Scaphoid Bone Nonunions: Clinical and Functional Outcomes of Collagen/PGA Scaffolds and Cell-Based Therapy.

In this study, the procedure for treating the nonunion complication of scaphoid fractures using collagen/poly glycolic acid (CPGA) scaffolds with bone marrow mesenchymal stem cell (BM-MSC) therapy was adopted and compared with the commonly employed autologous bone tissue graft. With conducting a two-armed clinical trial, 10 patients with scaphoid nonunions were enrolled in this investigation. Patients were randomly assigned to two groups treated with (1) CPGA + cell therapy and (2) autologous iliac crest bone graft standard therapy. Treatment outcomes were evaluated three months after surgery, measuring the grip and pinch strengths and wrist range of motion, with two questionnaires: Patient-Rated Wrist Evaluation (PRWE) and Quick form of Disabilities of the Arm, Shoulder, and Hand (QDASH). We have also assessed the union rate using clinical and radiologic healing criteria one and three months post-operatively. Restorative effects of CPGA + cell therapy were similar to those of the autologous bone graft standard therapy, except for the grip strength (P = 0.048) and QDASH score (P = 0.044) changes, which were higher in the CPGA + cell therapy group. Three months following the surgery, radiographic images and computed tomography (CT) scans also demonstrated that the scaphoid union rate in the test group was comparable to that of scaphoids treated with the standard autograft method. Our findings demonstrate that the CPGA + cell therapy is a potential alternative for bone grafting in the treatment of bone nonunions.

High-density lipoprotein lipid peroxidation as a diagnostics biomarker in coronary artery disease.

This study aimed at evaluating the serum High-density lipoprotein lipid peroxidation (HDLox) levels and their association with coronary artery disease (CAD). This case-control study comprised 572 patients with stable CAD and 281 healthy subjects with no history of cardiovascular disease (control group). Based on the results of coronary angiography, the patient group was divided into two groups: CAD- and CAD+. HDLox was measured using a fluorimetric method. The ability of HDLox and serum high-density lipoprotein cholesterol (HDL-C) to detect CAD and coronary artery stenosis ≥50% was also compared using the receiver operating characteristic (ROC) curve analysis. The CAD patients showed significantly higher serum HDLox levels, compared to the control group [1.15 (1.01-1.31) vs. 0.85 (0.62-1.06), no units, p < 0.001]. Moreover, serum HDLox levels were significantly lower in CAD- patients, compared to the CAD+ patients [1.05 (0.92-1.22) vs. 1.24 (1.12-1.35), no units, p < 0.001]. According to the results of univariate and multivariate logistic regression, the HDLox showed association with the presence of CAD (odds ratio [OR]: 1.754; 95% confidence interval [CI]: 1.564-1.968; p < 0.001) and coronary artery stenosis ≥50% (OR: 1.729; 95% CI: 1.534-1.949; p < 0.001). The results obtained from the area under the ROC curve revealed that the HDLox could better detect the risk of CAD and coronary artery stenosis ≥50% compared to serum HDL-C level. The oxidation of HDL leads to a reduction in its antioxidant function and it has a crucial role in the development of atherosclerosis. HDLox is suggested as a diagnostics biomarker for CAD.

Harnessing CRISPR/Cas9 technology in cardiovascular disease.

The CRISPR/Cas9 system is a precisely targeted bacterial defense system, used to control invading viruses. This technology has many potential applications including genetic changes in somatic and germ cells and the creation of knockout animals. Compared to other genome editing techniques such as zinc-finger nucleases and transcription activator-like effector nucleases (TALENS), the CRISPR/Cas9 system is much easier and more efficient. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. The CRISPR/Cas9 system also potentially has the ability to prevent and treat human diseases. The present article addresses some key points related to the use of the CRISPR/Cas9 system as a powerful tool in cardiovascular research and as a new strategy for the treatment of cardiovascular disease (CVD).

Prevalence of combined and noncombined dyslipidemia in an Iranian population.

BACKGROUND: Combination of dyslipidemic phenotypes, including elevated plasma levels of low-density lipoprotein cholesterol (LDL-C), elevated plasma triglycerides (TG), and decreased low-density lipoprotein cholesterol (HDL-C) concentrations, is important because of the association of individual phenotypes with increased risk of cardiovascular disease (CVD). We investigated the prevalence of combined dyslipidemias and their effects on CVD risk in an Iranian large population. METHOD: A total of 9847 individuals were recruited as part of the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. Anthropometric parameters and biochemical indices were measured in all of the subjects. Different types of combined dyslipidemias including high TG + low HDL-C, high TG + low HDL-C + high LDL-C, low HDL-C + high LDL-C, high TG + high LDL-C, and finally high TG + high LDL-C + low HDL-C were considered. Ten-year CVD risk was calculated using the QRISK2 risk algorithm and adjustments were made as suggested by the Joint British Societies' (JBS2). Logistic regression analyses were performed to determine the association between different combined dyslipidemias and categorical QRISK. RESULTS: A total of 3952 males and 5895 females were included in this current study. Among the included subjects, 83.4% had one form of dyslipidemia, and 16.6% subjects were not dyslipidemic. The mean age was 48.88 ± 7.9 and 47.02 ± 8.54 years for dyslipidemic and nondyslipidemic groups, respectively. The results showed that the frequency of dyslipidemia was 98%, 87.1%, and 90% in subjects with metabolic syndrome, CVD, and diabetes, respectively. Our results suggested that around 15.7% of study population were at 10 years CVD risk (high ≥20) and it was higher in men than women (P < .001). Moreover, risk of CVD was higher in TG↑ & HDL↓ & LDL↑ group than other groups. CONCLUSION: Prevalence of dyslipidemia was 83.4% among Iranian adults. The results showed that individuals with increased plasma TG and LDL-C, and low HDL-C levels had the highest 10 years CVD risk compared to other combined dyslipidemic phenotypes.

Evaluation of the effects of Iranian propolis on the severity of post operational-induced peritoneal adhesion in rats.

BACKGROUND: Peritoneal adhesion is a major complication of surgery that can lead to serious problems such as bowel obstruction, pain, infertility and even mortality. Propolis is a honey bee product with anti-inflammatory and anti-oxidant activities that could potentially protect against adhesive surgical complications. METHODS: Forty 8-weeks-old rats (275 ±â€¯25 g) were divided into five groups: normal group without any surgical procedure, and experimental groups treated with normal saline, 50 mg/kg, 100 mg/kg and 200 mg/kg of propolis. Peritoneal adhesions were examined macroscopically and also, the levels of inflammatory factors (IL-6, IL-1ß and TNF-α), growth factors (TGF-ß1 and VEGF) were evaluated in the study groups using ELISA. Biochemical indices of oxidative status including Nitric Oxide (NO), Malondialdehyde (MDA) and Glutathione (GSH) were also measured. RESULTS: Peritoneal adhesion scores, IL-1ß, IL-6, TNF-α, TGF-ß1, VEGF, NO, GSH and MDA levels were significantly different between the study groups (p < 0.001). Propolis treatment reduced peritoneal adhesion (p < 0.001), TNF-α (p < 0.001), IL-1ß (p < 0.001), IL-6 (p < 0.001), TGF-ß1 (p < 0.001), VEGF (p < 0.001), NO (p < 0.001) and MDA (p < 0.001), while GSH levels were increased (p < 0.001) compared with the vehicle group. Our results showed that higher dose of propolis was associated with significantly greater reductions in peritoneal adhesion (p < 0.001), TNF-α (p < 0.001), IL-1ß (p < 0.001), IL-6 (p < 0.001), VEGF (p < 0.001), NO (p < 0.001) and MDA (p < 0.001), a greater increase in GSH levels (p < 0.001) compared with the lower dose. CONCLUSIONS: Propolis treatment can dose-dependently reduce peritoneal adhesion through its anti-inflammatory, anti-angiogenic and antioxidant properties. Therefore, propolis might serve as a protective agent against post-surgical adhesive complications.

ß-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances.

BACKGROUND: Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of ß-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells. MATERIALS AND METHODS: Cytotoxicity of ß-Amyrin (3-100) µM on microglial cells was evaluated using the MTT assay. Also, the protective effect of various ß-Amyrin (2-16 µM) concentrations with LPS/IFN-γ-induced mice microglial cells was studied. The concentrations of TNF-α (Tumor Necrosis Factor-α), IL-1ß (Interleukin-1ß), IL-6 (Interleukin-6) and PGE-2 (Prostaglandin E2) were evaluated using ELISA. Gene expressions of TNF-α, IL-1ß, IL-6, COX-2 (Cyclooxygenase-2), iNOS and arginase-1 were also evaluated using the Real-Time PCR method. Nitrite oxide and urea were measured using biochemical methods. RESULTS: The studied concentrations ​​of ß-Amyrin had no significant effects on the viability of microglial cells. Interestingly, ß-Amyrin concentration dependently and significantly increased the reduced cell proliferation concerning to LPS/IFN-γ exposure (p < 0.001). The concentrations and expression levels of pro-inflammatory factors including TNF-α, IL-1ß, IL-6, PGE-2, COX-2 were significantly reduced after ß-Amyrin treatment in LPS/IFN-γ-induced microglial cells (p < 0.05-0.001). ß-Amyrin also decreased the levels of nitric oxide, increased urea and down regulated the expression of nitric oxide synthesis while arginase-1 expression was enhanced (p < 0.001). The ratio of NO/urea and iNOS/Arg1 were also markedly increased in comparison to the LPS/IFN-g group (p < 0.001). CONCLUSION: ß-Amyrin reduces inflammation in microglial cells and can be used as a potential anti-inflammatory agent in central nervous system neurodegenerative diseases such as Alzheimer and multiple sclerosis, by affecting the inflammatory cytokine and differentiation of microglia as resident CNS macrophages.

Antibiotic Resistance of Helicobacter pylori in Iranian Children: A Systematic Review and Meta-Analysis.

Antibiotic therapy for children infected with Helicobacter pylori is important. However, resistance to antibiotics is one of the main causes of treatment failure. This study was designed to evaluate the prevalence pattern of antibiotic resistance of H. pylori in Iranian children using a systematic review and meta-analysis of literature. A computerized search (until June 10, 2017) using related keywords in the national and international databases was performed. A total of 261 original articles on antibiotic resistance of H. pylori in Iranian children were collected. After screening for inclusion and exclusion criteria, six eligible articles were included in the meta-analysis. Resistance rates of H. pylori to different antibiotics were as follows: metronidazole: 71%, clarithromycin: 12.2%, amoxicillin: 20.4%, tetracycline: 8.4%, ampicillin: 21.4%, rifampin: 28.6%, furazolidone: 8.4%, ciprofloxacin: 16.2%, azithromycin: 19%, erythromycin: 15.3%, and nitrofurantoin: 0%. The prevalence of H. pylori resistance to metronidazole, amoxicillin, ampicillin, and rifampin among Iranian children was high. Therefore, a careful monitoring of antibiotic resistance to select the best treatment options and prevent treatment failure is required. Although resistance to some antibiotics such as clarithromycin, tetracycline, furazolidone, and ciprofloxacin was less prevalent, frequent consumption of these drugs in children should be controlled owing to their known adverse events.

The effects of crocin on the symptoms of depression in subjects with metabolic syndrome.

BACKGROUND: Studies have suggested that metabolic syndrome (MetS) is associated with increased depressive symptoms, and reducing depression in subjects with MetS is important. Crocin, an active component of saffron, has useful properties for subjects with MetS, including antidepressant properties. OBJECTIVES: The aim of the study was to assess the effect of a preparation of crocin on the symptoms of depression in subjects with MetS, and the relationship between changes in those symptoms and the serum pro-oxidant/anti-oxidant balance (PAB). MATERIAL AND METHODS: This sub-study was carried out on 34 subjects with MetS from the authors' previous randomized double-blind controlled clinical trial (RCT), all of whom met the inclusion criteria for this study. The subjects were randomly assigned to treatment and placebo groups (n = 17 in each group) and received each 30 mg of crocin (2 tablets of 15 mg) or placebo for 8 weeks. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). The BDI questionnaire was completed for each subject at the baseline and at the end of the 8th week of treatment. Blood samples were taken from the subjects before and after the intervention period. Statistical analyses were performed using the SPSS for Windows, v. 16 (SPSS Inc., Chicago, USA). RESULTS: Out of the 34 participants enrolled, 33 completed the trial. The degree of depression decreased significantly in the crocin group (p = 0.005), but not in the placebo group (p > 0.05), and the difference between the 2 groups was statistically significant (p = 0.013). No significant relationship was observed between changes in depression symptoms and changes in the serum PAB (p > 0.05). CONCLUSIONS: This study demonstrates that at a dose of 30 mg per day for 8 weeks, crocin reduced the symptoms of depression in subjects with MetS compared to the control group, and this effect was independent of its effect on the serum PAB.

Characterization of clarithromycin-resistant Helicobacter pylori strains in Iran: A systematic review and meta-analysis.

BACKGROUND: The high prevalence of clarithromycin-resistant strains of Helicobacter pylori is a main challenge for the successful treatment of gastrointestinal infections. Point mutations in the 23S rRNA gene are one of the main mechanisms leading to the resistance to clarithromycin in Iran. The purpose of the present review was to evaluate the prevalence of clarithromycin-resistant H. pylori strains in Iran and to identify the major molecular mechanisms of resistance in the resistant isolates. METHODS: Using related keywords and computer search in English and Persian databases (up to November 21, 2016), available data about prevalence of clarithromycin-resistant H. pylori strains and molecular mechanisms of resistance in Iran were retrieved. Relevant articles were selected using pre-defined inclusion and exclusion criteria. RESULTS: The results of the meta-analysis showed that the overall prevalence of clarithromycin-resistant H. pylori strains in Iran is 14.7%. The highest and the lowest resistance to clarithromycin were reported from Kashan (33.7%) and Rasht (5.5%), respectively. The most prevalent point mutations in Iran were A2143G (59.1%), A2142G (17.8%), A2142C (8.8%), and A2144G (6.2%), respectively. CONCLUSION: The prevalence of clarithromycin-resistant H. pylori strains was in an acceptable level in our region. Therefore, clarithromycin can be used for the eradication of H. pylori infection in Iran. However, it seems that investigation about the role of other mechanisms involved in the induction of resistance to clarithromycin is needed.

Comparison of honey and dextrose solution on post-operative peritoneal adhesion in rat model.

BACKGROUND: Peritoneal adhesion between abdominal organs is a complication of surgery. It causes major complications like pain, bowel obstruction, infertility and increases risk of death. Honey is known to have anti-inflammatory and antioxidant properties potentially relevant for adhesive protection. METHODS: Thirty rats were divided into five groups: negative control without any surgical procedure (normal group), control group treated with normal saline, experimental group I treated with 1ml of 10% honey, experimental group II treated with honey at half concentration of group I (honey0.5), and positive control group receiving 1ml of dextrose 5%. Inflammatory, growth and angiogenesis factors (TNF-α, Il-6, IL-1ß, TGF-ß1 and VEGF) of the adhesion tissue were assessed using ELISA. Antioxidant factors (NO, GSH and MDA) were also assessed using biochemical procedures. RESULTS: The difference between peritoneal adhesion scores, TNF-α, IL-1ß, IL-6, TGF-ß1, VEGF, NO, GSH and MDA value of all groups was strongly significant (p<0.001). We showed that honey can decrease peritoneal adhesion (p<0.001), TNF-α (p<0.001), IL-1ß (p<0.001), IL-6 (p<0.001), TGF-ß1 (p<0.001), VEGF (p<0.001), NO (p<0.001), MDA (p<0.001) and increase GSH (p<0.001) compared with control group. Honey 0.5 also significantly decreased peritoneal adhesion (p<0.001), TNF-α (p<0.001), IL-1ß (p<0.01), IL-6 (p<0.001), VEGF (p<0.001), NO (p<0.001), MDA (p<0.01) and increase GSH (p<0.001) compared with control group. CONCLUSIONS: We find that honey can decrease inflammatory, growth and angiogenesis factors which can advance peritoneal adhesion and increase antioxidant factors. Honey could serve as a protective agent for peritoneal adhesion.

Simvastatin Treatment Does Not Affect Serum Vitamin D Concentrations in Patients with Dyslipidemia: A Randomized Double-blind Placebo-controlled Cross-over Trial.

BACKGROUND: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are antihyperlipidemic drugs with an established efficacy in stabilizing atherosclerotic plaques and preventing atherogenesis and reducing cardiovascular events. The purpose of this study was to determine the effect of simvastatin on serum Vitamin D status in dyslipidemic patients as Vitamin D status has an impact on monocyte/macrophage function and may also contribute to cardiovascular risk. METHODS: Selected individuals (n = 102) were treated with simvastatin (40 mg/day), or matching placebo in a randomized, double-blind, placebo-controlled, crossover trial. Each treatment period (with simvastatin or placebo) lasted for 30 days and was separated by a 2-week washout phase. Serum Vitamin D concentration was assessed pre- and post-treatment. RESULTS: Seventy-seven completed the trial, noncompliance with the study protocol and drug intolerance or relocation were the causes for drop-out. No significant carry-over effect was observed for the assessed parameters. There was a reduction in the serum levels of low-density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), and triglycerides (P < 0.05). Nevertheless, simvastatin therapy did not significantly affect serum level of high-density lipoprotein cholesterol and Vitamin D level (P > 0.05). CONCLUSIONS: Short-term treatment with simvastatin (40 mg/day) does not have a significant affect on serum levels of Vitamin D.