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1.
Regulation of the Notch signaling pathway by natural products for cancer therapy.
Cai, J, Qiao, Y, Chen, L, Lu, Y, Zheng, D
The Journal of nutritional biochemistry. 2024;:109483
Abstract
The Notch signaling pathway is an evolutionarily conserved pathway that modulates normal biological processes involved in cellular differentiation, apoptosis, and stem cell self-renewal in a context-dependent fashion. Attributed to its pleiotropic physiological roles, both overexpression and silencing of the pathway are associated with the emergence, progression, and poorer prognosis in various types of cancer. To decrease disease incidence and promote survival, targeting Notch may have chemopreventive and anti-cancer effects. Natural products with profound historical origins have distinguished themselves from other therapies due to their easy access, high biological compatibility, low toxicity, and reliable effects at specific physiological sites in vivo. This review describes the Notch signaling pathway, particularly its normal activation process, and some main illnesses related to Notch signaling pathway dysregulation. Emphasis is placed on the effects and mechanisms of natural products targeting the Notch signaling pathway in diverse cancer types, including curcumin, ellagic acid (EA), resveratrol, genistein, epigallocatechin-3-gallate (EGCG), quercetin, and xanthohumol and so on. Existing evidence indicates that natural products are feasible solution to fight against cancer by targeting Notch signaling, either alone or in combination with current therapeutic agents.
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Physiological and Molecular Response of Liriodendron chinense to Varying Stand Density.
Chen, J, Li, T, Cai, J, Yu, P, Guo, Y
Plants (Basel, Switzerland). 2024;(4)
Abstract
Stand density affects the potentially superior productivity of forest ecosystems directly by regulating the light and nutrient availability of trees. Understanding how stand density influences the growth and development of trees is crucial for supporting forest management in the context of climate change. We focused on Liriodendron chinense in experimental plantations created in 2003, with planting densities ranging from 277 to 10,000 trees per hectare at six plots. The leaf structure and photosynthetic capacity of L. chinense changed significantly under different stand densities, which had a negative impact on their biomass (leaf mass) and nutrient (total carbohydrate content) accumulation. Transcriptional differences were observed among samples from plots with different planting densities. The expression of 1784 genes was negatively dependent on stand density, participating mainly in the biological processes of "circadian rhythm", "carbon metabolism", and "amino acid biosynthesis". Furthermore, we identified a photosynthesis-related module and constructed a gene regulatory network to discover that the transcription factors of MYB and bHLH may have important roles in the transcriptional regulation of photosynthesis biosynthesis by activating or repressing the expression of petA (Litul.15G096200), psbE (Litul.10G033900), and petD (Litul.17G061600) at different stand densities. Our study quantified the impact of stand density on tree growth at physiological and molecular levels. Our observations provide theoretical support for plantation establishment of L. chinense.
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Research progress and future development potential of Flammulina velutipes polysaccharides in the preparation process, structure analysis, biology, and pharmacology: A review.
Ye, S, Gao, Y, Hu, X, Cai, J, Sun, S, Jiang, J
International journal of biological macromolecules. 2024;(Pt 1):131467
Abstract
In recent years, Flammulina velutipes (F. velutipes) has attracted consequential attention in various research fields due to its rich composition of proteins, vitamins, amino acids, polysaccharides, and polyphenols. F. velutipes polysaccharides (FVPs) are considered as key bioactive components of F. velutipes, demonstrating multiple physiological activities, including immunomodulatory, anti-inflammatory, and antibacterial properties. Moreover, they offer health benefits such as antioxidant and anti-aging properties, which have exceptionally valuable clinical applications. Polysaccharides derived from different sources exhibit a wide range of biomedical functions and distinct biological activities. The varied biological functions of polysaccharides, coupled with their extensive application in functional foods and clinical applications, have prompted a heightened focus on polysaccharide research. Additionally, the extraction, deproteinization, and purification of FVPs are fundamental to investigate the structure and biological activities of polysaccharides. Therefore, this review provides a comprehensive and systematic overview of the extraction, deproteinization, purification, characterization, and structural elucidation of FVPs. Furthermore, the biological activities and mechanisms of FVPs have been further explored through in vivo and in vitro experiments. This review aims to provide a theoretical foundation and guide future research and development of FVPs.
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4.
Ferroptosis: underlying mechanisms and involvement in neurodegenerative diseases.
Wang, Y, Li, H, He, Q, Zou, R, Cai, J, Zhang, L
Apoptosis : an international journal on programmed cell death. 2024;(1-2):3-21
Abstract
Ferroptosis, a mode of cell death that was recently identified in 2012, is driven by iron-dependent lipid peroxidation and distinct from other mechanisms of cell death such as autophagy and apoptosis. Ferroptosis has the unique features of disruptions in iron equilibrium, iron-induced lipid peroxidation, and the accumulation of glutamate-induced cellular toxicity. The regulation of ferroptosis mainly involves the iron, lipid, and amino acid metabolic pathways, which are controlled by system Xc-, voltage-dependent anion channels, p53 and other pathways. Neurodegenerative diseases involve gradual neuronal loss predominantly within the central nervous system and are categorized into both sporadic and rare hereditary disorders. These diseases result in the progressive decline of specific neuron populations and their interconnections. Recent investigations have revealed a strong correlation between the manifestation and progression of neurodegenerative diseases and ferroptosis. The pharmacological modulation of ferroptosis, whether by induction or inhibition, exhibits promising prospects for therapeutic interventions for these diseases. This review aims to examine the literature on ferroptosis and its implications in various neurodegenerative diseases. We hope to offer novel insights into the potential therapies targeting ferroptosis in central nervous system neurodegenerative diseases. However, there are still limitations of this review. First, despite our efforts to maintain objectivity during our analysis, this review does not cover all the studies on ferroptosis and neurodegenerative diseases. Second, cell death in neurodegenerative diseases is not solely caused by ferroptosis. Future research should focus on the interplay of different cell death mechanisms to better elucidate the specific disease pathogenesis.
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Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance.
Cai, J, Xu, X, Saw, PE
Science China. Life sciences. 2024;(1):19-40
Abstract
A potential reason for the failure of tumor therapies is treatment resistance. Resistance to chemotherapy, radiotherapy, and immunotherapy continues to be a major obstacle in clinic, resulting in tumor recurrence and metastasis. The major mechanisms of therapy resistance are inhibitions of cell deaths, like apoptosis and necrosis, through drug inactivation and excretion, repair of DNA damage, tumor heterogeneity, or changes in tumor microenvironment, etc. Recent studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell death. Some ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor therapy. Notably, versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance, including directly triggering ferroptosis and feedback regulation. Herein, we provide a detailed description of the design, mechanism, and therapeutic application of ferroptosis-mediated synergistic tumor therapeutics. We also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.
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6.
Iron Deposition in Parkinson's Disease: A Mini-Review.
Zeng, W, Cai, J, Zhang, L, Peng, Q
Cellular and molecular neurobiology. 2024;(1):26
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Abstract
Iron deposition is crucial pathological changes observed in patients with Parkinson's disease (PD). Recently, scientists have actively explored therapeutic approaches targeting iron deposition in PD. However, several clinical studies have failed to yield consistent results. In this review, we provide an overview of iron deposition in PD, from both basic research and clinical perspectives. PD patients exhibit abnormalities in various iron metabolism-related proteins, leading to disruptions in iron distribution, transport, storage, and circulation, ultimately resulting in iron deposition. Excess iron can induce oxidative stress and iron-related cell death, and exacerbate mitochondrial dysfunction, contributing to the progression of PD pathology. Magnetic resonance imaging studies have indicated that the characteristics of iron deposition in the brains of PD patients vary. Iron deposition correlates with the clinical symptoms of PD, and patients with different disease courses and clinical presentations display distinct patterns of iron deposition. These iron deposition patterns may contribute to PD diagnosis. Iron deposition is a promising target for PD treatment. However, further research is required to elucidate the underlying mechanisms and their impacts on PD.
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7.
Composition of gut microbiota and non-alcoholic fatty liver disease: A systematic review and meta-analysis.
Su, X, Chen, S, Liu, J, Feng, Y, Han, E, Hao, X, Liao, M, Cai, J, Zhang, S, Niu, J, et al
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2024;(1):e13646
Abstract
The present systematic review and meta-analysis aimed to summarize the associations between gut microbiota composition and non-alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α-diversity index and relative abundance of gut microbes. The β-diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α-diversity indices including Shannon (SMD = -0.36, 95% CI = [-0.53, -0.19], p < 0.001) and Chao 1 (SMD = -0.42, 95% CI = [-0.68, -0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance-based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in β-diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti-inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.
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Management of Hypertension in the Asia-Pacific Region: A Structured Review.
Rahman, ARA, Magno, JDA, Cai, J, Han, M, Lee, HY, Nair, T, Narayan, O, Panyapat, J, Van Minh, H, Khurana, R
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2024;(2):141-170
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Abstract
This article reviews available evidence regarding hypertension management in the Asia-Pacific region, focussing on five research questions that deal with specific aspects: blood pressure (BP) control, guideline recommendations, role of renin-angiotensin-aldosterone system (RAAS) inhibitors in clinical practice, pharmacological management and real-world adherence to guideline recommendations. A PubMed search identified 2537 articles, of which 94 were considered relevant. Compared with Europeans, Asians have higher systolic/diastolic/mean arterial BP, with a stronger association between BP and stroke. Calcium channel blockers are the most-commonly prescribed monotherapy in Asia, with significant variability between countries in the rates of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin-receptor blockers (ARBs) and single-pill combination (SPC) use. In clinical practice, ARBs are used more commonly than ACEis, despite the absence of recommendation from guidelines and clinical evidence supporting the use of one class of drug over the other. Ideally, antihypertensive treatment should be tailored to the individual patient, but currently there are limited data on the characteristics of hypertension in Asia-Pacific individuals. Large outcome studies assessing RAAS inhibitor efficacy and safety in multi-national Asian populations are lacking. Among treated patients, BP control rates were ~ 35 to 40%; BP control in Asia-Pacific is suboptimal, and disproportionately so compared with Western nations. Strategies to improve the management of hypertension include wider access/availability of affordable treatments, particularly SPCs (which improve adherence), effective public health screening programs targeting patients to drive health-seeking behaviours, an increase in physician/patient awareness and early implementation of lifestyle changes. A unified Asia-Pacific guideline on hypertension management with pragmatic recommendations, particularly in resource-limited settings, is essential.
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Improvement of Lung Function by Micronutrient Supplementation in Patients with COPD: A Systematic Review and Meta-Analysis.
Li, M, Zhao, L, Hu, C, Li, Y, Yang, Y, Zhang, X, Li, Q, Ma, A, Cai, J
Nutrients. 2024;(7)
Abstract
BACKGROUND A healthy, well-balanced diet plays an essential role in respiratory diseases. Since micronutrient deficiency is relatively common in patients with chronic obstructive pulmonary disease (COPD), micronutrient supplementation might have the beneficial health effects in those patients. This systematic review and meta-analysis aimed to demonstrate the impact of micronutrient supplementation on the lung function of patients with COPD. METHODS The PubMed, Cochrane Library, and Web of Science databases were searched from their corresponding creation until February 2024. Search terms included 'chronic obstructive pulmonary disease', 'COPD', 'micronutrients', 'dietary supplements', 'vitamins', 'minerals', and 'randomized controlled trials'. Meta-analysis was performed to evaluate the effects of micronutrient supplementation alone or complex on lung function in patients with COPD. RESULTS A total of 43 RCTs fulfilled the inclusion criteria of this study. Meta-analysis revealed that vitamin D supplementation could significantly improve FEV1% (WMDdifferences between baseline and post-intervention (de): 6.39, 95% CI: 4.59, 8.18, p < 0.01; WMDpost-intervention indicators (af): 7.55, 95% CI: 5.86, 9.24, p < 0.01) and FEV1/FVC% (WMDde: 6.88, 95%CI: 2.11, 11.65, WMDaf: 7.64, 95% CI: 3.18, 12.10, p < 0.001), decrease the odds of acute exacerbations, and improve the level of T-cell subsets, including CD3+%, CD4+%, CD8+%, and CD4+/CD8+% (all p < 0.01). The effects of compound nutrients intervention were effective in improving FEV1% (WMDde: 8.38, 95%CI: 1.89, 14.87, WMDaf: 7.07, 95%CI: -0.34, 14.48) and FEV1/FVC% (WMDde: 7.58, 95% CI: 4.86, 10.29, WMDaf: 6.00, 95% CI: 3.19, 8.81). However, vitamin C and vitamin E supplementation alone had no significant effects on lung function (p > 0.05). CONCLUSIONS Micronutrient supplementation, such as vitamin D alone and compound nutrients, has improved effect on the lung function of patients with COPD. Therefore, proper supplementation with micronutrients would be beneficial to stabilize the condition and restore ventilation function for COPD patients.
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Effect of dietary supplementation with multinutrient soy flour on body composition and cognitive function in elderly individuals at the risk of low protein: a randomized, double-blind, placebo-controlled study.
Liu, Y, Yuan, Y, Yang, Y, Gao, T, Cai, J, Wen, H, Wu, X, Zhou, Y, Ma, A, Ma, Y, et al
Food & function. 2023;(21):9734-9742
Abstract
Insufficient protein intake and cognitive decline are common in older adults; however, there have been few studies on low protein risk screening and complex nutrient interventions for elderly individuals in rural communities. This study aimed to evaluate the effect of dietary multinutrient soy flour (MNSF) on body composition and cognitive function in elderly individuals who are at risk of protein deficiency in a randomized, double-blind, placebo-controlled clinical trial. Nutritional interventions were given to those found to have low protein levels using bioelectrical impedance analysis (BIA). Among 733 older adults screened, 62 participants were included and randomly assigned into two groups, one taking soy flour and the other taking MNSF for 12 weeks. A previous cross-sectional survey found that 35.1% of the elderly people with an average age of 71.61 ± 5.94 years had an inadequate body protein mass proportion. After the intervention, the MNSF group demonstrated a significant improvement in protein mass, muscle mass, mineral levels, skeletal muscle mass, and fat-free mass compared with baseline (all P < 0.05), as well as a better upward trend compared with the soy flour group (P = 0.08; P = 0.07; P = 0.05; P = 0.08; P = 0.07). Regarding the mini-mental state examination (MMSE) scores, the MNSF group showed a significant decrease after 12 weeks (P < 0.05), which were significantly different compared with the soy flour group (P < 0.05). In the future, the application of MNSF as a food-based supplement to improve nutrition and delay cognitive decline in older adults at the risk of protein deficiency may be considered.