Investigation of the association between the genetic polymorphisms of the co-stimulatory system and systemic lupus erythematosus

Human leukocyte antigen genes have been shown to have the strongest association with autoimmune disease (AD). However, non-HLA genes would be risk factors of AD. Many genes encoding proteins that are related to T- and B-cell function have been identified as susceptibility genes of systemic lupus erythematosus (SLE). In this study, we explored the correlation between SLE and the genetic polymorphisms of co-stimulatory/co-inhibitory molecules, including CTLA4, CD28, ICOS, PDCD1, and TNFSF4. We found that there were nine single-nucleotide polymorphisms (SNPs) associated with SLE, namely, rs11571315 (TT vs. CT vs. CC: p < 0.001; TT vs. CT: p = 0.001; p = 0.005; TT vs. CT +CC: p < 0.001; TT+CT vs. CC: p = 0.032), rs733618 (CC vs. CT vs. TT: p = 0.002; CC vs. CT: p = 0.001; CC vs. TT: p = 0.018; CC vs. CT + TT: p = 0.001), rs4553808 (AA vs. AG: p < 0.001), rs62182595 (GG vs. AG vs. AA: p < 0.001; GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs16840252 (CC vs. CT vs. TT: p < 0.001; CC vs. CT: p < 0.001; CC vs. CT + TT: p < 0.001), rs5742909 (CC vs. CT: p = 0.027; CC vs. CT + TT: p = 0.044), rs11571319 (GG vs. AG vs. AA: p < 0.001, GG vs. AG: p < 0.001; GG vs. AG+AA: p < 0.001), rs36084323 (CC vs. CT vs. TT: p = 0.013, CC vs. TT: p = 0.004; CC vs. CT + TT: p = 0.015; CC +CT vs. TT: p = 0.015), and rs1234314 (CC vs. CG vs. GG: p = 0.005; CC vs. GG: p=0.004; CC+ CG vs. GG: p=0.001), but not in CD28 and ICOS by using the chi-square test. Additionally, rs62182595 and rs16840252 of CTLA and rs1234314 and rs45454293 of TNFSF4 were also associated with SLE in haplotypes. These SLE-related SNPs also had an association with several diseases. It was indicated that these SNPs may play an important role in immune regulation and pathogenic mechanisms

Risk factors associated with brachial–ankle pulse wave velocity among peritoneal dialysis patients in Macao

BACKGROUND: Cardiovascular disease is the leading cause of mortality among peritoneal dialysis (PD) patients in Macao. Increased arterial stiffness determined by pulse wave velocity (PWV) has been established as an independent predictor of cardiovascular mortality in end-stage renal disease patients. The present study aims to investigate the relationship between arterial stiffness and its associated risk factors in chronic PD patients. METHODS: A total of 96 chronic PD patients (48 males/48 females) were included in the cross-sectional study. Arterial stiffness was assessed by brachial-ankle PWV (baPWV). Patients were divided into two subgroups according to mean baPWV value. On enrollment, clinical characteristics and biochemical parameters were collected. RESULTS: Compared with low baPWV group patients, high baPWV group patients were significant older (p<0.001) and more likely to have a high proportion of female gender (p=0.004) as well as previous CVD history (p=0.008). Serum albumin, pre-albumin levels and residual renal creatinine clearance (CCr) were significantly lower but the serum ferritin level was significantly higher in high baPWV group patients than in low baPWV group patients (all p<0.01). BaPWV was positively associated with age (r=0.534, p<0.001), Charlson comorbidity index (r=0.350, p<0.001) and serum ferritin level (r=0.340, p=0.001). Meanwhile, baPWV negatively correlated with serum albumin (r=−0.479, p<0.001), pre-albumin levels (r=−0.320, p=0.003) and residual renal CCr (r=−0.177, p=0.048). Age-adjusted partial correlation test found a significant correlation between baPWV and CRP (r=0.462, p<0.001). Multivariate regression analysis showed that baPWV was independently associated with age (p<0.001), serum albumin level (p=0.015), CRP (p=0.019) and residual renal CCr (p=0.045). CONCLUSION: Arterial stiffness, assessed by baPWV, had an independent correlation with age, serum albumin level, CRP level and residual renal CCr among PD patients in Macao

The susceptibility of single nucleotide polymorphisms located within co-stimulatory pathways to systemic lupus erythematosus

IntroductionAutoimmune diseases result from the loss of immune tolerance, and they exhibit complex pathogenic mechanisms that remain challenging to effectively treat. It has been reported that the altered expression levels of co-stimulatory/inhibitory molecules will affect the level of T/B cell activation and lead to the loss of immune tolerance.MethodsIn this study, we evaluated the gene polymorphisms of the ligand genes corresponding co-stimulatory system that were expressed on antigen-presenting cells (CD80, CD86, ICOSLG, and PDL1) from 60 systemic lupus erythematosus (SLE) patients and 60 healthy controls.ResultsThe results showed that rs16829984 and rs57271503 of the CD80 gene and rs4143815 of the PDL1 gene were associated with SLE, in which the G-allele of rs16829984 (p=0.022), the A-allele of rs57271503 (p=0.029), and the GG and GC genotype of rs4143815 (p=0.039) may be risk polymorphisms for SLE.DiscussionThese SNPs are in the promoter and 3’UTR of the genes, so they may affect the transcription and translation activity of the genes, thereby regulating immune function and contributing to the development of SLE

miR-382 Contributes to Renal Tubulointerstitial Fibrosis by Downregulating HSPD1

Redox imbalance plays an important role in the pathogenesis of CKD progression. Previously, we demonstrated that microRNA-382 (miR-382) contributed to TGF-β1-induced loss of epithelial polarity in human kidney epithelial cells, but its role in the development of renal tubulointerstitial fibrosis remains unknown. In this study, we found that with 7 days of unilateral ureteral obstruction (UUO) in mice, the abundance of miR-382 in the obstructed kidney was significantly increased. Meanwhile, the protein expression of heat shock protein 60 (HSPD1), a predicted target of miR-382, was reduced after 7 days of UUO. Expression of 3-nitrotyrosine (3-NT) was upregulated, but expression of thioredoxin (Trx) was downregulated. Anti-miR-382 treatment suppressed the upregulation of miR-382, attenuated renal interstitial fibrosis in the obstructed kidney, and reversed the downregulation of HSPD1/Trx and upregulation of 3-NT after UUO. Furthermore, in vitro study revealed that overexpression of HSPD1 significantly restored Trx expression and reversed TGF-β1-induced loss of E-cadherin, while in vivo study found that direct siRNA-mediated suppression of HSPD1 in the UUO kidney promoted oxidative stress despite miR-382 blockade. Our clinical data showed that upregulation of miR-382/3-NT and downregulation of HSPD1/Trx were also observed in IgA nephropathy patients with renal interstitial fibrosis. These data supported a novel mechanism in which miR-382 targets HSPD1 and contributes to the redox imbalance in the development of renal fibrosis

Primulina pingnanensis, a new species of Gesneriaceae from Guangxi, China

A new species of Primulina, P. pingnanensis, from the Guangxi Zhuangzu Autonomous Region, China, is described and illustrated here. It is morphologically similar to P. orthandra but has significant differences in the bracts, corolla tube and lobes shape, as well as in the indumentum of the outer surface of the corolla, the filaments, the staminodes and the anthers. Colorful photographs and essential information of this new taxon are also provided, including detailed taxonomic description, distribution, habitat, the comparison table, and the IUCN conservation status. We also discuss a validation of new combination P. crassifolia and Chirita crassifolia

Vertex functions for d-wave mesons in the light-front approach

While the light-front quark model (LFQM) is employed to calculate hadronic transition matrix elements, the vertex functions must be pre-determined. In this work we derive the vertex functions for all d-wave states in this model. Especially, since both of $^3D_1$ and $^3S_1$ are $1^{--}$ mesons, the Lorentz structures of their vertex functions are the same. Thus when one needs to study the processes where $^3D_1$ is involved, all the corresponding formulas for $^3S_1$ states can be directly applied, only the coefficient of the vertex function should be replaced by that for $^3D_1$. The results would be useful for studying the newly observed resonances which are supposed to be d-wave mesons and furthermore the possible 2S-1D mixing in $\psi'$ with the LFQM.Comment: 12 pages, 2 figures, some typos corrected and more discussions added. Accepted by EPJ

High myopia at high altitudes

Background: Optic nerve sheath diameter (ONSD) increases significantly at high altitudes, and is associated with the presence and severity of acute mountain sickness (AMS). Exposure to hypobaria, hypoxia, and coldness when hiking also impacts intraocular pressure (IOP). To date, little is known about ocular physiological responses in trekkers with myopia at high altitudes. This study aimed to determine changes in the ONSD and IOP between participants with and without high myopia (HM) during hiking and to test whether these changes could predict symptoms of AMS.Methods: Nine participants with HM and 18 without HM participated in a 3-day trek of Xue Mountain. The ONSD, IOP, and questionnaires were examined before and during the trek of Xue Mountain.Results: The ONSD values increased significantly in both HM (p = 0.005) and non-HM trekkers (p = 0.018) at an altitude of 1,700 m. In the HM group, IOP levels were greater than those in the non-HM group (p = 0.034) on the first day of trekking (altitude: 3,150 m). No statistically significant difference was observed between the two groups for the values of ONSD. Fractional changes in ONSD at an altitude of 1,700 m were related to the development of AMS (rpb = 0.448, p = 0.019) and the presence of headache symptoms (rpb = 0.542, p = 0.004). The area under the ROC curve for the diagnostic performance of ONSD fractional changes at an altitude of 1,700 m was 0.859 for predicting the development of AMS and 0.803 for predicting the presence of headache symptoms.Conclusion: Analysis of changes in ONSD at moderate altitude could predict AMS symptoms before an ascent to high altitude. Myopia may impact physiological accommodation at high altitudes, and HM trekkers potentially demonstrate suboptimal regulation of aqueous humor in such environments