-
1.
SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion.
Ding, X, Zhu, C, Wang, W, Li, M, Ma, C, Gao, B
Pharmacological research. 2024;:106957
-
-
Free full text
-
Abstract
SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.
-
2.
ZNF217: An Oncogenic Transcription Factor and Potential Therapeutic Target for Multiple Human Cancers.
Wang, Y, Ma, C, Yang, X, Gao, J, Sun, Z
Cancer management and research. 2024;:49-62
Abstract
Zinc finger protein 217 (ZNF217) is one of the well-researched members of the Krüppel-like factor transcription factor family. ZNF217 possesses a characteristic structure of zinc finger motifs and plays a crucial role in regulating the biological activities of cells. Recent findings have revealed that ZNF217 is strongly associated with multiple aspects of cancer progression, impacting patient prognosis. Notably, ZNF217 is subject to regulation by non-coding RNAs, suggesting the potential for targeted manipulation of such RNAs as a robust therapeutic avenue for managing cancer in the future. The main purpose of this article is to provide a detailed examination of the role of ZNF217 in human malignant tumors and the regulation of its expression, and to offer new perspectives for cancer treatment.
-
3.
Standardizing Randomized Controlled Trials in Celiac Disease: An International Multidisciplinary Appropriateness Study.
Lebwohl, B, Ma, C, Lagana, SM, Pai, RK, Baker, KA, Zayadi, A, Hogan, M, Bouma, G, Cellier, C, Goldsmith, JD, et al
Gastroenterology. 2024;(1):88-102
Abstract
BACKGROUND & AIMS There is a need to develop safe and effective pharmacologic options for the treatment of celiac disease (CeD); however, consensus on the appropriate design and configuration of randomized controlled trials (RCTs) in this population is lacking. METHODS A 2-round modified Research and Development/University of California Los Angeles Appropriateness Method study was conducted. Eighteen gastroenterologists (adult and pediatric) and gastrointestinal pathologists voted on statements pertaining to the configuration of CeD RCTs, inclusion and exclusion criteria, gluten challenge, and trial outcomes. Two RCT designs were considered, representing the following distinct clinical scenarios for which pharmacotherapy may be used: trials incorporating a gluten challenge to simulate exposure; and trials evaluating reversal of histologic changes, despite attempted adherence to a gluten-free diet. Each statement was rated as appropriate, uncertain, or inappropriate, using a 9-point Likert scale. RESULTS For trials evaluating prevention of relapse after gluten challenge, participants adherent to a gluten-free diet for 12 months or more with normal or near-normal-sized villi should be enrolled. Gluten challenge should be FODMAPS (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) free, and efficacy evaluated using histology with a secondary patient-reported outcome measure. For trials evaluating reversal of villus atrophy, the panel voted it appropriate to enroll participants with a baseline villus height to crypt depth ratio ≤2 and measure efficacy using a primary histologic end point. Guidance for measuring histologic, endoscopic, and patient-reported outcomes in adult and pediatric patients with CeD are provided, along with recommendations regarding the merits and limitations of different end points. CONCLUSIONS We developed standardized recommendations for clinical trial design, eligibility criteria, outcome measures, gluten challenge, and disease evaluations for RCTs in patients with CeD.
-
4.
Recommendations for Standardizing MRI-based Evaluation of Perianal Fistulizing Disease Activity in Pediatric Crohn's Disease Clinical Trials.
Crowley, E, Ma, C, Guizzetti, L, Zou, G, Lewindon, PJ, Gee, MS, Hyams, JS, Rosen, MJ, von Allmen, D, de Buck van Overstraeten, A, et al
Inflammatory bowel diseases. 2024;(3):357-369
Abstract
BACKGROUND Perianal fistulas and abscesses occur commonly as complications of pediatric Crohn's disease (CD). A validated imaging assessment tool for quantification of perianal disease severity and activity is needed to evaluate treatment response. We aimed to identify magnetic resonance imaging (MRI)-based measures of perianal fistulizing disease activity and study design features appropriate for pediatric patients. METHODS Seventy-nine statements relevant to MRI-based assessment of pediatric perianal fistulizing CD activity and clinical trial design were generated from literature review and expert opinion. Statement appropriateness was rated by a panel (N = 15) of gastroenterologists, radiologists, and surgeons using modified RAND/University of California Los Angeles appropriateness methodology. RESULTS The modified Van Assche Index (mVAI) and the Magnetic Resonance Novel Index for Fistula Imaging in CD (MAGNIFI-CD) were considered appropriate instruments for use in pediatric perianal fistulizing disease clinical trials. Although there was concern regarding the use of intravascular contrast material in pediatric patients, its use in clinical trials was considered appropriate. A clinically evident fistula tract and radiologic disease defined as at least 1 fistula or abscess on pelvic MRI were considered appropriate trial inclusion criteria. A coprimary clinical and radiologic end point and inclusion of a patient-reported outcome were also considered appropriate. CONCLUSION Outcomes of treatment of perianal fistulizing disease in children must include MRI. Existing multi-item measures, specifically the mVAI and MAGNIFI-CD, can be adapted and used for children. Further research to assess the operating properties of the indices when used in a pediatric patient population is ongoing.
-
5.
Adversarial learning-based domain adaptation algorithm for intracranial artery stenosis detection on multi-source datasets.
Gao, Y, Ma, C, Guo, L, Liu, G, Zhang, X, Ji, X
Computers in biology and medicine. 2024;:108001
Abstract
Intracranial arterial stenosis (ICAS) is characterized by the pathological narrowing or occlusion of the inner lumen of intracranial blood vessels. However, the retina can indirectly react to cerebrovascular disease. Therefore, retinal fundus images (RFI) serve as valuable noninvasive and easily accessible screening tools for early detection and diagnosis of ICAS. This paper introduces an adversarial learning-based domain adaptation algorithm (ALDA) specifically designed for ICAS detection in multi-source datasets. The primary objective is to achieve accurate detection and enhanced generalization of ICAS based on RFI. Given the limitations of traditional algorithms in meeting the accuracy and generalization requirements, ALDA overcomes these challenges by leveraging RFI datasets from multiple sources and employing the concept of adversarial learning to facilitate feature representation sharing and distinguishability learning. In order to evaluate the performance of the ALDA algorithm, we conducted experimental validation on multi-source datasets. We compared its results with those obtained from other deep learning algorithms in the ICAS detection task. Furthermore, we validated the potential of ALDA for detecting diabetic retinopathy. The experimental results clearly demonstrate the significant improvements achieved by the ALDA algorithm. By leveraging information from diverse datasets, ALDA learns feature representations that exhibit enhanced generalizability and robustness. This makes it a reliable auxiliary diagnostic tool for clinicians, thereby facilitating the prevention and treatment of cerebrovascular diseases.
-
6.
Exploring the link between vitamin D deficiency and obstructive sleep apnea: A comprehensive review.
Yao, N, Ma, C, Dou, R, Shen, C, Yuan, Y, Li, W, Qu, J
Journal of sleep research. 2024;:e14166
Abstract
Despite the high prevalence and significant health burden of obstructive sleep apnea (OSA), its underlying pathophysiology remains incompletely understood. This comprehensive review explores the emerging connection between vitamin D deficiency and OSA, discusses potential mechanisms underlying this association, and explores the therapeutic implications of these findings. Recent research has consistently highlighted the high incidence of vitamin D deficiency among patients with OSA, which often occurs independently of geographical location. This suggests that factors beyond lack of sunlight exposure may be involved. This review also discusses how reduced vitamin D may be associated with more severe manifestations of OSA. In addition, it explores the potentiality of using vitamin D supplements as a therapeutic strategy for OSA, noting that some studies have found improvements in sleep quality and a reduction in OSA severity. Potential mechanisms are proposed, including the role of vitamin D deficiency in promoting inflammation, oxidative stress, hypoxia, impairing immune function, muscle function, and gene polymorphism of vitamin D receptors, all of which could contribute to the pathogenesis of obstructive sleep apnea. The paper underscores the need for future research to validate these observations, to determine optimal vitamin D supplementation dosage and duration, to explore potential side effects and risks, and to investigate potential interactions with other treatments.
-
7.
Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: A systematic review and meta-analysis of randomized controlled trials.
Zheng, S, Lai, Y, Jiang, C, He, L, Zhao, Z, Li, W, Tang, R, Sang, C, Long, D, Du, X, et al
Pacing and clinical electrophysiology : PACE. 2024;(1):58-65
Abstract
BACKGROUND Sodium-glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear. SS AIMS To investigate the effect of SGLT2i on the incidence of CV events in patients with AF. METHODS Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all-cause mortality. RESULTS Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow-up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74-0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69-0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64-0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta-regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i. CONCLUSIONS The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.
-
8.
1-Phosphate receptor agonists: A promising therapeutic avenue for ischemia-reperfusion injury management.
Wang, L, Zhang, X, Ma, C, Wu, N
International immunopharmacology. 2024;:111835
Abstract
Ischemia-reperfusion injury (IRI) - a complex pathological condition occurring when blood supply is abruptly restored to ischemic tissues, leading to further tissue damage - poses a significant clinical challenge. Sphingosine-1-phosphate receptors (S1PRs), a specialized set of G-protein-coupled receptors comprising five subtypes (S1PR1 to S1PR5), are prominently present in various cell membranes, including those of lymphocytes, cardiac myocytes, and endothelial cells. Increasing evidence highlights the potential of targeting S1PRs for IRI therapeutic intervention. Notably, preconditioning and postconditioning strategies involving S1PR agonists like FTY720 have demonstrated efficacy in mitigating IRI. As the synthesis of a diverse array of S1PR agonists continues, with FTY720 being a prime example, the body of experimental evidence advocating for their role in IRI treatment is expanding. Despite this progress, comprehensive reviews delineating the therapeutic landscape of S1PR agonists in IRI remain limited. This review aspires to meticulously elucidate the protective roles and mechanisms of S1PR agonists in preventing and managing IRI affecting various organs, including the heart, kidney, liver, lungs, intestines, and brain, to foster novel pharmacological approaches in clinical settings.
-
9.
Withdrawal of Immunomodulators or TNF Antagonists in Patients With Inflammatory Bowel Diseases in Remission on Combination Therapy: A Systematic Review and Meta-analysis.
Katibian, DJ, Solitano, V, Polk, DB, Nguyen, T, Ma, C, Syal, G, Kobayashi, T, Hibi, T, Buhl, S, Ainsworth, MA, et al
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2024;(1):22-33.e6
Abstract
BACKGROUND & AIMS Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy. METHODS Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence. RESULTS We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy. CONCLUSIONS In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.
-
10.
Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis.
Ma, C, Liu, M, Cheng, Y, Wang, X, Zhao, Y, Wang, K, Wang, W
Frontiers in immunology. 2024;:1382728
Abstract
INTRODUCTION We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). METHODS Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493. RESULTS According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events. DISCUSSION In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.