Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 µg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

Spatial Cluster Analysis of Stomach Neoplasms in the Center of Iran Based on a Population-Based Study, 2009-2014: Application of the Poisson-Based Probability Model.

Background: A better understanding of the spatial pattern of stomach cancer can be helpful in the implementation of preventive strategies. This study is one of the first studies to establish a study unit based on the smallest possible size for cluster analysis. This study includes a novel evaluation of spatial differences in different geographical areas of Arak. The present study seeks to discover the spatial clusters of stomach cancer from 2009 to 2014 in Arak. Methods: All of the addresses of the stomach cancer cases were geocoded. After that, the number of stomach cancer cases in each census block was calculated to be entered in the SaTScan software. A discrete Poisson-based probability model was used to analyze this cluster. Results: In Arak, there are 5502 census blocks with a population of about 526,182. The number of identified and registered stomach cancer cases with an acceptable residence address was 392. Totally, 11 stomach cancer clusters were established in the area of Arak, from these; two clusters were detected statistically significant. Relative risks of the first and second clusters were 1.75 (P = 0.01) and 17.60 (P = 0.04) and those are located within the radius of 1.73 and 0.085 km, respectively. Conclusions: Our results have confirmed that two areas are at a higher risk than others. However, based on the results of this study, community-based interventions in certain geographical areas can be designed to reduce and control the incidence of stomach cancer.

Safety and effectiveness of enhanced external counterpulsation (EECP) in refractory angina patients: A systematic reviews and meta-analysis.

Enhanced external counterpulsation (EECP) is believed to be a non-invasive treatment for coronary artery disease and angina. The aim of this study was to determine the safety and effectiveness of EECP in refractory angina patients through a systematic reviews and meta-analysis. We conducted a comprehensive search of the literature published on PubMed, Cochrane library, Scopus, ScienceDirect, Trip Database and Google Scholar databases using appropriate keywords and specific strategy with no time limit. Having selected and screened the studies based on the defined inclusion and exclusion criteria and evaluating their quality based on the Cochrane checklist. For the meta-analysis,the Mantel-Haenszel method or the generic Inverse Variance was used. Analyses were done with Review Manager 5.2 software. A number of 299 studies were initially reviewed and finally, seventeen studies were included in the meta-analysis based on the inclusion and exclusion criteria. Also, thirteen outcomes were analyzed and the results of meta-analysis in twelve outcomes including (Systolic Blood Pressure (7 studies), Diastolic Blood Pressure (7 studies), Pulse Pressure (4 studies), Mean Arterial Pressures (4 studies), Heart Rate (6 studies), Angina episodes (7 studies), Walking distance (2 studies),Canadian Cardiovascular Society classification (6 studies), Flow-Mediated Dilation (3 studies), Daily Nitrate Usage (4 studies), Exercise Treadmill Test-Time (2 studies), ST-segment depression (2 studies)demonstrated a significant clinical advantage in the EECP treatment effectiveness in patients with angina. No significant difference was observed regarding EECP usefulness (P = 0.18) in the outcome of brachial artery diameter (2 studies). Based on the meta-analysis, the results indicate the safety and effectiveness of EECP in patients with angina pectoris and indicate the usefulness of this treatment in these patients. In general, the authors believe that the general conclusion in this regard requires some studies with a large sample size and a control group assignment.

Normative Data for the Balance Error Scoring System in Iranian Adults.

CONTEXT: The Balance Error Scoring System (BESS), originally designed to diagnose and assess athletes with concussion syndrome, is now widely used to evaluate postural stability. To interpret balance status, a normative database can be a reliable source. However, different anthropometric characteristics and sociocultural backgrounds across populations hinder the application of previously developed databases in different populations. OBJECTIVE: The present study was designed to develop a normative data set for the general population of healthy Iranian adults according to their age groups and to study the correlation between BESS scores and the participants' sex, height, weight, and body mass index. DESIGN: A cross-sectional study. PARTICIPANTS: A total of 1051 community-dwelling adults aged 20-69 years not suffering from balance disorders, dizziness, or other neurological or musculoskeletal diseases were recruited and stratified into 5 different age groups by decade. MAIN OUTCOME MEASURES: The BESS tests were composed of single-leg, double-leg, and tandem stances, each on a rigid surface and a foam pad. The individuals maintained each position for 20 seconds with eyes closed. The assessor recorded the total number of errors as the individuals' BESS score (range: 0-60). RESULTS: Significant but weak correlations were found between BESS score and height (r = -.13, P < .001) and between BESS score and body mass index (r = .11, P < .001), and the difference between sexes in BESS score was statistically significant in the 50- to 59-year-old (P = .021) and 60- to 69-year-old (P < .001) groups. The BESS scores were significantly different between all age groups (P < .05), except between the 20- to 29-year-old and 30- to 39-year-old groups (P = 1.000) and between the 40- to 49-year-old and 50- to 59-year-old groups (P = .086). CONCLUSIONS: This study provided a normative database for different age groups of asymptomatic Iranian adults. The BESS score had weak correlations with height and body mass index and no correlation with weight, and significant differences were found between sexes in 50- to 69-year-old individuals. This study emphasizes the importance of obtaining specific normative data for different populations.

Effectiveness of Low-Level Laser Therapy compared to Ultrasound in Patients With Carpal Tunnel Syndrome: A Systematic Review and Meta-analysis.

Introduction: Carpal tunnel syndrome (CTS) is the most common type of peripheral entrapment neuropathy that occurs in the wrist area in a space called the carpal tunnel. Low-level laser therapy (LLLT) and ultrasound are among the most common methods of physical modalities for treating CTS; the effectiveness of these 2 methods and the superiority of one over the other are not agreed among experts. Methods: In the present systematic review and meta-analysis study, the most important databases including PubMed, Cochrane Library, Scopus, Centre for Reviews and Dissemination, Science Direct, Trip medical database and Google Scholar were searched using appropriate keywords and specific strategies without time limitation to collect data. The collected data was analyzed using the meta-analytic method and the random-effects model. The heterogeneity among studies was examined using I2 . The data were analyzed using Review Manager Software. Results: From among 108 related studies, 49 cases were entered for the first stage. After the final examination, 6 studies were selected for meta-analysis. The total number of patients in these 6 studies was 403; 204 subjects were in the LLLT group and 199 subjects were in the ultrasound group. The results of the meta-analyses showed that there was no significant difference between these 2 therapeutic methods in terms of pain relief, symptom severity scale (SSS), functional status scale (FSS), motor latency, sensory latency, hand grip strength, and motor amplitude. Conclusion: Based on the meta-analyses, there was no significant difference between the 2 LLLT and ultrasound methods; in other words, they had similar effectiveness in improving the condition of patients with CTS. However, the authors believe that arriving at conclusions in this area requires high-quality and large size studies.

Safety and Effectiveness of Low-Level Laser Therapy in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Introduction: Low-level laser therapy (LLLT) was introduced as an alternative non-invasive treatment for osteoarthritis, but its effectiveness is still controversial. The main objective of this article was to determine the safety and efficacy of LLLT in patients with knee osteoarthritis (KOA). Methods: In order to gather evidence, main medical databases as well as relevant websites were browsed without time limit. We searched with appropriate keywords and strategies. After quality assessment of studies, study data were extracted by two reviewers. Standard mean difference proposed through inverse variance was used in the meta-analysis using the random-effects model. Twelve values were used for the evaluation of heterogeneity. Results: A total of 823 studies, 14 randomized controlled trials (RCTs) were selected after final review. There was a significant difference between LLLT and placebo in pain at rest (P=0.02), pain at activity (P=0.01), total pain (P=0.03), WOMAC function (P=0.01), WOMAC stiffness (P=0.02) and WOMAC total (P<0.0001) in favor of the LLLT. There was no significant difference between LLLT and Placebo in WOMAC pain (P=0.09) and range of motion (P=0.1). Conclusion: In spite of some positive findings, this meta-analysis lacked data on how LLLT effectiveness is affected with important factors: wavelength, energy density, treatment duration, numbers of sessions the treatment, severity of KOA and site of application.

The Effect of Transcutaneous Electrical Nerve Stimulation of Sympathetic Ganglions and Acupuncture Points on Distal Blood Flow.

Transcutaneous electrical nerve stimulation (TENS) is a widely-practiced method to increase blood flow in clinical practice. The best location for stimulation to achieve optimal blood flow has not yet been determined. We compared the effect of TENS application at sympathetic ganglions and acupuncture points on blood flow in the foot of healthy individuals. Seventy-five healthy individuals were randomly assigned to three groups. The first group received cutaneous electrical stimulation at the thoracolumbar sympathetic ganglions. The second group received stimulation at acupuncture points. The third group received stimulation in the mid-calf area as a control group. Blood flow was recorded at time zero as baseline and every 3 minutes after baseline during stimulation, with a laser Doppler flow-meter. Individuals who received sympathetic ganglion stimulation showed significantly greater blood flow than those receiving acupuncture point stimulation or those in the control group (p<0.001). Data analysis revealed that blood flow at different times during stimulation increased significantly from time zero in each group. Therefore, the application of low-frequency TENS at the thoracolumbar sympathetic ganglions was more effective in increasing peripheral blood circulation than stimulation at acupuncture points.

Degarelix for the treatment of advanced prostate cancer compared with GnRh-Agonists: a systematic review and meta-analysis.

BACKGROUND: Hormone therapy is currently the mainstay in the management of locally advanced and metastatic prostate cancer. We performed a systematic review to compare safety, efficacy and effectiveness of degarelix, a new gonadotropin-releasing hormone (GnRH) antagonist (blocker), versus gonadotropin-releasing hormone (GnRH) agonists. METHODS: MEDLINE, Web of Science and the Cochrane library were searched to identify all of the published Randomized Controlled Trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists with or without anti-androgen therapy for the treatment of prostate cancer. We performed meta-analysis of extracted data on safety and efficacy of the target medication. RESULTS: Six studies were included. They involved a total of 2296 patients which were used in the meta-analysis. Follow-up times after treatment were between 12 weeks and 12 months. Three of six RCTs compared degarelix with goserelin and the others compared it with leuprolide. Meta-analysis on safety outcomes revealed that the only statistically significant difference between the degarelix treated group and GnRH agonists treated group was complication in the injection site which was higher in degarelix-treated group (OR= 46.34, 95% CI: 15.79 to 136, p<0.001). Although general mortality rate was lower in degarelix-treated group (OR= 2.06, 95% CI: 1.08 to 3.93, p=0.03); mortality due to the drug side effects was not different. Meta-analysis of efficacy data also showed that International Prostate Symptom Score (IPSS) reduction at week 12, (MD=-1.85, 95% CI: -2.97 to - 0.72, p=0.001) and Testosterone reduction between day 1-28, (OR=11.58, 95% CI: 5.77 to 23.22, p<0.001) was statistically higher in degarelix-treated group. Testosterone reduction after day 28 and prostate volume reduction did not have significant difference. CONCLUSION: Our meta-analysis indicates that, compared with GnRH agonists, degarelix has significantly more effects on lower urinary tract symptoms and also Prostate Specific Antigen (PSA) and testosterone reduction in the first month of the treatment. Except minor complications in the injection site like pain, erythema and swelling, there is no increase in major side effects and mortality due to degarelix. This is while the effect on testosterone and PSA after the first month of treatment is not statistically different between the two groups.

Derivation of Adipocytes from Human Endometrial Stem Cells (EnSCs).

BACKGROUND: Due to increasing clinical demand for adipose tissue, a suitable cell for reconstructive adipose tissue constructs is needed. In this study, we investigated the ability of Human Endometrial-derived stem cells (EnSCs) as a new source of mesenchymal stem cells to differentiate into adipocytes. EnSCs are the abundant and easy available source with no immunological response, for cell replacement therapy. METHODS: Single-cell suspensions of EnSCs were obtained from endometrial tissues from 10 women experiencing normal menstrual cycles, and were cultured at clonal density (10 cells/cm (2) ) or limiting dilution. Endometrial mesenchymal stem cell markers were examined flow cytometry. These cells were treated with adipogenic-inducing medium for 28 days. The adipogenic differentiation of the EnSC was assessed by cellular morphology and further confirmed by Oil Red O staining and RT-PCR. The BM-MSC differentiated into adipocytes in the presence of adipogenic stimuli for 3 weeks. RESULTS: The flow cytometric analysis showed that the cells were positive for CD90, CD105, CD146 and were negative for CD31, CD34.We showed that the key adipocytes marker PPARa was expressed in mRNA level after 28 days post treatment (PT). CONCLUSION: According to our finding, it can be concluded that EnSCs represent a useful in vitro model for human adipogenesis, and provide opportunities to study the stages prior to commitment to the adipocyte lineage.

Functionalization of carboxylated multiwall nanotubes with imidazole derivatives and their toxicity investigations.

Imidazoles and their derivatives are compounds with chemotherapeutic applications. In this study, we investigated the chemical functionalization of carboxylated multiwalled carbon nanotubes (MWNT-COOH) by 1,2-phenylendiamine. Multiwalled nanotube (MWNT)-benzimidazole was obtained by an MWNT-amide reaction with POCl(3) after 72 hours, which was confirmed by Fourier transform infrared, scanning electron microscopy, thermal gravimetric analysis, and elemental analysis. These functionalizations were chosen due to -NH(2) and NHCO active sites in MWNT-amide for future application. Toxicity assays with fibroblast cells and MTT test for measurement of viable cell numbers were also performed. Cellular results did not show any toxicity change in modified samples from that of the reference samples.

Types of neural guides and using nanotechnology for peripheral nerve reconstruction.

Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed.