Therapeutic Opportunities Presented by Modulation of Cellular Senescence.

Cellular senescence is a permanent state of growth arrest coupled with profound changes in phenotype that can be triggered by multiple extrinsic or intrinsic stimuli. Senescence is a process-level example of the evolution of ageing mechanisms through antagonistic pleiotropy and plays a primary role in tumour suppression, although evidence is mounting for its involvement in other fundamental physiological processes. Evidence from human premature ageing diseases and from transgenic mice in which it is possible to specifically delete senescent cells is consistent with a model in which the accumulation of senescent cells through the life course is responsible for later life chronic disease and impairment. The removal of senescent cells or their reversion to a phenotypically benign state is thus an important emerging goal of translational medicine.Modern bioinformatic approaches based on text mining have compiled co-mentions of cell senescence and age-related diseases allowing an impartial ranking of the impairments most closely associated with this process. Following this schema, the evidence for the involvement of senescence in several highly ranked pathologies is reviewed, alongside potential methods for the ablation of senescent cells or their reversion to their primary phenotype with polyphenolics or inhibitors of p38 MAP kinase. Lastly, the potential for senescence to act as a barrier to the development of bioartificial organs designed to treat some of these conditions is discussed.

Regulation of the Th17/Treg balance by human umbilical cord mesenchymal stem cell-derived exosomes protects against acute experimental colitis.

Increasing evidence suggests that mesenchymal stem cells (MSCs) have immunosuppressive properties mediated by MSC-derived small extracellular vesicles (sEV). Exosomes are small extracellular vesicles that contain components that regulate immune cell function. We investigated the immunomodulatory effects of MSC-derived Exosome (MSC-Exo) on the severity of colitis using the dextran sulfate sodium (DSS)-induced colitis model. Exosomes were administrated intraperitoneally. Daily changes in body weight, stool consistency, and bleeding were assessed to determine the impact of MSC-Exos on colitis. Several measurements were taken, including the colon weight, length, and histological analysis of the colon tissues. The percentage of regulatory T cells and IL-10, TGF-ß, IL-17, TNF-α, and IFN-γ levels were calculated in the mesenteric lymph node (MLN) and spleen. The results showed MSC-Exos improved clinical manifestations of colitis. Colon macroscopic and histological observations also showed improvement in tissue destruction. The results illustrated that MSC-Exos might attenuate colitis by regulating Treg/Th17 balance, increasing anti-inflammatory, and decreasing pro-inflammatory cytokines expression. As a result, MSC-Exos could be used as an immunomodulatory approach to treating bowel inflammation.

Effects of resveratrol and its analogues on the cell cycle of equine mesenchymal stem/stromal cells.

Resveratrol (RSV; trans-3,5,4'-trihydroxystilbene) strongly activates sirtuin 1, and it and its analogue V29 enhance the proliferation of mesenchymal stem/stromal cells (MSCs).Although culture medium containing 5-azacytydine and RSV inhibits senescence of adipose tissue-derived MSCs isolated from horses with metabolic syndrome, few studies have reported the effects of RSV on equine bone marrow-derived MSCs (eBMMSCs) isolated from horses without metabolic syndrome. The aim of this study was to investigate the effects of RSV and V29 on the cell cycle of eBMMSCs. Following treatment with 5 µM RSV or 10 µM V29, the cell proliferation capacity of eBMMSCs derived from seven horses was evaluated by EdU (5-ethynyl-2'-deoxyuridine) and Ki-67 antibody assays. Brightfield images of cells and immunofluorescent images of EdU, Ki-67, and DAPI staining were recorded by fluorescence microscopy, and the number of cells positive for each was quantified and compared by Friedman's test at P<0.05. The growth fraction of eBMMSCs was significantly increased by RSV and V29 as measured by the EdU assay (control 28.1% ± 13.8%, V29 31.8% ± 14.6%, RSV 32.0% ± 10.8%; mean ± SD; P<0.05) but not as measured by the Ki-67 antibody assay (control 27.0% ± 11.2%, V29 27.4% ± 10.8%, RSV 27.7% ± 6.8%). RSV and V29 promoted progression of the cell cycle of eBMMSCs into the S phase and may be useful for eBMMSC expansion.

Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is an inflammatory condition that results in gastrointestinal tract damage. Various factors, including environmental and genetic agents, disrupt the function of the intestinal immune system that can lead to IBD. Mesenchymal stem cells (MSCs) display an immunoregulatory function and demonstrate regenerative potential by paracrine action. In this study, we evaluated the immunomodulatory effects of MSCs' derived exosomes in the acute form of dextran sulfate sodium (DSS)-induced colitis. Exosomes were isolated from adipose-derived MSCs. Acute colitis was induced by DSS. The exosome was used by intraperitoneal injection into mice with acute colitis. Stool consistency, body weight changes, bleeding severity, colon length, and weight were examined. At the experimental endpoint (Day 7), the changes in the colon tissue were evaluated. The level of cytokines of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-4, IL-12, transforming growth factor-ß (TGF-ß) and, IL-10, and Treg cells percentage were assayed. Results showed that exosome administration diminished colon shortening, bodyweight loss, bleeding, and colon injury. The levels of IFN-γ, TNF-α, IL-12, and IL-17 were decreased, and the level of TGF-ß, IL-4, and IL-10 were increased in lymph node and spleen of mice treated with exosome.  Percentages of CD4+ CD25+ Foxp3+ Treg cells were grown in the lymph node and spleen of mice treated with exosomes. Overall, current data suggest that MSC-derived exosome could regulate the Treg population and improves inflammation in DSS-induced acute colitis.

Comparing Hemodynamic Responses to Diazepam, Propofol and Etomidate During Anesthesia Induction in Patients with Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Graft Surgery: a Double-blind, Randomized Clinical Trial.

BACKGROUND: Anesthesia induction is often accompanied by a period of hemodynamic instability, which could be deleterious in patients with coronary artery disease (CAD) and left ventricular dysfunction undergoing coronary artery bypass graft (CABG) surgery. The aim of this study was to compare the hemodynamic responses to propofol, etomidate, and diazepam following anesthesia induction, laryngoscopy and intubation in CABG surgery patients with low ejection fraction (EF). METHODS: A double-blind randomized, clinical study was performed on 150 patients with CAD and left ventricular dysfunction (EF≤35%) scheduled for elective CABG surgery with Cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups A, B, and C. These patients received propofol, etomidate or diazepam at induction of anesthesia, respectively. Hemodynamic variables (systolic and diastolic blood pressure [SBP, DBP], mean arterial pressure [MAP] and heart rate [HR]) were measured and recorded at baseline, immediately before laryngoscopy and tracheal intubation and one and three minutes after intubation. RESULT: One minute after induction and before laryngoscopy, there was a statistically significant decrease from the baseline in SBP, DBP and MAP in all three groups, but these variables in each hemodynamic parameters in diazepam group were less than other two groups (p<0.001). Moreover, the mean HR decreased in patients receiving propofol and etomidate one minute after induction and before laryngoscopy, but did not decreased in the diazepam group (p=0.005). CONCLUSION: The present study showed that in patients undergoing CABG surgery with low EF, diazepam is more favorable in terms of hemodynamic stability compared to propofol and etomidate and this drug can be used safely for induction of anesthesia in patients with impaired ventricular function.

A SIRT1-independent mechanism mediates protection against steroid-induced senescence by resveralogues in equine tenocytes.

Tendinopathy is a common age-related disease which causes significant morbidity for both human athletes and performance horses. In the latter, the superficial digital flexor tendon is an excellent model for human tendinopathies because it is a functional homologue of the human Achilles tendon and a primary site of injuries with strong similarities to the human disease. Corticosteroids have been previously used clinically to treat tendinopathic inflammation, but they upregulate the p53-p21 axis with concomitant reductions in cell proliferation and collagen synthesis in human tenocytes. This phenotype is consistent with the induction of cellular senescence in vitro and in vivo and probably represents an important clinical barrier to their effective use. Because of the many differences in senescence mechanisms between species, this study aimed to evaluate these mechanisms after corticosteroid treatment in equine tenocytes. Exposure to clinically reflective levels of dexamethasone for 48 hours drove equine tenocytes into steroid induced senescence (SIS). This was characterised by permanent growth arrest and upregulation of p53, the cyclin dependent kinase inhibitors p21waf and p16ink4a as well as the matrix degrading enzymes MMP1, MMP2 and MMP13. SIS also induced a distinctive equine senescence associated secretory phenotype (eSASP) characterised by enhanced secretion of IL-8 and MCP-1. Preincubation with resveratrol or the potent SIRT1 activator SRT1720 prevented SIS in equine tenocytes, while treatment with the non-SIRT1 activating resveratrol analogue V29 was equally protective against SIS, consistent with a novel, as yet uncharacterised SIRT1-indendent mechanism which has relevance for the development of future preventative and therapeutic strategies.

Exosomes Derived from Heat-shocked Tumor Cells Promote In vitro Maturation of Bone Marrow-derived Dendritic Cells.

Dendritic cells (DCs), professional antigen-presenting cells that process and deliver antigens using MHC II/I molecules, can be enhanced in numerous ways.  Exosomes derived from heat-shocked tumor cells (HS-TEXs) contain high amounts of heat-shock proteins (HSPs). HSPs, as chaperons, can induce DC maturation. This study aimed to investigate whether HS-TEXs can promote DC maturation. To generate DC, bone marrow-derived cells were treated with Interleukin-4 and GM-CSF. Exosomes were isolated from heat-treated CT-26 cells. The expression level of HSP in exosomes was checked by western blot and the increase in the expression of this protein was observed. Then, HS-TEXs were co-cultured with iDCs to determine DC maturity, and then DCs were co-cultured with lymphocytes to determine DC activity. Our results showed that  DCs treated with HS-TEXs express high levels of molecules involved in DC maturation and function including MHCII, CD40, CD83, and CD86. HS-TEXs caused phenotypic and functional maturation of DCs. In addition, flow cytometric results reflected a higher proliferative response of lymphocytes in the iDC / Tex + HSP group. HS-TEXs could be used as a strategy to improve DC maturation and activation.

Resveralogues protect HepG2 cells against cellular senescence induced by hepatotoxic metabolites.

Progressive liver disease and dysfunction cause toxic metabolites including ammonia and unconjugated bilirubin to accumulate in plasma. As the population ages alternatives to liver transplantation become increasingly important. One approach for use as a bridge to transplant or recovery is the use of bioartificial liver systems (BALS) containing primary or immortalised hepatocytes as ex-vivo replacements or supports for endogenous liver function. However, exposure to the hepatotoxic metabolites present in plasma causes the rapid failure of these cells to carry out their primary metabolic functions despite remaining viable. Hypothesizing that this loss of core hepatocyte phenotypes was caused by cell senescence we exposed HepG2 cell populations, grown in both standard two-dimensional tissue culture systems and in three dimensional cultures on novel alginate modified HEMA-MBA cryogels, to physiologically reflective concentrations of hepatotoxic metabolites and cytokines. HepG2 cells are forced into senescence by the toxic metabolites in under six hours (as measured by loss of thymidine analog incorporation or detectable Ki67 staining) which is associated with a ten to twenty-fold reduction in the capacity of the cultures to synthesise albumin or urea. This state of senescence induced by liver toxins (SILT) can be prevented by preincubation with either 2-5 µM resveratrol, its major in vivo metabolite dihydroresveratrol or a series of novel resveralogues with differential capacities to scavenge radicals and activate SIRT1 (including V29 which does not interact with the protein). SILT appears to be a previously unrecognised barrier to the development of BALS which can now be overcome using small molecules that are safe for human use at concentrations readily achievable in vivo.

A Simple High Yield Technique for Isolation of Wharton's Jelly-derived Mesenchymal Stem Cell.

Background: The isolation of Mesenchymal Stem Cells (MSCs) from various tissues is possible, with the umbilical cord emerging as a competitive alternative to bone marrow. In order to fulfill the demands of cell therapy, it is essential to generate stem cells on a clinical scale while minimizing time, cost, and contamination. Here is a simple and effective protocol for isolating MSC from Wharton's Jelly (WJ-MSC) using the explant method with various supplements. Methods: Utilizing the explant method, small fragments of Wharton's jelly from the human umbilical cord were cultured in a flask. The multipotency of the isolated cells, were confirmed by their differentiation ability to osteocyte and adipocyte. Additionally, the immunophenotyping of WJ-MSCs showed positive expression of CD73, CD90, and CD105, while remaining negative for hematopoietic markers CD34 and CD45, meeting the criteria for WJ-MSC identification. Following that, to evaluate cells' proliferative capacity, various supplements, including basic Fibroblast Growth Factor (bFGF), Non-Essential amino acids (NEA), and L-Glutamine (L-Gln) were added to either alpha-Minimal Essential Medium (α-MEM) or Dulbecco's Modified Eagle's Medium-F12 (DMEM-F12), as the basic culture media. Results: WJ-MSCs isolated by the explant method were removed from the tissue after seven days and transferred to the culture medium. These cells differentiated into adipocyte and osteocyte lineages, expressing CD73, CD90, and CD105 positively and CD34 and CD45 negatively. The results revealed that addition of bFGF to α-MEM or DMEMF12 media significantly increased the proliferation of MSCs when compared to the control group. However, there were no significant differences observed when NEA or LGln were added. Conclusion: Although bFGF considerably enhances cell proliferation, our study demonstrates that MSCs can grow and expand when properly prepared Wharton's jelly tissues of the human umbilical cord.

The potential application of encapsulated exosomes: A new approach to increase exosomes therapeutic efficacy.

Cell therapy is one of the methods that have shown promising results in treating diseases in recent decades. However, the use of different types of cells comes with limitations. The application of immune cells in cell therapy can lead to cytokine storms and inappropriate responses to self-antigens. Also, the use of stem cells has the potential to create tumors. Also, cells may not migrate to the injury site after intravenous injection. Therefore, using exosomes from different cells as therapeutic candidates were proposed. Due to their small size and favorable characteristics, such as biocompatibility and immunocompatibility, the easy storage and isolation, exosomes have attracted much attention. They are used in treating many diseases, including cardiovascular diseases, orthopedic diseases, autoimmune diseases, and cancer. However, the results of various studies have shown that the therapeutic efficiency of exosomes (Exo) can be increased by loading different drugs and microRNAs inside them (encapsulated exosomes). Therefore, analyzing studies investigating encapsulated exosomes' therapeutic ability is critical. In this study, we have examined the studies related to the use of encapsulated exosomes in treating diseases such as cancer and infectious diseases and their use in regenerative medicine. Compared to intact exosomes, the results show that the application of encapsulated exosomes has a higher therapeutic ability. Therefore it is suggested to use this method depending on the treatment type to increase the treatment's efficiency.

Oleuropein reduces LPS-induced inflammation via stimulating M2 macrophage polarization.

Oleuropein (OLEU) is the most prevalent phenolic component in olive varieties, and it has been considered for its powerful antioxidant properties in therapeutic applications. OLEU has anti-inflammatory properties and performs this property by suppressing inflammatory cells' function and reducing oxidative stress caused by various factors. This study investigated the ability of OLEU to polarize LPS-stimulated murine macrophage (MQ) cell RAW 264.7 into M1/M2 macrophages. As a first step, the cytotoxicity effects of OLEU were evaluated on LPS-stimulated RAW 264.7 cells using the thiazolyl blue (MTT) colorimetric test. Then, cytokines production, gene expression (Real-Time PCR), and functions (Nitrite oxide assay and phagocytosis assay) of OLEU-treated LPS-stimulated RAW 264.7 cells were evaluated. Our findings demonstrated that OLEU could reduce nitrite oxide (NO) production in LPS-stimulated RAW 264.7 cells by downregulating the inducible nitric oxide synthase gene expression. Furthermore, OLEU therapy decreases the expression of M1-associated pro-inflammatory cytokines production (IL-12, IFN-γ, and TNF-α) and genes expression (iNOS, TNF-α) while increasing the M2-associated anti-inflammatory gene expression and cytokines production (IL-10, and TGF-ß). Based on the result, OLEU may be considered a potential therapeutic approach for inflammatory diseases due to its possible effects on oxidative stress-related factors, cytokine expression and production, and phagocytosis.

Cancer-associated mesenchymal stem/stromal cells: role in progression and potential targets for therapeutic approaches.

Malignancies contain a relatively small number of Mesenchymal stem/stromal cells (MSCs), constituting a crucial tumor microenvironment (TME) component. These cells comprise approximately 0.01-5% of the total TME cell population. MSC differentiation potential and their interaction with the tumor environment enable these cells to affect tumor cells' growth, immune evasion, metastasis, drug resistance, and angiogenesis. This type of MSC, known as cancer-associated mesenchymal stem/stromal cells (CA-MSCs (interacts with tumor/non-tumor cells in the TME and affects their function by producing cytokines, chemokines, and various growth factors to facilitate tumor cell migration, survival, proliferation, and tumor progression. Considering that the effect of different cells on each other in the TME is a multi-faceted relationship, it is essential to discover the role of these relationships for targeting in tumor therapy. Due to the immunomodulatory role and the tissue repair characteristic of MSCs, these cells can help tumor growth from different aspects. CA-MSCs indirectly suppress antitumor immune response through several mechanisms, including decreasing dendritic cells (DCs) antigen presentation potential, disrupting natural killer (NK) cell differentiation, inducing immunoinhibitory subsets like tumor-associated macrophages (TAMs) and Treg cells, and immune checkpoint expression to reduce effector T cell antitumor responses. Therefore, if these cells can be targeted for treatment so that their population decreases, we can hope for the treatment and improvement of the tumor conditions. Also, various studies show that CA-MSCs in the TME can affect other vital aspects of a tumor, including cell proliferation, drug resistance, angiogenesis, and tumor cell invasion and metastasis. In this review article, we will discuss in detail some of the mechanisms by which CA-MSCs suppress the innate and adaptive immune systems and other mechanisms related to tumor progression.

In vitro comparative study of the microbial leakage of one-step, thermafil and lateral condensation techniques.

AIM: To compare the apical seal of lateral condensation technique, thermafil and one-step by using this model. MATERIALS AND METHODS: A two-chamber bacterial microleakage model using E. faecalis as microbial marker was used for evaluation of the leakage. Bacterial penetration was monitored over a 60-day period. Leakage was recorded when turbidity was observed in the lower chamber. RESULTS: After comparing the bacterial penetration values, total penetration was observed 45% in lateral condensation technique, 80% in thermafil and 75% in one-step. There was no significant difference between groups after 60 days; however, the microleakage in lateral condensation group was seen later than one-step and thermafil. CONCLUSION: Thermafil and one-step obturator can be advocated as effective obturation techniques for achieving predictable success in endodontic therapy. CLINICAL SIGNIFICANCE: Thermafil and one-step obturator are suitable devices for obturation.

Study of immunomodulatory effects of mesenchymal stem cell-derived exosomes in a mouse model of LPS induced systemic inflammation.

BACKGROUND: Sepsis is a debilitating systemic inflammation that resulted from infection or injury. Despite many advances in treatment, the resulting mortality rate has remained high due to increasing antibiotic resistance and aging communities. The present study investigated the effects of stem cell-derived exosomes in a mouse model of LPS-induced systemic inflammation. MATERIALS AND METHODS: To induce sepsis, the LPS model was used. Mice were divided into three groups: normal, patient group (LPS + PBS), and treatment group (LPS + exosome). The treatment group received an intravenous exosome 1 h after induction of the model. Patient and treatment groups were sacrificed at 4, 6, 24, and 48 h after induction of the model, and their tissues were isolated. Blood samples were taken from animal hearts to perform biochemical and immunological tests. The study results were analyzed using Graph Pad Prism software version 9. RESULTS: Mesenchymal stem cell-derived exosomes decreased serum levels of ALT and AST liver enzymes, decreased neutrophil to lymphocyte ratio (NLR), and improved kidney, liver, and lung tissue damage at 4, 6, and 24 h after model induction. At 24 h, the exosomes were able to reduce serum urea levels. This study revealed decreased levels of inflammatory cytokines such as IL-6, IL-1ß, and TNF-α after exosome injection. CONCLUSION: Our findings suggest that treating mice with stem cell-derived exosomes can ameliorate the destructive effects of inflammation caused by sepsis by reducing inflammatory factors and tissue damage.

Exosome-mediated miR-33 transfer induces M1 polarization in mouse macrophages and exerts antitumor effect in 4T1 breast cancer cell line.

Macrophages are the most abundant tumor-infiltrating immune cells. Macrophages are conventionally classified as M1 or M2 types. M2 type is the dominant phenotype of macrophages in the tumor microenvironment. M2 macrophages support different aspects of tumor development, including tumor formation, growth, and metastasis. MicroRNAs (miRNAs) have been demonstrated to regulate numerous cellular processes, including macrophage polarization. To determine whether miR-33 containing exosomes can alter macrophage polarization, we used the exosomes isolated from 4T1 breast cancer cells to deliver miR-33 mimic into IL-4 induced M2 macrophages and treated macrophages with 4T1-conditioned media. Then, we assayed the expression of M1 specific markers and the production of cytokines using real-time PCR and ELISA, respectively. Additionally, we performed MTT, migration, and invasion assays to detect the effect of miRNA-mediated macrophage repolarization on cancer cell proliferation, migration, and invasion. The results of this study showed that miR-33 containing exosomes could convert M2 to M1 phenotype as indicated by an increase in expression of M1 markers, including Irf5, Nos2, and CD86, and a decrease in M2 markers including Arg, Ym1, and CD206. Furthermore, the secretion of TNF-α and IL-1ß as M1 specific cytokines increased, while the secretion of IL-10 and TGF-ß as M2 specific cytokines decreased. Incubation of 4T1 cells with conditioned media of treated macrophages showed reduced proliferation, invasion, and migration of these cells. So, our data suggests that exosomes can be used as an efficient nanocarrier for miR-33 delivery into macrophages. Also, miR-33 is capable of inducing M1 polarization in macrophages, which is essential for suppressing tumor growth and metastasis.

Effect of COVID-19 pandemic on medical waste management: a case study.

Covid-19 Pandemic leads to medical services for the society all over the world. The Covid-19 pandemic influence the waste management and specially medical waste management. In this study, the effect of the Covid-19 outbreak on medical waste was evaluated via assessing the solid waste generation, composition, and management status in five hospitals in Iran. The results indicated that the epidemic Covid-19 leads to increased waste generation on average 102.2 % in both private and public hospitals. In addition, the ratio of infectious waste in the studied hospitals increased by an average of 9 % in medical waste composition and 121 % compared with before COVID-19 pandemic. Changes in plans and management measurement such as increasing the frequency of waste collection per week leads to lower the risk of infection transmission from medical waste in the studied hospitals. The results obtained from the present research clearly show the changes in medical waste generation and waste composition within pandemic Covid-19. In addition, established new ward, Covid-19 ward with high-infected waste led to new challenges which should be managed properly by change in routine activities.

Application of ultrasound irradiation in landfill leachate treatment.

Landfilling is known to be the most widely used method in municipal solid waste management in many countries. Landfill leachate containing different recalcitrant compounds are recognized to contaminate the soil and water and accordingly threat both the human health and environment. A variety of chemical and biological methods have recently been employed for landfill leachate treatment, one of which is the ultrasonic process. In this review, the efficiency of the ultrasound-assisted method for leachate treatment, factors influencing the treatment process are studied by defining a search protocol. The results showed that ultrasound can reduce pollutants by creating cavitation, microstreaming, and microturbulence. Increasing turbidity in initial of irradiation time and increasing the cost of treatment are the disadvantages of using ultrasonic in leachate treatment. Moreover, ultrasound-assisted method leads to improve the leachate quality, especially the COD/BOD. Therefore, ultrasound can be considered a good pretreatment for biological processes. Although, the application of this process in combination with other treatment processes such as biological processes and advanced oxidation increases the efficiency of leachate treatment, its efficiency depends on several factors such as exploitation features and leachate quality.

Synergistic therapeutic effect of mesenchymal stem cells and tolerogenic dendritic cells in an acute colitis mouse model.

Cell-based therapy with tolerizing cells has been applied for the treatment of inflammatory bowel disease (IBD) in previous experimental and clinical studies with promising results. In the current study, we utilized the dextran sulfate sodium (DSS)-induced colitis model, to investigate if tolerogenic dendritic cell-mesenchymal stem cell (tDC-MSC) combination therapy can augment the therapeutic effects of single transplantation of each cell type. The effect of MSC and tDC co-transplantation on the severity of colitis was assessed by daily monitoring of body weight, stool consistency, and rectal bleeding, and compared with control groups. Moreover, the colon length, colon weight, myeloperoxidase (MPO) activity were measured and evaluated with histological analysis of colon tissues. The Treg cell percentage and cytokine levels in spleens and mesenteric lymph nodes (MLNs) were measured by flow cytometry and ELISA, respectively. The results showed co-transplantation of MSCs and tDCs was more effective in alleviating the clinical and histological manifestations of colitis than monotherapy, especially when compared with MSC alone. The protective effects of tDC-MSC were accompanied by the induction of Treg cells and increased the production of anti-inflammatory cytokines in spleens and mesenteric lymph nodes. Together, co-transplantation of MSCs and tDCs could be a promising and effective therapeutic approach in the treatment of IBD.

Assess the annual effective dose and contribute to risk of lung cancer caused by internal radon 222 in 22 regions of Tehran, Iran using geographic information system.

Radon gas is one of the most influential sources of indoor exposure. All its physical properties together make it a significant risk factor for lung cancer in the population. The research aims are outlined as (1) to measure the radon concentration in Tehran city and compare results with the international standards (2) to determine spatial distribution of radon gas concentration using Geographical Information System (GIS) software and (3) to estimate the annual effective dose and potential risk of lung cancer by radon-222 in Tehran city. In this study, 800 Alpha Track detectors were installed in houses in 22 regions of Tehran city and retrieved after 3 months. The measurements were repeated for spring and summer and autumn seasons. The annual effective dose and risk of lung cancer were assessed using standard equations. Data were analyzed using SPSS 20. Result showed the minimum and maximum radon concentration were observed in and Ghalee-kobra (0.13 Bq.m-3) and Charbagh-ponak district (661.11 Bq.m-3) respectively. There was no observed relationship between radon concentration and houses' model, cracking condition and constructionn materials. Expectedly, the storehouses and basements had significantly higher (P = 0.016) radon concentration than occupied rooms. The min and max of the estimated annual effective dose were 0.65 and 2.03 mSv, respectively. Result showed that around 5% of the sampling sites had higher level of radon than the maximum allowed by EPA. A rough estimation of the expected radon-attributed lung cancer incidences yielded approximately 5958 cases in the total population of Tehran every year. In view of the growing trend in cancer incidences, appropriate measures addressing radon should be undertaken in areas of increased exposure to this noble gas.