![[PukiWiki]](image/pukiwiki.png "[PukiWiki]")
Dexmedetomidine (DEX) has multiple biological effects. Here, we investigated the neuroprotective role and molecular mechanism of DEX against lipopolysaccharide (LPS)-induced hippocampal neuronal apoptosis. Sprague Dawley rats were intraperitoneally injected with LPS (10 mg/kg) and/or DEX (30 µg/kg). We found that DEX improved LPS-induced alterations of hippocampal microstructure (necrosis and neuronal loss in the CA1 and CA3 regions) and ultrastructure (mitochondrial damage). DEX also attenuated LPS-induced inflammation and hippocampal apoptosis by inhibiting the increase of interleukin-1β, interleukin-6, interleukin-18, and tumor necrosis factor-α levels and downregulating the expression of mitochondrial apoptosis pathway-related proteins. Moreover, DEX prevented the LPS-induced activation of the c-Myc/chloride intracellular channel 4 (CLIC4) pathway. DEX inhibited the p38 MAPK pathway, but not JNK and ERK. To further clarify whether DEX alleviated LPS-induced neuronal apoptosis through the p38 MAPK/c-Myc/CLIC4 pathway, we treated PC12 cells with p38 MAPK inhibitor SB203582 (10 µM). DEX had the same effect as SB203582 in reducing the protein and mRNA expression of c-Myc and CLIC4. Furthermore, DEX and SB203582 diminished LPS-induced apoptosis, indicated by decreased Bax and Tom20 fluorescent double-stained cells, reduced annexin V-FITC/PI apoptosis rate, and reduced protein expression levels of Bax, cytochrome C, cleaved caspase-9, and cleaved caspase-3. Taken together, the findings indicate that DEX attenuates LPS-induced hippocampal neuronal apoptosis by regulating the p38 MAPK/c-Myc/CLIC4 signaling pathway. These findings provide new insights into the mechanism of Alzheimer's disease and depression and may help aid in drug development for these diseases.A Gram-reaction-negative halotolerant bacterial strain, designated Ka21T, was isolated from agricultural soil and characterised using a polyphasic approach to determine its taxonomic position. On the basis of 16S rRNA gene sequence analysis, highest similarity was found with Sphingobacterium alkalisoli Y3L14T (96.72%). Cells were observed to be aerobic, non-motile rods. The isolate was found to be able to grow between 0 and 10% of NaCl concentration. The assembled genome of strain Ka21T has a total length of 5.2 Mb with a G + C content of 41.0 mol%. According to the genome analysis, Ka21T encodes several glycoside hydrolases that may play a role in the degradation of accumulated plant biomass in the soil. Based on phenotypic characteristics and phylogenetic analysis, it is concluded that strain Ka21T represents a novel species in the Sphingobacterium genus for which the name Sphingobacterium pedocola sp. https://www.selleckchem.com/products/shp099-dihydrochloride.html nov. is proposed. The type strain of the species is strain Ka21T (= LMG 31575T = NCAIM B.02636T). To study the correlation between retinoblastoma (RB) associated with orbital pseudocellulitis and high-risk histopathology features. Retrospective study of 32 patients who underwent primary enucleation for RB presenting with orbital pseudocellulitis. All RB patients presented with orbital pseudocellulitis. The mean age at presentation of RB was 30months (median, 24months; range, 3-70months). There were 14 (44%) males and 18 (56%) females. All patients were referred with a diagnosis of RB with orbital pseudocellulitis. Tumor was bilateral in 12 (38%) patients but orbital pseudocellulitis was unilateral in all cases. The pseudocellulitis features included proptosis (n = 9; 28%), eyelid edema (n = 22; 69%), conjunctival congestion (n = 23; 72%), and conjunctival chemosis (n = 15; 47%). Based on clinical features and orbital imaging, all patients were diagnosed to have group E intraocular RB. All patients received intravenous steroids prior to enucleation. On histopathology, tumor necrosis was present in all cases with a mean % necrosis of 60% (median, 60%; range, 10% to 90%). Most tumors (72%) were poorly differentiated. High-risk histopathology features were noted in 23 (72%) cases and adjuvant chemotherapy was advised for all these patients. The most common high-risk histopathology features included post-laminar optic nerve infiltration (34%) and scleral infiltration (22%). Over a mean follow-up period of 34months (median, 9months; range, < 1-188months), there was no event of metastasis or death in any patient. RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.RB presenting with orbital pseudocellulitis is associated with high incidence of high-risk histopathology features.Seminal studies on negation revealed that negative sentences are difficult to process, as they require an extra mental step. Similarly, at the discourse level, concession has been repeatedly shown to be more complex than other relations such as result because it implies the denial of an inference. The affinity between negation and concession prompted the present study to test whether overt verb polarity would affect the processing of upcoming discourse relations. In particular, it investigated whether negation can act as a cue to help process concessive relations. Results from four self-paced reading experiments indeed show a robust facilitation effect of negation on concession that cancels the baseline difference between concessive and result relations, thus nuancing existing context-blind categorizations of concession as a highly complex relation. This study furthers our understanding of how various types of cues interact in discourse processing and switches the focus from "what makes negation easier to process" to "what is made easier thanks to negation".We propose that negative clauses are generally interpreted as if the affirmative portion of the clause is under discussion, a likely topic. This predicts a preference for affirmative (topical) antecedents over negative antecedents of a following missing verb phrase (VP). Three experiments tested the predictions of this hypothesis in sentences containing negation in the first clause followed by an ambiguous as-clause as in Don't cross on red as a stupid person would and its counterpart with smart replacing stupid. In Experiment 1 sentences containing an undesirable attribute adjective such as stupid were rated as more natural, and read faster, than their desirable attribute counterparts (smart), with or without a comma preceding as. The second experiment indicated that the interpretation of the missing VP reflected the attribute adjective's desirability, with processing difficulty presumably reflecting reanalysis from the initial affirmative antecedent (cross on red) to include negation when the initial interpretation violated plausibility. A third experiment generalized the effect beyond sentences with an initial contracted don't.Using a selection of molecular biomarkers, we evaluated responses in freshwater mussels (Anodonta anatina) exposed to effluent from an industrial wastewater treatment facility. The aims of this work were to (1) assess biomarkers of general toxicity under sublethal exposure to an anthropogenic mixture of chemicals, represented by an arbitrary effluent, and (2) evaluate the potential of A. anatina as a bioindicator of pollution. Adult mussels (n = in total 32; 24 males and 8 females) were exposed (96 h) in the laboratory to a fixed dilution of effluent or to a control treatment of standardized freshwater. Metal concentrations were in general higher in the effluent, by an order of magnitude or more, compared to the control. Toxic unit estimates were used as proxies of chemical stress, and Cu, Ni, and Zn were identified as potential major contributors (Cu> Ni > Zn). Six transcriptional (cat, gst, hsp70, hsp90, mt, sod) and two biochemical (AChE, GST) biomarkers were analyzed in two tissues, gills, and digestive glands. Out of the 16 responses (eight biomarkers × two tissues), 14 effect sizes were small (within ± 28 % of control) and differences non-significant (p > 0.05). Results did however show that (1) AChE activity increased by 40% in gills of exposed mussels compared to control, (2) hsp90 expression was 100% higher in exposed female gills compared to control, and (3) three marker signals (AChE in both tissues, and hsp70 in gills) differed between sexes, independent of treatment. link2 Results highlight a need for further investigation of molecular biomarker variability and robustness in A. anatina.The effects of daily mean temperature on health outcomes have been discussed in many previous studies, but few have considered the adverse impacts on upper respiratory tract infection (URTI) due to variance of temperature in one day. Diurnal temperature range (DTR) was a novel indicator calculated as maximum temperature minus minimum temperature on the same day. In this study, generalized additive model (GAM) with quasi-Poisson distribution was used to investigate the association between DTR and the number of daily outpatient visits for URTI among college students. Data about meteorological factors and air pollutants were provided by Hubei Meteorological Bureau and Wuhan Environmental Protection Bureau, respectively. Outpatient visits data were collected from the Hospital of Wuhan University from January 1, 2016, to December 31, 2018. Short-term exposure to DTR was associated with the increased risk of outpatient for URTI among all college students. Per 1 °C increased in DTR was associated with 0.73% (95%CI 0.24, 1.21) increased in outpatient visits of all college students for URTI at lag 0 day. The greatest effect values were observed in males [1.35% (95%CI 0.33,2.39)] at lag 0-6 days, and in females [0.86% (95%CI 0.24, 1.49)] at lag 0-1 days. DTR had more adverse health impact in autumn and winter. Public health departments should consider the negative effect of DTR to formulate more effective prevention and control measures for protecting vulnerable people.Fine particles (especially PM2.5 particles) in ambient air can cause irreversible effects on human health. In the present study, seasonal variations in toxicity PM2.5 (cell viability and release of pro-inflammatory cytokines) were exposed human lung cells (A549) to concentrations of PM2.5 samples in summer (sPM2.5) and winter (wPM2.5) seasons. Cells were separately exposed to three concentrations of PM2.5 (25, 50, and 100 μg/mL) and three times (12 h, 1 and 2 days). We evaluated cell viability by MTT assay [3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide] and liberation of pro-inflammatory cytokines (interleukin-6 and interleukin-8) by the ELISA method. The toxicological results of this study showed that increasing the concentration of PM2.5 particulates and contact time with it reduces cell viability and increases inflammatory responses. Seasonal cytotoxicity of PM2.5 particles in high-traffic areas at summer season compared to winter season was lower. The lowest percent of viability at 2 days of exposure and 100 μg/mL exposure in the winter sample was observed. Also, PM2.5 particles were influential in the amount of interleukins 8 and 6. The average release level of IL-6 and IL-8 in the cold season (winter) and the enormous exposure time and concentrations (2 days-100 μg/mL) was much higher than in the hot season (summer). These values were twice as high for winter PM2.5 samples as for summer samples. The compounds in PM2.5 at different seasons can cause some biological effects. The samples' chemical characteristics in two seasons displayed that the PMs were diverse in chemical properties. In general, heavy metals and polycyclic aromatic hydrocarbons were more in the winter samples. However, the samples of wPM2.5 had a lower mass quota of metals such as aluminum, iron, copper, zinc, and magnesium. link3 Concentrations of chromium, cadmium, arsenic, mercury, nickel, and lead were more significant in the sample of wPM2.5.
