kazem baesi

The use of a combination of three-drug regimen has improved HIV-1 infected patients' life span and quality; however the emergence of drug-resistant strains remains a main problem. Reverse transcriptase inhibitors (RTIs) consist of a main part of highly active anti-retroviral therapy (HAART) regimen. The present study aimed to investigate resistant mutations to RTI drugs in both treatment naïve and under treatment HIV patients in Mashhad city, north-eastern Iran. RNA was extracted from sera of 22 treatment naïve and 22 under treatment patients. The mean age of under treated and treatment naive groups were 38.5±6.7 and 40.8±7.9 respectively. cDNA was synthesized and amplified with Nested PCR assay targeting specific sequences of RT gene. The PCR products were sent for sequencing. Bidirectional sequencing results were analysed using HIV drug resistance database supplied by Stanford University (HIV Drug Resistance Database, https://hivdb.stanford.edu). Among under treatment patients 10 out of 22 (45%) had at least one high-level resistance mutation which was higher than high level resistance mutation rate among treatment naive cases (P<0.01). Detected resistance mutations were as follows: K101E, K103N, K103E, V106M, V108I, E138A, V179T, Y181C, M184V, Y188L, Y188H, Y188F, G190A, L210W, T215F, T215Y, K219Q, and P225H. A high level of resistance mutations to RT inhibitors was observed that causes drug resistance especially against lamivudine (3TC). Such mutations should be considered as probable responsible for therapeutic failure. Serial surveillance studies of circulating drug resistance mutations are recommended.

Since the beginning of the SARS-CoV-2 pandemic, there have been mutations caused by new SARS-CoV-2 variants, such as Alpha, Beta, Gamma, Delta, and Omicron, recognized as the VOC worldwide. These variants can affect vaccine efficacy, disease control, and treatment effectiveness. The present study aimed to evaluate the levels of total and neutralizing antibodies produced by PastoCoAd vaccine candidates against the VOC strains at different time points.

Two vaccine candidates were employed against SARS-CoV-2 using adenoviral vectors: prime only (a mixture of rAd5-S and rAd5 RBD-N) and heterologous prime-boost (rAd5-S/SOBERANA vaccine). The immunogenicity of these vaccine candidates was assessed in mouse, rabbit, and hamster models using ELISA assay and virus neutralization antibody test.

The immunogenicity results indicated a significant increase in both total and neutralizing antibodies titers in the groups receiving the vaccine candidates at various time points compared to the control group (p < 0.05). The results also showed that the PastoCoAd vaccine candidates Ad5 S & RBD-N and Ad5 S/SOBERANA could neutralize the VOC strains in the animal models.

The ability of vaccine candidate to neutralize the VOC strains in animal models by generating neutralizing antibodies at different time points may be attributed to the use of the platform based on the Adenoviral vector, the N proteins in the Ad5 S & RBD-N vaccine candidate, and the SOBERANA Plus booster in the Ad5 S/SOBERANA vaccine candidate.

Mda-7 could complement cancer gene therapy and tethering tumor-homing peptides (THPs) to the structure might improve the therapeutic efficacy. Herein, an Adenovector expressing Mda7-tLyp1 (Ad-Mda7-tLyp1) was prepared and evaluated on breast, liver and gastric cancer cell lines.

 After preparation of recombinant Ad-Mda7-tLyp1 and Ad-Mda7, the expression of recombinant proteins was analyzed by ELISA. Adenovectors were transduced (MOI=2-5) into Hep-G2, MCF7, MKN-45, and normal fibroblast, then tumor killing effect was measured by cytopathic effect monitoring, MTT viability test, BAX gene expression analysis, and Caspase3/7 colorimetric assay.

 The ELSA revealed a sustained level of recombinant proteins secretion following vector transduction. The CPE and viability test showed that Ad-Mda7 and Ad-Mda7-tLyp1 have a significant killing effect on MCF-7, Hep-G2 and MKN-45 compared to fibroblast cell. The BAX expression analysis and caspase 3/7 activity was also showed a significant increase(P<0.05) in apoptosis level following Adenovector transduction into cancer but not fibroblast cells.

 The newly constructed Ad-Mda-tlyp1 showed a suitable tumor cell killing activity and either enough specificity.

We aimed to investigate  miR-21-5p inhibition effect on lncRNA-XIST expression and apoptosis status of MCF-7 cells.

The MCF-7 cells were cultured and transfected by the anti-miR-21-5p oligonucleotide and expression of miR-21-5p, lncRNA-XIST, apoptosis-associated genes (bax and p53) and one miR-21-5p-unrelated lncRNA (BC200) was assessed by RT-qPCR. Furthermore, cell viability checked by MTT assay and apoptosis and cell cycle in transfected cells were detected by flow cytometry. Also, bioinformatics analysis on the transcriptome data confirmed that the lncRNA XIST might have a critical role in breast cancer (BC) cell apoptosis through ceRNAs mechanism and possible regulatory interactions with miR-21-5p.

Expression of miR-21-5p and lncRNA-XIST was significantly down- and up-regulated respectively (P<0.05). However, there was no significant change in lncRNA-BC200 expression. Also, the expression of bax and p53 upraised significantly (P<0.05). In transfected cells, MTT and flow cytometry assays reported a highly significant decrease and increase in viability and apoptosis respectively.

Inhibition of miR-21-5p resulted in significant upregulation of lncRNA-XIST and apoptosis-associated genes bax and p53, which led to the induction of apoptosis in MCF-7 cells. Therefore, more investigations may provide a valuable target for studies on molecular therapies for BC.

Background and Objectives One of the most important proteins of the SARS-COV-2 virus is S protein, which consists of S1 and S2 subunits. The most important region insubunit S1 is the receptor binding region (RBD), which plays a key role in binding toACE receptors. The RBD is a conserved region in S protein that is the target of theimmune system and the production of antibodies against the virus. Due to theimportance of this region in the production of neutralizing antibodies, it can be a goodcandidate for vaccine development and production of diagnostic kits. Therefore, thepresent study aimed to assess the response rate of antibodies in the serum ofrecovered COVID-19 cases using recombinant RBD protein produced in the prokaryoticexpression system as an inexpensive expression system.Subjects and Methods In this study, the recombinant PET22b-RBD construct wastransformed to the Escherichia coli (BL21) host, and the bacterial cells were culturedin a culture medium; thereafter, protein expression was induced using isopropyl beta-D-thiogalactoside (IPTG). The expression of recombinant RBD protein was confirmedby acrylamide gel (SDS-PAGE) and Western blotting. Finally, the desired protein wasextracted using a Ni-NTA column and applied in an indirect ELISA.Results In comparison with the serum of healthy individuals (cut off: 0.412), nosignificant increase was observed in the response of 30 serum samples to therecombinant RBD protein.Conclusion The recombinant RBD protein produced in the prokaryotic host did notrespond significantly to the antibodies in the serum of recovered COVID-19 patientsand cannot be used for diagnostic purposes.

Antiretroviral therapy (ART) should significantly improve the recovery of the immune system in Human immunodeficiency virus (HIV) infected patients. In some patients under ART, it was not possible to increase CD4+ cells reasonably in spite of effective virological control, which is known as discordant immune response (DIR). The aim of this study is the evaluation of the expression of C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 5 (CCR5), interleukin 12B (IL12B), cluster of differentiation 3(CD3), tumor necrosis factor alpha (TNFα), protein tyrosine kinase 2 beta (PTK2B), and t-cell receptor beta TCR β genes in patients with DIR.

In this case-control study, peripheral blood mononuclear cell (PBMC) specimens from patients of the two groups were isolated, RNA was extracted: patients of the control group who were immunologic responders and patients of the case group, which were non-immunologic responders. Real-time relative quantitative polymerase chain reaction (PCR) was performed in duplicate using One Step PrimeScript™ RT-PCR Kit and data analyzed by using GraphPad prism software version 8.0.2.

The expression levels in the patients of the case group in comparison with the patients of the control group were measured for CXCR4, CCR5, IL12B, TNF-α, CD3, PTK2B and TCR-β. The Fold change ratio for CCR5, TCR-β, and CD3 were (0.225), (0.12), (0.09), respectively, and in all three of them, a significant decrease was observed with confidence values. p <0.05, p <0.02 and p <0.01, respectively. None of the CXCR4, IL12B, TNF-α, and PTK2B was statistically significantly different and their fold change ratio was (1.01), (0.6), (1.04), and (0.718) respectively.

we showed significant decrease in the expression of CCR5, TCR-β, and CD3 genes in the patients of the case group in comparison with the patients of the control group, but we could not verify this low expression of these genes are the reason of the low CD4+ T-cell count. Further investigation is necessary, if the suppression of these genes can influence the proliferation or development of CD4 T cells, in-vitro.

In spite of many reports on persistent low CD4 T cell counts and change in immune-related gene expression level in patients with HIV infection, there is still uncertainty about significant association between gene expression level and HIV infection in patients with and without DIR. The aim of this study was to compare the expression level of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes in HIV-1-positive patients with and without DIR.

In this study, 30 HIV-1-positive patients (15 patients with and 15 patients without DIR [control group]) were included. PBMCs of the patients were collected through density radient centrifugation with Ficoll-Hypaque. RNeasy Plus Mini kit was used to extract RNA. Relative expression levels of CD4, CCL5, IFN-γ, STAT1, APOBEC3G, CD45, and ICAM-1 genes were evaluated by real-time PCR.  The data were analyzed using one-way ANOVA.

CD4 T cell counts were significantly lower in DIR patients than the control group (p < 0.01). While there was no significant difference in the relative expression levels of CD4, CCL5, IFN-γ, STAT1, CD45, and ICAM-1 between patients with DIR and control group, APOBEC3G expression level was significantly higher in the patients with DIR as compare to the control group (p < 0.01).

Our findings suggest a significantly higher APOBEC3G expression level in patients with DIR, suggesting the potential role of APOBEC3G in patients with immunological discordance besides its suppressing role in HIV-1 infection. Confirmation of this hypothesis requires further research.

Multiple myeloma is the second most common blood malignancy which has remained incurable with current therapies. However, gene therapy using suicide viral vectors such as adenoviral vectors appear more promising than other treatments. The aim of this study was to evaluate the effects of an adenoviral vector vaccine candidate containing HSV-TK gene on tumor reduction and autophagy mechanism in animal model.

Myeloma tumor was created in mouse models using myeloma SP2/0 cell line. Three groups of negative control, positive control and target group of BALB/c mice were formed. Candidates for the Ad-HSV-tk /GCV vaccine at high titer (108) were then injected three times every 72 hours at target mice and metformin was injected into the control group for 12 consecutive days. Tumor size was measured in all 15 mice studied every three days, and finally, three days after the last dose of the vaccine, the tumors were removed for Western blotting and LC3B expression.

Examination of tumor size showed that injection of the vaccine and autophagy-inducing drug reduced tumor size compared to the negative control group. Western blotting indicated that LC3B expression was significantly higher in the target and positive control groups than in the negative control group. (Mean Diff: -0.4921; P value < 0.05; q: 7.911).

The results suggest that Ad-HSV-tk/GCV vaccine candidate was able to induce autophagy and reduce the growth of tumor cells in the animal model studied due to the ability of adenovirus to induce the immune system response, the anti-myeloma nature of adenovirus and the function of HSV-tk suicide gene

Anti-Retroviral Therapy (ART) should considerably ameliorate the recovery of the immune system in HIV infected patients. In some patients a failure to satisfactorily increase CD4 counts on ART despite successful virological control did occur, named discordant immune response (DIR).  The aim of this study is the evaluation of CD28, CXCL12, FOS genes in patients with DIR.

In current study, after PBMC isolation, RNA was extracted for two groups; Control group (immunologic responders) and case group (non immunologic responders). Real-time relative quantitative PCR was performed in duplicate using One Step PrimeScript™ RT-PCR Kit and data analyzed by using GraphPad prism software version 8.0.2.

The expression levels in the case group compared to the control group were measured for CD28, CXCL12, FOS. The Fold change ratio for CD28 and CXCL12 were (0.46), (0.19) respectively and in both of them, a significant decrease was observed. The Fold change ratio for FOS was (0.70) and no statistically significant was observed.

we showed significantly decrease in the expression of CD28 and CXCL12 genes in the case group compared to control group, but we couldn’t say, this low expression of these genes are the reason of the low count of CD4 T cells. The more investigation is necessary for it, if the suppression of these genes can impact on proliferation of CD4 T cells, in-vitro.

A simple and sensitive diagnosis method is needed to identify HIV infection in sera of untreated, treated, and drug-resistant patients. The purpose of this study is to determine whether heat shock proteins (Hsp)-27 and -20 and HP91 peptide along with HIV-1 polypeptides can serve as potential biomarkers to distinguish HIV infection in untreated, treated, and drug-resistant individuals compared to HIV-negative subjects.

At first, human sera were obtained from 141 participants, including 20 naïve HIV-infected, 71 treated, 30 drug-resistant, 20 HIV-negative (healthy/control) individuals. The recombinant Hsp27, Hsp20, and five designed HIV-1 polypeptides were expressed in Escherichia coli and purified by affinity chromatography under denaturing or native conditions. Finally, the antibodies against these antigens were quantified in sera using ELISA.

Our data showed that HIV-infected patients significantly displayed higher serum levels of anti-Hsp27, anti-HP91, and anti-Nef-Tat-Gp160-P24, anti-Nef-Vpr-Gp160-P24, anti-Nef-Vif-Gp160-P24, anti-Nef-Vpu-Gp160-P24, and anti-Nef-Rev-Gp160-P24 polypeptide antibodies than healthy groups (p < 0.05), but not for anti-Hsp20. Moreover, the serum levels of antibodies against Hsp27, Hsp20, HP91, and HIV-1 polypeptides were not statistically significant between different groups of patients (p > 0.05).

The levels of anti-Hsp27 and anti-HP91 antibodies in serum increased in HIV-1 seropositive subjects along with antibodies against five HIV-1 polypeptides suggesting their potential value as a diagnostic marker for HIV-1 infections.

Cardiomyopathy is one of adverse effects of diabetes that associated with cardiac muscle metabolism and function disruption. Exercise training decreases adverse effects of diabetes on heart by changing genes involved in cardiac metabolism and increasing myokines secretion. So, the aim of this study was to investigate of 8 weeks aerobic training on cardiac PGC-1α gene expression and plasma irisin in STZ-induced diabetics’ rats.

16 STZ-induced diabetics Wistar rats (10 weeks old) divided into control and aerobic training groups. Time and intensity of exercise session began with 15 minutes and 10 m/min, and gradually increased to 40 minutes and 25 m/min at seventh week and kept to the end of eighth’s week (8 weeks). Cardiac PGC-1α gene expression analyzed by PCR, and plasma concentration of insulin, glucose were analyzed by ELISA method 48 hours after the last session of exercise training. Data were analyzed by independent t test at alpha level of 0/05.

the results showed that aerobic exercise training increased PGC-1α concentration (P<0/001) and plasma irisin (P<0/001). Further analysis showed that aerobic exercise training decreased glucose concentration (P<0/001) and increased insulin concentration (P<0/001), but had no effect of insulin resistance (P=0/79). In addition, the results revealed that there is a positive correlation between PGC-1α and plasma irisin (P<0/001) and insulin (P=0/019), but it has a negative correlation with plasma glucose (P=0/001). There is also a positive significant correlation between isirin and insulin (P=0/001), and a negative correlation between irisin and glucose (P=0/002).

The findings suggest that aerobic exercise training induces increased cardiac PGC-1α gene expression and plasma irisin. These changes have a significant correlation with lowered glucose and increased plasma insulin insulin in STZ-induced diabetics’ rats.

Antiretroviral (ARV) therapy extends life for persons living with HIV. Antiretroviral treatment (ART) has been rapidly expanding coverage around the world, including in Iran. However, ART drug resistance also rapidly develops with expanding use and limits effectiveness and treatment options. The aim of this study was to monitor the appearance of new mutations conferring HIV pretreatment drug resistance in the treatment of naïve patients with HIV in Iran. Blood samples were obtained from ARV treatment‑naïve patients from 8 different provinces in Iran in 2016 for genotyping for drug resistance mutations. Sequences were successfully obtained from 90 specimens. Of these, 2 (2%) mutations conferring resistance to protease inhibitors, 2 (3%) conferring resistance to nucleoside reverse transcriptase inhibitors (NRTIs), and 9 (13%) conferring resistance to non‑NRTI (NNRTI) were detected. Any ARV‑resistant drug mutation was found in 11 patients (12%). Nearly one in 8 ARV‑naïve patients had mutations associated with NNRTI resistance in diverse areas of Iran in 2016. Iranian ARV therapy guideline for HIV could consider non‑NNRTI‑based first‑line therapies and expand routine drug resistance testing before treatment initiation as according to HIV drug resistance recommendations of the World Health Organization.

The human immunodeficiency virus type 1 (HIV-1) is an infectious viral agent that gradually extinguishes the immune system, resulting in acquired immune deficiency syndrome (AIDS). The aim of this study was to construct an RNA-positive control based on armored (AR) RNA technology, using HIV-1 RNA as a model. The MS2 maturase, a coat protein gene (at positions 1765 to 1787) and HIV-1 pol gene were cloned into pET-32a plasmid. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and the expression of the construct was induced by 1 mM of isopropyl-L-thio-D-galactopyranoside (IPTG) at 37 °C for 16 h to obtain the fabricated AR RNA. The AR RNA was precipitated and purified using polyethylene glycol and Sephacryl S-200 chromatography. The stability of AR RNA was evaluated by treatment with DNase I and RNase A and confirmed by transmission electron microscopy and gel agarose electrophoresis. Tenfold serial dilution of AR RNA from 101 to 105 was prepared. Real-time PCR assays had a range of detection between 101 and 105. In addition, R2 value was 0.998, and the slope of the standard curve was -3.33. Prepared AR RNA, as a positive control, could be used as a basis for launching an in-house HIV-1 virus assay and other infectious agents. It can be readily available to laboratories and HIV research centers. The AR RNA is non-infectious and highly resistant to ribonuclease enzyme and can reduce the risk of infection in the clinical laboratory.

Due to the significant role of PGC1α in glucose metabolism, insulin has also been induced by the Myokines with sports activities, which is reduced with type 2 diabetes. The gene expression of PGC1α in diabetic people is reduced up to 50%. The purpose of this study was to explore the Effect of 8 weeks of resistance training on IRISIN plasma serum and the gene expression of PGC1α cardiac muscle in (streptozetosin) induced diabetic rats. Sixteen male Wistar rats with an average weight of 200 ± 20 g were randomly assigned to one of the two groups of the diabetic control (n = 8) and the diabetic resistance (n = 8) and were kept in vitro. The experimental group received resistance training for 8 weeks. The following factors were measured: Blood samples were taken and then their heart was abroad and using the Real Time-PCR method, the gene expression of PGC1α of the left ventricle were measured. Independent sample t-test was used. The results showed that there was a significant difference between the average Irisin (p=0/002), gene expression of PGC1α (p=0/001), glucose level (p=0/001) and insulin (p=0/004) between the resistance diabetic group and the control diabetic group. Based on the results of the present study, it seems that resistance training is recommended as an important strategy for improving the gene expression of PGC1α and glucose metabolism in diabetics. Therefore, it can be considered as an effective interference method.

Aim: Here, we use miR-122a that exhibits liver-specific expression for developing a post-transcriptional regulative system mediated by microRNAs.
Gene therapy with adenovirus (Ad) vectors that express herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) have been suggested as a therapeutic strategy to cancer. However, Ad vectors injected into tumors are dispersed into the systemic circulation and transduce liver cells, resulting in severe hepatotoxicity. To be effective, the delivery and expression of suicide genes to cancer treatment ought to be specific to tumor cells, and avoid death of healthy cells. Researchers have demonstrated that expression of transgene could be suppressed in healthy cells with use of vectors that are reactive to microRNA regulation.
We constructed an Ad vector carrying four tandem copies of target sequences of miR-122a that were incorporated into 3'-UTR of HSVtk gene. The expression level of miR-122a was quantified in HepG2 and Huh7 cell lines.
Quantitative RT- PCR analysis demonstrated that Huh7 cells express large amounts of miR-122a compared to HepG2 cells. The viability of Huh7 cells and HepG2 cells after infection by Ad-tk-122aT vector was 83% and 23.5%, respectively. The viability of Huh7 cells was not reduced in the presence of GCV after infection by Ad-tk-122a vector. In contrast, cytotoxicity of HSV-tk/GCV was similar in Huh7 cells and HepG2 cells by Ad-tk vector, with 35.3% and 27% viability, respectively.
Inclusion of the miR-122a target sequences in the HSVtk expression cassette yielded a feasible strategy for reducing cytotoxicity of suicide gene in a liver cell line with high miR-122a expression.

This study aimed to determine drug resistance mutations in patients with virological failure and find correlation between HIV drug resistance test and viral load.
Blood sample was collected from 51 patients who suspicious treatment failure in the center of Imam Khomeini Hospital, Tehran, Iran in 2015. Viral voluntary counseling and testing load test was done and the patients with viral load above 1000 copies choose for detection of drug resistance mutations by genotyping method (29 patients).
The majority of patients (82.75) harbored the HIV subtype CRF 35 A-D. The 86.2% patients compromised at least one resistance mutation. The analysis of reverse transcriptase showed M184V (68.9%), T215YISF (44.8%), K103N (27.6%) and the analysis results of protease revealed G73SC (13.8%) and I47VA (6.9%). Eventually, the significant correlation between viral load and drug resistance was found.
The result of our research stress the significance of recognizing drug resistant on time that prohibits the accumulation of drug resistance mutation and circulates the resistance strain of HIV-1 virus and the importance of national study according to the reliable findings for treatment guidelines.

Autophagy (self-digestion) is a highly regulated process for the degradation of damaged proteins and intracellular components. Autophagy has multifunctional roles in the protection of cellular homeostasis. Beclin1 is a key regulator molecule in autophagosome formation. Inhibition of autophagy by destruction of the Beclin 1 allele creates sensitivity to metabolic stress. Inhibition of the autophagy under conditions of nutrient deprivation in tumors resistant to apoptosis can lead to necrosis, inflammation and increased tumor growth. This study aims to assess the effect of autophagy induction on the necrosis pathway of MDCK cells.
We evaluated induction of autophagy by the Beclin1 gene in MDCK cells and assessed the percentage of necrosis cell death by flow cytometry using an Annexin V Staining kit. In order to induce autophagy, the recombinant pcDNA3.1-Beclin 1 was transfected into the MDCK cell line using lipofectamine TM 3000.
Overexpression of the Beclin1 gene in MDCK cells led to induction of autophagy as seen by intracellular autophagosomal indicator LC3-II staining. There were 9.92% positive LC3 structures in transfected cells and 0.15% in untransfected cells. In the transfected and control groups, the rate of necrosis cell death was 1.66% and 0.06%, respectively.
Crosstalk between autophagy and necrosis pathways might affect the fate of the cell life span. Strategies that involve in modulation of autophagy and cell death might lead to therapeutic interventions in diseases. Therefore manipulation of cell death pathways could create new areas in therapeutic uses and interventions.

Type 2 diabetes is a risk factor for heart disease and has a major contribution in mortality due to cardiovascular diseases. In the present study, the effect of 12-week resistance training was investigated on cardiac hypertrophy, glucose, level, insulin, and insulin resistance index in STZ-induced diabetic rats.
A total of 16 male Wistar rats (mean weight, 200±20g) were randomly divided into two groups of diabetic control and (N= 8), diabetic resistance (N= 8). The diabetic resistance training group performed a 12-week resistance training, and 48 hours after the end of the last training session, the rats were anesthetized and euthanized. The variables of interest (body weight, heart weight, left ventricular weight, percentage of heart weight to body weight, percentage of left ventricular weight to heart weight, resting heart rate, level of glucose, insulin, and insulin resistance index), were measured. Data analysis was performed using independent samples t-test at significance level of p≤0.05.
There was a significant difference among mean heart weight (p=0.050), left ventricular weight (p=0.002), level of glucose (p=0/000), insulin (p=0.000), and resting heart rate (p=0.021) in the resistance diabetic group compared to the control diabetic group.
According to the results of the present study, it seems that resistance training is an important strategy to improve the structure and function of the heart in diabetics and it can be considered as an effective intervention method.

Although less is known about the molecular mechanisms responsible for its genetic compatibility, regular training is identified as a non-pharmacological treatment for obesity and type-II diabetes. This study aimed to determine the effect of a 3 months aerobic training on pancreatic TCF7L2 expression and glycemic profile in type II diabetic rats.
In this experimental study, type II diabetes was induced in male Wistar rats (n=16, weight: 220±30 g) by intraperitoneal injection of streptozotocin- nicotinamide. Animals were randomly divided into Exercise (n=8) and Control (n=8) groups. Exercise group, but not Control group, was completed a 3 month aerobic training (3 sessions/week). Forty-eight hours after the last exercise session, the relative expression of pancreatic TCF7L2, fasting glucose and serum insulin were measured in two groups.
Compared to Control rats, exercise resulted in a significant decrease in fasting glucose in Exercise group (P=0.001). Serum insulin was increased significantly by aerobic training in Exercise group compared to Control one (P=0.014). However, pancreatic TCF7L2 expression did not change by aerobic training (P=0.876).
Based on these data, while we concluded that a long-term aerobic training effectively improves the glycemic profile and insulin concentration of type II diabetic rats, such improvements cannot be attributed to TCF7L2 expression in pancreatic tissue.

Type 2 diabetes is a multifactorial disease, but recently it has been found that increased expression of MTNR1B gene is associated with of the risk of type 2 diabetes. The aim of this study was to evaluate the effect of 12 weeks of resistance training on MTNR1B gene expression in the pancreas and glucose and insulin levels in male Wistar rats with type 2 diabetes.
This study was a fundamental and experimental approach. In this study 30 male Wistar rats weighing 220±20 g, were used. Rats were kept under the standard conditions of temperature of 22 °±2 C and humidity of 45% and consecutive 12-hour periods of light and darkness. Rats were divided into three groups: Control group, diabetic group, and diabetic plus resistant training group. Diabetes was induced by disolving nicotinamide and STZ in the drinking water. Resistance training was conducted for 12 weeks, 5 days a week in a 3 course with 6 repetitions. All rats were sacrificed 48 hours after the last training session.
A significant reduction in fasting glucose levels was observed in the diabetic resistant training group than the diabetic group (P The results showed that twelve weeks of resistance exercise significantly increased serum insulin, a significant reduction in blood glucose and a significant reduction in the MTNR1B gene expression in the pancreatic than diabetic group.

Protein tyrosine phosphatase 1B (PTP1B) is a key enzyme in dephosphorylation of the insulin receptor (IR) and it is a central factor to induce the insulin resistance. The purpose of this study was to evaluate the effect of 12-week aerobic training on protein tyrosine phosphatase 1B gene expression and insulin resistance in diabetic rats.
In this study, 16 Wistar rats were divided into aerobic training and control groups. After inducing diabetes intra protaneally, aerobic training group performed training protocol for 12 weeks and 5 session/week. The duration and speed of each session increased progressively as 18 to 26 m/min and 10 to 55 min, respectively. Then, blood and tissue (from gastrocnemius) sampling were carried out in diabetic rats. Insulin resistance markers and PTP1B gene expression were evaluated by commercial kits and Real-Time PCR method, respectively.
Findings showed that PTP1B significantly was decreased in diabetic rats of aerobic training group (p=0.0001). Also, glucose and insulin resistance significantly was decreased in aerobic training groups (p=0.02 and p=0.006, respectively). However, insulin in control rats was significantly increased (p=0.015).
It seems that, current aerobic training protocol has capability to decrease PTP1B and insulin resistance in diabetic rats. Furthermore, the direct correlation between PTP1B and insulin illustrated that any changes in insulin resistance due to exercise training associated with diminution of negative regulation of insulin signaling pathway.

Cardiomyopathy is a side effect caused by diabetes. Prolonged hyperglycemia gives rise to an increase in the expression of the receiver gene RAGE subsequently triggering pathogenesis cardiac signaling pathways in the heart of rats with type II diabetes. The present paper aims to examine how a 12 week Resistance training on gene expressions RAGE, ICAM, VCAM in the heart of diabetic rats with STZ.
16 male Wistar rats with weight mean ranging from 200 ± 20 g were randomly assigned to two groups of Resistance diabetes (n = 8) and control diabetes (n = 8) and were kept under lab circumstances. A 12 week Resistance training was administered with the experimental group and 48 hours after the end of the last training session the rats were made unconscious and examined. Their hearts were, afterwards, cut out and the extent of gene expressions RAGE, ICAM, VCAM in the left ventricular heart was measured using Real time-PCR method.
The results indicated there was a significant difference between left ventricular heart of the Resistance diabetes and that of control diabetes in terms of gene expression RAGE, yet no significant difference was detected between the two groups in terms of gene expressions ICAM, VCAM.
According to the results, in seems that Resistance trainings effectively reduce gene expressions RAGE and reduction pattern but non-significant in the Gene ICAM, VCAM in left ventricular heart of diabetic rats and therefore can be considered an effective way in reducing pathogenesis cardiac signaling pathways in the heart of rats with type II diabetes.

Resistance exercise is recommended as a useful therapeutic tool for the treatment of type 2 diabetes (T2D); however, the frequency of studies is inadequate to establish the precise mechanisms of any association between them.
In this study, we aimed to assess the effect of three months of resistance training on TCF7L2 expression in pancreatic tissues, serum insulin and glucose.
For this purpose, type 2 diabetes (T2D) was induced by intraperitoneal streptozotocin-nicotinamide in eighteen male Wistar rats aged 10 weeks (220 ± 30 g). Then, the rats were randomly divided into exercise and control groups. The exercise rats completed a three-month resistance training intervention that included climbing on a stepladder for 5 days weekly. The control group did not participate in exercise intervention. Fasting glucose and insulin were measured before and after injection (7 days) and after intervention. TCF7L2 gene expression of pancreatic tissues was measured in both groups after the exercise treatment, and the ratio between the two groups was calculated.
Fasting glucose increased and serum insulin decreased significantly by T2D induction in the two groups at baseline. Resistance training resulted in a decrease in fasting glucose and an increase in insulin in exercise rats. Data also showed that TCF7L2 gene expression decreased after resistance training compared with the control group.
Based on these data, increased serum insulin can be attributed to a decrease in TCF7L2 gene expression of pancreatic cells by resistance training in T2D rats.

Type 2 diabetes is a chronic disease with warning increasing rate in the world. Although type 2 diabetes is a multifactorial disease, it has been recently found that the incidence of type 2 diabetes is associated with MTNR1B gene and the growth of its expression increases the risk of type 2 diabetes. The objective of this study was to evaluate the effect of 12-week aerobic exercise on MTNR1B gene expression, glucose and fasting insulin in male Wistar rats with type 2 diabetes.
This fundamental study with experimental approach. included 30 male Wistar rats with weight of 220±20 gram. Sampls were kept under standard conditions: temperature of 22 ± 3° centigrade, 45% humidity and consecutive 12-hour periods of light and darkness. The rats were divided into three groups. Infusion of diabetes was conducted by Nicotinamide and streptozotocin solution.Training program was held on 5 days a week for 12 weeks with a gradual increasing of speed (18 to 26 meters per minute) and time (10 to 55 minutes) by running on a treadmill. Glucose level, insulin level and gene expression were measured by enzyme glucose oxidase colorimetric method, enzyme-linked immunosorbent assay, and Real-time polymerase chain reaction. All statistical analyses were performed by software SPSS, version16.
Training programme led to a significant reduction in fasting glucose levels in aerobic diabetic group compared to the control diabetic group (P The results showed that 12-week aerobic exercise led to a significant reduction in blood glucose and in gene expression MTNR1B in pancreatic tissue compared to the diabetic control group.

Designing novel therapeutic agents has been a critical challenge for HIV disease.
In current study a DNA sequence which was encoded the Tat protein was synthesized and inserted in pET 28 vector. Vector was cloned in BL21-DE3 E. coli and cultured in TB media. After protein expression, recombinant Tat protein was purified by NTA affinity chromatography. The Tat purified protein efficiency and confirmed by SDS-PAGE and Western blot, respectively. We were immunized the camel against HIV-1 Tat recombinant protein to made a camelid antibody library. Total RNA was extracted from camel lymphocytes and VHH fragments synthesized and amplified using RT-PCR and Nested- PCR methods by special primers.
The 350- 450 bp VHH gene fragment was produced by RT-PCR and Nested- PCR and extracted from agarose gel 1%. Then gel extraction was performed and pure fragments were inserted in HEN-4 vector by T4 DNA ligase.
The library can be applied for biopanning and isolation of nanobody against HIV-1 Tat Protein. Nanobody small size may be a useful drug for treatment of HIV disease because give them the potency of the recognizing the cryptic epitopes of tat and neutralized the virus.