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Objective:To identify the morphological alterations in the Golgi apparatus of skin fibroblasts in spinocerebellar ataxia type 3 (SCA3) patients.Methods:In this study, 3 SCA3 patients and 3 healthy volunteers were obtained in the First Affiliated Hospital of Zhengzhou University from 2016 to 2020. The cytosine, adenine, and guanine repeats of 3 SCA3 patients were 14/76, 20/80 and 21/82, respectively. Tissue mass culture was used to amplify skin fibroblasts derived from SCA3 patients and healthy volunteers. Cell viability and apoptosis were detected using cell counting kit-8 assay and flow cytometry, respectively. Western blotting and immunofluorescence assay were used to detect the protein expression of ataxin-3, Golgi reassembly stacking protein 2 (GORASP2), and Golgi matrix protein 130 (GM130) in the skin fibroblasts. The morphology of the Golgi apparatus in skin fibroblasts was detected using transmission electron microscopy.Results:Tissue culture of skin fibroblasts of both SCA3 patients and healthy volunteers was successfully established. The patient-derived dermal fibroblasts expressing mutant ataxin-3 protein exhibited reduced cell viability ( t=5.06,P=0.007), increased apoptosis ( t=3.77, P=0.020), fragmentation of the Golgi apparatus, increased expression of GM130 ( t=5.23, P=0.006), and decreased expression of GORASP2 ( t=4.35, P=0.012). Transmission electron microscopy revealed that the Golgi apparatus was disorganized in skin fibroblasts. Conclusion:Fragmentation of the Golgi apparatus occurs in the skin fibroblasts of SCA3 patients, and abnormal morphology and structure of the Golgi apparatus may be involved in the pathogenesis of SCA3.
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Objective: Although some studies have linked Asari Radix et Rhizoma (Asari Radix) administration to hepatocellular carcinoma (HCC), few studies have examined the association between the development of HCC and use of Asari Radix among patients in mainland China. This study aimed to evaluate the real-world association between Asari Radix and HCC in patients to strengthen the understanding of Asari Radix safety. Methods: A retrospective cohort study among hepatitis B virus (HBV)-monoinfected patients and non-HBV-monoinfected patients were performed. Patients over 18 years of age were eligible for inclusion. Prescription records of inpatients and outpatients were inquired to distinguish Asari Radix users and nonusers. The risk of developing HCC among Asari Radix users and nonusers in the HBV cohort and the non-HBV cohort was analyzed. Results: There were 49 500 HBV and 133 148 non-HBV patients involved in the two cohorts. Among HBV patients (2 901 users; 46 599 nonusers), the prevalence of HCC in Asari Radix users was lower than that in nonusers (145.70 vs. 265.43 per 10
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Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Subject(s)
Animals , Humans , Mice , Adenosine Triphosphate , Chemical and Drug Induced Liver Injury/etiology , Flavonoids , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NigericinABSTRACT
[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].
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Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
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Objective To investigate the application of remote monitoring systems for cardiac implantable electronic devices (CIED) and its success rate of data transmission in elderly patients.Methods A total of 97 elderly patients who had previously undergone procedures for pacemaker implantation,implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy (CRT) with remote monitoring capabilities between January 2013 and October 2016 at our hospital were enrolled.We evaluated the effect of the remote monitoring systems for data transmission,compared the outpatient follow-up rates between the groups one year after implantation,and conducted a telephone survey of patients.Results A total of 97 elderly patients,including 70 with pacemakers,20 with ICD and 7 with CRT,were enrolled in this study.Participants had a mean age of (78.2-±-6.4) years and 64 were male (66.0％).The Home Monitoring system was used for 85 cases and the Merlin.net remote monitoring system was used for 12 cases.Overall,95 patients (97.9 ％) completed the remote monitoring procedure,68 patients (70.1％) completed the outpatient follow-up,and 90 patients (92.8％) completed the telephone survey during a one-year follow-up period.The satisfaction rate for the remote monitoring systems was 94.4％ (85 patients),and 80 patients (90.0％％) expressed a willingness to continue to use the remote monitoring system if a replacement was needed.Conclusions For elderly patients with CIED,the remote monitoring systems can improve the follow-up rate with a high degree of satisfaction.
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This paper studied the influence ofsurface preponderantfungi on main effective substances of CitriReticulatae Pericarpium (CRP).Spreading plate method was used to isolatepredominant strains from the surface of CRP.Besides,the method combining microscopic and molecular identification was also adopted.HPLC and UVspectrophotometric methods were used to determine the main effective substances in CRP.From thesurface of CRP,the advantage strain fungi were Aspergillusniger and A.Flavus.After the inoculation of A.Niger and A.flavus against CRP,the effective compositionwas changed.And different A.niger strains had differenceeffectiveness oneffective chemical components,especially one strain of A.niger.Compared withthe control group,contents of total flavonoids and hesperidin were significantly increased (P＜0.01);and five types of obvious new chemical compositions were produced.It was concluded that the metabolic transformation of fungi was related tochanges ofeffective substances of CRP,which played a significant role in the aging process of CRP.The growth and metabolism of fungi consumeeffeetive substances and producechanges of composition.From the perspective of microorganisms,"the older,the better" of CRP hasa better explanation.
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Objective To investigate the way of pacemaker implantation in 127 elderly patients over 80 years old to reduce postoperative complications and improve the life quality. Methods One hundred and twenty-seven patients over 80 years old had the dual chamber pacing in 95 cases(74. 8%, including tri-chamber pacing) and the single ventricular pacing in 32 cases (25. 2%). Cephalic veins were used primarily in all patients with modified methods. The safe fixation of pacing leads were emphasized not only in the heart but also in the site of pacemaker pocket. The pacemaker package was made prior to the leads insertion in order to have enough time for stopping bleeding. It was necessary for some cases with diffused bleeding to use electric coagulation. All patients were told to get out of bed in the operating day or the day after procedure. Results Cephalic vein was well exposed. The successful rates of implanting pacing leads directly through cephalic vein were 92. 0% and 81. 5% in the single chamber and dual chamber patients, respectively. The overall complications observed in 5 cases(3. 9%) were pocket hematoma formation in 3 cases (2. 4%), cardiac tamponade in 1 case (0.8%), and disconnection of pacemaker with lead in 1 case (0.8%). There were no hemothorax, infection and lead dislodgement. Conclusions Insertion of pacing lead through cephalic vein is important, especially for the advanced aged patients. This operation can decrease the complications of subclavian vein puncture. Leads dislodgement are mainly due to the inadequate skill of operator, not to the patient s early activity out of bed. Appropriate way for stopping bleeding is the key to protect the patients from pacemaker pocket effusion and hemotama.