Sumnermygind4159

Furthermore, our findings also showed that the expression of MIAT was positively correlated with the expression of IL-1β and IL-6. These results suggest that MIAT might play important regulatory roles in alleviating inflammatory reactions and microangiopathy inducing by DR after transplantation of HUMSCs. © The author(s).Confocal Raman microspectral imaging was adopted to elucidate the cellular drug responses of osteosarcoma cells (OC) to N-[N-(3, 5-difluorophenyl acetyl)-L-alanyl]-sphenylglycine butyl ester (DAPT), a γ-secretase inhibitor, by identifying the drug induced subcellular compositional and structural changes. Methods Spectral information were acquired from cultured osteosarcoma cells treated with 0 (Untreated Group, UT), 10 (10 μM DAPT treated, 10T), 20 μM (20 μM DAPT treated, 20T) DAPT for 24 hours. A one-way ANOVA and Tukey's honest significant difference (HSD) post hoc multiple test were sequentially applied to address spectral features among three groups. Multivariate algorithms such as K-means clustering analysis (KCA) and Principal component analysis (PCA) were used to highlight the structural and compositional differences, while, univariate imaging was applied to illustrate the distribution pattern of certain cellular components after drug treatment. Results Major biochemical changes in DAPT-induced apoptosis came from changes in the content and structure of proteins, lipids, and nucleic acids. By adopted multivariate algorithms, the drug induced cellular changes was identified by the morphology and spectral characteristics between untreated cells and treated cells, testified that DAPT mainly acted in the nuclear region. With the increase of the drug concentration, the content of main subcellular compositions, such nucleic acid, protein, and lipid decreased. In an addition, DAPT-induced nuclear fragmentation and apoptosis was depicted by the univariate Raman image of major cellular components (nucleic acids, proteins and lipids). Conclusions The achieved Raman spectral and imaging results illustrated detailed DAPT-induced subcellular compositional and structural variations as a function of drug dose. Such observations can not only explain drug therapeutic mechanisms of OC DAPT treatment, and also provide new insights for accessing the medicine curative efficacy and predicting prognosis. © The author(s).Purpose We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT. © The author(s).Abnormal angiogenesis is one of the significant features in periodontitis leading to progressive inflammation, but angiogenic changes of periodontal ligaments under inflammatory condition were rarely reported. Periodontal ligament stem cells (PDLSCs) were a kind of dental stem cells associated with vascularization. Here we investigated the alteration of angiogenesis of periodontal ligament in periodontitis, and revealed an exosome-mediated pathway to support the effect of PDLSCs on angiogenic improvement. Vascular specific marker CD31 and VEGFA were found to be highly expressed in periodontal ligaments of periodontitis. The VEGFA expression was up-regulated in inflamed PDLSCs compared to control, meanwhile the tube formation of HUVECs was improved when co-cultured with inflamed PDLSCs. Exosomes secretion of PDSLCs was augmented by inflammation, and promoted angiogenesis of HUVECs, whereas blocking secretion of exosomes led to degenerated angiogenesis of HUVECs. Exosome-trasferred VEGFA was proven to be the crucial communicator between PDLSCs and HUVECs. Inflammation inhibited miR-17-5p expression of PDLSCs and relieved its target VEGFA. However, overexpression of miR-17-5p blocked the pro-angiogenic ability of inflamed PDLSCs. In conclusion, the findings indicated that vascularization of periodontal ligaments was enhanced, and inflammatory micro-environment of periodontitis facilitated pro-angiogenesis of PDLSCs through regulating exosome-mediated transfer of VEGFA, which was targeted by miR-17-5p. © The author(s).Estrous cycle is a repetitive phenomenon occurring during the reproductive life of a female dog. Mitapivat chemical structure The duration of the canine estrous cycle is considerably longer than one in the most of the other animals and is broadly grouped into follicular phase (proestrus and estrus), luteal phase (diestrus) and non-seasonal anestrus. Dogs in the same stage of cycle can be inadvertently assigned to same group during routine safety and metabolic studies leading to possible erroneous interpretation of test-item related effects. This retrospective analysis was conducted by analyzing data of 86 female beagle dogs from control/placebo treated groups to correlate any possible effect of estrous stages with electrocardiography, clinical pathology and ovarian weight. Different estrous cycle stages of beagles were confirmed histologically by evaluating ovary, uterus, vagina and mammary glands. The incidence of beagles in diestrus was the highest, followed by anestrus, proestrus and estrus. No significant effect was noticed on heart rate, P-A, P-D, RR, QRS and QT intervals across different stages of estrous cycle. However, significantly higher PQ (PR) interval in dogs in proestrus stage was observed compared to dogs in anestrus and estrus. Marginally higher WBCs, neutrophils, lymphocytes, RBCs, hemoglobin, AST and lower hematocrit, lipid profile (total cholesterol, HDL, LDL, triglycerides), ALP level was evident in estrous period. Relative ovary weight was significantly higher in dogs in diestrus stage. Considering these results, one may need to exercise caution while interpreting experimental data from female beagle dogs. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.In the bioethanol industry, per liter of the produced alcohol 9 to 14 liters of vinasse are obtained as a byproduct. If the vinasse is directly shed into bodies of water without an adequate treatment, it may have negative effects on the existing biota and human health due to its high turbidity and color, low pH and high content of organic material. The purpose of this study was to assess the acute toxicity of vinasse by means of a rapid test with Aliivibrio fischeri and compare it with a standard immobilization assay with Daphnia magna. The standard assay of D. magna by means of its EC50 of 4.7% showed that organism was more sensitive to the contaminant, in comparison with the 69.6% obtained with the A. fischeri which suggests that it should be continuesly used as one of the organisms of first choice for the evaluation of the acute toxicity of this effluent. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.Blood lead level (BLL) is insufficiently sensitive for early detection of Lead-induced neurotoxicity (LIN). This study determined the possible role of the combination of BLL, intelligent quotient (IQ) and erythrocyte acetylcholinesterase (AChE) activity in the early detection of LIN in Children. Apparently healthy children (n=309) from eight public primary schools in Ibadan, Nigeria were recruited and classified into children with Elevated BLL (EBLL) and children with Acceptable BLL (control) based on CDC cut-off for childhood lead exposure. Neurological indices (speech, memory, cranial nerves and cerebellar functions), IQ, BLL and erythrocyte AChE activity were assessed using standard methods, Standard Progressive Matrices, AAS and HPLC respectively. Statistical analysis involved Student's t-test, Pearson's correlation and multivariate regression. p less then 0.05 was considered significant. There were 169 (54.7%) children with EBLL while there were 140 (45.3%) control children. Both groups exhibited normal speech, memory, cranial nerves and cerebellar functions. However, IQ was lower in EBLL children (85.9±11.6) compared with control (91.5±14.0) while BLL and AChE activity were higher in EBLL children (0.4±0.1 μmol/l; 117.5±25.5 μkat/l) compared with control (0.2±0.0 μmol/l; 59.4±10.2 μkat/l). BLL showed inverse correlation with IQ (r=-0.134, p=0.019) but positive correlation with AChE (r=0.978, p≤0.001). 16.2% of the observed variation in BLL could be accounted for by AChE using the equation; [BLL=-0.007+0.003 AChE] p less then 0.05. Elevated blood lead level is prevalent among the school children and appears to have adverse effect on their IQ. Erythrocyte AChE could be a promising marker for early recognition of significant environmental lead exposure and lead-induced neurotoxicity in children. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.We have earlier demonstrated the potential of monocrotophos (MCP), a highly toxic organophosphorus insecticide (OPI), to elicit insulin resistance in rats after chronic exposure. Given the understanding of role of paraoxonase1 (PON1) in OPI toxicity and diabetes pathology, this study was envisaged to understand the effect of duration of exposure to MCP on plasma PON1 activity in rats. Rats were administered MCP per os at 1/20 and 1/10th LD50 as daily doses for 180 days. Interim blood samples were collected at 15, 30, 45, 90 and 180 d for analysis of plasma parameters. Exposure to MCP for 45 resulted in persistent trend of hyperinsulinemia, while significant increase in fasting glucose levels was observed after 180 days. MCP caused suppression of plasma cholinesterase activity though the study period, albeit extent of inhibition was more severe during the early phase of the study. Exposure to MCP for 180 d resulted in hypertriglyceridemia and marginal decrease in HDL-C levels. MCP failed to modulate PON1 activity in plasma during the early phase of the study (up to 45 d). However, prolonged exposure resulted in significant increase in the plasma PON1 activity. This suggests that manifestation of insulin resistance in rats subjected to chronic exposure to MCP is associated with increase in PON1 activity. Our work provides rationale for studying whether the increase in PON1 activity observed in the present study serves to counter the deleterious effect of long term exposure to organophosphorus insecticides on metabolic homeostasis. Copyright © 2019 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.