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1.
The role of Sirtuin 2 in liver - An extensive and complex biological process.
Li, S, Guo, L
Life sciences. 2024;:122431
Abstract
Liver disease has become one of the main causes of health issue worldwide. Sirtuin (Sirt) 2 is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and is expressed in multiple organs including liver, which plays important and complex roles by interacting with various substrates. Physiologically, Sirt2 can improve metabolic homeostasis. Pathologically, Sirt2 can alleviate inflammation, endoplasmic reticulum (ER) stress, promote liver regeneration, maintain iron homeostasis, aggravate fibrogenesis and regulate oxidative stress in liver. In liver diseases, Sirt2 can mitigate fatty liver disease (FLD) including non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), but aggravate hepatitis B (HBV) and liver ischemia-reperfusion injury (LIRI). The role of Sirt2 in liver cancer and aging-related liver diseases, however, has not been fully elucidated. In this review, these biological processes regulated by Sirt2 in liver are summarized, which aims to update the function of Sirt2 in liver and to explore the potential role of Sirt2 as a therapeutic target for liver diseases.
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2.
Non-coding RNAs and leaf senescence: Small molecules with important roles.
Li, S, Zhao, Y, Tan, S, Li, Z
Plant physiology and biochemistry : PPB. 2024;:108399
Abstract
Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.
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3.
Optimal vitamin D supplement dosage for improving insulin resistance in children and adolescents with overweight/obesity: a systematic review and network meta-analysis.
Zhu, L, Li, S, Zhong, L, Xu, S, Zhu, H
European journal of nutrition. 2024;(3):763-775
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Abstract
PURPOSE We conducted a network meta-analysis which aims to evaluate the comparative efficacy of different supplementation dosages of vitamin D on cardiometabolic and bone-metabolic indicators as well as insulin resistance in children and adolescents with overweight/obesity. METHODS Eligible studies published before December 10, 2022 were retrieved from PubMed, EMBASE, Cochrane Library, and Web of Science. Mean difference and 95% confidence interval (CI) were used to express pooled estimates. Network meta-analysis of multiple doses, including low (< 1000 IU/day, LDS), medium (1000-2000 IU/day, MDS), high (2000-4000 IU/day, HDS), and extremely high (> 4000 IU/day, EHDS) dosage strategy, was conducted using STATA/MP 14.0. RESULTS Our network meta-analysis of 15 RCTs suggested that, compared with placebo and LDS, EHDS was increased 25-(OH)-D, with a pooled MD of 8.65 (95% CI 4.72-12.58) and 7.66 (95% CI 0.91-14.41), respectively. Meanwhile, EHDS also decreased ho meostasis model assessment-insulin resistance (HOMA-IR) (MD: - 0.74; 95% CI: - 1.45 to - 0.04) and C-reactive protein (CRP) (MD: - 18.99; 95% CI - 21.60 to - 16.38), and EHDS was also better than LDS (MD: - 18.47; 95% CI - 20.66 to - 16.28) and MDS (MD: - 19.69; 95% CI - 22.17 to - 17.21) in decreasing CRP. Ranking probability suggested that EHDS ranked best for increasing 25-(OH)-D, and decreasing HOMA-IR and CRP, with a probability of 86.1%, 83.1%, and 76.6%, respectively. CONCLUSIONS The results of our network meta-analysis suggest that EHDS may be the best strategy for vitamin D supplementation to reduce inflammatory responses as well as improve insulin resistance in children and adolescents with overweight/obesity. PROSPERO REGISTRATION NUMBER CRD42023387775.
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The antitumor effects of herbal medicine Triphala on oral cancer by inactivating PI3K/Akt signaling pathway: based on the network pharmacology, molecular docking, in vitro and in vivo experimental validation.
Hu, S, Li, S, Xu, Y, Huang, X, Mai, Z, Chen, Y, Xiao, H, Ning, W, Gaus, S, Savkovic, V, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155488
Abstract
BACKGROUND This research aimed to investigate the anti-tumor effects and underlying genetic mechanisms of herbal medicine Triphala (TRP) in oral squamous cell carcinoma (OSCC). METHODS The target genes of Triphala (TRP) in oral squamous cell carcinoma (OSCC) were identified, and subsequent functional enrichment analysis was conducted to determine the enriched signaling pathways. Based on these genes, a protein-protein interaction network was constructed to identify the top 10 genes with the highest degree. Genes deregulated in OSCC tumor samples were identified to be hub genes among the top 10 genes. In vitro experiments were performed to investigate the influence of TRP extracts on the cell metabolic activity, migration, invasion, apoptosis, and proliferation of two OSCC cell lines (CAL-27 and SCC-9). The functional rescue assay was conducted to investigate the effect of applying the inhibitor and activator of an enriched pathway on the phenotypes of cancer cells. In addition, the zebrafish xenograft tumor model was established to investigate the influence of TRP extracts on tumor growth and metastasis in vivo. RESULTS The target genes of TRP in OSCC were prominently enriched in the PI3K-Akt signaling pathway, with the identification of five hub genes (JUN, EGFR, ESR1, RELA, and AKT1). TRP extracts significantly inhibited cell metabolic activity, migration, invasion, and proliferation and promoted cell apoptosis in OSCC cells. Notably, the application of TRP extracts exhibited the capacity to downregulate mRNA and phosphorylated protein levels of AKT1 and ESR1, while concomitantly inducing upregulation of mRNA and phosphorylated protein levels in the remaining three hub genes (EGFR, JUN, and RELA). The functional rescue assay demonstrated that the co-administration of TRP and the PI3K activator 740Y-P effectively reversed the impact of TRP on the phenotypes of OSCC cells. Conversely, the combination of TRP and the PI3K inhibitor LY294002 further enhanced the effect of TRP on the phenotypes of OSCC cells. Remarkably, treatment with TRP in zebrafish xenograft models demonstrated a significant reduction in both tumor growth and metastatic spread. CONCLUSIONS Triphala exerted significant inhibitory effects on cell metabolic activity, migration, invasion, and proliferation in OSCC cell lines, accompanied by the induction of apoptosis, which was mediated through the inactivation of the PI3K/Akt pathway.
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Perspective of Calcium Imaging Technology Applied to Acupuncture Research.
Li, S, Liu, Y, Zhang, N, Li, W, Xu, WJ, Xu, YQ, Chen, YY, Cui, X, Zhu, B, Gao, XY
Chinese journal of integrative medicine. 2024;(1):3-9
Abstract
Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
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Time-varying effects of sodium-glucose cotransporter-2 inhibitors in patients with heart failure: An updated meta-analysis.
Zou, X, Shi, Q, Li, S
Journal of evidence-based medicine. 2024;(1):13-16
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7.
Role of ferroptosis in chronic kidney disease.
Li, S, Han, Q, Liu, C, Wang, Y, Liu, F, Pan, S, Zuo, L, Gao, D, Chen, K, Feng, Q, et al
Cell communication and signaling : CCS. 2024;(1):113
Abstract
Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract.
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The significance of precisely regulating heme oxygenase-1 expression: Another avenue for treating age-related ocular disease?
Wei, D, Qu, C, Zhao, N, Li, S, Pu, N, Song, Z, Tao, Y
Ageing research reviews. 2024;:102308
Abstract
Aging entails the deterioration of the body's organs, including overall damages at both the genetic and cellular levels. The prevalence of age-related ocular disease such as macular degeneration, dry eye diseases, glaucoma and cataracts is increasing as the world's population ages, imposing a considerable economic burden on individuals and society. The development of age-related ocular disease is predominantly triggered by oxidative stress and chronic inflammatory reaction. Heme oxygenase-1 (HO-1) is a crucial antioxidant that mediates the degradative process of endogenous iron protoporphyrin heme. It catalyzes the rate-limiting step of the heme degradation reaction, and releases the metabolites such as carbon monoxide (CO), ferrous, and biliverdin (BV). The potent scavenging activity of these metabolites can help to defend against peroxides, peroxynitrite, hydroxyl, and superoxide radicals. Other than directly decomposing endogenous oxidizing substances (hemoglobin), HO-1 is also a critical regulator of inflammatory cells and tissue damage, exerting its anti-inflammation activity through regulating complex inflammatory networks. Therefore, promoting HO-1 expression may act as a promising therapeutic strategy for the age-related ocular disease. However, emerging evidences suggest that the overexpression of HO-1 significantly contributes to ferroptosis due to its dual nature. Surplus HO-1 leads to excessive Fe2+ and reactive oxygen species, thereby causing lipid peroxidation and ferroptosis. In this review, we elucidate the role of HO-1 in countering age-related disease, and summarize recent pharmacological trials that targeting HO-1 for disease management. Further refinements of the knowledge would position HO-1 as a novel therapeutic target for age-related ocular disease.
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Association of possible sarcopenia with all-cause mortality in patients with solid cancer: A nationwide multicenter cohort study.
Yin, L, Song, C, Cui, J, Lin, X, Li, N, Fan, Y, Zhang, L, Liu, J, Chong, F, Cong, M, et al
The journal of nutrition, health & aging. 2024;(1):100023
Abstract
OBJECTIVES The concept of possible sarcopenia (PS) was recently introduced to enable timely intervention in settings without the technologies required to make a full diagnosis of sarcopenia. This study aimed to investigate the association between PS and all-cause mortality in patients with solid cancer. DESIGN Retrospective observational study. SETTING AND PARTICIPANTS 13,736 patients with 16 types of solid cancer who were ≥18 years old. MEASUREMENTS The presence of both a low calf circumference (men <34 cm or women <33 cm) and low handgrip strength (men <28 kg or women <18 kg) was considered to indicate PS. Harrell's C-index was used to assess prognostic value and the association of PS with mortality was estimated by calculating multivariable-adjusted hazard ratios (HRs). RESULTS The study enrolled 7207 men and 6529 women (median age = 57.8 years). During a median follow-up of 43 months, 3150 deaths occurred. PS showed higher Harrell's C-index (0.549, 95%CI = [0.541, 0.557]) than the low calf circumference (0.541, 95%CI = [0.531, 0.551], P = 0.037) or low handgrip strength (0.542, 95%CI = [0.532, 0.552], P = 0.026). PS was associated with increased mortality risk in both univariate (HR = 1.587, 95%CI = [1.476, 1.708]) and multivariable-adjusted models (HR = 1.190, 95%CI = [1.094, 1.293]). Sensitivity analyses showed that the association of PS with mortality was robust in different covariate subgroups, which also held after excluding those patients who died within the first 3 months (HR = 1.162, 95%CI = [1.060, 1.273]), 6 months (HR = 1.150, 95%CI = [1.039, 1.274]) and 12 months (HR = 1.139, 95%CI = [1.002, 1.296]) after enrollment. CONCLUSION PS could independently and robustly predict all-cause mortality in patients with solid cancer. These findings imply the importance of including PS assessment in routine cancer care to provide significant prognostic information to help mitigate sarcopenia-related premature deaths.
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Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.
Chen, JY, Li, S, Silva, GL, Chandler, JD, Prausnitz, MR, Guglani, L
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2024;(1):112-119
Abstract
BACKGROUND The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. METHODS We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. RESULTS Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. CONCLUSIONS Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.