ABSTRACT
Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.
ABSTRACT
Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.
ABSTRACT
The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.
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Under the hypoxic condition, organs or cells trigger a series of reactions or responses to adapt to the physiological requirement. These responses involve a complex regulation at different levels from organs, in particular the kidney (producing erythropoietin), to cells throughout the body. Actually, the responses to hypoxia from adaption to injury largely depend on the degree and time of hypoxia. In the past two decades, with the discovery of hypoxia-inducible factor (HIF), the mechanisms of erythropoiesis regulation were elucidated gradually, which has provided a novel therapeutic strategy for hypoxia-related diseases, especially renal anemia. In this review we focus on the latest advances in oxygen sensing and adaptive mechanism.
Subject(s)
Humans , Anemia , Hypoxia , Kidney , Kidney Diseases , OxygenABSTRACT
OBJECTIVE: To explore the composition of microbial communities in vagina and intestine of the mother,the placenta and the neonatal meconium after cesarean section and to analyze the origin of neonatal intestinal microbiota.METHODS: Samples of intestine,vagina and placenta and neonatal meconium from 4 women who underwent cesarean section in Yan'an Hospital of Kunming City in October 2016 were collected.The high-throughput sequencing technology was used to sequence the 16 S rRNA gene,and the composition of the microbial communities and the relationship among the samples were analyzed.RESULTS: Firstly,comparing the number of OTUs in different samples,it was found that the number in placenta was the highest,followed by the intestine and vagina,and the least was in the neonatal meconium.Secondly,each sample was analyzed by PCA clustering,and it was found that the neonatal meconium was affected least by individual differences but the vagina was affected most.The intestinal and placental microbial communities had certain similarities.Finally,comparing the microbial community composition of each sample,it was found that the highest abundance in the neonatal meconium and placenta was Proteobacteria,and in the intestine and vagina it was the Firmicutes.CONCLUSION: During the caesarean section,maternal microbiota transfer may be from the mother's intestine to the placenta and then to the infant's intestine.
ABSTRACT
The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.
Subject(s)
Humans , Apoptosis , Autophagy , Carcinoma, Hepatocellular , Drug Therapy , Pathology , Cell Line, Tumor , Cell Proliferation , Complex Mixtures , Pharmacology , Up-RegulationABSTRACT
<p><b>OBJECTIVE</b>To study the effects of Tianwang Buxinwan decoction on the contents of amino acids neurotransmitters in corpus striatum of rats to implicate the mechanism of Tianwang Buxinwan promoting and Improving sleeping.</p><p><b>METHOD</b>Contents of two amino acids neurotransmitters in corpus striatum of rats were prepared by microdialysis technology and were determined by HPLC which involved pre-column derivation with orthophthaladehyde, recersed-phase gradient elution and fluorescence detection.</p><p><b>RESULT</b>In the experimental separation condition, Tianwang Buxinwan seemed do not influence three kinds of contents of amino acids neurotransmiters (glutamic acid, glycin, aspartic acid), but TBW seemed increase the content of gamma-GABA in corpus striatum of rats.</p><p><b>CONCLUSION</b>The effects of Tianwang Buxinwan to relieve uneasiness may relate with the inhibitory amino acids gamma-GABA. Tianwang Buxinwan may promote increasing the content of gamma-GABA. This discovery may be helpful for the deep study of related mechanism of Tianwang Buxinwan.</p>
Subject(s)
Animals , Male , Rats , Brain , Metabolism , Brain Chemistry , Drugs, Chinese Herbal , Microdialysis , Neurotransmitter Agents , Metabolism , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of mesenchymal stem cells (MSCs)on cranial suture under mechanical strain in growing goats.</p><p><b>METHODS</b>10 growing goats were used in this study. A customized distractor was used for distraction of the coronal suture at a rate of 0.4 mm/day for 8 days. The experimental group(5 goats) was injected with autologous MSCs into the distracted region, whereas the control group (5 goats) with injection of physiological saline. All animals were killed at 4 weeks after the end of distraction. Scanning electron microscopy and histological analysis were taken to observe the samples.</p><p><b>RESULTS</b>4 weeks after the end of distraction, the cranial sutures in all animals were separated successfully. The new bone formation at the edge of suture in the experimental group was superior to that in the control group.</p><p><b>CONCLUSION</b>Autologous MSCs transplantation may promote the cranial suture distraction osteogenesis in the growing goats.</p>