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1.
Metabolism-regulated ferroptosis in cancer progression and therapy.
Ye, L, Wen, X, Qin, J, Zhang, X, Wang, Y, Wang, Z, Zhou, T, Di, Y, He, W
Cell death & disease. 2024;(3):196
Abstract
Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with each other to adapt to the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent lipid peroxidation, which is morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cell death and cuprotosis. Cancer metabolism plays opposite roles in ferroptosis. On the one hand, carbohydrate metabolism can produce NADPH to maintain GPX4 and FSP1 function, and amino acid metabolism can provide substrates for synthesizing GPX4; on the other hand, lipid metabolism might synthesize PUFAs to trigger ferroptosis. The mechanisms through which cancer metabolism affects ferroptosis have been investigated extensively for a long time; however, some mechanisms have not yet been elucidated. In this review, we summarize the interaction between cancer metabolism and ferroptosis. Importantly, we were most concerned with how these targets can be utilized in cancer therapy.
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2.
The Role of p53 in Regulating Chronic Inflammation and PANoptosis in Diabetic Wounds.
He, W, Tang, M, Gu, R, Wu, X, Mu, X, Nie, X
Aging and disease. 2024
Abstract
Diabetic wounds represent a formidable challenge in the clinical management of diabetes mellitus, markedly diminishing the patient's quality of life. These wounds arise from a multifaceted etiology, with the pathophysiological underpinnings remaining elusive and complex. Diabetes precipitates neuropathies and vasculopathies in the lower extremities, culminating in infections, ulcerations, and extensive tissue damage. The hallmarks of non-healing diabetic wounds include senescence, persistent inflammation, heightened apoptosis, and attenuated cellular proliferation. The TP53 gene, a pivotal tumor suppressor frequently silenced in human malignancies, orchestrates cellular proliferation, senescence, DNA repair, and apoptosis. While p53 is integral in cell cycle regulation, its role in initial tissue repair appears to be deleterious. In typical cutaneous wounds, p53 levels transiently dip, swiftly reverting to baseline. Yet in diabetic wounds, protracted p53 activation impedes healing via two distinct pathways: i) activating the p53-p21-Retinoblastoma (RB) axis, which halts the cell cycle, and ii) upregulating the cGAS-STING and nuclear factor-kappaB (NF-κB) cascades, instigating ferroptosis and pyroptosis. Furthermore, p53 intersects with various metabolic pathways, including glycolysis, gluconeogenesis, oxidative phosphorylation, and autophagy. In diabetic wounds, p53 may drive metabolic reprogramming, thus potentially derailing macrophage polarization. This review synthesizes case studies investigating the therapeutic modulation of p53 in diabetic wounds care. In summation, p53 modulates chronic inflammation and cellular aging within diabetic cutaneous wounds and is implicated in a novel cell death modality, encompassing ferroptosis and pyroptosis, which hinders the reparative process.
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3.
Function and regulation of plant ARGONAUTE proteins in response to environmental challenges: a review.
Zaheer, U, Munir, F, Salum, YM, He, W
PeerJ. 2024;:e17115
Abstract
Environmental stresses diversely affect multiple processes related to the growth, development, and yield of many crops worldwide. In response, plants have developed numerous sophisticated defense mechanisms at the cellular and subcellular levels to react and adapt to biotic and abiotic stressors. RNA silencing, which is an innate immune mechanism, mediates sequence-specific gene expression regulation in higher eukaryotes. ARGONAUTE (AGO) proteins are essential components of the RNA-induced silencing complex (RISC). They bind to small noncoding RNAs (sRNAs) and target complementary RNAs, causing translational repression or triggering endonucleolytic cleavage pathways. In this review, we aim to illustrate the recently published molecular functions, regulatory mechanisms, and biological roles of AGO family proteins in model plants and cash crops, especially in the defense against diverse biotic and abiotic stresses, which could be helpful in crop improvement and stress tolerance in various plants.
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4.
Progress and Challenges in Tumor Ferroptosis Treatment Strategies: A Comprehensive Review of Metal Complexes and Nanomedicine.
Su, Y, Liu, B, Wang, B, Chan, L, Xiong, C, Lu, L, Zhang, X, Zhan, M, He, W
Small (Weinheim an der Bergstrasse, Germany). 2024;:e2310342
Abstract
Ferroptosis is a new form of regulated cell death featuring iron-dependent lipid peroxides accumulation to kill tumor cells. A growing body of evidence has shown the potential of ferroptosis-based cancer therapy in eradicating refractory malignancies that are resistant to apoptosis-based conventional therapies. In recent years, studies have reported a number of ferroptosis inducers that can increase the vulnerability of tumor cells to ferroptosis by regulating ferroptosis-related signaling pathways. Encouraged by the rapid development of ferroptosis-driven cancer therapies, interdisciplinary fields that combine ferroptosis, pharmaceutical chemistry, and nanotechnology are focused. First, the prerequisites and metabolic pathways for ferroptosis are briefly introduced. Then, in detail emerging ferroptosis inducers designed to boost ferroptosis-induced tumor therapy, including metal complexes, metal-based nanoparticles, and metal-free nanoparticles are summarized. Subsequently, the application of synergistic strategies that combine ferroptosis with apoptosis and other regulated cell death for cancer therapy, with emphasis on the use of both cuproptosis and ferroptosis to induce redox dysregulation in tumor and intracellular bimetallic copper/iron metabolism disorders during tumor treatment is discussed. Finally, challenges associated with clinical translation and potential future directions for potentiating cancer ferroptosis therapies are highlighted.
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5.
Efficacy of vitamin D supplementation on child and adolescent overweight/obesity: a systematic review and meta-analysis of randomized controlled trials.
Gou, H, Wang, Y, Liu, Y, Peng, C, He, W, Sun, X
European journal of pediatrics. 2023;(1):255-264
Abstract
The global prevalence of overweight and obesity in children and adolescents has been increasing. Child and adolescent overweight/obesity has been demonstrated to be partially associated with vitamin D deficiency. This systematic review and meta-analysis aims to assess the efficacy of vitamin D supplementation on child and adolescent overweight/obesity. PubMed, Embase, Cochrane Library, and Web of science were searched from inception to June 20th, 2022. Randomized controlled trials (RCTs) assessing the efficacy of vitamin D on child and adolescent overweight/obesity were included. The Cochrane bias risk assessment tool was used to assess the bias risk of included studies, and subgroup analysis was conducted based on different administration dosages. All data-analyses were performed using R 4.2.1. There were 1502 articles retrieved, and 10 eligible studies were finally included, with a total of 595 participants. Meta-analysis showed no differences in LDL, TC, TG, BMI, ALP, Ca, and PTH between vitamin-D (Vit-D) group and placebo, while Vit-D group resulted in improved HOMA-IR[WMD = - 0.348, 95%CI (- 0.477, - 0.219), p = 0.26]. Subgroup-analysis showed no significant difference in the increase of 25-(OH)-D between subgroups (p = 0.39), whereas the serum 25-(OH)-D level was increased under different Vit-D doses [WMD = 6.973, 95%CI (3.072, 10.873)]. High daily dose (≥ 4000 IU/d) of Vit-D might decrease CRP and increase HDL levels. Conclusion: High dose of Vit-D supplementation (over 4000 IU/d) would reduce several cardiometabolic risk indicators and improve insulin resistance. More high-quality and large-scale RCTs are needed to provide more robust evidence. What is Known: • Vit-D deficiency is common in overweight/obesity (OW/OB) children and adolescents. • Previous randomized studies on the benefit of Vit-D supplementation to OW/OB children and adolescents are inconsistent. What is New: • This is the first meta-analysis conducted to assess the efficacy of Vit-D supplementation on child and adolescent OW/OB. • High dose of Vit-D supplementation is beneficial to cardiovascular metabolism, and improve insulin resistance on child and adolescent OW/OB.
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6.
Different definitions of feeding intolerance and their associations with outcomes of critically ill adults receiving enteral nutrition: a systematic review and meta-analysis.
Li, J, Wang, L, Zhang, H, Zou, T, Kang, Y, He, W, Xu, Y, Yin, W
Journal of intensive care. 2023;(1):29
Abstract
BACKGROUND A unified clinical definition of feeding intolerance (FI) is urged for better management of enteral nutrition (EN) in critically ill patients. We aimed to identify optimum clinical FI definitions based on reported evidence. METHODS We searched clinical studies comparing FI with non-FI with a clear definition, summarized the evidence by random-effect meta-analyses, and rated the certainty of evidence by the Grading of Recommendations Assessment, Development and Evaluation frameworks. RESULTS Five thousand five hundred twenty-five records were identified, of which 26 eligible studies enrolled 25,189 adult patients. Most patient-centered outcomes were associated with FI overall. Low to very low certainty evidence established FI defined as large gastric residual volume (GRV) ≥ 250 ± 50 mL combined with any other gastrointestinal symptoms (GIS) had a significant association with high mortalities in particular all-cause hospital mortality (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.40-2.57), the incidence of pneumonia (OR 1.54, 95% CI 1.13-2.09) and prolonged length of hospital stay (mean difference 4.20, 95% CI 2.08-6.32), with a moderate hospital prevalence (41.49%, 95% CI 31.61-51.38%). 3-day enteral feeding (EF) delivered percentage < 80% had a moderate hospital prevalence (38.23%, 95% CI 24.88-51.58) but a marginally significant association with all-cause hospital mortality (OR 1.90, 95% CI 1.03-3.50). CONCLUSIONS In critically ill adult patients receiving EN, the large-GRV-centered GIS to define FI seemed to be superior to 3-day EF-insufficiency in terms of both close associations with all-cause hospital mortality and acceptable hospital prevalence (Registered PROSPERO CRD42022326273). TRIAL REGISTRATION The protocol for this review and meta-analysis was registered with PROSPERO CRD42022326273. Registered 10 May 2022.
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7.
Clinical Trials in Hypertrophic Cardiomyopathy Therapy: A Comprehensive Analysis of Trials Registered in Global Clinical Databases.
Zhang, H, Yu, C, Cheng, Y, Chen, Z, Chen, M, He, W, Jin, Z, Cai, S, Yu, L
Drug design, development and therapy. 2023;:1863-1877
Abstract
BACKGROUND With the disappointing results associated with the use of cardiac myosin inhibitors in the treatment of hypertrophic cardiomyopathy (HCM), the development of new therapies in clinical trials for HCM has rapidly increased. We assessed the characteristics of therapeutic intervention in HCM registered on ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). METHODS We conducted a cross-sectional, descriptive study of clinical trials for therapeutic intervention in HCM registered on ClinicalTrials.gov and ICTRP. RESULTS This study analyzed 137 registered trials. Regarding study designs of these trials, 77.37% were purpose of treatment, 59.12% were randomized, 50.36% were parallel assignment, 45.26% were performed with masking, 48.18% recruited less than 50 participants, and 27.74% were Phase 2 trials. In total, 67 trials were new drug trials, of which 35 drugs were tested in these trials, and 13 trials involved treatment with mavacamten. Of these 67 clinical drug trials, 44.78% of trials involved the study of amines, and 16.42% involved 1-ring heterocyclic compounds. Regarding the NCI Thesaurus Tree, 23.81% of trials involved myosin inhibitors, 23.81% of trials involved drugs belonging to agents affecting the cardiovascular system, and 20.63% were involved in testing cation channel blockers. The drug-target network showed that myosin-7, potassium voltage-gated channel subfamily h member 2, beta-1 adrenergic receptor, carnitine o-palmitoyltransferase 1, and liver isoform were the most targeted pathways of the clinical trials analyzed in the drug-target network. CONCLUSION The number of clinical trials investigating therapeutic interventions for HCM has increased in recent years. Ultimately, recent HCM therapeutic clinical trials generally did not incorporate either randomized controlled trials or masking and were small studies recruiting fewer than 50 participants. Although recent research has focused on targeting myosin-7, the molecular signaling mechanisms involved in the pathogenesis of HCM have the potential to elucidate novel target pathways.
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8.
Application of Dexmedetomidine in Surgical Anesthesia for Gastric Cancer and Its Effects on IL-1β, IL-6, TNF-α and CRP.
Zheng, W, Tian, X, Fan, J, Jiang, X, He, W
Cellular and molecular biology (Noisy-le-Grand, France). 2023;(3):177-181
Abstract
This study was performed to analyze the application of dexmedetomidine (Dex) in anesthesia for gastric cancer surgery and its effect on serum inflammatory factors in patients. In this regard, a total of 78 patients with gastric cancer who were hospitalized in our hospital from January 2020 to September 2023 and received general intravenous anesthesia were randomly divided into two groups (n=39 in each group). The conventional group was given the same volume of 0.9% sodium chloride solution 10min before induction of anesthesia, and the Dex group was given Dex1μg/kg intravenous pump 10min before induction of anesthesia. The hemodynamics, serum levels of IL-1β, IL-6, TNF-α, CRP, propofol, remifentanil, and the total incidence of adverse reactions were compared between the two groups at different periods. The results showed that the mean arterial pressure (MAP), heart rate (HR), serum IL-1β, IL-6, TNF-α and CRP in the Dex group were compared with those in the routine group (P>0.05). MAP and HR in T1, T2 and T3Dex groups were lower than those in the conventional group (P<0.05). The serum levels of IL-1β, IL-6, TNF-α and CRP in T4 and T5 of the Dex group were lower than those of the routine group (P<0.05). The dosage of propofol and remifentanil in the Dex group was lower than those in the conventional group (P<0.05). The total incidence of adverse reactions in the Dex group (5.13%) was compared with that in the conventional group (10.26%), P>0.05. It was concluded that Dex can effectively maintain the stability of hemodynamics during gastric cancer surgery, reduce the dosage of propofol and other anesthetic drugs, reduce inflammation, and has a certain safety without obvious adverse reactions.
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9.
Blue light promotes zero-valent sulfur production in a deep-sea bacterium.
Cai, R, He, W, Zhang, J, Liu, R, Yin, Z, Zhang, X, Sun, C
The EMBO journal. 2023;(12):e112514
Abstract
Increasing evidence has shown that light exists in a diverse range of deep-sea environments. We unexpectedly found that blue light is necessary to produce excess zero-valent sulfur (ZVS) in Erythrobacter flavus 21-3, a bacterium that has been recently isolated from a deep-sea cold seep. E. flavus 21-3 is able to convert thiosulfate to ZVS using a novel thiosulfate oxidation pathway comprising a thiosulfate dehydrogenase (TsdA) and a thiosulfohydrolase (SoxB). Using proteomic, bacterial two-hybrid and heterologous expression assays, we found that the light-oxygen-voltage histidine kinase LOV-1477 responds to blue light and activates the diguanylate cyclase DGC-2902 to produce c-di-GMP. Subsequently, the PilZ domain-containing protein mPilZ-1753 binds to c-di-GMP and activates TsdA through direct interaction. Finally, Raman spectroscopy and gene knockout results verified that TsdA and two SoxB homologs cooperate to regulate ZVS production. As ZVS is an energy source for E. flavus 21-3, we propose that deep-sea blue light provides E. flavus 21-3 with a selective advantage in the cold seep, suggesting a previously unappreciated relationship between light-sensing pathways and sulfur metabolism in a deep-sea microorganism.
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10.
Iron accumulation and its impact on osteoporotic fractures in postmenopausal women.
Cai, H, Zhang, H, He, W, Zhang, H
Journal of Zhejiang University. Science. B. 2023;(4):301-311
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Abstract
Postmenopausal osteoporosis is a kind of degenerative disease, also described as "invisible killer." Estrogen is generally considered as the key hormone for women to maintain bone mineral content during their lives. Iron accumulation refers to a state of human serum ferritin that is higher than the normal value but less than 1000 μg/L. It has been found that iron accumulation and osteoporosis could occur simultaneously with the decrease in estrogen level after menopause. In recent years, many studies indicated that iron accumulation plays a vital role in postmenopausal osteoporosis, and a significant correlation has been found between iron accumulation and fragility fractures. In this review, we summarize and analyze the relevant literature including randomized controlled trials, systematic reviews, and meta-analyses between January 1996 and July 2022. We investigate the mechanism of the effect of iron accumulation on bone metabolism and discuss the relationship of iron accumulation, osteoporosis, and postmenopausal fragility fractures, as well as the main clinical treatment strategies. We conclude that it is necessary to pay attention to the phenomenon of iron accumulation in postmenopausal women with osteoporosis and explore the in-depth mechanism of abnormal bone metabolism caused by iron accumulation, in order to facilitate the discovery of effective therapeutic targets for postmenopausal osteoporosis.