Eye-Related Adverse Events After I-131 Radioiodine Therapy: A Systematic Review of the Current Literature.

OBJECTIVE: Although I-131 is relatively safe, there is limited focus on probable eye-related side effects after radioactive iodine (RAI) therapy. Thus, we aimed to provide evidence for the adverse outcomes of I-131, exclusively in patients with thyroid cancer. METHODS: A systematic review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was designed to examine the ocular complications of RAI therapy. Databases including PubMed, Scopus, and Web of Science were searched until October 2023 with specific thyroid neoplasms, ophthalmology and iodine terms. After thorough screening and review, relevant data were extracted. RESULTS: The database search yielded 3434 articles, which resulted in the final 28 eligible studies. These studies investigated ophthalmic symptoms following RAI therapy, classifying them as obstructive diseases (for example, nasolacrimal duct obstruction; median incidence rate: 6.8%), inflammatory symptoms (median incidence rate: 13%), and cataracts (median incidence rate: 2.5 and 5%). The most common time interval between RAI therapy and the onset of symptoms was within the first 12 months and then declined in the preceding years. A strong positive correlation was observed between higher I-131 doses of more than 100 to 150 mCi (3.7-5.55 GBq) and the risk of symptom development. Ages older than 45 also showed a significant association with nasolacrimal duct obstruction. CONCLUSION: The risk of ophthalmic complications is associated with various factors, including the administration of high I-131 doses, age of more than 45 years, and time to event within the first 12 months. Considering these conditions may help enhance patient care and prevent adverse outcomes that may limit patients' quality of life.

The effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy in type II diabetes mellitus patients: A clinical trial.

INTRODUCTION: Diabetic retinopathy (DR) is one of the most threatening complications of diabetes and a leading cause of visual loss in working-age population. Although exercise is beneficial in diabetes, previous studies have showed contradictory and inconclusive results on how it effects DR. In this study, we aimed to investigate the effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy. MATERIALS & METHODS: In this before-after clinical trial, 40 patients with diabetic retinopathy were enrolled by convenient sampling method in Shahid Labbafinejad Hospital in Tehran during 2021-2022. Before the intervention, central macular thickness (CMT, microns) measured by optical coherence tomography (OCT) and fasting blood sugar (FBS, mg/dl) were obtained. Then, patients took part in a 12-week moderate-intensity aerobic exercise (3 sessions per week, each session 45 min). Data were analyzed using SPSS version 26.0. RESULTS: Out of 40 examined patients, 21 (52.5 %) were male and 19 (47.5 %) were female. The mean age of the patients was 50.8 years. The mean rank of FBS (mg/dl) significantly decreased from 21.12 before the exercise to 8.75 after the exercise (p < 0.001). Also, the mean rank of CMT (microns) showed a significant decrease from 21.11 before the intervention to 16.20 after the exercise (p < 0.001). There was a significant positive correlation between patients' age and FBS (mg/dl) before (rho = 0.457, p = 0.003) and after (rho = 0.365, p = 0.021) the intervention. Also, a significant positive correlation was found between patients' age and CMT (microns) before (rho = 0.525, p = 0.001) and after (rho = 0.461, p = 0.003) moderate exercise. CONCLUSION: Moderate-intensity aerobic exercise leads to lower FBS (mg/dl) and CMT (microns) in patients with diabetic retinopathy, so it may be beneficial for diabetic patients to avoid sedentary lifestyle.

Antileishmanial effects and drugability characteristics of a heterocyclic copper complex: An in silico, in vitro and molecular study.

Leishmaniasis caused by the protozoan Leishmania presents a severe illness, principally in tropical and subtropical areas. Antileishmanial metal complexes, like Glucantime®ï¸ with proven activity, are routinely studied to probe their potency. We investigated the effects of a Cu (II) homoleptic complex coordinated by two dimethyl-bipyridine ligands against Leishmania major stages in silico and in vitro. The affinity of this heterocyclic Cu (II) complex (CuDMBP) towards a parasitic metacaspase was studied by molecular docking. Key pharmacokinetic and pharmacodynamic properties of the complex were predicted using three web-based tools. CuDMBP was tested for in vitro antileishmanial activities using MTT assay, model murine macrophages, flow cytometry, and quantitative real-time polymerase chain reaction (qPCR). Molecular docking confirmed the tendency between the target macromolecule and the complex. ADMET evaluations highlighted CuDMBP's key pharmacological features, including P-glycoprotein-associated GI absorption and lack of trans-BBB permeability. MTT showed significant inhibitory effects against promastigotes. CuDMBP significantly increased the level of cellular IL-12 expression (p < 0.05), while the upregulation observed in the expression of iNOS was considered not significant (p > 0.05). It decreased the expression of IL-10 significantly (p < 0.05). Findings demonstrated that CuDMBP deserves to be introduced as a leishmanicidal candidate provided further studies are carried out.

Association of interleukin 33 gene polymorphisms with susceptibility and regulation of inflammatory mediators in Systemic lupus erythematosus patients.

BACKGROUND: Studies have indicated the involvement of interleukin (IL)-33 in the pathogenesis of Systemic lupus erythematosus (SLE). This research intended to evaluate the association of IL33 gene rs1929992 and rs7044343 Single nucleotide polymorphisms (SNPs) with risk of SLE. In addition, the association between these SNPs and inflammatory cytokines was determined. METHODS: In this study, 200 SLE cases and 200 healthy subjects were recruited. Using allelic discrimination Real-time PCR, IL33 gene rs1929992 and rs7044343 SNPs were genotyped. The mRNA expression levels of IL-1ß, IL-6, IL-33, TNF-α were determined in the peripheral blood mononuclear cells (PBMCs). The serum levels of cytokines were also measured. RESULTS: The G allele (OR = 1.57, CI: 1.18-2.08, P = 0.0017), GG genotype (OR = 2.52, CI: 1.33-4.77, P = 0.0043), and GA genotype (OR = 2.12, CI: 1.34-3.34, P = 0.0011) of rs1929992 SNP was significantly associated with an increased SLE risk. The C allele (OR = 1.44, CI: 1.08-1.90; P = 0.0105), CC genotype (OR = 2.07, CI: 1.15-3.71; P = 0.0146), and CT genotype (OR = 1.61, CI: 1.02-2.53, P = 0.0395) of rs7044343 was significantly associated with increased SLE risk. The PBMC mRNA expression and serum levels of IL-1ß, IL-6, IL-33, TNF-α were significantly increased in the SLE patients compared to controls. However, there was no significant difference in the mRNA expression and serum levels of IL-1ß, IL-6, IL-33, and TNF-α among the SLE patients with three genotypes for both rs1929992 and rs7044343 polymorphisms. CONCLUSIONS: IL33 gene rs1929992 and rs7044343 SNPs are involved in SLE pathogenesis but they might not influence on the inflammatory pathway.

The modulatory effects of exercise on lipopolysaccharide-induced lung inflammation and injury: A systemic review.

Recent studies have shown that proper exercise significantly restricts inflammatory responses through regulation of the immune system. This review discusses mechanisms of protective effects of exercise in lipopolysaccharide (LPS)-induced lung injury. We performed a systematic search in PubMed, Scopus, and Web of Sciences using the search components "physical exercise", "lung" and "LPS" to identify preclinical studies, which assessed physical activity effects on LPS-induced pulmonary injury. Articles (n = 1240) were screened and those that had the eligibility criteria were selected for data extraction and critical appraisal. In all of the 21 rodent-model studies included, pulmonary inflammation was induced by LPS. Exercise protocols included low and moderate intensity treadmill training and swimming. The results showed that aerobic exercise would prevent LPS-induced oxidative stress and inflammation as well as airways resistance, exhaled nitric oxide, protein leakage, increase in total WBC, macrophage and neutrophil population, levels of interleukin (IL)-6, IL-1ß, IL-17, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor and CXCL1/KC, and improved IL-10 and IL-ra in lung tissue, bronchoalveolar lavage fluid (BALF) and serum. In addition, in trained animals, the expression of some anti-inflammatory factors such as heat shock protein72, IL-10, triggering receptor expressed on myeloid cells-2 and irisin was increased, thus ameliorating lung injury complications. Aerobic exercise was shown to alleviate the LPS-induced lung injury in rodent models by suppressing oxidative stress and lowering the ratio of pro-inflammatory to anti-inflammatory cytokines.

Survival Rates and Prognostic Factors in Patients with Coronavirus Disease 2019: A Registry-Based Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a newly identified coronavirus. Our knowledge about the survival rate and prognostic factors of the disease is not established well. Therefore, this study aimed to identify the risk factors associated with the survival of COVID-19 cases in Hamadan province, West of Iran. STUDY DESIGN: A retrospective cohort study METHODS: This retrospective cohort study was performed in Hamadan province, West of Iran. The study included patients that referred to the provincial hospitals from February 20 to September 20, 2020. The follow-up of each subject was calculated from the date of onset of respiratory symptoms to the date of death. Demographic and clinical characteristics were extracted from patients' medical records. Kaplan-Meier method, Flemington-Harrington test, and Cox regression were used for data analysis. RESULTS: The overall 1, 5, 10, 20, 30 and 49-day survival rates were estimated at 99.57%, 95.61%, 91.15%, 87.34%, 86.91%, and 86.74%, respectively. Furthermore, survival time showed a significant association with age, gender, history of traveling to contaminated areas, co-morbidity, neoplasms, chronic diseases, and hospital units. CONCLUSION: In conclusion, elderly people, male gender, and comorbidities presented a greater risk of death. Therefore, it is important to pay more attention to this group of people to reduce the incidence and consequences after infection.

Evaluation of Apoptotic Gene Expression in Hepatoma Cell Line (HepG2) Following Nisin Treatment.

OBJECTIVE: The present study aims to examine the effects of nisin on the survival and apoptosis of the hepatoma cell line HepG2 and to investigate possible apoptosis pathways activated by nisin. MATERIALS AND METHODS: For this purpose, viability and apoptosis of the cells were accomplished by the nisin treatment using the MTT assay and Annexin-V-fluorescein/propidium iodide (PI) double staining, respectively. Additionally, the human apoptosis PCR array was performed to determine pathways or genes activated by nisin during possible apoptosis. RESULTS: The results of the present study showed that nisin was able to decrease cell viability (IC50 ~ 40 µg/ml) in a dose-dependent manner and could induce apoptosis in HepG2 cells. PCR data indicated a considerable increase in the expression of genes, such as caspase and BCL2 families, involved in the induction of apoptosis. CONCLUSIONS: The data from this study showed that overexpression of genes involved in the intrinsic pathway of apoptosis, especially caspase-9 and BID, increased apoptosis in HepG2 cells treated by nisin, compared to the control group.

Identifying risk factors for late HIV diagnosis and survival analysis of people living with HIV/AIDS in Iran (1987-2016).

BACKGROUND: Late-diagnosis of HIV is a major challenge for the control and prevention of AIDS in the world. The present study aimed to specify factors associated with the late diagnosis of HIV in Iran from 1987 to 2016. METHODS: In this retrospective cohort study, data for 4402 diagnosed HIV/AIDS patients were extracted from 158 behavioral disease counseling centers of 31 Iranian provinces. We defined late diagnosis as having a CD4 count less than 350 within 3 months after diagnosis. Multiple logistic regression analysis was used to determine the factors influencing late diagnosis. Moreover, we used multivariate Cox regression to assess the association of these factors with the patients' survival. RESULTS: In this study, the prevalence of late diagnosis among the patients was 58.2%. People aged 50 years and over (adjusted OR = 3.55), transmission through blood transfusion (adjusted OR = 2.89), co-infection with tuberculosis (adjusted OR = 2.06), and male gender (adjusted OR = 1.38) were the strongest predictors for late diagnosis of HIV. On the other hand, baseline CD4 (adjusted HR = 2.21), people aged 50 and over (adjusted HR = 1.81), male gender (adjusted HR = 1.76), being a widow (adjusted HR = 1.68), people with unknown transmission way (adjusted HR = 18.24), people who inject drugs (adjusted HR = 1.87), diagnosis at previous years (adjusted HR = 2.45) and co-infection with tuberculosis (adjusted OR = 1.77) significantly associated with the survival of patients. CONCLUSION: The prevalence of late diagnosis is high among Iranian HIV/AIDS. The risk factors of late diagnoses include being males and aged 50 years and over, transmission through blood transfusion, and co-infection with tuberculosis. Therefore, implementation of screening programs for early diagnosis of HIV these high risk groups is recommended to Iranian health providers and policymakers.

Diosgenin and 4-Hydroxyisoleucine from Fenugreek Are Regulators of Genes Involved in Lipid Metabolism in The Human Colorectal Cancer Cell Line SW480.

OBJECTIVE: Diosignin and 4-hydroxy-L-isulosine (4-OH-Ile) are the two active ingredients of Fenugreek (Trigonella foenumgraecum). Thus, in this study, we examined the effects of hydroalcoholic extract of fenugreek seeds (HEFS), diosgenin and 4-OH-Ile on the expression of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), peroxisome proliferator-activated receptor gamma (PPARγ) and low-density lipoprotein (LDL) receptor (LDLR) which are involved in lipid metabolism in SW480 cell line. MATERIALS AND METHODS: In this experimental study, SW480 cells were cultured in RPMI-1640 medium and treated with HEFS, diosignin, 4-OH-Ile or orlistat for 24 and 48 hours. Inhibitory concentration of 20% (IC20) was calculated using MTT method and cells were then pre-treated with the IC20 concentrations for 24 and 48 hours before RNA extraction and cDNA synthesis. Changes in the expression of ACC, FAS, PPARγ and LDLR genes were assayed by employing the real time-polymerase chain reaction (PCR) method. RESULTS: Our results showed a significant down-regulation in the expression of ACC (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and FAS genes (P<0.001 and P<0.001 after 24 and 48 hours, respectively) in SW480 cells treated with HEFS, diosignin, 4-OH-Ile, or orlistat, but significant up-regulation in the expression of PPARγ (P<0.001 and P<0.001 after 24 and 48 hours, respectively) and LDLR (P=0.005 and P=0.001 after 24 and 48 hours, respectively). CONCLUSION: According to the results of the present study, HEFS, diosgenin and 4-OH-Ile up or down-regulate the expression of some predominant genes involved in lipid metabolism pathway, similar to that observed for orlistat. These types of regulatory effects are presumably proper for the treatment of obesity and overweight.

A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells.

Hydrophobin-1 (HFB-1) found on the surface of fungal spores, plays a role in the lack of antigen recognition by the host immune system. The present study aimed to evaluate the potential application of HFB-1 for the delivery of doxorubicin (Dox) into different cell lines. Coating the surface of niosomes (Nio) with HFB-1 leads to the hypothesis that this protein can confer protection against in vivo immune-system recognition and prevent the immune response. Thus, HFB-1 could become a promising alternative to polyethylene glycol (PEG). Here, HFB-1-coated niosome loaded with doxorubicin (Dox) based on Span 40, Tween 40 and cholesterol was prepared and compared with the PEG-coated niosome. Physicochemical characteristics of the prepared formulations in terms of size, zeta potential, polydispersity index (PDI), morphology, entrapment efficiency (EE), and release rate were evaluated at different pH levels (2, 5.2, and 7.4). In the end, the in vitro cytotoxicity assay was performed on four different cancer cell lines namely A549, MDA-MB-231, C6 and PC12 in addition to one control cell line (3 T3) to ensure the formulation's selectivity against cancer cells. Results showed that the niosomes coated with HFB-1 presented better size distribution, higher EE, more sustained release profile, enhanced biocompatibility and improved anticancer effects as compared to the PEG-coated niosomes. Interestingly, the viability percentage of the control cell line was higher than different cancer cells when treated with the formulations, which indicates the higher selectivity of the formulation against cancer cells. In conclusion, loading the niosomes with Dox and coating them with HFB-1 enhanced their efficacy and selectivity toward cancer cells, presenting a promising drug delivery system for sustained drug release in cancer treatment.

The effects of transplanted mesenchymal stem cells treated with 17-b estradiol on experimental autoimmune encephalomyelitis.

The present study was conducted aimed at exploring the modulatory effects of 17-b estradiol (17-bED) on mesenchymal stem cells (MSCs) in the EAE (experimental autoimmune encephalomyelitis) animal model of multiple sclerosis (MS). Following the isolation of bone marrow-derived MSCs from the bilateral femurs and tibias of the male Wistar rats, the cells were harvested and cultured in the presence of 100 nM 17-bED for 24 h. EAE was induced in male Wistar rats (8-12 weeks old) using guinea pig spinal cord homogenate, in combination with the complete Freund's adjuvant. The MSC therapy was triggered when all of the animals obtained a disability score. The symptoms were monitored on a daily basis throughout the study until the rats were euthanized. The mRNA expression of cytokines, including IL-17, IFN-γ, TNF-α, IL-10, IL-4, and TGF-ß together with MMP8 and MMP9 as the family members of matrix metalloproteinases (MMPs) in the brain and spinal cord tissues were examined using real-time PCR. The levels of splenocytes-originated IL-10 and IFN-γ cytokines were also measured by ELISA. The MTT-based research findings showed that the infiltration of lymphocytes into the spleen decreased considerably. It was also observed that the mRNA expression of proinflammatory cytokines decreased significantly, while the mRNA levels of anti-inflammatory cytokines increased remarkably. It was also found that the mRNA levels of the examined matrix metalloproteinases (MMP8 and MMP9) were downregulated significantly. The findings of the present study indicated that the administration of 17-bED enhanced the efficacy of MSCs transplantation and modulated immune responses relatively in the EAE model, via the regulation of either pro- or anti-inflammatory cytokines and matrix metalloproteinases.

The New Compound of (2R, 4S)-N-(2, 5-difluorophenyl)-4-Hydroxy-1-(2, 2, 2-Trifluoroacetyl) Pyrrolidine-2-Carboxamide to Mediate the Expression of Some Apoptosis Genes by the HepG2 Cell Line

Objectives: Hepatocellular carcinoma is one of the most frequent cancers worldwide, for the treatment of which various therapy protocols and drugs have been introduced; however, none of them has suppressed cancer tissues completely. New research programs have been developed on cancer and the accompanied effects of novel synthesized compounds on cancer cell lines. Our latest reports on the molecular basis of cancer revealed a pattern of changes in gene expression triggered in the cancer pathway. Methods: HepG2 cell lines were cultured under similar conditions in both test and control groups. The IC50 concentration of the (2R, 4S)-N-(2, 5-difluorophenyl)-4-hydroxy-1-(2, 2, 2-trifluoroacetyl) pyrrolidine-2-carboxamide compound was used in the treatment group. After 48 hours from the culture, the expressional profiles of apoptosis pathway genes (84 genes) were studied using the PCR array method. Results: The findings demonstrated that the expression of some apoptosis-related genes pertaining to TNF, BCL2, IAP, and caspase families was regulated by (2R, 4S)-N-(2, 5-difluorophenyl)-4-Hydroxy-1-(2, 2, 2-Trifluoroacetyl) Pyrrolidine-2-Carboxamide. In the same vein, an alteration was observed in the expression of both pro-apoptotic and anti-apoptotic genes associated with the extrinsic and intrinsic apoptosis signaling pathways. Conclusions: According to the data obtained, the pyrrolidine-2-carboxamide compound was demonstrated to be able to regulate the apoptotic activities of HepG2 cells by affecting both pro-apoptotic and anti-apoptotic relevant genes.

Evaluation of Carum-loaded Niosomes on Breast Cancer Cells:Physicochemical Properties, In Vitro Cytotoxicity, Flow Cytometric, DNA Fragmentation and Cell Migration Assay.

Thymoquinone (TQ), a phytochemical compound found in Carum carvil seeds (C. carvil), has a lot of applications in medical especially cancer therapy. However, TQ has a hydrophobic nature, and because of that, its solubility, permeability and its bioavailability in biological mediums are poor. To diminish these drawbacks, we have designed a herbal carrier composed of Ergosterol (herbal lipid), Carum carvil extract (Carum) and nonionic surfactants for herbal cancer treatment. C. carvil was extracted and characterized by GC/Mass. Two different formulations containing TQ and Carum were encapsulated into niosomes (Nio/TQ and Nio/Carum, respectively) and their properties were compared together. Morphology, size, zeta potential, encapsulation efficiency (EE%), profile release rate, in vitro cytotoxicity, flow cytometric, DNA fragmentation and cell migration assay of formulations were evaluated. Results show that both loaded formulations have a spherical morphology, nanometric size and negative zeta potential. EE% of TQ and Carum loaded niosomes was about 92.32% ± 2.32 and 86.25% ± 1.85, respectively. Both loaded formulations provided a controlled release compared with free TQ. MTT assay showed that loaded niosomes have more anti-cancer activity compared with Free TQ and free Carum against MCF-7 cancer cell line and these results were confirmed by flow cytometric analysis. Cell cycle analysis showed G2/M arrest in TQ, Nio/TQ and Nio/Carum formulations. TQ, Nio/TQ and Nio/Carum decreased the migration of MCF7 cells remarkedly. These results show that the TQ and Carum loaded niosomes are novel carriers with high efficiency for encapsulation of low soluble phytochemicals and also would be favourable systems for breast cancer treatment.

A novel copper (II) complex activated both extrinsic and intrinsic apoptotic pathways in liver cancerous cells.

Recent advances have put fundamental focus on the application of copper (II) (Cu [II]) complexes as agents for fighting against cancer. To determine whether [Cu(L)(2imi)] complex as a novel Cu complex can induce apoptosis in HepG2 as cancerous cells and L929 as normal cells via extrinsic or intrinsic apoptotic pathways, both cell lines were treated for 24 and 48 hours at IC50 concentrations of [Cu(L)(2imi)] complex. Then, the expression of some apoptosis-related genes including p53, caspase-8, bcl-2, and bax were assayed by real-time polymerase chain reaction. The [Cu(L)(2imi)] complex seems to inhibit the expression of bcl-2 in complex-treated HepG2 cancerous cells following the 24- and 48-hour treatment. The complex upregulated the p53, bax, and caspase-8 genes, therefore treatment of HepG2 cancerous cells with [Cu(L)(2imi)] complex induces programmed cell death via the upregulation of relative bax/bcl-2 ratio. Finally, this copper complex triggered apoptosis in HepG2 cells via both intrinsic and extrinsic pathway, whereas treatment of normal L929 cells with this complex induce apoptosis only via intrinsic pathway with the upregulation of relative bax/bcl-2 ratio and does not affect the expression level of caspase-8 gene and does not trigger the extrinsic pathway. Finally, these results obtained from present study confirm the role of a novel Cu complex on the induction of apoptosis process in HepG2 and L929 cells by overexpression of bax, inhibition of bcl-2 and increase of the relative bax/bcl-2 ratio. These results support that the [Cu(L)(2imi)] complex is able to induce apoptosis in cancerous cells, therefore, it has a potential for development as a novel anticancer drug.

Evaluating of Induction of Apoptosis by Cornus mass L. Extract in the Gastric Carcinoma Cell Line (AGS)

Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS and L929 cells were cultured and treated with different concentrations (0­10 mg/ml) of Cornus mass L. extract for 48 and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC50 value in AGS cells (evaluated after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometry indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.

Neuroprotective and antihyperalgesic effects of orexin-A in rats with painful diabetic neuropathy.

AIM OF STUDY: Diabetes mellitus is related to the development of neuronal tissue injury in different peripheral and central nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy (PDN). We have studied the neuroprotective and anti-nociceptive properties of neuropeptide orexin-A in an animal experimental model of diabetic neuropathy. METHODS: All experiments were carried out on male Wistar rats (220-250 g). Diabetes was induced by a single intraperitoneal injection of 55 mg/kg (i.p.) streptozotocin (STZ). Orexin-A was chronically administrated into the implanted intrathecal catheter (0.6, 2.5 and 5 nM/L, daily, 4 weeks). The tail-flick and rotarod treadmill tests were used to evaluate the nociceptive threshold and motor coordination of these diabetic rats, respectively. Cleaved caspase-3, Bax, Bcl2 and the Bax/Bcl-2 ratio, as the biochemical indicators of apoptosis, were investigated in the dorsal half of the lumbar spinal cord tissue by western blotting method. RESULTS: Treatment of the diabetic rats with orexin-A (5 nM/L) significantly attenuated the hyperalgesia and motor deficit in diabetic animals. Furthermore, orexin-A (5 nM/L) administration suppressed pro-apoptotic cleaved caspase-3 and Bax proteins. Also, orexin-A (5 nM/L) reduced the expression of Bax/Bcl-2 ratio in spinal cord dorsal half of rats with PDN. CONCLUSIONS: Altogether our data suggest that the orexin-A has anti-hyperalgesic and neuroprotective effects in rats with PDN. Cellular mechanisms underlying the observed effects may, at least partially, be related to reducing the neuronal apoptosis.

Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway.

Adipose derived mesenchymal stem cells (ASCs) transplantation is a novel immunomodulatory therapeutic tool to ameliorate the symptom of inflammatory bowel disease (IBD). The objective of this study was to investigate the therapeutic effects of combined sufasalazine and ASCs therapy in a rat model of IBD. After induction of colitis in rats, ASCs were cultured and intraperitoneally injected (3 × 106 cells/kg) into the rats on Days 1 and 5 after inducing colitis, in conjunction with daily oral administration of low dose of sulfasalazine (30 mg/kg). The regenerative effects of combination of ASCs and sulfasalazine on ulcerative colitis were assessed by measuring body weight, colonic weight/length ratio, disease activity index, macroscopic scores, histopathological examinations, cytokine, and inflammation markers profiles. In addition, western blot analysis was used to assess the levels of nuclear factor-kappa B (NF-κB) and apoptosis related proteins in colitis tissues. Simultaneous treatment with ASCs and sulfasalazine was associated with significant amelioration of disease activity index, macroscopic and microscopic colitis scores, as well as inhibition of the proinflammatory cytokines in trinitrobenzene sulfonic acid (TNBS)-induced colitis. Moreover, combined ASCs and sulfasalazine therapy effectively inhibited the NF-κB signaling pathway, reduced the expression of Bax and prevented the loss of Bcl-2 proteins in colon tissue of the rats with TNBS-induced colitis. Furthermore, combined treatment with ASCs and sulfasalazine shifted inflammatory M1 to anti-inflammatory M2 macrophages by decreasing the levels of MCP1, CXCL9 and increasing IL-10, Arg-1 levels. In conclusion, combination of ASCs with conventional IBD therapy is potentially a much more powerful strategy to slow the progression of colitis via reducing inflammatory and apoptotic markers than either therapy alone.

Comparison of the effects of 17ß- estradiol treated and untreated mesenchymal stem cells on ameliorating animal model of multiple sclerosis.

OBJECTIVES: The current investigation was undertaken to evaluate the effects of 17ß- estradiol (17ß-ED) on the potential of the mesenchymal stem cells (MSCs) for modulation of immunity responses in an animal model of multiple sclerosis (MS). MATERIALS AND METHODS: After isolation of MSCs, cells were cultured in presence of 100 nM 17ß-ED for 24 hr. Modeling of experimental autoimmune encephalomyelitis (EAE) was achieved by using guinea pig spinal cord homogenate, in addition to complete Freund's adjuvant in male Wistar rats. The processes of cell therapy were started following 12 days post-immunization. This duration allows all animals to develop a disability score. The achieved EAE clinical symptoms were regularly monitored every day until day 36, when all of examined rats were euthanized. RESULTS: Cell therapy in the EAE rats with 17ß-ED-primed MSCs exhibited more desirable consequences, which in turn lead to regression of the cumulative clinical score and neuropathological changes that are more than the therapy with untreated MSCs. The serum measures of myeloperoxidase (MPO), nitric oxide (NO) as well as splenocytes-originated pro-inflammatory interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) were significantly decreased in EAE rats treated by 17ß-ED primed-MSCs compared to EAE rats that received untreated MScs. CONCLUSION: Combination of 17ß-ED and MSCs more effectively improved the signs and symptoms of EAE.