association-between-atherogenic-index-plasma-hypertension-patients

Association between Atherogenic Index of Plasma and Hypertension in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome&#8212;A Retrospective Study

This study aimed to investigate the relationship between the atherogenic index of plasma (AIP) and hypertension in patients with obstructive sleep ...

TRIB3 has been reported to mediate breast cancer (BC) proliferation and metastasis by interacting with AKT1, and blocking the interaction between TRIB3 and AKT1 can inhibit the progression of BC. Besides, inhibiting TRIB3 to turn "cold tumor" hot has also been proved to be an effective therapeutic strategy for BC. Thus, this study aim to find drugs that can bind to TRIB3 to inhibit BC progression, and further elucidate its mechanism.

Parishin B blocking TRIB3-AKT1 interaction inhibits breast cancer lung metastasis.

It is well‑established that steroid‑resistant nephrotic syndrome commonly involves podocytic injury, however, the underlying mechanism remains to be elucidated. Previous studies have demonstrated that glucocorticoids enhance podocytic recovery predominantly through the functional isoform, glucocorticoid receptor (GR)α. Our previous study demonstrated the reduced expression of GRα in podocytes from patients with steroid‑resistant nephrotic syndrome compared with those with steroid‑sensitive syndromes, which suggested that microRNAs (miRNAs) may be a potential therapeutic target in the modulation of steroid sensitivity. The present study screened miRNAs in murine injured podocytes by microarray and identified 10 miRNAs significantly upregulated, including miR‑30a, miR‑30d, miR‑100, miR181c, miR‑5099, miR‑3535, miR‑140‑3p, miR‑148‑3p and miR‑103‑3p. Bioinformatic target prediction indicated that the GR was a candidate target gene of miR‑30a. The data also indicated that miR‑30a negatively regulated GRα in normal and injured podocytes induced by puromycin aminonucleoside (PAN). In addition, the inhibition of miR‑30a prevented podocytic apoptosis induced by PAN. However, luciferase reporter assay data suggested an indirect effect on the transcriptional activity of GRα. The present study indicated that silencing of miR‑30a may improve steroid sensitivity in injured podocytes, although the mechanism cannot be explained by conventional means and remains to be elucidated.

Inhibition of microRNA-30a prevents puromycin aminonucleoside-induced podocytic apoptosis by upregulating the glucocorticoid receptor α.

Vascular calcification (VC) is an independent risk factor for cardiovascular disease and mortality in uremia. Post-translational core fucosylation is implicated in a number of pathological processes. First, we investigated the role of core fucosylation and key TGF-β1 pathway receptors in calcified arteries in vivo. To determine whether blocking core fucosylation effectively inhibited VC and TGF-β/Smad signaling pathway, we established an in vitro model of phosphate-induced calcification in rat vascular smooth muscle cells (VSMCs) to assess the role of core fucosylation in VC. Core fucose could be detected at markedly higher levels in calcified VSMCs than control cells. Fut8 (α-1,6 fucosyltransferase), the only enzyme responsible for core fucosylation in humans, was significantly upregulated by high phosphate. Exposed to high phosphate media and blocking core fucosylation in VSMCs by knocking down Fut8 using a siRNA markedly reduced calcium and phosphorus deposition and Cbfα1 expression (osteoblast-specific transcription factor), and increased α-Sma expression (smooth muscle cell marker). Fut8 siRNA significantly inhibited TGF-β/Smad2/3 signaling activation in VSMCs cultured in high phosphate media. In conclusion, this study provides evidence to suggest core fucosylation plays a major role in the process of VC and appropriate blockade of core fucosylation may represent a potential therapeutic strategy for treating VC in end-stage renal disease.

Inhibiting post-translational core fucosylation prevents vascular calcification in the model of uremia.

Core fucosylation (CF), catalyzed by α-1,6 fucosyltransferase (Fut8) in mammals, plays an important role in pathological processes through posttranslational modification of key signaling receptor proteins, including transforming growth factor (TGF)-β receptors and platelet-derived growth factor (PDGF) receptors. However, its effect on peritoneal fibrosis is unknown. Here, we investigated its influence on epithelial-mesenchymal transition (EMT) of rat peritoneal mesothelial cells (PMCs) in vitro induced by a high-glucose (HG) culture solution.

Blocking Posttranslational Core Fucosylation Ameliorates Rat Peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition.

Pericytes have been identified as a major source of myofibroblasts in renal interstitial fibrosis (RIF). The overactivation of several signaling pathways, mainly the TGF-β and PDGF pathways, initiates the pericyte-myofibroblast transition during RIF. Key receptors in these two pathways have been shown to be modified by fucosyltransferase 8 (FUT8), the enzyme that catalyzes core fucosylation. This study postulated that core fucosylation might play an important role in regulating the pericyte transition in RIF. The data showed that core fucosylation increased with the extent of RIF in patients with IgA nephropathy (IgAN). Similarly, core fucosylation of pericytes increased in both a unilateral ureteral occlusion (UUO) mouse model and an in vitro model of pericyte transition. Inhibition of core fucosylation by adenoviral-mediated FUT8 shRNA in vivo and FUT8 siRNA in vitro significantly reduced pericyte transition and RIF. In addition, the activation of both the TGF-β/Smad and PDGF/ERK pathways was blocked by core fucosylation inhibition. In conclusion, core fucosylation may regulate the pericyte transition in RIF by modifying both the TGF-β/Smad and PDGF/ERK pathways. Glycosylation might be a novel "hub" target to prevent RIF.

Novel Mechanism of the Pericyte-Myofibroblast Transition in Renal Interstitial Fibrosis: Core Fucosylation Regulation.

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

Renal interstitial fibrosis (RIF) is an incurable pathological lesion in chronic kidney diseases. Pericyte activation is the major pathological characteristic of RIF. Fibroblast and macrophage activation are also involved in RIF. Studies have revealed that core fucosylation (CF), an important post-translational modification of proteins, plays a key role in pericyte activation and RIF by regulating multiple profibrotic signaling pathways as a hub-like target. Here, we reveal that mesenchymal stem cell (MSC)-derived exosomes reside specifically in the injured kidney and deliver microRNA (miR)-34c-5p to reduce cellular activation and RIF by inhibiting CF. Furthermore, we showed that the CD81-epidermal growth factor receptor (EGFR) ligand-receptor complex aids the entry of exosomal miR-34c-5p into pericytes, fibroblasts, and macrophages. Altogether, our findings reveal a novel role of MSC-derived exosomes in inhibiting multicellular activation via CF and provide a potential intervention strategy for renal fibrosis.

Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins.

The purpose of this study was to evaluate the feasibility and outcomes of conduction system pacing (CSP) in patients with heart failure (HF) who had a severely reduced left ventricular ejection fraction (LVEF) of less than 30% (HFsrEF).

The feasibility and safety of his-purkinje conduction system pacing in patients with heart failure with severely reduced ejection fraction.

The fluid status and rate of blood flow through the arteriovenous fistula (AVF) are two important factors affecting hemodynamic in hemodialysis patients; however, their effects on pulmonary hypertension have rarely been studied. Hence, we aimed to evaluate the effects of these factors in hemodialysis patients with pulmonary hypertension.

Clinical influencing factors affecting pulmonary hypertension in hemodialysis patients.

Cognitive impairment is widely prevalent in maintenance hemodialysis (MHD) patients, and seriously affects their quality of life. The intestinal flora likely regulates cognitive function, but studies on cognitive impairment and intestinal flora in MHD patients are lacking.

Analysis of intestinal flora and cognitive function in maintenance hemodialysis patients using combined 16S ribosome DNA and shotgun metagenome sequencing.

Intensive Care Unit (ICU) nurses experience many difficulties and challenges in caring for delirium patients. Identifying and measuring these difficulties experienced by nurses is critical for implementing precise interventions. We currently lack a standard tool for assessing the level of difficulty faced by ICU nurses in caring for delirium patients that fits the nursing context in China. This study aimed to translate the Difficulty Scale for Nurses who Care for Patients with Delirium in the Intensive Care Unit (DSNCPD-ICU) into Chinese (C-DSNCPD-ICU) and psychometrically validate the translated scale.

Psychometric properties of the Chinese version of difficulty scale for nurses who care for patients with delirium in the intensive care unit.

Hypoxia inducible factor (HIF-1α) is a major transcriptional factor regulating gene expression under hypoxic conditions. HIF-1α expression was closely correlated with the oxygenation status of tumor and could serve as an important biomarker for tumor hypoxia, aggressiveness, or radiation resistance. High expression of HIF-1α contributes to high aggressiveness or poor prognosis of endometrial cancer.

Amide proton transfer-weighted imaging combined with multiple models diffusion-weighted imaging of endometrial cancer: correlations between multi-modal MRI parameters and HIF-1α expression.

Uremic cardiomyopathy (UCM) is the leading cause of hemodialysis patient mortality. Indoxyl sulfate (IS), a key uremic toxin, activates multiple signaling pathways, causing cardiac hypertrophy and apoptosis. We previously demonstrated that core fucosylation (CF), a post-translational modification, is crucial in activating these pathways. Additionally exosome-mediated cardiac microvascular endothelial cell (CMEC)-cardiomyocyte (CM) crosstalk is important for UCM progression. However, the characteristics and roles of CF modification in IS-induced CMEC-derived exosomes (IS-Exos) that cause CM injury remain unexplored. Our studies have revealed that hemodialysis patients had significantly higher serum IS and α1,6-fucosyltransferase (FUT8), which were positively correlated with the severity of cardiac injury. Using a microfluidic chip model of IS-induced cardiac injury, we visualized exosome transfer from CMECs to CMs, which caused mitochondrial impairment, hypertrophy and apoptosis in CMs, with elevated CF levels playing critical roles. To investigate this further, we performed FUT8 knockout in IS-mice treated with IS-Exos and transfected FUT8 siRNA into CMs exposed to IS-Exos. We found that the inhibition of FUT8 leads to a reduction in ARG2 expression, which consequently diminishes reactive oxygen species (ROS) and ameliorates cardiac hypertrophy and apoptosis. Mechanistically, miR-27a-5p was markedly downregulated in IS-Exos. CD44 on IS-Exos interacts with EGFR in CMs, enhancing cardiac injury. Supplementation with miR-27a-5p in vivo and in vitro specifically targets USF2, leading to a downregulation of FUT8 expression. This cascade leads to a diminished expression of ARG2, alleviation of ROS, and the reversal of cardiac hypertrophy and apoptosis. Our findings offer new insights, suggesting that targeting CF modification may represent a promising therapeutic strategy for alleviating UCM in the future.

Exosomal miR-27a-5p inhibits indoxyl sulfate-induced cardiac dysfunction by targeting the USF2/FUT8 axis.

Fibroblast activation protein inhibitor (FAPI) PET imaging in pulmonary fibrosis: pathophysiology, clinical utility, and emerging theranostic applications.

Article	Year
Parishin B blocking TRIB3-AKT1 interaction inhibits breast cancer lung metastasis. Frontiers in pharmacology\| PubMed ID: 39881875	2024
Inhibition of microRNA-30a prevents puromycin aminonucleoside-induced podocytic apoptosis by upregulating the glucocorticoid receptor α. Molecular medicine reports\| PubMed ID: 26299668	2015
Inhibiting post-translational core fucosylation prevents vascular calcification in the model of uremia. The international journal of biochemistry & cell biology\| PubMed ID: 27521658	2016
Blocking Posttranslational Core Fucosylation Ameliorates Rat Peritoneal Mesothelial Cell Epithelial-Mesenchymal Transition. Chinese medical journal\| PubMed ID: 28875950	2017
Novel Mechanism of the Pericyte-Myofibroblast Transition in Renal Interstitial Fibrosis: Core Fucosylation Regulation. Scientific reports\| PubMed ID: 29209018	2017
Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats. Kidney international\| PubMed ID: 29571940	2018
Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins. Molecular therapy : the journal of the American Society of Gene Therapy\| PubMed ID: 34678513	2022
The feasibility and safety of his-purkinje conduction system pacing in patients with heart failure with severely reduced ejection fraction. Frontiers in cardiovascular medicine\| PubMed ID: 37283576	2023
Clinical influencing factors affecting pulmonary hypertension in hemodialysis patients. Kidney research and clinical practice\| PubMed ID: 38062624	2025
Analysis of intestinal flora and cognitive function in maintenance hemodialysis patients using combined 16S ribosome DNA and shotgun metagenome sequencing. Aging clinical and experimental research\| PubMed ID: 38334873	2024
Psychometric properties of the Chinese version of difficulty scale for nurses who care for patients with delirium in the intensive care unit. BMC nursing\| PubMed ID: 40200341	2025
Amide proton transfer-weighted imaging combined with multiple models diffusion-weighted imaging of endometrial cancer: correlations between multi-modal MRI parameters and HIF-1α expression. Frontiers in oncology\| PubMed ID: 40444079	2025
Exosomal miR-27a-5p inhibits indoxyl sulfate-induced cardiac dysfunction by targeting the USF2/FUT8 axis. Free radical biology & medicine\| PubMed ID: 40992517	2025
Fibroblast activation protein inhibitor (FAPI) PET imaging in pulmonary fibrosis: pathophysiology, clinical utility, and emerging theranostic applications. Respiratory research\| PubMed ID: 41981646	2026

Nan Wang

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