. The mean age was 25.78 ± 6.06 years with 56% (n = 1683) female. The prevalence of general obesity was 15.80% (95% CI 14.50-17.11) and central obesity was 28.41% (95% CI 26.80-30.02). The risk of general obesity increased with increasing age (OR = 1.053, P < 0.0001), being married (OR = 1.658, P < 0.0001), history of diabetes (OR = 1.609, P = 0.0185), history of hypertension (OR = 1.609, P < 0.0001), elevated triglyceride (OR = 1.007, P < 0.0001) and LDL (OR = 1.015, P < 0.0001), while decreasing with being employed (OR = 0.748, P = 0.0002) and elevated HDL (OR = 0.975, P < 0.0001). Prevalence of obesity was high in study population. Marital status, increasing age, and history of chronic diseases were associated with obesity. Preventing programs should be developed against obesity and for promoting healthy habits in young adult especially during education at schools.

Cardiovascular risk factors in diabetic patients with and without metabolic syndrome: a study based on the Rafsanjan cohort study.

Cardiovascular disease (CVD) is the leading cause of death and disability in people with diabetes mellitus (DM), since finding the correlation between DM and CVD risk factors can be effective in preventing the incidence of morbidity and mortality in patients. This study aimed to determine the prevalence of cardiovascular risk factors in people with and without metabolic syndrome (MtS) in DM. This cross-sectional study was part of the Rafsanjan Cohort Study as part of the comprehensive Persian (Prospective Epidemiological Research Studies in IRAN) on 35-70-year old adults with and without MtS in DM. Indicators of CVD risk factors, including gender, age, blood pressure, dyslipidemia, smoking, alcohol consumption, fasting blood sugar, creatinine, blood urea, waist circumference, body mass index, family history, physical inactivity, and fruit and vegetable consumption, were collected in the Persian Cohort Questionnaire. The data was analyzed by SPSS software version 22. The prevalence of MtS in 1933 participants was estimated to be 80% (95% confidence interval 78.1-81.8%). In the logistic regression model, smoking, alcohol consumption, and triglycerides were identified as the factors associated with MtS. Our results show that, based on our study, the prevalence of cardiovascular risk factors in DM was high. The suggested solutions in this field are to reduce smoking and alcohol consumption, as well as to control hypertension, hyperlipidemia, and being overweight.

Positive Association between Hemoglobin Concentration and Blood Pressure in Adults: A Cross-Sectional Study Based on Rafsanjan Cohort Study.

Introduction: Identification of factors associated with blood pressure (BP), including hemoglobin, can be used in diagnosing, controlling, and predicting the prognosis of patients. This study aims to investigate the cross-sectional association between hemoglobin concentration and BP in people aged 35-70 years in a cohort study of Rafsanjan, Iran. Method: This cross-sectional study was conducted on 9398 urban and rural population of Rafsanjan adult cohort study as a part of the prospective epidemiological research studies in Iran (PERSIAN). Demographic information, medical history, history of smoking and alcohol intake, systolic and diastolic BP, and hemoglobin concentration were collected. A logistic regression test was performed to evaluate the relationship between hemoglobin concentration and BP in 4 unadjusted and adjusted models based on demographic indicators, clinical and laboratory findings using SPSS.24 software and SAS software version 9.2. Results: The mean age of the participants was 49.78 ± 9.53 years, and 53.2% (5002 people) were women. Adjusted models 3 and 4 showed a positive association between BP and hemoglobin. For each unit increase in hemoglobin, the odds ratio (OR) of BP in the adjusted model 3 was 1.062 (95% CI: 1.005-1.121), and in the adjusted model 4, it was 1.090 (95% CI: 1.031-1.153). Conclusion: Based on the results, the positive trend of BP and hemoglobin levels may indicate the need to pay more attention to these people as higher-risk groups for hypertension.

Calcium Dobesilate Ameliorates Cisplatin-induced Hepatotoxicity by Inhibiting Liver Oxidative Stress in Mice.

Background: Cisplatin has potent antitumor properties. It has several toxic side effects, such as hepatotoxicity. It is thought that hepatotoxicity induced by cisplatin is caused by oxidative stress. Objectives: It has shown that calcium dobesilate (CD) has potent antioxidant properties. The present study aimed to assess CD protective effects on cisplatin-induced hepatotoxicity in mice. Methods: In this study, 28 mice were selected randomly and were divided into four groups, including control, cisplatin (20 mg/kg, i.p., only on the first day of the experiment), Cisplatin+CD 50 (50 mg/kg CD, orally), and Cisplatin+CD 100 (cisplatin with 100 mg/kg CD, orally). A 4-day oral gavage of CD was applied to the treated groups. The mice were sacrificed on the 5th day, and serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), malondialdehyde (MDA) and reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme activity levels in liver tissue were evaluated. Histopathological evaluation was assessed using hematoxylin and eosin-stained liver tissue sections. Results: The results indicated that there was a significant increase in GSPT, SGOT, ALP, and MDA and also a significant reduction in the liver activity of SOD and GPx in cisplatin-treated animals. Treatment with CD (100 mg/kg) remarkably attenuated the GSPT, SGOT, ALP, MDA, and ROS levels. Moreover, CD (100 mg/kg) elevated the SOD and GPx activity in the liver tissue of cisplatin-treated mice. Conclusions: The findings showed that CD has a protective effect against cisplatin-induced hepatotoxicity, at least by improving the antioxidant parameters.

The Therapeutic Activities of Metformin: Focus on the Nrf2 Signaling Pathway and Oxidative Stress Amelioration.

In the present study, the health-protective and therapeutic properties of MET have been discussed, focusing on the effect of MET on the Nrf2 expression in patients with different pathological conditions. Metformin (MET) regulates high blood glucose, thus being an integral part of the antidiabetic medications used to treat type 2 diabetes mellitus. It belongs to biguanide class medications that are administered through the oral route. Moreover, the agent is widely known for its anti-cancer, anti-oxidant, anti-inflammatory, and neuroprotective effects. The MET modulates the nuclear factor erythroid-2 related factor-2 (Nrf2) signaling pathway, which in turn yields the above-mentioned medical benefits to patients. The Nrf2 signaling pathways are modulated in multiple ways described subsequently: 1) MET acts on the cancer cells and inactivates Raf-ERK signaling, thus reducing Nrf2 expression, 2) MET obstructs the expression of proteins that are involved in apoptosis of tumor cells and also prevents tumor cells from oxidation through an AMPK-independent pathway; 3) MET carries out Keap1-independent mechanism for reducing the levels of Nrf2 protein in cancer cells; 4) MET upregulates the Nrf2-mediated transcription to stimulate the anti-oxidant process that prevents oxidative stress in cells system and consequently gives neuroprotection from rotenone and 5) MET downregulates p65 and upregulates Nrf2 which helps improve the angiogenesis impairment stimulated by gestational diabetes mellitus. This article presents an analysis of the health-protective properties of MET and also sheds light on the effect of MET on the Nrf2 expression in patients with different pathological conditions.

A comprehensive view on the apigenin impact on colorectal cancer: Focusing on cellular and molecular mechanisms.

Colon cancer (CC) is one of the most common and deadly cancers worldwide. Oncologists are facing challenges such as development of drug resistance and lack of suitable drug options for CC treatment. Flavonoids are a group of natural compounds found in fruits, vegetables, and other plant-based foods. According to research, they have a potential role in the prevention and treatment of cancer. Apigenin is a flavonoid that is present in many fruits and vegetables. It has been used as a natural antioxidant for a long time and has been considered due to its anticancer effects and low toxicity. The results of this review study show that apigenin has potential anticancer effects on CC cells through various mechanisms. In this comprehensive review, we present the cellular targets and signaling pathways of apigenin indicated to date in in vivo and in vitro CC models. Among the most important modulated pathways, Wnt/ß-catenin, PI3K/AKT/mTOR, MAPK/ERK, JNK, STAT3, Bcl-xL and Mcl-1, PKM2, and NF-kB have been described. Furthermore, apigenin suppresses the cell cycle in G2/M phase in CC cells. In CC cells, apigenin-induced apoptosis is increased by inhibiting the formation of autophagy. According to the results of this study, apigenin appears to have the potential to be a promising agent for CC therapy, but more research is required in the field of pharmacology and pharmacokinetics to establish the apigenin effects and its dosage for clinical studies.

STAT3 Signaling Axis and Tamoxifen in Breast Cancer: A Promising Target for Treatment Resistance.

Signal transducers and activators of transcription 3 (STAT 3) have been proposed to be responsible for breast cancer development. Moreover, evidence depicted that upregulation of STAT3 is responsible for angiogenesis, metastasis, and chemo-resistance of breast cancer. Tamoxifen (TAM) resistance is a major concern in breast cancer management which is mediated by numerous signaling pathways such as STAT3. Therefore, STAT3 targeting inhibitors would be beneficial in breast cancer treatment. The information on the topic in this review was gathered from scientific databases such as PubMed, Scopus, Google Scholar, and ScienceDirect. The present review highlights STAT3 signaling axis discoveries and TAM targeting STAT3 in breast cancer. Based on the results of this study, we found that following prolonged TAM treatment, STAT3 showed overexpression and resulted in drug resistance. Moreover, it was concluded that STAT3 plays an important role in breast cancer stem cells, which correlated with TAM resistance.

A comprehensive review on Ellagic acid in breast cancer treatment: From cellular effects to molecular mechanisms of action.

Globally, breast cancer (BC) is the leading cause of cancer-related deaths in women. Hence, developing a therapeutic plan to overcome the disease is crucial. Numerous factors such as endogenous hormones and environmental factors may play a role in the pathophysiology of BC. Regarding the multi-modality treatment of BC, natural compounds like ellagic acid (EA) received has received increased interest in antitumor efficacy with lower adverse effects. Based on the results of this comprehensive review, EA has multiple effects on BC cells including (1) suppresses the growth of BC cells by arresting the cell cycle in the G0/G1 phase, (2) suppresses migration, invasion, and metastatic, (3) stimulates apoptosis in MCF-7 cells via TGF-ß/Smad3 signaling axis, (4) inhibits CDK6 that is important in cell cycle regulation, (5) binds to ACTN4 and induces its degradation via the ubiquitin-proteasome pathway, inducing decreased cell motility and invasion in BC cells, (6) inhibits the PI3K/AKT pathway, and (7) inhibits angiogenesis-associated activities including proliferation (reduces VEGFR-2 tyrosine kinase activity). In conclusion, EA exhibits anticancer activity through various molecular mechanisms that influence key cellular processes like apoptosis, cell cycle, angiogenesis, and metastasis in BC. However, further researches are essential to fully elucidate its molecular targets and implications for clinical applications.