Fibroblast Growth Factor-9 Enhances M2 Macrophage Differentiation and Attenuates Adverse Cardiac Remodeling in the Infarcted Diabetic Heart

Inflammation has been implicated as a perpetrator of diabetes and its associated complications. Monocytes, key mediators of inflammation, differentiate into pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages upon infiltration of damaged tissue. However, the inflammatory cell types, which propagate diabetes progression and consequential adverse disorders, remain unclear. The current study was undertaken to assess monocyte infiltration and the role of fibroblast growth factor-9 (FGF-9) on monocyte to macrophage differentiation and cardioprotection in the diabetic infarcted heart. Db/db diabetic mice were assigned to sham, myocardial infarction (MI), and MI+FGF-9 groups. MI was induced by permanent coronary artery ligation and animals were subjected to 2D transthoracic echocardiography two weeks post-surgery. Immunohistochemical and immunoassay results from heart samples collected suggest significantly increased infiltration of monocytes (Mean +/- SEM; MI: 2.02% +/- 0.23% vs. Sham 0.75% +/- 0.07%; p \u3c 0.05) and associated pro-inflammatory cytokines (TNF-alpha, MCP-1, and IL-6), adverse cardiac remodeling (Mean +/- SEM; MI: 33% +/- 3.04% vs. Sham 2.2% +/- 0.33%; p \u3c 0.05), and left ventricular dysfunction (Mean +/- SEM; MI: 35.4% +/- 1.25% vs. Sham 49.19% +/- 1.07%; p \u3c 0.05) in the MI group. Importantly, treatment of diabetic infarcted myocardium with FGF-9 resulted in significantly decreased monocyte infiltration (Mean +/- SEM; MI+FGF-9: 1.39% +/- 0.1% vs. MI: 2.02% +/- 0.23%; p \u3c 0.05), increased M2 macrophage differentiation (Mean +/- SEM; MI+FGF-9: 4.82% +/- 0.86% vs. MI: 0.85% +/- 0.3%; p \u3c 0.05) and associated anti-inflammatory cytokines (IL-10 and IL-1RA), reduced adverse remodeling (Mean +/- SEM; MI+FGF-9: 11.59% +/- 1.2% vs. MI: 33% +/- 3.04%; p \u3c 0.05), and improved cardiac function (Fractional shortening, Mean +/- SEM; MI+FGF-9: 41.51% +/- 1.68% vs. MI: 35.4% +/- 1.25%; p \u3c 0.05). In conclusion, our data suggest FGF-9 possesses novel therapeutic potential in its ability to mediate monocyte to M2 differentiation and confer cardiac protection in the post-MI diabetic heart

Bioethanol fuel production from rambutan fruit biomass as reducing agent of global warming and greenhouse gases

The depletion of fossil fuels impacts on the increase of petroleum price and has triggered the finding of alternative and renewable energy. Biofuel has attracted the attention of researchers all over the world due to reducing the environmental impacts of elevated carbon monoxide. Abundant of fruits waste can be reused in the bioethanol production. Hence, it can reduce pollution and waste material, thus, helps in waste disposal management and reducing global warming. The aim of the study of producing bioethanol from rotten rambutan was to manage rambutan wastes, cleaning the environment and reduction of greenhouse gases and global warming. This study was conducted from rambutan fruit waste biomass in different parameters using yeast (Saccharomyces cerevisiae) fermentation. The optimum condition of bioethanol yield was having 3 g of yeast at 30°C by following pH 6 for two days of incubation. Glucose content, total soluble solid (TSS) and pH values reduced after fermentation due to the conversion of glucose to ethanol and carbon dioxide in case of all parameters. The chemical content, viscosity and acid values of the bioethanol produced were within ASTM (American Society for Testing and Materials) standard specifications with less hazardous chemical content in produced bioethanol. Furthermore, the engine test result showed that greenhouse gas emission like hydrocarbon (HC), NOx and SO2 content in E5 and E10 were significantly lower in bioethanol than in 100% gasoline tested in (proton Gen 2 multicylinder) car. Thus, it can potentially be used as good biofuel for petrol engine purposes.Key words: Bioethanol, fruit waste, emission, renewable energy, global warming

Mifepristone alone versus mifepristone-misoprostol combination regimen for management of intrauterine fetal death

Background: Early pregnancy failure is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to remove the products of conception from the uterus. Curettage, although highly effective, is associated with a risk of complications; medical treatment with misoprostol is a safe and less expensive alternative. Unfortunately, after 1 week of expectant management in case of EPF, medical treatment with misoprostol has a complete evacuation rate of approximately 50%. Misoprostol treatment results may be improved by pre-treatment with mifepristone; its effectiveness has already been proven for other indications of pregnancy termination. The study objective was to compare the outcome of Mifepristone alone with the Mifepristone- Misoprostol combination regimen for the management of IUFD.Methods: This was a Prospective clinical trial at the department of obstetrics and gynecology, Chittagong Medical College Hospital, Chittagong. From March 2016 (Actual patient enrolment started after obtaining ethical clearance i.e. March 2018) to September 2018.Results: A subjects delivered earlier than group B and the mean induction delivery interval in Group A is significantly less in comparison to Group B (p=<0.001). Out of 50 women, 2(4%) and 10(20%) women in Groups A and B required oxytocin infusion to establish good contractions, and completion of termination who regarded as a failure. In the mifepristone alone group, the success rate is significantly higher than in the combination group.Conclusions: The efficacy of mifepristone alone was found superior to that of the mifepristone misoprostol combination regimen in the present study.

Pengaruh Ovitrap Sebagai Monitoring Keberadaan Vektor Aedes SP Di Kelurahan Bulusan Kecamatan Tembalang Kota Semarang

Penyakit Demam Berdarah Dengue (DBD) merupakan salah satu masalah kesehatan yang penting di Indonesia. Penularan Penyakit di sebarkan oleh nyamuk Aedes sp. Penularan Virus Dengue (VirDen) terjadi secara transexual atau induk jantan ke induk betina namun juga secara transovarial dari induk betina ke keturunan-keturunanya. Tempat Perkembangbiakan (TP) nyamuk vektor DBD adalah wadah (container) yang berisi air jernih yang ada di dalam dan sekitar rumah. Survai yang dilakukan, angka jentik Aedes sp. di beberapa daerah masih tinggi. Angka CFR DBD Kota Semarang di tahun 2012 meningkat dari tahun 2011 sebanyak 0,77% menjadi 1,76%. Jumlah Penderita DBD di wilayah kerja Puskesmas Rowosari dari bulan Januari-Oktober 2013 mencapai 49 kasus dari 38.396 jiwa dengan IR/10.000 penduduk adalah 11,72. Di Kelurahan Bulusan Kecamatan Tembalang terdapat 5 kasus dari 3924 penduduk RW 03 merupakan kejadian yang paling tinggi yaitu 3 kasus dari 932 penduduk. IR/10.000 sebesar 32,19. Kegiatan monitoring dengan cara survei telur memasang ovitrap dinilai sangat efektif untuk mendeteksi keberadaan nyamuk Aedes sp di suatu daerah dan bahkan pada level yang rendah

A Comparative Study of Perceived Stress among Female Medical and Non-Medical University Students in Dammam, Saudi Arabia

Objectives: The objective of this study was to investigate any differences between female undergraduate medical and non-medical students for: 1) prevalence and causes of perceived academic stress, and 2) changes in physical, mental, psychological and emotional health as well as life-style since starting college studies. Methods: A cross-sectional study was conducted at Dammam University, Dammam, Saudi Arabia, in January 2008. All 319 pre-clinical female medical students were included in the study and 297 non-medical students from the College of Applied Studies and Community Services (CASCS) were selected by stratified random sampling. The study instrument was a questionnaire on the “Influence of Studying on Students’ Health”. Results: More medical students (48.6%) reported being frequently stressed due to studies than CASCS students (38.7%, P <0.01). Unsuitable teaching methods, an unsatisfactory study environment, and fear of failure in examinations were more frequently mentioned by medical than non-medical students (P <0.05). While underlying social problems were significantly more common in medical students, economic problems were more prevalent among CASCS students (P <0.05, P <0.05). More medical than non-medical students reported a worse status of physical and mental health, anxiety and depression and negative life-style changes since initiation of the college programme. Conclusion: Medical students were at higher risk of physical and mental health problems than non-medical students due to academic stress. Since a substantial proportion of CASCS students also experienced academic stress, we recommend that a student support committee be established for both colleges to provide counselling and guidance in healthy ways to cope with stress

Regulation of PTEN/Akt Pathway Enhances Cardiomyogenesis and Attenuates Adverse Left Ventricular Remodeling following Thymosin beta 4 Overexpressing Embryonic Stem Cell Transplantation in the Infarcted Heart

Thymosin beta 4 (T beta 4), a small G-actin sequestering peptide, mediates cell proliferation, migration, and angiogenesis. Whether embryonic stem (ES) cells, overexpressing T beta 4, readily differentiate into cardiac myocytes in vitro and in vivo and enhance cardioprotection following transplantation post myocardial infarction (MI) remains unknown. Accordingly, we established stable mouse ES cell lines, RFP-ESCs and T beta 4-ESCs, expressing RFP and an RFP-T beta 4 fusion protein, respectively. In vitro, the number of spontaneously beating embryoid bodies (EBs) was significantly increased in T beta 4-ESCs at day 9, 12 and 15, compared with RFP-ESCs. Enhanced expression of cardiac transcriptional factors GATA-4, Mef2c and Txb6 in T beta 4-EBs, as confirmed with real time-PCR analysis, was accompanied by the increased number of EB areas stained positive for sarcomeric alpha-actin in T beta 4-EBs, compared with the RFP control, suggesting a significant increase in functional cardiac myocytes. Furthermore, we transplanted T beta 4-ESCs into the infarcted mouse heart and performed morphological and functional analysis 2 weeks after MI. There was a significant increase in newly formed cardiac myocytes associated with the Notch pathway, a decrease in apoptotic nuclei mediated by an increase in Akt and a decrease in levels of PTEN. Cardiac fibrosis was significantly reduced, and left ventricular function was significantly augmented in the T beta 4-ESC transplanted group, compared with controls. It is concluded that genetically modified T beta 4-ESCs, potentiates their ability to turn into cardiac myocytes in vitro as well as in vivo. Moreover, we also demonstrate that there was a significant decrease in both cardiac apoptosis and fibrosis, thus improving cardiac function in the infarcted heart

Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation

233294Human hepatocellular carcinomas (HCCs), which arise on a background of chronic liver damage and inflammation, express c-Fos, a component of the AP-1 transcription factor. Using mouse models, we show that hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced HCCs, whereas liver-specific c-Fos expression leads to reversible premalignant hepatocyte transformation and enhanced DEN-carcinogenesis. c-Fos-expressing livers display necrotic foci, immune cell infiltration, and altered hepatocyte morphology. Furthermore, increased proliferation, dedifferentiation, activation of the DNA damage response, and gene signatures of aggressive HCCs are observed. Mechanistically, c-Fos decreases expression and activity of the nuclear receptor LXRα, leading to increased hepatic cholesterol and accumulation of toxic oxysterols and bile acids. The phenotypic consequences of c-Fos expression are partially ameliorated by the anti-inflammatory drug sulindac and largely prevented by statin treatment. An inverse correlation between c-FOS and the LXRα pathway was also observed in human HCC cell lines and datasets. These findings provide a novel link between chronic inflammation and metabolic pathways important in liver cancer.We thank Drs. N. Djouder, M. Petruzzelli, R. Ricci, F.X Real, K.D. Bissig, and members of the Wagner laboratory for critical reading of the manuscript and valuable sugges- tions; Dr. H. Schönthaler for help with the bioinformatics analysis; V. Bermeo for technical help; and G. Luque, S. Leceta, and G. Medrano for assisting with mouse experiments. The E.F. Wagner laboratory is supported by grants from the Spanish Ministry of Economy, Industry, and Competitiveness (BFU2012-40230 and SAF2015-70857, co- funded by the European Regional Development Fund), a European Research Council– advanced grant (ERC-FCK/2008/37), and Worldwide Cancer Research (13-0216). R. Hamacher was supported by the Deutsche Forschungsgemeinschaft (HA 6068/1-1), M.K. Thomsen by AUFF Nova, and S.C. Hasenfuss by a Boehringer Ingelheim Fonds PhD fellowship. The authors declare no competing financial interests. Author contributions: L. Bakiri and R. Hamacher designed and performed exper- iments, analyzed data, prepared figures, and wrote the manuscript. O. Graña analyzed RNA-seq and public microarray data, A. Guío-Carrión provided expert technical assis- tance, R. Campos-Olivas acquired and analyzed NMR data, L. Martinez analyzed flow cytometry data, M.K. Thomsen performed experiments with human cell lines, S.C. Hasenfuss performed experiments with primary hepatocytes and data mining, and H.P. Dienes performed pathological analysis on tissue sections. E.F. Wagner directed the study, approved the data, and wrote and edited the paper. All authors read and commented on the manuscript.S

Associations of cardiovascular risk factors in Al Ain- United Arab Emirates

<p>Abstract</p> <p>Background</p> <p>Over the last 30 years the citizens of the United Arab Emirates have experienced major changes in life-style secondary to increased affluence. Currently, 1 in 5 adults have diabetes mellitus, but the associations (clustering) among risk factors, as well as the relevance of the concept of the metabolic syndrome, in this population is unknown.</p> <p>Aim</p> <p>To investigate the prevalence and associations among cardiovascular risk factors in this population, and explore to what extent associations can be explained by the metabolic syndrome according to ATP-III criteria.</p> <p>Method</p> <p>A community based survey, of conventional risk factors for cardiovascular disease was conducted among 817 national residents of Al Ain city, UAE. These factors were fasting blood sugar, blood pressure, lipid profile, BMI, waist circumference, smoking, or CHD family history. Odds ratios between risks factors, both unadjusted and adjusted for age and sex as well as adjusted for age, sex, and metabolic syndrome were calculated.</p> <p>Results</p> <p>Various risk factors were positively associated in this population; associations that are mostly unexplained by confounding by age and sex. For example, hypertension and diabetes were still strongly related (OR 2.5; 95% CI 1.7–3.7) after adjustment. An increased waist circumference showed similar relationship with hypertension (OR 2.3; 95% CI 1.5–3.5). Diabetes was related to an increased BMI (OR 1.5; 96% CI 1.0–2.3). Smoking was also associated with diabetes (OR 1.9, 95% CI 1.0–3.3).</p> <p>Further adjustment for metabolic syndrome reduced some associations but several remained.</p> <p>Conclusion</p> <p>In this population risk-factors cluster, but associations do not appear to be explained by the presence/absence of the ATP-III metabolic syndrome. Associations provide valuable information in planning interventions for screening and management.</p

Wnt signaling and Loxl2 promote aggressive osteosarcoma

Osteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better therapies. Using genetically modified mouse models (GEMMs), we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2. c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding, and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2. Concordantly, inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS. Wls-deficient osteosarcomas proliferate less, are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers. Importantly, Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models. Finally, OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies. Congruently, a strong correlation between c-FOS, LOXL2 and WNT7B/WNT9A expression is observed in human OS samples, and c-FOS/LOXL2 coexpression correlates with OS aggressiveness and decreased patient survival. Therefore, therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric, recurrent, and metastatic OS