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1.
Therapeutic application and potential mechanism of plant-derived extracellular vesicles in inflammatory bowel disease.
Li, J, Luo, T, Wang, D, Zhao, Y, Jin, Y, Yang, G, Zhang, X
Journal of advanced research. 2024
Abstract
BACKGROUND Plant-derived extracellular vesicles (PDEVs) are membrane vesicles characterized by a phospholipid bilayer as the basic skeleton that is wrapped by various functional components of proteins and nucleic acids. An increasing number of studies have confirmed that PDEVs can be a potential treatment of inflammatory bowel disease (IBD) and can, to some extent, compensate for the limitations of existing therapies. AIM OF REVIEW This review summarizes the recent advances and potential mechanisms underlying PDEVs obtained from different sources to alleviate IBD. In addition, the review discusses the possible applications and challenges of PDEVs, providing a theoretical basis for exploring novel and practical therapeutic strategies for IBD. KEY SCIENTIFIC CONCEPTS OF REVIEW In IBD, the crosstalk mechanism of PDEVs may regulate the intestinal microenvironment homeostasis, especially immune responses, the intestinal barrier, and the gut microbiota. In addition, drug loading enhances the therapeutic potential of PDEVs, particularly regarding improved tissue targeting and stability. In the future, not only immunotherapy based on PDEVs may be an effective treatment for IBD, but also the intestinal barrier and intestinal microbiota will be a new direction for the treatment of IBD.
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2.
Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration.
Zhou, H, Qian, Q, Chen, Q, Chen, T, Wu, C, Chen, L, Zhang, Z, Wu, O, Jin, Y, Wang, X, et al
Small (Weinheim an der Bergstrasse, Germany). 2024;(13):e2308167
Abstract
Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.
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3.
Resveratrol protects mesangial cells under high glucose by regulating the miR-1231/IGF1/ERK pathway.
Zhang, M, Jin, Y, Guo, X, Shan, W, Zhang, J, Yuan, A, Shi, Y
Environmental toxicology. 2024;(4):2326-2339
Abstract
Diabetic nephropathy (DN) is one of the complications of diabetes mellitus and the main cause of end-stage renal disease (ESRD), which is a serious threat to human health. In DN, mesangial cells (MCs) are a critical target cell that perform a variety of key functions, and abnormal proliferation of MCs is a common and prominent pathological change in DN. In recent years, the investigation of Chinese medicine interventions for DN has increased significantly in recent years due to the many potential adverse effects and controversies associated with the treatment of DN with Western medicines. In this study, we evaluated the protective effect of resveratrol (RES), an active ingredient known as a natural antioxidant, on HMCs under high glucose and explored its possible mechanism of action. We found that RES inhibited the proliferation of human mesangial cell (HMC) under high glucose and blocked cell cycle progression. In the high glucose environment, RES upregulated miR-1231, reduced IGF1 expression, inhibited the activity of the extracellular signal-regulated kinase (ERK) signaling pathway and reduced levels of the inflammatory factors TNF-α and IL-6. In addition, we found that miR-1231 mimics were synergistically inhibited with RES, whereas miR-1231 inhibitor attenuated the protective effect of RES on HMCs. Thus, our results suggest that the protective effect of RES on HMCs under high glucose is achieved, at least in part, through modulation of the miR-1231/IGF1/ERK pathway. The discovery of this potential mechanism may provide a new molecular therapeutic target for the prevention and treatment of DN, and may also bring new ideas for the clinical research in DN.
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4.
Effect of humic substances on nitrogen cycling in soil-plant ecosystems: Advances, issues, and future perspectives.
Jin, Y, Yuan, Y, Liu, Z, Gai, S, Cheng, K, Yang, F
Journal of environmental management. 2024;:119738
Abstract
Nitrogen (N) cycle is one of the most significant biogeochemical cycles driven by soil microorganisms on the earth. Exogenous humic substances (HS), which include composted-HS and artificial-HS, as a new soil additive, can improve the water retention capacity, cation exchange capacity and soil nutrient utilization, compensating for the decrease of soil HS content caused by soil overutilization. This paper systematically reviewed the contribution of three different sources of HS in the soil-plant system and explained the mechanisms of N transformation through physiological and biochemical pathways. HS convert the living space and living environment of microorganisms by changing the structure and condition of soil. Generally, HS can fix atmospheric and soil N through biotic and abiotic mechanisms, which improved the availability of N. Besides, HS transform the root structure of plants through physiological and biochemical pathways to promote the absorption of inorganic N by plants. The redox properties of HS participate in soil N transformation by altering the electron gain and loss of microorganisms. Moreover, to alleviate the energy crisis and environmental problems caused by N pollution, we also illustrated the mechanisms reducing soil N2O emissions by HS and the application prospects of artificial-HS. Eventually, a combination of indoor simulation and field test, molecular biology and stable isotope techniques are needed to systematically analyze the potential mechanisms of soil N transformation, representing an important step forward for understanding the relevance between remediation of environmental pollution and improvement of the N utilization in soil-plant system.
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5.
Impacts of prothioconazole and prothioconazole-desthio on bile acid and glucolipid metabolism: Upregulation of CYP7A1 expression in HepG2 cells.
Hu, L, Wang, X, Qian, M, Zhang, H, Jin, Y
Pesticide biochemistry and physiology. 2024;:105702
Abstract
As an efficient triazole fungicide, prothioconazole (PTC) is widely used for the prevention and control of plant fungal pathogens. It was reported that the residues of PTC and prothioconazole-desthio (PTC-d) have been detected in the environment and crops, and the effects of PTC-d may be higher than that of PTC. Currently, PTC and PTC-d have been proven to induce hepatic metabolic disorders. However, their toxic effects on cellular bile acid (BA) and glucolipid metabolism remain unknown. In this study, HepG2 cells were exposed to 1-500 μM of PTC or PTC-d. High concentrations of PTC and PTC-d were found to induce cytotoxicity; thus, subsequent experimental exposure was conducted at concentrations of 10-50 μM. The expression levels of CYP7A1 and TG synthesis-related genes and levels of TG and total BA were observed to increase in HepG2 cells. Molecular docking analysis revealed direct interactions between PTC or PTC-d and CYP7A1 protein. To further investigate the underlying mechanisms, PTC and PTC-d were treated to HepG2 cells in which CYP7A1 expression was knocked down using siCYP7A1. It was observed that PTC and PTC-d affected the BA metabolism process and regulated the glycolipid metabolism process by promoting the expression of CYP7A1. In summary, we comprehensively analyzed the effects and mechanisms of PTC and PTC-d on cellular metabolism in HepG2 cells, providing theoretical data for evaluating the safety and potential risks associated with these substances.
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6.
Resveratrol rescues cutaneous radiation-induced DNA damage via a novel AMPK/SIRT7/HMGB1 regulatory axis.
Jin, Y, Liu, X, Liang, X, Liu, J, Liu, J, Han, Z, Lu, Q, Wang, K, Meng, B, Zhang, C, et al
Cell death & disease. 2023;(10):847
Abstract
Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to be the key interacting partner of SIRT7 to mediate the radioprotective function of RSV. Mechanistic study elucidated that SIRT7 interacts with and deacetylates HMGB1 to redistribute it into nucleus and "switch on" its function for DNA damage repair. Our findings establish a novel AMPK/SIRT7/HMGB1 regulatory axis that mediates the radioprotective function of RSV to alleviate IR-induced cutaneous DNA injury, providing an efficiently-curative option for patients with CRI during radiotherapy.
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7.
Body Composition in Inflammatory Bowel Disease.
Wei, H, Yuan, Z, Ren, K, Jin, Y, Ren, L, Cao, B, Zhou, Y, Chen, L
Archives of Iranian medicine. 2023;(3):172-175
Abstract
Inflammatory bowel disease (IBD) is associated with body composition changes, which are associated with clinical prognosis, response to therapy, and quality of life in IBD patients. Therefore, it is critical to review the body composition distribution in IBD, summarize the potential factors affecting body composition distribution, and take steps to improve the body composition distribution of IBD patients as early as possible. In the current review, we searched PubMed via keywords 'inflammatory bowel disease', or 'IBD', or 'Crohn's disease', or 'CD', or 'ulcerative colitis', or 'UC', and 'body composition'. Malnutrition and sarcopenia are common in IBD patients and are associated with the clinical course, prognosis, and need for surgery. Disease activity, reduced nutrition intake, vitamin D deficiency, and intestinal dysbiosis are factors contributing to changed body composition. Early use of biological agents to induce remission is critical to improving body composition distribution in IBD patients, supplementation of vitamin D is also important, and moderate physical activity is recommended in IBD patients with clinical remission.
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8.
Ketonization of Ginsenoside C-K by Novel Recombinant 3-β-Hydroxysteroid Dehydrogenases and Effect on Human Fibroblast Cells.
Jin, Y, Wang, D, Im, WT, Siddiqi, MZ, Yang, DC
Molecules (Basel, Switzerland). 2023;(9)
Abstract
BACKGROUND AND OBJECTIVE The ginsenoside compound K (C-K) (which is a de-glycosylated derivative of major ginsenosides) is effective in the treatment of cancer, diabetes, inflammation, allergy, angiogenesis, aging, and has neuroprotective, and hepatoprotective than other minor ginsenosides. Thus, a lot of studies have been focused on the conversion of major ginsenosides to minor ginsenosides using glycoside hydrolases but there is no study yet published for the bioconversion of minor ginsenosides into another high pharmacological active compound. Therefore, the objective of this study to identify a new gene (besides the glycoside hydrolases) for the conversion of minor ginsenosides C-K into another highly pharmacological active compound. METHODS AND RESULTS Lactobacillus brevis which was isolated from Kimchi has showed the ginsenoside C-K altering capabilities. From this strain, a novel potent decarboxylation gene, named HSDLb1, was isolated and expressed in Escherichia coli BL21 (DE3) using the pMAL-c5X vector system. Recombinant HSDLb1 was also characterized. The HSDLb1 consists of 774 bp (258 amino acids residues) with a predicted molecular mass of 28.64 kDa. The optimum enzyme activity was recorded at pH 6.0-8.0 and temperature 30 °C. Recombinant HSDLb1 effectively transformed the ginsenoside C-K to 12-β-hydroxydammar-3-one-20(S)-O-β-D-glucopyranoside (3-oxo-C-K). The experimental data proved that recombinant HSDLb1 strongly ketonized the hydroxyl (-O-H) group at C-3 of C-K via the following pathway: C-K → 3-oxo-C-K. In vitro study, 3-oxo-C-K showed higher solubility than C-K, and no cytotoxicity to fibroblast cells. In addition, 3-oxo-C-K induced the inhibitory activity of ultraviolet A (UVA) against matrix metalloproteinase-1 (MMP-1) and promoted procollagen type I synthesis. Based on these expectations, we hypothesized that 3-oxo-C-K can be used in cosmetic products to block UV radiations and anti-ageing agent. Furthermore, we expect that 3-oxo-C-K will show higher efficacy than C-K for the treatment of cancer, ageing and other related diseases, for which more studies are needed.
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9.
Effect of temporary cements and their removal methods on the bond strength of indirect restoration: a systematic review and meta-analysis.
Ding, J, Jin, Y, Feng, S, Chen, H, Hou, Y, Zhu, S
Clinical oral investigations. 2023;(1):15-30
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Abstract
OBJECTIVES For a conventional indirect restoration, temporary cementation inevitably contaminated collapsed dentin collagen. The purpose of this review was to evaluate the optimal strategy for minimizing its negative effects. MATERIAL AND METHODS Databases such as PubMed, Web of Science, EMBASE, and the Cochrane Library were searched for in vitro studies, involving the influence of immediate dentin sealing (IDS), different temporary cements, and their removal strategies on dentin bond strength. The meta-analysis used the inverse variance method with effect method of the standardized mean difference and statistical significance at p ≤ 0.05. The I2 value and the Q-test were used to assess the heterogeneity. RESULTS A total of 14 in vitro trials were subjected to the meta-analysis. Within the study's limitations, we assumed that IDS eliminated the negative effects of temporary bonding, achieving the comparable immediate bond strength with the control (p = 0.46). In contrast, under delayed dentin sealing (DDS), temporary cementation statistically decreased bond strength (p = 0.002). Compared with resin-based and non-eugenol zinc oxide cements, polycarboxylate and calcium hydroxide cements performed better on bond strength with no statistical difference from the control group (p > 0.05). Among the removal methods of temporary cements, the Al2O3 abrasion restored the decreased bond strength (p = 0.07) and performed better than hand instruments alone (p = 0.04), while pumice removal slightly reduced the bond strength in contrast with the control group (p = 0.05, 95% CI = - 1.62 to 0). CONCLUSIONS The choices of IDS, polycarboxylate and calcium hydroxide temporary cements, Al2O3 abrasion removal method were feasible and efficient to enhance the bond strength. CLINICAL RELEVANCE It is worthwhile applying IDS technique, polycarboxylate and calcium hydroxide temporary cements during indirect restoration. The Al2O3 abrasion of cleaning dentin can minimize the negative effects of temporary cement.
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10.
Benefits and harms of drug treatment for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.
Shi, Q, Nong, K, Vandvik, PO, Guyatt, GH, Schnell, O, Rydén, L, Marx, N, Brosius, FC, Mustafa, RA, Agarwal, A, et al
BMJ (Clinical research ed.). 2023;:e074068
Abstract
OBJECTIVE To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN Systematic review and network meta-analysis. DATA SOURCES Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022325948.