TNF-α/calreticulin dual signaling induced NLRP3 inflammasome activation associated with HuR nucleocytoplasmic shuttling in rheumatoid arthritis

Inflammation Research - The present study was undertaken to validate whether TNF-α and calreticulin (CRT) serve as dual signaling to activate nucleotide-binding oligomerization domain-,...     

Novel missense mutation in VPS33B is associated with isolated low gamma‐glutamyltransferase cholestasis: Attenuated,incomplete phenotype of arthrogryposis,renal dysfunction,and cholestasis syndrome

The typical phenotype of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome involves three cardinal symptoms as the name describes, harboring biallelic mutations on VPS33B or VIPAS39. Except for ARC syndrome, low gamma‐glutamyltransferase (GGT) cholestasis often implies hereditary hepatopathy of different severity; however, some remain undiagnosed. Several monogenic defects typically with multiorgan manifestations may only present liver dysfunction at times, such as DGUOK defect and AGL defect. Previously, four VPS33B mutated cases were reported without arthrogryposis, or with less severe symptoms and longer lifespan, indicating the possibility of incomplete ARC phenotype of isolated hepatopathy. So we retrospectively reviewed all patients with confirmed VPS33B/VIPARS39 defect in our center and identified three presenting isolated low‐GGT cholestasis with intractable pruritus. Distinguished from others with typical ARC phenotype, these patients did not suffer the other two typical characteristics, survived much longer, and shared a novel missense VPS33B variation c.1726T>C, p.Cys576Arg, causing declined protein expression and abolished interaction with VIPAS39 in‐vitro. Serum bile acid profiles of our VPS33B/VIPAS39 mutated patients revealed similar changes to primary defect of bile salt export pump, among which those with isolated cholestasis phenotype had a higher level of total secondary bile acids than that with typical ARC phenotype, indicating the partial residual function of VPS33B.     

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C‐Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.     

中医辨证治疗高血压的效果分析

目的:分析中医辨证治疗高血压的效果.方法:随机抽取2015年3月～2016年9月128例高血压患者,分为对照组(n=64)与观察组(n=64),对照组予以西医的治疗方法,即服用常规的降血压药物;观察组予以中医辨证治疗的方法,即依据不同的症状服用不同的中药药剂,观察两组临床效果、治疗后的血压与不良反应.结果:观察组临床有效率为89.06％,明显高于对照组的70.31％(P<0.05);同时两组血压变化明显,并且两组均未出现不良反应.结论:采取中医辨证治疗高血压,可获得良好的治疗效果,提升康复率,值得临床推广.     

Peripheral blood leukocyte telomere length is associated with age but not renal function: A cross-sectional follow-up study

Objectives

We aimed to evaluate the relationship between baseline renal function and changes in telomere length in Han Chinese.

Methods

The telomere restriction fragment (TRF) length of leukocytes in the peripheral blood was measured in healthy volunteers recruited in 2014. The estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)-eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI) equation. The correlation between telomere length changes over time and renal function was analyzed.

Results

Leukocyte TRF lengths were negatively correlated to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r = 0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of telomere length was 46 bp/years. When adjusted for age, the associations between telomere length changes and baseline, subsequent TRF lengths, and serum CysC were no longer present. No association was observed between TRF length changes and renal function.

Conclusion

The rate of telomere length changes was affected by age and baseline telomere length. The telomere length changes might be important markers for aging.

     

The Closing Digital Divide: Delivery Modality and Family Attendance in the Pathways for African American Success (PAAS) Program

Although family-focused, evidence-based programs (EBPs) have the potential to reduce disparities in health and behavioral outcomes for youth, access to such programs is severely limited in the most affected areas, including African American communities in the rural South. As expanding the reach of EBPs is the primary goal of translational research, interest is growing in the potential of technology as a viable platform to disseminate services to areas with limited resources. To test whether African American families in the rural South would be willing to engage in a technology-based family-focused EBP to prevent adolescent risk behavior, we examined attendance using data from two arms of a three-arm community-based trial of the Pathways for African American Success (PAAS) program. In the overall study, sixth graders (N?=?412) and their primary caregivers were randomly assigned to the following conditions: (a) in-person, small group sessions led by facilitators; (b) self-directed, technology-based sessions; or (c) a literature control with home-mailed educational materials. Results indicated that attendance was higher in the technology condition than in the small group condition. Parental age, education, and socioeconomic status did not limit attendance in the technology condition. We conclude from these results that the use of technology can be an acceptable strategy for disseminating parenting EBPs to African American families in the rural South.     

Assessment of the Remediation Effect of Nano-hydroxyapatite in Exogenous Pb-contaminated Soil Using Toxicity Characteristic Leaching Procedure and Soil Enzyme Activities

This study assessed the level of Pb in soil and five wild plant species (Calotropis procera, Datura alba, Parthenium hysterophorus, Cenchrus ciliaris and Ricinus communis) during all the four seasons. Two busy roads varying in age and traffic volume were selected i.e., Faisalabad–Sargodha road (FSR) and Pindi Bhattian to Lillah (M-2) in the Punjab, Pakistan. Results showed raised levels of Pb in both plants and soil samples along both roads. The range of Pb concentration in plants was 0.08–3.98 and 1.95–4.74 mg kg^??1 for soil. Higher Pb contamination was recorded along FSR road as compared to M-2. Among seasons, the higher Pb concentration was found during summer, probably due to very high temperature. Among all the plants studied, Calotropis procera accumulated the highest level (3.98 mg kg^??1 dry wt.) of Pb; Thus, it can be used as good biomonitor/phytoremediator at Pb contaminated areas.