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Background and purpose: Depression is a growing public health concern worldwide, characterized by cognitive impairment and structural abnormalities of the hippocampus. Current antidepressant treatment sometimes causes the late onset of results and the much faster occurrence of side effects. For this reason, the interest in new treatment strategies including exercise and natural products such as curcumin has increased to treat depression. The present study investigated the role of curcumin and exercise in improving depressive-like behavior and hippocampal damage induced by mild unpredictable chronic stress in male rats. Experimental approach: This study analyzed the effects of curcumin (100 mg/kg/day, P.O for 14 days) and exercise (treadmill running, 45 min/day for 14 days) on immobility behavior (forced swimming test), locomotor activity (open field test), anhedonia (sucrose preference test) and cell survival (Nissl staining) of the hippocampal CA3 region in chronically stressed depression rats. Findings/Results: In the current study, curcumin treatment combined with exercise effectively improved immobility behavior, locomotor activity, and increased hippocampal cell survival resulted in preventing the development of hippocampus dysfunction and depressive-like behaviors. Conclusion and implications: This study demonstrated a new prospect for treating depression. The current findings give researchers the confidence to continue the investigations on the effects of curcumin accompanied with exercise as a novel therapy for the treatment of depression.

Background and purpose: Epilepsy is a group of chronic neurological diseases caused by a complex set of neuronal hyper electrical activities and oxidative stress of neurons. Crocin is a natural bioactive agent of saffron with different pharmacological properties and low bioavailability. This study aimed to evaluate crocin-loaded solid lipid nanoparticles (SLNC) for neuroprotection activity and efficacy against pentylenetetrazol (PTZ)- induced epilepsy. Experimental approach: The rats were pretreated with SLNC and pure-crocin (PC; 25 and 50 mg/kg/day; P.O.) for 28 days before PTZ induction. Behavioral functions were evaluated by passive avoidance learning (PAL) tasks. Then, total antioxidant capacity (TAC), malondialdehyde (MDA), and pro-inflammatory factors were measured in the brain tissue using ELISA kits. Gene expression levels were analyzed with real-time polymerase chain reaction and immunohistochemical assay was used to assess the protein expression of sirtuin1 SIRT 1). Findings/Results: SLNC was prepared with an average particle size of 98.25 nm and 98.33% encapsulation efficiency. Memory deficit improved in rats treated with SLNC. Administering SLNC at 25 and 50 mg/kg significantly reduced MDA and proinflammatory cytokines while increasing TAC. Additionally, administering SLNC before treatment increased the levels of SIRT1, peroxisome proliferator-activated receptor coactivator 1α, cAMP-regulated enhancer binding protein, and brain-derived neurotrophic factor. Furthermore, SLNC administration resulted in the downregulation of caspase-3 and inflammation factor expression. Conclusion and implications: Overall, the obtained results showed that SLNC has better protective effects on oxidative stress in neurons, neurocognitive function, and anti-apoptotic and neuromodulatory activity than PC, suggesting that it is a promising therapeutic strategy for inhibiting seizures.

Background: Cardiovascular disease (CVD) is the most important comorbid condition in rheumatoid arthritis (RA) patients. Dysregulated expression of non-coding RNA families has a critical role in RA-associated inflammatory events, including cardiovascular manifestations. The long non-coding RNA (lncRNA)- HIX003209 has a role in RA associated inflammation. In the current study, we investigated the association of HIX003209 and its downstream microRNA, miR-6089, with various cardiovascular and inflammatory biomarkers in RA patients. Material and methods: 60 RA patients, including 30 newly diagnosed and 30 on-treatment patients were recruited in this study, and 30 healthy people were selected as a control group. The gene expression of HIX003209, miR-6089, and CXCR3 were measured using Real-time PCR. The CVD risk was measured using Systematic Coronary Risk Evaluation (SCORE) and Framingham Risk Score (FRS). Results: The gene expression of LncRNA-HIX003209 was elevated significantly in newly-diagnosed compared to under-treatment and control groups (p

Epilepsy is a condition resulting from complex interactions involving excessive neuronal electrical activity and oxidative stress, which can lead to chronic neurological conditions. This study evaluates crocin encapsulated in SLNC for neuroprotective and countering pentylenetetrazole (PTZ) -induced oxidative damage. The rats were pre-treated with SLNC and FC (25, 50 mg/kg/day; P.O.) for 28 days before being induced with PTZ. Various standard tests were conducted to assess their behavioral functions, such as Y-maze, Open field test (OFT), and elevated plus maze (EPM) tests. ELISA measured brain tissue catalase activity (CAT) and nitric oxide status (NO). The expression of Nuclear factor kappa B (NF-κB) and the number of dendrite spines were examined through Immunohistochemical and Golgi–Cox staining, respectively. The Pretreating rats with SLNC plus PTZ significantly boosted memory and reduced anxiety levels in Y-maze, OFT, and EPM tests. In addition, it decreased NO levels and increased CAT levels. SLNC also showed a significant decrease in NF-κB expression and an increase in neurons and the number of spines. The positive effects of SLNC in improving memory and learning deficits after PTZ injection can be attributed to its anti-inflammatory and anti-oxidative effects.

For the first time, a novel electrochemical biosensor was fabricated based on modification of a rotating glassy carbon electrode with multi-walled carbon nanotubes-ionic liquid, and molecularly imprinted polymers (MIPs) in which renin (Rn), and aliskiren (AK) were used as templates. By immersion the biosensor in Rn, AK, and their binary system (AK-Rn) solutions, the species (Rn, AK, and AK-Rn) were entrapped within the pathways of the MIPs. These processes and investigation of the inhibition of the Rn by AK helped us to obtain higher electrochemical signals for a good monitorization of the system. The effects of experimental parameters on response of the biosensor to AK were optimized by a small central composite design to obtain the highest response. Hydrodynamic cyclic voltametric (HCV), hydrodynamic differential pulse voltammetric (HDPV), and hydrodynamic linear sweep voltammetric (HLSV) data obtained and recorded in order to be analyzed by classical methods and multivariate curve resolution-alternating least squares (MCR-ALS) as an advanced chemometric method. The results of molecular dockings, classical and chemometric analyses confirmed that the Rn was strongly inhibited by the AK which was good evidence to develop a novel biosensing system for determination of Rn. A novel biosensor was developed for determination of the Rn which had an acceptable performance in determination of Rn in the range of 0–9 fM. This approach opened a new way for investigation of enzymes' inhibition, and developing a new generation of electrochemical biosensors for medical and biomedical applications.

In this work, a novel electrochemical thyroglobulin (Tg) biosensor was fabricated based on modification of a glassy carbon electrode with chitin-ionic liquid (Ch-IL) and gold nanoparticles (Au NPs). Surface of the Au NPs/Ch-IL/GCE was investigated and optimized by the image processing method. Drop-casting of the Ch-IL was performed onto the surface of Au NPs/Ch-IL/GCE to fabricate Ch-IL/Au NPs/Ch-IL/GCE. Then, sortilin (ST) was immobilized onto its surface by the use of glutaraldehyde. Biosensing of Tg in the range of Tg in the range of 0.1 to 8.5 fM was based on its interaction with the ST and change in hydrodynamic differential pulse voltammetric (DPV) response of the biosensor. The second-order calibration methods by U-PLS/RBL, N-PLS/RBL, MCR-ALS and PARAFAC2 were used to determination of Tg in the presence of thyroxine and triiodothyronine as uncalibrated interference, and our results confirmed the best performance was observed for exploiting second-order advantage by PARAFAC2 (sensitivity: 2.8 μA/fM, selectivity: 0.49, inverse of analytical sensitivity: 0.11 fM−1, limit of detection: 0.01fM) which was used to determination of Tg in human serum samples the presence of triiodothyronine and thyroxine as uncalibrated interference with the aim of detection of thyroid cancer treatment success. The ST/Ch-IL/Au NPs/Ch-IL/GCE assisted by PARAFAC2 was an excellent electronic device for medical diagnostic purposes.

Abstract Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats’ testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.

Abstract Background Two important virulence factors, urease and cagA, play an important role in Helicobacter pylori (H. pylori) gastric cancer. Aim of this study was to investigate the expression level and function of ureB and cagA using small interfering RNAs (siRNA). Methods SS1 strain of H. pylori was considered as host for natural transformation. siRNA designed for ureB and cagA genes were inserted in pGPU6/GFP/Neo siRNA plasmid vector to evaluate using phenotypic and genotypic approaches. Then, qPCR was performed for determining inhibition rate of ureB and cagA gene expression. Results The expression levels of siRNA-ureB and siRNA-cagA in the recombinant strain SS1 were reduced by about 5000 and 1000 fold, respectively, compared to the native H. pylori strain SS1. Also, preliminary evaluation of siRNA-ureB in vitro showed inhibition of urea enzyme activity. These data suggest that siRNA may be a powerful new tool for gene silencing in vitro, and for the development of RNAi-based anti-H. pylori therapies. Conclusion Our results show that targeting ureB and cagA genes with siRNA seems to be a new strategy to inhibit urease enzyme activity, reduce inflammation and colonization rate.

Aflatoxins B1 (AFB1) a dangerous type of aflatoxin, poses a serious threat to human health. Meanwhile, Taraxasterol, a bioactive compound in dandelion, exhibits strong anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to investigate the impact of AFB1 on the intrinsic and extrinsic pathways of apoptosis, as well as evaluate the protective role of taraxasterol in the TM3 Leydig cell line. Cell viability was evaluated using an MTT assay, measuring the effects of 3.6 µM AFB1 and varying concentrations of taraxasterol. Expression levels of Caspase 3,8, and 9 were analyzed with RT-qPCR, and flow cytometry was used to assess cell cycle progression and apoptotic alterations. The findings of this study demonstrated that exposure to 3.6 µM of AFB1 resulted in an upregulation of Caspase 3 and Caspase 9 expression, indicating an activation of apoptotic pathways in TM3 cells. Additionally, the analysis of apoptosis revealed a significant increase in cellular apoptosis at this AFB1 concentration. However, when TM3 cells were exposed to 5 µM of taraxasterol, a downregulation of Caspase 3 and Caspase 9 expression was observed, suggesting a protective effect against apoptosis. Moreover, the apoptotic rate in TM3 cells was reduced in the presence of 5 µM of taraxasterol. Consequently, this study highlights the potential of taraxasterol as a protective agent against AFB1-induced apoptosis and suggest its potential application in regulating cell survival and apoptosis-related processes. Further investigations are necessary to elucidate the underlying mechanisms and evaluate the clinical implications of taraxasterol in the context of fertility disorders and other conditions associated with AFB1 exposure.

Objective: Mitochondrial oxidative stress is an important factor in infertility. The mitochondrial thioredoxin systemplays an important role in this condition. N-acetyl-5-methoxy tryptamine (melatonin) plays a role in reducing oxidativestress and apoptosis in spermatogonial stem cells (SSCs). In this study, we explore the probable protective effects ofmelatonin on the mitochondrial thioredoxin system [thioredoxin 2 (Trx2)/Txnip] in SSCs under oxidative stress.Materials and Methods: In this experimental study, SSCs were co-cultured two-dimensionally (2D) with Sertoli cellsin DMEM culture medium that contained 10% fetal bovine serum (FBS), 1% antibiotics, and 10 ng/ml glial cell-derivedneurotrophic factor (GDNF) for 30 days. The cultured cells were subsequently divided into four groups: control; melatonin(250 μM, 24 hours); melatonin (250 μM, 24 hours)+hydrogen peroxide (H2O2, 50 μM, 24 hours); and H2O2 (50 μM, 24hours). Intracellular reactive oxygen species (ROS) production was determined by flow cytometry. Malondialdehyde(MDA) levels were measured by Fluorometry. The expressions of apoptotic and antioxidant genes and nuclear factorerythroid 2-related factor 2 (Nrf2), Trx2, and nicotinamide nucleotide transhydrogenase (NNT) proteins were determinedby quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Adenosine triphosphate (ATP) levelswere measured by fluorometry.Results: Melatonin reduced H2O2-induced ROS levels and apoptosis in the SSCs. Melatonin also increased mRNAexpression of Nrf2, Trx2, NNT, Sirtuin 3 (Sirt3), and decreased mRNA expression of Txnip, and increased proteinexpressions of Nrf2, Trx2, NNT thereby increasing activity of the mitochondrial thioredoxin system. In addition, melatoninincreased ATP levels.Conclusion: Melatonin increased Trx2 expression through the Nrf2 pathway. This study suggests that melatonin mayprotect SSCs from oxidative stress in diseases related to infertility.

Breast and gynecological cancers are the most common malignancies in females. Early-stage detection and treatment could significantly reduce the mortality rate in patients. However, common treatments such as chemotherapy and radiotherapy fail after a while and lead to recurrence and drug resistance in cancer cells. The recent use of nanotechnology has enabled the development of novel approaches for diagnosing and treating oncological diseases. Chitosan-based polymer nanoparticles (CHPNPs) with unique properties such as non-toxicity, biocompatibility, and anti-carcinogenic effects are promising tools for the clinical development of targeted delivery systems. So far, various methods have been applied to use these nanoparticles in the diagnosis and treatment of various cancers. Identifying the most practical methods is one of the most important challenges in achieving effective treatments. A review of these studies can provide better horizons to realize effective treatment. In this review, we evaluate and discuss the use of CHPNPs from published literature to assess diagnostic and therapeutic strategies in breast and gynecological cancers, including ovarian and uterine neoplasms, as well as their advantages and challenges.

Objective(s): This study examined the effects of melatonin treatment on steroidogenesis dysfunction and testosterone impairment, following CoCl2-induced hypoxia in TM3 Leydig cells. Materials and Methods: The TM3 cells were divided into four groups. The first group received no treatment. The MLT group was treated with a concentration of 1 mM melatonin. In the CoCl2 group, 0.2 mM CoCl2 was added to the medium to induce Hif1α overexpression. The MLT+CoCl2 group received 0.2 mM CoCl2 and 1 mM melatonin. After 24 hr treatment, the cells and supernatants were collected and used for further determination. The MTT assay was performed to estimate the decrease in cell viability throughout the CoCl2 and melatonin treatment. The mRNA and the protein levels were evaluated using Real-time PCR and Western blot analysis. The ELISA assay kit was used to detect the testosterone content.Results: CoCl2 treatment caused Hif1α overexpression in TM3 Leydig cells. Moreover, CoCl2 treatment of these cells led to considerable downregulation of Star, Hsd3b1, and Gata4 well as Mtnr1a and Mtnr1b mRNA/protein expression coupled with testosterone content repression in the cell culture medium. Melatonin administration in CoCl2 -treated cells decreased Hif1α mRNA/protein expression, but had no significant effect on Star, Hsd3b1, Gata4, Mtnr1a mRNA/protein expression, and the testosterone level in the cell culture medium. Melatonin caused recovery of decrease in the Mtnr1b gene and protein expression. Conclusion: There was no significant effect on steroidogenesis-related genes, proteins, and testosterone synthesis in the absence of gonadotropin treatment plus melatonin following CoCl2-induced hypoxia in TM3 Leydig cells.

Objective: Mercuric chloride (Merc; HgCl2) is toxic to humans and animals and contributes to environmental pollution, which usually results in nerve and systemic harm to different organs. Falcaria vulgaris (FV) is a medicinal plant rich in antioxidants. This research aimed to assess the FV hydroalcoholic extract effects on kidney toxicity induced by Merc.Materials and Methods: Forty-eight male rats were divided into eight groups: the control group: received saline; the Merc group: received 0.5 ml/day of 0.5 ppm aqueous Merc; FV1, 2, and 3 groups: received 50, 100, 150 mg/kg FV, respectively; and Merc + FV1, 2, and 3 groups: received Merc and FV at three doses. The administration period was 14-days. Subsequently, kidneys and sera were cumulated from each group for the analysis. Samples were analyzed via hematoxylin-eosin staining and biochemical tests.Results: The rats that received Merc displayed significant decrement in the kidney index, the diameter of renal corpuscles, total antioxidant capacity levels, superoxide dismutase activity (all, p

Background and Objectives: Colorectal cancer (CRC) is a common type of cancer that has a high death rate and is becoming more common in developed countries. Currently, there are several treatment options available for CRC patients, and clinical trials are being conducted to improve conventional therapies. This study investigates the combined impact of Bacillus coagulans (B.C) and Newcastle disease virus (NDV) on the growth of human colorectal adenocarcinoma cells (HT29 cell line). Materials and Methods: The HT29 cell line was cultured under controlled laboratory conditions. They were treated with Fluorouracil (5-FU), NDV, and B.C., after which various assessments were conducted to determine the effects of these treatments. These assessments included MTT assay for cytotoxicity, evaluation of cell viability, and measurement of caspase 8 and 9 activity levels. The significance of the data was determined at a threshold of P

Background and purpose: Daunorubicin is an effective drug in chemotherapy, but its clinical use is limited due to serious side effects. Royal jelly as a natural compound obtained from bees can be helpful in preventing the damage caused by daunorubicin. The present study aimed to evaluate the effects of royal jelly on the number of apoptotic cells and the expression of genes involved in apoptosis in mice treated with daunorubicin. Materials and methods: In this experimental study, 77 Balb/c mice were randomly divided into seven groups (n= 11 per group): sham, control, royal jelly (50 and 100 mg/kg), daunorubicin (2 mg/kg), and royal jelly (50 and 100 mg/kg) + daunorubicin. The mice received saline (0.09%), IP daunorubicin, and royal jelly orally for eight weeks. To estimate the number of apoptotic cells and the expression of genes related to apoptosis in testis, we used ELISA test and Real-time PCR assay, respectively. Data analysis was done applying One-way Analysis of Variance and Tukey's test in SPSS. Results: Daunorubicin caused significant increase in the number of apoptotic cells, and expression levels of p53, Bax, caspase 3, caspase 8, and caspase 9 (P

Abstract Alzheimer's disease (AD) is one of the chief neurological difficulties in the aged population, identified through dementia, memory disturbance, and reduced cognitive abilities. β‐amyloid (Aβ) plaques aggregations, generation of reactive oxygen species, and mitochondrial dysfunction are among the major signs of AD. Regarding the urgent need for the development of novel treatments for neurodegenerative diseases, researchers have recently perused the function of natural phytobioactive combinations, such as resveratrol (RES), in vivo and in vitro (animal models of AD). Investigations have shown the neuroprotective action of RES. This compound can be encapsulated by several methods (e.g. polymeric nanoparticles (NPs), solid lipid nanoparticles, Micelles, and liposomes). This antioxidant compound, however, barely crosses the blood–brain barrier (BBB), thereby limiting its bioavailability and stability at the target sites in the brain. Thanks to nanotechnology, the efficiency of AD therapy can be improved by encapsulating the drugs in a NP with a controlled size (1–100 nm). This article addressed the use of RES, as a Phytobioactive compound, to decrease the oxidative stress. Encapsulation of this compound in the form of nanocarriers to treat neurological diseases to improve BBB crossing is also discussed.

Abstract Background This systematic review and dose–response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. Methods Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. Results Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose–response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. Conclusion The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.

Objective(s): Therapeutic strategies that facilitate extinction are promising in the treatment of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has a crucial role in neural plasticity, a process needed for the retention of fear extinction. In this study, we investigated the effects of local administration of a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaBu), on BDNF transcription and behavioral markers of extinction in the single prolonged stress (SPS) model of PTSD. Materials and Methods: NaBu was infused into the infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) of male rats. The freezing response was recorded as the criterion to assess fear strength on the day of extinction as well as 24 hr later in the retention test. Other behavioral tests were also measured to evaluate the anxiety level, locomotor activity, and working memory on the retention day. HDAC activity and BDNF mRNA expression were evaluated after the behavioral experiments. Results: NaBu facilitated the recall of fear extinction in SPS rats (P

Background: Polycystic ovary syndrome (PCOS) is known as the most common endocrine and metabolic disorder inthe reproductive-age women. Due to the effects of PCOS on the physical and mental health, the investigation of the factorsaffecting the development of PCOS is crucial. Hexose-6-phosphate dehydrogenase (H6PD) is a microsomal enzymethat catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway. The present study examinedthe polymorphisms of the H6PD gene (R453Q and D151A) in PCOS patients of Iranian Kurdish women.Materials and Methods: In this case-control study, a total, of 200 female volunteers in two equal groups participatedin our study. The PCOS patients were selected based on the Rotterdam diagnostic criteria. The association of H6PDgene polymorphisms, D151A and R453Q, with the development of PCOS were investigated. The polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. Statistical analysiswas applied by the SPSS (version 16) software.Results: Statistically significant lower frequencies of AA+AG genotype (37% vs. 55%, P=0.01) and A allele (22.5%vs. 34%, P=0.01) of R453Q were observed in the patients compared to the controls. In the case of D151A, no significantdifferences were observed in the frequency of genotypes and alleles between the two groups.Conclusion: The findings of this study suggest that variants of H6PD R453Q affect the risk of PCOS.

Abstract Background Nicotine administration can generate severe oxidative stress and lipid peroxidation. Royal jelly, with its antioxidant properties, acts as a scavenger of reactive oxygen species. This study describes the apitherapy effects of royal jelly on testicular damage following nicotine administration. Methods Forty‐eight male BALB/c mice were divided into 8 groups (n = 6): saline, 3 different doses of royal jelly (100, 150, and 200 mg/kg body weight (BW) per day), nicotine (1.5 mg/kg), and 3 different groups of Nic + Roy (1.5 mg/kg of Nic + 100, 150, and 200 mg/kg BW per day of royal jelly). Nicotine was administrated intraperitoneally, and royal jelly was prescribed orally for 10 consecutive days. Serum levels of hormones (testosterone, luteinizing hormone, and follicle‐stimulating hormone), total antioxidant capacity, nitric oxide (NO) status, malondialdehyde levels, sperm DNA fragmentation, sperm parameters, histopathological changes (H&E staining), immunohistochemistry against apoptotic proteins, and gene expression of Bcl‐2, p53, Caspase‐3, and Nrf2 (real‐time PCR) were assessed to evaluate the molecular and histological changes. Results Hormone levels, sperm parameters, and status of antioxidants were decreased significantly (p

Background and Aim: Daunorubicin is an effective antibiotic for the chemotherapy of various cancers. To prevent damage to healthy cells during chemotherapy, it is recommended to change this treatment or protect healthy cells from chemotherapeutic agents by protective compounds. The present study aimed to check the protective effect of royal jelly on male reproductive system against the side effects induced by daunorubicin injection in mice. Materials and Methods: In this study, 77 adult BALB/c mice were randomly divided into seven groups including sham, control, royal jelly 1, royal jelly 2, daunorubicin, royal jelly 1+daunorubicin, and royal jelly 2+daunorubicin. Mice received saline (0.09%), and daunorubicin (2 mg/kg) intraperitoneally, and royal jelly (50 and 100 mg/kg) orally for 8weeks. The sperm parameters, testis weight, and oxidative stress parameters were evaluated. Using SPSS software (version 16), data were analyzed by one-way analysis of variance and Tukey test. P

Background and purpose: Aflatoxins are highly toxic compounds that can cause acute and chronic toxicity in humans and animals. This study aimed to evaluate the expression of BDNF and GFAP, histopathological changes, and oxidative stress factors in brain tissue exposed to aflatoxin G1 (AFG1) in male rats. Experimental approach: Twenty-eight male Wistar rats were used. Animals were randomly divided into 4 groups of 7 each. The control group received 0.2 mL of corn oil and the treatment groups were exposed to AFG1 (2 mg/kg) intra-peritoneally for 15, 28, and 45 days. The tissue was used for histopathological studies, and the level of TAC, SOD, and MDA, and the expression of BDNF and GFAP genes were evaluated. Findings/Results: Real-time PCR results showed that AFG1 increased GFAP expression and decreased BDNF expression in AFG1-treated groups compared to the control group. The tissue level of TAC and SOD over time in the groups receiving AFG1 significantly decreased and the tissue level of MDA increased compared to the control group. Histopathological results showed that AFG1 can cause cell necrosis, a reduction of the normal cells number in the hippocampal region of CA1, cerebral edema, shrinkage of nerve cells, formation of space around neuroglia, and diffusion of gliosis in the cerebral cortex after 45 days. Conclusion and implication: AFG1, by causing pathological complications in cortical tissue, was able to affect the exacerbation of nerve tissue damage and thus pave the way for future neurological diseases.

Background and purpose: Cisplatin is a chemotherapeutic drug used to treat cancer, however, causes kidney toxicity. Harmine is a plant-derived alkaloid with a wide range of therapeutic applications. The effects of harmine on the renal side effects of cisplatin in mice were studied in this study. Experimental approach: Forty-eight male BALB/c mice were randomly divided into eight groups (n = 6). They were treated with saline, cisplatin (5.5 mg/kg), harmine (5, 10, and 15 mg/kg/day), cisplatin + harmine (5, 10, and 15 mg/kg/day), respectively. All administrations were done daily and intraperitoneally for 4 days. The criteria related to histology, oxidation, anti-oxidation, inflammation, and apoptosis of renal tissue were evaluated. Findings / Results: There was a significant decrease in total antioxidant capacity of renal tissue, renal corpuscles diameter, and IL-10 expression level in the cisplatin group than in the control group, while the values of these parameters were significantly similar to the control group in the moderate or high doses of harmine + cisplatin groups. There were significant increases in serum urea and creatinine levels, bowman space, the amounts of malondialdehyde, apoptosis rate, and TNF-α, NF-κB, IL-1β, and caspase-3 gene expressions in kidney tissue of the cisplatin group compared to the control group, while these criteria did not differ in the moderate or high doses of harmine + cisplatin groups. Conclusion and implications: Harmine protected the kidneys against cisplatin-induced damage. Antioxidant, anti-inflammatory, and anti-apoptotic harmine properties were involved in this healing effect.

Background and Aim: Breast cancer is the second leading cause of death among women worldwide. Despite recent advances in cancer treatment, this disease remains one of the leading causes of death. Snake venom is a mixture of various molecules such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Previous studies have shown that the venom of some snakes have anti-cancer effects on human cell lines. In the present study, the effect of Vipera raddei kurdistanica venom on breast cell lines was investigated. Materials and Methods: The effect of increasing concentrations of snake venom on breast cells viability was investigated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay and lactate dehydrogenase measurement. Apoptotic cell death was evaluated by fluorescent dye staining and DNA fragmentation assay. Changes in the expression levels of some apoptotic-related genes were investigated by using real time PCR. Data were analyzed by one-way ANOVA followed by Tukey's test. P

Background and objectives: Doxorubicin, an effective anticancer agent, might impair the function of testicular tissue and lead to infertility. Royal jelly can heal male infertility because of its antioxidant activities. This study aimed to evaluate the histologic, genetic and biochemical repair potential of royal jelly on doxorubicin-induced male reproductive system side effects during eight chemotherapy cycles in mice. Methods: In this study, 77 male Balb/c mice (11 mice in each group) were divided to: no medication as sham group, normal saline (0.09%), royal jelly (50, 100 mg/kg), doxorubicin (2 mg/kg), and royal jelly+doxorubicin groups, receiving treatment once a week for six weeks. Histological and biochemical factors of male reproductive system were evaluated. Results: There was a significant reduction in testicular weight, spermatozoa parameters, diameter of seminiferous tubules, and total antioxidant capacity levels in the doxorubicin group compared to the control group (p

Background and purpose: Dichlorvos, an organophosphate insecticide, induces side effects on normal tissues. On the other hand, Royal jelly (RJ) with antioxidant activities has many medical benefits including liver toxicity. In this study, we investigated the role of RJ in improving dichlorvos adverse impact on the liver of male rats. Experimental approach: Forty-eight male rats were randomly divided into 8 groups (n = 6); receiving by gavage normal saline (0.09%), dichlorvos (4 mg/kg/day), RJ (50, 100, 150 mg/kg/day; RJ 1, 2, 3) or dichlorvos + RJs, daily for 28 consecutive days. At the end of experiments, histopathology alterations, apoptosis induction, and biochemical factors related to the liver were evaluated. Findings/Results: There was a significant reduction in the number of hepatocytes and total antioxidant capacity (TAC) levels in the dichlorvos group compared to the control group, whereas these parameters in the dichlorvos + RJs groups, were significantly increased compared to the dichlorvos group. Central vein diameter, liver enzymes (aspartate transaminase, alanine transaminase, and alkaline phosphatase) serum levels of nitric oxide, and apoptotic index were significantly higher in the dichlorvos group than in the control, while these parameters were decreased in the dichlorvos + RJs groups versus the dichlorvos group. Conclusion and implications: RJ at 50 mg/kg protected dichlorvos-induced liver damage in rats. Dichlorvos- hepatitis mechanism could be oxidative induction as long as antioxidant reduction leads to apoptosis in this organ, while RJ due to its antioxidant potential suppresses this hazardous cellular and molecular process.

BackgroundCeliac disease (CD) is an autoimmune disease affecting around 1.4% of the total human population. Local and systemic manifestations are described in CD. Viral infections seem to trigger CD or even have a worse outcome in CD patients. The evidence on the relationship between CD and coronavirus disease (COVID-19) is limited. To evaluate existing evidence on the association between CD and COVID-19, we conducted the current systematic review.MethodsWe systematically searched Pubmed, Scopus, and Embase databases to find articles that reported risks or outcomes of COVID-19 in CD patients. Papers in any language published up to November 17, 2022, were evaluated for possible inclusion. The results were analyzed qualitatively. This study is registered with PROSPERO(CRD42022327380).ResultsWe identified 509 studies by searching databases; 14 reported data on the risk or outcome of COVID-19 in CD patients and were eligible for qualitative synthesis. We found that the relative risk of acquiring COVID-19 in CD patients may be lower than in the general population. Approximately 90% of infected patients were treated as an outpatient, and 10% were hospitalized. GFD adherence and Health-related quality of life (HR-QOL) were more or less the same before and during the pandemic. The gluten-free products (GFP) supply seems to be plunged during the pandemic. The data on the psychological effects of the pandemic were conflicting.ConclusionThe risk of acquiring COVID-19 in CD patients is lower than in the general population. Females were more likely to be infected by COVID-19, and the most common comorbidity in infected patients was a chronic lower respiratory disease; around 10% of infected patients needed hospitalization, GFD adherence, and HR-QOL was more or less the same before and during the pandemic, depression, anxiety, and stress levels of patients varied among studies. Patients had more difficulties accessing GFPs based on limited data.

Background & objective: Exercise has been shown to improve cognitive function in patients with multiple sclerosis (MS). Experimentally, glucocorticoids (GCs) treatment has been observed to improve cognitive deterioration in an autoimmune model for MS, experimental autoimmune encephalomyelitis (EAE). We aimed to determine the combined effect of exercise and 4 mg/kg of dexamethasone (Dex) for 4 weeks on spatial memory in EAE. Materials & Methods: Rats with EAE were subjected to the Morris water maze (MWM) for four days and a prop test for one day. The prop test was repeated on day 40 post-induction (dpi). Rats were randomly assigned to one of four groups (10 rats per group): control EAE without treatment; EAE + dexamethasone, (EAE + Dex); EAE + exercise (EAE + Ex); and EAE+Dex+Ex. Rats receiving dexamethasone were administered 4 mg/kg injections daily for two weeks after EAE induction. Exercise training was initiated on a motorized treadmill 2 weeks before EAE induction and continued until 14 dpi. On day 41, animals were dissected and CORT level was assessed by enzyme-linked immunosorbent assay corticosterone kit. Results: One-way analysis of variance (ANOVA) with repeated measures followed by a protected LSD post hoc test indicated that, EAE+Ex group increased body weight (P < 0.001) and it displayed a significantly lower CORT concentration (P 0.001) and swimming speed (p>0.002). Conclusion: The protocol selected in this study was an effective treatment for the EAE model to improve spatial memory and regulate corticosterone concentrations.

Background and objectives: Despite clinical use, the efficacy of methotrexate is often limited by some adverse effects, mainly nephrotoxicity. The most common mechanism of methotrexate-induced kidney damages is oxidative stress. Harmine as a plant-derived compound has antioxidant and anti-inflammatory properties, The aim of this study was to evaluate the therapeutic effect of harmine, against methotrexate -induced nephrotoxicity. Methods: The mice were divided into six groups: control (saline only); 20 mg/kg methotrexate; 20 mg/kg harmine, and 20 mg/kg methotrexate + harmine at three doses of 5, 10, or 20 mg/kg. Administrations were intraperitoneally and the treatment period was a 14-days. After this time, the sera and kidneys were collected from each group for the following analyses. Samples were analyzed by hematoxylin-eosin (H&E) staining, qRT-PCR, and biochemical assays. Results: The mice that received methotrexate showed significant increase in creatinine and blood urea nitrogen levels, and 10, or 20 mg/kg harmine mitigated these results. The number and diameter of glomeruli were improved by harmine in methotrexate -treated groups. Moreover, malondialdehyde and nitric oxide levels showed significant increase in the kidney of the mice that received methotrexate, while total antioxidant capacity and superoxide dismutase were diminished. Harmine treatment suppressed oxidative stress markers and also enhanced antioxidant defense parameters. Harmine inhibited methotrexate-induced oxidative stress as shown by the decreased expression of Nqo1, Ho-1, Trx1 and Nrf2 at mRNA level. Harmine also ameliorated histological alterations induced by methotrexate. Conclusion: Our results suggested that harmine has the potential to protect against methotrexate-induced nephrotoxicity.

Abstract Background Endometriosis can lead to infertility. Since there is no definitive treatment for endometriosis, animal modelling seems necessary to examine the possible treatments. Mouse endometrium cannot be separated for endometriosis induction. In addition, transplantation of uterus into the abdominal viscera to induce endometriosis causes organ damage. In this study, we defined a new model of endometriosis leading to separability of endometrium and a safe anatomical region for transplantation. Methods Forty female mice were allocated to 5 groups: 1, sham; 2, allograft uterus transplantation of mice to anterior abdominal wall of mice; 3, allograft uterus transplantation of mice to mesentery of mice; 4, xenograft endometrial transplantation of rat to anterior abdominal wall of mice; 5, xenograft endometrial transplantation of rat to mesentery of mice. Adult female rats with a previous pregnancy experience were selected and placed in the vicinity of male rats for 2 weeks to induce estrogen secretion and increase endometrial thickness. Results In the 4th group of animals, compared to sham, the peritoneal concentrations of VEGF‐A, TNF‐α, NO, MDA, and serum levels of CA‐125 and IL‐37 were increased and total body weight was decreased, while weight and size of endometrial lesions were increased significantly (P

Background and purpose: Previous studies have shown the adverse effects of aflatoxin G1 on testicular tissue and the process of spermatogenesis. The aim of this study was to investigate changes in the expression of Cyclin D1, the estrogen receptor ERα and the levels of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in testicular tissue following exposure to AFG1. Materials and methods: Twenty four mice were divided into four groups (n=6 per group); a control group (saline) and three treatment groups to receive AFG1 for 7, 15, and 28 days intraperitoneally. Histopathological changes caused by this toxin along with the expression of Cyclin D1 and Erα, as well as Nitric oxid (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) levels in testicular tissue were measured. Results: The expression of Cyclin D1 in testicular tissue in AFG1 receiving groups increased in a time-dependent manner and the expression of ERα decreased in testicular tissue in AFG1 receiving groups (P

Background: Prior to chemotherapy interventions, in vitro maturation (IVM) of folliclesthrough vitrification can be used to help young people conserve their fertility. Materials and Methods: This experimental study was conducted on immature female BALB/c mice (12-14 days). Follicles were gathered mechanically and placed in α-Minimal Essential Medium (α-MEM) containing 5% fetal bovine serum (FBS). Some pre-antral follicles were frozen. The fresh and vitrified follicles were cultured in different concentrations of sodium alginate (0.25%, 0.5%, and 1%) and two dimensional (2D) medium for 12 days. The samples were evaluated for viability percentage, the number of MII-phase oocytes and reactive oxygen specious (ROS) level. Additionally, Gdf9, Bmp15, Bmp7, Bmp4, Gpx, mnSOD and Gcs gene expressions were assessed in the samples. Results: The highest and lowest percentages of follicle viability and maturation in the fresh and vitrified groups were respectively 0.5% concentration and 2D culture. There was no significant difference among the concentrations of 0.25% and 1%. Viability and maturation of follicles showed a significant increase in the fresh groups in comparison with the vitrified groups. ROS levels in the both fresh and vitrified groups with different concentrations of alginate showed a significant decrease compared to the control group. ROS levels in follicles showed a significant decrease in the fresh groups in comparison with the vitrified groups (P≤0.0001). The highest gene expression levels were observed in the 0.5% alginate (P≤0.0001). Moreover, the viability percentage, follicle maturation, and gene expression levels were higher in the fresh groupsthan the vitrified groups (P≤0.0001). Conclusion: Alginate hydrogel at a proper concentration of 5%, not only helps follicle get mature, but also promotes the expression of developmental genes and reducesthe level of intracellular ROS. Follicular vitrification decreases quality of the follicles, which are partially compensated using a three dimensional (3D) cell culture medium.

Background and objective: The mercury-induced liver pathogenesis is mainly mediated by oxidative stress. The aim of the current study was to evaluate the possible ameliorative effect of harmine, a natural compound, on liver toxicity induced by mercury chloride (HgCl2). Methods: Forty-two male Balb/c mice were randomly divided into six groups (n = 7): Control, HgCl2 (0.5 mg/kg), harmine (20 mg/kg), and HgCl2 (0.5 mg/kg) + harmine (5, 10, or 20 mg/kg). The mice received treatments once per day for two weeks. After this period, the blood and tissue samples were collected for analyses. Results: HgCl2 caused a significant increase in levels of hepatic enzymes alanine aminotransferase, aspartate transaminase, and alkaline phosphatase; while harmine ameliorated these effects. Harmine in HgCl2-intoxicated mice, showed protective effects as evidenced by the increase in liver relative weight to body as well as the diameter of central vein in the co-treated group. Serum levels of malondialdehyde and nitric oxide increased in HgCl2, while they were declined in harmine co-treated groups compared to HgCl2 group. The serum level of superoxide dismutase and total antioxidant capacity improved following harmine treatment in the co-administrated group compared to HgCl2 group. Moreover, gene expression analysis demonstrated that harmine treatment improved the HgCl2-induced decreasing of Ho-1, Nrf2, Hqo1, and Trx1. The histopathological examination confirmed the protective effects of harmine. Conclusion: Mercury can induce toxicity by elevation of oxidative stress in the liver and harmine attenuates hepatic injury induced by HgCl2, at least in part, through its antioxidant activities.

Background Ischemia–reperfusion (Isc/Rep) incidence can damage kidneys and long-distance organs such as the liver. Due to the increasing use of herbs in medicine, this study was designed to assess the effects of Acacetin (ACA) on pathophysiology of liver following renal Isc/Rep induction. Methods: 84 male Balb/C mice were divided into 12 groups including control, control + ACAs groups (0.01% DMSO or 50, 25, 10 mg/kg of ACA.) sham group (a period of 60 min laparotomy with 0.01% DMSO treatment) sham + ACAs groups (0.01% DMSO + 50, 25, 10 mg/kg of ACA) Isc/Rep treatment groups (laparotomy and bilateralrenal occlusion for 60 min with/without administration of 50, 25, 10 mg/kg ACA). All experimental groups were treated intraperitoneally daily for 4 consecutive days. The values of quantitative histology, Total Antioxidant Capacity (TAC), Nitric oxide (NO), TNFα, IL1β, and the serum levels of hepatic enzymes were evaluated. Results: In the Isc/Rep and Isc/Rep + ACA (10 mg/kg) groups, there were a significant decrease in the level of albumin and TAC, while the other evaluated parameters were significantly increased (p

Background: Among aflatoxins, the subtype aflatoxin G1 is one of the most toxic, commonly found in cereals, legumes, dairy and non-alcoholic beers. Aflatoxins have been known as nephrotoxic compounds. In this study, changes in the expression of aquaporin-1, the histopathology of renal tissue and plasma biochemical factors after exposure to aflatoxin G1 were investigated in mice. Methods: Twenty-four adult male mice (weighing 20±2 g) were divided into four groups of six. The control group received the vehicle (0.2 ml) and the three experimental groups were injected intraperitoneally with aflatoxin G1 at 20 μg/kg for 7, 15 or 35 days, respectively. On days 7, 15 and 35, blood samples were drawn from the mice for biochemical analysis of plasma and the kidney tissues were sampled for real-time PCR and histopathological studies. Results: The real PCR results showed a reduction in aquaporin-1 expression in the experimental groups compared to those in the controls (P

Background: Polycystic ovary syndrome (PCOS) is the known endocrinopathy disorder in the reproductive phase ofwomen’s life. More than half of the women with PCOS suffer from obesity which impacts the ovarian functions byleptin levels. Here the R223Q and P1019P polymorphisms of leptin receptor (LEPR) gene were examined in PCOSpatients of Kurdish women from west of Iran.Materials and Methods: In this case-control study, one hundred women with PCOS and 100 healthy women bearingsimilar age range were selected based on Rotterdam diagnostic criteria. Polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) method was used to genotype polymorphisms LEPR (R223Q and P1019P),by respectively the BsaWI and NcoI restriction enzymes. Pearson’s chi-square (χ2) test was used to analyze the variationin genetic distributions and unconditional logistic regression model was used to calculate the odds ratio (OR;95% CI).Results: Genotype frequencies of the R223Q and P1019P polymorphisms showed significant difference between thepatients with PCOS compared to the controls. G allele (R223Q) reduced the risk of PCOS about 0.49-fold (p

Background and Objective: Self-handicapping is a set of behaviors to externalize failures and internalize success. The present study aimed to determine the status of self-handicapping and its association with some academic variables among students of Kermanshah University of Medical Sciences. Materials and Methods: This cross-sectional study was conducted on 296 students of Kermanshah University of Medical Sciences. The participants were selected via random sampling and probability proportional to size sampling. Data were collected using a self-report questionnaire. Data were analyzed in SPSS software (Version 16) using descriptive and analytical tests at 95% confidence level. Results: The mean age of students was reported as 22.21±2.10 (age range of 18-years). The mean score of self-handicapping was 16.64±3.48, which indicated that the participants obtain 66.56% of the maximum score of self-handicapping. Dental students were engaged in more self-handicapping, compared to other students (P=0.011). Moreover, it was shown that married students self-handicapped more than single students (P=0.025), and older students obtained higher scores in self-handicapping (r=0.144; P= 0.025). Conclusion: Due to the fact that students gained more than 50% of the maximum self-handicapping score, it is essential to plan relevant intervention programs and conduct further studies to identify the effective causes of self-handicapping.

Background and purpose: Aflatoxin (AF) is a mycotoxin produced by various strains of the Aspergillus family. AFG1 as one of the most important types is highly found in cereals and grains. AF affects sperm production or even its quality. This study was designed to test the effects of AFG1 on mice testicular tissue. Experimental approach: Twenty-four Albino mice were divided into four groups of 6 each; a control group (0.2 mL corn oil and ethanol), three treatment groups with different periods (20 μg/kg AFG1 for 7, 15, and 35 consecutive days). All treatments were applied intraperitoneally. Biosynthesis of cyclin D1, p21, and estrogen receptor alpha (ERα) proteins was evaluated by immunohistochemistry (IHC) staining. Levels of cyclin D1, p21, and ERa mRNA were evaluated by the real-time polymerase chain reaction (RT-PCR) technique. Tubular differentiation index (TDI), reproductive index (RI), and spermiogenesis indices were also analyzed. Findings/Results: AFG1 increased the percentage of seminiferous tubules with negative TDI, RI, and SPI compared to the control group (P < 0.05). RT-PCR and IHC analyses illustrated time-dependent enhancement in p21 expression and cyclin D1 biosynthesis in AFG1-treated groups significantly (P < 0.05). While the protein and mRNA levels of ERa were significantly (P < 0.05) decreased in a time-dependent manner. Conclusion and implications: The chronic exposure to AFG1 reduced the expression and synthesis of ERa, increased the expression and synthesis of p21 and cyclin D1, impaired apoptosis, which in turn could impair spermatogenesis.

Background and purpose: Nicotine is an alkaloid found in many nutrients and tobacco that can cause infertility in men. Gallic acid is a powerful antioxidant that possesses antimutagenic and anticancer activities. This study aimed to determine the potential protective effect of gallic acid against nicotine-induced testicular toxicity in male mice. Experimental approach: In this in vivo study, forty-eight mice were equally divided into eight groups intraperitoneally receiving normal saline (control), nicotine (0.6 mg/kg), gallic acid (5, 10, and 15 mg/kg), and gallic acid (5, 10, and 15 mg/kg) plus nicotine. Nicotine was injected intraperitoneally for 14 days and gallic acid was administered concomitantly with nicotine and continued for 7 days later. Then, body and testicular weights, the sperm parameters (viability, number, motility, and morphology of sperm), and testicular histology were evaluated. Also, serum levels of nitric oxide, total antioxidant, superoxide dismutase, malondialdehyde, and testosterone were measured. Findings/Results: The results showed that the administration of nicotine significantly reduced testis and body weight, sperm count, viability, normal morphology and motility, seminiferous tubules diameter, testosterone levels, serum levels of total antioxidants, and superoxide dismutase compared to the control group (P < 0.05). It also significantly increased the level of nitric oxide and malondialdehyde (P < 0.05). Increasing the dose of gallic acid along with nicotine significantly increased body weight, sperm count, viability, normal morphology and motility, the diameter of seminiferous, testosterone concentration, total antioxidant levels (P < 0.05). This combination also significantly decreased malondialdehyde and nitric oxide levels compared to the nicotine-receiving group (P < 0.05). Conclusion and implications: Gallic acid had a protective effect on nicotine-induced testicular toxicity in mice. It can neutralize the harmful effect of nicotine on male fertility in smokers.

Background: The improvement of in vitro maturation methods, which can activate the preantral follicle growth, plays a crucial role in the production of mature oocytes in reproductive technology. Objective: To evaluate the different concentrations of 3D scaffolds of sodium alginate on hormones and gene expression in mice preantral follicles. Materials and Methods: Immature female BALB/c mice (12-14 days) were sacrificed. The follicles were removed mechanically and transferred into α minimal essential medium with 5% fetal bovine serum. The preantral follicles were incubated with different concentrations of sodium alginate (0.25%, 0.5%, and 1%) and 2D medium for 12 days. The follicles were examined for antral formation following the 10th day and the diameter on days 6 th and 12 th . The levels of hormones (AMH, androstenedione, 17 β -estradiol, and progesterone) and the expression of genes (CYP11a1, CYP17a1, CYP19a1, AMH, and GnRH) at the end of the 12 th day. Results: Maximum follicle diameter and highest percentage of antrum formation were related to 0.5% concentration (p = 0.00). The levels of hormones in different doses of sodium alginate were increased significantly compared to the control group (p = 0.00). The highest and lowest levels of these hormones were related to 0.5% concentration and 2D medium, respectively. The highest level of genes expression was observed in 0.5% sodium alginate, which showed a significant increase compared to the control group (p = 0.00). Conclusion: Proper concentration of alginate hydrogel increases follicle growth, causes follicle maturation, produces steroid hormones, and increases appropriate expression of steroidogenesis-related genes.

Background and purpose: Breast cancer is the most commonly occurring cancer in women around the world. Despite new advances in cancer therapy, breast cancer remains a disease with high morbidity and mortality. Snake venom is a poisonous mixture of different molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins, and peptides. Previous studies demonstrated that some snake venoms showed in vitro anti-cancer effects. In this study, the effects of the Iranian snake (Vipera raddei kurdistanica) venom on breast cancer cells were investigated. Experimental approach: The effect of increasing concentrations of snake venom on breast cell viability was assessed by trypan blue, MTT, and lactate dehydrogenase measurements. Apoptosis was detected and quantified by fluorescent staining and DNA fragmentation assay. The expression level of some apoptotic-related genes was investigated using real-time polymerase chain reaction (RT-PCR). The Western blotting method was also used to detect the protein expression profiles in the cells. Findings / Results: After treatment for 24, 48, 72, and 96 h, the cell viability was significantly reduced in a time- and dose-dependent manner (P < 0.05). The venom effect on normal breast cells was significantly smaller than cancer cells (P > 0.05). Apoptosis was significantly increased (P < 0.05). The RT-PCR and western blot data confirmed the increase of apoptosis in cells treated with venom. Conclusion and implications: These data suggested that the vipera raddei kurdistanica venom had a cytotoxic property via activation of apoptosis in breast cancer cells.

Background and purpose: Mercuric chloride (Merc) can cause kidney toxicity. Harmine (Harm), an herbal alkaloid has various pharmacological and medicinal effects mainly because of its antioxidant activity. In this study, therefore, Harm's protective mechanisms on Merc-induced nephrotoxicity in BALB/c male mice were investigated. Experimental approach: Forty-eight male mice were randomly divided into six groups (n = 8). Groups were received saline, Merc (0.5 mL/day of 0.5 ppm aqueous), Harm (5, 10, 15 mg/kg/day), Merc + Harm (5, 10, 15 mg/kg/day) for 14 consecutive days. Saline and Harm were administrated intraperitoneally and Merc dissolved in drinking water. Urea and creatinine serum levels, body weight, kidney weight, quantitative and qualitative histological alterations, apoptosis rate, total antioxidant capacity (TAC), superoxide dismutase (SOD), and nitric oxide (NO) levels were evaluated. Findings/Results: There was a significant reduction in total body and kidney weights, renal histological criteria, TAC, SOD levels in the Merc group compared to the control group (P < 0.05), whereas these parameters in the Merc + Harm groups, were significantly increased compared to the Merc group (P < 0.05). Urea and creatinine serum levels, levels of NO, and apoptosis were significantly higher in the Merc group than the control, while these parameters were decreased in the Merc + Harms groups in comparison with the Merc group (P < 0.05). Conclusion and implications: Harm protected Merc-induced renal damage in mice. This protection was observed in both histological and biochemical respects. The beneficial effect of Harm was related to its antioxidant properties that diminish NO production and apoptosis induction in the kidney.

Introduction: Morphine (MOR) as a psychoactive agent in the opium family causes free radicals accumulation which leads to failure in spermatogenesis. Gallic acid (GA), a polyphenolic acid, is found in various plants with antioxidant, anti-fungal, anti-viral, and anti-allergic activities. The purpose of this study was to evaluate the effects of GA against MOR-induced damage to the reproductive parameter of rats. Methods: Sixty-four male Wistar rats (8 weeks, 220-250 g) were categorized into 8 groups by random (n=8/each); normal control and MOR control groups; GA groups (5, 10, 20 mg/kg) and MOR + GA groups (5, 10, 20 mg/kg). Treatments were administered intraperitoneally (i.p), daily for 4 weeks. The sperm parameters, spermatogenesis index (SI), total antioxidant capacity, testosterone level, and seminiferous tube diameter (STD) were assessed. Results: All sperm parameters reduced significantly in the MOR control group than to the normal control group (P < 0.01). All parameters were significantly improved in GA and GA + MOR treatment groups compared to the MOR control group (P < 0.01). Conclusion: MOR caused a detrimental effect on male reproductive parameters. Also, no significant modifications were observed in all doses of GA treatments in comparison with the normal control group. GA compensates the toxic effect of MOR on reproductive parameters. Hence, GA administration is beneficial in MOR users.

Introduction: Methotrexate (Met) as a chemotherapy drug has many side effects, such as infiltration of neutrophils and the development of oxidative stress. Crocin (Cro), a carotenoid isolated from saffron, has numerous therapeutic characteristics including anticancer and antioxidant activities. This study was designed to evaluate the effects of Cro against hepatic damage in rats induced by Met. Methods: In this study, 48 male Wistar rats were randomly assigned into 8 groups, control normal (saline), Met control-treated group (20 mg/kg), Cro groups (12.5, 25, 50 mg/kg) and Met + Cro treated groups (12.5, 25, 50 mg/kg). Treatments were administered by intraperitoneal injection daily for 28 days. Griess technique was hired for the determination of serum nitrite oxide (NO) level. Concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were determined in order to assess liver function disturbances. In addition, Thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes and central hepatic vein (CHV) were investigated. Results: Met administration significantly increased the liver malondialdehyde (MDA) and NO level, the mean diameter of CHV, hepatocytes and hepatic enzymes. Met also decreased the tissue FRAP level compared to the normal control group (P < 0.01). The Cro and Cro + Met treatments in all doses significantly reduced the mean diameter of hepatocytes and CHV, hepatic enzymes, hepatic MDA and NO levels and increased the tissue FRAP level compared to the Met control group (P < 0.01). Conclusion: It seems that the Cro administration improves liver injury induced by Met in rats.

Background: The application of methotrexate (MTX) as a chemotherapy agent and immune system suppressant has various side effects. Crocin, a xanthine derivative plant, has many therapeutic benefits. This study was planned to assess the effect of crocin on renal toxicity of MTX in a rat model. Methods: Forty eight rats were divided randomly into eight groups (n = 6), which received normal saline, MTX, crocin, and MTX + crocin for 28 days intraperitoneally. The levels of oxidative stress in kidney and blood serum were measured, and the kidney was analyzed histologically. Results: MTX caused an enhancement in the levels of thiobarbituric acid reactive substances and biochemical marker (creatinine and BUN). Besides, a significant decrease was observed in tissue parameters and antioxidant capacity compared to the normal control group (p < 0.001). The crocin and crocin + MTX decreased the biochemical markers, the levels of thiobarbituric acid reactive species, and tissue parameters considerably at entire dose (12.5, 25, and 50 mg/kg) and enhanced the antioxidant capacity levels compared to the MTX group (p < 0.001). Conclusion: Administration of crocin improves the damage caused by MTX in rats. The crocin by the establishment of balance in the levels of antioxidant prevents the damage to the renal cell membrane, and subsequently the renal damage repairs.

Background: Pentoxifylline (PEN) is a xanthine derivative with different functional characteristics including dilution of blood and increase in tissue oxygenation rate. Nitrosamines (NITs) are well known as strong carcinogenic agents. This study attempts to show the histopathological and biochemical effects of PEN against hepatotoxicity induced by NIT in rats. Methods: Sixty-four rats were assigned to eight groups including the groups of sham: NIT (40 mg/kg); PEN (25, 50, and 100 mg/kg); and NIT + PEN. Experimental treatments were applied either intraperitoneally (for NIT) or orally (for PEN) daily for 4 weeks. The relative expression level of p53 and Bax genes and hepatocyte apoptotic index were analyzed. Liver malondialdehyde (MDA), tissue ferric-reducing ability of plasma (FRAP), the diameters of hepatocytes (DH) and central hepatic vein (CHV), and biochemical liver function indicators (LFI) were investigated. Griess technique was hired for the determination of the level of serum nitrite oxide (NO). Results and Conclusions: NIT significantly increased the level of apoptotic gens and index, MDA, NO, diameter of CHV and DH, and LFI and decreased the FRAP level compared to the sham group (P < 0.01). All parameters in PEN and PEN + NIT groups significantly reduced (except FRAP level, which was decreased) in compared to the NIT group (P < 0.01) . By summarizing the results of this research, it is concluded that the PEN administration alleviates the hepatotoxicity due to oxidative stress produced by NIT in rats.

Background: As a major tumor suppressor gene, P53 plays a principal role in the apoptosis of cancer cells. Harmine is a harmal-derived alkaloid with antioxidant and anticancer properties. This study was designed to assess the ability of harmine to express P53 gene and stimulate apoptosis in breast cancer cell line. Methods: MCF-7 cell line was cultured and treated with harmine. Half maximal inhibitory concentration (IC50) assay was carried out through MMT method following 24 h of treatment. Flow cytometry technique was employed to measure apoptotic cells and real-time PCR was performed to estimate P53 gene expression in tumor cells. Results: The IC50 for the harmine extract in MCF-7 cells was 30 μM. Harmine administration in all treated groups resulted in a significant increase in apoptosis and P53 gene expression in MCF-7 cells (P < 0.00001). Conclusions: It seems that harmine administration is able to induce apoptosis in MCF-7 cells through the up-regulation of P53 expression.

Purpose: Adipose stem cells (ASCs) are pluripotent cells with the ability of self-renewal and differentiation into different types of mesenchymal cells. As cartilage repair is difficult due to lack of blood capillary, resveratrol (Res) is a polyphenolic compound with diverse biological properties to be possibly used in this case. The aim of the present study was to investigate the effect of Res on differentiation of ASCs into chondrocyte in a three-dimensional (3D) culture model. Methods: Subcutaneous adipose tissues were prepared and digested enzymatically, and passed through cell strainer. ASCs were harvested in the fourth passage, and divided into five groups. The control group received chondrogenic differentiation medium (CDM) while the experimental groups received CDM plus different doses of Res (1, 10, 20, and 50 µM) for 21 days. Expression of cartilage specific genes and Sirtuin1 (SIRT 1), cell viability, apoptosis and ferric reducing antioxidant power (FRAP) were detected using reverse transcription polymerase chain reaction (RT-PCR), MTT assay, TUNEL and acridine orange/ethidium bromide (AO/EB) staining. One-way ANOVA and non-parametric Mann-Whitney U test were used for data analyses. Results: ASCs were differentiated to chondrocyte by CDM in a three-dimensional culture. 10 and 20 µM doses of Res showed the most proliferating effect on ADSCs. The SIRT 1 genes expression and FRAP level also increased significantly compared to the control group (P

Background: Tribulus terrestris has antioxidant and free-radical-scavenging properties. Malathion is the most common organophosphate, which is capable to produce free radicals and induce disturbance on some of male reproductive parameters. This study was designed to evaluate the effects of T. terrestris extract against damage induced by Malathion to the reproductive parameter of male rats. Materials and Methods: In this experimental study, 48 male Wistar rats were randomly assigned to eight groups: first group, sham group (normal saline); second group, Malathion (250 mg/kg) group; third to fifth groups, T. terrestris groups (2.5, 5, and 10 mg/kg body weight, respectively); and sixth to eight groups, Malathion + T. terrestris groups (2.5, 5, and 10 mg/kg). Tribulus terrestris extract (2.5, 5, and 10 mg/kg body weight, respectively) administrated orally, and daily for 8 weeks. The sperm parameters, testis malondialdehyde (MDA), serum total antioxidant capacity, serum testosterone level, and the height of germinal layer were evaluated and analyzed statistically. Results: All the values of male reproductive parameters reduced significantly in the Malathion group as compared to the sham group (P < 0.01) except MDA level, which increased significantly. The T. terrestris and T. terrestris + Malathion treatments in all doses increased the whole parameters significantly as compared to the Malathion group (P < 0.01) except MDA level, which decreased significantly. No significant changes were observed in all T. terrestris groups as compared to the sham group (P > 0.05). Conclusion: Tribulus terrestris extract administration attenuates the toxic effects of Malathion on some of the male reproductive parameters.

Background: The study aimed to assess the effect of anti-tumor and anti-proliferative properties of Sambucus nigra (SNA) on MCF-7 and MDA MB-231 breast tumor cell lines. Methods: The cytotoxicity of SNA was assessed based on dose/time by the MTT assay. Also, the influence of SNA on apoptotic pathways, cellular and metabolic resistance in these cell lines was examined by real-time PCR, lipid peroxidase was measured by malondialdehyde (MDA) and the effect of apoptosis and necrosis was determined by flow cytometry. Results: Our data showed that DOX, SNA, and DOX + SNA treatment induced the expression of p53, Bax, Bcl-2, Caspase-3, and 8 levels involved in the apoptotic pathways. ATP binding cassette subfamily B member 4 (ABCB4) gene expression was decreased in MDA‑MB-231 breast cancer cells compared to MCF-7. Also, we observed that DOX, SNA, and DOX + SNA treatment induced expression of Monocarboxylate transporters (MCTs) metabolic pathways such as MCT1 and MCT4. Conclusion: Overall, the outcomes of this investigation show that the combination of SNA-Doxorubicin (DOX) in different groups of these cancer cells, especially in the MDA‑MB-231 cell lines synergistically intensified the induction of apoptosis in them. SNA enhances the anti-cancer effects of DOX to induce cellular apoptosis, alter metabolic pathways, and reduce cellular resistance. The research highlights the promising use of SNA as a chemosensitizer in the chemotherapy.