ABSTRACT
Our previous study showed that feeding mice with vitamin D deficiency diet markedly alleviated high-fat-diet-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency up-regulated the expression of uncoupling protein 3 (Ucp3) in white adipose tissue (WAT) and brown adipose tissue (BAT). The present study aimed to further investigate the effects of vitamin D and vitamin D receptor (Vdr) on Ucp1-3 (Ucps) expression in brown adipocyte and the mechanism involved in it. Rat primary brown adipocytes were separated and purified. The effects of the 1,25(OH)2D3 (1,25-dihydroxyvitamin D3; the hormonal form of vitamin D) and Vdr system on Ucps expression in brown adipocytes were investigated in basal condition and activated condition by isoproterenol (ISO) and triiodothyronine (T3). Ucps expression levels were significantly down-regulated by 1,25(OH)2D3 in the activated brown adipocyte. Vdr silencing reversed the down-regulation of Ucps by 1,25(OH)2D3, whereas Vdr overexpression strengthened the down-regulation effects. Hairless protein did express in brown adipocyte and was localized in cell nuclei. 1,25(OH)2D3 increased Hairless protein expression in the cell nuclei. Hairless (Hr) silencing notably elevated Ucps expression in activated condition induced by ISO and T3. Moreover, immunoprecipitation results revealed that Vdr could interact with Hairless, which might contribute to decreasing expression of Vdr target gene Ucps. These data suggest that vitamin D suppresses expression of Ucps in brown adipocyte in a Vdr-dependent manner and the corepressor Hairless protein probably plays a role in the down-regulation.
Subject(s)
Adipocytes, Brown/drug effects , Calcitriol/pharmacology , Mitochondrial Uncoupling Proteins/metabolism , Receptors, Calcitriol/agonists , Transcription Factors/metabolism , Vitamins/pharmacology , Adipocytes, Brown/metabolism , Animals , Cells, Cultured , Gene Expression Regulation , Male , Mitochondrial Uncoupling Proteins/genetics , Rats, Sprague-Dawley , Rats, Wistar , Receptors, Calcitriol/genetics , Receptors, Calcitriol/metabolism , Signal Transduction , Transcription Factors/genetics , Uncoupling Protein 1/genetics , Uncoupling Protein 1/metabolism , Uncoupling Protein 2/genetics , Uncoupling Protein 2/metabolism , Uncoupling Protein 3/genetics , Uncoupling Protein 3/metabolismABSTRACT
Our study aimed to explore the molecular mechanisms involved in the improvement of postoperative cognitive dysfunction (POCD) by dexmedetomidine (DEX). BV2 microglia cells were cultured under normal condition, DEX exposure (0.1 µg/mL), and lipopolysacchride (LPS) treatment (0.1 µg/mL) or with pretreatment of DEX before LPS incubation. For BV2 microglia cells, LPS induced markedly increased release of pro-inflammatory cytokines (interleukin [IL]-1ß, IL-6, and tumor necrosis factor-alpha [TNF-α]) and expressions of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB), while DEX pretreatment inhibited the LPS-induced production of pro-inflammatory cytokines and expressions of TLR4 and NF-κB. The spatial memory function was impaired in the aged mice following partial hepatectomy since the percentage of time spent in the target quadrant and the number of crossings over the former platform location were reduced. Pretreatment of DEX may attenuate neuroinflammation and improve POCD in aged mice through inhibiting the TLR4-NF-κB signaling pathway in the hippocampus.
Subject(s)
Adrenergic alpha-2 Receptor Agonists/pharmacology , Aging/genetics , Dexmedetomidine/pharmacology , Hippocampus/drug effects , Postoperative Cognitive Complications/drug therapy , Signal Transduction/drug effects , Toll-Like Receptor 4/genetics , Aging/metabolism , Animals , Cell Line , Gene Expression Regulation , Hepatectomy/adverse effects , Hepatectomy/methods , Hippocampus/metabolism , Hippocampus/physiopathology , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Liver/innervation , Liver/surgery , Male , Mice , Mice, Inbred C57BL , Microglia/cytology , Microglia/drug effects , Microglia/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Postoperative Cognitive Complications/etiology , Postoperative Cognitive Complications/genetics , Postoperative Cognitive Complications/physiopathology , Spatial Memory/drug effects , Spatial Memory/physiology , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
To investigate the effects of dexmedetomidine (DEX) on lipopolysaccharide (LPS)-induced neuroinflammation in BV2 microglia. BV2 microglial cells were treated with various concentrations of DEX (0, 1, 10, and 100 ng/mL) for 1 hour, and then incubated in the presence or absence of 0.1 µg/mL LPS for 24 hours. Cell viability was assessed by Cell Counting Kit-8 assays. The expression levels of IL-1ß, IL-6, and TNF-α were determined using enzyme-linked immunosorbent assay (ELISA). The expressions of TLR4 and NF-кB were detected by western blotting. Moreover, BV2 microglial cells were transfected with small interfering RNA (siRNA) specific for TLR4 (si-TLR4 group) or negative control siRNA (si-NC group) for 24 hours, followed by exposing to 0.1 µg/mL LPS for 24 hours. TLR4, IL-1ß, IL-6, and TNF-α expressions were detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR). There were no significant differences in cell viability with the different treatments. Compared with the control group, LPS markedly increased the release of IL-6, TNF-α, IL-1ß, TLR4, and NF-κB, but these increases were significantly attenuated by pretreatment with 10 or 100 ng/mL DEX in a dose-dependent relationship, but not with 1 ng/mL DEX. Gene expression levels of IL-1ß, IL-6, and TNF-α were obviously upregulated in si-NC group and si-TLR4 group when cells were exposed to 0.1 µg/mL LPS for 24 hours. Meanwhile, si-TLR4 group had significantly lower IL-1ß, IL-6, and TNF-α expressions than si-NC group. The anti-inflammatory effects of DEX on LPS-induced BV2 microglia may be mediated through pathway involving TLR4 and NF-κB.
Subject(s)
Dexmedetomidine/pharmacology , Inflammation/chemically induced , Inflammation/metabolism , Lipopolysaccharides/toxicity , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Animals , Blotting, Western , Cell Line , Cell Survival , Enzyme-Linked Immunosorbent Assay , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Mice , Microglia/drug effects , Microglia/metabolism , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Biological denitrification is now one of the most widely applied techniques to remove nitrogen from the aquatic environment, and mixotrophic denitrification has gained attention as it takes the characteristics of both heterotrophic and autotrophic denitrification. This study investigated the biological denitrification efficiency and the bacterial community structure of sludge sampled from a mixotrophic denitrification reactor, before and after adding a certain amount of phosphate. The results showed that the bacteria have the capability of denitrification even without phosphorus, but the addition of phosphorus could significantly improve the biomass and the denitrification activity. After phosphate was added, the autotrophic and heterotrophic denitrification activity increased to 0.056 mg·(L·min·g)-1 and 0.232 mg·(L·min·g)-1 on N/VSS, which was 2.9 and 3.9 times that of the sludge activity before phosphorus addition, respectively. The bacterial community structure illustrated that the denitrifiers increased remarkably from 13.47% to 44.82% and that the dominate bacteria have also changed. Meanwhile, the growth of autotrophic, heterotrophic, and mixtrophic bacteria were all improved significantly after phosphorus was added.
Subject(s)
Bacteria/drug effects , Denitrification , Nitrogen/isolation & purification , Phosphorus/pharmacology , Sewage/microbiology , Autotrophic Processes , BioreactorsABSTRACT
Translocator protein 18 kDa (TSPO) is now an attractive drug target for controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of neuroinflammation caused by systemic LPS administration. C57/BL6 mice were treated with lipopolysaccharide (LPS, 500 µg/kg, i.p.) three days after PK11195 administration (3mg/kg, i.p.). The drugs were not discontinued until the mice were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven days after LPS injection. Chronic LPS-injection in mice was characterized by cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, elevated Aß content with increased expression of ß-site APP cleaving enzyme-1 (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain progesterone and brain-derived neurophic factor (BDNF) level. PK11195 pretreatment protected cognitive function in LPS-injected animals and normalized the inflammatory proteins. Moreover, PK11195 pre-administration decreased elevated hippocampal Aßx-42 levels and increased brain levels of progesterone, allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 administration. Our data demonstrated that PK11195 could protect cognitive deficits induced by chronic LPS administration. The underling mechanism may involve alleviated neuroinflammation, increased synthesis of neurosteroid and decreased Aß accumulation accompanied by down-regulation of BACE-1.
Subject(s)
Amyloid beta-Peptides/metabolism , Anti-Inflammatory Agents/therapeutic use , Encephalitis/drug therapy , Gene Expression Regulation/drug effects , Isoquinolines/therapeutic use , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/metabolism , Animals , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Brain-Derived Neurotrophic Factor/metabolism , Cyclooxygenase 2/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Encephalitis/chemically induced , Encephalitis/metabolism , Encephalitis/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Lipopolysaccharides/toxicity , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL , Pregnanolone/metabolism , Progesterone/metabolism , Receptors, GABA/metabolismABSTRACT
AIM: To investigate the differences in family history of inflammatory bowel disease (IBD) and clinical outcomes among individuals with Crohn's disease (CD) residing in China and the United States. METHODS: We performed a survey-based cross-sectional study of participants with CD recruited from China and the United States. We compared the prevalence of IBD family history and history of ileal involvement, CD-related surgeries and IBD medications in China and the United States, adjusting for potential confounders. RESULTS: We recruited 49 participants from China and 145 from the United States. The prevalence of family history of IBD was significantly lower in China compared with the United States (China: 4.1%, United States: 39.3%). The three most commonly affected types of relatives were cousin, sibling, and parent in the United States compared with child and sibling in China. Ileal involvement (China: 63.3%, United States: 63.5%) and surgery for CD (China: 51.0%, United States: 49.7%) were nearly equivalent in the two countries. CONCLUSION: The lower prevalence of familial clustering of IBD in China may suggest that the etiology of CD is less attributed to genetic background or a family-shared environment compared with the United States. Despite the potential difference in etiology, surgery and ileal involvement were similar in the two countries. Examining the changes in family history during the continuing rise in IBD may provide further insight into the etiology of CD.
ABSTRACT
Endoscopic variceal obturation of gastric varices with tissue glue is considered the first choice for management of gastric varices, and is usually safe and effective. However, there is still a low incidence of complications and some are even fatal. Here, we present a case in which endoscopic variceal ligation caused laceration of the esophageal varicose vein with tissue glue emboli and massive bleeding after 3 mo. Cessation of bleeding was achieved via variceal sclerotherapy using a cap-fitted gastroscope. Methods of recognizing an esophageal varicose vein with tissue glue plug are discussed.
Subject(s)
Embolization, Therapeutic/adverse effects , Enbucrilate/adverse effects , Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/surgery , Hemostasis, Endoscopic/adverse effects , Lacerations/etiology , Embolization, Therapeutic/methods , Endoscopy, Gastrointestinal , Esophageal and Gastric Varices/diagnosis , Female , Gastrointestinal Hemorrhage/diagnosis , Gastrointestinal Hemorrhage/etiology , Gastroscopes , Hemostasis, Endoscopic/methods , Humans , Lacerations/diagnosis , Lacerations/surgery , Ligation , Middle Aged , Recurrence , Sclerotherapy/instrumentation , Treatment OutcomeABSTRACT
Objective@#To understand knowledge of comprehensive sexuality education and its associated factors among junior high school teachers in six provinces in China, in order to provide a scientific basis for teacher training.@*Methods@#From June to December 2021, a convenience sampling method was used to select 1 016 junior high school teachers from Beijing, Chongqing, Liaoning, Sichuan, Yunnan and Guangdong provinces. A structured questionnaire was used to investigate teachers knowledge of comprehenswe sexuality education. Binary Logistic regression was used to analyze the related influencing factors of the knowledge of comprehensive sexuality education among junior high school teachers.@*Results@#The study showed that the knowledge rate of comprehensive sexuality education among middle school teachers was 58.1%, and the knowledge rate was higher in teachers who had conducted sexuality education to students( χ 2=9.42, P <0.01). The percentage of the correct answer on the prevention and control of sexually transmitted diseases(26.0%), the impact of inequality on love relationships( 33.6 %), and the impact of mass media on sexual cognition(68.8%) was the lowest. Regardless of whether they had implemented sexuality education for students, the knowledge and awareness rate of sexual knowledge among biology teachers, school doctors/health teachers and mental health teachers was higher( OR=2.32, 4.17, P <0.05).@*Conclusion@#Knowledge of comprehensive sexuality education among middle school teachers still needs to be improved. It is advisable to strengthen the training of comprehensive sexuality education for middle school teachers and focus on teachers of subjects related to comprehensive sexuality education.
ABSTRACT
The metabolism of scutellarein was investigated in rats. Four metabolites (M1-M4) together with scutellarein were detected and identified as scutellarein-glucuronides in rat plasma by HPLC-DAD, HPLC-MS, and HPLC-MS/MS.