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.

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.

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.

A systematic review on the role of melatonin and its mechanisms on diabetes-related reproductive impairment in non-clinical studies.

Background: Diabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin's effect on the reproductive system adversely affected by diabetes mellitus (DM). Methods: A comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria. Results: The results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis. Conclusion: Melatonin exerted a protective action on the impaired reproductive system in in-vivo and in-vitro models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.

The neuroprotective effects of melatonin against diabetic neuropathy: A systematic review of non-clinical studies.

Backgrounds: Diabetes can cause diabetic neuropathy (DN), a nerve injury. High blood sugar (glucose) levels can harm nerves all over your body. The nerves in your legs and feet are the most commonly affected by DN. The purpose of this study was to conduct a review of melatonin's potential neuroprotective properties against DN. Method: A full systematic search was conducted in several electronic databases (Scopus, PubMed, and Web of Science) up to March 2022 under the PRISMA guidelines. Forty-seven studies were screened using predefined inclusion and exclusion criteria. Finally, the current systematic review included nine publications that met the inclusion criteria. Result: According to in vivo findings, melatonin treatment reduces DN via inhibition of oxidative stress and inflammatory pathways. However, compared to the diabetes groups alone, melatonin treatment exhibited an anti-oxidant trend. According to other research, DN also significantly produces biochemical alterations in neuron cells/tissues. Additionally, histological alterations in neuron tissue following DN were detected. Conclusion: Nonetheless, in the majority of cases, these diabetes-induced biochemical and histological alterations were reversed when melatonin was administered. It is worth noting that the administration of melatonin ameliorates the neuropathy caused by diabetes. Melatonin exerts these neuroprotective effects via various anti-oxidant, anti-inflammatory, and other mechanisms.

Investigation of anti-cancer effects of new pyrazino[1,2-a]benzimidazole derivatives on human glioblastoma cells through 2D in vitro model and 3D-printed microfluidic device.

AIMS: Recent studies show targeted therapy of new pyrazino[1,2-a]benzimidazole derivatives with COX-II inhibitory effects on different cancer cells. This study aimed to investigate 2D cell culture and 3D spheroid formation of glioblastoma multiforme (GBM) cells using a microfluidic device after exposure to these compounds. MAIN METHODS: After isolating astrocytes from human GBM samples, IC50 of 2,6-dimethyl pyrazino[1,2-a]benzimidazole (L1) and 3,4,5-trimethoxy pyrazino[1,2-a]benzimidazole (L2) were determined as 13 µM and 85 µM, respectively. Then, in all experiments, cells were exposed to subtoxic concentrations of L1 (6.5 µM) and L2 (42.5 µM), which were ½IC50. In the following, in two phases, cell cycle, migration, and gene expression through 2D cell culture and tumor spheroid formation ability using a 3D-printed microfluidic chip were assessed. KEY FINDINGS: The obtained results showed that both compounds have positive effects in reducing G2/M cell population and GBM cell migration. Furthermore, real-time gene expression data showed that L1 and L2 significantly impact the upregulation of P21 and P53 and down-regulation of cyclin D1, MMP2, and MMP9. On the other hand, GBM spheroids exposed to L1 and L2 become smaller with fewer live cells. SIGNIFICANCE: Our data on human isolated astrocyte cells in 2D and 3D cell culture conditions showed that L1 and L2 compounds could reduce GBM cells' invasion by controlling gene expressions associated with migration and proliferation. Moreover, designing microfluidic platform and related cell culture protocols facilitates the broad screening of 3D multicellular tumor spheroids derived from GBM tumor biopsies and provides effective drug development for brain gliomas.

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.

The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment.

BACKGROUND: Aluminum phosphide (AlP) toxicity is associated with a high risk of death due to heart, liver, and kidney failure as the target organs. Phosphine gas released due to the ingestion is the main factor involved in the multi-organ failure with various mechanisms. Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs. This study aimed to investigate whether LEV can alleviate AlP-induced nephrotoxicity in the rat model. METHOD: Six groups included control group (almond oil only), sole LEV group (48 µg/kg), AlP group (LD50=10 µg/kg), and the poisoned groups treated with LEV at doses of 12, 24, and 48 µg/kg 30 min after AlP gavage. After 24 hours of treatment, serum and kidney samples were taken for biochemical and histopathological analyses. RESULT: Biochemical analysis of the AlP group showed that the activity of complexes I, II, and IV was significantly reduced, while the levels of lipid peroxidation (LPO) and reactive oxygen species (ROS), lactate, and myeloperoxidase (MPO) activity significantly increased. Also, AlP reduced live renal cells and elevated necrosis. However, the levels of serum creatinine and blood urea nitrogen were not affected by the poisoning. LEV co-treatment could increase mitochondrial complex activity and reduce MPO activity, LPO, ROS, and lactate levels. Additionally, the histopathological analysis showed the detrimental effects of AlP on kidney tissue, which was mitigated by LEV administration. CONCLUSION: Our findings showed that LEV can potentially improve oxidative stress, imbalance in the redox status, necrosis, and pathological injuries in kidney tissue following AlP-poisoning.

Combination therapy of cisplatin and resveratrol to induce cellular aging in gastric cancer cells: Focusing on oxidative stress, and cell cycle arrest.

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease's high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested. Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest. Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol. Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.

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.

Assessment of cytotoxic effects of new derivatives of pyrazino[1,2-a] benzimidazole on isolated human glioblastoma cells and mitochondria.

AIMS: Glioblastoma multiforme (GBM) is a highly devastating malignant brain tumor with poor pharmacotherapy. Based on COX-2 inhibitory effects in preventing cancer progression, new pyrazino[1,2-a]benzimidazole derivatives were assessed on isolated human GBM cells. MAIN METHODS: In this study, firstly, primary culture of astrocytes from human GBM samples was prepared and exposed to 2,6-dimethyl pyrazino[1,2-a]benzimidazole (L1) and 3,4,5-trimethoxy pyrazino[1,2-a]benzimidazole (L2) for finding their half-maximal inhibitory concentration (IC50). In the following, in two phases, cell apoptosis pathway and mitochondrial markers were investigated on GBM and also HEK293 cells (as non-cancerous normal cells). KEY FINDINGS: The MTT results represented a remarkable selective cytotoxic effect of both L1 and L2 on GBM cells, and interestingly not on normal cells. After 48 h, IC50 of L1 and L2 were calculated as 13 µM and 85 µM, respectively. Annexin/PI staining showed that L1 and L2 induce apoptosis in GBM cells, and caspase measurement showed that apoptosis occurs through mitochondrial signaling. In the clonogenic assay, GBM cells formed more paraclones and fewer holoclones after treating with L1 and L2. L1 and L2 also selectively enhanced mitochondrial damaged markers, including reactive oxygen species (ROS) formation, and mitochondrial swelling, decreased mitochondrial membrane potential (MMP) and cytochrome c release in isolated cancerous GBM mitochondria. SIGNIFICANCE: Our findings on human primary astrocyte cells illustrated that L1 and L2 compounds, with COX-2 inhibitory effect, through the intrinsic pathway of apoptosis concerning mitochondrial damage enhancement have therapeutic potentials on GBM.

Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model.

Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10 mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2 mg/kg) injected intraperitoneally 30 min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180 min. Blood glucose level was measured in the study groups 30 min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24 h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24 h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.

Insights Into Parkin-Mediated Mitophagy in Alzheimer's Disease: A Systematic Review.

Background: Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's disease (AD). The role of this mitophagy pathway in neurodegenerative diseases has drawn attention in recent years. The two main pathological proteins in AD, amyloid ß (Aß) and human Tau (hTau), interfere with mitochondrial dynamics through several pathways. However, taking into consideration the specific interactions between Aß/hTau and Parkin, special focus is required on this mitophagy pathway and AD. In this review, these interactions are fully discussed, and an overview of the neuroprotective drugs that enhance Parkin-mediated mitophagy is presented. Methods: This systematic review was performed according to PRISMA guidelines, and a comprehensive literature search was done in the electronic databases up to September 2020, using search terms in the titles and abstracts to identify relevant studies. One hundred eighty-six articles were found, and 113 articles were screened by title and abstract. Finally, 25 articles were included in this systematic review according to our inclusion and exclusion criteria. Results: Accumulation of Aß and hTau affects mitophagy, including Parkin-mediated. Tau seems to prevent Parkin translocation directly. A Parkin level in the cell appears to be of importance in determining the damage caused by Aß and hTau and in the future therapeutic approaches. Parkin controls the PINK1 level via the presenillins, suggesting that mutations in presenillins affect Parkin mitophagy. Significance: Parkin mitophagy is a process affected by several AD pathological events multidimensionally.

Toxic potential of botulinum toxin type A on senescence in a Drosophila melanogaster model.

Botulinum toxin type-A (BoNT/A) application, especially neurological disorders, has been spread nowadays while it may cause side effects. The current study aimed to assess the BoNT/A dose-dependent effect on induction of aging in the Drosophila melanogaster model. The third instar larvae of Drosophila melanogaster were exposed to » LC50, ½ LC50, and LC50 of BoNT/A in the Drosophila diet for 48 h while H2O2 1% was used as a positive control. After the exposure time, some larvae were collected for molecular study, including gene expression analysis, comet assay, oxidative stress markers, and the phenotype changes. BoNT/A induced dose-dependent cytotoxicity, elevated reactive oxygen species (ROS) levels, and superoxide dismutase (SOD) enzyme activity. In addition, it caused DNA damage and activated caspase-3 and -9, and reduced the body size of the fly, especially in high doses. In line with the purpose of the study, aging markers, including ß-galactosidase (ß-gal), p16, p21, p38, and p53, were up-regulated by BoNT/A low dose. BoNT/A activates the aging pathway in the low dose, and increasing the dose induces toxicity, including oxidative stress, DNA damage, and apoptosis.

Vinpocetine Effect on the Juncture of Diabetes and Aging: An in-vitro study.

BACKGROUND: The rapid-growing population of diabetic patients and the elderly are among the direst challenges that the science of medicine is facing today. Targeting these two challenges can shed light on new means to control and ideally reverse this trend. In this experiment, Vinpocetine's effect on aged pancreatic beta-cell functions in correlation with oxidative stress was studied. METHODS: Islet cells were isolated from the pancreas of aged rats and exposed to Vinpocetine, dissolved in acetone and RPMI, for 48 h. Then, senescence-associated molecular parameters, including P16 and P38 gene expressions and ß-galactosidase activity, were investigated along with diabetic and inflammation markers. RESULTS: Experimental results showed that Vinpocetine could significantly increase aged islets insulin secretion and also make a meaningful reduction in oxidative stress markers. This drug can also decrease expression levels of P16 and P38, the primary genes responsible for the aging pathway. TNF-α, IL-6, and NF-κB expressions were also reduced noticeably after treatment with Vinpocetine. CONCLUSION: The current study showed that Vinpocetine, a derivative of the secondary plant metabolite called Vincamine, could break this vicious cycle of oxidative stress and aging by reducing oxidative stress and inflammation, thus inhibiting cellular aging.

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.

On the mechanisms of taurine in alleviating electrocardiographic, hemodynamic, and biochemical parameters following aluminum phosphide cardiotoxicity.

BACKGROUND: Aluminum phosphide (AlP) causes severe cardiotoxicity. Taurine has been chosen for the present study because of its positive known effects on cardiac injuries. METHOD: To evaluate AlP-induced cardiotoxicity, the animals were divided into seven groups, including the control group, the taurine group (500 mg/kg), AlP with LD50 dose, AlP + taurine 20, 50, 100, and 200 mg/kg group. To assess cardiac hemodynamic parameters, Wistar rats received taurine intraperitoneally 60 min after AlP gavage. Cardiac hemodynamic parameters were evaluated for 180 min. To study biochemical parameters, 24 h after AlP treatment, the animals were sacrificed, and heart tissues were collected. RESULT: ECG, BP, and HR abnormalities of AlP poisoning were improved by taurine treatment. AlP induced biochemical alterations including complexes I and IV activities, the ADP/ATP ratio, mitochondrial membrane potential, cytochrome C release, and oxidative stress biomarkers ameliorated by taurine. Moreover, taurine improved apoptosis, as well as lessened CK-MB and troponin I levels. Also, there were no significant changes between taurine 500 mg/kg and the control group in tests. CONCLUSION: The present findings showed that taurine could be a possible candidate for AlP cardiotoxicity treatment via the effect on mitochondrial electron transfer chain and maintaining intracellular ATP balance.

Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer.

The conventional cancer treatment modalities such as radiotherapy and chemotherapy suffer from several limitations; hence, their efficiency needs to be improved with other complementary modalities. Hyperthermia, as an adjuvant therapeutic modality for cancer, can result in a synergistic effect on radiotherapy (radiosensitizer) and chemotherapy (chemosensitizer). Conventional hyperthermia methods affect both tumoral and healthy tissues and have low specificity. In addition, a temperature gradient generates in the tissues situated along the path of the heat source, which is a more serious for deep-seated tumors. Nanoparticles (NPs)-induced hyperthermia can resolve these drawbacks through localization around/within tumoral tissue and generating local hyperthermia. Although there are several review articles dealing with NPs-induced hyperthermia, lack of a paper discussing the combination of NPs-induced hyperthermia with the conventional chemotherapy or radiotherapy is tangible. Accordingly, the main focus of the current paper is to summarize the principles of NPs-induced hyperthermia and more importantly its synergic effects on the conventional chemotherapy or radiotherapy. The heat-producing nanostructures such as gold NPs, iron oxide NPs, and carbon NPs, as well as the non-heat-producing nanostructures, such as lipid-based, polymeric, and silica-based NPs, as the carrier for heat-producing NPs, are discussed and their pros and cons highlighted.

An Updated Review of Various Medicinal Applications of p-Co umaric Acid: From Antioxidative and Anti-Inflammatory Properties to Effects on Cell Cycle and Proliferation.

P-Coumaric acid (p-CA) is a hydroxycinnamic acid, an organic compound that is a hydroxyl derivative of cinnamic acid. P-CA is the most abundant isomer in nature and can be found in a wide variety of edible plants such as fungi, peanuts, navy beans, tomatoes, carrots, basil, and garlic. Recently, the therapeutic properties of p-CA have received a great deal of attention from scientific society. Here, we described the medicinal effects of p-CA on various pathological conditions. This review was performed via evaluating PubMed reported studies from January 2010 to January 2020. Also, reference lists were checked to find additional studies. All intermediation or complementarity of animal models, case-control and cohort studies, in vitro studies, and controlled trials (CTs) on p-CA were acceptable. However plant extract studies without indication of main active substances were excluded due to the considerable diversities and heterogeneities. According to recent evidence regarding the beneficial effects of p-CA, numerous diseases such as nephropathies, cardiovascular diseases, neuroinflammatory diseases, liver diseases, cancers, and some metabolic disorders could potentially be controlled by this natural herb. Interestingly, autophagy is a novel molecular mechanism involved in the crosstalk between classic effects of p-CA and introduces alternative therapeutic pathways for this compound. Much work remains in clarifying the main therapeutic properties among the various p-CA effects; these will be the subject of forthcoming work, resulting in presenting further mechanism of action.

LncRNA-miRNA-mRNA Networks of Gastrointestinal Cancers Representing Common and Specific LncRNAs and mRNAs.

Gastrointestinal (GI) cancers are responsible for approximately half of cancer-related deaths, highlighting the need for the identification of distinct and common features in their clinicopathological characteristics. Long ncRNA (lncRNAs), which are involved in competitive endogenous RNA (ceRNA) networks with critical roles in biological processes, constitute a substantial number of non-coding RNAs. Therefore, our study aimed to investigate the similarities and differences in the ceRNA networks of The Cancer Genome Atlas (TCGA)-GI cancers. We performed a comprehensive bioinformatics analysis of ceRNA networks for TCGA-GI cancers in terms of the deferential mRNA, lncRNA, and miRNA expression levels, ceRNA networks, overall survival analysis, correlation analysis, pathological cancer stages, and gene set enrichment analysis. Our study revealed several common and distinct mRNAs and lncRNAs with prognostic values in these networks. It was specifically noteworthy that MAGI2-AS3 lncRNA was found to be shared in almost all GI cancers. Moreover, the most common shared mRNAs between GI cancers were MEIS1, PPP1R3C, ADAMTSL3, RIPOR2, and MYLK. For each cancer ceRNA network, we found that the expression level of a number of lncRNAs and mRNAs was specific. Furthermore, our study provided compelling evidence that several genes, most notably KDELC1, can act as novel proto-oncogenes in cancers. This, in turn, can highlight their role as new prognostic and therapeutic targets. Moreover, we found cell cycle and extracellular matrix structural constituent as the top shared KEGG and molecular function, respectively, among GI cancers. Our study revealed several known lncRNAs and known and unknown mRNAs in GI cancers with diagnostic and prognostic values.