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Creutzfeldt-Jakob disease is a type of fatal central nervous system degeneration caused by infectious pathogenic prion protein. The early clinical manifestations of the disease are diverse and lack of specificity, so it is difficult to distinguish it from other neurological diseases. Researchers have made long-term exploration and clinical applications in imaging, electroencephalography, and detection of special proteins in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease. In recent years, the development of new methods for the detection of pathogenic prion protein has provided great help for the early diagnosis of the disease, and it has great clinical application prospects. This article reviews the current research on the epidemiology, etiology and pathological mechanism and early diagnosis biomarkers of Creutzfeldt-Jakob disease, in order to help clinical colleagues to further enhance the understanding of Creutzfeldt-Jakob disease.
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Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.
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The central nervous system inflammatory response plays an important role in the pathogenesis of AD.Pro-inflammatory cytokines can induce inflammatory reactions in the body,enhance the neurotoxic effects caused by Aβ,promote the pathogenesis of AD and anti-inflammatory factors can down-regulate the inflammatory response,play a protective role and promote the reconstruction of damaged tissue.However,due to the existence of genetic polymorphisms,the influence of inflammatory factors on AD is complicated,especially in different population groups.Studing and clarifying the relationship between gene polymorphisms of inflammatory factors and and the pathogenesis of AD will promote the study of the mechanism of AD and provide a new method for the treatment of AD.Therefore,this article mainly reviews this.
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Objective To observe the effect and molecular mechanism of lipopolysaccharide (LPS) on activation and differentiation of microglia (MG) cells. Methods Routinely in vitro cultured BV2 microglia cells were divided into control group and LPS group: BV2 microglia cells in the LPS group were treated with 200 ng/mL LPS; cells in the control group were added the same amount of medium. Six h after treatment, real-time quantitative (qRT)-PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the inflammatory factors, interleukin (IL)-1β and tumor necrosis factor (TNF)-α mRNA and protein expressions in supernatant of cell culture medium. The iNOS, CD32, Arg1 and CD206 mRNA and protein expressions were detected by qRT-PCR and immunofluorescence, respectively. The mRNA and protein expressions of Notch1, Hes1 and Hes5 were detected by qRT-PCR and Western blotting. Results After LPS stimulation, BV2 microglia cells were activated and the morphological changes were observed. The IL-1β and TNF-α protein and mRNA expressions in the LPS group were significantly increased as compared with those in the control group (P<0.05). The iNOS and CD32 protein and mRNA expressions in the LPS group were significantly increased as compared with those in the control group (P<0.05). The Arg1 and CD206 mRNA and protein expressions showed no significant differences between the two groups (P>0.05). The Notch1 and Hes1 mRNA and protein expressions in the LPS group were significantly increased as compared with those in the control group (P<0.05), while no significant differences on Hes5 mRNA and protein expressions were noted between the two groups (P>0.05). Conclusion LPS activates MG cells, which may regulate the differentiation of MG cells into M1 through Notch signaling pathway and promote inflammatory response; therefore, Notch signaling pathway may be a target for regulating MG cells differentiation and reducing inflammatory damage.
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The etiology underlying ischemic stroke is still elusive. Previous studies have indicated that inflammation might play a key role in the pathogenesis, which provided a novel insight into the therapeutic strategy of ischemic stroke. In this review, we summarize some drugs which regulate the activation and polarization of microglia and further alleviate neurological symptoms.
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Aquaporin 4 (AQP4) is the most abundant aquaporin type in the brain.It is mainly expressed in the perivascular end feet of astrocytes.A large number of studies have shown that AQP4 is involved in the formation and elimination of brain edema in intracerebral hemorrhage,and plays important roles in the maintenance of the integrity of blood-brain barrier,secondary neuroinflammation,and apoptosis after intracerebral hemorrhage.More and more studies focus on the roles and mechanisms of AQP4 in intracerebral hemorrhage,however,the results are not completely consistent.This article reviews the roles and mechanisms of AQP4 in intracerebral hemorrhage
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Objective To analyze the causes of 652 hospitalizations in the patients with autosomal dominant polycystic kidney disease (ADPKD).Methods The medical records of all ADPKD inpatients in our hospital from January 1,1990 to December 31,2010 were collected.The differences of hospitalization causes in different age,gender and period were analyzed.Results (1)In 652 hospitalizations,the most common cause was lumbar pain (15.2％),followed by cystic bleeding (14.6％),aggravating renal failure (10.1％),dialysis-related problems (9.4％),renal transplant related issues (8.3％),renal replacement therapy for ESRD (8.0％),urinary tract infection (6.4％),end stage renal failure (5.8％),hypertension (4.1％),renal cyst volume enlargement (3.7％),finding polycystic kidney disease (2.1％),urinary lithiasis (1.8％) and others (10.4％).(2)Younger patients were admitted into hospital because of polycystic kidney bleeding and finding PKD.With the increase of patients age,hospitalization due to dialysis-related problems increased,while many middle-aged patients were hospitalized because of back pain.(3)Male patients were admitted into hospital for aggravating renal failure,ESRD,kidney transplantation-related problems and urinary lithiasis,while female patients mainly for lumbar pain,dialysis-related problems and urinary tract infection.(4)The proportion was significantly reduced with time of finding PKD,renal failure and polycystic kidney bleeding,the proportion of renal cysts increasing and aggravating renal failure increased,there was a significant increase in the proportion of patients with hypertension,while a significant decrease in the proportion of patients with uncontrolled hypertension,and the average SBP was also significantly reduced.Conclusions The highest rate of hospitalization of ADPKD patients is in 40 to 60 age group.Cause of admission varies with age and gender,and changes with the change of time.Over the past decade,the proportion of hospitalization due to renal cysts enlargement and renal failure aggravation increased significantly.The incidence of hypertension is higher than that in the first 10 years,but hypertension control rate increases compared with the previous.Prevention should focus on finding the suppression measures of renal cysts enlargement.
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Objective To summarize the clinical characteristics and outcome of renal cyst infection in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods Clinical data of 40 ADPKD patients with 43 episodes of renal cyst infection admitted in Shanghai Changzheng Hospital from 1st January 1991 to 31st December 2010 were retrospectively analyzed.Differences of microbiological data and treatments between 1st January 1991 to 31st December 2000 and 1st January 2001 to 31st December 2010 were compared. Results Among 473 identified patients with ADPKD and 662 episodes of hospitalization,40 patients had 43 episodes of renal cyst infection,including 8 definite and 35 likely cases.Microbiological documentation was available for 34 episodes (79.0％),Escherichia coli accounting for 82.4％ of all retrieved bacterial strains.Resistant Escherichia coli to quinolone and certain β-lactamine increased in recent decade.Clinical efficacy of initial antibiotic treatment was noted in 69.8％ of episodes. Antibiotic treatment modification was more frequently required for patients receiving initial monotherapy compared with those receiving combination therapy.In the first ten-year group,initial combination therapy and clinical efficacy were noted in 30.0％ and 60.0％ of episodes respectively,and hospital stay was (20.2±6.7) d.In the second ten-year group,initial combination therapy and clinical efficacy were noted in 61.9％ and 78.2％ of episodes respectively,and hospital stay was (16.3±3.2) d.Large infected cysts (diameter ＞5 cm) frequently required drainage. Conclusions In renal cyst infection,the source of the organisms is often a gram negative enteric organism.Empiric therapy is often initiated with two antibiotics.The drainage of large infected cysts remains the main treatment for cyst infection.
