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Background: Several studies have indicated an association between cadmium (Cd) exposure and the induction of thyroid dysfunction in animal models. Objective and Aims: There are inconsistent findings on the effect of Cd on the thyroid gland. Therefore, this systematic study was designed to determine the association between changes in thyroid function markers and Cd exposure in animals., Method: The search was performed on Scopus, PubMed, Web of Science and databases, and Google Scholar until May 2023. Studies on the relationship between Cd exposure and fish's thyroid function were conducted on rodents and fish., Results: In total, 171 articles were obtained from the main databases using the search strategy mentioned in this study. Finally, 24 articles were selected according to our inclusion criteria for systematic studies. The findings indicated an increase/decrease or no change in triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels in rodents, fish, and animals exposed to Cd., Conclusion: Our findings indicated an association between Cd exposure and thyroid dysfunction in rodents, fish, and other animals. However, the association between urinary and blood Cd levels and thyroid function remains unclear in humans because of controversial findings and a lack of strong mechanistic evidence. We perform large cohort human studies to the answer to this question., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: Chlorpyrifos (CPF), which is classified as an Organophosphorus Pesticide (OP), has been identified as a toxic agent for the reproductive system due to its capacity to induce oxidative stress and inflammation. Curcumin (CUR) has been reported as a natural antioxidant and anti-inflammatory agent that could combat toxicity in various tissues. This study aims to examine the protective effects of CUR and its nanoformulation against reproductive impairment induced by CPF., Method: Forty-eight female Wistar albino rats were randomly allocated to six groups (n=8): control (0.5 mL of corn oil, the solvent for CPF), CPF (10 mg/kg), CPF + CUR 100 mg/kg/day, CPF + CUR 300 mg/kg/day, CPF + nano-micelle curcumin (NMC) 2.5 mg/kg/day, and CPF + NMC 5 mg/kg/day. The experimental treatment was performed for 30 days. Then, brain, ovary and uterus tissues were collected for measuring oxidative stress and inflammatory indices., Result: MDA, NO, IL-6, and TNF-α concentrations significantly increased in the brain, ovary and uterus of the CPF group versus the control group (p < 0.001). The levels of GSH and SOD in the uterus, ovaries, and brain exhibited a significant decrease in the CPF group compared to the control group (p < 0.05). However, CUR (300 mg/kg) and NMC (5 mg/kg) significantly decreased MDA, NO, TNF-α, and Il-6 and increased SOD and GSH levels in the uterus, ovaries and brain of the CPF-exposed animals versus the CPF-exposed non-treated animals (p < 0.001)., Conclusion: Our findings indicated that CUR and NMC could be effective in alleviating CPFinduced reproductive toxicity., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: This study aimed to evaluate the hepatotoxicity of buprenorphine in lactating rat pups of buprenorphine-injected mothers. Buprenorphine (BUP), a semisynthetic opioid, is increasingly administrated as a first-line standard maintenance treatment for opioid dependence due to its high safety and efficacy compared to other opioids. Numerous studies have confirmed the safety of BUP maintenance treatment in addicted patients., Objectives: This study was designed to assess the effects of BUP on the activities of liver enzymes, oxidative parameters, and liver histopathological changes in pups born to a mother exposed to this drug during lactation., Methods: BUP at a dose of 0.5 or 0.1 mg/kg was subcutaneously administrated to lactating rats for 28 days. At the end of the experiment, the pups were anesthetized, and blood samples were obtained from their hearts for measuring liver enzymes. Then the livers of the animals were dissected to measure oxidative stress parameters. In addition, the liver samples were fixed for histopathological evaluation., Results: The findings indicated a decrease in the activities of serum liver enzymes (ALT and AST) of the pups born to mothers exposed to 0.5 and 1 mg/kg of BUP during lactation. BUP could not change malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO) levels, nor superoxide dismutase (SOD) activity in the liver tissue of animals. Some vacuolated hepatocytes with dark, eccentric nuclei, necrosis with karyolytic nuclei, mitotic figures, and multiple binucleated cells were seen in the pups which received 1 mg/kg of BUP., Conclusion: In conclusion, BUP may induce liver dysfunction in pups born to mothers exposed to this drug during lactation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: This study was performed to evaluate the protective effects of chrysin (CH) on metabolic impairment and pancreatic injury caused by sub-chronic chlorpyrifos (CPF) intoxication in male rats., Methods: Forty male Wistar rats were randomly allocated into five groups (n=8). Intraperitoneal injections of chrysin (12.5, 25 and 50 mg/kg for 45 days) and CPF (10 mg/kg for 45 days) gavage were performed. Present findings indicated that the serum levels of glucose, total cholesterol, and lowdensity lipoprotein-cholesterol, as well as body weight, were increased in the CPF-exposed group., Results: It was also found that CPF decreased superoxide dismutase activity as well as increased malondialdehyde and nitric oxide levels in the pancreatic tissue of exposed animals. Histopathological examination also confirmed the toxic effects of CPF on pancreatic tissue as mostly evidenced by infiltration of inflammatory cells and necrosis. CH (50 mg/kg) decreased blood glucose concentration (p < 0.05), TG (p < 0.05), and LDL-C in CPF-exposed animals. CH decreased the pancreas levels of MDA in all treated CPF-exposed groups versus the non-treated CPF-exposed group (p < 0.05, p < 0.001, p < 0.001, respectively). A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. A significant difference was not seen in the NO and MDA levels and SOD activity between CHtreated (50 mg/kg) animals exposed to CPF and controls., Conclusion: A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. In conclusion, CH could prevent initiate and progress of CPF-induced metabolic impairment by modulating oxidative stress in pancreatic tissue as a target organ of organophosphorus pesticides., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Numerous evidence indicates the association between polychlorinated biphenyls (PCBs), an endocrine disrupter, with thyroid hormone disruption, contradictory findings also exist. Herein, we tried to address this question by performing a scoping review., Content: The search was performed on PubMed, Scopus, Web of Science, and Google Scholar databases from 2010 onwards. Animal studies on PCBs' effect on thyroid function were searched. The SYRCLE's RoB scale assessed the risk of bias. I2 and Q tests are used for investigating heterogeneity. A random-effects model with the pooled standard means difference (SMD) and 95 % confidence interval (CI) was performed for the TSH, TT4, TT3, and FT4 outcomes using Comprehensive Meta-Analyses (CMA) Software version 3. Also, we conducted subgroup analyses based on the different types of PCB. The initial search identified 1,279 publications from the main databases 26 of them fulfilled our eligibility criteria for the study, and then five studies among selected studies had sufficient data for analysis. Meta-analysis of data revealed that Aroclor 1260 (SDM: -0.47, 95 % CI: -0.92, -0.01, p=0.044) and PCB 126 (SDM: 0.17, 95 % CI: -0.40, 0.75, p=0.559) significantly increased TSH concentration in the exposed groups vs. the control groups. Related to the effects of PCBs on the TT4, our findings indicated a significant reduction the TT4 concentration of animals exposed to Aroclor 1260 (SDM: -5.62, 95 % CI: -8.30, -2.94, p=0.0001), PCB 118 (SDM: -6.24, 95 % CI: -7.76, -4.72, p=0.0001), PCB 126 (SDM: -1.81, 95 % CI: -2.90, -0.71, p=0.001), and PCB 153 (SDM: -1.32, 95 % CI: -2.29, -0.35, p=0.007) vs. the controls. Our meta-analysis indicated a significant increase in TT3 concentration following exposure to PCB 118 and PCB 153 (SDM: -0.89, 95 % CI: -1.36, -0.42, p=0.0001, and SDM: -1.45, 95 % CI: -2.15, -0.75, p=0.0001, respectively). Aroclor 1254 and PCB 126 significantly decreased TT3 concentration (SDM: 1.25, 95 % CI: 0.29, 2.21, p=0.01 and SDM: 3.33, 95 % CI: 2.49, 4.18, p=0.0001, respectively). PCB 126 significantly decreased FT4 in the exposed groups vs. the control groups (SDM: -7.80, 95 % CI: -11.51, -5.35, p=0.0001)., Summary: Our findings showed an association between PCBs exposure and hypothyroidism in rodents, fish, and chicken embryos., Outlook: Regarding to the most evidence of hypothyroidism effects of PCBs in animal species, it is necessary to consider large cohort studies to address the association between PCBs exposure and thyroid function impairment in humans., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Amniotic fluid in the uterus is beneficial for the fetus growth and protection due to its nutritional elements as well as its antibacterial and anti-inflammatory properties. Today, body membranes are increasingly being used in multiple fields. The purpose of the current study was evaluation of the antibacterial effects of amniotic fluid and comparison of its effects on pathogenic and probiotic bacteria., Methods: This experimental study was conducted on amniotic fluid obtained from 43 healthy mothers who gave birth by selective cesarean section. Then, antibacterial effects of amniotic fluids were investigated on 8 standard bacterial strains, including Bacillus cereus, Escherichia coli, Staphylococcus aureus, Shigella flexneri, Pseudomonas aeruginosa, Klebsiella pneumoniae, Bacillus cereus, and Lactobacillus plantarum by agar well-diffusion method. Data analysis was performed by SPSS software, vs . 22 (IBM, US)., Results: Amniotic fluid revealed an inhibitory effect on the growth of bacterial strains. Staphylococcus aureus and Streptococcus pyogenes strains showed growth inhibition in 39% and 17% of samples, respectively. In other bacterial strains, there was growth inhibition in less than 5% of the samples. Also, the zone of growth inhibition for Staphylococcus aureus and Streptococcus pyogenes was significantly higher than the other strains. Amniotic fluid samples had an antibacterial effect on all pathogen strains in general, but not on the Lactobacillus plantarum probiotic strain., Conclusion: Our findings suggest that the antibacterial effect of amniotic fluid on pathogenic bacteria is significantly higher than the Lactobacillus plantarum as a probiotic one. Overall, the findings support the use of natural substances as alternative therapeutic agents to combat antibiotic resistance., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright© 2023, Avicenna Research Institute.)

This study investigated the effect of buprenorphine (BUP) on the livers of pups exposed to this drug during the fetal stage. BUP decreased the activities of serum liver enzymes in exposed animals versus the controls. BUP (0.5 mg/kg) decreased malondialdehyde levels and increased the glutathione levels in the liver of animals versus other groups. The superoxide dismutase activity was elevated in the BUP 0.5 mg/kg group versus the control group. BUP (1 mg/kg) induced histopathological changes in the livers of pups. In conclusion, BUP may induce hepatotoxicity in pups exposed to this drug during the fetal stage.

Background: Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity., Objective: The aim of this study was to evaluate the protective effect of dantrolene on digoxininduced cardiotoxicity in male rats., Methods: This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n = 6) as follows: Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group, Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group, Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group, Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group, Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals' cavernous sinus and each animal's heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20°C. The heart samples were fixed in formalin 10% for histopathological evaluation., Results: K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group ( p < 0.001). Dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group ( p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group., Conclusion: dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene's cardioprotective and cardiotoxic doses in animal models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Purpose: Medicinal plants have been used to cure numerous diseases compared to orthodox medicines. The present study estimated the antidiabetic activity of ethanolic extract of Salvia tebesana Bunge in streptozotocin-induced diabetic rats., Experimental Approach: In this study type 2 diabetes was induced in male rats by streptozotocin (65 mg/kg, i.p.). After diabetes induction, normal control groups were treated with distilled water, the positive control group received metformin (500 mg/kg), and the other groups were orally treated with ethanolic extracts of S. tebesana (100, 200, and 400 mg/kg) for 4 weeks. Changes in body weight and some biochemical parameters were determined., Findings / Results: The ethanolic extract of S. tebesana in all doses considerably declined serum glucose, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and triglyceride compared with the diabetic control rats. Administration of ethanolic extract of S. tebesana reduced the serum of kidney and liver function factors and decreased the side effects on the function of these., Conclusion and Implications: These results revealed the potential of S. tebesana for the cure of diabetes and its problems., Competing Interests: The authors declared no conflict of interest in this study., (Copyright: © 2022 Research in Pharmaceutical Sciences.)

We performed a systematic and meta-analysis study to find the association between cadmium (Cd) exposure and blood pressure (BP)/hypertension (HTN) in exposed general populations. We searched main databases for literature published between year 2000 and April 15, 2021. Quality assessment was performed with the Joanna Briggs Institute (JBI) critical appraisal tools. Heterogeneity between studies was determined by I-squared (I 2 ) statistic. The random effects model was used to determine the association between blood and urine Cd levels with hypertension. The overall standard differences in mean for Cd level in hypertensive and control groups were 3.34, 1.79, and 8.09 based on samples from blood, urine, and hair, respectively. The overall standard differences in mean for Cd level in the low and high exposure groups were - 0.795 and - 1.036 based on blood and urinary samples, respectively. Our findings indicate a positive relationship between blood and hair Cd levels and hypertension. We also found that hair is the optimal biological sample to find the relationship between Cd exposure and hypertension for both genders. However, more studies are needed to confirm these findings., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of the present study was to investigate the protective effect of the Sophora pachycarpa (S. pachycarpa) seed extract against carbon tetrachloride-induced toxicity on body organs, blood, and biochemical factors. In this investigation, 40 male Wistar rats weighing 200-250 g were randomly divided into 5 groups: group I was used as control, group II received carbon tetrachloride (CCl 4 ) (IP, 1 mL/kg) on day 21, group III and group IV received S. pachycarpa seed extract at doses of 150 mg/kg and 300 mg/kg, respectively for 21 days by oral gavage and CCl 4 on day 21, group V received silymarin (300 mg/kg) for 21 days by oral gavage and CCl 4 on day 21. CCl 4 showed an increase of serum renal and hepatic markers creatinine, urea, blood urea nitrogen (BUN), and uric acid, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Also, it significantly increased MDA level, and decreased CAT, FRAP, GSH, and SOD in the liver and kidney tissues. These changes and also hematological and histopathological alterations were significantly ameliorated by S. pachycarpa seed extract before CCl 4 administration. In conclusion, the data obtained in our investigation confirm the protective effect of S. pachycarpa against acute exposure to CCl 4 -induced organ toxicity in rats., (© 2022. The Author(s).)

The study investigated the effect of buprenorphine (BUP) on oxidative indices and gene expression of apoptotic molecules in the hippocampus of neonates during the fetal stage. BUP (1 or 0.5 mg/kg) was subcutaneously administrated to pregnant rat dams. After parturition, the pups were maintained to the end of breastfeeding period, then hippocampi were assessed for oxidative stress indices [glutathione (GSH), thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), total antioxidant capacity (TAC)] and mRNA expression of apoptotic markers (Bax, Bcl2 and caspase 3). Our data indicated that BUP (0.5 mg/kg) administration during gestation significantly increased GSH and TAC concentrations in the hippocampus of pups versus control group (p < 0.05). BUP (0.5 and 1 mg/kg) administration significantly elevated the expression levels of Bcl2 in the hippocampus of neonates compared with controls. BUP injection (0.5 and 1 mg/kg) to pregnant rats markedly reduced the expression levels of caspase 3 in the hippocampus of neonates in BUP 0.5 group (p < 0.01) and BUP 1 group (p < 0.05) versus the controls. Our study indicated that BUP may potentiate antioxidant system and inhibit apoptosis and oxidative stress in the hippocampus of neonates received this drug during the fetal stage., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier B.V.)

This study aimed to assess the effects of Buprenorphine (BUP) on oxidative parameters in pups born to mothers exposed to the drug during gestation and lactation. Pregnant and lactating rats received BUP, 0.5 or 0.1 mg/kg subcutaneously for 21 and 28 days, respectively. At the end of the study, the pups were anesthetized, and the hearts were dissected out to measure oxidative stress indices, including the levels of Malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), and the activity of Superoxide dismutase (SOD). Our findings indicated that BUP did not alter MDA, NO, GSH levels, nor SOD activity in the cardiac tissue of pups exposed to this drug during the fetal period and through breast milk. We suggest performing additional studies to determine the association between BUP and oxidative modifications in cardiac tissues of pups born to mothers under BUP therapy during gestation and lactation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We aimed to review the literature to find the specific effect of opioids on the activity of cholinesterase (ChE) enzyme which plays a substantial role in the functioning of cholinergic system. Literature search was performed by two independent reviewers in order to find relevant articles about the changes in the activity of ChE in mice or rat following opioid administration. Based on findings from literature review, opioid administration is able to induce cholinergic modulation via decreasing or increasing the activity of ChE enzyme. However, the degree of variation of ChE in various brain regions is different. No gender differences was reported in the effect of opioids on ChE activity. Although chronic opioid administration may decrease enzyme function, ChE activity might be unchanged following opioid withdrawal using naloxone or the development of tolerance. Opioid type affects whether or not naloxone can reverse the changes of ChE. Direct inhibitory action of morphine and the other opioid ligands believed responsible for the decrease in the ChE activity. Moreover, the potency of codeine to induce allosteric enhancement of acetylcholine receptor signaling might be involved in the cholinergic modulation of codeine and other opioids. Animal studies on rat and mice showed that opioids may change the activity of ChE. These changes can pertain an increase or decrease in enzyme activity; as there might be no change. The type of opioid used may have an effect on the cholinergic modulation. It is beneficial to conduct cross-sectional and cohort studies on addicted individuals, especially opium abusers, to find the precise association of opioids with alterations in human acetyl cholinesterase or butyrylcholinesterase. Simulation studies can also examine the structure-function relationships and provide important details to better understand the mechanism of action of opioid compounds on ChE activity. In addition, understanding how opioids impact ChE activity may help perform proper interventions for drug abstinence., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Teucrium polium (TP) has been traditionally used for treatment of the diabetes mellitus, kidney and liver diseases, and inflammations but some studies have reported the hepatotoxicity effects of this plant. Therefore, this study was conducted to investigate the effect of TP aqueous extract on the liver of the diabetic rats., Methods: Adult male Wistar rats were randomly divided into five groups: (Control) Normal rats that were gavaged with normal saline (1 mL), (TP100) Normal rats (Non-diabetic) that were gavaged with TP (100 mg/kg), (DM) diabetic model rats, which became diabetic by intraperitoneal injection of streptozotocin (50 mg/kg), (DTP100) diabetic rats that were gavaged with TP (100 mg/kg), and (DTP200) diabetic rats that were gavaged with TP (200 mg/kg). The effects of the aqueous extract on the blood glucose, body weight, the activities of enzyme markers of liver damage (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)) were investigated in the serum of the control and treated groups. At the end of study liver histopathology and the total antioxidant activity (TAA) test were evaluated. Finally, obtained data were analyzed by the SPSS software (version 16)., Results: Results showed that the AST and ALT levels were significantly increased in the diabetic rats (p<0.001). A comparison of 100 mg/kg and 200 mg/kg doses of TP administration in diabetic rats also showed a significant difference (p=0.01), indicating a better performance of 100 mg/kg dose. No significant difference was found between the control group and rats treated by the TP (TP100) (p=0.382). Also, triglyceride (TG) and cholesterol levels were significantly decreased in the treated groups compared to the diabetic untreated group., Conclusions: Findings of the study revealed no hepatotoxicity, and the hepatoprotective effects of the TP were proved in the present study., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Urinary tract stones are one of the most common diseases in the urinary tract. Lack of kidney stone treatment causes irreparable damages to the kidneys, which has many harmful effects. Date palm pits are recommended in traditional medicine as an effective drug in the treatment of kidney stones. The aim of this study was to investigate the effect of aqueous extract of date palm pits on kidney stones induced by ethylene glycol in male rats., Methods: In this study, 40 rats were classified into five groups (n = 8), including the healthy group receiving normal water, the negative control group, the therapeutic groups with doses of 150 mg/kg and 300 mg/kg, and the prevention group with a dose of 300 mg/kg. In order to induce kidney stones, ethylene glycolated water (1%) was used as drinking water in the studied groups. Blood and urine of rats were collected on days 14 and 28 of the study to assess urinary parameters of calcium, creatinine, uric acid and phosphorus, and serum parameters of blood urea nitrogen, creatinine, uric acid, calcium, and phosphorus. Also, the kidneys of rats were removed from the body on day 28 of the study and were given to a pathologist for examination., Results: Results of serum parameters shows that the use of date palm pits extract in the treatment and prevention groups with a dose of 300 mg/kg significantly (P < .05) has reduced the levels of blood urea nitrogen, uric acid, calcium, creatinine and phosphorus. Also, the results of urinary parameters show that the use of the extract caused a significant decrease (P < .05) in creatinine, uric acid and calcium in the prevention group and a significant decrease (P < .05) in creatinine and uric acid in the therapeutic group with a dose of 300 mg/kg. Pathological results show a decrease in the number and size of calcium oxalate crystals in renal tubules in the treatment and prevention groups in a dose-dependent manner., Conclusion: The results of this study showed that the use of aqueous extract of date palm pits has been effective in the treatment and prevention of kidney stones induced by ethylene glycol in rats.

Organophosphate (OP) pesticides, including chlorpyrifos (CPF), can alter metabolic hemostasis. The current systematic study investigated blood glucose, lipid profiles, and body weight alterations in rodents and fish exposed to CPF. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines, querying online databases, including Web of Science, PubMed, and Scopus and also search engine including Google Scholar, through January 2021. Studies on rodent and fish exposed to CPF assessing metabolic functions were selected. All studies were in the English language, with other languages being excluded from the review. Two investigators independently assessed each of the articles. The first author's name, publication date, animal model, age, sample size, gender, dose, duration, and route of exposure and outcomes were extracted from each publication. The present review summarizes findings from 61 publications on glycemic, lipid profile, insulin, and body weight changes in rodents and fish exposed to CPF exposure. Most of the studies reported hyperglycemia, hyperlipidemia, and decreased insulin levels and body weight following exposure to CPF. Additionally, we confirmed that the CPF-induced metabolic alterations were both dose- and time-dependent. Our findings support an association between CPF exposure and metabolic diseases. However, more studies are needed to identify the metabolic-disrupting effects of CPF and their underlying mechanisms., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Introduction: Our aim was to investigate and evaluate the influence of metformin on cancer-related biomarkers in clinical trials., Methods: This systematic study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Major databases, including Scopus, Web of Sciences, PubMed, Ovid-Medline, and Cochrane, were systematically reviewed by February 2020. Clinical trials investigating metformin effects on the evaluation of homeostatic models of insulin resistance (HOMA-IR), Ki-67, body mass index (BMI), fasting blood sugar (FBS), and insulin were selected for further analysis. Quality assessment was performed with version 2 of the Cochrane tool for determining the bias risk for randomized trials (RoB 2). Heterogeneity among the included studies was assessed using the Chi-square test. After quality assessment, a random effects model was performed to summarize the data related to insulin, HOMA-IR, Ki-67, and a fixed-effect model for FBS and BMI in a meta-analysis., Results: Nine clinical trials with 716 patients with operable breast and endometrial cancer and 331 with primary breast cancer were involved in the current systematic and meta-analysis study. Systematic findings on the nine publications indicated metformin decreased insulin levels in four studies, FBS in one, BMI in two, Ki-67 in three studies, and HOMA-IR in two study. The pooled analysis indicated that metformin had no significant effect on the following values: insulin (standardized mean differences (SMD) = -0.87, 95% confidence intervals (CI) (-1.93, 0.19), p = 0.11), FBS (SMD = -0.18, 95% CI (-0.30, -0.05), p = 0.004), HOMA-IR (SMD = -0.17, 95% CI (-0.52, 0.19), p = 0.36), and BMI (SMD = -0.13, 95% CI (-0.28, 0.02), p = 0.09). Metformin could decrease Ki-67 in patients with operable endometrial cancer versus healthy subjects (SMD = 0.47, 95% CI (-1.82, 2.75), p = 30.1). According to Egger's test, no publication bias was observed for insulin, FBS, BMI, HOMA-IR, and Ki-67., Conclusions: Patients with operable breast and endometrial cancer under metformin therapy showed no significant changes in the investigated metabolic biomarkers in the most of included study. It was also found that metformin could decrease Ki-67 in patients with operable endometrial cancer. In comparison to the results obtained of our meta-analysis, due to the high heterogeneity and bias of the included clinical trials, the present findings could not confirm or reject the efficacy of metformin for patients with breast cancer and endometrial cancer.

Background and Objectives: Dental caries is one of the most common chronic diseases around the world. Inhibitory effects of Magnolia Grandiflora bark extract has been proved on tooth decay both in vitro and by using free sugar chewing gum. This research aimed to examine the effect of Magnolia Grandiflora bark mouth-wash on the prevalence of Streptococcus mutans in dental plaque., Materials and Methods: This crossover, placebo-controlled, clinical trial study, was performed on a total of twenty participants (aged 18 to 35 years) in both control and intervention groups and four phases. The prevalence of S. mutans was measured in a certain volume of volunteer's dental plaque at the beginning of the project (phase 1), after the first prescription (phase 2), following the washout period (phase 3) and finally after the second prescription (phase 4) by culture on bacteriology medium. Plaque index and saliva sampling were carried out in follow-up visits by a dentist. The data were analyzed using T-Test (paired and independent) quantitatively., Results: There was a significant difference in S. mutans frequency in dental plaque between when the participants used Magnolia mouthwash and when they washed out or used a placebo (p<0.005). Results also showed a significant difference between Magnolia and Placebo groups in the mean count of saliva bacterial colony counts after oral administration in the first and second time (P<0.001 and P<0.004, respectively)., Conclusion: The current trial showed that Magnolia Grandiflora %0.3 mouthwash tends to decrease the number of S. mutans in dental plaque significantly. Therefore, its mass production and release to the oral health community are suggested. However, further studies with larger sample sizes and varying treatment are required to substantiate the findings of this study., (Copyright © 2021 The Authors. Published by Tehran University of Medical Sciences.)

Though evidence exists on the association between diazinon (DZN), an organophosphate pesticide, with hyperglycemia, contrasting reports also exist. Herein, we performed a systematic and meta-analysis study to address this issue. A systematic search was conducted in PubMed, Ovid Medline, Google Scholar, Scopus, and Web of Science up to April 5, 2020, searching for animal studies (rodents and fish) that assessed the impact of DZN on blood glucose concentration. The risk of bias was assessed by the SYRCLE's RoB scale. Once each article's quality was assessed, a random-effects meta-regression was used to pool the data into a meta-analysis. Heterogeneity between the studies was evaluated with the I square and Q test. Random-effect meta-analysis of 19 studies (I 2 = 90.5%, p < 0.001) indicated low heterogeneity between the studies. DZN significantly increased blood glucose levels in the exposed versus control groups (95% CI: 2.46-4.94; Z = 5.86; p < 0.001). Subgroup analysis indicated that the effect of high-dose (3.40 (95% CI: 2.03-4.76)) DZN on changes in blood glucose was more pronounced than in the low dose (4.83 (95% CI: 1.56-8.11)). It was also ascertained that the blood glucose level was significantly higher in females (3.55 (95% CI: 2.21-4.89)) versus males (4.87 (95% CI: 0.20-9.55)) exposed to DZN. No publication bias was observed. Sensitivity analysis showed the robustness of the (standardized mean differences: 3.26-4.03). Our findings establish an association between DZN exposure and hyperglycemia in rodents and fish, which is both dose- and gender-dependent.

The effects of diazinon (DZN), an organophosphate pesticide, on lipid profiles have been extensively reported. However, controversy on this issue persists. Here, we performed a systematic and meta-analysis study to investigate the association between DZN exposure and dyslipidemia in rodents and fish species. This systematic review was prepared according to the PRISMA guidelines. Main databases, including Google Scholar, Scopus, PubMed, Ovid MEDLINE, and Web of Science, were systematically searched through March 4, 2020. The risk of bias was evaluated with the SYRCLE's RoB tool. Once all articles were assessed for scientific quality, a random-effects model was applied to perform a pooled analysis. I 2 and Q test were used to assess the heterogeneity between articles, and Forest plots, indicating point and pooled estimates, were drawn. Twenty-eight articles were included; between them, 13 publications were selected for meta-analysis. Random-effects meta-analysis showed low heterogeneity between the articles. A pooled analysis indicated that DZN significantly increased total cholesterol levels (95% CI: 0.86-3.79; Z = 3.10; p = 0.002), triglyceride (95% CI: 0.38-3.22; Z = 2.48; p = 0.09), low-density lipoprotein cholesterol (95% CI: 0.25-2.85; Z = 2.34; p = 0.7) in the DZN vs. control groups. In addition, DZN significantly decreased high-density lipoprotein cholesterol (95% CI: - 2.92, - 0.42; Z = 2.62; p = 0.07) in the DZN vs. control groups. No publication bias was observed. Our findings suggest that DZN induces dyslipidemia in rodents and fish species in a dose-dependent manner.

Heavy metals in drinking water can threat human health and may induce several diseases. The association between heavy metals exposure and chronic kidney disease (CKD) has been indicated by few epidemiological studies. We conducted a systematic review of the epidemiologic publications of the association between exposure to heavy metals through drinking water and CKD. Keywords related to heavy metals and kidney diseases on MeSH were identified and searched in PubMed, Google Scholar, Scopus, Ovid-Medline and Web of Science until July 2020. 14 publications met our inclusion criteria and included in the current review. The included articles were conducted on the association between arsenic, cadmium, lead and chromium in drinking water and CKD. Our study could not find strong evidence between heavy exposure to through drinking water and CKD, except for arsenic. The negative association was found between arsenic and lead and glomerular filtration rate (eGFR). The positive correlation was observed between cadmium exposure and urinary N-acetyl- β -d-glucosaminidase (NAG) concentrations, and also arsenic and chromium exposure and kidney injury molecule (KIM-1). Assessment of studies showed an association between arsenic, cadmium, lead and chromium and albuminuria and proteinuria, without CKD outcomes. Current systematic study showed few evidence for exposure to arsenic, cadmium, lead and chromium through drinking water and incidence of kidney problems. However, more epidemiological studies are required to confirm this association., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Deposition of Amyloid-beta (Aβ) peptide in the brain is the leading source of the onset and progression of Alzheimer's Disease (AD). Recent studies have suggested that anti-amyloidogenic agents may be a suitable therapeutic strategy for AD. The current review was proposed to address the beneficial effects of cannabis-based drugs for the treatment of AD, focusing primarily on Aβ modifications. Keywords related to AD, Aβ, and cannabis-based on MeSH were identified and were searched in PubMed, Google Scholar, Scopus, Ovid-Medline, and Web of Science from inception until 15 March 2020. The full text of identified papers was obtained and assessed based on exclusion and inclusion criteria. The review is based on articles that have focused on AD and the amyloidogenic pathway. A total of 17 studies were identified based on the inclusion criteria; however, nine studies qualified for this systematic review. The maximum and minimum cannabis dosages, mostly CBD and THC in animal studies, were 0.75 and 50 mg/kg, respectively. Cannabis (CBD and THC) was injected for 10 to 21 days. The findings of the 9 articles indicated that cannabis-based drugs might modulate Aβ modifications in several AD models. Our findings establish that cannabis-based drugs inhibited the progression of AD by modulating Aβ modifications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway has a main role against oxidative stress and inflammation. Spinal Cord Injury (SCI) leads to the high secretion of inflammatory cytokines and reactive oxygen species, which disturbs nervous system function and regeneration. Several studies have indicated that the activation of the Nrf2 signaling pathway may be effective against inflammation after SCI. The experimental studies have indicated that many chemical and natural agents act as Nrf2 inducer, which inhibits the SCI progression. Thus, the finding of novel Nrf2- inducer anti-inflammatory agents may be a valuable approach in drug discovery. In the present review, we discussed the Nrf2 signal pathway and crosstalk with the NF-κB pathway and also the impact of this pathway on inflammation in animal models of SCI. Furthermore, we discussed the regulation of Nrf2 by several phytochemicals and drugs, as well as their effects on the SCI inhibition. Therefore, the current study presented a new hypothesis of the development of anti-inflammatory agents that mediate the Nrf2 signaling pathway for treating the SCI outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)