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The onset and progression of ulcerative colitis (UC) are intricately linked to the worsening of intestinal inflammation, an imbalance in oxidative stress, and impairment of the intestinal mucosal barrier. Although chlorogenic acid (CA) shows potential in effectively alleviating the symptoms of UC, its clinical application is hindered by its poor bioavailability, stability, rapid metabolism, and quick excretion. This study utilized a one-step enzyme-catalyzed polymerization technique to create chlorogenic acid nanoparticles (CA NPs), aiming to improve the bioavailability and stability of CA. The CA NPs exhibited an optimal nanosize (106.65 ± 4.12 nm) and showed increased cellular uptake over time. Importantly, CA NPs significantly prolonged retention time in inflamed colonic tissues, enhancing accumulation and providing a targeted therapy for UC. Animal studies confirmed the substantial benefits of CA NPs, including reduced weight loss, lessened reduction in colon length, and a lowered disease activity index (DAI) score in DSS-induced UC mice. Moreover, CA NPs effectively reduced oxidative stress and levels of inflammatory factors in the colonic tissues of UC mice, thus mitigating tissue damage and restoring the integrity of the intestinal mucosal barrier. In conclusion, our research proposes a novel approach to increase the bioavailability and stability of CA, offering a promising avenue for its effective application in preventing UC.
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In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention. Abundant research underscores CGA's robust biological activity, showcasing notable preventive and therapeutic efficacy across diverse diseases. This article commences with a comprehensive overview, summarizing the dietary sources and primary biological activities of CGA. These encompass antioxidant, anti-inflammatory, antibacterial, anti-cancer, and neuroprotective activities. Next, a comprehensive overview of the current research on nutrient delivery systems incorporating CGA is provided. This exploration encompasses nanoparticle, liposome, hydrogel, and emulsion delivery systems. Additionally, the article explores the latest applications of CGA in the food industry. Serving as a cutting-edge theoretical foundation, this paper contributes to the design and development of CGA in the realms of nutrition delivery and the food industry. Finally, the article presents informed speculations and considerations for the future development of CGA.
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Ácido Clorogênico , Indústria Alimentícia , Ácido Clorogênico/química , Ácido Clorogênico/farmacologia , Humanos , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Sistemas de Liberação de Medicamentos/métodosRESUMO
Inflammatory bowel disease (IBD) is a chronic and idiopathic condition that results in inflammation of the gastrointestinal tract, leading to conditions such as ulcerative colitis and Crohn's disease. Commonly used treatments for IBD include anti-inflammatory drugs, immunosuppressants, and antibiotics. Fecal microbiota transplantation is also being explored as a potential treatment method; however, these drugs may lead to systemic side effects. Oral administration is preferred for IBD treatment, but accurately locating the inflamed area in the colon is challenging due to multiple physiological barriers. Nanoparticle drug delivery systems possess unique physicochemical properties that enable precise delivery to the target site for IBD treatment, exploiting the increased permeability and retention effect of inflamed intestines. The first part of this review comprehensively introduces the pathophysiological environment of IBD, covering the gastrointestinal pH, various enzymes in the pathway, transport time, intestinal mucus, intestinal epithelium, intestinal immune cells, and intestinal microbiota. The second part focuses on the latest advances in the mechanism and strategies of targeted delivery using oral nanoparticle drug delivery systems for colitis-related fields. Finally, we present challenges and potential directions for future IBD treatment with the assistance of nanotechnology.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/metabolismo , Colite Ulcerativa/tratamento farmacológico , Inflamação/tratamento farmacológicoRESUMO
Background: Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection). Methods: A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant. Results: Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1ß, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1ß, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05). Conclusion: This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs.
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Anti-Inflamatórios , Citocinas , Transplantados , Vitamina D , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Humanos , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Citocinas/efeitos dos fármacos , Estudos de Casos e Controles , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Suplementos NutricionaisRESUMO
BACKGROUND: Chronic allograft dysfunction (CAD) is a common cause of allograft loss in kidney transplant recipients (KTRs). Our previous study found that elevated serum soluble T cell immunoglobulin mucin-3 (sTim-3) was positively associated with the severity of CAD in KTRs. sTim-3 was reported to be generated from ADAM10/ADAM17-mediated ectodomain shedding of membrane Tim-3 (mTim-3) in humans. However, whether mTim-3 shedding-related molecules participate in the progression of CAD remains unknown. Here, we explored the relationships between different forms of Tim-3, including mTim-3 on different peripheral blood cell subsets, serum and urine sTim-3, and ADAM10/17 expression and active status to investigate their roles in CAD. METHODS: 63 KTRs with stable grafts, 91 KTRs with CAD and 42 healthy controls (HCs) were enrolled. Total Tim-3, pADAM10/17 and mADAM10/17 proteins were semiquantified by western blot. Serum and urine sTim-3 concentrations were determined by ELISA. mTim-3 and ADAM10/17 expression on leukocyte subpopulations was determined by flow cytometry. RESULTS: The KTR groups displayed significantly higher levels of urine sTim-3 pg/µmol creatinine than the HC group, while no difference was found between the two KTR groups. KTRs with CAD presented reduced nonactive pADAM10 protein but unaltered active mADAM10 when compared to the Stable group; no difference was found between the KTR groups regarding total Tim-3 and p/m ADAM17 protein levels. In addition, the CAD group showed lower mTim-3 expression on BDCA3+ DC than the Stable group; no other difference was observed in its expression on B, T, NK, NKT, monocyte subsets and other DC subsets among groups. With the deterioration of allograft function, ADAM10 expression densities on classical, intermediate, and non-classical monocytes were significantly decreased. Correlation analyses revealed that eGFR and serum sTim-3 exhibited weak to modest correlations with ADAM10 on monocyte and DC subsets. CONCLUSIONS: Our data indicated that ADAM10, especially its decreased expression on monocytes, may play an important role in the progression of CAD in KTRs. However, whether there is an interaction between ADAM10 and mTim-3 in the pathogenesis of CAD in KTRs needs to be further studied.
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Receptor Celular 2 do Vírus da Hepatite A , Transplante de Rim , Humanos , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Monócitos/metabolismo , Transplante Homólogo , Proteína ADAM10/metabolismo , Proteína ADAM17/metabolismo , Aloenxertos , Proteínas de Membrana/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismoRESUMO
Introduction: Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation. Materials and methods: Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23-KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients. Results: Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion: Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.
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Background: Although posttransplant anemia (PTA) is a common complication after kidney transplant, it has not been thoroughly evaluated for appropriate treatment. Roxadustat can stimulate erythropoiesis by increasing erythropoietin (EPO) production and improving the utilization of iron. However, there are currently a few case reports describing its effect on PTA in kidney transplant recipients (KTRs). Our purpose was to evaluate the efficacy and safety of roxadustat in KTRs with PTA. Methods: In this retrospective study, KTRs with early PTA were divided into a roxadustat group, erythropoiesis-stimulating agent (ESA) group, and untreated group (neither roxadustat nor ESA) according to the treatment prescribed by their physicians. We compared the levels of hemoglobin (Hb), creatinine, lipids, hepcidin, intact fibroblast growth factor 23 (iFGF23) and iron-related indices, at baseline and different time points posttransplant. Outcome was assessed at both month 3 and month 12 posttransplant. Adverse events during the treatment course were also recorded. Results: A total of 57 KTRs were included (n=22 roxadustat group, n=13 ESA group, n=22 untreated group). There was no difference in age, sex, body mass index, dialysis method and duration, donor type among three groups at baseline. The mean Hb levels at month 3 posttransplant (128.00±19.62 vs. 118.59±11.60 g/L, P=0.048) and the average change in Hb levels from week 2 to month 3 (48.05±22.53 vs. 31.45±12.96 g/L, P=0.005) in the roxadustat group were significantly higher than those in the untreated group. However, there was no significant difference in the above indices between the roxadustat and ESA groups. At month 3, the total iron binding capacity (TIBC) and levels of transferrin were significantly higher while levels of ferritin, hepcidin and iFGF23 were significantly lower in the roxadustat group than in other groups (P<0.05). No significant difference was found in creatinine or estimated glomerular filtration rate (eGFR) levels among the three groups at month 3. During the follow-up, no adverse events related to roxadustat were reported. Conclusions: Administration of roxadustat in KTRs with early PTA could elevate Hb levels effectively and safely by enhancing endogenous EPO production and improving iron utilization. Further randomized studies with larger sample size are necessary to verify our results.
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BACKGROUND: To develop and validate predictive nomograms for 5-year graft survival in kidney transplant recipients (KTRs) with easily-available laboratory data derived markers and clinical variables within the first year post-transplant. METHODS: The clinical and routine laboratory data from within the first year post-transplant of 1289 KTRs was collected to generate candidate predictors. Univariate and multivariate Cox analyses and LASSO were conducted to select final predictors. X-tile analysis was applied to identify optimal cutoff values to transform potential continuous factors into category variables and stratify patients. C-index, calibration curve, dynamic time-dependent AUC, decision curve analysis, and Kaplan-Meier curves were used to evaluate models' predictive accuracy and clinical utility. RESULTS: Two predictive nomograms were constructed by using 0-6- and 0-12- month laboratory data, and showed good predictive performance with C-indexes of 0.78 and 0.85, respectively, in the training cohort. Calibration curves showed that the prediction probabilities of 5-year graft survival were in concordance with actual observations. Additionally, KTRs could be successfully stratified into three risk groups by nomograms. CONCLUSIONS: These predictive nomograms combining demographic and 0-6- or 0-12- month markers derived from post-transplant laboratory data could serve as useful tools for early identification of 5-year graft survival probability in individual KTRs.
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Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Nomogramas , Transplantados , Adulto , Feminino , Humanos , Masculino , Prognóstico , Medição de RiscoRESUMO
Many animal experiments and clinical trials showed that probiotics are effective for the treatment of alcoholic liver disease. Alcohol disrupts the composition of intestinal flora; probiotics modulate the gut microbiota and reverse alcohol-associated intestinal barrier dysfunction by decreasing intestinal mucosal permeability and preventing intestinal bacteria from translocating. Probiotics enhance immune responses and reduce the levels of alcohol-induced inflammatory cytokines and reactive oxygen species (ROS) production in the liver and intestine. Probiotics also increase fatty acid ß-oxidation and reduce lipogenesis, combating alcohol-induced hepatic steatosis. In this review, we summarize the current knowledge regarding the mechanism of action of probiotics for reducing the effects of alcoholic liver disease.
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Succinic acid is widely applied to chemical, pharmaceutical, food, and agricultural industries. With the rapid development of these industries, a great demand of succinic acid is required. The acid-tolerance and succinic acid production of Actinobacillus succinogenes strain were improved by using genome shuffling. Results showed that one modified strain AS-F32, with the best acid resistance and the highest succinic acid production, was obtained after 3 cycles of genome shuffling. The minimum growth pH of AS-F32 was 3.5, and the acid production and cell dry weight were 5.1 and 4.8 g/L in flask, improved 2.6 and 1.85 times over the start strain As-R2. Furthermore, the succinic acid yield of As-32 was 31.2 g/L and the dry cell weight was increased 44.4% by maintaining pH 4.8 with 7.0 M NH4OH in 5 L bioreactor, increased 1.1 times than the original strain As-R2.