Metformin ameliorates cardiopulmonary toxicity induced by chlorpyrifos.

Chlorpyrifos (CPF) is a widely used pesticide that can impair body organs. Nonetheless, metformin is known for its protective role against dysfunction at cellular and molecular levels led by inflammatory and oxidative stress. This study aimed to investigate the modulatory impacts of metformin on CPF-induced heart and lung damage. Following the treatment of Wistar rats with different combinations of metformin and CPF, plasma, as well as heart and lung tissues, were isolated to examine the level of oxidative stress biomarkers like reactive oxygen species (ROS) and malondialdehyde (MDA), inflammatory cytokines such as tumor necrosis alpha (TNF-α), high mobility group box 1 (HMGB1) gene, deoxyribonucleic acid (DNA) damage, lactate, ADP/ATP ratio, expression of relevant genes (TRADD, TERT, KL), and along with histological analysis. Based on the findings, metformin significantly modulates the impairments in heart and lung tissues induced by CPF.

Modification of the hemodynamic and molecular features of phosphine, a potent mitochondrial toxicant in the heart, by cannabidiol.

Aluminum phosphide (AlP) poisoning is common in many countries responsible for high mortality. The heart is the main target organ in AlP poisoning. Several studies have reported the beneficial effects of cannabidiol (CBD) in reducing heart injuries. This study aimed to investigate the possible protective effect of CBD on cardiac toxicity caused by AlP poisoning. Study groups included almond oil, normal saline, sole CBD (100 µg/kg), AlP (11.5 mg/kg), and four groups of AlP + CBD (following AlP gavage, CBD administrated at doses of 5, 25, 50, and 100 µg/kg via intravenous (iv) injection). Thirty minutes after AlP treatment, an electronic cardiovascular device (PowerLab) was used to record electrocardiographic (ECG) changes, heart rate (HR), and blood pressure (BP) for three hours. Cardiac tissue was examined for the activities of mitochondrial complexes, ADP/ATP ratio, the release of cytochrome C, mitochondrial membrane potential (MMP), apoptosis, oxidative stress parameter, and cardiac biomarkers at 12 and 24 hours time points. AlP administration caused abnormal ECG, decreased HR, and BP. AlP also significantly reduced mitochondrial complex I and IV activity and ADP/ATP ratio. The level of cytochrome C release, apoptosis, oxidative stress, and cardiac biomarkers was considerably increased by AlP, which was compensated following CBD administration. CBD was able to improve hemodynamic function to some extent in AlP poisoned rats. CBD restored ATP levels and mitochondrial function and decreased oxidative damage and thus, prevented the heart cells from entering the apoptotic stage. Further clinical trials are needed to explore any possible benefits of CBD in AlP-poisoned patients.

Molecular Evidence of the Inhibitory Potential of Melatonin against NaAsO2-Induced Aging in Male Rats.

Arsenic (As) poisoning is widespread due to exposure to pollution. The toxic level of (As) causes oxidative stress-induced aging and tissue damage. Since melatonin (MLT) has anti-oxidant and anti-aging properties, we aimed to evaluate the protective effect of MLT against the toxicity of sodium arsenite (NaAsO2). Healthy male NMRI mice were divided into eight different groups. The control group received a standard regular diet. Other groups were treated with varying diets, including MLT alone, NaAsO2, and NaAsO2 plus MLT. After one month of treatment, biochemical and pathological tests were performed on blood, heart, and lung tissue samples. NaAsO2 increased the levels of TNF-α, 8-hydroxy-2-deoxy guanosine (8OHdG), malondialdehyde (MDA), reactive oxygen species (ROS), and high mobility group box 1 (HMGB1), increased the expression of TNF receptor type 1-associated death domain (TRADD) mRNA and telomerase reverse transcriptase, and decreased the expression of Klotho (KL) mRNA in both plasma and tissues. In contrast, MLT reduced MDA, ROS, HMGB1, lactate, and TNF-α enhanced the mRNA expression of KL, and suppressed the mRNA expression of the TERT and TRADD genes. Thus, MLT confers potent protection against NaAsO2- induced tissue injury and oxidative stress.

The role of levosimendan in phosphine-induced cardiotoxicity: evaluation of electrocardiographic, echocardiographic, and biochemical parameters.

Aluminum phosphide (AlP) causes serious poisoning in which severe cardiac suppression is the significant lethal consequence. According to evidence, levosimendan can exert outstanding cardiac support and protection in different pathological conditions. This study aimed to investigate the mechanisms by which levosimendan may alleviate cardiovascular toxicity due to AlP intoxication in the rat model. The groups included control group (normal saline only), sole levosimendan groups (12, 24, 48 µg/kg), AlP group (10 mg/kg), and AlP + levosimendan groups receiving 12, 24, 48 µg/kg levosimendan intraperitoneally 30 min after AlP administration. Electrocardiographic (ECG) parameters (QRS and PR duration and ST height), heart rate, and blood pressure were monitored for 180 minutes. Also, after 24 h of poisoning, echocardiography was applied to assess left ventricle function. Evaluation of the biochemical parameters in heart tissue, including mitochondrial complexes I, II, IV activity, ADP/ATP ratio, the rate of apoptosis, malondialdehyde (MDA), lactate, and troponin I levels, were done after 12 and 24 h. AlP-induced ECG abnormalities (PR duration and ST height), reduction in heart rate, blood pressure, cardiac output, ejection fraction, and stroke volume were improved by levosimendan administration. Besides, levosimendan significantly improved complex IV activity, the ADP/ATP ratio, apoptosis, MDA, lactate, and troponin I level following AlP-poisoning. Our results suggest that levosimendan might alleviate AlP-induced cardiotoxicity by modulating mitochondrial activity and improving cardiac function. However, the potential clinical use of levosimendan in this toxicity needs more investigations.

Effect of the herbal medicines in obesity and metabolic syndrome: A systematic review and meta-analysis of clinical trials.

Obesity is a medical situation in which excess body fat has gathered because of imbalance between energy intake and energy expenditure. In spite of the fact that the variety of studies are available for obesity treatment and management, its "globesity" still remains a big challenge all over the world. The current systematic review and meta-analysis aimed to evaluate the efficacy, safety, and mechanisms of effective herbal medicines in the management and treatment of obesity and metabolic syndrome in human. We systematically searched all relevant clinical trials via Web of Science, Scopus, PubMed, and the Cochrane database to assess the effects of raw or refined products derived from plants or parts of plants on obesity and metabolic syndrome in overweight and obesity adult subjects. All studies conducted by the end of May 2019 were considered in the systematic review. Data were extracted independently by two experts. The quality assessment was assessed using Consolidated Standards of Reporting Trials checklist. The main outcomes were anthropometric indices and metabolic syndrome components. Pooled effect of herbal medicines on obesity and metabolic syndrome were presented as standardized mean difference (SMD) and 95% confidence interval (CI). A total of 279 relevant clinical trials were included. Herbals containing green tea, Phaseolus vulgaris, Garcinia cambogia, Nigella sativa, puerh tea, Irvingia gabonensis, and Caralluma fimbriata and their active ingredients were found to be effective in the management of obesity and metabolic syndrome. In addition, C. fimbriata, flaxseed, spinach, and fenugreek were able to reduce appetite. Meta-analysis showed that intake of green tea resulted in a significant improvement in weight ([SMD]: -0.75 [-1.18, -0.319]), body mass index ([SMD]: -1.2 [-1.82, -0.57]), waist circumference ([SMD]: -1.71 [-2.66, -0.77]), hip circumference ([SMD]: -0.42 [-1.02, -0.19]), and total cholesterol, ([SMD]: -0.43 [-0.77, -0.09]). In addition, the intake of P. vulgaris and N. sativa resulted in a significant improvement in weight ([SMD]: -0.88, 95 % CI: [-1.13, -0.63]) and triglyceride ([SMD]: -1.67, 95 % CI: [-2.54, -0.79]), respectively. High quality trials are still needed to firmly establish the clinical efficacy of the plants in obesity and metabolic syndrome.

Therapeutic Effects of Gallic Acid in Regulating Senescence and Diabetes; an In Vitro Study.

Gallic acid (GA), a plant-derived ubiquitous secondary polyphenol metabolite, can be a useful dietary supplement. This in vitro study's primary purpose was to assess the anti-aging properties of GA using rat embryonic fibroblast (REF) cells, antidiabetic effects via pancreatic islet cells, and finally, elucidating the molecular mechanisms of this natural compound. REF and islet cells were isolated from fetuses and pancreas of rats, respectively. Then, several senescence-associated molecular and biochemical parameters, along with antidiabetic markers, were investigated. GA caused a significant decrease in the ß-galactosidase activity and reduced inflammatory cytokines and oxidative stress markers in REF cells. GA reduced the G0/G1 phase in senescent REF cells that led cells to G2/M. Besides, GA improved the function of the ß cells. Flow cytometry and spectrophotometric analysis showed that it reduces apoptosis via inhibiting caspase-9 activity. Taken together, based on the present findings, this polyphenol metabolite at low doses regulates different pathways of senescence and diabetes through its antioxidative stress potential and modulation of mitochondrial complexes activities.

Regulation of tumor angiogenesis by microRNAs: State of the art.

MicroRNAs (miRNAs, miRs) are small (21-25 nucleotides) endogenous and noncoding RNAs involved in many cellular processes such as apoptosis, development, proliferation, and differentiation via binding to the 3'-untranslated region of the target mRNA and inhibiting its translation. Angiogenesis is a hallmark of cancer, which provides oxygen and nutrition for tumor growth while removing deposits and wastes from the tumor microenvironment. There are many angiogenesis stimulators, among which vascular endothelial growth factor (VEGF) is the most well known. VEGF has three tyrosine kinase receptors, which, following VEGF binding, initiate proliferation, invasion, migration, and angiogenesis of endothelial cells in the tumor environment. One of the tumor microenvironment conditions that induce angiogenesis through increasing VEGF and its receptors expression is hypoxia. Several miRNAs have been identified that affect different targets in the tumor angiogenesis pathway. Most of these miRNAs affect VEGF and its tyrosine kinase receptors expression downstream of the hypoxia-inducible Factor 1 (HIF-1). This review focuses on tumor angiogenesis regulation by miRNAs and the mechanism underlying this regulation.

A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer.

BACKGROUND: Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation-induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function. METHODS: To illuminate the radiation-induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study. RESULTS: According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle-stimulating hormone levels after prostate radiotherapy were significantly higher in comparison with the pretreatment levels. Around 60% of the studies showed that testosterone levels after prostate radiotherapy were significantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is significantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy. CONCLUSION: The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life.

Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells.

Aging contributes to an increased risk of developing a number of neurodegenerative and chronic disorders, predominantly related to oxidative stress (OS) and defects in the antioxidant balance. This study focused on the antisenescence effect of four plant species (Falcaria vulgaris, Ixiolirion tataricum, Ajuga chamaecistus, and Scabiosa flavida) on H2 O2 -induced premature senescence in rat NIH3T3 fibroblasts, which were found to be rich in effective phytochemicals with traditional ethnobotanical backgrounds. Plant materials were collected, identified, and extracted. To determine the viability of NIH3T3 cells, an MTT assay was conducted. The levels of OS markers and the senescence-associated ß-galactosidase (SA-ß-GAL) activity were analyzed by the Elisa reader. The cell cycle pattern was evaluated by flow cytometry. The expression of senescence-related inflammatory cytokines and the molecules involved in aging signaling pathways were investigated using the real-time reverse transcription polymerase chain reaction (RT-PCR). H2 O2 treatment decreased cell viability and increased lipid peroxidation (LPO) and the reactive oxygen species (ROS) in NIH3T3s. However, S. flavida exhibited low cytotoxicity, reduced OS and SA-ß-GAL activities in NIH3T3 cells compared with the H2 O2 -treated group. I. tataricum was the second best plant, although it was more toxic to NIHT3T cells. S. flavida decreased G0/G1 arrest and facilitated the G2/M transition of NIH3T3s, also downregulated the expression of p38, p53, p16, and the related inflammatory mediators. S. flavida potentially modulated senescence-associated hallmarks in fibroblasts exposed to H2 O2 , thus it may inhibit the aging process via controlling the OS. Therefore it is a promising candidate for future antiaging explorations.

Thyroid function following breast cancer chemotherapy: A systematic review.

BACKGROUND: Chemotherapy, as a systemic therapy, is one of the most effective modalities for cancer treatment. However, the use of chemotherapeutic drugs in patients with breast cancer can lead to thyroid dysfunction. This systematic review summarizes the available data on thyroid function following breast cancer chemotherapy. METHODS: To illuminate the thyroid toxicities induced by different chemotherapy regimens in patients with breast cancer, a systematic search was done in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in Scopus, Embase, PubMed and Web of Science electronic databases up to December 2018. On the basis of a set of prespecified inclusion and exclusion criteria, eight eligible articles providing data on thyroid function following chemotherapy in patients with breast cancer were included in the study. RESULTS: According to the obtained results, it was found that for most cases, the levels of triiodothyronine (T3), free T3 (FT3), thyroxin (T4) and free T4 (FT4) hormones decrease following breast cancer chemotherapy regimens used in these eligible studies. However, alteration of thyroid-stimulating hormone (TSH) level after breast cancer chemotherapy was not clear. CONCLUSION: The findings showed that thyroid function and TSH hormone level can change in patients with breast cancer receiving different chemotherapy regimens.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

Regulation of aging and oxidative stress pathways in aged pancreatic islets using alpha-lipoic acid.

Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study investigates the anti-aging, anti-apoptotic, and antioxidant properties of alpha-lipoic acid (ALA), aiming to improve aged rat pancreatic cells. In this regard, half maximal effective concentration (EC50) of ALA based on the survival of aged pancreatic islet cells was determined as 100 µM. Following this, p38 and p53 genes expression as key factors in aging, oxidative stress biomarkers, insulin secretion, and Pdx1 protein expression were evaluated using real-time PCR, ELISA reader, and fluorescence microscope. It was revealed that ALA reduces and controls the effects of aging on beta cells mainly by suppressing p38 and p53 at the gene level (P < 0.001 and P < 0.01), respectively, reducing reactive oxygen species (P < 0.001) and enhancing levels of thiols (P < 0.05) compared with the aged islets. Furthermore, both qualitative and quantitative investigations of insulin secretion have shown that ALA can improve aged cells' function and increase insulin secretion specially in the stimulating concentration of glucose. Also, the expression of Pdx1 was considerably increased by ALA in comparison to the aged pancreatic islets (P < 0.001). As far as the authors of the present study are concerned, this is the first study, which evaluated aging associated with p38 and p53 pathways, oxidative stress parameters, and the expression of insulin in beta cells of an aged rat and reaffirmed the fact that ALA has a significant antioxidant role in reducing the aging process.

A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: An introductory review.

Irisin is a hormone-like molecule mainly released by skeletal muscles in response to exercise. Irisin induces browning of the white adipose tissue and has been shown to regulate glucose and lipid homeostasis. Keeping its energy expenditure and metabolic properties in view, numerous studies have focused on its therapeutic potential for the treatment of metabolic disorders like obesity and type 2 diabetes. Recently, the anti-inflammatory, anti-apoptotic and anti-oxidative properties of irisin have received a great deal of attention of the scientific society. These pathogenic processes are often associated with initiation, progression, and prognosis of numerous diseases like myocardial infarction, kidney diseases, cancer, lung injury, inflammatory bowel diseases, atherosclerosis, liver diseases, obesity and type 2 diabetes. In the current review, we present evidence regarding the anti-inflammatory, anti-apoptotic and anti-oxidative potential of irisin pertaining to various pathological conditions. Here, we explore multiple molecular pathways targeted by irisin therapy. Given the promising effects of irisin, many diseases with evident oxidative stress, inflammation and apoptosis can be targeted by irisin.

Expression of MT1 receptor in patients with gastric adenocarcinoma and its relationship with clinicopathological features.

Gastric cancer accounts 8% of the total cancer cases leading to 10% of total cancer deaths worldwide. The indoleamine N-acetyl-5-methoxytryptamine, better known as melatonin, is the principal hormone produced by the pineal gland. Recently, it has been well documented some anti-cancer roles of melatonin in some malignancies as breast and colon cancer; as well as some its protective roles in the GI tract that have been known as free radical scavenger, antimitogenic and apoptotic properties. According to the anti-cancer effects of melatonin, wide distribution of this neurohormone in GI tract and some proposed physiologic and pharmacologic roles for this neurohormone and following our previous study which has shown expression of MT2 receptor in gastric adenocarcinoma, this study initially scheduled to determine the expression of melatonin receptor MT1 in tissue samples of adenocarcinoma cancer patients. A total of 10 gastric adenocarcinoma patients and 10 normal individuals were examined for MT1 gene expression by real-time PCR. Additionally, for screening of different alleles of MT1 in our samples, the SSCP-PCR procedure was developed. Our results have shown interestingly high expression for MT1 receptor in cancer and marginal cancer groups comparing with normal group. Our findings also have shown that a remarkable association between MT1 receptor mRNA levels and grade in individuals over age 50. PCR-SSCP analysis results showed a variation between individuals which may be effective on their gene expression patterns. According to our knowledge, for the first time this study evaluated the expression of MT1 receptor gene in gastric adenocarcinoma tissues which consistent with our previous study but with some difference in comparisons between kind of tissue expression and difference in polymorphisms. Moreover, these results show the defending role of melatonin in the GI system.

Melatonin as an angiogenesis inhibitor to combat cancer: Mechanistic evidence.

Melatonin, a pineal indolamine, participates in different body functions and is shown to possess diverse biological activities such as anti-tumor action. Angiogenesis inhibition is one of the mechanisms by which melatonin exerts its oncostatic effects. Increased angiogenesis is a major feature of tumor progression, thus angiogenesis inhibition is a critical step in cancer therapy. Melatonin employs a variety of mechanisms to target nutrients and oxygen supply to cancer cells. At the transcriptional level, hypoxia induced factor-1α (HIF-1α) and the genes under its control, such as vascular endothelial growth factor (VEGF) are the main targets of melatonin for inhibition of angiogenesis. Melatonin prevents translocation of HIF-1α into the nucleus thereby hindering VEGF expression and also prevents the formation of HIF-1α, phospho-STAT3 and CBP/p300 complex which is involved in the expression of angiogenesis-related genes. Angiostatic properties of melatonin could be also due to its ability to inhibit VEGFR2's activation and expression. Other angiostatic mechanisms of melatonin include the inhibition of endothelial cell migration, invasion, and tube formation. In the present study, we have reviewed the molecular anti-angiogenesis pathways mediated by melatonin and the responsible mechanisms in various types of cancers both in vitro and in vivo.

An ethanol extract of Origanum vulgare attenuates cyclophosphamide-induced pulmonary injury and oxidative lung damage in mice.

CONTEXT: Injury to normal tissues is the major limiting side effect of using cyclophosphamide (CP), an antineoplastic alkylating compound. OBJECTIVE: This study was undertaken to evaluate the protective effect of an extract of Origanum vulgare L. (Lamiaceae), an antioxidative medicinal plant, against CP-induced oxidative lung damage in mice. MATERIALS AND METHODS: Mice were pre-treated with various doses of O. vulgare extract (50, 100, 200, and 400 mg/kg) for 7 consecutive days followed by an injection with CP (200 mg/kg b.w.) One hour after the injection of O. vulgare on the last day, mice were injected with CP; 24 h later, they were euthanized, their lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with O. vulgare significantly reduced the levels of lipid peroxidation and attenuated the alterations in glutathione content and superoxide dismutase activity induced by CP in lung tissue. In addition, O. vulgare effectively alleviated CP-induced histopathological changes in lung tissue. CONCLUSIONS: Our results revealed that O. vulgare protects lung tissues from CP-induced pulmonary damage and suggest a role for oxidative stress in the pathogenesis of lung disease produced by CP. Because O. vulgare has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a supplement for reducing lung damage in patients undergoing chemotherapy.

Unveiling the Protective Role of Metformin against Chemotherapyinduced Cardiotoxicity: A Comprehensive Scoping Review on Nonclinical Studies.

INTRODUCTION: Chemotherapy therapies are effective in treating cancer, but they can have harmful effects on the cardiovascular system. This study explores the possible role of metformin in reducing the cardiac damage caused by chemotherapy. METHODS: In this scoping review, we conducted a comprehensive literature search on electronic databases (PubMed, Scopus, and Web of Science (ISI)) until November 2023. The manuscript was screened regarding the role of metformin in chemotherapy-induced cardiotoxicity. Finally, 26 papers were selected after double screening. RESULT: Chemotherapy has the potential to damage and cause cell death in the heart, resulting in molecular, biochemical, and histological changes compared to an untreated group. However, co-treatment with metformin may offer protection by preventing or reversing these harmful effects on cardiac cells. Metformin's cardioprotective properties are thought to be due to its ability to modulate oxidative stress, inflammation, autophagy, and the apoptotic pathway. CONCLUSION: The present study strongly suggests that metformin is an effective solution to chemotherapy-induced cardiotoxicity. Metformin can alleviate the harmful effects of chemotherapy on the heart by affecting oxidative stress, inflammation, autophagy, and apoptosis pathways. However, it is essential to note that the use of metformin may have some drawbacks, as it is a non-targeted therapy and could potentially reduce the effectiveness of targeted cancer drugs. Despite this, the potential benefits of using metformin in clinical settings cannot be ignored. Further studies are necessary to determine the specifics of this interaction. Still, the promising results of this review suggest that metformin may be an essential tool in the fight against chemotherapy-induced cardiotoxicity.

The Protective Effect of N-acetylcysteine against Deltamethrin-Induced Hepatotoxicity in Mice.

Background: Exposure to pesticides is of concern to public health officials worldwide. Deltamethrin is a synthetic pyrethroid pesticide which is widely used in agriculture and veterinary medicine. Deltamethrin poisoning is always one of the concerns in medical centers due to the deltamethrin induced hepatotoxicity. This study evaluated the hepato-protective effects of N-acetylcysteine (NAC) against deltamethrin induced hepatotoxicity in mice. Methods: A total of 40 BALB/c male mice were randomly divided into four groups; the first group was used as a control (0.5 ml normal saline); Groups 2-4 were treated with NAC [160 mg/kg Body Weight (BW)], deltamethrin (50 mg/kg BW), and NAC plus deltamethrin. At 1 and 24 hr after treatment, the animals were sacrificed and blood and liver samples were obtained for analysis and the liver/body ration, hepatic enzymes as Aspartate aminotransferase (AST), Alanine Transaminase (ALT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), Glutathione (GSH) content and Reactive Oxygen Species (ROS) level were measured. For comparison between more than two experimental groups, one-way ANOVA following Tukey test was used by SPSS software. Results: The deltamethrin significantly increased AST, ALT, ALP, and the level of ROS level at the end of 1 and 24 hr after treatment; while the LDH level and GSH content were decreased. Mice in the deltamethrin treated group had a higher liver/body weight ratio than in other treated groups after 24 hr. On the other hand, NAC in combination with deltamethrin significantly reduced the activities of AST, ALT, ALP, and increased GSH levels. Conclusion: This study demonstrated that NAC has a hepatoprotective role against deltamethrin-induced toxicity.

Involvement of N4BP2L1, PLEKHA4, and BEGAIN genes in breast cancer and muscle cell development.

Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (N4BP2L1), pleckstrin homology domain-containing family A member 4 (PLEKHA4), and brain-enriched guanylate kinase-associated protein (BEGAIN) that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of PLEKHA4 in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified N4BP2L1 and BEGAIN as potential biomarkers of HER2-positive breast cancer. Furthermore, low BEGAIN expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed N4BP2L1 as a promising diagnostic protein biomarker in breast cancer. In addition, the in silico data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.

The role of ginseng derivatives against chemotherapy-induced cardiotoxicity: A systematic review of non-clinical studies.

Aims: Although chemotherapy agents are used to treating cancers, they have serious side effects, like their harmful effects on the cardiovascular system, limiting the clinical use of these chemotherapy agents. This study aimed to systematically investigate the potential role of ginseng derivatives in the prevention of chemotherapy-induced cardiac toxicity. Methods: This systematic review was performed according to PRISMA guidelines strategy in databases till August 2022. First, identify studies related to using search terms in titles and abstracts. After studying and screening 209 articles, 16 articles were selected in this study according to our inclusion and exclusion criteria. Results: According to the findings of this study, ginseng derivatives showed significant changes in biochemical, histological, and heart weight loss, as well as a reduction in mortality, which occurred in the groups treated with chemotherapy agents compared to the control groups. Co-administration of ginseng derivatives with chemotherapy agents inhibited or reversed these changes to near-moderate levels. The protective effects of ginseng derivatives can be due to their anti-inflammatory, anti-oxidant, and anti-apoptotic action. Conclusion: This systematic review shows evidence that concomitant administration of ginseng derivatives improves chemotherapy-induced cardiac toxicity. However, for better conclusions about the practical mechanisms of ginseng derivatives in reducing the cardiac toxic effects of chemotherapy agents and evaluating the efficacy and safety of the compound simultaneously, it is necessary to design comprehensive studies.