Background/Aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy. Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics. Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data. Conclusions Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.

Breast cancer is one of the most common causes of death all over the world. Therapeutic options applied to the patients include surgery, chemotherapy, and radiotherapy.However, far advanced disease often leads to chemoresistance and toxicity. Innovative therapies are needed to address these challenges. Melatonin has the potential to prevent and treat cancer, as it has been revealed in numerous clinical studies. Melatonin is a nontoxic agent that is mostly produced in the pineal gland, inducing various mechanisms of action such as the induction of apoptosis, antiangiogenic, antiproliferative, and metastasis-inhibitory effects. Therefore, melatonin increases therapeutic sensitivity when combined with conventional medication in breast cancer. Melatonin (3-20 mg/day) may reduce breast cancer cell growth in preclinical studies and enhance chemotherapy efficacy. Small human trials suggest potential benefits, but larger studies are needed. Higher doses (≥20 mg/day) are sometimes used alongside chemotherapy. This manuscript reviews research that has demonstrated the antitumor properties of melatonin, thereby focusing on its actions on angiogenesis, apoptosis, metastasis, and antiproliferative properties. We also discuss recent advances in the understanding of the actions of melatonin on epigenetic mechanisms (especially DNA methylation) and telomere length. The data in this review were obtained from journal articles up to May 2024.Regarding the study, Google Scholar and ScienceDirect were used as engines to search for open access. We searched the ISI, Pubmed and Scopus as valid external databases, and as internal databases, ISC and Iran medex. By finding mean keywords such as ‘breast cancer’, ‘estrogen’, ‘melatonin’, ‘cell death’, ‘cell proliferation’, ‘telomerase’ and ‘DNA methylation’, we reached to the formula with maximum collectivity in searching, then equivalent terms were found by Mesh database. The review also covers recent clinical investigations of melatonin in breast cancer.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility. This experimental study was conducted to elucidate the role of adiponectin signaling in rats with PCOS treated with exenatide. Twenty-eight adult female Wistar rats were divided into four groups of seven. The normal group did not receive any drug. The PCOS+vehicle (Veh) group received estradiol valerate to induce PCOS, then was divided into PCOS +E50 and PCOS+E100 groups and treated with 50 or 100 mg/kg doses of exenatide, respectively. The mRNA expression of adiponectin and adiponectin receptor 1 (Adipo-R1) was evaluated using a semi-quantitative real-time polymerase chain reaction. The results indicated that the level of adiponectin diminished in the PCOS rats while exenatide increased adiponectin expression at both doses. Adiponectin receptor mRNA levels were higher in the PCOS rats than in the normal rats (p<0.05). In addition, exenatide decreased the levels of Adipo-R1 expression. Taken together, our results showed that exenatide may improve PCOS characteristics in rats through the molecular regulation of adiponectin and its receptor.

Objective: Phenanthrene, a polycyclic aromatic hydrocarbon, is found in abundance in environmental pollutants, food, and drinking water. This substance can accumulate in body tissues and exert harmful effects. Moreover, phenanthrene can cross the placental barrier, potentially impacting fetal development. We aimed to explore the impacts of maternal exposure to phenanthrene on testicular tissue and Sertoli cell function in F1 mice. Methods: Female rats with vaginal plugs were randomly assigned to one of three groups: control, sham, or phenanthrene. The control group received no intervention during pregnancy. In the sham and phenanthrene groups, corn oil and a phenanthrene solution, respectively, were administered via gavage once every 2 days. Offspring were separated by sex 21 days after birth. At 56 days postnatal, male F1 offspring were euthanized, and their testes were harvested for histological and molecular analyses. Results: Phenanthrene exposure was associated with a lower testicular weight and volume, a smaller diameter of the seminiferous tubules, and a relative thinning of the germinal epithelium. These changes were associated with increased cellular apoptosis, as shown by the upregulation of caspase 3 expression. Additionally, we observed an increase in vacuolization and residual bodies within the tissue. Conversely, the number of Sertoli cells and expression levels of Sox9, as well as the Ocln and Itgb1 genes, were found to be lowered. Conclusion Maternal exposure to phenanthrene impacts both germ cells and Sertoli cells, disrupting their function and leading to fertility disorders in male F1 offspring mice.

The administration of botulinum toxin A (BTA) into the gastric wall has emerged as a novel endoscopic bariatric procedure. Although over 20 years have elapsed since the initial human trial of intragastric BTA injection, considerable debate remains surrounding the safety, efficacy, and procedural instructions of this approach. The current literature exhibits discrepancies in the methodologies employed across studies, including differences in the dosage of BTA administered, injection site, number and depth of injections, post-procedural dietary modifications, and follow-up duration. This study reviewed the state-of-the-art use of BTA for weight loss and focused on the clinical evidence of the therapeutic applications of BTA for obesity. Studies with consistent outcome measures and methodologies are necessary to thoroughly assess the potential effects of BTA on weight management.

Breast cancer is one of the most common causes of death all over the world. Therapeutic options applied to the patients include surgery, chemotherapy, and radiotherapy.However, far advanced disease often leads to chemoresistance and toxicity. Innovative therapies are needed to address these challenges. Melatonin has the potential to prevent and treat cancer, as it has been revealed in numerous clinical studies. Melatonin is a nontoxic agent that is mostly produced in the pineal gland, inducing various mechanisms of action such as the induction of apoptosis, antiangiogenic, antiproliferative, and metastasis-inhibitory effects. Therefore, melatonin increases therapeutic sensitivity when combined with conventional medication in breast cancer. Melatonin (3-20 mg/day) may reduce breast cancer cell growth in preclinical studies and enhance chemotherapy efficacy. Small human trials suggest potential benefits, but larger studies are needed. Higher doses (≥20 mg/day) are sometimes used alongside chemotherapy. This manuscript reviews research that has demonstrated the antitumor properties of melatonin, thereby focusing on its actions on angiogenesis, apoptosis, metastasis, and antiproliferative properties. We also discuss recent advances in the understanding of the actions of melatonin on epigenetic mechanisms (especially DNA methylation) and telomere length. The data in this review were obtained from journal articles up to May 2024.Regarding the study, Google Scholar and ScienceDirect were used as engines to search for open access. We searched the ISI, Pubmed and Scopus as valid external databases, and as internal databases, ISC and Iran medex. By finding mean keywords such as ‘breast cancer’, ‘estrogen’, ‘melatonin’, ‘cell death’, ‘cell proliferation’, ‘telomerase’ and ‘DNA methylation’, we reached to the formula with maximum collectivity in searching, then equivalent terms were found by Mesh database. The review also covers recent clinical investigations of melatonin in breast cancer.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility. This experimental study was conducted to elucidate the role of adiponectin signaling in rats with PCOS treated with exenatide. Twenty-eight adult female Wistar rats were divided into four groups of seven. The normal group did not receive any drug. The PCOS+vehicle (Veh) group received estradiol valerate to induce PCOS, then was divided into PCOS +E50 and PCOS+E100 groups and treated with 50 or 100 mg/kg doses of exenatide, respectively. The mRNA expression of adiponectin and adiponectin receptor 1 (Adipo-R1) was evaluated using a semi-quantitative real-time polymerase chain reaction. The results indicated that the level of adiponectin diminished in the PCOS rats while exenatide increased adiponectin expression at both doses. Adiponectin receptor mRNA levels were higher in the PCOS rats than in the normal rats (p<0.05). In addition, exenatide decreased the levels of Adipo-R1 expression. Taken together, our results showed that exenatide may improve PCOS characteristics in rats through the molecular regulation of adiponectin and its receptor.

Objective: Phenanthrene, a polycyclic aromatic hydrocarbon, is found in abundance in environmental pollutants, food, and drinking water. This substance can accumulate in body tissues and exert harmful effects. Moreover, phenanthrene can cross the placental barrier, potentially impacting fetal development. We aimed to explore the impacts of maternal exposure to phenanthrene on testicular tissue and Sertoli cell function in F1 mice. Methods: Female rats with vaginal plugs were randomly assigned to one of three groups: control, sham, or phenanthrene. The control group received no intervention during pregnancy. In the sham and phenanthrene groups, corn oil and a phenanthrene solution, respectively, were administered via gavage once every 2 days. Offspring were separated by sex 21 days after birth. At 56 days postnatal, male F1 offspring were euthanized, and their testes were harvested for histological and molecular analyses. Results: Phenanthrene exposure was associated with a lower testicular weight and volume, a smaller diameter of the seminiferous tubules, and a relative thinning of the germinal epithelium. These changes were associated with increased cellular apoptosis, as shown by the upregulation of caspase 3 expression. Additionally, we observed an increase in vacuolization and residual bodies within the tissue. Conversely, the number of Sertoli cells and expression levels of Sox9, as well as the Ocln and Itgb1 genes, were found to be lowered. Conclusion Maternal exposure to phenanthrene impacts both germ cells and Sertoli cells, disrupting their function and leading to fertility disorders in male F1 offspring mice.

The administration of botulinum toxin A (BTA) into the gastric wall has emerged as a novel endoscopic bariatric procedure. Although over 20 years have elapsed since the initial human trial of intragastric BTA injection, considerable debate remains surrounding the safety, efficacy, and procedural instructions of this approach. The current literature exhibits discrepancies in the methodologies employed across studies, including differences in the dosage of BTA administered, injection site, number and depth of injections, post-procedural dietary modifications, and follow-up duration. This study reviewed the state-of-the-art use of BTA for weight loss and focused on the clinical evidence of the therapeutic applications of BTA for obesity. Studies with consistent outcome measures and methodologies are necessary to thoroughly assess the potential effects of BTA on weight management.

Background/Aims: Amitriptyline is prescribed off-label for irritable bowel syndrome (IBS). We conducted a meta-analysis to assess its efficacy. Methods: A systematic literature review was conducted until November 10, 2023, using MEDLINE, Embase, Cochrane Library, and Web of Science to study the efficacy of amitriptyline in patients with IBS. We included all randomized controlled trials that compared amitriptyline to placebo. Revised Cochrane risk-of-bias tool was used to assess the quality of studies. Meta-analyses were performed using a bivariate random-effects model. Statistical analyses were performed using R Software 4.2.3 and heterogeneity was assessed with I 2 statistics. Results: Seven trials were included with 796 patients (61% female). Amitriptyline was associated with better treatment response (OR, 5.30; 95% CI, 2.47 to 11.39; P < 0.001), reduced Irritable Bowel Syndrome Symptom Severity Scores (MD, –50.72; 95% CI, –94.23 to –7.20; P = 0.020) and improved diarrhea (OR, 10.55; 95% CI, 2.90 to 38.41; P < 0.001). No significant difference between the 2 groups regarding the adverse effects was observed. Three trials showed an overall low risk of bias, 2 trials showed an overall high risk of bias due to randomization and missing data, and 2 trials had some concerns regarding missing data. Conclusions Amitriptyline was found to be well-tolerated and effective in treating IBS compared to placebo. These findings support the use of amitriptyline for the management of IBS, particularly among patients with the IBS diarrhea subtype. Future research should focus on the dose-dependent effects of amitriptyline in IBS to better guide clinicians in personalized titration regimens.