Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway.

Spinal cord injury (SCI), a severe health problem in worldwide, was commonly associated with functional disability and reduced quality of life. As the expression of brain-derived neurotrophic factor (BDNF) was substantial event in injured spinal cord, we hypothesized whether BDNF-overexpression could be in favor of the recovery of both sensory function and hindlimb function after SCI. By using BDNF-overexpression transgene mice [CMV-BDNF 26 (CB26) mice] we assessed the role of BDNF on the recovery of neurological behavior in spinal cord transection (SCT) model. BMS score and tail-flick test was performed to evaluate locomotor function and sensory function, respectively. Immunohistochemistry was employed to detect the location and the expression of BDNF, NeuN, 5-HT, GAP-43, GFAP as well as CGRP, and the level of p-AKT and AKT were examined through western blot analysis. BDNF overexpressing resulted in significant locomotor functional recovery from 21 to 28 days after SCT, compared with wild type (WT)+SCT group. Meanwhile, the NeuN, 5-HT and GAP-43 positive cells were markedly increased in ventral horn in BDNF overexpression animals, compared with WT mice with SCT. Moreover, the crucial molecular signal, p-AKT/AKT has been largely up-regulated, which is consistent with the improvement of locomotor function. However, in this study, thermal hyperpathia encountered in sham (CB26) group and WT+SCT mice and further aggravated in CB26 mice after SCT. Also, following SCT, the significant augment of positive-GFAP astrocytes and CGRP fibers were found in WT+SCT mice, and further increase was seen in BDNF over-expression transgene mice. BDNF-overexpression may not only facilitate the recovery of locomotor function via AKT pathway, but also contributed simultaneously to thermal hyperalgesia after SCT.

Constructing the coordination environment of Se-O in Cu2-xSe for electrochemical hydrogen evolution.

In this work, a Se-O bond is introduced by a simple oxidation method to realize the structural transformation from Cu2-xSe to Cu2O(SeO3) for enhanced electrocatalytic hydrogen evolution reaction (HER). The experiment and calculation results showed that Cu2O(SeO3) facilitated charge transfer and possessed a small barrier during the HER.

Paeoniflorin shows chondroprotective effects under IL-1ß stress by regulating circ-PREX1/miR-140-3p/WNT5B axis.

BACKGROUND: Osteoarthritis (OA) is a chronic and degenerative bone and joint disease, and paeoniflorin shows anti-arthritis role in OA. This study planned to investigate the mechanism related to chondroprotective role of paeoniflorin in OA. METHODS: Real-time quantitative PCR and western blotting were performed to measure expression levels of circ-PREX1, microRNA (miR)-140-3p, Wingless-type MMTV integration site family, member 5B (WNT5B), B cell lymphoma (Bcl)-2, and Bcl-2 Associated X Protein (Bax). MTT assay, EdU assay, flow cytometry and enzyme-linked immunosorbent assay evaluated cell viability, proliferation, apoptosis and inflammatory response, respectively. Dual-luciferase reporter assay and RNA immunoprecipitation assay identified the relationship among circ-PREX1, miR-140-3p, and WNT5B. RESULTS: IL-1ß highly induced apoptosis rate, Bax expression and TNF-α product, accompanied with decreased cell viability, cell proliferation and IL-10 secretion, whereas these effects were partially reversed after paeoniflorin pretreatment. Expression of circ-PREX1 was upregulated and miR-140-3p was downregulated in cartilage tissues of patients with knee OA (KOA) and IL-1ß-induced human chondrocytes (C28/I2). Circ-PREX1 overexpression and miR-140-3p silencing attenuated the suppressive effect of paeoniflorin in IL-1ß-induced C28/I2 cells. Furthermore, miR-140-3p was negatively regulated by circ-PREX1. WNT5B was a downstream target of miR-140-3p and could be modulated by the circ-PREX1/miR-140-3p pathway in IL-1ß-induced C28/I2 cells. CONCLUSION: Paeoniflorin might protect human chondrocytes from IL-1ß-induced inflammatory injury via circ-PREX1-miR-140-3p-WNT5B pathway, suggesting a potential preventative agent and a novel target for the treatment of KOA.

Relationship between gut microbiota and nutritional status in patients on peritoneal dialysis.

Malnutrition is a common complication in the dialysis population, both hemodialysis and peritoneal dialysis (PD). We report our exploratory study on the characteristics of intestinal microbiota and nutritional status in PD patients. The nutritional status of our PD patients were evaluated, and their feces were collected for 16S rRNA gene V3-V4 regions amplification and high-throughput sequencing. The characteristics and differences of microbiota between the well-nourished (W) and malnourished (M) groups were compared. We studied the genera and the operational taxonomic units (OTUs) within the genus of our patients, initially comparing the malnourished and the well- nourished groups and later on reanalyzing the whole group using these OTUs. At the OTU level, 6 bacteria were significantly correlated with the serum albumin level. The abundances of 2 OTUs (OTU208 Lachnospiraceae_incertae_sedi and OTU4 Bacteroides) were more in W group. Meanwhile, 4 OTUs (OTU225 Akkermansia, OTU87 Megasphaera, OTU31 Peptostreptococcaceae_incertae_sedi and OTU168 Clostridium_sensu_strictu) displayed higher abundance among individuals in M group. Notably, the OTU168 Clostridium_sensu_stricto was the only bacteria that significantly correlated with serum albumin (r = - 0.356, P = 0.05), pre-albumin (r = - 0.399, P = 0.02), and SGA (r = 0.458, P = 0.01). The higher the OTU168 Clostridium_sensu_strictu, the lower serum albumin and pre-albumin and a higher score of SGA signifying a worse nutritional status. Our preliminary findings suggested a relationship between the nutrition status and microbiota in PD patients. Our results provide a basis for further exploration of the interactions between malnutrition and intestinal flora in PD patients with potential interventions using probiotics and prebiotics.

A survey of cognitive function in peritoneal dialysis patients.

INTRODUCTION: The aim of this study was to investigate how peritoneal dialysis and other influencing factors affect patients' cognitive function. METHODS: The 85 subjects in the study group were regular patients in our center. The control group included 88 age and gender matched healthy individuals who were with normal renal function. The study subjects' cognitive levels and related factors were analyzed using several screening instruments: the cognitive function was measured using the Montreal Cognitive Assessment Scale and statistical analysis was conducted based on the relevant data. RESULTS: The results showed that cognitive impairment was higher in peritoneal dialysis patients than in non-dialysis subjects. Age and educational background were single factors that affected cognitive function, which was more likely to be impaired at a higher age level and/or a lower educational level. CONCLUSION: Cognitive function can be impaired by peritoneal dialysis, and age and education levels are influencing factors.

Grape Seed Proanthocyanidins (GSPs) Inhibit the Development of Cutaneous Squamous Cell Carcinoma by Regulating the hsa_circ_0070934/miR-136-5p/PRAF2 Axis.

BACKGROUND: Grape seed proanthocyanidins (GSPs) have been shown to inhibit the progression of many cancers, including cutaneous squamous cell carcinoma (CSCC). Circular RNA (circRNA) is a key regulator for cancer progression. However, it is unclear whether GSPs can mediate the progression of CSCC by regulating circRNA. METHODS: Quantitative real-time PCR was conducted to determine the expression of hsa_circ_0070934, microRNA (miR)-136-5p and prenylated Rab acceptor family 2 (PRAF2). MTT assay and colony formation assay were used to assess cell proliferation. Cell cycle process and apoptosis were detected by flow cytometry, and cell migration and invasion were measured by transwell assay. Western blot analysis was utilized to examine protein expression. In addition, dual-luciferase reporter assay and RIP assay were used to evaluate the interaction between miR-136-5p and hsa_circ_0070934 or PRAF2. Subcutaneous xenograft models were constructed to explore the function of GSPs on CSCC tumor growth in vivo. RESULTS: GSPs could reduce hsa_circ_0070934 expression and inhibit CSCC cell proliferation, cell cycle process, migration, invasion, while promote apoptosis. Overexpressed hsa_circ_0070934 could reverse the suppressive effect of GSPs on CSCC cell progression. MiR-136-5p could be sponged by hsa_circ_0070934, and its overexpression also abolished the positively regulation of hsa_circ_0070934 on the progression of GSPs-induced CSCC cells. PRAF2 was a target of miR-136-5p, and its expression could be decreased by GSPs and increased by hsa_circ_0070934. The inhibitory effect of miR-136-5p on CSCC cell progression could be reversed by PRAF2 overexpression. Additionally, GSPs also could inhibit CSCC tumor growth in vivo. CONCLUSION: Our data showed that GSPs regulated the hsa_circ_0070934/miR-136-5p/PRAF2 axis to restrain CSCC progression.

Protein-protein interactions between lens vimentin and alphaB-crystallin using FRET acceptor photobleaching.

PURPOSE: The R120G mutation of alphaB-crystallin is known to cause desmin-related myopathy, but the mechanisms underlying the formation of cataract are not clearly established. We hypothesize that alteration of protein-protein interaction between R120G alphaB-crystallin and lens intermediate filament proteins is one of the mechanisms of congenital cataract. METHODS: Protein-protein interactions were determined by confocal fluorescence resonance energy transfer (FRET) microscopy using green fluorescence protein (GFP) as the donor and red fluorescence protein (RFP) as the acceptor. The lens vimentin gene was fused into a GFP vector and the alphaB-crystallin (WT or R120G mutant) gene was fused into the RFP vector. The donor-acceptor plasmid pairs of intermediate filament (IF)-GFP and alphaB-RFP were co-transfected into HeLa cells. After incubation, confocal fluorescence images of the transfected cells were taken. FRET was estimated by the acceptor photobleaching method. Protein-protein interaction was evaluated by FRET efficiency. RESULTS: The confocal fluorescence images showed that the cells expressing vimentin and R120G alphaB-crystallin contained large amounts of protein aggregates while few vimentin fibers were observed. FRET efficiency analyses indicated that vimentin had a significantly greater protein-protein interaction with R120G alphaB-crystallin than with WT alphaB-crystallin. CONCLUSIONS: Our results show that the R120G alphaB-crystallin mutant promoted vimentin aggregation through increased protein-protein interaction. This process may contribute to the formation of congenital cataract.

Protein-protein interactions involving congenital cataract T5P gammaC-crystallin mutant: a confocal fluorescence microscopy study.

The human lens crystallin gene CRYGC T5P is associated with Coppock-like cataract and has a phenotype of a dust-like opacity of the fetal lens nucleus and deep cortical region. Previous in vitro mutation studies indicate that the protein has changed conformation, solubility, and stability, which may make it susceptible to aggregation, as seen in cataractous lens and cell culture expression. To investigate the mechanisms leading to these events, we studied protein-protein interactions using confocal fluorescence resonance energy transfer (FRET) microscopy. The method detects protein-protein interactions in the natural environment of living cells. Crystallin genes (CRYGC T5P, CRYGC, and CRYAA) were fused to either the green fluorescence protein (GFP) or red fluorescence protein (DsRED or RFP) vector. Each of the following GFP-RFP (donor-acceptor) plasmid pairs was cotransfected into HeLa cells: gammaC-gammaC, gammaC-gammaCT5P, gammaCT5P-gammaCT5P, alphaA-gammaC, and alphaA-gammaCT5P. After culture, confocal fluorescence cell images were taken. Protein-protein interactions in the form of net FRET were evaluated. The confocal fluorescence images show that cells expressing T5P gammaC-crystallin contain many protein aggregates, but cells co-expressing with either gammaC- or alphaA-crystallin reduce the aggregation considerably. FRET determination indicates that gammaCT5P-gammaCT5P shows less protein-protein interaction than either gammaC-gammaC or gammaC-gammaCT5P. Cotransfection with alphaA-crystallin (alphaA-gammaC or alphaA-T5PgammaC) increases nFRET compared with gammaC-gammaC or gammaC-T5PgammaC. Our results demonstrate that T5P gammaC-crystallin shows more protein aggregates and less protein-protein interaction than WT gammaC-crystallin. Chaperone alphaA-crystallin can rescue T5P gammaC-crystallin from aggregation through increased protein interaction. The formation of congenital cataract may be due to reduced protein-protein interactions and increased aggregation from an insufficient amount of alpha-crystallin for protection.

Clinical observation on the treatment of childhood refractory idiopathic thrombocytopenic purpura with Dihuang Zhixue Capsule.

OBJECTIVE: To observe the clinical effect of Dihuang Zhixue Capsule (DZC, a Chinese preparation for cooling blood and dispelling toxic substances) in the treatment of childhood refractory idiopathic thrombocytopenic purpura (RITP), with cyclosporin A (CsA) used as the control. METHODS: Forty-one children of RITP were randomized into the treated group and the control group. The 21 patients in the treated group were orally given 2 to 3 DZC capsules each time, thrice a day and the 20 in the control group were given 3 mg/kg CsA per day, with 3 months as one therapeutic course. The therapeutic efficacy, platelet count and adverse reaction in the two groups were compared at the end of the course. RESULTS: (1) In the treated group, 1 (4.8%) patient was evaluated as cured, 3 (14.3%) as markedly effective, 5 (23.8%) as effective, 5 (23.8%) as improved, 7 (33.3%) as ineffective, with the total effective rate being 66.7%; while in the control group, the corresponding numbers were 0, 2 (10.0%), 2 (10.0%), 3 (15.0%), 13 (65.0%) and 35.0%, respectively, showing statistical significance in difference between the total effective rates of the two groups (xi(2)=4.11, P=0.0426). (2) As compared with the baseline, the platelet count increased in both groups after 2 months' treatment (P<0.05). After 3 months' treatment, the platelet count was higher in the treated group than in the control group (P<0.05). (3) The improvement of hemorrhage in the treated group after 8 weeks' treatment was better than that in the control group (P<0.05). (4) No apparent adverse reaction was observed in the treated group, while in the control group, hirsutism was shown in 15 cases; gingival hyperplasia in 10; digestive reaction in 5, liver function impairment in 5, hypertension in 2 and renal impairment in 2. CONCLUSION: The therapeutic efficacy of DZC is better than that of CsA, and DZC shows good compliance but brings no obvious adverse reaction.

Cholesterol-derived bile acids enhance the chaperone activity of α-crystallins.

Human lens membranes contain the highest cholesterol concentration of any known biological membranes, but it significantly decreases with age. Oxygenation of cholesterol generates numerous forms of oxysterols (bile acids). We previously showed that two forms of the bile acid components--ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA)--suppressed lens epithelial cell death and alleviated cataract formation in galactosemic rat lenses. We investigated whether these compounds also suppress the thermal aggregation of human lens crystallins. Total water-soluble (WS) proteins were prepared from human lenses, and recombinant human crystallins (αA-, αB-, ßB2-, and γC-crystallin) were generated by a prokaryotic expression system and purified by liquid chromatography. The light scattering of proteins in the presence or absence of UDCA or TUDCA was measured using a spectrofluorometer set at Ex/Em = 400/400 nm. Protein blot analysis was conducted for detection of α-crystallins in the human lens WS proteins. High concentrations of UDCA and TUDCA significantly suppressed thermal aggregation of total lens WS proteins, which contained a low level of αA-/αB-crystallin. Spectroscopic analysis with each recombinant human lens crystallin indicated that the bile acids did not suppress the thermal aggregation of γC-, ßB2-, αA-, or αB-crystallin. Combination of α-crystallin and bile acid (either UDCA or TUDCA) suppressed thermal aggregation of each individual crystallin as well as a non-crystallin protein, insulin. These results suggest that UDCA or TUDCA protects the chaperone activity of α-crystallin. It is believed that these two naturally occurring intermediate waste products in the lens enhance the chaperone activity of α-crystallin. This finding may lead to the development of UDCA and TUDCA as anticataract agents.

Functions of the intermediate filament cytoskeleton in the eye lens.

Intermediate filaments (IFs) are a key component of the cytoskeleton in virtually all vertebrate cells, including those of the lens of the eye. IFs help integrate individual cells into their respective tissues. This Review focuses on the lens-specific IF proteins beaded filament structural proteins 1 and 2 (BFSP1 and BFSP2) and their role in lens physiology and disease. Evidence generated in studies in both mice and humans suggests a critical role for these proteins and their filamentous polymers in establishing the optical properties of the eye lens and in maintaining its transparency. For instance, mutations in both BFSP1 and BFSP2 cause cataract in humans. We also explore the potential role of BFSP1 and BFSP2 in aging processes in the lens.