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1.
Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.
Dong, M, Zhang, T, Liang, X, Cheng, X, Shi, F, Yuan, H, Zhang, F, Jiang, Q, Wang, X
Biochemical and biophysical research communications. 2024;:149815
Abstract
Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.
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2.
The role of ncRNAs-mediated pyroptosis in diabetes and its vascular complications.
Feng, X, Yang, X, Zhong, Y, Cheng, X
Cell biochemistry and function. 2024;(2):e3968
Abstract
Over the past decade, the prevalence of diabetes has increased significantly worldwide, leading to an increase in vascular complications of diabetes (VCD), such as diabetic cardiomyopathy (DCM), diabetic nephropathy (DN), and diabetic retinopathy (DR). Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long Noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), play a key role in cellular processes, including the pathophysiology of diabetes and VCD via pyroptosis. ncRNAs (e.g., miR-17, lnc-MEG3, and lnc-KCNQ1OT1) can regulate pyroptosis in pancreatic β cells. Some ncRNAs are involved in VCD progression. For example, miR-21, lnc-KCNQ1OT1, lnc-GAS5, and lnc-MALAT1 were reported in DN and DCM, and lnc-MIAT was identified in DCM and DR. Herein, this review aimed to summarize recent research findings related to ncRNAs-mediated pyroptosis at the onset and progression of diabetes and VCD.
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3.
The development of magnesium-based biomaterials in bone tissue engineering: A review.
Wu, J, Cheng, X, Wu, J, Chen, J, Pei, X
Journal of biomedical materials research. Part B, Applied biomaterials. 2024;(1):e35326
Abstract
Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.
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4.
C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.
Zhang, X, Xia, F, Zhang, X, Blumenthal, RM, Cheng, X
Journal of molecular biology. 2024;(7):168343
Abstract
In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin genes in adult human erythroid cells; (3) a few other transcription factors of different structural classes that might indirectly influence HbF gene expression; and (4) DNA methyltransferase 1 (DNMT1) that maintains the DNA methylation marks that attract the MBD2-associated NuRD complex to DNA as well as associated histone H3 lysine 9 methylation. Here we briefly discuss the effects of these regulators, particularly C2H2 ZFs, in inducing HbF expression for treating β-hemoglobin disorders, together with recent advances in developing safe and effective small-molecule therapeutics for the regulation of this well-conserved hemoglobin switch.
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5.
LCN2: Versatile players in breast cancer.
Bao, Y, Yan, Z, Shi, N, Tian, X, Li, J, Li, T, Cheng, X, Lv, J
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:116091
Abstract
Lipocalin 2 (LCN2) is a secreted glycoprotein that is produced by immune cells, including neutrophils and macrophages. It serves various functions such as transporting hydrophobic ligands across the cellular membrane, regulating immune responses, keeping iron balance, and fostering epithelial cell differentiation. LCN2 plays a crucial role in several physiological processes. LCN2 expression is upregulated in a variety of human diseases and cancers. High levels of LCN2 are specifically linked to breast cancer (BC) cell proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, chemotherapy resistance, and prognosis. As a result, LCN2 has gained attention as a potential therapeutic target for BC. This article offered an in-depth review of the advancement of LCN2 in the context of BC occurrence and development.
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6.
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.
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7.
Design strategies and recent development of bioactive modulators for glutamine transporters.
Cheng, X, Wang, Y, Gong, G, Shen, P, Li, Z, Bian, J
Drug discovery today. 2024;(2):103880
Abstract
Glutamine transporters are integral to the metabolism of glutamine in both healthy tissues and cancerous cells, playing a pivotal role in maintaining amino acid balance, synthesizing biomolecules, and regulating redox equilibrium. Their critical functions in cellular metabolism make them promising targets for oncological therapies. Recent years have witnessed substantial progress in the field of glutamine transporters, marked by breakthroughs in understanding of their protein structures and the discovery of novel inhibitors, prodrugs, and radiotracers. This review provides a comprehensive update on the latest advancements in modulators targeting the glutamine transporter, with special attention given to LAT1 and ASCT2. It also discusses innovative approaches in drug design aimed at these transporters.
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8.
Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).
Huang, X, Bao, H, Ding, C, Li, J, Cao, T, Liu, L, Wei, Y, Zhou, Z, Zhang, N, Song, Y, et al
European journal of nutrition. 2024
Abstract
BACKGROUND While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER NCT03472508 (Registration Date: March 21, 2018).
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9.
Design and preparation of an artificial vascular scaffold with internal surface modification.
Jin, W, Liu, H, Nie, P, Li, Z, Cheng, X, Jiao, K, Zhao, G, Zheng, G
Artificial organs. 2024;(5):456-471
Abstract
BACKGROUND Advances in regeneration methods have brought us improved vascular scaffolds with small diameters (φ < 6 mm) for enhancing biological suitability that solve their propensity for causing intimal hyperplasia post-transplantation. METHODS The correlation between the rehydration ratio of the hydrogel and its material concentration is obtained by adjusting the material ratio of the hydrogel solution. The vascular model with helical structure has been established and analyzed to verify the effect of helical microvascular structure on thrombosis formation by the fluid simulation methods. Then, the helical structure vascular has been fabricated by self-developed 3D bioprinter, the vascular scaffolds are freeze-dried and rehydrated in polyethylene glycol (PEG) solution. RESULTS The experimental results showed that the hybrid hydrogel had a qualified rehydration ratio when the content of gelatin, sodium alginate, and glycerol was 5, 6, and 3 wt%. The established flow channel model can effectively reduce thrombus deposition and improve long-term patency ratio. After PEG solution modification, the contact angle of the inner wall of the vascular scaffold was less than 30°, showing better hydrophilic characteristics. CONCLUSION In study, a small-diameter inner wall vascular scaffold with better long-term patency was successfully designed and prepared by wrinkling and PEG modification of the inner wall of the vascular scaffold. This study not only creates small-diameter vascular scaffolds with helical structure that improves the surface hydrophilicity to reduce the risk of thrombosis but also rekindles confidence in the regeneration of small caliber vascular structures.
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10.
Effect of light quality on polyphenol biosynthesis in three varieties of mung bean sprouts with different color seed coats.
Cheng, Y, Chen, H, Zhao, Y, Cheng, X, Wang, L, Guo, X
Plant cell reports. 2023;(2):253-268
Abstract
We investigated the mechanism of the effect of different light qualities on the synthesis and regulation of mung bean sprouts. Light quality acts as a signal molecule, strongly enhancing polyphenol biosynthesis in sprouts. Mung bean (Vigna radiata) sprouts are a popular sprouting vegetable all over the world and are an excellent source of polyphenols with high antioxidant activity. This study investigated the effects of light qualities on the kinetic changes and metabolic regulation mechanism of light signal-mediating polyphenols in three mung bean sprout cultivars. Experimental results showed that three light qualities significantly enhanced the contents of caffeic acid, rutin, vitexin, genistin and delphinidin 3-glucoside. Interestingly, ferulic acid and vitexin responded selectively to blue light and red light, severally. Most genes involved in polyphenol biosynthesis were activated under different light quality conditions, resulting in an overaccumulation of phenylpropanoids. Pearson correlation analysis showed that PAL, F3H, F3'H and F3'5'H expression correlated highly with rutin, whereas ANS expression paralleled anthocyanin biosynthesis. Moreover, MYB111, MYB3, MYB4, MYB1 and MYC2 were critical regulators of polyphenol biosynthesis in mung bean sprouts. These changes were likely due to the changes in the expression of the photoreceptor genes CRY-D, PHOT2, PHYE and light response genes (PIF3 and HY5). Our results provide insights into polyphenol biosynthesis in sprouts and microgreens.