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1.
Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.
Xu, X, Yang, Z, Li, S, Pei, H, Zhao, J, Zhang, Y, Xiong, Z, Liao, Y, Li, Y, Lin, Q, et al
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2024;(2):251-263
Abstract
BACKGROUND To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.
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2.
Crosstalk between intestinal flora and human iron metabolism: the role in metabolic syndrome-related comorbidities and its potential clinical application.
Yan, Y, Zhang, W, Wang, Y, Yi, C, Yu, B, Pang, X, Li, K, Li, H, Dai, Y
Microbiological research. 2024;:127667
Abstract
The interaction of iron and intestinal flora, both of which play crucial roles in many physiologic processes, is involved in the development of Metabolic syndrome (MetS). MetS is a pathologic condition represented by insulin resistance, obesity, dyslipidemia, and hypertension. MetS-related comorbidities including type 2 diabetes mellitus (T2DM), obesity, metabolism-related fatty liver (MAFLD), hypertension polycystic ovary syndrome (PCOS), and so forth. In this review, we examine the interplay between intestinal flora and human iron metabolism and its underlying mechanism in the pathogenesis of MetS-related comorbidities. The composition and metabolites of intestinal flora regulate the level of human iron by modulating intestinal iron absorption, the factors associated with iron metabolism. On the other hand, the iron level also affects the abundance, composition, and metabolism of intestinal flora. The crosstalk between these factors is of significant importance in human metabolism and exerts varying degrees of influence on the manifestation and progression of MetS-related comorbidities. The findings derived from these studies can enhance our comprehension of the interplay between intestinal flora and iron metabolism, and open up novel potential therapeutic approaches toward MetS-related comorbidities.
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3.
Mitochondrial diseases and mtDNA editing.
Song, M, Ye, L, Yan, Y, Li, X, Han, X, Hu, S, Yu, M
Genes & diseases. 2024;(3):101057
Abstract
Mitochondrial diseases are a heterogeneous group of inherited disorders characterized by mitochondrial dysfunction, and these diseases are often severe or even fatal. Mitochondrial diseases are often caused by mitochondrial DNA mutations. Currently, there is no curative treatment for patients with pathogenic mitochondrial DNA mutations. With the rapid development of traditional gene editing technologies, such as zinc finger nucleases and transcription activator-like effector nucleases methods, there has been a search for a mitochondrial gene editing technology that can edit mutated mitochondrial DNA; however, there are still some problems hindering the application of these methods. The discovery of the DddA-derived cytosine base editor has provided hope for mitochondrial gene editing. In this paper, we will review the progress in the research on several mitochondrial gene editing technologies with the hope that this review will be useful for further research on mitochondrial gene editing technologies to optimize the treatment of mitochondrial diseases in the future.
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4.
Proteome-wide profiling reveals dysregulated molecular features and accelerated aging in osteoporosis: A 9.8-year prospective study.
Xu, J, Cai, X, Miao, Z, Yan, Y, Chen, D, Yang, ZX, Yue, L, Hu, W, Zhuo, L, Wang, JT, et al
Aging cell. 2024;(2):e14035
Abstract
The role of circulatory proteomics in osteoporosis is unclear. Proteome-wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography-tandem mass spectrometry (LC-MS/MS) at baseline, and the 2nd, and 3rd follow-ups (7704 person-tests) in the prospective Chinese cohorts with 9.8 follow-up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA) at follow-ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)-related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed-effects model (LMM). Meta-analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta-analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD-year increase in KDM-Proage was associated with higher risk of LS-OP (hazard ratio [HR], 1.25; 95% CI, 1.14-1.36, p = 4.96 × 10-06 ), and FN-OP (HR, 1.13; 95% CI, 1.02-1.23, p = 9.71 × 10-03 ). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging.
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5.
Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis.
Hao, X, Li, S, Yang, Y, Dai, H, Yan, Y, Li, D
Nutrition journal. 2024;(1):21
Abstract
BACKGROUND Several studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial. OBJECTIVE We sought to examine whether a dose-response association of DII and SARS-CoV-2 infection exists. DESIGN A dose-response meta-analysis was performed to investigate the association of DII and SARS-CoV-2 infection. We conducted a systematic search of PubMed, Embase and Web of Science up to March 15th, 2023. The odds ratios (OR) of DII and COVID-19 risk and severity were computed. RESULTS Totally, 5 studies were included (1 from UK and 4 from Iran), consisting of 197,929 participants with 12,081 COVID-19 cases. Although there was heterogeneity among studies, the results indicated that higher DII was independently related to higher SARS-CoV-2 infection incidence (OR = 1.57, 95% CI: 1.14, 2.17) and COVID-19 severity (OR = 1.11, 95% CI: 1.07, 1.15) but not COVID-19 mortality (risk ratio = 1.13, 95% CI: 1.00, 1.27). The incidence of SARS-CoV-2 infection increased by 31% for each 1-point increase in the E-DII (OR = 1.31, 95% CI: 1.20, 1.43). CONCLUSIONS This meta-analysis suggests that an elevated DII score is associated with increased SARS-CoV-2 infectious risk and severity of COVID-19. There were not enough studies on COVID-19 mortality. Further large prospective studies in different countries are warranted to validate our results.
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6.
The key mediator of diabetic kidney disease: Potassium channel dysfunction.
Guo, J, Zhang, C, Zhao, H, Yan, Y, Liu, Z
Genes & diseases. 2024;(4):101119
Abstract
Diabetic kidney disease is a leading cause of end-stage renal disease, making it a global public health concern. The molecular mechanisms underlying diabetic kidney disease have not been elucidated due to its complex pathogenesis. Thus, exploring these mechanisms from new perspectives is the current focus of research concerning diabetic kidney disease. Ion channels are important proteins that maintain the physiological functions of cells and organs. Among ion channels, potassium channels stand out, because they are the most common and important channels on eukaryotic cell surfaces and function as the basis for cell excitability. Certain potassium channel abnormalities have been found to be closely related to diabetic kidney disease progression and genetic susceptibility, such as KATP, KCa, Kir, and KV. In this review, we summarized the roles of different types of potassium channels in the occurrence and development of diabetic kidney disease to discuss whether the development of DKD is due to potassium channel dysfunction and present new ideas for the treatment of DKD.
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7.
Ferritinophagy induced ferroptosis in the management of cancer.
Liu, YC, Gong, YT, Sun, QY, Wang, B, Yan, Y, Chen, YX, Zhang, LJ, Zhang, WD, Luan, X
Cellular oncology (Dordrecht). 2024;(1):19-35
Abstract
BACKGROUND Ferroptosis, a newly form of regulated cell death (RCD), is characterized by iron dyshomeostasis and unrestricted lipid peroxidation. Emerging evidence depicts a pivotal role for ferroptosis in driving some pathological processes, especially in cancer. Triggering ferroptosis can suppress tumor growth and induce an anti-tumor immune response, denoting the therapeutic promises for targeting ferroptosis in the management of cancer. As an autophagic phenomenon, ferritinophagy is critical to induce ferroptosis by degradation of ferritin to release intracellular free iron. Recently, a great deal of effort has gone into designing and developing anti-cancer strategies based on targeting ferritinophagy to induce ferroptosis. CONCLUSION This review delineates the regulatory mechanism of ferritinophagy firstly and summarizes the role of ferritinophagy-induced ferroptosis in cancer. Moreover, the strategies targeting ferritinophagy to induce ferroptosis are highlighted to unveil the therapeutic value of ferritinophagy as a target to manage cancer. Finally, the future research directions on how to cope with the challenges in developing ferritinophagy promoters into clinical therapeutics are discussed.
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8.
The association between interleukin family and diabetes mellitus and its complications: An overview of systematic reviews and meta-analyses.
Jin, Z, Zhang, Q, Liu, K, Wang, S, Yan, Y, Zhang, B, Zhao, L
Diabetes research and clinical practice. 2024;:111615
Abstract
OBJECTIVE To evaluate and summarize the association between interleukin (IL) concentrations and diabetes mellitus (DM) and its complications. METHODS Meta-analyses and eligible individual studies of observational studies investigating the associations between IL and DM and its complications were included. The random-effects model was used to estimate the summary effect, and the heterogeneity among studies was assessed using the Q-statistic and the I2 metric; The Egger's regression and the χ2 test were used to test for small study effects and excess significance bias. RESULTS This overview identified 34 meta-analyses that investigated the association between IL concentrations and DM and its complications. Meta-analyses of prospective studies indicated that elevated circulating IL-6 and IL-1β had predictive value for the incident of type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM) as well as gestational diabetes mellitus (GDM), and the overall Hazard Ratio (HR) of T2DM was 1.28 (95 % CI: 1.17, 1.40; P<0.001) per 1 log pg/ml increment in IL-6 levels, however, there was no correlation between circulating IL-10 levels and DM. Meanwhile, the increased level of IL-6 was significantly associated several diabetic complications (Diabetic kidney disease[DKD], diabetic peripheral neuropathy[DPN], and cognitive impairment[CI]), and for the diabetic retinopathy (DR), the levels of IL-1β, IL-8 and IL-10 in the aqueous humor and vitreous humor, but not the blood were significantly correlated with it. CONCLUSION Multiple ILs, such as the IL-6 and IL-1β, are definitively linked to DM and its complications, and they may be new targets for the diagnosis and treatment, but stronger evidence needs to be confirmed by prospective studies with larger sample sizes and longer observation periods.
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9.
The Method and Study of Detecting Phenanthrene in Seawater Based on a Carbon Nanotube-Chitosan Oligosaccharide Modified Electrode Immunosensor.
Wu, Y, Qu, W, Qiu, C, Chen, K, Zhuang, Y, Zeng, Z, Yan, Y, Gu, Y, Tao, W, Gao, J, et al
Molecules (Basel, Switzerland). 2023;(15)
Abstract
Phenanthrene (PHE), as a structurally simple, tricyclic, polycyclic aromatic hydrocarbon (PAHs), is widely present in marine environments and organisms, with serious ecological and health impacts. It is crucial to study fast and simple high-sensitivity detection methods for phenanthrene in seawater for the environment and the human body. In this paper, a immunosensor was prepared by using a multi-wall carbon nanotube (MWCNTs)-chitosan oligosaccharide (COS) nanocomposite membrane loaded with phenanthrene antibody. The principle was based on the antibody-antigen reaction in the immune reaction, using the strong electron transfer ability of multi-walled carbon nanotubes, coupled with chitosan oligosaccharides with an excellent film formation and biocompatibility, to amplify the detection signal. The content of the phenanthrene in seawater was studied via differential pulse voltammetry (DPV) using a potassium ferricyanide system as a redox probe. The antibody concentration, pH value, and probe concentration were optimized. Under the optimal experimental conditions, the response peak current of the phenanthrene was inversely proportional to the concentration of phenanthrene, in the range from 0.5 ng·mL-1 to 80 ng·mL-1, and the detection limit was 0.30 ng·mL-1. The immune sensor was successfully applied to the detection of phenanthrene in marine water, with a recovery rate of 96.1~101.5%, and provided a stable, sensitive, and accurate method for the real-time monitoring of marine environments.
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10.
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis.
Liu, X, Nie, L, Zhang, Y, Yan, Y, Wang, C, Colic, M, Olszewski, K, Horbath, A, Chen, X, Lei, G, et al
Nature cell biology. 2023;(3):404-414
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Abstract
SLC7A11-mediated cystine uptake suppresses ferroptosis yet promotes cell death under glucose starvation; the nature of the latter cell death remains unknown. Here we show that aberrant accumulation of intracellular disulfides in SLC7A11high cells under glucose starvation induces a previously uncharacterized form of cell death distinct from apoptosis and ferroptosis. We term this cell death disulfidptosis. Chemical proteomics and cell biological analyses showed that glucose starvation in SLC7A11high cells induces aberrant disulfide bonds in actin cytoskeleton proteins and F-actin collapse in a SLC7A11-dependent manner. CRISPR screens and functional studies revealed that inactivation of the WAVE regulatory complex (which promotes actin polymerization and lamellipodia formation) suppresses disulfidptosis, whereas constitutive activation of Rac promotes disulfidptosis. We further show that glucose transporter inhibitors induce disulfidptosis in SLC7A11high cancer cells and suppress SLC7A11high tumour growth. Our results reveal that the susceptibility of the actin cytoskeleton to disulfide stress mediates disulfidptosis and suggest a therapeutic strategy to target disulfidptosis in cancer treatment.