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1.
RNA modifications in cellular metabolism: implications for metabolism-targeted therapy and immunotherapy.
Liu, WW, Zheng, SQ, Li, T, Fei, YF, Wang, C, Zhang, S, Wang, F, Jiang, GM, Wang, H
Signal transduction and targeted therapy. 2024;(1):70
Abstract
Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding of pathophysiology, and inspiring development of therapeutics. As a crucial component of epigenetics at post-transcription level, RNA modification significantly determines RNA fates, further affecting various biological processes and cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts. In this review, we characterize the distribution features, modifying mechanisms and biological functions of 8 RNA modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively the most studied types. Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described, categorized as glucose, lipid, amino acid, and mitochondrial metabolism. And we highlight the regulation of RNA modifications on immunometabolism, further influencing immune responses. Above all, we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy, progression of RNA modification-targeted agents, and its potential in RNA-targeted therapeutics. Eventually, we give legitimate perspectives for future researches in this field from methodological requirements, mechanistic insights, to therapeutic applications.
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2.
Performance of Artificial Intelligence in Detecting Diabetic Macular Edema From Fundus Photography and Optical Coherence Tomography Images: A Systematic Review and Meta-analysis.
Lam, C, Wong, YL, Tang, Z, Hu, X, Nguyen, TX, Yang, D, Zhang, S, Ding, J, Szeto, SKH, Ran, AR, et al
Diabetes care. 2024;(2):304-319
Abstract
BACKGROUND Diabetic macular edema (DME) is the leading cause of vision loss in people with diabetes. Application of artificial intelligence (AI) in interpreting fundus photography (FP) and optical coherence tomography (OCT) images allows prompt detection and intervention. PURPOSE To evaluate the performance of AI in detecting DME from FP or OCT images and identify potential factors affecting model performances. DATA SOURCES We searched seven electronic libraries up to 12 February 2023. STUDY SELECTION We included studies using AI to detect DME from FP or OCT images. DATA EXTRACTION We extracted study characteristics and performance parameters. DATA SYNTHESIS Fifty-three studies were included in the meta-analysis. FP-based algorithms of 25 studies yielded pooled area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of 0.964, 92.6%, and 91.1%, respectively. OCT-based algorithms of 28 studies yielded pooled AUROC, sensitivity, and specificity of 0.985, 95.9%, and 97.9%, respectively. Potential factors improving model performance included deep learning techniques, larger size, and more diversity in training data sets. Models demonstrated better performance when validated internally than externally, and those trained with multiple data sets showed better results upon external validation. LIMITATIONS Analyses were limited by unstandardized algorithm outcomes and insufficient data in patient demographics, OCT volumetric scans, and external validation. CONCLUSIONS This meta-analysis demonstrates satisfactory performance of AI in detecting DME from FP or OCT images. External validation is warranted for future studies to evaluate model generalizability. Further investigations may estimate optimal sample size, effect of class balance, patient demographics, and additional benefits of OCT volumetric scans.
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3.
Extraction, purification, structural characteristics and biological properties of the polysaccharides from Armillaria mellea (Vahl) P. Kumm.: A review.
Chen, X, Liu, Y, Ren, L, Dai, X, Zhao, J, Gao, C, Zhang, S, Dong, J, Zhao, Z, Li, Y, et al
International journal of biological macromolecules. 2024;(Pt 1):129175
Abstract
Armillaria mellea (Vahl) P. Kumm. is a well-known homoeopathic plant with medicinal and culinary uses. Modern phytochemical researchers have successfully extracted and purified over 40 types of A. mellea polysaccharides (AMPs) from the fruiting bodies, hyphae and fermentation broth of A. mellea, and some of them have been analyzed and identified by their chemical structures. The impressive biological activity of these polysaccharides has been recognized by scientists worldwide. Many studies show that AMPs have remarkable antioxidant, anti-diabetic, anti-tumor, anti-inflammatory, immunoregulatory, hypolipidemic, thrombectomy, anti-aging, pulmonary protective, hepatic protective, anti-Alzheimer's properties, etc. However, the current understanding of the relationships between their chemical structure and biological activity, toxicological effects and pharmacokinetics remains limited. This article provides a systematic review of the research conducted over the past decades on the extraction and purification methods, structural characteristics, biological activity and mechanism of action of AMPs. The aim is to provide a research base that will benefit the future application of AMPs as therapeutic drugs and functional foods, and also provide insights for the further development of AMPs.
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PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.
Liu, P, Sun, D, Zhang, S, Chen, S, Wang, X, Li, H, Wei, F
Cell & bioscience. 2024;(1):21
Abstract
BACKGROUND Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. MAIN BODY In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. CONCLUSION Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.
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5.
Exploring the relationship between hyperlactatemia and anemia.
Zhang, S, Liu, W, Ganz, T, Liu, S
Trends in endocrinology and metabolism: TEM. 2024;(4):300-307
Abstract
Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers, and genetic disorders. For instance, hyperlactatemia leads to iron restriction by upregulating hepatic hepcidin expression. Increasing evidence also points to lactate as a crucial signaling molecule rather than merely a metabolic byproduct. Here, we discuss the mutual influence between anemia and hyperlactatemia. This opinion calls for a reconsideration of the multifaceted roles of lactate and lactylation in anemia and emphasizes the need to fill knowledge gaps, including the dose dependence of lactate's effects, its sources, and its subcellular localization.
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Multimodal prerehabilitation for elderly patients with sarcopenia in colorectal surgery.
Wu, J, Chi, H, Kok, S, Chua, JMW, Huang, XX, Zhang, S, Mah, S, Foo, LX, Peh, HY, Lee, HB, et al
Annals of coloproctology. 2024;(1):3-12
Abstract
Sarcopenia, which is characterized by progressive and generalized loss of skeletal muscle mass and strength, has been well described to be associated with numerous poor postoperative outcomes, such as increased perioperative mortality, postoperative sepsis, prolonged length of stay, increased cost of care, decreased functional outcome, and poorer oncological outcomes in cancer surgery. Multimodal prehabilitation, as a concept that involves boosting and optimizing the preoperative condition of a patient prior to the upcoming stressors of a surgical procedure, has the purported benefits of reversing the effects of sarcopenia, shortening hospitalization, improving the rate of return to bowel activity, reducing the costs of hospitalization, and improving quality of life. This review aims to present the current literature surrounding the concept of sarcopenia, its implications pertaining to colorectal cancer and surgery, a summary of studied multimodal prehabilitation interventions, and potential future advances in the management of sarcopenia.
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7.
Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence.
Zhu, XB, Xu, YY, Li, LC, Sun, JB, Wang, YZ, Chen, J, Wang, C, Zhang, S, Jin, LY
Drug development research. 2024;(1):e22131
Abstract
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has attracted lots of attention in preventing the clearance of plasma low-density lipoprotein cholesterol (LDL-C). PCSK9 inhibitors are developed to primarily reduce the cardiovascular risk by lowering LDL-C level. Recently, a number of pleiotropic extrahepatic functions of PCSK9 beyond the regulation of cholesterol metabolism, particularly its effects on central nervous system (CNS) diseases have been increasingly identified. Emerging clinical evidence have revealed that PCSK9 may play a significant role in neurocognition, depression, Alzheimer's disease, and stroke. The focus of this review is to elucidate the functions of PCSK9 and highlight the effects of PCSK9 in CNS diseases, with the aim of identifying the potential risks that may arise from low PCSK9 level (variant or inhibitor) in the clinical practice.
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8.
Research progress of N1-methyladenosine RNA modification in cancer.
Liu, Y, Zhang, S, Gao, X, Ru, Y, Gu, X, Hu, X
Cell communication and signaling : CCS. 2024;(1):79
Abstract
N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays a pivotal role in the regulation of various biological functions and activities. Especially in cancer cell invasion, proliferation and cell cycle regulation. Over recent years, there has been a burgeoning interest in investigating the m1A modification of RNA. Most studies have focused on the regulation of m1A in cancer enrichment areas and different regions. This review provides a comprehensive overview of the methodologies employed for the detection of m1A modification. Furthermore, this review delves into the key players in m1A modification, known as the "writers," "erasers," and "readers." m1A modification is modified by the m1A methyltransferases, or writers, such as TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed by the demethylases, or erasers, including FTO and ALKBH1, ALKBH3. It is recognized by m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, and TYHDC1, also known as "readers". Additionally, we explore the intricate relationship between m1A modification and its regulators and their implications for the development and progression of specific types of cancer, we discuss how m1A modification can potentially facilitate the discovery of novel approaches for cancer diagnosis, treatment, and prognosis. Our summary of m1A methylated adenosine modification detection methods and regulatory mechanisms in various cancers provides useful insights for cancer diagnosis, treatment, and prognosis. Video Abstract.
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9.
Health outcomes associated with phytosterols: An umbrella review of systematic reviews and meta-analyses of randomized controlled trials.
Liu, B, Chen, K, Chen, X, Wang, J, Shu, G, Ping, Z, Zhang, S
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155151
Abstract
BACKGROUND Phytosterols (PS), as a kind of plant active ingredients, have many benefits to human health. However, there is currently no comprehensive overview of the clinical evidence and an assessment of the evidence quality. PURPOSE We conducted an umbrella review, which incorporated verification spanning a number of meta-analyses and systematic reviews to clarify the link that existed between PS consuming and health outcomes. METHODS The databases PubMed, Embase, Web of Science and The Cochrane Library were searched for appropriate research and ultimately included 23 articles involving 79 results. Methodological quality and the validity of evidence received designation in the included meta-analyses leveraging the Assessment of Multiple Systematic Reviews (AMSTAR-2) and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). RESULTS The consumption of PS makes a contribution to the alleviation of metabolic conditions such as hypercholesterolemia, diabetes, obesity, and hypertension. Its most essential function is to decrease cholesterol absorption, leading to dramatically reductions in total cholesterol and low density lipoprotein cholesterol. Furthermore, utilizing PS products can have a favorable impact on managing apolipoprotein levels along with decreasing the probability of obtaining atherosclerotic cardiovascular disease. CONCLUSION This umbrella review summarized a range of beneficial functions of PS to humans, highlighting the promising potential for the development of PS into functional foods.
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10.
Recent advances in the application of Mendelian randomization to chronic kidney disease.
Wen, C, Chen, L, Jia, D, Liu, Z, Lin, Y, Liu, G, Zhang, S, Gao, B
Renal failure. 2024;(1):2319712
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Abstract
OBJECTIVE Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. METHODS Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. RESULTS Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. CONCLUSION This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.