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1.
Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.
Zhao, T, Chen, L, Yu, C, He, G, Lin, H, Sang, H, Chen, Z, Hong, Y, Sui, W, Zhao, J
RSC advances. 2024;(3):2016-2026
Abstract
Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis. Nevertheless, its clinical application is hindered by the limitations of monotherapy and its rapid release characteristics, which compromise its efficacy and delivery efficiency. In this context, calcium alginate hydrogel, recognized for its superior physicochemical properties and biocompatibility, emerges as a candidate for developing a synergistic bioengineered drug delivery system. This study describes the synthesis of an injectable calcium amelogenin/calcium alginate hydrogel using calcium alginate loaded with amelogenin. We comprehensively investigated its physical properties, its role in modulating the immunological environment conducive to bone healing, and its osteogenic efficacy in areas of jawbone defects. Our experimental findings indicate that this synthesized composite hydrogel possesses desirable mechanical properties such as injectability, biocompatibility, and biodegradability. Furthermore, it facilitates jawbone formation by regulating the bone-healing microenvironment and directly inducing osteogenesis. This research provides novel insights into the development of bone-tissue regeneration materials, potentially advancing their clinical application.
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2.
Squalene Epoxidase: Its Regulations and Links with Cancers.
Zhang, L, Cao, Z, Hong, Y, He, H, Chen, L, Yu, Z, Gao, Y
International journal of molecular sciences. 2024;(7)
Abstract
Squalene epoxidase (SQLE) is a key enzyme in the mevalonate-cholesterol pathway that plays a critical role in cellular physiological processes. It converts squalene to 2,3-epoxysqualene and catalyzes the first oxygenation step in the pathway. Recently, intensive efforts have been made to extend the current knowledge of SQLE in cancers through functional and mechanistic studies. However, the underlying mechanisms and the role of SQLE in cancers have not been fully elucidated yet. In this review, we retrospected current knowledge of SQLE as a rate-limiting enzyme in the mevalonate-cholesterol pathway, while shedding light on its potential as a diagnostic and prognostic marker, and revealed its therapeutic values in cancers. We showed that SQLE is regulated at different levels and is involved in the crosstalk with iron-dependent cell death. Particularly, we systemically reviewed the research findings on the role of SQLE in different cancers. Finally, we discussed the therapeutic implications of SQLE inhibitors and summarized their potential clinical values. Overall, this review discussed the multifaceted mechanisms that involve SQLE to present a vivid panorama of SQLE in cancers.
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3.
Radioiodine-refractory differentiated thyroid cancer: Molecular mechanisms and therapeutic strategies for radioiodine resistance.
Shen, H, Zhu, R, Liu, Y, Hong, Y, Ge, J, Xuan, J, Niu, W, Yu, X, Qin, JJ, Li, Q
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy. 2024;:101013
Abstract
Radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) is difficult to treat with radioactive iodine because of the absence of the sodium iodide transporter in the basement membrane of thyroid follicular cells for iodine uptake. This is usually due to the mutation or rearrangement of genes and the aberrant activation of signal pathways, which result in abnormal expression of thyroid-specific genes, leading to resistance of differentiated thyroid cancer cells to radioiodine therapy. Therefore, inhibiting the proliferation and growth of RAIR-DTC with multikinase inhibitors and other drugs or restoring its differentiation and then carrying out radioiodine therapy have become the first-line treatment strategies and main research directions. The drugs that regulate these kinases or signaling pathways have been studied in clinical and preclinical settings. In this review, we summarized the major gene mutations, gene rearrangements and abnormal activation of signaling pathways that led to radioiodine resistance of RAIR-DTC, as well as the medicine that have been tested in clinical and preclinical trials.
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4.
Amyloplast is involved in the MIZ1-modulated root hydrotropism.
Hong, Y, Liu, S, Chen, Y, Yao, Z, Jiang, S, Wang, L, Zhu, X, Xu, W, Zhang, J, Li, Y
Journal of plant physiology. 2024;:154224
Abstract
Roots exhibit hydrotropism in response to moisture gradients, with the hydrotropism-related gene Mizu-kussei1 (MIZ1) playing a role in regulating root hydrotropism in an oblique orientation. However, the mechanisms underlying MIZ1-regulated root hydrotropism are not well understood. In this study, we employed obliquely oriented experimental systems to investigate root hydrotropism in Arabidopsis. We found that the miz1 mutant displays reduced root hydrotropism but increased root gravitropism following hydrostimulation, as compared to wild-type plants. Conversely, overexpression of AtMIZ1 leads to enhanced root hydrotropism but decreased root gravitropism following hydrostimulation, as compared to wild-type plants. Using co-immunoprecipitation followed by mass spectrometry (IP-MS), we explored proteins that interact with AtMIZ1, and we identified PGMC1 co-immunoprecipitated with MIZ1 in vivo. Furthermore, the miz1 mutant exhibited higher expression of the PGMC1 gene and increased phosphoglucomutase (PGM) activity, while AtMIZ1 overexpressors resulted in lower expression of the PGMC1 gene, reduced amyloplast amount, and reduced PGM activity in comparison to wild-type roots. In addition, different Arabidopsis natural accessions having difference in their hydrotropic response demonstrated expression level of PGMC1 was negatively correlated with hydrotropic root curvature and AtMIZ1 expression. Our results provide valuable insights into the role of amyloplast in MIZ1-regulated root hydrotropism.
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5.
Structural characteristics, digestion properties, fermentation properties, and biological activities of butyrylated starch: A review.
Zhang, Y, Li, L, Sun, S, Cheng, L, Gu, Z, Hong, Y
Carbohydrate polymers. 2024;:121825
Abstract
Butyrylated starch is produced by the esterification of hydroxyl groups in starch with butyryl groups, which improves the structural diversity of starch and expands its function and biological activity. The paper summarizes the structural properties and digestive properties, fermentation properties, and biological activities of butyrylated starch and describes the conformational relationships generated by the butyryl groups to reveal the underlying mechanisms. The butyryl groups replace the hydroxyl groups in starch and break the hydrogen bonds, which consequently changes the molecular, crystal, and granular structures of starch, while the starch structure also affects the distribution of the butyryl groups. Binding to the butyryl groups gives starch efficacy in resisting digestion, lowering the glycaemic index, releasing butyric acid in the colon, and regulating intestinal flora and metabolites. Relationships between starch structural parameters and butyric acid production and intestinal flora were also concluded to provide guidance for the rational design of butyrylated starch to improve efficacy. Moreover, based on its digestive and fermentation properties, butyrylated starch has exhibited good therapeutic efficacy for intestinal diseases, diabetes, polycystic ovary syndrome, and chronic restraint stress-induced abnormalities. This review provides a valuable reference for butyrylated starch advancement and utilization.
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6.
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease.
Hong, Y, Zhang, Z, Yangzom, T, Chen, A, Lundberg, BC, Fang, EF, Siller, R, Sullivan, GJ, Zeman, J, Tzoulis, C, et al
International journal of biological sciences. 2024;(4):1194-1217
Abstract
Alpers' syndrome is an early-onset neurodegenerative disorder usually caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG), which is essential for mitochondrial DNA (mtDNA) replication. The disease is progressive, incurable, and inevitably it leads to death from drug-resistant status epilepticus. The neurological features of Alpers' syndrome are intractable epilepsy and developmental regression, with no effective treatment; the underlying mechanisms are still elusive, partially due to lack of good experimental models. Here, we generated the patient derived induced pluripotent stem cells (iPSCs) from one Alpers' patient carrying the compound heterozygous mutations of A467T (c.1399G>A) and P589L (c.1766C>T), and further differentiated them into cortical organoids and neural stem cells (NSCs) for mechanistic studies of neural dysfunction in Alpers' syndrome. Patient cortical organoids exhibited a phenotype that faithfully replicated the molecular changes found in patient postmortem brain tissue, as evidenced by cortical neuronal loss and depletion of mtDNA and complex I (CI). Patient NSCs showed mitochondrial dysfunction leading to ROS overproduction and downregulation of the NADH pathway. More importantly, the NAD+ precursor nicotinamide riboside (NR) significantly ameliorated mitochondrial defects in patient brain organoids. Our findings demonstrate that the iPSC model and brain organoids are good in vitro models of Alpers' disease; this first-in-its-kind stem cell platform for Alpers' syndrome enables therapeutic exploration and has identified NR as a viable drug candidate for Alpers' disease and, potentially, other mitochondrial diseases with similar causes.
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7.
Predictive value of atherogenic index of plasma and atherogenic index of plasma combined with low-density lipoprotein cholesterol for the risk of acute myocardial infarction.
Chen, M, Fang, CY, Guo, JC, Pang, LM, Zhou, Y, Hong, Y, Yang, LF, Zhang, J, Zhang, T, Zhou, BF, et al
Frontiers in cardiovascular medicine. 2023;:1117362
Abstract
BACKGROUND AND AIMS Acute myocardial infarction (AMI) is a prevalent medical condition associated with significant morbidity and mortality rates. The principal underlying factor leading to myocardial infarction is atherosclerosis, with dyslipidemia being a key risk factor. Nonetheless, relying solely on a single lipid level is insufficient for accurately predicting the onset and progression of AMI. The present investigation aims to assess established clinical indicators in China, to identify practical, precise, and effective tools for predicting AMI. METHODS The study enrolled 267 patients diagnosed with acute myocardial infarction as the experimental group, while the control group consisted of 73 hospitalized patients with normal coronary angiography. The investigators collected general clinical data and relevant laboratory test results and computed the Atherogenic Index of Plasma (AIP) for each participant. Using acute myocardial infarction status as the dependent variable and controlling for confounding factors such as smoking history, fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), blood pressure at admission, and diabetes history, the researchers conducted multivariate logistic regression analysis with AIP as an independent variable. Receiver operating characteristic (ROC) curves were employed to determine the predictive value of AIP and AIP combined with LDL-C for acute myocardial infarction. RESULT The results of the multivariate logistic regression analysis indicated that the AIP was an independent predictor of acute myocardial infarction. The optimal cut-off value for AIP to predict AMI was -0.06142, with a sensitivity of 81.3%, a specificity of 65.8%, and an area under the curve (AUC) of 0.801 (95% confidence interval [CI]: 0.743-0.859, P < 0.001). When AIP was combined with LDL-C, the best cut-off value for predicting acute myocardial infarction was 0.756107, with a sensitivity of 79%, a specificity of 74%, and an AUC of 0.819 (95% CI: 0.759-0.879, P < 0.001). CONCLUSIONS The AIP is considered an autonomous determinant of risk for AMI. Utilizing the AIP index alone, as well as in conjunction with LDL-C, can serve as effective predictors of AMI.
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8.
Evidence for Improved Cognitive Health with Diet: A Narrative Review.
Hong, Y, Clark, E, Furbish, K, Maggiolo, N, West, E, Sylvia, L
Alternative therapies in health and medicine. 2023;(7):12-17
Abstract
BACKGROUND Despite growing interest in nutrition as a behavioral intervention to improve cognitive health in clinical populations, many providers find it challenging to provide specific nutritional recommendations. We aimed to review and synthesize current empirical research on this topic and provide considerations for healthcare providers working with adults who wish to optimize their cognition via dietary improvements. METHODS We performed a narrative review of research published between January 2009 and May 2021 on 5 popular dietary interventions: the Mediterranean diet, Dietary Approaches to Stop Hypertension (DASH), the Mediterranean-DASH Intervention Diet for Neurodegenerative Delay (MIND), the ketogenic diet and intermittent fasting. RESULTS AND CONCLUSIONS Of the 5 dietary interventions, the Mediterranean diet has been the most extensively investigated, and there is evidence supporting its cognitive benefits. However, operationalization of the Mediterranean diet varies across studies, rendering the results inconclusive. The DASH diet and the MIND diet have stronger operationalization and showed evidence of cognitive benefits. More longitudinal studies and/or randomized clinical trials should be conducted on these 2 relatively new interventions. Finally, there is limited research with human participants regarding the ketogenic diet and intermittent fasting, which are found to be cognitively protective within stringent parameters. Definitions for these 5 dietary patterns and practice tips and recommendations are provided.
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9.
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases.
Ji, S, Xiong, M, Chen, H, Liu, Y, Zhou, L, Hong, Y, Wang, M, Wang, C, Fu, X, Sun, X
Signal transduction and targeted therapy. 2023;(1):116
Abstract
The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition to deteriorated disorders. Rejuvenation refers to giving aged cells or organisms more youthful characteristics through various techniques, such as cellular reprogramming and epigenetic regulation. The great leaps in cellular rejuvenation prove that ageing is not a one-way street, and many rejuvenative interventions have emerged to delay and even reverse the ageing process. Defining the mechanism by which roadblocks and signaling inputs influence complex ageing programs is essential for understanding and developing rejuvenative strategies. Here, we discuss the intrinsic and extrinsic factors that counteract cell rejuvenation, and the targeted cells and core mechanisms involved in this process. Then, we critically summarize the latest advances in state-of-art strategies of cellular rejuvenation. Various rejuvenation methods also provide insights for treating specific ageing-related diseases, including cellular reprogramming, the removal of senescence cells (SCs) and suppression of senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune rejuvenation and heterochronic transplantation, etc. The potential applications of rejuvenation therapy also extend to cancer treatment. Finally, we analyze in detail the therapeutic opportunities and challenges of rejuvenation technology. Deciphering rejuvenation interventions will provide further insights into anti-ageing and ageing-related disease treatment in clinical settings.
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10.
Risk factors based vessel-specific prediction for stages of coronary artery disease using Bayesian quantile regression machine learning method: Results from the PARADIGM registry.
Park, HB, Lee, J, Hong, Y, Byungchang, S, Kim, W, Lee, BK, Lin, FY, Hadamitzky, M, Kim, YJ, Conte, E, et al
Clinical cardiology. 2023;(3):320-327
Abstract
BACKGROUND AND HYPOTHESIS The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. METHODS From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. RESULTS The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. CONCLUSIONS This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.