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1.
Encapsulated cell technology: Delivering cytokines to treat posterior ocular diseases.
Wang, J, Fan, W, Liu, B, Pu, N, Wu, H, Xue, R, Li, S, Song, Z, Tao, Y
Pharmacological research. 2024;:107159
Abstract
Encapsulated cell technology (ECT) is a targeted delivery method that uses the genetically engineered cells in semipermeable polymer capsules to deliver cytokines. Thus far, ECT has been extensively utilized in pharmacologic research, and shows enormous potentials in the treatment of posterior segment diseases. Due to the biological barriers within the eyeball, it is difficult to attain effective therapeutic concentration in the posterior segment through topical administration of drug molecules. Encouragingly, therapeutic cytokines provided by ECT can cross these biological barriers and achieve sustained release at the desired location. The encapsulation system uses permeable materials that allow growth factors and cytokines to diffuse efficiently into retinal tissue. Moreover, the ECT based treatment can be terminated timely when we need to retrieve the implant, which makes the therapy reversible and provides a safer alternative for intraocular gene therapy. Meanwhile, we also place special emphasis on optimizing encapsulation materials and enhancing preservation techniques to achieve the stable release of growth factors and cytokines in the eyeball. This technology holds great promise for the treatment of patients with dry AMD, RP, glaucoma and MacTel. These findings would enrich our understandings of ECT and promote its future applications in treatment of degenerative retinopathy. This review comprises articles evaluating the exactness of artificial intelligence-based formulas published from 2000 to March 2024. The papers were identified by a literature search of various databases (PubMed/MEDLINE, Google Scholar, Cochrane Library and Web of Science).
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2.
Review: Protein O-GlcNAcylation regulates DNA damage response: A novel target for cancer therapy.
Zhu, Z, Li, S, Yin, X, Sun, K, Song, J, Ren, W, Gao, L, Zhi, K
International journal of biological macromolecules. 2024;(Pt 1):130351
Abstract
The DNA damage response (DDR) safeguards the stable genetic information inheritance by orchestrating a complex protein network in response to DNA damage. However, this mechanism can often hamper the effectiveness of radiotherapy and DNA-damaging chemotherapy in destroying tumor cells, causing cancer resistance. Inhibiting DDR can significantly improve tumor cell sensitivity to radiotherapy and DNA-damaging chemotherapy. Thus, DDR can be a potential target for cancer treatment. Post-translational modifications (PTMs) of DDR-associated proteins profoundly affect their activity and function by covalently attaching new functional groups. O-GlcNAcylation (O-linked-N-acetylglucosaminylation) is an emerging PTM associated with adding and removing O-linked N-acetylglucosamine to serine and threonine residues of proteins. It acts as a dual sensor for nutrients and stress in the cell and is sensitive to DNA damage. However, the explanation behind the specific role of O-GlcNAcylation in the DDR remains remains to be elucidated. To illustrate the complex relationship between O-GlcNAcylation and DDR, this review systematically describes the role of O-GlcNAcylation in DNA repair, cell cycle, and chromatin. We also discuss the defects of current strategies for targeting O-GlcNAcylation-regulated DDR in cancer therapy and suggest potential directions to address them.
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3.
E. coli phage transport in porous media: Response to colloid types and water saturation.
Zhang, W, Li, S, Zhao, K, Chai, J, Wan, B, Qin, Y, Huan, H, Sun, S, Yang, Y, Jat Baloch, MY
The Science of the total environment. 2024;:167635
Abstract
Because of its long survival time, high migration ability and high pathogenicity, the migration of the virus in the subsurface environment deserves in-depth exploration and research. In this study we investigated the migration behavior of E. coli phage (VI) with organic colloids (HA) or inorganic colloids (SiO2) in the saturated or unsaturated bands and compared the differences in their migration mechanisms.The effects of different colloids on the surface characteristics of VI were analyzed according to particle size and zeta potential. Column experiments were conducted to simulate their migration in the subsurface environment. The results show that HA enhances the stability of VI-HA, promotes VI migration and plays a dominant role in its migration process under both saturated and unsaturated conditions. In contrast, SiO2 puts VI-SiO2 in an unstable state and is easily separated in the unsaturated state, thus promoting VI migration. Based on migration experiments, the extent of influence factors on VI migration was quantified and compared. The effect of colloids on VI migration is greater than that of moisture content, where the effect of HA is greater than that of SiO2. This study provides an experimental research idea to determine the dominant factors affecting virus migration, and provides a general direction and theoretical basis for the biological risk assessment of pathogenic microorganisms in complex underground environments, in order to enable the decision makers to make a response in time, accurately, and efficiently.
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4.
Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges.
Zou, Y, Li, S, Chen, W, Xu, J
Endocrine. 2024;(2):270-284
Abstract
Diabetes mellitus (DM) is a chronic and relentlessly progressive metabolic disease characterized by a relative or absolute deficiency of insulin in the body, leading to increased production of advanced glycosylation end products that further enhance oxidative and nitrosative stresses, often leading to multiple macrovascular (cardiovascular disease) and microvascular (e.g., diabetic nephropathy, diabetic retinopathy, and neuropathy) complications, representing the ninth leading cause of death worldwide. Existing medical treatments do not provide a complete cure for DM; thus, stem cell transplantation therapy has become the focus of research on DM and its complications. Urine-derived stem cells (USCs), which are isolated from fresh urine and have biological properties similar to those of mesenchymal stem cells (MSCs), were demonstrated to exert antiapoptotic, antifibrotic, anti-inflammatory, and proangiogenic effects through direct differentiation or paracrine mechanisms and potentially treat patients with DM. USCs also have the advantages of simple noninvasive sample collection procedures, minimal ethical issues, low cost, and easy cell isolation methods and thus have received more attention in regenerative therapies in recent years. This review outlines the biological properties of USCs and the research progress and current limitations of their role in DM and related complications. In summary, USCs have shown good versatility in treating hyperglycemia-impaired target organs in preclinical models, and many challenges remain in translating USC therapies to the clinic.
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An antibacterial packaging film based on amylose starch with quaternary ammonium salt chitosan and its application for meat preservation.
Deng, B, Chen, J, Li, S, Liu, J, Zhou, Z, Qin, Z, Wang, H, Su, M, Li, L, Bai, Z
International journal of biological macromolecules. 2024;(Pt 2):129706
Abstract
A new generation of food packaging films is gradually replacing traditional plastic packaging films because of their biodegradability, safety, and some functional properties such as anti-bacterial and oxidant resistance. In the present work, an antibacterial packing film based on amylose starch and 2-hydroxypropyl-trimethylammonium chloride chitosan (HTCC) was prepared for meat preservation. The interfacial bonding mechanism between amylose, HTCC, and glutaraldehyde (GA) was determined experimentally and through molecular dynamics (MD) simulation. The macromolecular chains of amylose starch and HTCC became entangled via inter-molecular H-bonds and then cross-linked with GA via the Schiff base reaction. The interaction of amylose starch and HTCC improved the mechanical properties of the amylose films. Compared with the amylose films, the tensile strength and elongation at break of the optimal HTCC/amylose films reached to 16.13 MPa (an increase of 206.65 %) and 53.86 % (an increase of 109.49 %). The HTCC/amylose films were found to provide obvious bacteriostatic performance, a relatively low cytotoxicity, the lower transmittance in the UV region, and thus the ability to enhance the preservation of fresh meat. These excellent characteristics therefore suggest that HTCC/amylose films might be promising candidates for application in antibacterial food packaging films.
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Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.
Xu, B, Kang, B, Li, S, Fan, S, Zhou, J
Journal of endocrinological investigation. 2024
Abstract
BACKGROUND The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated. OBJECTIVE This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer. METHODS We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0. RESULTS A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03). CONCLUSION SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.
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7.
Dyslipidemia is associated with sarcopenia of the elderly: a meta-analysis.
Bi, B, Dong, X, Yan, M, Zhao, Z, Liu, R, Li, S, Wu, H
BMC geriatrics. 2024;(1):181
Abstract
PURPOSE Sarcopenia is a pathological change characterized by muscle loss in older people. According to the reports, there is controversy on the relationship between dyslipidemia and sarcopenia. Therefore, this meta-analysis aimed to explore the association between sarcopenia and dyslipidemia. METHODS We searched the Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Wan Fang, China Science and Technology Journal Database (VIP Database) for case‒control studies to extract data on the odds ratio (OR) between sarcopenia and dyslipidemia and the MD(mean difference) of TC, LDL-C, HDL-C, TG, and TG/HDL-C between sarcopenia and nonsarcopenia. The JBI(Joanna Briggs) guidelines were used to evaluate the quality. Excel 2021, Review Manager 5.3 and Stata 16.0 were used for the statistical analysis. RESULTS Twenty studies were included in the meta-analysis, 19 of which were evaluated as good quality. The overall OR of the relationship between sarcopenia and dyslipidemia was 1.47, and the MD values of TC, LDL-C, HDL-C, TG, and TG/HDL-C were 1.10, 1.95, 1.27, 30.13, and 0.16 respectively. In female, compared with the non-sarcopnia, the MD of TC, LDL-C, HDL-C, TG of sarcopenia were - 1.67,2.21,1.02,-3.18 respectively. In male, the MD of TC, LDL-C, HDL-C, TG between sarcopenia and non-sarcopenia were - 0.51, 1.41, 5.77, -0.67. The OR between sarcopenia and dyslipidemia of the non-China region was 4.38, and it was 0.9 in China. In the group(> 60), MD of TC between sarcopenia and non-sarcopenia was 2.63, while it was 1.54 in the group(20-60). CONCLUSION Dyslipidemia was associated with sarcopenia in the elderly, which was affected by sex, region and age.
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8.
Effect of mind-body exercise on risk factors for metabolic syndrome including insulin resistance: a meta-analysis.
Li, S, Wang, P, Wang, J, Zhao, J, Wang, X, Liu, T
Frontiers in endocrinology. 2024;:1289254
Abstract
OBJECTIVE To systematically evaluate the effects of mind-body exercise on risk factors of metabolic syndrome such as insulin resistance. METHODS Web of Science, PubMed, The Cochrane Library, EBSCO host, Embase, China Knowledge Network, China Biomedical Literature Database, Wanfang, and VIP were searched for the period from the establishment of the database to 1 July 2023, and randomized controlled trials of mind-body exercise interventions in patients with metabolic syndrome were collected. We applied the Cochrane Risk of Bias tool RoB2 to evaluate the methodological quality of the included literature and used RevMan5.4 software and Stata15.1 for statistical analysis. RESULTS A total of 14 randomized controlled trials with 1148 patients were included in this study. Meta-analysis showed that mind-body exercise significantly improved insulin resistance [SMD=-0.78, 95% CI: (-1.13, -0.43), P<0.0001], waist circumference [SMD=-2.20, 95% CI: (-3.34, -1.06), P=0.0001], body mass index (SMD=-1.50, 95% CI: [-2.03, -0.97), P<0.00001], systolic blood pressure [SMD=-3.65, 95% CI: 9-5.56, -1.74), P=0.0002], diastolic blood pressure [SMD=-3.32, 95% CI: (- 3.77, -2.87), P<0.00001], fasting blood glucose [SMD=-0.57, 95% CI: (-0.99, -0.15), P=0.008], triglycerides [SMD=-0.27, 95% CI: (-0.46, -0.08), P=0.004], high-density lipoprotein cholesterol [SMD=0.58, the 95% CI: (0.28, 0.87), P=0.0001]. Subgroup analysis showed that the intervention program with exercise form of fitness qigong, exercise cycle of 24-48 weeks, and exercise frequency of 6-7 times/week could significantly improve each risk factor. CONCLUSION Mind-body exercise is effective in improving risk factors in patients with metabolic syndrome. Current evidence recommends an intervention program of low to moderate intensity fitness qigong, with 6-7 sessions per week for 24-48 weeks in patients with metabolic syndrome. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/prospero/, identifier CRD42023454135.
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Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: current strategies and future prospective.
Li, S, Li, F, Wang, Y, Li, W, Wu, J, Hu, X, Tang, T, Liu, X
Drug delivery. 2024;(1):2298514
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Abstract
Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.
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Causal role of lipid metabolism in pulmonary alveolar proteinosis: an observational and mendelian randomisation study.
Huang, J, Lin, Z, Lin, J, Xie, S, Xia, S, Chen, G, Zheng, Z, Xu, Z, Liu, F, Wu, H, et al
Thorax. 2024;(2):135-143
Abstract
BACKGROUND Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterised by the accumulation of lipoprotein material in the alveoli. Although dyslipidaemia is a prominet feature, the causal effect of lipid traits on PAP remains unclear. This study aimed to explore the role of lipid traits in PAP and evaluate the potential of lipid-lowering drug targets in PAP. METHODS Clinical outcomes, lipid profiles and lung function tests were analysed in a clinical cohort of diagnosed PAP patients and propensity score-matched healthy controls. Genome-wide association study data on PAP, lipid metabolism, blood cells and variants of genes encoding potential lipid-lowering drug targets were obtained for Mendelian randomisation (MR) and mediation analyses. FINDINGS Observational results showed that higher levels of total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) were associated with increased risks of PAP. Higher levels of TC and LDL were also associated with worse PAP severity. In MR analysis, elevated LDL was associated with an increased risk of PAP (OR: 4.32, 95% CI: 1.63 to 11.61, p=0.018). Elevated monocytes were associated with a lower risk of PAP (OR 0.34, 95% CI: 0.18 to 0.66, p=0.002) and mediated the risk impact of LDL on PAP. Genetic mimicry of PCSK9 inhibition was associated with a reduced risk of PAP (OR 0.03, p=0.007). INTERPRETATION Our results support the crucial role of lipid and metabolism-related traits in PAP risk, emphasising the monocyte-mediated, causal effect of elevated LDL in PAP genetics. PCSK9 mediates the development of PAP by raising LDL. These finding provide evidence for lipid-related mechanisms and promising lipid-lowering drug target for PAP.