Cell Journal (Yakhteh)
Volume:22 Issue: 3, Autumn 2020

Severe combined immunodeficiency (SCID) is classified as a primary immunodeficiency, which is characterized by impaired T-lymphocytes differentiation. IL2RG, IL7Ralpha, JAK3, ADA, RAG1/RAG2, and DCLE1C (Artemis) are the most defective genes in SCID. The most recent SCID therapies are based on gene therapy (GT) of hematopoietic stem cells (HSC), which are faced with many challenges. The new studies in the field of stem cells have made great progress in overcoming the challenges ahead. In 2006, Yamanaka et al. achieved "reprogramming" technology by introducing four transcription factors known as Yamanaka factors, which generate induced pluripotent stem cells (iPSC) from somatic cells. It is possible to apply iPSC-derived HSC for transplantation in patients with abnormality or loss of function in specific cells or damaged tissue, such as T-cells and NK-cells in the context of SCID. The iPSC-based HSC transplantation in SCID and other hereditary disorders needs gene correction before transplantation. Furthermore, iPSC technology has been introduced as a promising tool in cellular-molecular disease modeling and drug discovery. In this article, we review iPSC-based GT and modeling for SCID disease and novel approaches of iPSC application in SCID.

Leishmaniasis is of public health problems, especially in endemic areas. The activation of macrophages, as the main host of leishmania and promotion of the TH1 immune responses, are the main goal of im-munotherapy methods. Recently, the immunomodulatory role of mesenchymal stem cells (MSCs) in infectious disease has been considered. Different in vitro studies demonstrated the immunostimulatory effect of MSCs on macrophages in response to L.major. In this study, the effect of MSCs on cutaneous leishmaniasis in BALB/c mice was assessed.

To do this experimental research, BALB/c mice infected with L. major that was followed by multiple subcutaneous injections of MSCs at infection site at different intervals. Footpad thickness, spleen parasite burden, lymph node, and spleen cytokine production were measured to determine the efficacy of cell therapy.

Significant (P<0.05) reduction in footpad thickness and delayed wound formation was observed in MSCs treated group. The spleen of the MSCs-treated group indicated a two-fold reduction in parasite burden compared with non-treated infected mice. In addition, nitric oxide (NO), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α) production of lymph node isolated cells and splenocytes changed to the benefit of macrophage activation in response to L. major in MSCs treated group. A two-fold increase in interferon-gamma (IFN-γ) production in the lymph node was determined in the MSCs-treated group.

Although MSCs therapy could not clear the parasite, the results confirm the ability of MSCs to enhance immune responses against leishmania by induction of inflammatory responses and slowing down the spread of parasites. However, further studies needed to improve the efficacy of this method and provide a therapeutic protocol.

Researchers have been interested in the creation of a favorable cellular model for use in vascular-muscle tissue engineering. The main objective of this study is to determine the myogenic effects of vascular endothelial growth factor (VEGF) and human umbilical vein endothelial cells (HUVECs) on adipose-derived stem cells (ADSCs) to achieve an in vitro vascular-muscle cellular model.

The present experimental research was conducted on two primary groups, namely ADSCs monoculture and ADSCs/HUVECs co-culture that were divided into control, horse serum (HS), and HS/VEGF differentiation subgroups. HUVECs were co-cultured by ADSC in a ratio of 1:1. The myogenic differentiation was evaluated using the reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence in different experimental groups. The interaction between ADSCs and HUVECs, as well as the role of ADSCs conditional medium, was investigated for endothelial tube formation assay.

Immunofluorescence staining indicated that Tropomyosin was positive in ADSCs and ADSCs and HUVECs co-culture groups on HS and HS/VEGF culture medium. Furthermore, the MyHC2 gene expression significantly increased in HS and HS/VEGF groups in comparison with the control group (P<0.001). More importantly, there was a significant difference in the mRNA expression of this gene between ADSCs and ADSCs and HUVECs co-culture groups on HS/VEGF culture medium (P<0.05). Current data revealed that the co-culture of ADSCs and HUVECs could develop endothelial network formation in the VEGF-loaded group. Also, the ADSCs-conditioned medium improved the viability and formation of the endothelial tube in the HS and VEGF groups, respectively.

It was concluded that ADSCs/HUVECs co-culture and dual effects of VEGF can lead to the formation of differentiated myoblasts in proximity to endothelial network formations. These in vitro cellular models could be potentially used in vascular-muscle tissue engineering implanted into organ defects where muscle tissue and vascular regeneration were required.

Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed.

In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out.

Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap).

Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.

This study aimed to investigate the reliability of diabetic adipose-derived stem cells (ADSCs) for autologous cell-based therapies by exploring the functionality of signalling pathways involved in regulating oxidative stress and apoptosis.

In this experimental study, ADSCs were isolated from streptozotocin (STZ)-induced diabetic rats (dADSCs) and normal rats (nADSCs). The colonies derived from dADSCs and nADSCs were compared by colony-forming unit (CFU) assay. Reactive oxygen species (ROS) formation and total antioxidant power (TAP) were also measured. Furthermore, the expression of antioxidant enzymes, including catalase (Cat), superoxide dismutase (Sod)-1 and -3, glutathione peroxidase (Gpx)-1, -3 and -4 was measured at mRNA level by semi-quantitative reverse transcriptase polymerase chain reaction assay. The expression of Bax, Bcl2, caspase-3, total and phosphorylated c-Jun N-terminal kinase (JNK) and P38 Mitogen-Activated Protein Kinase (MAPK) at protein level was analyzed by western blotting.

The results of this study indicated that viability and plating efficiency of dADSCs were significantly lower than those of nADSCs. ROS generation and TAP level were respectively higher and lower in dADSCs. The gene expression of antioxidant enzymes, including Cat, Sod-1, Gpx-3 and Gpx-4 in dADSCs was significantly greater than that in nADSCs. However, Sod-3 and Gpx-1 mRNA levels were decreased in dADSCs. Moreover, Bax/Bcl-2 protein ratio, caspase-3 protein expression and phosphorylation of JNK and P38 proteins were increased in dADSCs compared to nADSCs.

Taken together, diabetes might impair the cellular functions of dADSCs as candidates for autologous cellbased therapies. This impairment seems to be m

In the present study, the applicability of hyaluronic acid-alginate (HAA) hydrogel and ovarian cells (OCs) for the culture of mouse ovarian follicles were investigated and compared with those of alginate (ALG) and fibrin-alginate (FA) hydrogels.

In the first step of this experimental study, mechanically isolated preantral follicles from the ovaries of two-week-old mice were encapsulated in the absence or presence of OCs in ALG, HAA, and FA hydrogels and cultured for 14 days. The morphology, diameter, survival and antrum formation rates of the follicles and the maturation and quality of the oocytes were evaluated during culture. In the second step, preantral follicles were cultured similar to the first step, but for 13 days, and their gene expressions and hormonal secretion were assessed on the last day of culture.

In the absence of OCs, higher numbers of ALG- and HAA-encapsulated follicles reached the antral stage compared to FA-encapsulated follicles (P<0.05). However, a higher percentage of HAA-developed oocytes resumed meiosis up to the germinal vesicle breakdown (GVBD)/metaphase II (MII) stages in comparison with ALG-developed oocytes (P<0.05). HAA-encapsulated follicles had significant overexpression of most of the growth and differentiation genes, and secreted higher levels of estradiol (E2) compared to ALG- and FA-encapsulated follicles (P<0.05). The co-culture condition increased the diameter of ALG-encapsulated follicles on day 13 of culture (P<0.05). It also increased the survival and maturation rates of ALG- and FA-encapsulated follicles, respectively (P<0.05). The co-culture condition improved cortical granule distribution in all groups, increased E2 and progesterone (P4) secretions in the ALG and FA groups, and androstenedione (A4) secretion in the FA group (P<0.05).

The present study results show that HAA hydrogel is a promising hydrogel for follicle culture. OCs utilization could ameliorate the culture conditions regardless of the type of hydrogel.

Adiponectin has a crucial role in the function, proliferation and viability of β-cell via action of two receptors: AdipoR1 and AdipoR2. Nevertheless, age related change of Adiponectin system genes in pancreas is unclear or controversial. This study sought to investigate the effects of aging process on serum Adiponectin levels, Adiponectin and its receptor expression in the rat pancreas.

In this experimental study, insulin resistance markers including serum insulin and glucose concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), glucose induced insulin secretion (GIIS), serum Adiponectin levels, pancreatic expression of Adiponectin and its receptors were studied in male Sprague-Dawley rats at the age of 2, 5, 10, 18, 52 and 72 weeks of age.

We found that aging triggered signs of insulin resistance characteristics in rats at 72 age weeks including marked insulin reduction, hyperglycemia and increased HOMA-IR. Circulating Adiponectin as well as pancreatic expression of Adiponectin and AdipoR1 was gradually decreased with age, while the opposite expression pattern of AdipoR2 was observed in the old rats.

Because Adiponectin and Adiponectin signaling have crucial role in β-cell function and viability, we concluded that reduction of Adiponectin signaling may be involved in aging induced β-cell dysfunction. As a result, manipulation of Adiponectin signaling may be a beneficial approach for improvement of β-cell function in the old people.

This study aimed to explore the potential mechanism of MYC proto-oncogene, BHLH Transcription Factor (MYC) gene, on sepsis.

In this experimental study, rat-derived H9C2 cardiomyocyte cells were cultured in vitro, followed by lipopolysaccharide (LPS) treatment with different concentration gradients. The cholecystokinin octapeptide (CCK-8) assay, enzyme-linked immunoassay (ELISA) assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell transfection, Western blot and flow cytometry were used to observe the cellular apoptosis and proliferation of cells in both treated LPS groups and normal control group.

The result of CCK-8 assay showed that silencing MYC inhibited cellular proliferation of sepsis in absence or presence of LPS treatment. ELISA assay showed that the expressions of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were decreased in MYC silenced group, but they were increased after LPS treatment. Moreover, Flow cytometry assay showed that MYC silencing contributed to the apoptosis of sepsis cells. Furthermore, the expression of inflammatory factors showed that MYC silencing elevated the expression of inflammation factors.

MYC might take part in the process of LPS induced sepsis through suppressing apoptosis and inducing cell proliferation. Moreover, MYC might reduce inflammation during the progression of LPS induced sepsis.

The Hippo pathway plays an important role in embryo development, and separation of trophectoderm (TE) and inner cell mass (ICM) cell lines. Therefore, this study investigated effect of maternal age on activity of Hippo pathway in human embryos.

In this experimental study, the developed up embryos to the blastocyst stage and the embryos whose growth stopped at the morula stage were collected from women aged 20-30 years old (young group, 94 embryos) and >37 years (old group, 89 embryos). Expression of OCT4, SOX2, CDX2, GATA3, YAP genes and the relevant proteins, in the both groups were evaluated using respectively quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunofluorescence methods.

There was no significant difference in the expression level of OCT4, SOX2, CDX2, GATA3 and YAP genes in blastocyst and morula stages, between the two groups. However, SOX2 and CDX2 gene expressions in morula stage embryos of the old group was statistically lower than that of the young group (P=0.007 and P=0.008, respectively). Additionally, in the embryos collected from women with >37 years of age, at the blastocyst stage, phospho-YAP (p-YAP) protein was found to be accumulated in the TE, but it was almost disappeared from the ICM. Additionally, in the old group, contrary to the expectation, YAP protein was expressed in the ICM, rather than TE.

The results of this study showed that YAP and P-YAP among the Hippo signalling pathway may be altered by increasing age.

Vitrification of the ovarian tissue is one of the techniques recommended for preserving the fertility of women who are dealing with infertility. Despite its benefits, our information about the molecular aspects of ovarian follicles vitrification is somehow ambiguous. Therefore, the aim of this study was to evaluate the expression pattern of DNA repair genes in vitrified preantral follicles.

In this experimental study, the isolated preantral follicles (n=906) from 14-16 days old mice (n=12) were divided into three groups: fresh, toxic and vitrified which were cultured in vitro for 12 days. Preantral follicles were vitrified using cryotop followed by exposure to equilibration solution for five minutes and vitrification solution (VS) for 30 seconds. In the toxic group, preantral follicles were only placed in equilibration and vitrification media and they were then placed in the warming solutions without exposure to liquid nitrogen. On the second and sixth days of the culture period, real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to evaluate expression of the selected genes involved in DNA repair, including Msh6 (MutS homolog 6), Mre11 (Meiotic recombination 11), Brca1 (Breast cancer type 1), Rad51 (RAD51 recombinase), Pcna (Proliferating cell nuclear antigen) and Atm (ATM serine/threonine kinase). In addition, developmental parameters including growth, survival rate, antrum cavity formation and ovulation were analyzed.

The relative mRNA expression of Msh6, Mre11, Brca1, Rad51, Pcna and Atm on the second and sixth days of the culture period in vitrified group was significantly higher than those of the control and toxic groups, but there was no significant difference between the toxic and control groups. In addition, developmental parameters of follicles were similar in both toxic and control groups, while both were significantly higher than that of vitrified group.

Vitrification changes the expression pattern of DNA repair genes of the mouse preantral follicles

Explore the effect of GATA5 expression on Paclitaxel inhibiting growth of hepatocellular carcinoma (HCC) cells.

In the experimental study, HCC cell lines (HLE, Bel7402 and PLC/PRF/5) were treated with different concentrations of Paclitaxel (5-20 mg/ml) for 24 hours. HLE cells were transfected with GATA5-siRNA vector, while Bel7402 and PLC/PRF/5 cells were transfected with overexpressed GATA5 vector for 24 hours, followed by treatment of the cells with Paclitaxel (10 mg/ml) for 24 hours and subsequently 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay to detect growth of HCC cells. Soft agar cultured was used to analyze formation of colony. Apoptosis of HCC cells were detected by Flow cytometer. Migration of HCC cells was observed by trawell assays. Western blotting and laser confocal microscopy were utilized to detect expression and location of the proteins.

Inhibiting expression of GATA5 reduced sensitivity of HLE cells to Paclitaxel, while overexpression of GATA5 increased sensitivity of Bel7402 cells and PLC/PRF/5 cells to Paclitaxel. Overexpression of GATA5 played a role in stimulating Paclitaxel to inhibit growth, colony formation and migration, as well as enhance apoptosis in HCC cells. Overexpression of GATA5 also promoted Paclitaxel to inhibit expression of reprogramming genes, such as Nanog, EpCAM, c-Myc and Sox2 in Bel7402 and PLC/PRF/5 cells. Inhibited expression of GATA5 led to enhancement of the expression of CD44 and CD133, in HLE cells. Overexpression of GATA5 was not only alone but also synergized with Paclitaxel to inhibit expression of CD44 and CD133 in Bel7402 or PLC/PRF/5 cells.

Overexpression of GATA5 played a role in enhancing Paclitaxel to inhibit the malignant behaviors of HCC cells. It was involved in suppressing expression of the reprogramming genes and stemness markers. Targeting GATA5 is an available strategy for applying paclitaxel to therapy of patients with HCC.

Bacterial toxin can cause cell death through induction of apoptosis in cancer cell lines as well as changes in the expression patterns of long non-coding RNAs (lncRNAs) and genes. In the present study, the effect of tst gene on ACHN cell lines was reported along with proposing a novel pathway of apoptosis in kidney cancer.

In this experimental study, effective lncRNAs and genes were predicted from different criteria for renal cell carcinoma (RCC) by bioinformatics methods and lncRNA-miRNA-mRNA interaction was constructed; then the effect of Staphylococcus aureus tst gene on induction of apoptosis pathways on ACHN and HDF cell lines was investigated.

After creation of lncRNA-miRNA-mRNA interaction, changes in expression levels of lncRNA LINC00847 (P=0.0024) and PTEN gene (P=0.0027) were identified, as potential apoptosis biomarkers for kidney cancer, after treating ACHN cell line by pCDNA3.1 (+)-tst compared to the empty vector. In contrast, there was no statistically significant difference in DICER1 expression levels in ACHN-tst cell (P≥0.05). In addition, transfection by pcDNA3.1 (+)-tst could increase ACHN cell apoptosis level (P<0.0001) compared to the pcDNA3.1 (+) group; but no significant effect was observed on normal cells.

It is suggested that lncRNA LINC00847, discovered in this study, could provide a new landscape for researches aimed to determine relationship between functional lncRNA and RCC pathways. pcDNA3.1 (+)-tst was found to increase apoptosis in the transfected cells.

Thirteen million cancer deaths and 21.7 million new cancer cases are expected in the world by 2030. Breast cancer is considered as the main cause of cancer mortality in women aged 20-59 years. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and they are highly expressed in malignancies, including breast cancer. The role of miRNAs in the pathogenesis of breast cancer is not fully understood. In the present study, for the first time, the impact of hsa-miR-423 rs6505162 on breast cancer risk was investigated in the central province of Iran, Isfahan.

This case-control study was conducted on 153 clinicopathological proven breast cancer patients and 153 sex-matched healthy women with no history of any cancer type and relative patients. The patients and controls were genotyped and association of their clinical characteristics with hsa-miR-423 rs6505162 genotype was analyzed.

The findings indicated that CC genotype of hsa-miR-423 rs6505162 was associated with the increased risk of breast cancer [odds ratio (OR)=2.37, 95% confidence interval (CI)=1.29-4.35 and P=0.0023, CC vs. AA].

The data suggested that hsa-miR-423 rs6505162 could be considered as a novel risk factor in breast cancer pathogenesis in Isfahan province of Iran.

There are controversial data about the prooxidant-antioxidant balance in hypothyroidism. We aimed to investigate the effect of α-lipoic acid (ALA) on oxidative stress parameters in the liver and brain of propylthiouracil (PTU)-induced hypothyroid rats.

In this experimental study, PTU (500 mg/L) was given to rats in drinking water for 10 weeks. ALA (0.2% in diet) alone and together with thyroxine (T4, 20 µg/kg body weight, s.c) were given to hypothyroid rats in the last 5 weeks of the experimental period. The levels of reactive oxygen species, malondialdehyde, protein carbonyl, ferric reducing antioxidant power (FRAP) and glutathione (GSH) levels, superoxide dismutase, and GSH peroxidase activities were determined in the liver and brain of rats. Histopathological examinations were also performed.

Prooxidant parameters were increased in the brain but not liver in hypothyroid rats. ALA treatment alone lowered enhanced brain oxidative stress in hypothyroid rats. Also, ALA was found to ameliorate the changes as a result of oxidative stress arising from T4 replacement therapy.

Our results indicate that ALA alone and together with T4 may be useful in reducing oxidative stress in thyroid dysfunctions

Nicotinamide phosphoribosyltransferase (NAMPT), which is responsible for biosynthesis of nicotinamide adenine dinucleotide (NAD), has a regulatory role in cellular metabolism and thus, might be implicated in non-alcoholic fatty liver disease (NAFLD). This study aimed to show how NAMPT down-regulation in liver cells influences lipid metabolism and sirtiun 1 (SIRT1), as the main NAD-dependent deacetylase enzyme.

In this experimental study, HepG2 cells were transfected with NAMPT siRNA and hepatic triglyceride (TG) content and SIRT1 deacetylase activity were measured by colorimetric and fluorometric methods, respectively. Gene expression of fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP1c) was evaluated by real-time polymerase chain reaction (PCR). Total protein level and the phosphorylated form of acetyl-CoA carboxylase (ACC) and AMP-activated protein kinase (AMPK) were also investigated by western blotting.

Knockdown of NAMPT significantly promoted the accumulation of TG in HepG2 cells, accompanied by a remarkable decline in SIRT1 deacetylase activity. A significant rise in the gene expression of two key lipogenic factors, FAS and SREBP-1c was also observed. These effects were also accompanied by decreased phosphorylation of ACC and AMPK. On the other hand, treatment of transfected cells with either NAD, as the SIRT1 substrate or resveratrol, as the SIRT1 activator reversed the outcomes.

These results demonstrated a protective role for NAMPT against NAFLD and its involvement in the regulation of de novo lipogenesis through the SIRT1/AMPK pathway.

MicroRNAs (miRNAs) play a key role in the development of the heart. Recent studies have shown that miR1 and miR-133 are key regulators of cardiac hypertrophy. Therefore, we aimed to evaluate the effect of an endurance training (ET) program on the expressions of these miRNAs and their transcriptional network.

In this experimental study, cardiac hypertrophy was induced by 14 weeks of ET for 1 hour per day, 6 days per week at 75% VO2 max). The rats (221 ± 23 g) in the experimental (n=7) and control (n=7) groups were anesthetized to evaluate heart morphology changes by echocardiography. Next, we evaluated expressions of miR-1 and miR-133, and heart and neural crest derivatives express 2 (Hand2), Mef2c, histone deacetylase 4 (Hdac4) and serum response factor (Srf) gene expressions by real-time polymerase chain reaction (PCR). Finally, the collected data were evaluated by the independent t test to determine differences between the groups

The echocardiography result confirmed physiological hypertrophy in the experimental group that underwent ET as shown by the increased left ventricular weight/body surface area (LVW/BSA) (P=0.004), LVW/body weight (BW) (P=0.011), left ventricular diameter end-diastolic (LVDd) (P=0.003), and improvements in heart functional indexes such as fractional shortness (FS) (P=0.036) and stroke volume (SV) (P=0.002). There were significant increases in the expressions of miR-1 (P=0.001) and miR-133 (P=0.004). The expressions of Srf, Hdac4, and Hand2 genes significantly increased (P<0.001) in the experimental group Compared with the control group. The expression of Mef2c did not significantly change.

The expressions of miR-1 and miR-133 and their target genes appeared to be involved in physiological hypertrophy induced by ET in these rats.

The aim of this study was to investigate the possibility of producing safe hematopoietic stem cells without the use of viral infectious agents that can be used in stem cell transplantation.

In this experimental study, after single layer cell formation, human primary fibroblast cells were treated with static electromagnetic fields of 10 and 15 milli Tesla (mT) for 20 minutes each day for seven consecutive days. On the seventh day and immediately after the last radiation, the cells were added to the wells containing specific hematopoietic stem cell expansion media. After 21 days and colony formation, the cells belonging to each group were evaluated in terms of the expression of CD34, CD38, and GATA-1 genes using quantitative real-time polymerase chain reaction (PCR), as well as surface marker expression of CD34 by flow cytometry.

Exposure to 10 mT and 15 mT electromagnetic field increased the expression of CD34 and CD38 genes (P<0.05). This increase in gene expression levels were 2.85 and 1.84 folds, respectively, in the 10mT group and 6.36 and 3.81 folds, respectively, in the 15 mT group. The expression of the GATA-1 gene in the 10 mT and 15 mT groups was not significantly different from that of the control group (P<0.05). Electromagnetic waves caused a marked increase in the expression of the CD34 marker at the surface of reprogrammed cells. The rate of expression was about 42.3% in the 15 mT group and 23.1% in the 10 mT group.

The presence of human primary fibroblasts exposed to electromagnetic fields can increase the expression of specific hematopoietic genes. This method can be suitable for reprogramming cells differentiated into hematopoieticlike stem cells and does not pose the risks of retroviral use

The etiologic agent SARS-CoV-2 has caused the outbreak of COVID-19 which is spread widely around the world. It is vital to uncover and investigate the full genome sequence of SARS-CoV-2 throughout the world to track changes in this virus. To this purpose, SARS-CoV-2 full genome sequence profiling of 20 patients in Iran and different countries that already had a travel history to Iran or contacts with Iranian cases were provided from the GISAID database. The bioinformatics analysis showed 44 different nucleotide mutations that caused 26 nonsynonymous mutations in protein sequences with regard to the reference full genome of the SARS-CoV-2 sequence (NC_045512.2). R207C, V378I, M2796I, L3606F, and A6407V in ORF1ab were common mutations in these sequences. Also, some of the detected mutations only were found in Iranian data in comparison with all the available sequences of SARS-CoV-2. The position of S protein mutations showed they were far from the binding site of this protein with angiotensin-converting enzyme-2 (ACE2) as the host cell receptor. These results can be helpful to design specific diagnostic tests, trace the SARS-CoV-2 sequence changes in Iran, and explore therapeutic drugs and vaccines.

Inflammatory bowel diseases (IBDs) are chronic disorders of the gastrointestinal tract. The goal of IBD treatment is to reduce the inflammation period and induce long-term remission. Use of anti-inflammatory drugs including corticosteroids, immunosuppressants and biologicals, is often the first step in the treatment of IBD. Therefore, IBD patients in pandemic of infectious diseases are considered a high-risk group. The public believes that IBD patients are at a higher risk in the current coronavirus 2 pandemic. Nevertheless, these patients may experience mild or moderate complications compared to healthy people. This might be because of particular anti-TNF-α treatment or any immunosuppressant that IBD patients receive. Moreover, these patients might be silent carrier for the virus.

The novel coronavirus has been spreading since December 2019. It was initially reported in Wuhan, Hubei province of China. Coronavirus disease 2019 (COVID-19) has currently become a pandemic affecting over seven million people worldwide, and the number is still rising. Wenzhou, as the first hit city out of Hubei Province, achieved a remarkable success in effectively containing the disease. A great record was also observed in Wenzhou for the clinical management of COVID-19 patients, leading to one of the lowest death rates in China. Researchers and clinical specialists proposed and formulated combined approaches such as computerized tomography (CT)- scans and molecular assays, as well as using both allopathic and traditional medications to mitigate its effects. Iranian and Chinese specialists and scientists had a communication in clinical, molecular and pharmaceutical aspects of COVID-19. A proper guideline was prepared according to the experiences of Chinese clinicians in managing the full spectrum of COVID-19 patients, from relatively mild to highly complex cases. The purpose of this guideline is to serve a reference in the hospital for specialists so that they may better diagnose cases and provide effective therapies and proposed antiviral and anti-inflammatory drugs for patients.

Mankind is witnessing economic uncertainty due to a health crisis as never before. In the era of industrialization where the emergence of invisible enemies of humans is causing a great death toll, "nothing seems more universal than health", the old proverb in nearly all human cultures is once again rebirthed by the current COVID-19 pandemic. Nevertheless what is distinctive is that the SARS-CoV-2 seems to be unequally targeting a particular sector of the populations with risk factors for preventable diseases. Comorbidities, mainly non-communicable diseases (NCDs), seem to be the primary contributors of the current pandemic and not the SARS-CoV-2 per se. The present letter attempts to underscore the converging pattern of communicable (CDs) and NCDs in human toll. For the tens of thousands of lives coming to an end since the turn of the year, we are all truly sad, but thankful to the virus for unearthing the grave need of the mankind to improve his life style and behaviors. It directs us to revisit the values and ultimately save millions of lives in future.