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1.
Article in Chinese | WPRIM | ID: wpr-885132

ABSTRACT

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

2.
Article in Chinese | WPRIM | ID: wpr-882507

ABSTRACT

In recent years, immunotherapy with immune checkpoint inhibitor (ICI) as the representative drug has become an important treatment method for advanced malignant tumors. Preclinical studies have found that disorders of the gut microbiota can reduce the clinical benefit of patients treated with ICI. The latest data indicate that antibiotics may further affect the occurrence and development of tumors and the efficacy of immunotherapy by changing the abundance and composition of intestinal microbiota. To sum up the role of anti-biotics in the immunotherapy of advanced malignant tumor may provide a new idea for the optimization of treatment strategies for patients with advanced cancer.

3.
Article in Chinese | WPRIM | ID: wpr-907601

ABSTRACT

N 6-methyladenosine (m 6A) methylation modification is defined as the methylation at the N 6 position of adenosine. This dynamic process is regulated by writer, eraser and reader. Accumulating evidence indicates that m 6A methylation modification is involved in the initiation and development of various digestive system neoplasms including proliferation, invasion, metastasis and chemoresistance. A further understanding about the role of m 6A methylation modification in digestive system neoplasms will benefit the development of a novel precise diagnostic and therapeutic strategy and finally improve the overall prognosis of patients.

4.
Article in Chinese | WPRIM | ID: wpr-668152

ABSTRACT

Objective:To investigate the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) in type 2 diabetic rats with periodontitis.Methods:46 male Wistar rats were randomly divided into the healthy group(n =10),the periodontitis group(n =12),the type 2 diabetes mellitus group(n =12) and the type 2 diabetic periodontitis group(n =12).Animal models were prepared respectively.The expression of OPG and RANKL protein in alveolar bone was detected by immunohistochemistry(IHC).Results:Compared with the healthy group,the expression of OPG in the type 2 diabetes mellitus group,the periodontitis group,the type 2 diabetes mellitus with periodontitis group decreased in turn,however the expression of RANKL increased in turn.The expression of OPG and RANKL had no significant difference between periodontitis group and type 2 diabetes periodontitis group,while there was statistically significant difference among the other groups (P < 0.05).Conclusion:Inflammation may lcad to upregulation of RANKL in osteoclasts and immune cells,and downregulation of OPG in osteoblasts.

5.
Protein & Cell ; (12): 804-819, 2016.
Article in English | WPRIM | ID: wpr-757370

ABSTRACT

Axonal transport of mitochondria is critical for neuronal survival and function. Automatically quantifying and analyzing mitochondrial movement in a large quantity remain challenging. Here, we report an efficient method for imaging and quantifying axonal mitochondrial transport using microfluidic-chamber-cultured neurons together with a newly developed analysis package named "MitoQuant". This tool-kit consists of an automated program for tracking mitochondrial movement inside live neuronal axons and a transient-velocity analysis program for analyzing dynamic movement patterns of mitochondria. Using this method, we examined axonal mitochondrial movement both in cultured mammalian neurons and in motor neuron axons of Drosophila in vivo. In 3 different paradigms (temperature changes, drug treatment and genetic manipulation) that affect mitochondria, we have shown that this new method is highly efficient and sensitive for detecting changes in mitochondrial movement. The method significantly enhanced our ability to quantitatively analyze axonal mitochondrial movement and allowed us to detect dynamic changes in axonal mitochondrial transport that were not detected by traditional kymographic analyses.


Subject(s)
Animals , Axonal Transport , Physiology , Cerebral Cortex , Cell Biology , Metabolism , Drosophila melanogaster , Cell Biology , Metabolism , Embryo, Mammalian , Gene Expression , Lab-On-A-Chip Devices , Microscopy, Confocal , Mitochondria , Metabolism , Motor Neurons , Metabolism , Movement , Mutation , Primary Cell Culture , RNA-Binding Protein FUS , Genetics , Metabolism , Rats , Rats, Sprague-Dawley , Software
6.
Chongqing Medicine ; (36): 4615-4617,4620, 2015.
Article in Chinese | WPRIM | ID: wpr-602635

ABSTRACT

Objective To explore the effects of visfatin in glucose metabolism by testing the expression of visfatin in liver of rats in different glucose metabolic statuses .Methods SD rats were randomly divided into five groups :normal control group (NC group) ,diet induce obesity group (DIO group) ,diabetes mellitus group (DM group) ,diabetes controlled by insulin group (INS group)and diabetes controlled by metformin group (MET group) .Tested the data of blood glucose (FPG) ,triglyceride(TG) ,total cholesterol(TC) ,free fat acid(FFA) ,fasting insulin(Fins) .The liver of rats was used to test visfatin ,glucose‐6‐phosphatase(G‐6‐pase) mRNA by RT‐PCR and visfatin ,AMP‐activated protein kinase‐α (AMPKα) ,phosphor‐AMP‐activated protein kinase‐α (p‐AMPKα) protein by Western blot .Results FBG of group DM increased than group NC and DIO (P< 0 .01) ;FBG of group INS and MET decresed than group DM (P < 0 .01) ;HOMA‐IR of group DIO and DM increased than group NC (P < 0 .01) ;HOMA‐IR of group DM increased than group DIO (P< 0 .01) .ISI of group DIO and DM decresed than group NC (P< 0 .01) ;ISI of group DM de‐creased than group DIO(P< 0 .01) .TG of group DIO increased than group NC (P< 0 .01) .TG of group INS and MET decreased than group DM (P< 0 .05) .The level of TG and TC of group DM ,INS and MET increased than group NC (P< 0 .05) .The level of serum FFA of group DM ,INS and MET were significantly higher than group NC (P < 0 .05) ;FFA of group DM increased than group DIO(P< 0 .05) .The expression of visfatin mRNA of group DM increased than group NC and DIO (P< 0 .05) ;visfatin mRNA of group INS and MET decreased than group DM (P< 0 .01) .Group DM ,INS and MET had a significantly higher level of G‐6‐Pase mRNA of than group DIO( P < 0 .05) ;Group MET had a significantly lower level of G‐6‐Pase mRNA of than group DM (P <0 .05) .The expression of visfatin protein of group DM ,INS and MET increased than group NC ( P < 0 .05) .The expression of AMPKα protein of group DM ,INS and MET decresed than group NC(P< 0 .05) ;AMPKα of group DM decresed than group DIO (P<0 .05) .The expression of p‐AMPKα protein of group DIO ,DM ,INS and MET decresed than group NC (P< 0 .01) .Conclusion The ex‐pression of visfatin in liver of SD rats might have something to do with insulin resistance and diabetes .We could′t consider that visfatin can affect the pathway of metformin activated AMPK to decrease blood glucose .

7.
Article in Chinese | WPRIM | ID: wpr-815498

ABSTRACT

OBJECTIVE@#To investigate the effects of serum from the obesity patients and obesity patients with Diabetic mellitus on toll-like receptor 4/Nuclear factor -κB p65 (TLR/NF-κB) pathway in human THP-1 monocytes and to explore the inflammatory immune response in obesity.@*METHODS@#Peripheral serum was isolated from healthy volunteers (the control group), the obesity patients (Ob group) and the obesity patients with diabetic mellitus (the Ob with DM group), respectively, 20 in each group. THP-1 monocytes were incubated with the serum for 48 h. The monocytes and culture supernatant were collected. The phosphorylation level of NF-κB p65 protein in THP-1 monocytes was evaluated by Western blot as well as immunofluorescence assay. The TLR4 mRNA expression was evaluated by RT-PCR. ELISA was used to measure the monocyte chemotactic protein-1 (MCP-1) levels in the culture supernatant.@*RESULTS@#In the presence of serum, the obesity group and the obesity with diabetic mellitus group showed the up-regulated phosphorylation level of NF-κB p65 protein and TLR4 mRNA expression in THP-1 monocytes compared with the healthy control group (both P<0.05), and the MCP-1 levels in the obesity patients were up-regulated significantly compared with the healthy control group [healthy control group (26.4 ± 3.9) pg/mL, Ob group (45.8 ± 10.0) pg/mL, Ob with DM group (58.0 ± 15.3) pg/mL; P<0.05]. These parameters were further up-regulated in the obesity patients with diabetic mellitus patients.@*CONCLUSION@#The serum from the obesity patients or the obesity patients with diabetes can induce monocyte dysfunction, which might be related to the activation of TLR4/NF-κB signaling pathway.


Subject(s)
Cell Line , Chemokine CCL2 , Diabetes Mellitus , Blood , Humans , Monocytes , Cell Biology , Metabolism , Obesity , Blood , Phosphorylation , Serum , Signal Transduction , Toll-Like Receptor 4 , Metabolism , Transcription Factor RelA , Metabolism , Up-Regulation
8.
Article in Chinese | WPRIM | ID: wpr-814629

ABSTRACT

OBJECTIVE@#To characterize the expression of Toll-like receptor 4 (TLR4) in monocytes of diabetic nephropathy (DN) patients and the response of TLR4 to lipopolysaccharide (LPS), and, further, to explore the potential effects of inflammatory immune response in DN.@*METHODS@#Thirty DN patients with uremia, ten early-type 2 DN patients, and twenty healthy volunteers were enrolled for the determination of TLR4 expression in monocytes by using peripheral blood flow cytometry. Peripheral blood mononuclear cells (PBMCs) were isolated and subjected to 1 μg/mL LPS for 24 h. Monocytes were collected to assay NF-κB p65 and Notch1 expression by Western blot, with immuneofluorescence detection. Serum and supernatants were sampled for the determination of interleukin-6 (IL-6) concentration by using ELISA. Serum C-reactive protein (CRP) level was determined by using the immunoturbidimetry.@*RESULTS@#Compared with the normal control, type 2 DN uremic patients had a significantly higher TLR4 fluorescence-blot intensities (FI), and serum CRP and IL-6 levels [TLR4 FI: DN uremia patients 2.8±0.9; early type 2 DN patients 3.4 ±0.7; healthy subjects 1.6±0.7. IL-6 concentration: DN uremia patients (84.8±20.7) pg/mL; early type 2 DN patients (63.20±14.4) pg/mL; healthy subjects (11.0±2.0) pg/mL. CRP concentraton: DN uremia patients (5.4±2.8) mg/L; early type 2 DN patients (3.7±1.7) mg/L; healthy subjects (1.7±0.7) mg/L. P<0.01 for any DN-group vs control]. In early type 2 DN patients, following exposure to LPS, PBMCs showed a significant upregulation in TLR4 and NF-κB p65 expression and a remarked increase in serum IL-6 level (all P<0.05), and NF-κB p65 transfer to the nucleus is enhanced. Notch1 protein expression was not significantly altered in any group.@*CONCLUSION@#A disturbance in proinflammatory CD14(+)CD16(+) monocytes occurs in type 2 DN patients. Such immunological dysfunction may be related to activation in NF-κB/TLR4 signaling pathways, and have nothing to do with the Notch1 signaling pathway.


Subject(s)
Adult , Aged , Diabetes Mellitus, Type 2 , Blood , Diabetic Nephropathies , Blood , Female , Humans , Lipopolysaccharides , Pharmacology , Male , Middle Aged , Monocytes , Metabolism , Receptor, Notch1 , Genetics , Metabolism , Signal Transduction , Toll-Like Receptor 4 , Genetics , Metabolism , Transcription Factor RelA , Genetics , Metabolism
9.
Protein & Cell ; (12): 477-486, 2011.
Article in English | WPRIM | ID: wpr-757074

ABSTRACT

Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.


Subject(s)
Aged , Aging , Genetics , Metabolism , Pathology , Amyotrophic Lateral Sclerosis , Genetics , Metabolism , Pathology , Animals , Animals, Genetically Modified , Disease Models, Animal , Drosophila melanogaster , Genetics , Metabolism , Gene Expression , Humans , Microscopy, Electron, Scanning , Motor Neurons , Metabolism , Pathology , Mushroom Bodies , Metabolism , Pathology , Mutant Proteins , Genetics , Metabolism , Mutation , Photoreceptor Cells, Invertebrate , Metabolism , Pathology , Plasmids , RNA-Binding Protein FUS , Genetics , Metabolism , Recombinant Fusion Proteins , Genetics , Metabolism , Retinal Degeneration , Pathology , Transfection
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