iraj rashidi

Breast cancer is one of the most common global malignancy with high rate of mortality and morbidity.

This study aimed to evaluation of the effect of melittin on autophagy induced by everolimus in breast cancer cells.

MCF-7 cell line was treated with some concentrations of melittin and everolimus, and according to the IC 50 , the cells were treated to IC 50 dose, higher and lower doses than IC 50 in combination or separately. Then, combination index (CI), dose reduction index parameters, and occurrence of autophagy were evaluated. Also, the expression levels of genes related to the autophagy pathway were investigated.

The results of this study indicated that melittin and everolimus decreased viability in a concentration- and time-dependent manner, and the combined treatment had a synergistic effect. After 24 hr treatment with IC 50 concentration, autophagy was decreased significantly in the combined group compared to the group treated with everolimus (P < 0.05). Also the results of molecular analysis confirmed the data.

Melittin reduces the resistance of human breast cancer cells or increases their sensitivity to everolimus through blocking of autophagy process and consequently more breast cancer cells eliminate.

Some scorpion venoms contain compounds with potential anti-cancer properties. Colorectal cancer is the second most common cancer in women and the third most common in men. This study aimed to investigate the effects of Hemiscorpius lepturus scorpion venom on the HT-29 colorectal cancer cell line.

The effect of scorpion venom on the survival of cancer cells and fibroblasts was investigated using the MTT method. APC gene expression level were determined by Real-time PCR. PPAR protein levels were measured by ELISA, and nitric oxide secretion was assessed using the Griess reaction.

The viability of HT-29 cells and fibroblasts decreased significantly after 24, 48, 72, and 96 hours of treatment, depending on the concentration of scorpion venom and the duration of exposure (P≤0.05). The IC50 value for cancer cells was higher than that for fibroblast cells. The lactate dehydrogenase assay indicated that this decrease in viability was associated with the loss of cell membrane integrity. Treatment with the IC50 concentration of scorpion venom induced a significant increase in apoptosis and APC gene expression (P≤0.05) while significantly decreasing PARP protein levels and nitric oxide production (P≤0.05).

Based on the findings of the present study, it can be recommended that Hemiscorpius lepturus scorpion venom has cytotoxic effects through the stimulation of apoptosis. Additionally, it exerts anti-colorectal cancer effects by reducing APC gene expression and PARP protein levels.

Fumaria Parviflora L. (FP) is a well-known herb in Iranian traditional medicine, widely used for gastrointestinal diseases. Additionally, the detrimental effects of carbon tetrachloride (CT) on the liver and kidneys have been scientifically established.

This study was designed to assess the therapeutic effects of FP on HepG2 cells exposed to CT toxicity.

After treatment with hydroalcoholic extract of the FP plant and/or CT, cell viability (using the MTT technique and lactate dehydrogenase assay) and apoptosis (using the diphenylamine assay and Annexin V/PI staining) were investigated. The ratio of BCL2/BAX mRNA expression levels was measured using real-time PCR. Data were analyzed using SPSS software.

A significant (P < 0.05) reduction in cell viability was observed at doses of 100 and 200 µg/mL of FP in HepG2 cells. The decreased survival rate following CT exposure was concentration-dependent and significant (P < 0.05). The IC50 of CT was determined to be 1.05 μg/mL for 24 hours. Effective detoxification associated with CT was found at 6.25 µg/mL in both the pre-treatment and simultaneous treatment groups. Cell apoptosis was significantly (P < 0.05) decreased following FP administration in CT-treated cells, with an increase in the ratio of BCL2/BAX mRNA expression levels.

The hydroalcoholic extract of FP demonstrated hepatoprotective effects on CT-treated HepG2 cells.

Melanoma, one of the most lethal cancers, originates from epidermal layer. An advanced type of malignant melanoma represents a poor response to chemotherapy or other medications due to intrinsic and/or acquired resistance to antineoplastic drugs. Taraxasterol is a pentacyclic-triterpene agent mainly extracted from Dandelion herb with anti-proliferative and apoptotic features on cancer cells. Thus, this paper investigated the apoptosis pathway caused by Taraxasterol in the human melanoma cell line (hMCL).

hMCLs were treated with Taraxasterol and IC50 index was calculated using MTT assay. Then, apoptosis rate was evaluated by DNA Fragmentation Calorimetric technique. Finally, apoptosis pathway was investigated through various molecular laboratory assays.

Low cellular viability level was found as concentration and time-dependent routes. Induction of apoptosis by IC50 value of Taraxasterol was found significantly (p<0.05) effective. Mitochondria membrane potential index was reduced by Taraxasterol significantly (p<0.05). Also, the cytosolic levels of cytochrome C and expression level of caspase 3, 8, and 9 genes in hMCL were increased significantly (p<0.05) following Taraxasterol administration.   

Taraxasterol represents anti-proliferative and toxic effects against hMCL by induction of apoptosis.

In this research, the role of green management of human resources in improving environmental health was investigated in the National Company of Southern Oil-rich Regions. In terms of practical purpose and in terms of implementation method, it is a descriptive-survey research with cross-sectional approach. The statistical population includes the employees of southern oil-rich areas (oil company), a sample of 300 people was selected. The results showed that the green management of human resources has a positive and significant effect on the green attitude; Green management of human resources has a positive and significant effect on green self-efficacy; Green management of human resources has a positive and significant effect on environmental interest; Green attitude has a positive and significant effect on green behavior; Green self-efficacy has a positive and significant effect on green behavior; Environmental interest has a positive and significant effect on green behavior. Finally, it was found that the green behavior of employees has a positive and significant effect on environmental health

Mitochondrial oxidative stress is an important factor in infertility. The mitochondrial thioredoxin system plays an important role in this condition. N-acetyl-5-methoxy tryptamine (melatonin) plays a role in reducing oxidative stress and apoptosis in spermatogonial stem cells (SSCs). In this study, we explore the probable protective effects of melatonin on the mitochondrial thioredoxin system [thioredoxin 2 (Trx2)/Txnip] in SSCs under oxidative stress.

In this experimental study, SSCs were co-cultured two-dimensionally (2D) with Sertoli cells in DMEM culture medium that contained 10% fetal bovine serum (FBS), 1% antibiotics, and 10 ng/ml glial cell-derived neurotrophic 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, 24 hours). 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 factor erythroid 2-related factor 2 (Nrf2), Trx2, and nicotinamide nucleotide transhydrogenase (NNT) proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Adenosine triphosphate (ATP) levels were measured by fluorometry.

Melatonin reduced H2O2-induced ROS levels and apoptosis in the SSCs. Melatonin also increased mRNA expression of Nrf2, Trx2, NNT, Sirtuin 3 (Sirt3), and decreased mRNA expression of Txnip, and increased protein expressions of Nrf2, Trx2, NNT thereby increasing activity of the mitochondrial thioredoxin system. In addition, melatonin increased ATP levels.

Melatonin increased Trx2 expression through the Nrf2 pathway. This study suggests that melatonin may protect SSCs from oxidative stress in diseases related to infertility.

Chronic low-grade inflammation is a common condition in obesity. The aim of the present study was to investigate the effects of aged garlic extract and aerobic training on TLR4/NFƙB inflammatory signaling pathway gene expression in obese male rats.

Forty male Sprague-Dawley rats were subjected to high-fat diet (n = 32) and standard diet group (n = 8) for 9 weeks. After inducing obesity in the rats fed high-fat diet, the rats of this group were divided into four subgroups (n = 8), including the obese control (OC), the supplemented with aged garlic extract (AGE), the aerobic training (AT), and the supplemented with aged garlic extract + aerobic training (AGE + AT). The rats in the standard diet group also continued their diet for 8 weeks and interventions continued for 8 weeks. AGE was fed to rats once daily at a dose of 600 mg/kg by gavage. AT also included running on a treadmill five days a week. The TLR4 and NFƙB gene expression was measured by Real-time PCR and lipid profile changes evaluated in plasma.

All interventions led to a significant decrease in TLR4 and NFƙB gene expression in visceral fat, as well as improving the lipid profile of obese rats (p = 0.001). TLR4 reduction was higher in AGE + AT group (p = 0.001). On the other hand, AGE and AGE + AT caused a greater decrease in NFƙB gene expression compared to AT (p = 0.001). AGE + AT also improved the lipid profile more compared to other interventions (p = 0.001).

The combining of interventions is more effective in reducing TLR4 and NFƙB gene expression in visceral fat as well as improving lipid profile.

Multiple sclerosis (MS) disease causes structural and functional damage to brain. Structural imaging of the MS-induced damage cannot adequately describe the functional impairment of the brain in MS patients. Therefore, it seems that advanced functional imaging analysis such as functional magnetic resonance imaging (fMRI) data is needed for better management of this disease. The aim of present study was to evaluate the effective connectivity within the Papez circuit in MS patients using resting-state fMRI. In this cross-sectional analytical study, 22 healthy individuals and 24 patients with MS underwent resting-state fMRI. After pre-processing of the obtained data, the time series of Cingulate gyrus (CG), Para hippocampus gyrus (PHG), anterior thalamic nuclei (ATN), Mammillary body (MB), and Hippocampus (HPC) were extracted as the main Papez circuit components. The obtained time series were statistically analyzed as an input of the dynamic causal model in order to evaluate the effective connectivity in the Papez circuit. The power of effective connectivity between each pair of tested nodes in Papez circuit was significantly lower in MS patients than healthy subjects. Also, the effective connectivity level of MS patients in direction of HPC→ATN was higher in men than women. In addition, effective self-connection in CG→CG and MB→MB regions in healthy subjects were higher in women than them in men. The present study reveals significant difference in effective connectivity of the Papez nodes in MS patients than control group, which can be exploited to diagnosis and predict or evaluate the treatment response of these patients.

Given the importance of education and institutionalization of the relevant discussions in scientific centers and universities, this article was to identify environmental strategies for managing human resources in the Islamic Azad University, Iran. This is an applied research in terms of purpose, a correlation study in terms of descriptive nature, and a survey in terms of method. The statistical population included experts of human resource management from the Islamic Azad universities. The researcher-made questionnaire consisted of 31 questions in the spectrum of very high to very low was used to collect data. The methods proposed by (Hui Law & Chen, 2017) were used to determine the content validity. Validity of the measurement tool was checked referring to the experts' opinions. The questionnaire was given to the experts to match the questions to the variables using three options of "necessary", "useful but not necessary" and "not necessary". An acceptable lavage coefficient of 0.42 was obtained for 20 experts. In addition, more than 70% of the respondents selected the option "appropriate" as the lavage option for all items, and the lavage coefficient of above 0.42 was obtained for all the items, and finally, their validity was confirmed. The Content Validity Index (CVI) was calculated to be 0.99 in most cases. Cronbach's alpha coefficient of the variables was higher than 0.7, indicating the internal consistency of the items and confirmation of reliability. In this article, 31 environmental strategies were presented for managing human resources as 4 general loops of recruitment and employment, education.

Blood-brain barrier (BBB) permeability is central in multiple sclerosis (MS) pathophysiology, and exercise may improve BBB integrity. The current study investigated the prophylactic and/ or therapeutic role of aerobic exercise (EX) training on BBB integrity in experimental autoimmune encephalomyelitis (EAE). 

Forty female Lewis rats were randomly divided into four groups. The experimental groups included: no-EAE induction+ no-exercise (no-EAE+ no-EX), no-EAE induction+ exercise (no-EAE+EX), EAE induction+ no-exercise (EAE+ no-EX), and EAE induction+ exercise (EAE+EX). The no-EAE+EX and EAE+EX groups performed six weeks of progressive aerobic exercise training. GFAP, angiopoietin 1 (Ang-1) expression, tight-junction (TJ) proteins of claudin-5 and occludin were measured as components of BBB integrity and the rate of neuronal apoptosis was evaluated in hippocampi. 

A significant increase in GFAP and Ang-1 expression (P<0.001) and conversely a down-regulation in TJ proteins (P<0.05) was found in the brains of the no-EAE+EX group compared with the no-EAE+ no-EX group. The expression of GFAP and Ang-1 proteins significantly increased in the hippocampi of the EAE+ no-EX group (P<0.001), whereas aerobic training (in the EAE+EX group) meaningfully reversed such increases (P<0.001). Besides, down-regulated TJ proteins and increased neuronal apoptosis induced by EAE induction (EAE+ no-EX group) were restored and reduced, respectively, by aerobic training in the CNS of the EAE+EX group (P<0.001). 

The provision of a six-week treadmill aerobic training buffered the detrimental effects of EAE on BBB integrity and consequently neuronal apoptosis.

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.

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. Dichlorvoshepatitis 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.

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.

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.

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 nicotinereceiving group (P < 0.05).

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.

 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.

 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.

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</em> < 0.05), whereas these parameters in the Merc + Harm groups, were significantly increased compared to the Merc group (P</em> < 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</em> < 0.05).

 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.

Green human resources is also one of the relevant topics and a subset of the topic of sustainable development and friendly environmental management, which has been considered by researchers, international institutions and other organizations since the beginning of this century. Ignoring it causes irreparable damage to organizations. This research has been conducted with the aim of designing a green human resource management model in Islamic Azad University and using a mixed method (quantitative and qualitative).

In the qualitative part, Delphi method was used. In this part, the research model was compiled by performing three rounds of Delphi method. In the quantitative part, using the scenario method and in SPSS and Vansim software environment, the proposed model and questions Presented in the qualitative stage were examined. The statistical population in the qualitative section included 15 experts in the field of human resource management who were selected by snowball method.

 The results showed that green analysis and design, green human resource planning, green employment, green selection, green socialization, green staff communication, green development, green reward management, green health management, discipline management Green and green performance evaluation are the explored dimensions of green human resource management. In this research, with the help of scenario writing, the green human resource management model was designed and compiled in Islamic Azad University.

It seems that the pattern of green human resources can affect the health of the community. In this regard, it is suggested that more research be done.

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.

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.

These data suggested that the vipera raddei kurdistanica venom had a cytotoxic property via activation of apoptosis in breast cancer cells

Knowledge of anatomy is the basis of medicine and clinical practices. This study aimed to determine factors affecting anatomy learning from the viewpoint of students at Kermanshah University of Medical Sciences. This cross-sectional study enrolled all students at basic sciences stage at the School of Medicine at Kermanshah University of Medical Sciences in 2016 and 2017. A questionnaire was delivered in classrooms by the researchers with the permission of the teachers. Data was analyzed in the SPSS-16 software, employing the Mann-Whitney and Kruskal-Wallis tests. Out of 300 questionnaires, 179 were returned, 71 from male students (39.7%) and 108 from female students (60.3%); 116 (64.8%) in the third semester, 31 (17.3%) in the fourth, and 32 (17.9%) in the physiopathology level. Significant differences were found between the viewpoints of male and female students on the following variables: Use of animation, use of moulages, questions based on references, frequent quizzes, classified tests during the term, and the teachers’ patience, indicating the ‘clear expression of teachers’ with a mean of 4.7 ± 0.47 as the main effective factor. There were significant differences between the mean scores for ‘design of questions based on the sources’ (P < 0.05) and also between the views of physiopathology students and third-year students (P < 0.05). Lecture-based education without proper audio-visual aids lacks popularity among students, resulting in a waste of time and low levels of student learning. Mentioning the clinical aspects and engaging students in clinical issues to improve learning is paramount.

Pentoxifylline (PX) prevents cAMP breakdown by inhibiting the activity of thecAMP-phosphatase and presumably, stimulates sperm motion. Incubation with PX causeshyperactivation of sperm, an important step in achieving fertilization, and leads to changes inmembranes associated with sperm capacitation.

The purpose of this study was to examine the effects of pentoxifylline on spermviability, motility and fertilization rate after mouse sperm preservation.

Epididymal spermatozoa from adult NMRI mice were collected in T6medium supplemented with 5% BSA and divided into four control and four experimental groups.The control groups included: (1) Fresh sperm sample (2) Preserved sperm sample at roomtemperature for 18 hours. (3) Preserved sperm sample at incubator 37°C for 18 hours. (4) Preservedsperm sample at 4°C for 18 hours. Experimental groups were the same groups after treatment with3mmol/L PX. All the samples were assessed according to World Health Organization Criteria.Oocytes from superovulated NMRI female mice were inseminated in-vitro incubated sperm of allthe control and experimental groups. After insemination and washing, the fertilization rate andcleavage rate were assessed by the presence of two pronucleus (2PN) and 2-cell stage embryos. Tostudy the acrosomal reaction of control and treated spermatozoa transmission electron microscopy(TEM) technique was used.

The results showed that addition of 3mmol PX to preserved mouse spermatozoa at 4 ºCand 37 ºC could increase the motility rate significantly (P<0.05) and also it could enhance abnormalmorphology rate. Significant increase of fertilization rate was seen after preservation of treatedsperm at 4 ºC (P<0.05), but there was not seen significant difference regarding cleavage ratecomparing treated and non-treated spermatozoa (P>0.05). Studies with electron microscopy showedthat addition of PX to the preserved spermatozoa prevent early acrosomal reaction.

The results of this study demonstrated that addition of pentoxifylline in mouse spermsamples after short time preservation can enhance the motility and fertilization rate, although it canenhance the abnormal morphology. It also can increase the number of intact sperm afterpreservation.