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Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy.
Xiang, D, Zhou, L, Yang, R, Yuan, F, Xu, Y, Yang, Y, Qiao, Y, Li, X
International journal of nanomedicine. 2024;:2091-2112
Abstract
Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.
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New strategies to address world food security and elimination of malnutrition: future role of coarse cereals in human health.
Zou, X, Zhang, J, Cheng, T, Guo, Y, Zhang, L, Han, X, Liu, C, Wan, Y, Ye, X, Cao, X, et al
Frontiers in plant science. 2023;:1301445
Abstract
As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.
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The regulation of tissue-specific farnesoid X receptor on genes and diseases involved in bile acid homeostasis.
Xiang, D, Yang, J, Liu, L, Yu, H, Gong, X, Liu, D
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2023;:115606
Abstract
Bile acids (BAs) facilitate the absorption of dietary lipids and vitamins and have also been identified as signaling molecules involved in regulating their own metabolism, glucose and lipid metabolism, as well as immunity. Disturbances in BA homeostasis are associated with various enterohepatic and metabolic diseases, such as cholestasis, nonalcoholic steatohepatitis, inflammatory bowel disease, and obesity. As a key regulator, the nuclear orphan receptor farnesoid X receptor (FXR, NR1H4) precisely regulates BA homeostasis by transcriptional regulation of genes involved in BA synthesis, metabolism, and enterohepatic circulation. FXR is widely regarded as the most potential therapeutic target. Obeticholic acid is the only FXR agonist approved to treat patients with primary biliary cholangitis, but its non-specific activation of systemic FXR also causes high-frequency side effects. In recent years, developing tissue-specific FXR-targeting drugs has become a research highlight. This article provides a comprehensive overview of the role of tissue-specific intestine/liver FXR in regulating genes involved in BA homeostasis and briefly discusses tissue-specific FXR as a therapeutic target for treating diseases. These findings provide the basis for the development of tissue-specific FXR modulators for the treatment of enterohepatic and metabolic diseases associated with BA dysfunction.
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Prospects of cereal protein-derived bioactive peptides: Sources, bioactivities diversity, and production.
Gong, X, An, Q, Le, L, Geng, F, Jiang, L, Yan, J, Xiang, D, Peng, L, Zou, L, Zhao, G, et al
Critical reviews in food science and nutrition. 2022;(11):2855-2871
Abstract
Cereals account for a large proportion of the human diet and are an important source of protein. The preparation of cereal protein peptides is a good way to utilize these proteins. Cereal protein peptides have good application potential as antioxidant, antibacterial, anti-inflammatory and anticancer compounds, in lowering blood pressure, controlling blood sugar, and inhibiting thrombosis. This article reviews the literature on the functional properties, mechanisms of action, and applications of cereal protein peptides in the food industry with two perspectives, and summarizes the methods for their preparation and identification. The biologically active peptides derived from different grain proteins have varied main functional properties, which may be related to the differences in the amino acid composition and protein types of different grains. On this basis, the structure-activity relationship of cereal protein peptides was discussed. The advancement of identification technology makes the integration of bioinformatics and bioactive peptide research closer. Bioinformatics by combination of online database, computer simulation and experimental verification is helpful to in-deep study the structure-activity relationship of biologically active peptides, and improve efficiency in the process of obtaining target peptides with less cost. In addition, the application of cereal protein peptides in the food industry is also discussed.
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Developmental and genomic architecture of plant embryogenesis: from model plant to crops.
Armenta-Medina, A, Gillmor, CS, Gao, P, Mora-Macias, J, Kochian, LV, Xiang, D, Datla, R
Plant communications. 2021;(1):100136
Abstract
Embryonic development represents an important reproductive phase of sexually reproducing plant species. The fusion of egg and sperm produces the plant zygote, a totipotent cell that, through cell division and cell identity specification in early embryogenesis, establishes the major cell lineages and tissues of the adult plant. The subsequent morphogenesis phase produces the full-sized embryo, while the late embryogenesis maturation process prepares the seed for dormancy and subsequent germination, ensuring continuation of the plant life cycle. In this review on embryogenesis, we compare the model eudicot Arabidopsis thaliana with monocot crops, focusing on genome activation, paternal and maternal regulation of early zygote development, and key organizers of patterning, such as auxin and WOX transcription factors. While the early stages of embryo development are apparently conserved among plant species, embryo maturation programs have diversified between eudicots and monocots. This diversification in crop species reflects the likely effects of domestication on seed quality traits that are determined during embryo maturation, and also assures seed germination in different environmental conditions. This review describes the most important features of embryonic development in plants, and the scope and applications of genomics in plant embryo studies.
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Upregulation of lncRNA NIFK-AS1 in hepatocellular carcinoma by m6A methylation promotes disease progression and sorafenib resistance.
Chen, YT, Xiang, D, Zhao, XY, Chu, XY
Human cell. 2021;(6):1800-1811
Abstract
Long non-coding RNAs (LncRNAs) have recently emerged as vital regulators in the development and progression of hepatocellular carcinoma (HCC), providing new opportunities as novel therapeutic targets. Here we identified the lncRNA NIFK-AS1 as being highly expressed in HCC tissues and cells and showed this up-regulation resulted from METTL3-dependent m6A methylation. Functionally, knockdown of NIFK-AS1 inhibited the proliferation, colony formation, migration, and invasion of HCC cells. Moreover, these effects were elicited though AKT1 and we uncovered a ceRNA network involving an NIFK-AS1/miR-637/AKT1 axis with downstream effects on HCC progression involving regulation of MMP-7 and MMP-9 expression. From the clinical perspective, we showed that knockdown of NIFK-AS1 sensitized HCC cells to sorafenib through the up-regulation of the drug transporters OATP1B1 and OATP1B3. Clinical investigations showed HCC patients with low NIFK-AS1 expression benefited from sorafenib therapy and this phenomenon was reproduced in patient-derived tumor xenograft models (PDX) comparing HCC with low and high expression of NIFK-AS1. Taken together, these results suggest an essential role for NIFK-AS1 in HCC progression and promote NIFK-AS1 as a new therapeutic target and predictor of sorafenib benefit in HCC patients.
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Effects of Isolated Impaired Fasting Glucose on Brain Injury During Cardiac Surgery Under Cardiopulmonary Bypass.
Zhou, T, Li, S, Xiang, D, Gao, L
Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2020;(4):350-358
Abstract
Objective: To evaluate the effects of isolated impaired fasting glucose (IIFG) on brain injury in patients undergoing cardiopulmonary bypass (CPB) surgery. Methods: Patients with rheumatic heart valve disease who underwent elective mitral valve replacement were included and divided into control and IIFG groups. Pre-, intra-, and postoperative blood glucose levels, serum insulin levels, insulin resistance index (HOMA-IR), lactic acid levels, and neuron-specific enolase (NSE) and S100B levels were measured. The cerebral oxygen extraction ratio (OER) was calculated. Cognitive function was assessed via the Mini-Mental State Examination (MMSE). Results: HOMA-IR levels were higher in the IIFG group than the control group 30 min after the beginning of CPB, at the termination of CPB, and 2 h after the termination of CPB. Cerebral OER and lactic acid increased intraoperatively in both groups, especially in the IIFG group. NSE and S100B levels were higher in the IIFG group than in the control group at the termination of CPB, 2 h after the termination of CPB, and at 24 h postoperatively. The MMSE scores did not significantly differ between the two groups. Delirium occurred in two patients in the IIFG group, and one in the control group. No other signs and symptoms of brain injuries were detected in either group. Conclusions: The increased postoperative NSE and S100B levels in the IIFG group compared with controls may be associated with severe insulin resistance and stress hyperglycemia. However, the IIFG group did not have clinical manifestations of brain injuries, including cognitive impairment.
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Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials.
Xiang, D, Zhang, Q, Wang, YT
Medicine. 2020;(29):e21235
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Abstract
BACKGROUND Lipid profiles and glycemic control play a critical role in subsequent atherosclerotic cardiovascular disease for patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the effectiveness of niacin supplementation on lipid profiles and glycemic control for patients with T2DM. METHODS The PubMed, Embase, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that investigated the effects of niacin supplementation for patients with T2DM throughout December 2019. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to calculate the pooled effect estimates using a random-effects model. RESULTS Eight RCTs comprised a total of 2110 patients with T2DM who were selected for final quantitative analysis. The patients' niacin supplementation was associated with lower levels of total cholesterol (WMD, -0.28; 95% CI, -0.44 to -0.12; P = .001), triglyceride (WMD, -0.37; 95% CI, -0.52 to -0.21; P < .001), and low-density lipoprotein (WMD, -0.42; 95% CI, -0.50 to -0.34; P < .001). Moreover, the level of high-density lipoprotein was significantly increased when niacin supplementation (WMD, 0.33; 95% CI, 0.21 to 0.44; P < .001) was provided. However, niacin supplementation produced no significant effects on plasma glucose (WMD, 0.18; 95% CI, -0.14 to 0.50; P = .275) and hemoglobin A1c (HbA1c) levels (WMD, 0.39; 95% CI, -0.15 to 0.94; P = .158). CONCLUSIONS This study found that niacin supplementation could improve lipid profiles without affecting the glycemic levels for patients with T2DM. Additional large-scale RCTs should be conducted to evaluate the long-term effectiveness of niacin supplementation.
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Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.
Zhu, L, She, ZG, Cheng, X, Qin, JJ, Zhang, XJ, Cai, J, Lei, F, Wang, H, Xie, J, Wang, W, et al
Cell metabolism. 2020;31(6):1068-1077.e3
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Plain language summary
The novel coronavirus disease 2019 (COVID-19) is caused by infection from the newly emerged, highly contagious coronavirus SARS-CoV-2. The aim of this study was to analyse the association between plasma glucose levels and clinic outcomes in COVID-19 patients with type 2 diabetes (T2D). The study is a retrospective longitudinal, multi-centre study from a cohort of 7,337 COVID-19 cases enrolled among 19 hospitals. Results show that patients with pre-existing T2D received significantly more intensive integrated treatments to manage their symptoms of COVID-19 than the non-diabetic subjects. Furthermore, findings indicate that well-controlled blood glucose was associated with a markedly improved outcome of patients with COVID-19 and pre-existing T2D. Authors conclude that T2D is an important risk factor for COVID-19 progression and adverse endpoints, and well-controlled blood glucose is associated with a significant reduction in the composite adverse outcomes and death.
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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10.
Molecular Mechanisms of Root Development in Rice.
Meng, F, Xiang, D, Zhu, J, Li, Y, Mao, C
Rice (New York, N.Y.). 2019;(1):1
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Abstract
Roots are fundamentally important for growth and development, anchoring the plant to its growth substrate, facilitating water and nutrient uptake from the soil, and sensing and responding to environmental signals such as biotic and abiotic stresses. Understanding the molecular mechanisms controlling root architecture is essential for improving nutrient uptake efficiency and crop yields. In this review, we describe the progress being made in the identification of genes and regulatory pathways involved in the development of root systems in rice (Oryza sativa L.), including crown roots, lateral roots, root hairs, and root length. Genes involved in the adaptation of roots to the environmental nutrient status are reviewed, and strategies for further study and agricultural applications are discussed. The growth and development of rice roots are controlled by both genetic factors and environmental cues. Plant hormones, especially auxin and cytokinin, play important roles in root growth and development. Understanding the molecular mechanisms regulating root architecture and response to environmental signals can contribute to the genetic improvement of crop root systems, enhancing their adaptation to stressful environmental conditions.