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1.
Int J Neurosci ; : 1-12, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38598305

ABSTRACT

INTRODUCTION: Social inequality conditions induce aversion and affect brain functions and mood. This study investigated the effects of chronic social equality and inequality (CSE and CSI, respectively) conditions on passive avoidance memory and post-traumatic stress disorder (PTSD)-like behaviors in rats under chronic empathic stress. METHODS: Rats were divided into different groups, including control, sham-observer, sham-demonstrator, observer, demonstrator, and co-demonstrator groups. Chronic stress (2 h/day) was administered to all stressed groups for 21 days. Fear learning, fear memory, memory consolidation, locomotor activity, and PTSD-like behaviors were evaluated using the passive avoidance test. Apart from the hippocampal weight, the correlations of memory and right hippocampal weight with serum corticosterone (CORT) levels were separately assessed for all experimental groups. RESULTS: Latency was significantly higher in the demonstrator and sham-demonstrator groups compared to the control group. It was decreased significantly in other groups compared to the control group. Latency was also decreased in the observer and co-demonstrator groups compared to the demonstrator group. Moreover, the right hippocampal weight was significantly decreased in the demonstrator and sham-demonstrator groups compared to the control group. Pearson's correlation of memory and hippocampal weight with serum CORT levels supported the present findings. CONCLUSION: Maladaptive fear responses occurred in demonstrators and sham-demonstrators. Also, extremely high levels of psychological stress, especially under CSI conditions (causing abnormal fear learning) led to heightened fear memory and PTSD-like behaviors. Right hippocampal atrophy confirmed the potential role of CSI conditions in promoting PTSD-like behaviors. Compared to inequality conditions, the abnormal fear memory was reduced under equality conditions.

2.
Cancer Lett ; 584: 216670, 2024 03 01.
Article in English | MEDLINE | ID: mdl-38307748

ABSTRACT

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor. After publication, the Editors were contacted by a concerned reader regarding alleged image duplication. These allegations are in regard to Fig. 3a being duplicated from a previously published paper in the journal Stem Cells (Stem Cells. 2008 Sep;26 (9):2332-8. doi: 10.1634/stemcells.2008-0084) and Fig. 8a being duplicated from a previously published paper in the journal Molecular Cancer (Mol Cancer 13, 255 (2014). https://doi.org/10.1186/1476-4598-13-255). After a thorough investigation by the editorial team, the Editors determined that there are multiple identical details between Fig. 5A (Cancer Letters) and Fig. 3A (Stem Cells) and the authors did not produce satisfactory evidence that the published images in Cancer Letters were original. Due to this, the Editor does not have confidence in the results and conclusions presented and has made the decision to retract.

3.
Sci Rep ; 12(1): 9228, 2022 06 02.
Article in English | MEDLINE | ID: mdl-35654803

ABSTRACT

Assessment of streamflow variations under the influence of climate change and human activity is crucial for sustainable water resource management, especially in semiarid areas. In this study, we first used the Hydrograph Separation Program to separate and analyze the base flow index (BFI) that was impacted directly by human activity and precipitation as an important climate factor from 1967 to 2016 in the Dez River Basin. Second, the Mann-Kendall trend test was used to identify trends and change points. Then, the elasticity coefficient method was applied to calculate the impacts of natural factors and anthropogenic activities. The results of the separation methods showed that the sliding interval method produced a better performance. Furthermore; the analyzed trend test at the annual scale showed a significant decreasing trend for runoff as well as increasing trends for the baseflow index in the four of five sub-basins of the Dez River at confidence levels of 95% and 99%, while the average precipitation in these sub-basins was not significant. Additionally, at the seasonal scale in these sub-basins, the average precipitation in winter showed a significant downward trend, while runoff showed a decreasing trend and the BFI index showed increasing trends in winter, spring and summer. The abrupt change point was determined after the change in the BFI index; the runoff was reduced. The maximum change occurred in the sub-basin tireh which after change point from 1977 to 1993,runoff reduced - 1.49% comparison with the base period( from 1967 to 1976) also elasticity estimation was - 0.46,but after change point in Baseflow index from 1994 to 2016 runoff reduced - 55.02% and elasticity estimation was - 0.65. The baseflow index trend and elasticity estimation also indicated that intensive human activities had more significant effects on the Dez Basin's hydrological processes and streamflow variation.


Subject(s)
Climate Change , Environmental Monitoring , Environmental Monitoring/methods , Human Activities , Humans , Hydrology , Rivers
4.
Res Pharm Sci ; 17(3): 242-251, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35531134

ABSTRACT

Background and purpose: MicroRNAs (miRNAs) are small non-coding RNA molecules acting as critical regulators of post-transcriptional gene expression. MiR-33a and miR-122 have a crucial role in cholesterol and lipid metabolism. Therefore, their dysregulation may contribute to metabolic abnormality and their inhibition may be a useful therapeutic strategy. The objective of the present study was to investigate the relationship between miR-33a, miR-122, erythrocyte membrane fatty acids profile, and serum lipids with components of metabolic syndrome in an Iranian population suffering from type 2 diabetes mellitus (T2DM). Experimental approach: Expression of miR-33a and miR-122 was measured by real-time polymerase chain reaction and erythrocyte membrane fatty acid profiles were analyzed by gas chromatography-mass spectrometry. Findings/Results: T2DM patients with and without metabolic syndrome had significantly higher miR-33a and miR-122 levels compared to controls. MiRNAs were significantly correlated with saturated fatty acid (SFAs), total SFAs/total polyunsaturated fatty acids (PUFAs) ratio, fasting plasma glucose, triacylglycerols, insulin and homeostatic model assessment of insulin resistance. In addition, there was a significant negative correlation between miR-33a and miR-122 levels and PUFAs, total PUFAs/total SFAs ratio and omega 6 fatty acids. Conclusion and implications: Considering the roles of miR-33a and miR-122 in cholesterol and lipids metabolism, it may be concluded that the measurement of their expression may be useful as a potential additional biomarker for cardiometabolic derangement in T2DM patients. In addition, these findings may suggest that the inhibition of these miRNAs by anti-miRNA therapies may be explored as a potential therapeutic strategy.

5.
Sci Rep ; 12(1): 7739, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35545656

ABSTRACT

The use of evolutionary algorithms (EAs) for solving complex engineering problems has been very promising, so the application of EAs for optimal operation of hydropower reservoirs can be of great help. Accordingly, this study investigates the capability of 14 recently-introduced robust EAs in optimization of energy generation from Karun-4 hydropower reservoir. The best algorithm is the one that produces the largest objective function (energy generation) and has the minimum standard deviation (SD), the minimum coefficient of variations (CV), and the shortest time of CPU usage. It was found that the best solution was achieved by the moth swarm algorithm (MSA), with the optimized energy generation of 19,311,535 MW which was 65.088% more than the actual energy generation (11,697,757). The values of objective function, SD and CV for MSA were 0.147, 0.0029 and 0.0192, respectively. The next ranks were devoted to search group algorithm (SGA), water cycle algorithm (WCA), symbiotic organism search algorithm (SOS), and coyote optimization algorithm (COA), respectively, which have increased the energy generation by more than 65%. Some of the utilized EAs, including grasshopper optimization algorithm (GOA), dragonfly algorithm (DA), antlion optimization algorithm (ALO), and whale optimization algorithm (WOA), failed to produce reasonable results. The overall results indicate the promising capability of some EAs for optimal operation of hydropower reservoirs.


Subject(s)
Algorithms , Whales , Animals , Biological Evolution , Physical Phenomena , Problem Solving
6.
Int J Endocrinol ; 2022: 2144615, 2022.
Article in English | MEDLINE | ID: mdl-35211170

ABSTRACT

BACKGROUND: Gamma-aminobutyric acid (GABA) and magnesium sulfate (MgSO4) play a crucial role in glycemic control. Therefore, we studied the effect of combination therapy with GABA and MgSO4 to improve insulin sensitivity in diabetes induced by streptozotocin as well as high-fat diet in a diabetic rat model. Design and Methods. Forty randomly selected rats were assigned to four groups: nondiabetic control group was fed the normal diet, insulin-resistant diabetic rat model was induced by streptozotocin and high-fat diet, GABA + MgSO4 group received GABA and MgSO4, and insulin group was treated with insulin. Body weight, abdominal fat, blood glucose, serum insulin, and glucagon concentration were measured. The glucose clamp technique, glucose tolerance test, and insulin tolerance test were performed to study insulin sensitivity. Also, the expressions of glucose 6 phosphatase, glucagon receptor, and phosphoenolpyruvate carboxykinase genes in liver were assessed for the gluconeogenesis pathway. Protein translocation and glucose transporter 4 (Glut4) genes expression in muscle were also assessed. RESULTS: Combination of GABA + MgSO4 or insulin therapy enhanced insulin level, glycemic control, glucose and insulin tolerance test, some enzymes expression in the gluconeogenesis pathway, body fat, body weight, and glucagon receptor in diabetic rats. Moreover, an increase was observed in protein and gene expression of Glut4. Insulin sensitivity in combination therapy was more than the insulin group. CONCLUSIONS: GABA and MgSO4 enhanced insulin sensitivity via increasing Glut4 and reducing the gluconeogenesis enzyme and glucagon receptor gene expressions.

7.
Sci Rep ; 11(1): 20326, 2021 Oct 13.
Article in English | MEDLINE | ID: mdl-34645872

ABSTRACT

Simultaneous optimization of several competing objectives requires increasing the capability of optimization algorithms. This paper proposes the multi-objective moth swarm algorithm, for the first time, to solve various multi-objective problems. In the proposed algorithm, a new definition for pathfinder moths and moonlight was proposed to enhance the synchronization capability as well as to maintain a good spread of non-dominated solutions. In addition, the crowding-distance mechanism was employed to select the most efficient solutions within the population. This mechanism indicates the distribution of non-dominated solutions around a particular non-dominated solution. Accordingly, a set of non-dominated solutions obtained by the proposed multi-objective algorithm is kept in an archive to be used later for improving its exploratory capability. The capability of the proposed MOMSA was investigated by a set of multi-objective benchmark problems having 7 to 30 dimensions. The results were compared with three well-known meta-heuristics of multi-objective evolutionary algorithm based on decomposition (MOEA/D), Pareto envelope-based selection algorithm II (PESA-II), and multi-objective ant lion optimizer (MOALO). Four metrics of generational distance (GD), spacing (S), spread (Δ), and maximum spread (MS) were employed for comparison purposes. The qualitative and quantitative results indicated the superior performance and the higher capability of the proposed MOMSA algorithm over the other algorithms. The MOMSA algorithm with the average values of CPU time = 2771 s, GD = 0.138, S = 0.063, Δ = 1.053, and MS = 0.878 proved to be a robust and reliable model for multi-objective optimization.

8.
J Res Med Sci ; 26: 39, 2021.
Article in English | MEDLINE | ID: mdl-34484371

ABSTRACT

Insulin resistance (IR) is mentioned to be a disorder in insulin ability in insulin-target tissues. Skeletal muscle (SkM) and liver function are more affected by IR than other insulin target cells. SkM is the main site for the consumption of ingested glucose. An effective treatment for IR has two properties: An inhibition of ß-cell death and a promotion of ß-cell replication. Gamma-aminobutyric acid (GABA) can improve beta-cell mass and function. Multiple studies have shown that GABA decreases IR probably via increase in glucose transporter 4 (GLUT4) gene expression and prevention of gluconeogenesis pathway in the liver. This review focused on the general aspects of IR in skeletal muscle (SkM), liver; the cellular mechanism(s) lead to the development of IR in these organs, and the role of GABA to reduce insulin resistance.

9.
Sci Rep ; 11(1): 15611, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34341441

ABSTRACT

Deriving optimal operation policies for multi-reservoir systems is a complex engineering problem. It is necessary to employ a reliable technique to efficiently solving such complex problems. In this study, five recently-introduced robust evolutionary algorithms (EAs) of Harris hawks optimization algorithm (HHO), seagull optimization algorithm (SOA), sooty tern optimization algorithm (STOA), tunicate swarm algorithm (TSA) and moth swarm algorithm (MSA) were employed, for the first time, to optimal operation of Halilrood multi-reservoir system. This system includes three dams with parallel and series arrangements simultaneously. The results of mentioned algorithms were compared with two well-known methods of genetic algorithm (GA) and particle swarm optimization (PSO) algorithm. The objective function of the optimization model was defined as the minimization of total deficit over 223 months of reservoirs operation. Four performance criteria of reliability, resilience, vulnerability and sustainability were used to compare the algorithms' efficiency in optimization of this multi-reservoir operation. It was observed that the MSA algorithm with the best value of objective function (6.96), the shortest CPU run-time (6738 s) and the fastest convergence rate (< 2000 iterations) was the superior algorithm, and the HHO algorithm placed in the next rank. The GA, and the PSO were placed in the middle ranks and the SOA, and the STOA placed in the lowest ranks. Furthermore, the comparison of utilized algorithms in terms of sustainability index indicated the higher performance of the MSA in generating the best operation scenarios for the Halilrood multi-reservoir system. The application of robust EAs, notably the MSA algorithm, to improve the operation policies of multi-reservoir systems is strongly recommended to water resources managers and decision-makers.

10.
Eur J Pharmacol ; 909: 174418, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34411605

ABSTRACT

In the present study, first, the role of high-fat diet (HFD) in insulin resistance (IR) in offspring with diabetic and non-diabetic parents, and then the effect of magnesium sulfate (Mg) administration on improved IR in HFD diabetic parents, and their offspring were investigated. Induction of diabetes was carried out by eating HFD and a low dose of streptozotocin (STZ). Diabetic rats were divided into three groups: diabetic control (DC), insulin, and Mg-treated (Mg). The non-diabetic control (NDC) group received a normal diet. Their offspring were fed on a regular diet for four months. Blood glucose and body weight of all animals were measured weekly, and IPGTT, urine volume, and water intake were measured monthly. In both parents and their offspring, the hyperinsulinemic euglycemic clamp was conducted, and blood samples were obtained. In all groups, the expression of IRS1, Akt and GLUT4 genes in muscle was measured. The HFD-fed rats exhibited a significant increase in blood glucose, body weight and IPGTT. In diabetic parents and their offspring, Mg or insulin therapy lowered blood glucose, IPGTT, and HbA1c relative to the DC group. They also increased GIR in parents and their offspring. Compared to the DC group, the expression of IRS1, Akt and GLUT4 genes was increased in both parents. Mg had positive effects on the expression of IRS1, Akt and GLUT4 genes in Mg treated offspring and reduced IR in them. As a result, magnesium may have beneficial effects on IR by increasing the expression of IRS1, Akt and GLUT4 genes.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance , Animals , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Female , Glucose Clamp Technique , Humans , Magnesium Sulfate/therapeutic use , Male , Rats , Streptozocin/administration & dosage , Streptozocin/toxicity
11.
Biomed Pharmacother ; 138: 111440, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33667789

ABSTRACT

The role of gamma-aminobutyric acid (GABA) in attenuates insulin resistance (IR) in type 2 diabetic (T2D) patients and the reduction of the risk of IR in their offspring, and the function of GLUT4, IRS1 and Akt2 genes expression were investigated. T2D was induced by high fat diet and 35 mg/kg of streptozotocin. The male and female diabetic rats were then divided into three groups: CD, GABA, and insulin. NDC group received a normal diet. All the animals were studied for a six-month. Their offspring were just fed with normal diet for four months. Blood glucose was measured weekly in patients and their offspring. Intraperitoneal glucose tolerance test (IPGTT), urine volume, and water consumption in both patients and their offspring were performed monthly. The hyperinsulinemic euglycemic clamp in both patients and their offspring was done and blood sample collected to measure Hemoglobin A1c (HbA1c). IRS1, Akt and GLUT4 gene expressions in muscle were evaluated in all the groups. GABA or insulin therapy decreased blood glucose, IPGTT, and HbA1c in patients and their offspring compared to DC group. They also increased GIR in patients and their offspring. IRS1, Akt and GLUT4 gene expressions improved in both patients in comparison with DC group. GABA exerts beneficial effects on IRS1 and Akt gene expressions in GABA treated offspring. GABA therapy improved insulin resistance in diabetic patients by increasing the expression of GLUT4. It is also indirectly able to reduce insulin resistance in their offspring possibly through the increased gene expressions of IRS1 and Akt.


Subject(s)
Blood Glucose/drug effects , Diabetes Mellitus, Type 2/drug therapy , GABA Agents/therapeutic use , Insulin Resistance/physiology , Prenatal Exposure Delayed Effects/drug therapy , gamma-Aminobutyric Acid/therapeutic use , Animals , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/metabolism , Female , GABA Agents/pharmacology , Humans , Male , Pregnancy , Prenatal Exposure Delayed Effects/metabolism , Rats , Rats, Wistar , Risk Factors , gamma-Aminobutyric Acid/pharmacology
12.
Data Brief ; 29: 105048, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31970276

ABSTRACT

This article describes the time series data for optimizing the hydropower operation of the Karun-4 reservoir located in Iran for a period of 106 months (from October 2010 to July 2019). The utilized time-series data included reservoir inflow, reservoir storage, evaporation from the reservoir, precipitation on the reservoir, and release of water through the power plant. In this data article, a model based on Moth Swarm Algorithm (MSA) was developed for the optimization of water resources. The analysis showed that the best solutions achieved by the MSA, Genetic Algorithm (GA), and Particle Swarm Optimization (PSO) were 0.147, 0.3026, and 0.1584, respectively. The analysis of these datasets revealed that the MSA algorithm was superior to GA and PSO algorithms in the optimal operation of the hydropower reservoir problem.

13.
Fundam Clin Pharmacol ; 32(6): 603-616, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29869808

ABSTRACT

This study attempted to elucidate the possible mechanism of magnesium sulfate (MgSO4 ) administration on reducing insulin resistance in type 2 diabetic rats. Fifty Wistar rats were divided into five groups: NDC was fed the normal diet, CD received high-fat diet with 35 mg/kg of streptozotocin, CD-Mg animals received MgSO4 via drinking water, CD-Ins1, and CD-Ins2 animals treated with low or high dose of insulin. Body weight and blood glucose levels were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test, and metabolic cage assessment were performed monthly. After 12 weeks, the hyperinsulinemic-euglycemic clamp was performed for all animals and blood sample was taken to measure glycated hemoglobin (HbA1c), plasma insulin, glucagon, calcium, and magnesium levels. Liver and gastrocnemius muscle were isolated to measure glucagon receptor (GR), Glucose 6 phosphatase (G6Pase), Phosphoenolpyruvate carboxykinase (Pepck) and Glucose transporter 4 (Glut4) genes expression and GLUT4 protein translocation into the cell membrane. Consuming of high-fat diet generated insulin-resistant rats. Magnesium or insulin therapy altered insulin resistance, blood glucose, IPGTT, gluconeogenesis pathway, GR, body weight, the percentage of body fat, and HbA1C in diabetic rats. Administrations of MgSO4 or insulin in Type 2 diabetes mellitus animals increase GLUT4 gene and protein expression. Mg could improve glucose tolerance via stimulation of Glut4 gene expression and translocation and also suppression of the gluconeogenesis pathway and GR gene expression. Mg also increased glucose infusion rate and displayed beneficial effects in the treatment of glucose metabolism and improved insulin resistance.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Insulin Resistance/physiology , Magnesium Sulfate/pharmacology , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat , Disease Models, Animal , Gluconeogenesis/drug effects , Glucose/metabolism , Glucose Clamp Technique/methods , Glucose Tolerance Test/methods , Glucose Transporter Type 4/metabolism , Hypoglycemic Agents/pharmacology , Insulin/metabolism , Liver/drug effects , Liver/metabolism , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Rats , Rats, Wistar , Streptozocin/pharmacology
14.
Eur J Pharmacol ; 826: 75-84, 2018 May 05.
Article in English | MEDLINE | ID: mdl-29391158

ABSTRACT

Skeletal muscle, hepatic insulin resistance, and beta cell dysfunction are the characteristic pathophysiological features of type 2 diabetes mellitus. GABA has an important role in pancreatic islet cells. The present study attempted to clarify the possible mechanism of GABA to improve glucose tolerance in a model of type 2 diabetes mellitus in rats. Fifty Wistar rats were divided into five groups: NDC that was fed the normal diet, CD which received a high-fat diet with streptozotocin, CD-GABA animals that received GABA via intraperitoneal injection, plus CD-Ins1 and CD-Ins2 groups which were treated with low and high doses of insulin, respectively. Body weight and blood glucose were measured weekly. Intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (ITT), urine volume, amount of water drinking, and food intake assessments were performed monthly. The hyperinsulinemic euglycemic clamp was done for assessing insulin resistance. Plasma insulin and glucagon were measured. Abdominal fat was measured. Glucagon receptor, Glucose 6 phosphatase, Phosphoenolpyruvate carboxykinase genes expression were evaluated in liver and Glucose transporter 4 (GLUT4) genes expression and protein translocation were evaluated in the muscle. GABA or insulin therapy improved blood glucose, insulin level, IPGTT, ITT, gluconeogenesis pathway, Glucagon receptor, body weight and body fat in diabetic rats. GLUT4 gene and protein expression increased. GABA whose beneficial effect was comparable to that of insulin, also increased glucose infusion rate during an euglycemic clamp. GABA could improve insulin resistance via rising GLUT4 and also decreasing the gluconeogenesis pathway and Glucagon receptor gene expression.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , gamma-Aminobutyric Acid/pharmacology , Animals , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/etiology , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/etiology , Diabetes Mellitus, Type 2/metabolism , Diet, High-Fat/adverse effects , Gluconeogenesis/drug effects , Glucose Tolerance Test , Glucose Transporter Type 4/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Injections, Intraperitoneal , Insulin/blood , Insulin/therapeutic use , Insulin Resistance , Liver/metabolism , Male , Muscle, Skeletal/metabolism , Rats , Rats, Wistar , Receptors, Glucagon/metabolism , Streptozocin/toxicity , gamma-Aminobutyric Acid/therapeutic use
15.
Cancer Lett ; 419: 30-39, 2018 04 10.
Article in English | MEDLINE | ID: mdl-29331419

ABSTRACT

Interferon γ-induced protein 10 kDa (IP-10) is a potent chemoattractant and has been suggested to enhance antitumor activity and mediate tumor regression through multiple mechanisms of action. Multiple lines of evidence have indicated that genetically-modified adult stem cells represent a potential source for cell-based cancer therapy. In the current study, we assessed therapeutic potential of human adipose derived mesenchymal stem cells (hADSC) genetically-modified to express IP-10 for the treatment of lung metastasis in an immunocompetent mouse model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10 melanoma cells and significantly prolonged survival. Immunohistochemistry analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs, restricted angiogenesis and significantly prolonged survival. In conclusion, our results demonstrated that targeting metastatic tumor sites by hADSC expressing IP-10 could reduce melanoma tumor growth and lung metastasis.


Subject(s)
Chemokine CXCL10/metabolism , Lung Neoplasms/therapy , Melanoma, Experimental/therapy , Mesenchymal Stem Cells/metabolism , Adipose Tissue/cytology , Adult , Animals , Cell Line, Tumor , Cell- and Tissue-Based Therapy/methods , Cells, Cultured , Chemokine CXCL10/genetics , Disease Models, Animal , Genetic Therapy/methods , Humans , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Male , Melanoma, Experimental/genetics , Melanoma, Experimental/pathology , Mesenchymal Stem Cell Transplantation/methods , Mesenchymal Stem Cells/cytology , Mice , Mice, Inbred C57BL , Survival Analysis , Young Adult
16.
Pathol Oncol Res ; 24(1): 145-151, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28411308

ABSTRACT

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Colorectal Neoplasms/pathology , Drug Resistance, Neoplasm/genetics , Fluorouracil/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , MicroRNAs/genetics , Antigens, CD , Apoptosis/drug effects , Cadherins/genetics , Cadherins/metabolism , Cell Proliferation/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Humans , MicroRNAs/antagonists & inhibitors , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Tumor Cells, Cultured
17.
J Bodyw Mov Ther ; 21(1): 63-68, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28167192

ABSTRACT

Stress is one of the most significant causes of major health problems on a global scale. The beneficial effects of exercise on combating stress, however, are well-established. The present study investigated the stress biomarker responses, such as serum corticosterone, interlukin-1ß, and glucose levels, to different (preventive, therapeutic, protective, and continuous) protocols of forced exercise under stress. Male rats were randomly allocated to the following five groups: stressed, preventive, therapeutic, protective, and continuous (and/or pre-stress, post-stress, stress-accompanied, and both pre-stress and stress-accompanied exercise respectively) exercise groups. Stress was applied 6 h/day for 21 days and the treadmill running was employed at a speed of 20-21 m/min for 21 and 42 days. The findings showed that the therapeutic, protective, and continuous exercises led to reduced corticosterone and glucose levels. Whereas, the preventive exercise did not reverse the stress responses, and that the therapeutic exercise led to a significant decline in serum interlukin-1ß. It is concluded that protective, therapeutic, and, particularly, continuous exercises lead to significant reductions in serum corticosterone and the associated stress-induced hyperglycemia. Moreover, it appears that the timing and duration of exercise are the two factors contributing to changes in stress biomarker responses.


Subject(s)
Blood Glucose/metabolism , Corticosterone/metabolism , Interleukin-1beta/metabolism , Physical Conditioning, Animal/physiology , Stress, Psychological/physiopathology , Animals , Biomarkers , Body Weight/physiology , Disease Models, Animal , Male , Random Allocation , Rats , Rats, Wistar , Running/physiology
18.
Malays J Med Sci ; 23(5): 29-37, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27904422

ABSTRACT

BACKGROUND: Exercise plays a significant role in learning and memory. The present study focuses on the hippocampal corticosterone (CORT), interleukin-1 beta (IL-1ß), glucose, and brain-derived neurotrophic factor (BDNF) levels in preventive, therapeutic, and protective exercises in stressful conditions. METHODS: Forty male rats were randomly divided into four groups: the control group and the preventive, therapeutic, and protective exercise groups. The treadmill running was applied at a speed of 20-21m/min and a chronic stress of 6 hours/day for 21 days. Subsequently, the variables were measured in the hippocampus. RESULTS: The findings revealed that the hippocampal CORT levels in the preventive exercise group had a significant enhancement compared to the control group. In the protective and particularly the therapeutic exercise groups, the hippocampal CORT levels declined. Furthermore, the hippocampal BDNF levels in the preventive and the therapeutic exercise groups indicated significantly decreased and increased, respectively, in comparison with the control group. In the preventive exercise group, however, the hippocampal glucose level turned out to be substantially higher than that in the control group. CONCLUSION: It appears that the therapeutic exercise group had the best exercise protocols for improving the hippocampal memory mediators in the stress conditions. By contrast, the preventive exercise group could not improve these mediators that had been altered by stress. It is suggested that exercise time, compared to stress, can be considered as a crucial factor in the responsiveness of memory mediators.

19.
Adv Biomed Res ; 5: 21, 2016.
Article in English | MEDLINE | ID: mdl-26962523

ABSTRACT

BACKGROUND: Morphine is related to dysregulation of serum hormone levels. In addition, addict subjects interest to sugar intake. Therefore, this study investigated the effect of co-administration of glucose with Mo on the glucoregulatory hormones and causing of diabetes mellitus in rats. MATERIALS AND METHODS: Male rats were randomly divided into four groups including, control, morphine, Morphine-Glucose and diabetes groups. Morphine was undergone through doses of 10, 20, 30, 40, 50, and 60 mg/kg, respectively on days 1, 2, 3, 4, 5, and 6. Then, dose of 60 mg/kg was used repeated for 20 extra days. The Morphine-Glucose group received the same doses of morphine plus 1 g/kg glucose per day. Diabetes was induced by intraperitoneal injection of 65 mg/kg streptozotocin. At the end of experiment, the serum insulin, glucagon, growth hormone (GH), cortisol, and glucose levels were measured. The homeostasis model assessment (HOMA) indexes concluding the HOMA-insulin resistance (HOMA-IR) and HOMA-ß were evaluated. RESULTS: Morphine insignificantly induced a hyperglycemia condition and insulin resistance. Whereas, the beta-cell functions significantly (P < 0.05) decreased only in morphine group. The co-administration of glucose slightly increased the GH, and increased insulin and cortisol levels significantly (P < 0.05 and P < 0.01; respectively) in the Morphine-Glucose group. Furthermore, the co-administration of glucose with morphine could nearly modulate the morphine effects on body weight, glucose, and glucagon levels. CONCLUSION: It is probable that the co-administration of glucose with morphine modulate the serum glucose levels by stimulating the beta-cell functions and to increase insulin secretion.

20.
Exp Brain Res ; 233(10): 2789-99, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26070900

ABSTRACT

Evidence suggests that there are positive effects of exercise on learning and memory. Moreover, some studies have demonstrated that forced exercise plays the role of a stressor. This study was aimed at investigating the effects of different timing of exercise and exercise withdrawal on memory, and serum and hippocampal corticosterone (CORT) levels. Wistar rats were randomly divided into five groups: control, sham, exercise-rest (exercise withdrawal), rest-exercise (exercised group), and exercise-exercise (continuous exercise). Rats were forced to run on a treadmill for 1 h/day at a speed 20-21-m/min. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. Findings showed that after the exercise withdrawal, short-term and mid-term memories, had significant enhancement compared to the control group, while the long-term memory did not present this result. In addition, the serum and hippocampal CORT levels were at the basal levels after the rest period in the exercise-rest group. In the rest-exercise group, exercise improved mid- and long-term memories, whereas continuous exercise improved all types short-, mid- and long-term memories, particularly the mid-term memory. Twenty-one and forty-two days of exercise significantly decreased the serum and hippocampal CORT levels. It seems that exercise for at least 21 days with no rest could affect biochemical factors in the brain. Also, regular continuous exercise plays an important role in memory function. Hence, the duration and withdraw of exercise are important factors for the neurobiological aspects of the memory responses.


Subject(s)
Corticosterone/metabolism , Hippocampus/metabolism , Memory/physiology , Physical Conditioning, Animal/physiology , Animals , Corticosterone/blood , Male , Rats , Rats, Wistar
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