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

Neuroprotective mechanism of low-dose sodium nitrite in oxygen-glucose deprivation model of cerebral ischemic stroke in PC12 cells

The purpose of this study was to clarify the mechanisms of the protective effects of low-dose sodium nitrite (SN) on oxygen and glucose deprivation (OGD)-induced endoplasmic reticulum (ER) stress in PC12 cells. The PC12 cells were exposed to 4 h of OGD and treated with 100 μmol SN. The expression and activity of ER stress markers, including PKR-like endoplasmic reticulum kinase (PERK), transcription factor 6 (ATF6), CCAAT/enhancer binding protein homologous protein (CHOP), as well as caspase-12 and -3, were detected by immunoblotting assay. Fluorescence staining was used to detect the levels of reactive oxygen species (ROS) and Ca2+ release from the ER. Cell viability was also evaluated by MTT assay. It was found that SN significantly inhibited ROS production and Ca2+ release from the ER in OGD-injured PC12 cells. Moreover, ER stress marker expression and cleaved fragments of caspase-3 and -12 in OGD-injured PC12 cells were decreased after SN treatment. These findings were accompanied by a significant increase in cell viability. It seems that SN exerts a neuroprotective effect at least partially through reduction of ROS-mediated ER stress caused by OGD insult

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

The Neuroprotective Effect of Sodium Nitrite on Ischemic Stroke-Induced Mitochondrial Dysfunction via Downregulation of Intrinsic Apoptosis Pathway

Objective: Ischemic stroke leads to programmed cell death via intrinsic mitochondrial apoptosis pathways. Nitric oxide donors (NODs) are various kinds of drugs with the ability to produce nitric oxide (NO) as a potential bioregulator of apoptosis. Therefore, we aimed to evaluate the effect of sodium nitrite (SN) on ischemic injury-induced mitochondrial damage. Materials and Methods: A 4-hour oxygen-glucose deprivation (OGD) cellular model was developed to mimic cerebral ischemia injury. Cell viability was determined to demonstrate the efficiency of SN as a NO donor on OGD injured PC12 cells. Immunoblotting was performed to measure the expression of Bcl2, Bax and cleaved caspase 3 proteins. Mito Tracker Green label was used for staining the active mitochondria. Results: The present study confirmed that nitrite inhibited apoptosis via upregulation of Bcl-2 and downregulation of cleaved caspase-3 in OGD-injured PC12 cells as demonstrated by western blot analyses. In addition, nitrite restored mitochondrial vital activity and cell viability in OGD-injured cells. Conclusion: Resultant data illustrated the protective effects of nitrite and may suggest the in vivo use of nitrite for further confirmations

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

Serotonergic system modulation holds promise for L‐DOPA‐induced dyskinesias in hemiparkinsonian rats

The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically reviewed the serotonergic agents used for the treatment of LIDs in a 6-hydroxydopamine model of Parkinson’s disease in rats. We searched MEDLINE via PubMed, Embase, Google Scholar, and Proquest for entries no later than March 2018, and restricted the search to publications on serotonergic agents used for the treatment of LIDs in hemiparkinsonian rats. The initial search yielded 447 citations, of which 49 articles and one conference paper met our inclusion criteria. The results revealed ten different categories of serotonergic agents, including but not limited to 5-HT1A/BR agonists, 5-HT2AR antagonists, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), and tricyclic antidepressants (TCAs), all of which improved LIDs without imposing considerable adverse effects. Although there is promising evidence regarding the role of these agents in relieving LIDs in hemiparkinsonian rats, further studies are needed for the enlightenment of hidden aspect of these molecules in terms of mechanisms and outcomes. Given this, improving the quality of the pre-clinical studies and designing appropriate clinical trials will help fill the bench-to-bedside gap

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