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Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Sujets)
Animaux , Souris , Gouttelettes lipidiques , Autophagie , Autophagosomes , Homéostasie , TriglycérideRésumé
Objective To investigate the clinical and pathological characteristics of kidney disease by renal biopsy,thus to provide reference and help for the application of renal biopsy in the diagnosis and treatment of kidney diseases. Methods From January 2015 to June 2017,136 cases with kidney disease in Zhoushan Hospital were slected in the research. All patients received renal biopsy,histochemical staining of renal biopsy samples,immunohistochemical staining,and observed under light microscope, and the pathological changes of the situation, combined with clinical data,the clinical and pathological characteristics of renal biopsy patients were summarized. Results The distribution of pathological type of primary glomerulonephritis,the highest proportion (79. 41%),secondary glomerulonephritis (15. 44%),followed by the rest of the renal tubular and interstitial nephropathy (5. 15%). Of the primary glomerulo-nephritis,membranous nephropathy ( 28. 68%), IgA nephropathy ( 27. 94%) accounted for a relatively high proportion. However,in secondary glomerulonephritis,diabetic nephropathy (5. 88%) was the highest proportion. Of gender,the proportion of the male patients (59. 56%) was higher than that of the female patients (40. 44%,χ2 =9. 941,P<0. 05),primary glomerulonephritis in the male patients(62. 04%) was higher thanthat in the female patients (37. 96%) (χ2 =12. 519,P<0. 05). The age of renal biopsy was focused on the age of 41-50 years,>50-60 years,>60 -70 years old, which was mainly the elderly population. Conclusion Renal biopsy of kidney disease is mainly primary glomerulonephritis,the incidence of people mainly in the elderly male population. Compre-hensive diagnosis is needed for different kidney diseases with renal biopsy and the specific circumstances.
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Objective To observe the clinical efficacy of treatment of diabetic nephropathy with Shuxuening injection combined with benazepril.Methods 60 cases from January 2014 to January 2015,were randomly divided into observation group and control group of 30 patients.the control group were given benazepril treatment,observation group were based on Shuxuening injection treatment,patients were followed up and record changes related indicators.Results The urinary β2-MG and hs-CRP were after treatment(0.38±0.08,6.29±1.40)mg/L,than the control group(0.48±0.10,7.74±1.36)mg/L,and the difference was significant sex(P<0.05); after treatment observation group 24H urine protein quantitative detection of(0.69±0.50)g/24h,than the control group(1.04±0.63)g/24h,and the difference was statistically significant(P<0.05); After the observation group patients,low-density lipoprotein,serum creatinine value were(359.2±50.3mg/L,2.40±0.63mmol/L,95.6±22.3mol/L),were better than the control group(379.8±48.3mg/L,3.44±0.76mmol/L,108.5±34.2mol/L),and the difference was statistically significant(P<0.05); observation group total effective rate was 90.0%,higher than 73.0 percent,and the difference was statistically significant(P<0.05).Conclusion Shuxuening injection combined with benazepril clinical treatment of diabetic nephropathy exact,no significant side effects,is worthy of further research and application.
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<p><b>OBJECTIVE</b>To investigate the drug resistance, β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding genes of, and to explore its structure and pathogenic function.</p><p><b>METHODS</b>The strain was isolated by plate streaking method and identified by automatic bacteria detection system and 16S RNA gene PCR. Microdilution method was applied for drug susceptibility test. β-lactamases, extended spectrum β-lactamases (ESBL) and carbapenemases were detected using nitrocefin-disk, Kirby-Bauer disk, and Hodge test, respectively. Five β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding gene of the isolate were amplified by PCR for sequencing. Bioinformatic softwares were used to analyze the structure and function of the product of protoporphyrin ferrochelatase-encoding gene.</p><p><b>RESULTS</b>A strain belonging towas isolated. This isolate was sensitive to cefepime, ciprofloxacin, ofloxacin and tigecycline, but resistant to five penicillins, four cephalosporins and two carbapenems antibiotics. The isolate produced β-lactamases but did not produce ESBL and carbapenemases. The isolate had five distinct β-lactamase-encoding genes and protoporphyrin ferrochelatase-encoding gene. The product of protoporphyrin ferrochelatase-encoding gene contained two functional domains of protoporphyrin ferrochelatase belonging to type Ⅱ chelatase superfamily that presented the most closely genetic relationship with the protoporphyrin ferrochelatase of.</p><p><b>CONCLUSIONS</b>The isolate ofhas a higher resistance to β-lactam antibiotics and its β-lactamase-encoding genes are different with the common bacterial β-lactamase-encoding genes. Protoporphyrin ferrochelatase may act as an important virulence factor of.</p>
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Objective To study the clinical effect of tacrolimus combined with small dose of prednisolone in treatment of IgA nephropathy.Methods 84 cases with IgA nephropathy were randomly divided into study group and the control group in accordance with the digital table method.The control group was given simple hormone treatment, while the study group was treated with tacrolimus combined with small dose of prednisolone.The clinical efficacy and safety were compared between the two groups.Results The treatment effective rate (100.00%)and complete remis-sion rate (73.81%)of the study group were significantly higher than those in the control group (76.19%, 23.81%),and the differences were statistically significant (χ2 =21.01,11.35,P 0.05).When patients lighter (Lee's Ⅱ level),the team for complete response rate was significantly higher than the control group,and the difference was statistically significant (χ2 =5.01,P 0.05).The incidence rate of adverse reactions in the study group (19.05%)was not significantly different from that of the control group (16.67%)(χ2 =0.08,P >0.05 ).Conclusion Tacrolimus combined with small dose hormone for the treatment of IgA nephropathy has high clinical value,it can significantly reduce the level of IgA nephropathy 24h nephropathy,and adverse reactions.
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Objective To investigate the effects of astragalus membranaceus parenteral solution combined with recombinant human erythropietin (rHuEPO) on erythrocyte immunity function in patients with hemodialysis. Methods Fifty-one patients of chronic renal failure(CRF) with hemodialysis were divided into 2 groups randomly according to whether treated with astragalus membranaceus parenteral solution or not(therapeutic group, was 26 cases and control group was 25 cases). IgG, IgA, IgM, RBC-C3b,RR,RBC-ICR, erythrocyte percentage of CD35 positive and SOD was measured before treatment and 8 weeks after treatment. Results After 8 weeks' treatment, IgG,IgA,IgM levels in therapeutic group and IgG,IgA levels in control group were higher than those before treatment(P < 0.01 ). IgM [ (2.03±0.73 ) g/L ] was higher than that in control group (P< 0.05). RBC-C3B,RR, erythrocyte percentage of CD35 positive and SOD were higher and RBC-ICR was lower than those before treatment in two groups (P < 0.05 ) ;compared with that in control group, RBC-C3b, RR was higher [(10.85±2.31 )% ] and RBC-ICR was lower [(5.34±1.91 )% ] (P < 0.05 ).Conclusion Astragalus membranaceus parenteral solution combined with rHuEPO is superior to improve CRF patients' levels of immune globulin and erythrecyte immunity function.
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Objective To detect the relationship between plasma B-type natriuretic peptide(BNP) and left ventricular function in elderly patients with maintenance hemodialysis (MHD). Method Plasma BNP concentration were measured in 50 MHD patients (MHD group) and 30 healthy controls (control group). Echocardiographic examinations were performed including left ventricular ejection fraction (LVEF). Results The median plasma BNP level in MHD group before and after hemodialysis was 213.5 ng/L and 110.2 ng/L, and obviously higher than that in control group (20.2 ng/L) (P<0.01). Spearman rank correlation showed that plasma BNP level was significantly negatively correlated with LVEF (r=-0.4357, P< 0.05). The median plasma BNP level in the patients with LVEF < 50% before and after hemodialysis was 386.5 ng/L and 232.0 ng/L, significantly higher than that in the patients without left ventricular dysfunction (LVEF≥50%) (59.7 ng/L and 29.1 ng/L)(P<0.01). Conclusions The level of BNP may reflect dynamic change of left ventricular function in MHD patients. It can help to diagnose and treat cardiovascular disease in MHD patients early.