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1.
Cellular Advanced Glycation End Products Aggravate the Immune Response in Mononuclear Cells from Patients with Type 1 Diabetes.
Yang, L, Qian, Y, Lei, S, Sun, D
Frontiers in bioscience (Landmark edition). 2024;(2):85
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of advanced glycation end products (AGEs) in the regulation of the immune response in peripheral blood mononuclear cells (PBMCs) from patients with T1DM. METHODS PBMCs isolated from T1DM patients and control subjects were used in the current study. Cytokines, AGEs related to glyoxalase 1 (GLO1), methylglyoxal (MG)-derived AGEs were assessed longitudinally. RESULTS The results of published T1DM PBMC microarray datasets using random-effects meta-analysis models revealed immune responses in the PBMCs of patients with T1DM compared with control subjects. Moreover, the activity of GLO1, which is the key MG-metabolizing enzyme, was significantly reduced in PBMCs from T1DM patients. We confirmed that, compared to the control subjects, GLO1 expression and activity were markedly decreased and MG-derived AGEs were significantly accumulated in the PBMCs from T1DM patients. In addition, phytohemagglutinin stimulated the secretion of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) was positively correlated with the accumulation of cellular AGEs. Therefore, the exposure of PBMCs from control subjects to MG and a GLO1 inhibitor enhanced the accumulation of cellular MG-derived AGEs and the secretion of TNF-α and IFN-γ. CONCLUSIONS The results of this study showed that the accumulation of cellular AGEs causes a decline in the immune response of patients with T1DM.
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2.
Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial.
Xing, X, Jiang, RL, Lei, S, Zhi, YH, Zhu, MF, Huang, LQ, Hu, MH, Lu, J, Fang, K, Wang, QY
Chinese journal of integrative medicine. 2023;(8):721-729
Abstract
OBJECTIVE To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).
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3.
Vitamin interdependencies predicted by metagenomics-informed network analyses and validated in microbial community microcosms.
Hessler, T, Huddy, RJ, Sachdeva, R, Lei, S, Harrison, STL, Diamond, S, Banfield, JF
Nature communications. 2023;(1):4768
Abstract
Metagenomic or metabarcoding data are often used to predict microbial interactions in complex communities, but these predictions are rarely explored experimentally. Here, we use an organism abundance correlation network to investigate factors that control community organization in mine tailings-derived laboratory microbial consortia grown under dozens of conditions. The network is overlaid with metagenomic information about functional capacities to generate testable hypotheses. We develop a metric to predict the importance of each node within its local network environments relative to correlated vitamin auxotrophs, and predict that a Variovorax species is a hub as an important source of thiamine. Quantification of thiamine during the growth of Variovorax in minimal media show high levels of thiamine production, up to 100 mg/L. A few of the correlated thiamine auxotrophs are predicted to produce pantothenate, which we show is required for growth of Variovorax, supporting that a subset of vitamin-dependent interactions are mutualistic. A Cryptococcus yeast produces the B-vitamin pantothenate, and co-culturing with Variovorax leads to a 90-130-fold fitness increase for both organisms. Our study demonstrates the predictive power of metagenome-informed, microbial consortia-based network analyses for identifying microbial interactions that underpin the structure and functioning of microbial communities.
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4.
Precision Nutrition and Cardiovascular Disease Risk Reduction: the Promise of High-Density Lipoproteins.
Hong, BV, Agus, JK, Tang, X, Zheng, JJ, Romo, EZ, Lei, S, Zivkovic, AM
Current atherosclerosis reports. 2023;(10):663-677
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Abstract
PURPOSE OF REVIEW Emerging evidence supports the promise of precision nutritional approaches for cardiovascular disease (CVD) prevention. Here, we discuss current findings from precision nutrition trials and studies reporting substantial inter-individual variability in responses to diets and dietary components relevant to CVD outcomes. We highlight examples where early precision nutrition research already points to actionable intervention targets tailored to an individual's biology and lifestyle. Finally, we make the case for high-density lipoproteins (HDL) as a compelling next generation target for precision nutrition aimed at CVD prevention. HDL possesses complex structural features including diverse protein components, lipids, size distribution, extensive glycosylation, and interacts with the gut microbiome, all of which influence HDL's anti-inflammatory, antioxidant, and cholesterol efflux properties. Elucidating the nuances of HDL structure and function at an individual level may unlock personalized dietary and lifestyle strategies to optimize HDL-mediated atheroprotection and reduce CVD risk. RECENT FINDINGS Recent human studies have demonstrated that HDL particles are key players in the reduction of CVD risk. Our review highlights the role of HDL and the importance of personalized therapeutic approaches to improve their potential for reducing CVD risk. Factors such as diet, genetics, glycosylation, and gut microbiome interactions can modulate HDL structure and function at the individual level. We emphasize that fractionating HDL into size-based subclasses and measuring particle concentration are necessary to understand HDL biology and for developing the next generation of diagnostics and biomarkers. These discoveries underscore the need to move beyond a one-size-fits-all approach to HDL management. Precision nutrition strategies that account for personalized metabolic, genetic, and lifestyle data hold promise for optimizing HDL therapies and function to mitigate CVD risk more potently. While human studies show HDL play a key role in reducing CVD risk, recent findings indicate that factors such as diet, genetics, glycosylation, and gut microbes modulate HDL function at the individual level, underscoring the need for precision nutrition strategies that account for personalized variability to optimize HDL's potential for mitigating CVD risk.
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Resistant starch from sweet potatoes: Recent advancements and applications in the food sector.
Bodjrenou, DM, Li, X, Lu, X, Lei, S, Zheng, B, Zeng, H
International journal of biological macromolecules. 2023;:13-26
Abstract
In tropical and subtropical areas, tuber and root crops are staple foods and a key source of energy. Sweet potato (SP) is currently regarded as one of the world's top ten foods because of its diverse sizes, shapes, color, and health benefits. The resistant starch (RS) content of SP is substantial. It is predicted to become the cheapest item in the food industry due to its extensive variety, food stability, emulsifier and fat substitution capabilities, and as filler. As a result, interest in SP-sourced RS has recently increased. Due to their unique nutritional and functional qualities, novelty has become a popular research focus in recent years. This review will summarize the current understanding of SP starch components and their impact on the technological and physicochemical properties of produced starch for commercial viability. The importance of sweet potato RS in addressing future RS demand sustainability is emphasized. SPs are a viable alternative to tubers as a sustainable raw material for RS production. It has an advantage over tubers because of its intrinsic nutritional value and climatic endurance. Thermal, chemical, and enzymatic treatments are effective RS manufacturing procedures. The adaptability of sweet potato RS allows for a wide range of food applications.
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CRISPR/Cas-based gene editing in therapeutic strategies for beta-thalassemia.
Zeng, S, Lei, S, Qu, C, Wang, Y, Teng, S, Huang, P
Human genetics. 2023;(12):1677-1703
Abstract
Beta-thalassemia (β-thalassemia) is an autosomal recessive disorder caused by point mutations, insertions, and deletions in the HBB gene cluster, resulting in the underproduction of β-globin chains. The most severe type may demonstrate complications including massive hepatosplenomegaly, bone deformities, and severe growth retardation in children. Treatments for β-thalassemia include blood transfusion, splenectomy, and allogeneic hematopoietic stem cell transplantation (HSCT). However, long-term blood transfusions require regular iron removal therapy. For allogeneic HSCT, human lymphocyte antigen (HLA)-matched donors are rarely available, and acute graft-versus-host disease (GVHD) may occur after the transplantation. Thus, these conventional treatments are facing significant challenges. In recent years, with the advent and advancement of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) gene editing technology, precise genome editing has achieved encouraging successes in basic and clinical studies for treating various genetic disorders, including β-thalassemia. Target gene-edited autogeneic HSCT helps patients avoid graft rejection and GVHD, making it a promising curative therapy for transfusion-dependent β-thalassemia (TDT). In this review, we introduce the development and mechanisms of CRISPR/Cas9. Recent advances on feasible strategies of CRISPR/Cas9 targeting three globin genes (HBB, HBG, and HBA) and targeting cell selections for β-thalassemia therapy are highlighted. Current CRISPR-based clinical trials in the treatment of β-thalassemia are summarized, which are focused on γ-globin reactivation and fetal hemoglobin reproduction in hematopoietic stem cells. Lastly, the applications of other promising CRISPR-based technologies, such as base editing and prime editing, in treating β-thalassemia and the limitations of the CRISPR/Cas system in therapeutic applications are discussed.
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Management of traditional risk factors for the development and progression of chronic kidney disease.
Lo, R, Narasaki, Y, Lei, S, Rhee, CM
Clinical kidney journal. 2023;(11):1737-1750
Abstract
Chronic kidney disease (CKD) and its downstream complications (i.e. cardiovascular) are a major source of morbidity worldwide. Additionally, deaths due to CKD or CKD-attributable cardiovascular disease account for a sizeable proportion of global mortality. However, the advent of new pharmacotherapies, diagnostic tools, and global initiatives are directing greater attention to kidney health in the public health agenda, including the implementation of effective strategies that (i) prevent kidney disease, (ii) provide early CKD detection, and (iii) ameliorate CKD progression and its related complications. In this Review, we discuss major risk factors for incident CKD and CKD progression categorized across cardiovascular (i.e. hypertension, dyslipidemia, cardiorenal syndrome), endocrine (i.e. diabetes mellitus, hypothyroidism, testosterone), lifestyle (i.e. obesity, dietary factors, smoking), and genetic/environmental (i.e. CKDu/Mesoamerican nephropathy, APOL1, herbal nephropathy) domains, as well as scope, mechanistic underpinnings, and management.
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8.
Effect of Cerium on Inclusion Modification in a Secondary-Hardening Steel.
Han, S, Geng, R, Lei, S, Li, Y, Wang, C
Materials (Basel, Switzerland). 2023;(11)
Abstract
Owing to the continuous increasing of steel strength, mechanical properties including toughness and fatigue performance are becoming increasingly sensitive to inclusions in ultra-high strength steel. Rare-earth treatment is considered as an effective method to reduce the harmful effects of inclusions, but is rarely applied in secondary-hardening steel. In the present study, different amounts of cerium were added in a secondary-hardening steel to investigate the modification effect of Ce on non-metallic inclusions in steel. The characteristics of inclusions were observed experimentally using SEM-EDS and the modification mechanism was analyzed based on thermodynamic calculations. The results indicated that the main inclusions in Ce-free steel are Mg-Al-O + MgS. Thermodynamic calculation indicated that MgAl2O4 is firstly formed in liquid steel and then successively transformed into MgO and MgS during cooling process. When the Ce content is 0.0030%, the typical inclusions in steel were individual Ce2O2S and MgO + Ce2O2S complex inclusions. When the Ce content was increased to 0.0071%, the typical inclusions in steel were individual Ce2O2S- and Mg-containing inclusions. Ce treatment modifies the angular magnesium aluminum spinel inclusions into spherical and ellipsoidal Ce-containing inclusions, thus reducing the harmful effect of inclusion on steel properties.
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Stand Up to Stand Out: Natural Dietary Polyphenols Curcumin, Resveratrol, and Gossypol as Potential Therapeutic Candidates against Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
Wang, Z, Song, XQ, Xu, W, Lei, S, Zhang, H, Yang, L
Nutrients. 2023;(18)
Abstract
The COVID-19 pandemic has stimulated collaborative drug discovery efforts in academia and the industry with the aim of developing therapies and vaccines that target SARS-CoV-2. Several novel therapies have been approved and deployed in the last three years. However, their clinical application has revealed limitations due to the rapid emergence of viral variants. Therefore, the development of next-generation SARS-CoV-2 therapeutic agents with a high potency and safety profile remains a high priority for global health. Increasing awareness of the "back to nature" approach for improving human health has prompted renewed interest in natural products, especially dietary polyphenols, as an additional therapeutic strategy to treat SARS-CoV-2 patients, owing to its good safety profile, exceptional nutritional value, health-promoting benefits (including potential antiviral properties), affordability, and availability. Herein, we describe the biological properties and pleiotropic molecular mechanisms of dietary polyphenols curcumin, resveratrol, and gossypol as inhibitors against SARS-CoV-2 and its variants as observed in in vitro and in vivo studies. Based on the advantages and disadvantages of dietary polyphenols and to obtain maximal benefits, several strategies such as nanotechnology (e.g., curcumin-incorporated nanofibrous membranes with antibacterial-antiviral ability), lead optimization (e.g., a methylated analog of curcumin), combination therapies (e.g., a specific combination of plant extracts and micronutrients), and broad-spectrum activities (e.g., gossypol broadly inhibits coronaviruses) have also been emphasized as positive factors in the facilitation of anti-SARS-CoV-2 drug development to support effective long-term pandemic management and control.
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10.
Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.
Lin, Y, Qin, S, Yang, H, Shi, F, Yang, A, Han, X, Liu, B, Li, Z, Ji, Q, Tang, L, et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023;(15):2791-2799
Abstract
PURPOSE The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.