Amphotericin-B and vancomycin-loaded chitosan nanofiber for antifungal and antibacterial application

In the present study, a mucoadhesive non-woven fiber mat (d= 116 nm) was fabricated by the electrospinning method using chitosan (80% Wt), polyethylene oxide (10% Wt), cysteine (4% Wt) and drugs (6% Wt), respectively. In addition, a comparative study was conducted to define effect of drugs and mucoadhesive agent on the nanofiber formation. FTIR, SEM, DSC and DMA were used to investigate the chemical and physical properties of the nanofibers. In vitro release of the drugs was assessed over a 48-hour period by the total immersion method. Release data were fitted to kinetic models, including the zero-order, first-order, Higuchi matrix, and Hixson–Crowell. Zone inhibition investigations were used to describe the inhibition content of vancomycin and amphotericin B loaded in the mats. The SEM images displayed a slight decrease in the fiber diameter with adding drugs and mucoadhesive agents. FTIR spectra confirmed that any undesirable reaction between VAN–AMB and CS-PEO was not observed. DSC test recognized the uniform distribution of drugs in the polymeric bead of the fiber without any crystal form. The elasticity modulus of the nanofiber was in an acceptable range for oral mucosa (approximately 5 Mpa). The results indicated that biodegradable mucoadhesive nanofibrous membranes released high concentrations of VAN in the first 24 hours, but the AMB release was affected in more controlled phenomena

Moderate aerobic exercise training decreases middle-aged induced pathologic cardiac hypertrophy by improving Klotho expression, MAPK signaling pathway and oxidative stress status in Wistar rats

Objective(s): This study aimed to investigate the effect of aerobic training on serum levels of Klotho, cardiac tissue levels of H2O2 and phosphorylation of ERK1/2 and P38 as well as left ventricular internal diameter (LVID), the left ventricle wall thickness (LVWT) and fibrosis in middle-aged rats. Materials and Methods: Forty wistar rats, including young rats (n=10, 4 month-old) and middle-aged rats (n=30, 13-15 months-old) were enrolled in this experimental study. The all young and 10 middle-aged rats were sacrificed (randomly) under deep anesthesia without any exercise training as normal young control and normal middle-aged control respectively. The remaining 20 middle-aged rats participated in 4 (n=10) or 8-week (n=10) aerobic exercise training. Results: There were significant differences in the plasmatic Klotho levels and the heart tissue levels of phosphorylated-ERK1/2 (p-ERK1/2), P-P38 and H2O2, LVWT, LVID and fibrosis between young and middle-aged rats (P=0.01). Plasmatic Klotho level was significantly increased after eight weeks training (P=0.011). Also, p-ERK1/2 was significantly decreased after eight weeks and p-P38 was significantly decreased in the fourth (P=0.01) and eight weeks of training (P=0.01). A similar decrease was reported for aging-induced H2O2 in the fourth (P=0.016) and eighth weeks (P=0.001). LVID was significantly increased in eight weeks, but LVWT and fibrosis was significantly reduced in the eighth week (P=0.011, P=0.028, P=0.001 respectively).Conclusion: Moderate aerobic training attenuates aging-induced pathological cardiac hypertrophy at least partially by restoring the Klotho levels, attenuating oxidative stress, and reduction in the phosphorylation of ERK1/2, P38 and fibrosis

Thymol decreases apoptosis and carotid inflammation induced by hypercholesterolemia through a discount in oxidative stress

Objective: Atherosclerosis sclerosis is a chronic inflammatory disease that can lead to cardiovascular and cerebrovascular disorders that are generally along with hypercholesterolemia and oxidative stress. Various surveys have shown that thymol is a polyphenolic compound with anti-inflammatory and antioxidant properties. This study aimed to investigate the anti-inflammatory and antiapoptotic effects of thymol on carotid tissue of hypercholesterolemic rats. Materials and Methods: Forty male Wistar rats were randomly divided into 4 groups with 10 members each (n = 10): a control group with a normal diet (ND), a group with a high-cholesterol (2%) diet (HD), a group with a high-cholesterol diet combined with thymol (24 mg/kg HD + T), and a group with a thymol diet (T). After preparing serum from peripheral blood of rats, lipid measurements were obtained, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), by using a colorimetric method; the levels of oxidized LDL (OxLDL) were obtained through enzyme-linked immunosorbent assay (ELISA). The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) antioxidant enzymes, as well as the concentrations of malondialdehyde (MDA) and serum total antioxidant capacity (TAC), were determined with the use of colorimetric methods. The protein expressions of Bcl2 and cleaved caspase 3 and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in rat carotid tissue were determined by an immunoblotting method. Results: The rats fed with a high-cholesterol diet for 8 weeks increased TC and OxLDL in HD group compared with the ND group (P < 0.01; OxLDL HD vs ND (214.42 ± 17.46 vs 69.13 ± 9.92; P < 0.01); (229.39 ± 13.26 vs 67.89 ± 5-14 (215.58 ± 12.46 vs 229.35 ± 13.26; P < 0.05, OxLDL HD vs HD + T 105.53 ± 10.44; P < 0.01). Both of them were decreased with the intervention of thymol in the HD + T group compared with the HD group. The amount of phosphorylation of p38 (p-p38) and the protein expression of cleaved caspase 3 showed a significant increase in the HD group compared with the ND group (P < 0.01). In contrast, the expression of Bcl-2 in the high-cholesterol diet group decreased compared with the control group (P < 0.01). A comparison of the p-p38 and the protein expression of cleaved caspase 3 between the T + HD and the HD groups showed that in both cases, thymol caused a decrease (p<0.01), whereas Bcl-2 effected an increase (P < 0.05). Regarding the oxidant and antioxidant indices, thymol significantly decreased the MDA level and increased the total antioxidant content (P < 0.01). Conclusion: The results of this study indicate that thymol significantly decreases the expression of inflammatory and apoptotic proteins in carotid tissue. However, this decrease is probably not mediated by an effect on lipid metabolism because thymol decreases the total level of cholesterol but has no significant effect on the LDL-C level as the atherogenic index. In addition, thymol possibly exerts an antioxidant effect without the direct involvement of antioxidant enzymes

Saharan sand and dust storms and neonatal mortality: Evidence from Burkina Faso

West African populations are exposed to the longest and harshest dust storms on the planet, the Saharan sand and dust storms (SDS). Nonetheless, little is known about the effects of the severe storms on early-life health in West Africa. This study investigated the association of the risk of neonatal mortality, an indicator of the population's early-life health, with potential prenatal and neonatal exposure to the Saharan SDS. Data on 30,552 under-five children from Burkina Faso's 1993, 2003, and 2010 demographic and health surveys were matched to the particulate matters (PM) and terrestrial air temperature and precipitation forecasts. Exposure to dust events was measured by the number of days with average PM10 and PM2.5 concentrations above a series of threshold. Intensity-dependent patterns of associations between neonatal mortality and both prenatal and birth month exposure to dust events were identified. There was no association if average daily PM10 and PM2.5 levels were &lt;60 and 30 μg/m3, respectively. However, strong associations, which increase almost linearly with the intensity of exposure, were identified when daily PM10 and PM2.5 levels ranged from 70 to 150 and from 40 to 70 μg/m3, respectively. At the higher PM levels, the association for the gestation period decreased, but that for the birth month remained mostly unresponsive to changes in the PM levels. Larger associations were identified when siblings were compared. © 2020 Elsevier B.V

Therapeutic potential of genistein in ovariectomy-induced pancreatic injury in diabetic rats: The regulation of MAPK pathway and apoptosis

Objective(s): Genistein, as a phytoestrogen found in legumes, has several biological activities in general and anti-diabetic activity particularly. In this study, we investigated the effect of genistein on proteins involved in β-cell proliferation, survival and apoptosis to further reveal its anti-diabetic potential in the ovariectomized diabetic rat. Materials and Methods: We used three-month-old female Wistar rats that either underwent ovariectomy (OVX) or received a sham surgery (Sham). In a subsequent series of experiments, OVX rats received high-fat diet and low dose STZ to induce diabetes (OVX.D) and genistein treatment (OVX.D.G). Western blot analysis was used for the assessment of phosphorylation of ERK1/2 and AKT and expression of Bcl-2 and caspase-3 in pancreas tissue. Hematoxylin-Eosin (H&E) staining was used for histopathological assessment. Results: Genistein induced AKT and ERK1/2 phosphorylation protein expression of Bcl-2 in the pancreas. In addition, genistein suppressed protein level of caspase-3. Administration of genistein significantly improved hyperglycemia in ovariectomized diabetic rat, concomitant with improved islet β-cell morphology and mass. Conclusion: These findings suggest that the beneficial antidiabetic effect of genistein partially mediated by directly modulating pancreatic β-cell function via activation of the AKT, ERK1/2, and Bcl-2, as cell survival and anti-apoptotic factors, and decreasing of proapoptotic caspase-3

Saharan sand and dust storms and neonatal mortality: Evidence from Burkina Faso

This is an accepted manuscript of an article published by Elsevier in Science of the Total Environment on 29/04/2020, available online: https://doi.org/10.1016/j.scitotenv.2020.139053 The accepted version of the publication may differ from the final published version.West African populations are exposed to the longest and harshest dust storms on the planet, the Saharan sand and dust storms (SDS). Nonetheless, little is known about the effects of the severe storms on early-life health in West Africa. This study investigated the association of the risk of neonatal mortality, an indicator of the population's early-life health, with potential prenatal and neonatal exposure to the Saharan SDS. Data on 30,552 under-five children from Burkina Faso's 1993, 2003, and 2010 demographic and health surveys were matched to the particulate matters (PM) and terrestrial air temperature and precipitation forecasts. Exposure to dust events was measured by the number of days with average PM10 and PM2.5 concentrations above a series of threshold. Intensity-dependent patterns of associations between neonatal mortality and both prenatal and birth month exposure to dust events were identified. There was no association if average daily PM10 and PM2.5 levels were <60 and 30 μg/m3, respectively. However, strong associations, which increase almost linearly with the intensity of exposure, were identified when daily PM10 and PM2.5 levels ranged between 70 and 150 and 40–70 μg/m3, respectively. At the higher PM levels, the association for the gestation period decreased, but that for the birth month remained mostly unresponsive to changes in the PM levels. Larger associations were identified when siblings were compared.Published versio

Continuous exposure to ambient air pollution and chronic diseases: Prevalence, burden, and economic costs

This is an accepted manuscript of an article published by De Gruyter in Reviews on Environmental Health on 22/04/2020, available online: https://doi.org/10.1515/reveh-2019-0106 The accepted version of the publication may differ from the final published version.Studies that assess the connection between the prevalence of chronic diseases and continuous exposure to air pollution are scarce in developing countries, mainly due to data limitations. Largely overcoming data limitations, this study aimed to investigate the association between the likelihood of reporting a set of chronic diseases (diabetes, cancer, stroke and myocardial infarction, asthma, and hypertension) and continuous exposure to carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and coarse particulate matter (PM10). Using the estimated associations, the disease burden and economic costs of continuous exposure to air pollutants were also approximated. A 2011 Health Equity Assessment and Response Tool survey from Tehran, Iran, was used in the main analyses. A sample of 67,049 individuals who had not changed their place of residence for at least 2 years before the survey and reported all relevant socioeconomic information was selected. The individuals were assigned with the average monthly air pollutant levels of the nearest of 16 air quality monitors during the 2 years leading to the survey. Both single- and multi-pollutant analyses were conducted. The country’s annual household surveys from 2002 to 2011 were used to calculate the associated economic losses. The single-pollutant analysis showed that a one-unit increase in monthly CO (ppm), NO2 (ppb), O3 (ppb), and PM10 (μg/m3) during the 2 years was associated with 751 [confidence interval (CI): 512–990], 18 (CI: 12–24), 46 (CI: −27–120), and 24 (CI: 13–35) more reported chronic diseases in 100,000, respectively. The disease-specific analyses showed that a unit change in average monthly CO was associated with 329, 321, 232, and 129 more reported cases of diabetes, hypertension, stroke and myocardial infarction, and asthma in 100,000, respectively. The measured associations were greater in samples with older individuals. Also, a unit change in average monthly O3 was associated with 21 (in 100,000) more reported cases of asthma. The multi-pollutant analyses confirmed the results from single-pollutant analyses. The supplementary analyses showed that a one-unit decrease in monthly CO level could have been associated with about 208 (CI: 147–275) years of life gained or 15.195 (CI: 10.296–20.094) thousand US dollars (USD) in life-time labor market income gained per 100,000 30-plus-year-old Tehranis

Combination of Vildagliptin and Ischemic Postconditioning in Diabetic Hearts as a Working Strategy to Reduce Myocardial Reperfusion Injury by Restoring Mitochondrial Function and Autophagic Activity

Purpose: Diabetic hearts are resistant to cardioprotection by ischemic-postconditioning (IPostC). Protection of diabetic hearts and finding related interfering mechanisms would have clinical benefits. This study investigated the combination effects of vildagliptin (Vilda) and IPostC on cardioprotection and the levels of autophagy and mitochondrial function following myocardial ischemia/reperfusion (I/R) injury in type-II diabetic rats. Methods: Diabetes was established by high fat diet/low dose of streptozotocin and lasted for 12 weeks. The diabetic rats received Vilda (6 mg/kg/day, orally) for one month before I/R. Myocardial regional ischemia was induced through the ligation of left coronary artery, and IPostC was applied immediately at the onset of reperfusion. The infarct size was assessed by a computerised planimetry and left ventricles samples were harvested for cardiac mitochondrial function studies (ROS production, membrane potential and staining) and western blotting was used for determination of autophagy markers. Results: None of Vilda or IPostC but combination of them could significantly reduce the infarct size of diabetic hearts, comparing to control (P<0.001). IPostC could not significantly affect p62 expression level in diabetic hearts, but pre-treatment with Vilda alone (p<0.05) and in combination with IPostC (p<0.01) more significantly decreased p62 expression in comparison with corresponding control group. The expression of LC3B-II and LC3BII/LC3BI as well as mitochondrial ROS production were decreased significantly in treatment groups (p<0.001). Mitochondrial membrane depolarization was significantly higher and mitochondrial density was lower in untreated diabetic I/R hearts than treated groups (p<0.001). IPostC in combination with vildagliptin prevented the mitochondrial membrane depolarization and increased the mitochondrial content more potent than IPostC alone in diabetic hearts. Conclusion: Combination of vildagliptin and IPostC in diabetic hearts was a well-working strategy to reduce myocardial I/R damages by restoring mitochondrial membrane potential and ROS production and modulating the autophagic activity in I/R hearts