Search

Abstract Intrauterine adhesion (IUA), also referred to as Asherman’s syndrome, is characterized by fibrosis, inflammation, and can cause amenorrhea and infertility due to abnormal endometrial healing. Histological and Molecular methods were used to evaluate the efficacy of EPO, which is traditionally known for its anti-inflammatory and fibrinolytic properties, in preventing the formation of IUA. Oral administration of EPO reduced the formation of adhesion bands and promoted endometrial regeneration. EPO administration decreased extracellular matrix accumulation, evidenced by the down-regulation of tissue COL1A1 and COL3A1 expression. The anti-inflammatory effect of EPO was confirmed by a reduction in oxidants and down-regulation of pro-inflammatory cytokines including TNF-α, IL-6, IFN-γ, and IL-1β. Furthermore, EPO improved embryonic development parameters, including size and weight of embryo, as well as increased embryo count and live embryo percentage in the rat IUA model. EPO also positively enhanced implantation markers, particularly enlargement and mass gain in the placenta of the treated group, consequently improving pregnancy outcomes such as the number of babies, percent of live babies, baby weight and gestation time. Histopathological investigation provides evidence that oral administration of EPO showed no toxicity on the main three organs including liver, kidney and heart. These results showed that EPO can be considered as a safe and natural product with potent anti-inflammatory and fibrinolytic properties without any observed side effects for the treatment of IUA.

Objective: Muscle atrophy due to immobility is a common complication of many diseases and a consequence of therapeutic processes. Immobility and inactivity have been shown to be associated with increased inflammation. The aim of this study was to investigate the therapeutic potential of Wild Bitter Melon (WBM) (Momordica charantia Linn) on muscle atrophy due to immobility in a mouse model.Materials and Methods: This study was performed in two phases of atrophy and recovery on male BALB/c mice which were divided into 3 groups: control, immobilized, and experimental. The treatment period with WBM at a dose of 400 mg/kg daily by gavage was 17 days, including 7 days of being immobilized and 10 days of recovery. At the end of each phase, half of the mice from each group were examined regarding the four limb grip strength, and then histological and biochemical analyses were done.Results: The tissue level of malondialdehyde (MDA) oxidative stress index in the atrophy phase in the atrophy group (5.4567±0.522) nmol/g compared to the control group (3.455±0.065) nmol significantly (p 0.001)

Objective: Radiodermatitis (RD) is a frequent adverse event of radiotherapy (RT). Currently, there is no consensus and approved protocol for the treatment of RD. Curcumin (CUR) is a natural polyphenol obtained from turmeric and it has low intrinsic toxicity in humans. The aim of this systematic review was to explore the efficacy of CUR for prevention and treatment of RD.Materials and Methods: A systematic literature review was performed in the following online databases: Cochrane library, PubMed, Scopus, Web of Science, MEDLINE, and EMBASE. Among the 5 selected records, 3 had a randomized clinical trial (RCT)-design and the other had a pilot and controlled study designed. The included studies were performed on breast cancer (N=3), head and neck cancers (N=1) and different types of cancer (N=1).Results: Four of the studies reported that the application of curcumin in cancer patients undergoing radiotherapy is associated with decreased intensity of radiodermatitis. However, one study did not report any significant effect of CUR on radiodermatitis. This review provides substantial evidence which confirm the clinical value of CUR in cancer supportive care.Conclusion: Further prospective clinical trials in larger scales are warranted in order to determine the " supplemental form and dose of CUR" for RD prevention and treatment in patients receiving radiotherapy.

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P

Objective(s): Zirconium-based metal-organic frameworks (MOFs) nanostructures, due to their capability of easy surface modification, are considered interesting structures for delivery. In the present study, the surfaces of UIO-66 and NH2-UIO-66 MOFs were modified by polyethyleneimine (PEI) 10000 Da, and their efficiency for plasmid delivery was evaluated. Materials and Methods: Two different approaches, were employed to prepare surface-modified nanoparticles. The physicochemical characteristics of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: The sizes of DNA/nanocarriers for PEI-modified UIO-66 (PEI-UIO-66) were between 212–291 nm and 267–321 nm for PEI 6-bromohexanoic acid linked UIO-66 (PEI-HEX-UIO-66). The zeta potential of all was positive with the ranges of +16 to +20 mV and +23 to +26 mV for PEI-UIO-66 and PEI-HEX-UIO-66, respectively. Cellular assay results showed that the PEI linking method had a higher rate of gene transfection efficiency with minimal cytotoxicity than the wet impregnation method. The difference between transfection of modified nanoparticles compared to the PEI 10 kDa was not significant but the PEI-HEX-UIO-66 showed less cytotoxicity. Conclusion: The present study suggested that the post-synthetic modification of MOFs with PEI 10000 Da through EDC/NHS+6-bromohexanoic acid reaction can be considered as an effective approach for modifying MOFs’ structure in order to obtain nanoparticles with better biological function in the gene delivery process.

Abstract Studying the effects of the microbiome on the development of different types of cancer has recently received increasing research attention. In this context, the microbial content of organs of the gastrointestinal tract has been proposed to play a potential role in the development of pancreatic cancer (PC). Proposed mechanisms for the pathogenesis of PC include persistent inflammation caused by microbiota leading to an impairment of antitumor immune surveillance and altered cellular processes in the tumor microenvironment. The limited available diagnostic markers that can currently be used for screening suggest the importance of microbial composition as a non-invasive biomarker that can be used in clinical settings. Samples including saliva, stool, and blood can be analyzed by 16 s rRNA sequencing to determine the relative abundance of specific bacteria. Studies have shown the potentially beneficial effects of prebiotics, probiotics, antibiotics, fecal microbial transplantation, and bacteriophage therapy in altering microbial diversity, and subsequently improving treatment outcomes. In this review, we summarize the potential impact of the microbiome in the pathogenesis of PC, and the role these microorganisms might play as biomarkers in the diagnosis and determining the prognosis of patients. We also discuss novel treatment methods being used to minimize or prevent the progression of dysbiosis by modulating the microbial composition. Emerging evidence is supportive of applying these findings to improve current therapeutic strategies employed in the treatment of PC.

Abstract Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases that result from the accumulation of excess triglycerides in the liver, and which, in its early phases, is categorized NAFLD, or hepato-steatosis with pure fatty liver. The mortality rate of non-alcoholic steatohepatitis (NASH) is more than NAFLD; therefore, diagnosing the disease in its early stages may decrease liver damage and increase the survival rate. In the current study, we screened the gene expression data of NAFLD patients and control samples from the public dataset GEO to detect DEGs. Then, the correlation betweenbetween the top selected DEGs and clinical data was evaluated. In the present study, two GEO datasets (GSE48452, GSE126848) were downloaded. The dysregulated expressed genes (DEGs) were identified by machine learning methods (Penalize regression models). Then, the shared DEGs between the two training datasets were validated using validation datasets. ROC-curve analysis was used to identify diagnostic markers. R software analyzed the interactions between DEGs, clinical data, and fatty liver. Ten novel genes, including ABCF1, SART3, APC5, NONO, KAT7, ZPR1, RABGAP1, SLC7A8, SPAG9, and KAT6A were found to have a differential expression between NAFLD and healthy individuals. Based on validation results and ROC analysis, NR4A2 and IGFBP1b were identified as diagnostic markers. These key genes may be predictive markers for the development of fatty liver. It is recommended that these key genes are assessed further as possible predictive markers during the development of fatty liver.

Background: This investigation investigates the anti-inflammatory and fibrinolytic effects of a cocktail of probiotics derived from traditional dairy products in a murine model of ulcerative colitis (UC). Materials and Methods: A mix of newly isolated probiotics containing L. plantarum, L. brevis, L. delbrueckii, and L. helveticus was characterized and orally administered to inbred eight-week-old C57BL/6 male mice (n = 6). Clinical symptoms, pathohistological changes, and inflammatory and fibrosis markers were analyzed in the existence and absence of probiotics in colitis mice. Results: Dairy lactobacillus probiotics potently attenuated colitis symptoms by decreasing dextran sulfate sodium (DSS)-induced body weight loss, colon shortening, rectal bleeding, and rectal prolapse. Consistently, a cocktail of probiotics could significantly improve histopathological grading by suppressing crypt loss, mucosal damage, and inflammation scores in colitis tissues. Moreover, the mix of probiotics suppressed pro-inflammatory genes including interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), and increased anti-oxidant markers and activity such as superoxide dismutase and catalase in colon tissue. Furthermore, compared to the no-treated group, the administration of probiotics reduced fibrosis by decreasing collagen deposition in tissue sections and down-regulating levels of pro-fibrotic genes including alpha-actin-2 (Acta2), collagen (Col) 1a1, and Col 1a2 in colitis tissue homogenates. Conclusions: The results show the newly isolated cocktail of probiotics elicits a potent protective effect on UC symptoms in mice model. Further study on these probiotics is required to fully explore their effectiveness, strength, and safety considerations.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is associated with a very poor prognosis. Therefore, there has been a focus on identifying new biomarkers for its early diagnosis and the prediction of patient survival. Genome-wide RNA and microRNA sequencing, bioinformatics and Machine Learning approaches to identify differentially expressed genes (DEGs), followed by validation in an additional cohort of PDAC patients has been undertaken. To identify DEGs, genome RNA sequencing and clinical data from pancreatic cancer patients were extracted from The Cancer Genome Atlas Database (TCGA). We used Kaplan–Meier analysis of survival curves was used to assess prognostic biomarkers. Ensemble learning, Random Forest (RF), Max Voting, Adaboost, Gradient boosting machines (GBM), and Extreme Gradient Boosting (XGB) techniques were used, and Gradient boosting machines (GBM) were selected with 100% accuracy for analysis. Moreover, protein–protein interaction (PPI), molecular pathways, concomitant expression of DEGs, and correlations between DEGs and clinical data were analyzed. We have evaluated candidate genes, miRNAs, and a combination of these obtained from machine learning algorithms and survival analysis. The results of Machine learning identified 23 genes with negative regulation, five genes with positive regulation, seven microRNAs with negative regulation, and 20 microRNAs with positive regulation in PDAC. Key genes BMF, FRMD4A, ADAP2, PPP1R17, and CACNG3 had the highest coefficient in the advanced stages of the disease. In addition, the survival analysis showed decreased expression of hsa.miR.642a, hsa.mir.363, CD22, BTNL9, and CTSW and overexpression of hsa.miR.153.1, hsa.miR.539, hsa.miR.412 reduced survival rate. CTSW was identified as a novel genetic marker and this was validated using RT-PCR. Machine learning algorithms may be used to Identify key dysregulated genes/miRNAs involved in the disease pathogenesis can be used to detect patients in earlier stages. Our data also demonstrated the prognostic and diagnostic value of CTSW in PDAC.

Introduction Crop water productivity (CWP) is defined as the crop yield produced per unit of water consumed, which can be improved by increasing the crop yield with a given water usage or reducing water usage with a given yield. Increasing CWP can thus help to alleviate the water crisis while ensuring food security. Physical productivity alone is not enough to determine the crop pattern and economic productivity should also be considered. Economic water productivity (EWP) expressed as the gross income in USS per unit of water consumed, is relevant for farmers to pursue higher net benefits. Both CWP and EWP terms are important indices for water resource managers to consider when formulating planning policies. The simultaneous consideration of CWP and EWP allows for a more comprehensive and robust exploration when planning the process for developing regional agricultural water-saving measures, such as modifying the regional cropping distribution. This allows farmers to reduce irrigation water use and shift the area of water-intensive crops to ones with efficient water use or higher economic value. Determining crop pattern-based water productivity is especially important in countries with dry climates, whose agriculture depends solely on irrigation and also has low water consumption efficiency. Therefore, instead of consuming scarce water resources, in the production of products that consume a lot of water, it is possible to produce products with lower water consumption and avoid excessive pressure on water resources. Knowledge of crop-water requirements is crucial for water resources management and planning to improve water-use efficiency. Crop water requirements in the growing period depends on the crop growth stage, cropping technique, and irrigation method. About 99 % of the water uptake by plants from soil is lost as evapotranspiration (ET), so, it can be stated that the measurement of actual crop evapotranspiration (ETc) on a daily scale for the whole vegetative cycle is equal to the water requirement of the given crop. Evapotranspiration is defined as the water lost as vapor by an unsaturated vegetative surface and it is the sum of evaporation from soil and transpiration by plants. Knowledge of the exact water loss through actual evapotranspiration is necessary for accurate and effective water management. Materials and Methods For this purpose, in the first stage agricultural condition of the aquifer was investigated through a questionnaire by farmers and experts. To calculate the reference crop evapotranspiration we used the Penman-Monteith equation in this study crop coefficient curves have been prepared according to the agricultural calendar of the Basht aquifer. Net water requirement is calculated from the difference between effective rainfall and evapotranspiration. Water productivity per crop ( ) (kg.m-3) is an important index for determining the agricultural production system efficiency. Water productivity is defined as the proportion of crop yield (kg.ha-1) to irrigation water consumed by crops in the field (m-3.ha-1). Likewise, water economic productivity is measured about or with the economic benefits in a monetary value of outputs over the number of necessary inputs such as water depleted. To calculate the value of each cubic meter of water, the production costs (minus the water) need to be deducted from the income and the remainder needs to be divided by the volume of water. The calculation results are calculated separately for each product. To determine the suitable pattern crop in Basht aquifer, different cropping patterns were evaluated (eight different scenarios). Results and Discussion Based on the results of the Penman-Monteith method, it can be concluded that the gross water requirement (the amount of net irrigation requirement divided by the irrigation efficiency) in dominant crops of aquifer including rice, alfalfa, citrus, watermelon, corn, wheat, rapeseed, legumes, barley respectively were 20234, 14083, 9291, 9170, 7863, 5630, 5411, 5225, and 4821 m-3 ha, respectively. The amount of effective precipitation that provided a part of the crop’s water requirement through soil moisture (green water) for water crops such as Rice and Corn is close to zero. Autumn crops such as canola, citrus fruits, and cereals use green water. To determine the amount of irrigation per hectare of the current crop pattern of the aquifer, the hydro module of each crop was determined. As it is clear from hydromodule, the average required water flow (l s-1 ha-1) for rice, alfalfa, citrus, watermelon, corn, rapeseed, wheat, beans, and barley, equaled 0.63, 0.44, 0.29, 0.29, 0.24, 0.18, 0.17, 0.16 and 0.15 (l s-1 ha-1) respectively. In total, the amount of water consumed by the agricultural products in the aquifer's Basht is 45 millm3, that approximately equivalent to one m3 m-2 of the aquifer cultivation area and this amount is much more than the aquifer agriculture programmable water. The economic productivity of the aquifer’s current cultivation is 45,000 IRR m-3, on average. Also, most aquifer products' physical productivity was less than one. the comparison of different patterns showed that scenarios eight and twohad the highest and lowest amount of water consumption, 45 and 22 millm3, respectively. Conclusion The crop pattern will be influenced by parameters such as climatic compatibility of products, water, and soil potentials, needs, interests of agriculture producers, and production income. In the Basht aquifer, the availability of water and the amount of water consumed is one of the most important factors in choosing the cultivation pattern. In the current situation, due to the high temperature and increasing evaporation rate, and the use of seasonal rainfall, crops that spend their growth period in autumn and winter should be included in the cultivation pattern. The simultaneity of water requirements for crops planted together is one of the important parameters in choosing the cultivation pattern. In the Basht aquifer, the water requirement of corn, alfalfa, cucumber, and tomatoes coincide with the citrus water requirement during the time of high water consumption, and the cultivation of one of them may create water limitations for the other crop. In contrast, the cultivation of wheat, barley, and canola have a very small overlap with the citrus irrigation times. Choosing a combination of citrus, wheat, barley, and canola will optimize the cultivation pattern.

Abstract The modulating factors within the tumor microenvironment, for example, transforming growth factor beta (TGF-β), may limit the response to chemo and immunotherapy protocols in colorectal cancer (CRC). In the current study, the therapeutic potential of targeting the TGF-β pathway using Pirfenidone (PFD), a TGF-β inhibitor, either alone or in combination with five fluorouracil (5-FU) has been explored in preclinical models of CRC. The anti-proliferative and migratory effects of PFD were assessed by MTT and wound-healing assays respectively. Xenograft models were used to study the anti-tumor activity, histopathological, and side effects analysis. Targeting of TGF-β resulted in suppression of cell proliferation and migration, associated with modulation of survivin and MMP9/E-cadherin. Moreover, the PFD inhibited TGF-β induced tumor progression, fibrosis, and inflammatory response through perturbation of collagen and E-cadherin. Targeting the TGF-β pathway using PFD may increase the anti-tumor effects of 5-FU and reduce tumor development, providing a new therapeutic approach to CRC treatment.

Objective(s): Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer. Materials and Methods: Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR.Results: These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis. Conclusion: It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU.

Abstract Introduction Cervical cancer is one of lethal cancers in women. As a global concern, identifying important factors of cancer is a useful strategy for prevention. Due to the role of diet/nutrition factors for cancer, the purpose of our study was to determine the impact of 150 nutrition/vitamin factors and 50 non-nutritional factor in cervical cancer and phase. Methods Population samples of 2088 healthy subjects and patients with cervical cancer were investigated. 200 factors such as vitamin E, B1, B6, fruits, HPV, and age were gathered. Deep learning, Decision tree, and correlation matrix were used for modeling and identifying important factors. SPSS 26, R4.0.3, and Rapid miner were utilized for implementation. Results Our findings indicated that zinc, Iron, Niacin, Potassium, Phosphorous, and Cooper have a beneficial impact in reducing the risk of cervical cancer and progression of phase in Iranian women, as well as Salt, snacks and milk Were identified as high-risk food factors (P value 0.6). Also, alcohol, and sex patient with two groups, HPV positive have an impact on cervical cancer incidence. Phosphorus and selenium in the Micronutrients category (R2 = 0.85, AUC = 0.993) and polyunsaturated fatty acid and salt in the Macronutrients category and other categories of nutrients were identified as the most effective factors in cervical cancer using deep learning (R2 = 0.93, AUC = 0.999). Conclusions A diet and rich nutrition can be helpful for the prevention of cervix cancer and may reduce the risk of disease. Additional research is necessary for different countries.

Introduction and Objective Nowadays, it is necessary to use new methods to resolve the issue of soil erosion instead of traditional methods in order to achieve more accurate knowledge and appropriate planning. The cheapest and most appropriate way to conserve the soil is to use vegetation. Therefore, considering the high costs and adverse environmental effects of mechanical methods compared to biological methods of soil conservation, the present study aims to investigate the effect of planting two varieties of fodder vetch as a biological, economic and environmentally friendly solution to reduce runoff, sediment and improve soil properties.Materials and Methods This research was carried out using standard experimental plots with dimensions of 22 × 1.8 meters and a slope of 9%, so that totally nine experimental plots including three treatments and three replications were applied and executed in the form of a randomized complete block design. The three treatments studied in this experiment included Maragheh vetch, Golshan vetch and native wheat of the study region (control treatment), and the studied vetch varieties were planted simultaneously with wheat cultivation in the fall in two consecutive years, 2020 and 2021. Finally, the mean data of runoff, sedimentation and stability of soil aggregates were compared and statistically analyzed.Results and Discussion In general, the studied fodder plants had a significant effect on reducing the runoff and sediment generated from the experimental plots, which shows the importance and role of these plants for the purposes of soil and water conservation. In particular, Maragheh fodder vetch showed excellent performance in reducing runoff and sediment in the study area, therefore planting the mentioned varieties in order to conserve soil and water is prioritized in the study area. The stability of soil aggregates also did not show any significant difference in the studied treatments during the experimental period. Therefore, it can be concluded that the stability of soil aggregates will not change within two years, and more time is needed to observe the change in this soil characteristic.Conclusion and Suggestions The results of this research revealed the significant effect of using forage plants, especially Maragheh and Golshan forage plants, on reducing runoff and sediment in line with the goals of soil and water protection. The use of fodder legumes compatible with the climatic conditions of each region that have suitable plant characteristics such as a strong and dense root and stem system as well as a suitable canopy in order to conserve soil and water and improving the livelihood of the residents of the region and also carrying out early irrigation and supplementary irrigation is recommended in the important stages of the plant growth under drought and low rainfall conditions. Also, conducting researches that investigate the effect of rainfall intensity, amount of rainfall, soil moisture, soil texture and chemical properties of soil on the effectiveness of dry fodder plants in water and soil conservation, as well as the relationship between different climatic, morphological and hydrological conditions of upstream and the effectiveness of dry land fodder plants in the qualitative and quantitative control of runoff, is suggested.

IntroductionGroundwater, one of the most important sources of water supply, has faced a considerable decrease in quantity and quality in recent decades due to harvesting more than their natural recharge. Over-extraction of groundwater causes subsidence, soil salinity, reduction of the base flow of rivers due to the drying up of springs, the salinity of groundwater, and in a general view, land destruction and the creation and expansion of desert areas. Desertification is one factor that threaten human life, which causes the destruction of natural resources. Therefore, knowledge of desertification processes is important and necessary to reduce the severity of this phenomenon and prevent its spread by providing suitable management solutions and methods. The Iranian Model of Desertification Potential Assessment (IMDPA) is efficient to evaluate the intensity of desertification. In this model, nine key criteria including climate, land-geomorphology, soil, vegetation, economic-social, agricultural water, groundwater, erosion, and urban development technology are considered. According to the reports about the spread of desertification factors in the Maharloo-Bakhtegan watershed located in Fars province, the objective of the present study is to investigate the impact of the water table drop and variations in the groundwater quality and land subsidence in desertification and land degradation as well as to prepare relevant maps in the mentioned watershed. Materials and Methods Maharloo-Bakhtegan watershed is one of the closed watersheds of Iran, which is a subcategory of the Central Plateau and has 27 study areas. A zoning map of the risk of water table drop was prepared using the related tables that classify the watershed area into four classes: low, medium, severe and very severe. In the same way, the data of quality degradation indicators of water resources including electrical conductivity (EC) and sodium surface absorption ratio (SAR) were classified; then, EC and SAR zoning layers were prepared. Then, the final desertification intensity map was obtained from the integration of maps of the intensity of qualitative and water table drop of groundwater resources, as well as the land subsidence map as a soil criterion. Finally, the zoning map of desertification intensity was prepared using the final risk classes of desertification. Results and Discussion The EC map showed that 37.2% of the watershed is in the low or insignificant class, 24.8% is in the medium class, 9.5% is in a severe class, and 28.5% of the watershed area is in the very severe class. So, it can have a significant effect on increasing the intensity of desertification. However, the zoning map of the SAR showed that more than 99% of the watershed area has a value less than 18 and is placed in the negligible or low class. The zoning of the water table drop also shows that 65.6% of the studied watershed is placed at the low or insignificant class, only 3% is in the medium class, 5.7% is in a severe class, and 25.7% is in the very severe class. The map of different levels of land subsidence showed that more than 97% of the watershed area either has no subsidence or is placed in a low and negligible level. The desertification intensity map also showed that 83% of the watershed area has low and moderate desertification intensity and 17% of the watershed area has severe and very severe desertification intensity. Therefore, the general situation of the watershed is not critical in terms of the intensity of desertification, but the areas with a moderate degree of destruction are subject to transition to extreme class due to the change of land uses that are expanding today as well as the increase of agricultural areas in the watershed. Conclusion The present study was conducted with the aim of investigating the effect of the decrease and change in the quality of underground water and land subsidence in desertification and land degradation in Maharlu-Bakhtegan watershed. The results showed that the electrical conductivity factor of underground water can have a significant effect on the intensity of desertification. On the other hand, land subsidence index was not prioritized in determining the intensity of desertification. Also, the intensity of desertification in a major part of the watershed was in the low and medium classes, and with the change of current uses and the increase of the cultivated area, it is recommended to make the necessary plans to prevent the progress of the intensity of desertification in the mentioned areas. In this direction and considering the role of human activities in the drop of the underground water level, the quality drop of the underground water and finally the subsidence of the land, measures such as the preparation of technical guidelines for the use of underground water, the use of pressurized irrigation systems, the proper implementation of the balancing plan of the Ministry of Energy and the implementation Management plans are recommended to preserve the vegetation of forests and pastures and to modify the cultivation pattern. Also, the zoning maps of indicators and intensity of desertification prepared in this study can be used by experts to prepare the land and provide suggested solutions and apply appropriate management methods with the aim of preventing the expansion and advancement of saline and desert lands. Conducting research in the field of indicators and other factors affecting desertification, such as evaporative formations in the region, the gentle slope of the water table in the plain, the presence of semi-permeable or impermeable layers, the lack of underground water flow from upstream and the infiltration of salty water from salty rivers into the aquifers of the river in the watershed. Maharlo-Bakhtagan is also recommended.

Abstract Background Defining standards is the first step toward quality assurance and improvement of educational programs. This study aimed at developing and validating a set of national standards for the Undergraduate Medical Education (UME) program through an accreditation system in Iran using the World Federation for Medical Education (WFME) framework. Methods The first draft of standards was prepared through consultative workshops with the participation of different UME program stakeholders. Subsequently, standards were sent to medical schools and UME directors were asked to complete a web-based survey. The content validity index at the item level (I-CVI) was computed using criteria including clarity, relevance, optimization and evaluability for each standard. Afterward, a full-day consultative workshop was held and a wide range of UME stakeholders across the country (n = 150) discussed the survey results and made corrections to standards. Results Analysis of survey results showed that relevance criteria had the best CVI as only 15 (13%) standards demonstrated CVI

Abstract Gastric cancer is the high mortality rate cancers globally, and the current survival rate is 30% even with the use of combination therapies. Recently, mounting evidence indicates the potential role of miRNAs in the diagnosis and assessing the prognosis of cancers. In the state-of-art research in cancer, machine-learning (ML) has gained increasing attention to find clinically useful biomarkers. The present study aimed to identify potential diagnostic and prognostic miRNAs in GC with the application of ML. Using the TCGA database and ML algorithms such as Support Vector Machine (SVM), Random Forest, k-NN, etc., a panel of 29 was obtained. Among the ML algorithms, SVM was chosen (AUC:88.5%, Accuracy:93% in GC). To find common molecular mechanisms of the miRNAs, their common gene targets were predicted using online databases such as miRWalk, miRDB, and Targetscan. Functional and enrichment analyzes were performed using Gene Ontology (GO) and Kyoto Database of Genes and Genomes (KEGG), as well as identification of protein–protein interactions (PPI) using the STRING database. Pathway analysis of the target genes revealed the involvement of several cancer-related pathways including miRNA mediated inhibition of translation, regulation of gene expression by genetic imprinting, and the Wnt signaling pathway. Survival and ROC curve analysis showed that the expression levels of hsa-miR-21, hsa-miR-133a, hsa-miR-146b, and hsa-miR-29c were associated with higher mortality and potentially earlier detection of GC patients. A panel of dysregulated miRNAs that may serve as reliable biomarkers for gastric cancer were identified using machine learning, which represents a powerful tool in biomarker identification.

Background: Education through peer-teachers is one of the teaching-learning methods that is being increasingly used in various studies. The purpose of this study was to investigate the use of peer-teachers in teaching physiology on learning and satisfaction of medical students.Method: This semi-experimental study was conducted on medical students of the basic sciences in Mashhad Medical School in 2021-2022. Students were divided into two groups: conventional and Peer teaching methods. The average score of the quizzes at the beginning and end of each session, final exam score, and rate of information retention were compared between the two groups. A survey was also conducted among students to assess their satisfaction.Results: The mean scores of the quizzes in the peer-teaching group were significantly higher than the control group (p

Abstract Background Adhesion band formation is a common cause of morbidity for patients undergoing surgeries. Anti-inflammatory and anti-fibrotic properties of curcumin, a pharmacologically active component of Curcuma longa, have been investigated in several studies. The aim of this study is to explore the therapeutic potential of curcumin in attenuating post-operative adhesion band (PSAB) formation in both peritoneal and peritendinous surgeries in animal models. Methods Bio-mechanical, histological and quantitative evaluation of inflammation, and total fibrosis scores were graded and measured in the presence and absence of phytosomal curcumin. Results Results showed that phytosomal curcumin significantly decreased severity, length, density and tolerance of mobility of peritendinous adhesions as well as incidence and severity of abdominal fibrotic bands post-surgery. Curcumin may decrease inflammation by attenuating recruitment of inflammatory cells and regulating oxidant/anti-oxidant balance in post-operative tissue samples. Moreover, markedly lower fibrosis scores were obtained in the adhesive tissues of phytosomal curcumin-treated groups which correlated with a significant decrease in quantity, quality and grading of fibers, and collagen deposition in animal models. Conclusion These results suggest that protective effects of phytosomal curcumin against PSAB formation is partially mediated by decreasing inflammation and fibrosis at site of surgery. Further studies are needed to investigate the therapeutic potential of this molecule in preventing PSAB.

Objective: Thrombin is a proinflammatory and pro-coagulant agent which is upregulated in several human diseases. Thrombin has a critical role in promoting cell proliferation and microvascular leakage in malignant cells, resulting in cancer growth and progression. Here, we explored the potential therapeutic value of curcumin on permeability induced by thrombin in mice.Materials and Methods: To assess the activity of curcumin on thrombin-induced vascular permeability mice model, C57BL / 6 mice were randomly divided into four groups: (1) control (2) Thrombin (3) Thrombin + Curcumin and (4) Thrombin + Metformin. Thirty minutes after treatment, Evans blue was injected intravenously through the tail vein to mice. Then, animals were sacrificed and the dye was extracted from the skin tissue by incubation with formamide. Heatmap and correlation map were generated and protein-protein interaction network of the hub genes was drawn by Cytoscape software.Results: Hub DEG expression rate showed that Heat shock protein a1 (Hspa1) family (comprised of HSPa1a, b, and HSPa5), caspase 3, and minichromosome maintenance complex component 2 were overexpressed after treatment with curcumin. Functional modules of curcumin enriched through Enrich gene biological process and revealed positive association of gene expression of apoptosis process with the therapy. Curcumin was also found to reduce leucocyte migration in murine tissues. Additionally, treatment with curcumin resulted in downregulation of heat shock proteins and proinflammatory cytokines such as monocyte chemotactic protein 1, interleukin-6 and chemokine (C-X-C motif) ligand 3.Conclusion: Curcumin inhibited the proinflammatory cytokines and inflammatory HSPs in endothelial cells and reduced thrombin-induced barrier destabilization in vivo.

Abstract There are significant challenges in developing drug carriers for therapeutic perspective. We have investigated a novel nanocarrier system, based on combining functionalized magnetic nanocomposite with Metal–Organic Frameworks (MOFs). Magnetic nanoparticles modified using biocompatible copolymers may be suitable for delivering hydrophobic drugs, such as cisplatin. Furthermore, compared to polymeric nanocarriers, nanocomposite constructed from zeolitic imidazolate framework-8 (ZIF-8) have demonstrated better drug loading capacity, as well as excellent pH-triggered drug release. Cisplatin-encapsulated Fe3O4@SiO2-ZIF-8@N-Chit-FA has been evaluated to determine the antitumor effects of free cisplatin enhancement in cervical cancer cells. In order to increase the stability of the proposed nanocarrier in aqueous solutions, in addition to the density of functional groups, a nano-chitosan layer was coated on top of the magnetic nanocomposite. It was then added with cisplatin onto the surface of Fe3O4@SiO2-ZIF-8@N-Chit-FA to deliver anticancer treatment that could be targeted using a magnetic field. A mouse isograft model of TC1 cells was used to evaluate the in vivo tumor growth inhibition. In tumor-bearing mice, Fe3O4@SiO2-ZIF-8@N-Chit-FA-cisplatin was injected intraperitoneally, and the targeted delivery was amplified by an external magnet (10 mm by 10 mm, surface field strength 0.4 T) fixed over the tumor site. Based on in vivo results, cisplatin-Loaded Mesoporous Magnetic Nanobiocomposite inhibited the growth of cervical tumors (P

Objective: Rhabdomyolysis is a life-threatening disease caused by releasing myoglobin from injured myocytes, which results in acute kidney injury. In this study, the effect of aqueous-alcoholic extract of Nigella sativa (NS) and thymoquinone (TQ) on rhabdomyolysis-induced kidney damage in rats was investigated.Materials and Methods: There were five groups of rats (n=8): Control, rhabdomyolysis, rhabdomyolysis treated with NS aqueous-alcoholic extract (200 and 400 mg/kg) and TQ (15 mg/kg). Treatments were given for 7 days (two days before and four days after glycerol injection). Glycerol was injected intramuscularly on the third day of the experiment for induction of rhabdomyolysis. Renal function parameters on the first, fourth, and seventh days of the experiment and renal oxidative stress and histological changes at the end of this study were assessed.Results: Glycerol injection caused a significant increase in serum level of urea, creatinine, creatine phosphokinase, urine output and tissue MDA compared to the control animals (p

Objective(s): Ulcerative colitis (UC) is a chronic large intestinal condition, for treatment and prevention of which sulfasalazine (SSZ) is used. It functions by helping to reduce inflammation and other disease symptoms within the bowels, but this drug has many side effects. Various novel paths for UC treatment are being studied to solve the difficulties associated with present treatments and to design a more targeted therapy. Hydroxyapatite nanoparticles (HAP-NPs) form an inorganic portion of the natural bone and are primarily used in tissue engineering due to their anti-inflammatory and anti-toxicity character. This study aimed to investigate the anti-inflammatory character of sulfasalazine-containing HAP (SSZ-HAP-NPs) as a potential therapeutic agent.Materials and Methods: The therapeutic efficacy of SSZ-HAP-NPs compared with SSZ as a standard drug was examined in a mouse model of colitis by induction of DSS for 7 days. Drugs were given on the third day and continued for seven days. Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically.Results: Our results showed that SSZ-HAP-NPs clinically improved signs/symptoms more than SSZ, however, it was not statistically significant (P>0.05). Also, SSZ-HAP-NPs diminished histopathological evidence of injury, by decreasing inflammatory responses and balancing oxidative/anti-oxidative markers in colonic tissues (P>0.05). Conclusion: SSZ-HAP-NPs could be more effective than SSZ as standard drug in some laboratory and clinical signs/symptoms and side effects in colitis and this could be a good strategy for future studies to use nanoparticles with more anti-inflammatory effects to develop the efficiency of standard drugs in colitis treatment.

Introduction: Asherman's syndrome (AS) is an acquired and refractory disorder in women whose treatments are currently limited and ineffective. Stem cell-based therapies have recently become a new way to treat tissue damage and fibrosis. Cell therapy is now proposed as a new strategy for the reconstruction and management of endometrial disorders such as Asherman syndrome. The present study was performed aimed to review a summary of research showing the key role of cell therapy in the treatment of intrauterine disorders and adhesions. Methods:In this review article, the articles related to the role of stem cells in the prevention and treatment of intrauterine adhesions were searched in databases of ISI, Google scholar, PubMed, Scopus and SID using the keywords of Asherman's syndrome, Intrauterine adhesions, and Stem cell therapy without time limitation. At the end, the input data were qualitatively analyzed.Results: Studies show that stem cell transplants come from a variety of sources, including bone marrow (BMCS), adipose tissue (ASC), amniotic fluid (AFSC), placenta (PSC), and menstrual blood (MenSC) that regenerates the uterine endometrium and restores fertility in Asherman syndrome. Studies have shown that transplantation of BMSCs and MenSCs, not only in animal studies but also in clinical studies, has led to the regeneration and formation of damaged endometrial tissue structure. In preclinical models, Adipose tissue-derived stem cells (ASCs), amniotic fluid-derived stem cells (AFSCs) and placenta-derived stem cells (PSCs) have been able to play an effective role in regenerating and strengthening the uterine endometrium by increasing epithelial thickness and reducing collagen secretion and deposition. Conclusion: Use of stem cells can play an important role in the regeneration and formation of endometrial tissue of the uterus and thus has beneficial effects in prevention and treatment of intrauterine adhesions.

Abstract Mebendazole (MBZ) is an efficacious anthelmintic with known anti-inflammatory and fibrinolytic properties. In this study, we aimed to explore the protective effects of this FDA-approved drug against DSS-induced colitis in a murine model either alone or in combination with Sulfasalazine (SSZ), a standard therapy for ulcerative colitis. We found that MBZ significantly improved colitis disease activity index as assessed by changes in body weight, degree of stool consistency, rectal bleeding, and prolapse. We also found that MBZ ameliorated the colon histopathological score by attenuating crypt loss, mucosal damage, and inflammation score in colitis tissues. Similarly, DSS-induced colon shortening, colon weight loss, and increase in spleen weight were all abrogated in the presence of MBZ. Moreover, MBZ decreased inflammation, possibly by reducing oxidative stress markers, suppressing inflammatory cell infiltration, and down-regulation of inflammatory genes in colon tissues. Furthermore, MBZ potently reduced fibrosis by decreasing collagen deposition and down-regulating pro-fibrotic genes including Col 1a1 and Col 1a2 in colitis tissue homogenates. In conclusion, our study showed that this broad-spectrum anthelminthic could be repurposed as a novel therapy for ulcerative colitis without any observed side effects, however, regarding the concerns about the potential toxicity of MBZ in UC patients, future experiments on MBZ therapy in other models of UC is needed to completely address the toxicity concerns.

Abstract In this work, UiO-66-NH2 was used to prepare a new delivery system by incorporating copper sulfide (CuS) into the pores. The CuS nanoparticles (NPs) were prepared to enhance the anticancer effects of Oxaliplatin (OXA) against colorectal cancer. The oxaliplatin was loaded into CuS@UiO-66-NH2. To characterize and investigate their cytotoxicity effects, powder X-ray diffraction (PXRD), Fourier transformation infrared spectroscopy (FT-IR), Brunauer–Emmett–Teller (BET) analysis, UV-Visible analysis, inductively coupled plasma mass spectrometry (ICP-MS), and MTT assay were considered to be performed. According to the observations, the cytotoxicity of OXA-CuS@UiO-66-NH2 was greater than that of the OXA alone.

Skeletal muscle atrophy is associated with poor quality of life and disability. Thus, finding a new strategy for the prevention and treatment of skeletal muscle atrophy is very crucial. This study aimed to investigate the therapeutic potential of hydrogen-rich water (HRW) on muscle atrophy in a unilateral hind limb immobilization model. Thirty-six male Balb/C mice were divided into control (without immobilization), atrophy, and atrophy + hydrogen-rich water (HRW). Unilateral hind limb immobilization was induced using a splint for 7 days (atrophy) and removed for 10 days (recovery). At the end of each phase, gastrocnemius and soleus muscle weight, limb grip strength, skeletal muscle histopathology, muscle fiber size, cross-section area (CSA), serum troponin I and skeletal muscle IL-6, TNF-α and Malondialdehyde (MDA), and mRNA expression of NF-κB, BAX and Beclin-1 were evaluated. Muscle weight and limb grip strength in the H2-treated group were significantly improved during the atrophy phase, and this improvement continued during the recovery period. Treatment by HRW increased CSA and muscle fiber size and reduced muscle fibrosis, serum troponin I, IL-6, TNF-α and MDA which was more prominent in the atrophy phase. These data suggest that HRW could improve muscle atrophy in an immobilized condition and could be considered a new strategy during rehabilitation.

Introduction: Cervical cancer is the leading cause of cancer-related death in women, so novel therapeutic approaches are needed to improve the effectiveness of current therapies or extend their activity. In recent decades, graphene analogs, such as Mxene, an emerging class of two-dimensional (2D) graphene analogs, have been drawing considerable attention based on their intrinsic physicochemical properties and performance as potential candidates for tumor therapy, particularly for therapeutic purposes. Here we explored the targeted drug delivery in cervical cancer in in vivo model. Mxene-based nanocarriers are not able to be precisely controlled in cancer treatment.Method: To solve this problem, the titanium carbide-magnetic core-shell nanocarrier (Ti3C2-Fe3O4@SiO2-FA) is also developed to provide synergetic anticancer with magnetic controlling ability along with pH-responsive drug release. A xenograft model of the cervix was used to investigate the effects of Cisplatin alone, or in combination with Ti3C2@FA and Ti3C2@ Fe3O4@SiO2-FA, on tumor growth following histological staining for evaluation of necrosis.Result and Discussion: A significant tumor-growth suppression effect is shown when the Ti3C2-Fe3O4@SiO2-FA nanocarrier is magnetically controlled Cisplatin drug release. It reveals a synergistic therapeutic efficacy used in conjunction with pharmaceuticals (p < .001). According to the in vivo study, the Ti3C2@FA@Cisplatin nanocomposite exhibits less tumor growth than the drug alone or Ti3C2@FA@Cisplatin via increasing necrosis effect (p < .001). Through this study, Mxene nanosheets are expanded for biomedical applications, not only through the fabrication of biocompatible magnetic Mxene nanocomposite but also through the development of functionalization strategies that enable the magnetic Ti3C2 nanocomposite to load high levels of Cisplatin for cervical cancer treatment (242.5%). Hence, Ti3C2-Fe3O4@SiO2-FA nanocarriers would be promising candidates to improve cancer treatment efficiency.

Abstract With the growing demands for personalized medicine and medical devices, nanomedicine is a modern scientific field, and research continues to apply nanomaterials for therapeutic and damaged tissue diagnosis. In this regard, substantial progress has been made in synthesizing magnetic nanoparticles with desired sizes, chemical composition, morphologies, and surface chemistry. Among these materials, nanomagnetic iron oxides have demonstrated promise as unique drug delivery carriers due to cancer treatment. This carrier could lead to responsive properties to a specific trigger, including heat, pH, alternative magnetic field, or even enzymes, through functionalization and coating of magnetic nanoparticles, along with biocompatibility, good chemical stability, easy functionalization, simple processing, and ability to localize to the tumor site with the assistance of external magnetic field. Current studies have focused on magnetic nanoparticles’ utilities in cancer therapy, especially for colorectal cancer. Additionally, a bibliometric investigation was performed on the public trends in the field of the magnetic nanoparticle to drug delivery and anticancer, which represented progressing applications of these carriers in the multidisciplinary zones with a general view on future research and identified potential opportunities and challenges. Furthermore, we outline the current challenges and forthcoming research perspective for high performance and fostering advanced MNPs in colorectal cancer treatment. Graphical Abstract

Background: The goal was to assess the specific colon delivery and investigation of synergistic anti-inflammatory effects of the selenium nanoparticle (SeNPs) as a bioactive carrier for oral administration. Material and method: The sulfasalazine (SSZ)- SeNPs functionality and the drug link to SSZ-SeNPs were investigated using chemical methods and characterized by conventional techniques including Fourier transform infrared (FTIR), X-ray diffraction analysis (XRD) analysis, and field emission scanning electron microscopy (FESEM). Dextran sodium sulfate (DSS) was used to induce colitis. Clinical symptoms were monitored every day. Colon samples were evaluated macroscopically and microscopically. The levels of Malondialdehyde (MDA) and the antioxidant markers such as total thiol, superoxide dismutase (SOD) activity, and catalase (CAT) activity of the colon homogenates were also determined. Results: A significant reduction in body weight, colon length and increase in disease activity index, colon and spleen weight/length ratio was observed in colitis group compared to control. Treatment with SSZ-SeNP and SSZ significantly improved these, although there was no significant difference between SSZ-SeNP and SSZ groups. Moreover, evaluation of histological changes including inflammation, crypt loss, mucosal damage and colon fibrosis indicated that treatment by SSZ-SeNP and SSZ significantly improved histological changes and SSZ-SeNP is much more effective than SSZ (P

The purpose of this study is to investigate the effect of floodwater spreading on the vegetation of Abdalan plain after 24 years since the implementation of the project. For this purpose, the changes in vegetation density and diversity and soil characteristics of the floodwater spreading were considered as the basis for the effectiveness of various floods. To determine the characteristics of density and percentage of vegetation, percentage of rocks, gravels, litter, and bare soil as well as Physico-chemical characteristics of soil in each area of floodwater spreading and control, 3 transects with a length of 100 meters were deployed. Measuring and sampling were performed on one square meter plots. The results of field studies led to the identification of 36 plant species and 33 genera belonging to 14 plant families. The most important plant families in the region are Asteraceae, Poaceae, and Fabaceae. The results showed that there are 34 plant species in the floodwater spreading area and 25 plant species in the control area. Of these, 12 plant species were observed only in the floodwater spreading area and 2 plant species were observed only in the control area, and 23 plant species were common in both areas. According to the results, the percentage of cover and density of plants in the floodwater spreading area has increased compared to the control area by 32.8% and 4.4%, respectively. The percentage of clay, silt, and sand has increased compared to the control in the field of floodwater spreading. Sufficient moisture and suitable fine-grained sediments to maintain the required moisture for a longer time as well as the seeds in the sediments have caused the growth and increase of density and canopy cover of plants in the field of floodwater spreading. These operations on the Abdalan plain have caused the revitalization of the region by changing the physical characteristics of the surface soil and improving vegetation conditions.

Breast cancer is the second most common cancer worldwide. Prognosis and timely treatment can reduce the illness or improve it. The use of nanomaterials leads to timely diagnosis and effective treatment. MXenes are a 2D material with a unique composition of attributes, containing significant electrical conductance, high optical characteristics, mechanical consistency, and excellent optical properties. Current advances and insights show that MXene is far more promising in biotechnology applications than current nanobiotechnology systems. MXenes have various applications in biotechnology and biomedicine, such as drug delivery/loading, biosensor, cancer treatment, and bioimaging programs due to their high surface area, excellent biocompatibility, and physicochemical properties. Surface modifications MXenes are not only biocompatible but also have multifunctional properties, such as aiming ligands for preferential agglomeration at the tumor sites for photothermal treatment. Studies have shown that these nanostructures, detection, and breast cancer therapy are more acceptable than present nanosystems in in vivo and in vitro. This review article aims to investigate the structure of MXene, its various synthesis methods, its application to cancer diagnosis, cytotoxicity, biodegradability, and cancer treatment by the photothermal process (in-vivo and in-vitro).

Water shortage in the arid and semi-arid regions has necessitated subsurface dam construction for groundwater storage. The aim of this study was to determine the appropriate locations for subsurface dam construction using a set of field, laboratory and software methods in the arid and semi-arid regions of the provinces of Kohgiluyeh and Boyerahmad. Six axes were selected by examining the topographic maps and the drainage network. The most important factors influencing the subsurface dam construction were selected. Using the average expert opinion benefitting from a questionnaire and employing the FUZZY-AHP method, suitable places for subsurface dam construction were prioritized. Considering the geophysical studies, the characteristics of the affected strata were determined. The results of prioritization of suitable locations for subsurface dam construction showed that the Tang Nayab with a weight of 0.41 holds the top ranking. The study of the results of the most important factors affecting in subsurface dams construction indicated that water supply and bed-rock with a combined weight of 0.25 is the most effective factor in subsurface dam construction. The results of geophysical surveys also indicated that the alluvium strata had an electrical resistance of 300 to 400 ohm-meter. The results of geophysical surveys indicated that the alluvium thickness in selected site is 5 m.

Background: Ulcerative colitis is one of the major phenotypic forms of inflammatory bowel diseases. The present study aimed to investigate the effect of force swimming exercise on clinical symptoms (disease activity index; DAI), colon histopathology, inflammation and fibrosis, and oxidant/antioxidant balance in dextran sulfate sodium (DSS)-induced colitis mice. Methods: Male C57BL6 mice were randomly divided into five groups (n = 6 each): control, exercise, colitis, colitis + sulfasalazine, and colitis + exercise. Exercise was performed by forced swimming six weeks before and during the experiment. Colitis was induced by 1.5% DSS in drinking water. The animals were evaluated for body weight changes and DAI (including changes of body weight, stool consistency, rectal bleeding, and prolapse) during the induction of colitis and treatment. At the end of experiment, colons and spleens were evaluated by H and E and Masson Trichrome stainings. Oxidant (Malon dialdehyde; MDA), and antioxidant markers [total thiol groups, superoxide dismutase (SOD), and catalase activity] were also measured in colon tissue. Results: Results indicated that exercise in colitis mice significantly improved DAI, colon length, spleen weight, and histological injury score and alleviated fibrotic changes in colon tissue that were comparable to sulfasalazine group. Exercise also restored the oxidant/antioxidant balance in colitis mice by reducing MDA and increasing antioxidative markers including total thiol groups, SOD, and catalase activity. Conclusions: Taken together, aerobic exercise could improve clinical symptoms and colonic inflammation through, at least, the balancing the oxidative stress markers. Thus, it can be considered in management of colitis patients as effective method.

Background: Colorectal cancer is one of the most common cancers in Iran, and despite high cure rate, it still has high mortality. Some studies have shown that angiotensin-converting enzyme (ACE) inhibitors are effective in treating cancer in addition to treating hypertension. The aim of this study was to investigate the effect of enalapril on the proliferation, migration, and expression of ACE, angiotensin II type I receptor (AT1R), vascular endothelial growth factor-A (VEGF-A), and transforming growth factor beta 1 (TGF-β1) genes in colorectal cancer cells. Methods: In this study, the effect of enalapril on the survival rate of CT26, HT29, and SW480 colorectal cancer cells was determined using MTT assay, cell migration was assayed using migration assay technique, and cell cycle assay was performed using flow cytometry. Expression of matrix metalloproteinase 3 (MMP3), MMP9, and epithelial cadherin (E-cadherin), ACE, AT1R, VEGF-A, and TGF-β1 genes were also evaluated using real-time polymerase chain reaction (PCR) technique and reactive oxygen species in these three cell lines. Findings: Enalapril had anti-proliferative and anti-migrate effect on all three colorectal cancer cell lines compared to the control group. Expression of E-cadherin, MMP3, and MMP9 genes significantly decreased after treatment with enalapril (P < 0.001). Expression of ACE, AT1R, VEGF-A, and TGF-β1 genes showed a significant decrease in the three cell lines, and the level of reactive oxygen species significantly increased in the three cell lines compared to the control group. Conclusion: Given the various anticancer effects of enalapril, it seems that at least alongside standard chemotherapy drugs, enalapril may be useful in the treatment of colorectal cancer.

Introduction: Breast cancer is one of the most common cancers and the second leading cause of cancer deaths among women worldwide. There is direct relationship between hypertension and the risk of blood cancer. Since the studies have showed that renin-Angiotensin pathway can be involved in cancer progression, therefore, this study was performed with aim to investigate the effect of angiotensin-converting enzyme inhibitors (ACEI) on survival of breast cancer patients by meta-analysis method. Methods: In this systematic review and meta-analysis, the databases of pubmed, scopus, and web of science were systematically searched with the keywords of Breast cancer, neoplasm, tumor, Angiotensin receptor blockers, Angiotensin converting enzyme inhibitors and survival using OR and AND without a time limit until February 19, 2020. I2 index was used to assess the heterogeneity between the studies. Egger's test was used for assessment of publication bias. Data were analyzed by meta-analysis method using random effects model. Results: In this study, a total of 57708 papers were reviewed and 13 studies were included in this meta-analysis. The results of meta-Analysis showed that based on the random effects model, ACEI had no effect on the survival of patients with breast cancer (HR = 0.1; 95% CI: 12.1 to 0.89; p = 0.99). Conclusion: The results of the studies show that using angiotensin receptor blocker and renin-angiotensin system inhibitors had no effect on survival of patients with breast cancer.

Objective(s): The 5-hydroxytryptamine1A (5-HT1A) receptor is one of the serotonin receptors in the brain, which regulates cardiovascular responses, especially in hemorrhage. Presence of this receptor in the cuneiform nucleus (CnF) has been shown. The present study evaluates the cardiovascular effect of this receptor of the CnF in normal and hypotensive hemorrhagic rats.Materials and Methods: Agonist (8-OH-DPAT) and antagonist (WAY-100635) of 5-HT1A microinjected into the CnF in basal and hemorrhagic conditions and cardiovascular responses were evaluated. Hemorrhage induced by blood withdrawal from the femoral artery and 2 min after that drugs microinjected. Time course and peak changes (∆) of the mean arterial pressure (MAP), systolic blood pressure (SBP) and heart rate (∆HR) were obtained and compared to the control and hemorrhage groups.Results: In basal condition, 8-OH-DPAT significantly decreased ∆SBP, ∆MAP and ∆HR compared to the control (PConclusion: This study shows that 5-HT1A receptor of the CnF involves in regulation of the cardiovascular responses. However, this effect in basal and hemorrhage conditions is different.

Introduction: The underlying mechanism responsible for the cardiovascular response to hemorrhage (HEM) is still unknown; however, several brain areas, such as the cuneiform nucleus (CnF) have shown to be involved. In this study, the cardiovascular effect of the CnF during HEM was evaluated. Methods: The animals were divided into the following groups: 1. Vehicle; 2. HEM; 3. Cobalt chloride (CoCl2); 4. CoCl2+saline; and 5. CoCl2+HEM. Catheterization of the left and right femoral artery was performed to record blood pressure and blood withdrawal, respectively. Saline and CoCl2 were microinjected into the CnF nucleus, and then blood withdrawal was done for HEM induction. Cardiovascular regulation throughout the experiments was recorded and changes (∆) in the Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP) and Heart Rate (HR) were calculated over time and compared with those treated with saline and HEM, using repeated-measures ANOVA. Results: HEM significantly reduced ∆SBP and ∆MAP and augmented ∆HR than the vehicle group. CoCl2 did not significantly affect basic ∆SBP, ∆MAP, and ∆HR compared with the vehicle group. However, injection of CoCl2 into the CnF before HEM (CoCl2+HEM group) significantly decreased ∆SBP, ∆MAP, and tachycardia, induced by HEM. Conclusion: Our results indicated that blockade of the CnF by CoCl2 significantly reduced the hypotension and tachycardia, induced by HEM indicating the involvement of CnF in cardiovascular regulation during HEM.

Renin-angiotensin system as an important regulator of renal function has also a major role in inflammation. In the present study, the effects of captopril on renal dysfunction, renal cytokine levels, and renal tissue oxidative damage were investigated in lipopolysaccharide (LPS)-induced inflammation model in rats. Treatment of five groups of the rats was carried out as follows: (1) saline as a control, (2) LPS 1 mg/kg, and (3–5) 10, 50, or 100 mg/kg captopril 30 min, respectively, before LPS. The treatments were given for 12 days. Finally, the animals were deeply anesthetized, the blood samples were obtained, and the renal tissues were removed and kept for biochemical measurements. Administration of LPS increased serum blood urea nitrogen and creatinine (P < 0.001). Pretreatment with all doses of captopril decreased these parameters (P < 0.001). LPS also increased interleukin-6 (IL-6), malondialdehyde, and nitric oxide metabolites in the renal tissues (P

Objective(s): The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.Materials and Methods: The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.Results: In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone corrected these parameters. In the hippocampus of LPS group interleukin-6, tumor necrosis factor-α, nitric oxide metabolites, and malondialdehyde were higher while thiol, BDNF, and IL-10 concentrations and the activities of catalase (CAT) and superoxide dismutase (SOD) were lower than the control group. Treatment by both doses of 20 and 30 mg of pioglitazone corrected the biochemical parameters in the hippocampus. Conclusion: The current findings revealed that pioglitazone protected the rats from learning and memory impairment induced by LPS. The effects were associated with improvement of cytokines, oxidative stress criteria, and BDNF.

Introduction: Cancer is one of the most common causes of death in the world and breast cancer is known as the second leading cause of death in women worldwide. Breast cancer is a heterogeneous tumor; various studies have shown that angiogenesis plays an important role in progression and development of cancer. Clinical studies have been performed on the relationship between anti-angiogenic drugs along with chemotherapy in improvement of breast cancer treatment. This review article was performed with aim to evaluate the effect of anti-angiogenic drugs along with chemotherapy in breast cancer treatment. Methods: In this review study, the related articles were searched in databases of Scopus, PubMed, ISI and Google scholar by the key words including “Breast cancer”, “Anti-angiogenic drug”, ” Chemotherapy” and “Angiogenesis” in Mesh between 2000-2018. No time limitation was considered in selection of the articles. Selection of the articles was based on use of anti-angiogenic drugs along with chemotherapy or as part of chemotherapy drugs in breast cancer treatment. At the end of study, data were analyzed qualitatively. Results: According to the studies’ results, it was determined that use of anti-angiogenic drugs in improving breast cancer treatment could be more investigated. VEGF and VEGFR inhibitors have shown different clinical effects that could be due to differences in dosage, method of consumption or drug interactions. Conclusion: Although anti-angiogenic drugs have positive role in improving breast cancer treatment, since different results in doses and method of consumption of these drugs were observed in clinical trials, performing more studies in this regard is required. In general, it seems that these drugs in combination with standard chemotherapy agents could be a good candidate for treatment and increasing survival rate in breast cancer patients.

Introduction: Based on the evidence, the Pedunculopontine Tegmental nucleus (PPT) is involved in cardiovascular function regulation. In this study, the probable role of PPT on cardiovascular parameters in the hypotension induced by Hemorrhage (HEM) was evaluated. Methods: The study rats were divided up into 5 groups: 1. Control (Saline); 2. Cobalt(II) chloride (CoCl2); 3. HEM; 4. Saline+HEM; and 5. CoCl2+HEM. Their right and left femoral arteries were cannulated for recording the cardiovascular responses and blood withdrawal, respectively. Saline and CoCl2 were microinjected into the PPT using the stereotaxic apparatus. Maximum changes of Systolic Blood Pressure (SBP), Mean Arterial Pressure (MAP), and the Heart Rate (HR) after the microinjection of CoCl2 in normal and Hemorrhage conditions were recorded. Changes of SBP, MAP, and HR were calculated over time at 5-min intervals and compared with those of the control and HEM groups using repeated measures ANOVA. The Independent sample t-test was used to compare the changes in cardiovascular parameters between the control and HEM groups at 0 and 20 min after Hemorrhage. Results: The changes in SBP, MAP, and HR in the CoCl2 group were not significantly different from those in the control group. In the HEM group, the SBP and MAP changes significantly decreased (P

Objectives: Thymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats. Methods: Seventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3-5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1β, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically. Results: LPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations. Conclusion: TQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

Background: Changing the approach form professional education to interprofessional education is one of the new methods in health science education. The aim of this study was to evaluate improvement of learning and professional competency among postgraduate students through designing and implementation of interprofessional education (IPE). Methods: This method was started from 1st semester of educational year of 2016-2017. First, the Readiness for Interprofessional Learning Scale (RIPLS) questionnaire was completed by 80 postgraduate students. Then, IPE method was implemented through lecture/group discussion and practical/laboratory workshops with attendance of students/staffs from different disciplines. For evaluation of implementation, we used Interdisciplinary Education Perception Scale (IPES). Findings: Score of RIPLS questionnaire in four domains including team work and collaboration, negative professional identity, positive professional identity, and roles and responsibilities were more than average. In IEPS questionnaire, before and after implementation, the score improved in four fields of competency and autonomy (33.55 ± 0.5 vs. 38.84 ± 4.5), perceived needs for cooperation (7.50 ± 1.97 vs. 9.07 ± 2.32), perception of actual cooperation (18.20 ± 5.39 vs. 24.53 ± 2.60), and understanding others value (11.20 ± 3.11 vs. 14.84 ± 1.67); and the most improvement was observed in field of perception of actual cooperation. Conclusion: Considering high susceptibility of post-graduate students, using education strategy based on IPE can improve health system and its responsibility in our country, and should be noticed by policymakers.

Cancer remains a major cause of morbidity and mortality irrespective of the type of conventional chemotherapy. Therefore, there is an urgent need for new and effective anticancer therapeutic agents. Bacterial proteins and their derivative peptides appear as a promising approach for cancer treatment. Several, including an amphipathic, α-helical, 28-amino acid peptide derived from azurin, a 128-amino acid copper-containing redox protein secreted from Pseudomonas aeruginosa, show clinical promise in the treatment of adult and pediatric solid tumors. The peptide, p28, is a post-translational, multi-target anticancer agent that preferentially enters a wide variety of solid tumor cells. Mechanistically, after entry, p28 has two major avenues of action. It binds to both wild-type and mutant p53 protein, inhibiting constitutional morphogenic protein 1 (Cop1)-mediated ubiquitination and proteasomal degradation of p53. This results in increased levels of p53, which induce cell-cycle arrest at G2/M and an eventual apoptosis that results in tumor cell shrinkage and death. In addition, p28 also preferentially enters nascent endothelial cells and decreases the phosphorylation of FAK and Akt inhibiting endothelial cell motility and migration. Here, we review the current basic and clinical evidence suggesting the potential of p28 as a cancer therapeutic peptide.

BACKGROUND: Subclinical inflammation induced by persistent exposure to lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or diabetes. This study aimed to investigate the effect of recurrent LPS exposure on inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in male rats.METHODS: Male Wistar rats were divided into control and LPS-treated. LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left ventricles and kidneys were homogenized and stained with hematoxylin and eosin (H&E) and Masson trichrome for histological examination. Serum levels of nitrite, interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase were evaluated in the heart and kidney homogenates.RESULTS: Serum inflammatory markers were higher in LPS group than control (nitrite: 37.0 ± 2.2 vs. 25.5 ± 1.9 µmol/l; IL-6: 84 ± 3 vs. 98.0 ± 4.4 pg/ml; TNF-α: 75.5 ± 4.9 vs. 85.3 ± 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol concentration (heart: 10.0 ± 0.9 vs. 22.5 ± 1.2; kidney: 7.0 ± 0.5 vs. 27.8 ± 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 ± 0.03 vs. 0.66 ± 0.04; kidney: 0.17 ± 0.03 vs. 0.73 ± 0.03, U/g tissue, respectively) and SOD (heart: 8.01 ± 0.70 vs. 12.3 ± 0.4; kidney: 7.02 ± 0.60 vs. 12.0 ± 0.2, U/g tissue, respectively) showed lower levels in LPS-treated group compared to control; while MDA concentration in LPS group was higher than control (P < 0.05). Histopathological examination in LPS-treated group indicated infiltration of inflammatory cells and more collagen deposition in left ventricle wall and kidney compared to control group.CONCLUSION: We concluded that in clinical conditions with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding tissue injury due to imbalances in oxidative stress.

Objective: The present study was performed to evaluate the effects of hydro-alcoholic extract of Portulaca oleracea (P. oleracea) seeds and Vitamin C on biochemical and hemodynamic parameters in cardiac tissue of rats with subclinical hyperthyroidism. Materials and Methods: Forty eight male rats were divided into six groups of 8 and treated for 4 weeks. T4 group received daily injection of levothyroxine sodium (20 μg/kg) and control group was given daily injection of saline. T4-Po groups were given T4 plus 100, 200, and 400 mg/kg of P. oleracea seeds extract in drinking water daily. T4-Vit C group received T4 plus daily injection of Vitamin C (100 mg/kg). At the end of the experiment, body weight, serum free T4 level, left ventricular developed pressure (LVDP), malondialdehyde (MDA) and total thiol levels were measured. Results: Free T4 levels were increased in all groups that were treated with T4. Weight gain was decreased in T4 and T4-Po100 groups compared to control group (p Conclusion: The results showed that P. oleracea extract has a protective effect on cardiac dysfunction due to subclinical hyperthyroidism induced by levothyroxine sodium in rats.

Liver and renal dysfunction accompanying with the tissues' oxidative damage has been reported to occur during Inflammation. Nigella sativa has been well known for its antioxidant and anti-inflammatory effects. The aim of this study was to investigate preventive effects of N. sativa on liver and renal tissue damage in lipopolysaccharide (LPS) -treated rats. The rats were divided into five groups: (1) control; (2) LPS (1 mg/kg, IP, for 10 days), (3-5) N. sativa hydroethanolic extract (100, 200, or 400 mg/kg) before LPS. Compared to LPS group, treatment by the extract decreased alondialdehyde, nitric oxide (NO) metabolites, and interleukin-6 while increased thiol content and superoxide dismutase and catalase activities in both renal and liver tissues. N. sativa extract also decreased serum aspartate aminotransferase, alanine aminotrans-ferase, and alkaline phosphatase concentration, while it increased serum protein and albumin compared with LPS group. In LPS group, serum blood urea nitrogen and creatinine were higher than control group. The extract reversed the negative effects of LPS. The results demonstrated that the N. sativa prevented liver and renal tissue damage in LPS-treated rats. It is suggested that the effects are due to its antioxidant and anti-inflammatory effects.

Cisplatin is one of the important antineoplastic drugs. Its clinical use has been restricted due to severe kidney toxicity. Nigella sativa (N. sativa) is an herbaceous plant with many pharmacologic effects. In the present study, we evaluated the protective effects of aqueous-ethanolic extract of N. sativa and Vitamin E on cisplatin-induced nephrotoxicity in rats. Eighty male rats were divided into eight groups: control, cisplatin (6 mg/kg; ip), preventive Vitamin E (100 mg/kg), preventive N. sativa (100,200 mg/kg), preventive + treatment Vitamin E, and preventive + treatment N. sativa (100, 200 mg/kg). Duration of this study was 11 days and cisplatin was injected on the 6th day of the experiment. Tissue damage in all groups that received N. sativa extract and Vitamin E showed a significant improvement compared with the cisplatin group. In addition, serum and tissue total thiol content in preventive and preventive + treatment N. sativa groups showed significant increase compared with cisplatin group. There was no significant difference in serum malondialdehyde concentration of the control rats compared with the preventive and preventive + treatment N. sativa groups. N. sativa extract and viamin E improved the pathology and oxidative stress in the rat kidney. However, more studies are needed to determine the mechanism of action of N. sativa on cisplatin-induced kidney toxicity.

Saffron or Crocus sativus is a member of Iridacea which traditionally has been used as flavor and color in foods. Studies indicated that saffron has different pharmacological effects such as anti-inflammatory, antioxidant, antiproliferative, and apoptosis. Although, numerous in-vitro and in-vivo studies have been done to find the different effects of this herbal drug, however, clinical usage of it is very limited. Since using herbal drugs in treatment of disease is very popular, it should be more attention on the beneficial effects of saffron which lead to clinical usage of it. In this study, to understand more about the beneficial effects of this herbal drug, we reviewed clinical studies which have been done on saffron so far.