June 2024
Cell Death and Differentiation
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June 2024
Cell Death and Differentiation
May 2024
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8 Reads
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1 Citation
Cardiology Plus
Hypertension constitutes a critical risk factor for cardio-cerebrovascular disease. Despite the effectiveness of lifestyle adjustments and medications in blood pressure (BP) management, the hypertension control rates remain inadequate. Percutaneous renal denervation (RDN) has emerged as a forward-looking and evidence-supported interventional modality for the improvement of BP regulation and enhancement of hypertension control. Comprehensive evidence from randomized, sham-controlled clinical trials supports the sustained the efficacy and satisfactory safety profile of RDN in lowing BP. This scientific statement, endorsed by Chinese authorities, aims to provide a comprehensive overview of global and national clinical evidence on RDN. It seeks to highlight the therapeutic advancements of RDN, articulate expert consensus and recommendations for its utilization in hypertension management. Through the promotion of structured, safe, and standardized incorporation of RDN into clinical practice, this statement strives to optimize hypertension treatment within the Chinese medical community.
May 2024
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14 Reads
Cholangiocarcinoma (CCA) is characterized by rapid onset and high chance of metastasis. Therefore, identification of novel therapeutic targets is imperative. E26 transformation‐specific homologous factor (EHF), a member of the E26 transformation‐specific transcription factor family, plays a pivotal role in epithelial cell differentiation and cancer progression. However, its precise role in CCA remains unclear. In this study, through in vitro and in vivo experiments, we demonstrated that EHF plays a profound role in promoting CCA by transcriptional activation of glioma‐associated oncogene homolog 1 (GLI1). Moreover, EHF significantly recruited and activated tumor‐associated macrophages (TAMs) through the C‐C motif chemokine 2/C‐C chemokine receptor type 2 (CCL2/CCR2) axis, thereby remodeling the tumor microenvironment. In human CCA tissues, EHF expression was positively correlated with GLI1 and CCL2 expression, and patients with co‐expression of EHF/GLI1 or EHF/CCL2 had the most adverse prognosis. Furthermore, the combination of the GLI1 inhibitor, GANT58, and CCR2 inhibitor, INCB3344, substantially reduced the occurrence of EHF‐mediated CCA. In summary, our findings suggest that EHF is a potential prognostic biomarker for patients with CCA, while also advocating the therapeutic approach of combined targeting of GLI1 and CCL2/CCR2‐TAMs to inhibit EHF‐driven CCA development.
May 2024
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7 Reads
Cardiovascular Diabetology
Background Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. Objective This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. Methods We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). Results Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21–0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20–0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25–0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11–4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03–4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15–0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). Conclusion We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.
April 2024
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5 Reads
Annals of Hematology
Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Cytarabine (Ara-C)-based chemotherapy is the primary treatment for AML, but currently known prognostic risk stratification factors cannot fully explain the individual differences in outcome of patients. In this article, we reported that patients with homozygous GLI1 rs2228224 mutation (AA genotype) had a significantly lower complete remission rate than those with GG wild type (54.17% vs.76.02%, OR = 1.993, 95% CI: 1.062–3.504, P = 0.031). GLI1 rs2229300 T allele carriers had remarkably shorter overall survival (513 vs. 645 days, P = 0.004) and disease-free survival (342 vs. 456 days, P = 0.033) than rs2229300 GG carriers. Rs2229300 G > T variation increased the transcriptional activity of GLI1. CCND1, CD44 and PROM1 were potential target genes differentially regulated by GLI1 rs2229300. Our results demonstrated for the first time that GLI1 polymorphisms influence chemosensitivity and prognosis of young de novo AML patients treated with Ara-C.
April 2024
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14 Reads
Radiomics features have been widely used as novel biomarkers in the diagnosis of various diseases, but whether radiomics features derived from hematoxylin and eosin (H&E) images can evaluate muscle atrophy has not been studied. Therefore, this study aims to establish a new biomarker based on H&E images using radiomics methods to quantitatively analyze H&E images, which is crucial for improving the accuracy of muscle atrophy assessment. Firstly, a weightless muscle atrophy model was established by laying macaques in bed, and H&E images of the shank muscle fibers of the control and bed rest (BR) macaques were collected. Muscle fibers were accurately segmented by designing a semi-supervised segmentation framework based on contrastive learning. Then, 77 radiomics features were extracted from the segmented muscle fibers, and a stable subset of features was selected through the LASSO method. Finally, the correlation between radiomics features and muscle atrophy was analyzed using a support vector machine (SVM) classifier. The semi-supervised segmentation results show that the proposed method had an average Spearman’s and intra-class correlation coefficient (ICC) of 88% and 86% compared to manually extracted features, respectively. Radiomics analysis showed that the AUC of the muscle atrophy evaluation model based on H&E images was 96.87%. For individual features, GLSZM_SZE outperformed other features in terms of AUC (91.5%) and ACC (84.4%). In summary, the feature extraction based on the semi-supervised segmentation method is feasible and reliable for subsequent radiomics research. Texture features have greater advantages in evaluating muscle atrophy compared to other features. This study provides important biomarkers for accurate diagnosis of muscle atrophy.
April 2024
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20 Reads
Experimental Hematology and Oncology
Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs.
March 2024
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26 Reads
Inorganic Chemistry
March 2024
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7 Reads
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1 Citation
Biomedicine & Pharmacotherapy
February 2024
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16 Reads
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2 Citations
Gastroenterology
... Although molecular signaling pathways remain to be elucidated in more detail in the future, miR631 seems to be a key player in the regulation of PTPRE in RB. As small molecules and antibodies inhibiting the activity of tyrosine kinases are effective tools in cancer treatment [38], regulators of tyrosine kinase activity like the tyrosine phosphatase PTPRE hold the potential of new future RB therapy targets. ...
March 2024
Biomedicine & Pharmacotherapy
... These TFs may directly participate in the initiation of KDELR transcription, thereby influencing their mRNA expression levels. Previous research has implicated these TFs in cancer genesis, proliferation, invasion, and metastasis [42][43][44] . On the other hand, we employed the enrichment analysis to construct a regulatory network of 11 TFs-5 miRNAs-KDELR1/2/3 relevant to LUAD progression, encompassing. ...
February 2024
Biomarker Research
... Receptortriggered is the process by which targeted treatments are internalized after binding to cell-surface receptors. One of the most well-studied aptamer-drug combination therapy is doxorubicin [69][70][71][72][73][74]. For the first time, Tan et al. [75] have comprehensively examined the pharmacokinetics of radiolabeled aptamers in the human body. ...
January 2024
... The main driving force for both homotypic and heterotypic LLPSs of tau appears to be electrostatic interactions that can be modulated by post-translational modifications (PTMs). Phosphorylation and acetylation have been demonstrated to exert a regulatory effect on LLPS [58][59][60][61]. In neurodegenerative diseases, aberrant post-translational modifications of tau protein result in the loss of normal regulatory functions, which nega-tively impact the normal functioning of neurons and contribute to the onset and progression of neurological disorders. ...
January 2024
Journal of Molecular Medicine
... The gut microbiota plays crucial roles in the occurrence, development, and treatment of diseases, including cancers [1][2][3][4][5][6][7]. For example, Fusobacterium nucleatum participates in the regulation of colorectal cancer (CRC) development [8][9][10], and the abundances of Enterobacteriaceae and E. coli have been demonstrated to be significantly increased in patients with inflammatory bowel disease and type 2 diabetes mellitus [11,12]. ...
December 2023
Cell Host & Microbe
... Extensive research has highlighted the key signaling pathways involved in muscle atrophy, particularly the downregulation of the PI3K/Akt/mTOR pathway, which leads to reduced muscle protein synthesis, the dephosphorylation of FOXO, and increased expression of proteolytic genes. Therapeutic strategies are often aimed at blocking the ubiquitin-proteasome pathway [25,26]. Figure 8. Illustration of lactate treatment improving impaired metabolic pathways and reversing the altered concentration trends of key metabolites in the gastrocnemius muscles of DMA mice compared to controls. ...
November 2023
... The positive effects on therapeutic outcomes are further underscored by the augmentation of the TCF-1 regulatory network associated with LSD1 depletion 66 . In a separate study, the engineering of particles, specifically R848@M2pep-MPsAFP has been found to successfully reprogram macrophages within the HCC TME, thereby resulting in phenotypic transformation, improved antigen-presenting capabilities, activation of Tpex cells, and significant enhancement of αPD-1 therapy efficacy 52 . ...
September 2023
Nature Communications
... The induction chemotherapy schedule were as follows: patients received a standard-dose of Ara-C (100-200 mg/m 2 , intravenous drip, days 1-7) in combination with any one of the anthracyclines (daunorubicin 45-90 mg/ m 2 / idarubicin 10-20 mg/m 2 / aclarubicin 20 mg/m 2 / pirarubicin 30 mg/m 2 / mitoxantrone 8-16 mg/m 2 , intravenous drip, days 1-3). Besides, some elderly patients (> 60 years old) received a low-intensity induction regimen based on low-dose of Ara-C (10-20 mg/m 2 , subcutaneous injection, days [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Once CR was achieved, consolidation chemotherapy with either moderate dose (1-2 g/m 2 , intravenous drip, days 1-5) or high dose (3 g/m 2 , intravenous drip, days 1-3) of Ara-C was continued, or hematopoietic stem cell transplantation (HSCT) was performed directly. ...
September 2023
Annals of Hematology
... During the surgery, the intraventricular gradient was routinely reassessed before and after the resections by the direct needle puncture and manometric catheter [9]. Owing to the patient's physical position and the effect of anesthesia during the procedure, the directly measured gradient of MVO may vary compared with the gradient measured on Doppler echocardiography in the conscious state. ...
August 2023
Journal of the American College of Cardiology
... Experts are already foreseeing a broader classification encompassing both genetics, mitochondrial respiratory chain defects and epigenetics and possibly some yet to find newer dimensions to one of the emerfing menace of our civilizations. 9,23,14,39 The research challenge is still on with onslaught of molecular data and development of innovative therapies. The first and foremost approach remains to define the suboptimal response to metformin, where preliminary data suggests failure to achieve/maintain HbA1c <7% within 18 months of regular use metformin or needing an additional glucose lowering medication for managing diabetic hyperglycemia. ...
July 2023