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1.
The engineered exosomes targeting ferroptosis: A novel approach to reverse immune checkpoint inhibitors resistance.
Chen, A, Zhang, W, Jiang, C, Jiang, Z, Tang, D
International journal of cancer. 2024
Abstract
Immune checkpoint inhibitors (ICIs) have been extensively used in immunological therapy primarily due to their ability to prolong patient survival. Although ICIs have achieved success in cancer treatment, the resistance of ICIs should not be overlooked. Ferroptosis is a newly found cell death mode characterized by the accumulation of reactive oxygen species (ROS), glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, which has been demonstrated to be beneficial to immunotherapy and combining ferroptosis and ICIs to exploit new immunotherapies may reverse ICIs resistance. Exosomes act as mediators in cell-to-cell communication that may regulate ferroptosis to influence immunotherapy through the secretion of biological molecules. Thus, utilizing exosomes to target ferroptosis has opened up exciting possibilities for reversing ICIs resistance. In this review, we summarize the mechanisms of ferroptosis improving ICIs therapy and how exosomes regulate ferroptosis through adjusting iron metabolism, blocking the ROS accumulation, controlling ferroptosis defense systems, and influencing classic signaling pathways and how engineered exosomes target ferroptosis and improve ICIs efficiency.
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2.
Oxygen generating biomaterials at the forefront of regenerative medicine: advances in bone regeneration.
Zhao, J, Zhou, C, Xiao, Y, Zhang, K, Zhang, Q, Xia, L, Jiang, B, Jiang, C, Ming, W, Zhang, H, et al
Frontiers in bioengineering and biotechnology. 2024;:1292171
Abstract
Globally, an annual count of more than two million bone transplants is conducted, with conventional treatments, including metallic implants and bone grafts, exhibiting certain limitations. In recent years, there have been significant advancements in the field of bone regeneration. Oxygen tension regulates cellular behavior, which in turn affects tissue regeneration through metabolic programming. Biomaterials with oxygen release capabilities enhance therapeutic effectiveness and reduce tissue damage from hypoxia. However, precise control over oxygen release is a significant technical challenge, despite its potential to support cellular viability and differentiation. The matrices often used to repair large-size bone defects do not supply enough oxygen to the stem cells being used in the regeneration process. Hypoxia-induced necrosis primarily occurs in the central regions of large matrices due to inadequate provision of oxygen and nutrients by the surrounding vasculature of the host tissues. Oxygen generating biomaterials (OGBs) are becoming increasingly significant in enhancing our capacity to facilitate the bone regeneration, thereby addressing the challenges posed by hypoxia or inadequate vascularization. Herein, we discussed the key role of oxygen in bone regeneration, various oxygen source materials and their mechanism of oxygen release, the fabrication techniques employed for oxygen-releasing matrices, and novel emerging approaches for oxygen delivery that hold promise for their potential application in the field of bone regeneration.
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3.
Unleashing Axonal Regeneration Capacities: Neuronal and Non-neuronal Changes After Injuries to Dorsal Root Ganglion Neuron Central and Peripheral Axonal Branches.
Zhao, Q, Jiang, C, Zhao, L, Dai, X, Yi, S
Molecular neurobiology. 2024;(1):423-433
Abstract
Peripheral nerves obtain remarkable regenerative capacity while central nerves can hardly regenerate following nerve injury. Sensory neurons in the dorsal root ganglion (DRG) are widely used to decipher the dissimilarity between central and peripheral axonal regeneration as axons of DRG neurons bifurcate into the regeneration-incompetent central projections and the regeneration-competent peripheral projections. A conditioning peripheral branch injury facilitates central axonal regeneration and enables the growth and elongation of central axons. Peripheral axonal injury stimulates neuronal calcium influx, alters the start-point chromatin states, increases chromatin accessibility, upregulates the expressions of regeneration-promoting genes and the synthesis of proteins, and supports axonal regeneration. Following central axonal injury, the responses of DRG neurons are modest, resulting in poor intrinsic growth ability. Some non-neuronal cells in DRGs, for instance satellite glial cells, also exhibit diminished injury responses to central axon injury as compared with peripheral axon injury. Moreover, DRG central and peripheral axonal branches are respectively surrounded by inhibitory glial scars generated by central glial cells and a permissive microenvironment generated by Schwann cells and macrophages. The aim of this review is to look at changes of DRG neurons and non-neuronal cells after peripheral and central axon injuries and summarize the contributing roles of both neuronal intrinsic regenerative capacities and surrounding microenvironments in axonal regeneration.
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4.
Clinical interpretation of KCNH2 variants using a robust PS3/BS3 functional patch-clamp assay.
Thomson, KL, Jiang, C, Richardson, E, Westphal, DS, Burkard, T, Wolf, CM, Vatta, M, Harrison, SM, Ingles, J, Bezzina, CR, et al
HGG advances. 2024;(2):100270
Abstract
Long QT syndrome (LQTS), caused by the dysfunction of cardiac ion channels, increases the risk of sudden death in otherwise healthy young people. For many variants in LQTS genes, there is insufficient evidence to make a definitive genetic diagnosis. We have established a robust functional patch-clamp assay to facilitate classification of missense variants in KCNH2, one of the key LQTS genes. A curated set of 30 benign and 30 pathogenic missense variants were used to establish the range of normal and abnormal function. The extent to which variants reduced protein function was quantified using Z scores, the number of standard deviations from the mean of the normalized current density of the set of benign variant controls. A Z score of -2 defined the threshold for abnormal loss of function, which corresponds to 55% wild-type function. More extreme Z scores were observed for variants with a greater loss-of-function effect. We propose that the Z score for each variant can be used to inform the application and weighting of abnormal and normal functional evidence criteria (PS3 and BS3) within the American College of Medical Genetics and Genomics variant classification framework. The validity of this approach was demonstrated using a series of 18 KCNH2 missense variants detected in a childhood onset LQTS cohort, where the level of function assessed using our assay correlated to the Schwartz score (a scoring system used to quantify the probability of a clinical diagnosis of LQTS) and the length of the corrected QT (QTc) interval.
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5.
Designing salt stress-resilient crops: Current progress and future challenges.
Liang, X, Li, J, Yang, Y, Jiang, C, Guo, Y
Journal of integrative plant biology. 2024;(3):303-329
Abstract
Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide. Therefore, understanding the molecular mechanisms of plant salt tolerance has scientific importance and practical significance. In recent decades, studies have characterized hundreds of genes associated with plant responses to salt stress in different plant species. These studies have substantially advanced our molecular and genetic understanding of salt tolerance in plants and have introduced an era of molecular design breeding of salt-tolerant crops. This review summarizes our current knowledge of plant salt tolerance, emphasizing advances in elucidating the molecular mechanisms of osmotic stress tolerance, salt-ion transport and compartmentalization, oxidative stress tolerance, alkaline stress tolerance, and the trade-off between growth and salt tolerance. We also examine recent advances in understanding natural variation in the salt tolerance of crops and discuss possible strategies and challenges for designing salt stress-resilient crops. We focus on the model plant Arabidopsis (Arabidopsis thaliana) and the four most-studied crops: rice (Oryza sativa), wheat (Triticum aestivum), maize (Zea mays), and soybean (Glycine max).
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6.
Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial.
Wang, Y, Jiang, C, Dong, X, Chen, M, Gu, Q, Zhang, L, Fu, Y, Pan, T, Bi, Y, Song, W, et al
Diabetes, obesity & metabolism. 2024
Abstract
AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
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7.
Nutritional therapy of older osteoporotic people with supplemental calcium and vitamin D: side effects, fracture rates, and survival - an internationalised meta-analysis.
Jiao, D, Jiang, C
Asia Pacific journal of clinical nutrition. 2024;(1):1-10
Abstract
BACKGROUND AND OBJECTIVES Recent controversy over the bone benefits of calcium and vitamin D supplementation, and the potential detrimental effects of excess calcium supplementation, has confused clinicians. To systematically evaluate the effectiveness and safety of vitamin D combined with calcium in preventing and treating osteoporotic symptoms in the elderly. METHODS AND STUDY DESIGN Databases were searched to collect randomized controlled trials (RCTs) on vitamin D combined with calcium in the prevention and treatment of osteoporotic fractures in the elderly. After screening the literature, extracting data, and assessing the risk of bias in the included studies, the Meta-analysis was performed. RESULTS 19 RCTs were included, including 69,234 patients. Meta-analysis results showed that the mortality rate of the vitamin D combined with calcium group was not statistically significant compared with the control group; the calcium combined with vitamin D significantly reduced the incidence of fractures compared with the control group,Density and serum 25-hydroxyl concentration, adverse reactions of calcium combined with vitamin D were higher than those in the control group. CONCLUSIONS The combination of vitamin D and calcium has no difference in mortality rate, and it can prevent fractures in the elderly, and enhance bone density and serum 25-hydroxyvitamin D concentration, but still need to pay attention to adverse reactions in the gastrointestinal tract.
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8.
Effect of chemotherapy in tumor on coronary arteries: Mechanisms and management.
Jiang, C, Xu, H, Wu, Y
Life sciences. 2024;:122377
Abstract
Coronary artery disease (CAD) is an important contributor to the cardiovascular burden in cancer survivors. The development of coronary ischemia events, myocardial infarction, and heart failure has been associated with many conventional chemotherapeutic agents, new targeted therapies, and immunotherapy. The most frequent pathological manifestations of chemotherapy-mediated coronary damage include acute vasospasm, acute thrombosis, accelerated atherosclerosis development, and microvascular dysfunction. Potential screening techniques for CAD patients include baseline risk factor evaluation, polygenic risk factors, and coronary artery calcium scores. Determining the risk requires consideration of both the type of chemotherapy and the type of cancer being treated. Cardiology-oncology guidelines offer some suggestions for the care of coronary artery disease, which might involve medication, lifestyle changes, and coronary revascularization.
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9.
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.
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10.
Medium- and Long-Chain Triacylglycerol: Preparation, Health Benefits, and Food Utilization.
Cheng, X, Jiang, C, Jin, J, Jin, Q, Akoh, CC, Wei, W, Wang, X
Annual review of food science and technology. 2024
Abstract
Medium- and long-chain triacylglycerol (MLCT) is a structured lipid with both medium- and long-chain fatty acids in one triacylglycerol molecule. Compared with long-chain triacylglycerol (LCT), which is mainly present in common edible oils, and the physical blend of medium-chain triacylglycerol with LCT (MCT/LCT), MLCT has different physicochemical properties, metabolic characteristics, and nutritional values. In this article, the recent advances in the use of MLCT in food formulations are reviewed. The natural sources and preparation of MLCT are discussed. A comprehensive summary of MLCT digestion, absorption, transport, and oxidation is provided as well as its health benefits, including reducing the risk of overweight, hypolipidemic and hypoglycemic effects, etc. The potential MLCT uses in food formulations, such as infant formulas, healthy foods for weight loss, and sports foods, are summarized. Finally, the current safety assessment and regulatory status of MLCT in food formulations are reviewed. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 15 is April 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.