In this paper, we report in situ preparation of nickel hydroxide nanoflake array on carbon cloth (Ni(OH)
2
NA/CC) by a rapid and simple microplasma method. Using this technique, Ni(OH)
2
nanoflake ...can be prepared on carbon cloth in only 1.5 h at atmospheric pressure and ambient temperature. As an electrode with highly efficient catalytic and non-enzymatic sensor for detecting glucose, such a Ni(OH)
2
NA/CC electrode showed excellent electrocatalytic activity with a short response time within 5 s, low detection limit (LOD) of 62 nM (S/N=3), and response sensitivity of 2216.2 mA mM
−1
cm
−2
, meanwhile a satisfactory reproducibility and selectivity.
Abstract
Background and aims
Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and ...therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse.
Methods
We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse.
Result
Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse.
Conclusion
Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.
Recent advances in trans-differentiation of one type cell to another have made it possible to directly convert Huntington's disease (HD) patient fibroblasts into neurons by modulation of ...cell-lineage-specific transcription factors or RNA processing. However, this possibility has not been examined. Here, we demonstrate that HD patient-derived fibroblasts can be directly trans-differentiated into neuron-like cells by knockdown of the expression of a single gene encoding the polypyrimidine-tract-binding protein. The directly converted HD neuron-like cells were positive in expression of Tuj1, NeuN, DARPP-32, and γ-aminobutyric acid and exhibited neuritic breakdown, abnormal neuritic branching, increased cell death, and aggregation of mutant huntingtin. These observations indicate that the neuron-like cells directly converted from HD patient fibroblasts recapitulate the major aspects of neuropathological characteristics of HD and thus provide an additional model for understanding the disorder and validation of therapeutic reagents.
Although it is reported that the targeting ability of hyaluronic acid (HA)-based nanoparticles (NPs) is molecular weight (MW) dependent, the influence of HA MW on targeting efficiency of ...HA-functionalized NPs and the underlying mechanism remain elusive. In this study, we constituted three HA-functionalized Dox-loaded NPs (Dox/HCVs) different HA MWs (7, 63, and 102 kDa) and attempted to illustrate the effects of HA MW on the targeting efficiency. The three Dox/HCVs had similar physiochemical and pharmaceutical characteristics, but showed different affinity to CD44 receptor. Furthermore, Dox/HCV-63 exerted the best targeting effect and the highest cytotoxicity compared with Dox/HCV-7 and Dox/HCV-102. It was interesting to found that both the HA-CD44 binding affinity and induced CD44 clustering by HA-based NPs were HA MW-dependent, the two of which determine the apparent targeting efficacy of Dox/HCV NPs in the conflicting directions. Those results laid a good foundation for rationally designing HA-based NPs in cancer therapy.
Three active targeting nanoparticles with different hyaluronic acid molecular weight were prepared for exploring the relationship of hyaluronic acid molecular weight and active targeting efficacy and discussing potential mechanisms. Display omitted
Immunoglobulin G4 (IgG4)‐related disease is a chronic fibroinflammatory disease mediated by immune disorders. Given the challenging clinical diagnosis and treatment, knowledge of the pathogenesis of ...IgG4‐related disease is important. The typical elevation of serum IgG4 concentrations and infiltration of IgG4‐positive plasma cells in the involved tissues indicate the involvement of B lymphocytes in the pathogenesis of IgG4‐related disease. Mass production of autoantibodies reflects abnormal activation of B cells, which causes tissue damage. Circulating plasmablasts are recently discovered markers that correlate with serum IgG4 concentration, the extent of organ involvement and disease activity. B‐cell depletion therapy is an emerging curative strategy that can significantly alleviate clinical manifestations and achieve remission in patients with IgG4‐related disease. These findings highlight the potential role of B cells in IgG4‐related disease. In this review, we discuss the pathogenic impact of B lymphocytes on IgG4‐related disease and describe novel therapies targeting B cells.
In this article, we discuss the role of B cells in the pathogenesis of IgG4‐related disease and integrate an overview of the characteristics of B‐cell subsets. Advanced novel B‐cell targeted therapies of IgG4‐related disease are also described.
Stroke is a serious medical condition that causes long-term neurological disability in mainly elderly adults worldwide. Lack of therapy to improve functional recovery in the chronic phase of stroke ...is a major challenge for stroke research. Combining two hematopoietic growth factors, stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF), our previous studies have demonstrated the neurovascular restorative efficacy of this treatment in the chronic phase of experimental stroke. Elevated plasma fibrinogen has been thought to serve as a predictor for ischemic stroke. Here we have determined the treatment frequency in reducing plasma fibrinogen and in restoring motor function in aged mice with chronic stroke. Our findings show that SCF + G-CSF treatment in chronic stroke decreases plasma fibrinogen and improves motor function in aged mice. No differences have been found between a 2-week treatment regimen and 7-day treatment in the plasma fibrinogen assay, while the 7-day treatment regimen displays a better recovery pattern with regard to motor function. This study provides new insight into understanding the potential contribution of SCF + G-CSF in both reducing the risk of recurrent ischemic stroke and enhancing stroke recovery.
Objective. This study was to screen for the miRNAs differently expressed in peripheral blood mononuclear cells (PBMC) of RA, to further identify the expression of miR-155 in RA PBMC and ...fibroblast-like synoviocytes (FLS), and to evaluate the function of miR-155 in RA-FLS. Methods. Microarray was used to screen for differentially expressed miRNAs in RA PBMC. miR-155 expression in PBMC and FLS of RA were identified by real-time PCR. Enforced overexpression and downexpression of miR-155 were used to investigate the function of miR-155 in RA-FLS. Expression of IKBKE which was previously identified as the actual target of miR-155 was examined by Western blot and real-time PCR in RA-FLS. Results. miR-155 levels were increased in both PBMC and FLS of RA and could be induced by TNF-α. Upregulation of miR-155 decreased MMP-3 levels and suppressed proliferation and invasion of RA-FLS. Inverse relationship between the expressions of miR-155 and the MMPs production-related protein IKBKE was found. Conclusion. An inflammatory milieu may alter miRNA expression profiles in rheumatoid arthritis. miR-155 is upregulated in RA-FLS, and it may be a protective factor against the inflammatory effect in part by attenuating expression of IKBKE.
Objective
To explore whether cumulative serum urate (cumSU) is correlated with diabetes type II mellitus incidence.
Methods
In this study, we recruited individuals participating in all Kailuan health ...examinations from 2006 to 2013 without stroke, cancer, gestation, myocardial infarction, and diabetes type II diagnosis in the first three examinations. CumSU was calculated by multiplying the average serum urate concentration and the time between the two examinations (umol/L × year). CumSU levels were categorized into five groups:
Q
1
–
Q
5
. The effect of cumSU on diabetes type II incidence was estimated by logistic regression.
Results
A total of 36,277 individuals (27,077 men and 9200 women) participated in the final analysis. The multivariate logistic regression model showed the odds ratios (95% confidence intervals) of diabetes type II from
Q
1
to
Q
5
were 1.00 (reference), 1.25 (1.00 to 1.56), 1.43 (1.15 to 1.79), 1.49 (1.18 to 1.87), and 1.80 (1.40 to 2.32), respectively. Multivariable odds ratios per 1-standard deviation increase in cumSU were 1.26 (1.17 to 1.37) in all populations, 1.20 (1.10 to 1.32) for men, and 1.52 (1.27 to 1.81) for women, respectively.
Conclusions
CumSU is a significant risk factor for diabetes type II. Individuals with higher cumSU, especially women, are at a higher risk of diabetes type II independent of other known risk factors.
Key Points
• Cumulative exposure to serum urate is a significant risk factor for diabetes type II.
• Individuals with higher cumSU, especially women, are at a higher risk of diabetes type II.
Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a Notch3 dominant mutation-induced cerebral small vascular disease, is characterized by ...progressive degeneration of vascular smooth muscle cells (vSMCs) of small arteries in the brain, leading to recurrent ischemic stroke, vascular dementia and death. To date, no treatment can stop or delay the progression of this disease. Herein, we determined the therapeutic effects of stem cell factor (SCF) in combination with granulocyte colony-stimulating factor (G-CSF) (SCF + G-CSF) in a mouse model of CADASIL carrying the human mutant Notch3 gene. SCF + G-CSF was subcutaneously administered for 5 days and repeated 4 times with 1–4 month intervals. We found through water maze testing that SCF + G-CSF treatment improved cognitive function. SCF + G-CSF also attenuated vSMC degeneration in small arteries, increased cerebral blood vascular density, and inhibited apoptosis in CADASIL mice. We also discovered that loss of cerebral capillary endothelial cells and neural stem cells/neural progenitor cells (NSCs/NPCs) occurred in CADASIL mice. SCF + G-CSF treatment inhibited the CADASIL-induced cell loss in the endothelia and NSCs/NPCs and promoted neurogenesis. In an in vitro model of apoptosis, SCF + G-CSF prevented apoptotic cell death in vSMCs through AKT signaling and by inhibiting caspase-3 activity. These data suggest that SCF + G-CSF restricts the pathological progression of CADASIL. This study offers new insights into developing therapeutic strategies for CADASIL.
Rubinstein-Taybi syndrome (RTS) is a rare, congenital, plurimalformative, and neurodevelopmental disorder. Previous studies have reported that large deletions contribute to more severe RTS phenotypes ...than those caused by CREBBP point mutations, suggesting a concurrent pathogenetic role of flanking genes, typical of contiguous gene syndromes, but the detailed genetics are unclear.
This study presented a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. Based on the clinical and genetic analysis of the patient, the ADCY9 gene deletion was highlighted as a plausible explanation of cardiac abnormalities. In adcy9 morphant zebrafish, cardiac malformation was observed. Immunofluorescence study disclosed increased macrophage migration and cardiac apoptosis. RNA sequencing in zebrafish model highlighted the changes of a number of genes, including increased expression of the mmp9 gene which encodes a matrix metalloproteinase with the main function to degrade and remodel extracellular matrix.
In this study, we identified a plausible new candidate gene ADCY9 of CHD through the clinical and genetic analysis of a rare case of Rubinstein-Taybi (RT) syndrome with serious cardiac abnormalities. By functional study of zebrafish, we demonstrated that deletion of adcy9 is the causation for the cardiac abnormalities. Cardiac apoptosis and increased expression of the MMP9 gene are involved in the pathogenesis.
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