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Cyclodextrin-based metal-organic framework (CD-MOF) has been widely used in various delivery systems due to its excellent edibility and high drug loading capacity. However, its typically bulky size and high brittleness in aqueous solutions pose significant challenges for practical applications. Here, we proposed an ultrasonic-assisted method for rapid synthesis of uniformly-sized nanoscale CD-MOF, followed by its hydrophobic modification through ester bond cross-linking (Nano-CMOF). Proper ultrasound treatment effectively reduced particle size to nanoscale (393.14 nm). Notably, carbonate ester cross-linking method significantly improved water stability without altering its cubic shape and high porosity (1.3 cm3/g), resulting in a retention rate exceeding 90% in various media. Furthermore, the loading of quercetin did not disrupt cubic structure and showcased remarkable storage stability. Nano-CMOF achieved controlled release of quercetin in both aqueous environments and digestion. Additionally, Nano-CMOF demonstrated exceptional antioxidant (free radical scavenging 82.27%) and biocompatibility, indicating its significant potential as novel nutritional delivery systems in food and biomedical fields.
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Ciclodextrinas , Preparaciones de Acción Retardada , Portadores de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Estructuras Metalorgánicas , Quercetina , Quercetina/química , Estructuras Metalorgánicas/química , Ciclodextrinas/química , Portadores de Fármacos/química , Preparaciones de Acción Retardada/química , Nanopartículas/química , Materiales Biocompatibles/química , Tamaño de la Partícula , Humanos , Estabilidad de MedicamentosRESUMEN
Metal-organic frameworks (MOFs) are coordination compounds that possess an adjustable structure and controllable function. Despite their wide applications in various industries, the use of MOFs in the fields of food and biomedicine is limited mainly due to their potential biological toxicity. Researchers have thus focused on developing biocompatible MOFs to address this issue. Among them, cyclodextrin-based metal-organic frameworks (CD-MOFs) have emerged as a promising alternative. CD-MOFs are novel MOFs synthesized using naturally carbohydrate cyclodextrin and alkali metal cations, and possess renewable, non-toxic, and edible characteristics. Due to their high specific surface area, controllable porosity, great biocompatibility, CD-MOFs have been widely used in various delivery systems, such as encapsulation of nutraceuticals, flavors, and antibacterial agents. Although the field of CD-MOF materials is still in its early stages, they provide a promising direction for the development of MOF materials in the delivery field. This review describes classification and structural characteristics, followed by an introduction to formation mechanism and commonly used synthetic methods for CD-MOFs. Additionally, we discuss the status of the application of various delivery systems based on CD-MOFs. Finally, we address the challenges and prospects of CD-MOF materials, with the aim of providing new insights and ideas for their future development.
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Background: Hepatosplenic candidiasis is a rare but severe complication in immunocompromised patients undergoing chemotherapy. Antifungal agents are widely accepted as the first choices for therapy. However, resistance to or side-effect of antifungal agents may comxpromise its efficiency. Splenectomy has also been rarely performed as treatment for this disease. Methods: We present two cases of splenectomy for treating hepatosplenic candidiasis after failure of the initial drug therapy. Literatures on splenectomy as treatment for hepatosplenic candidiasis were searched in Pubmed and summarized. Results: Two leukemia patients developed hepatosplenic candidiasis after received chemotherapy for their primary diseases. Various antifungal agents including amphotericin B were all demonstrated failure to cure fever and the Candida abscesses due to resistance or intractable side-effect. Laparoscopic splenectomy were finally performed and resolved the candidiasis successfully. A total of 12 splenectomy cases for treating hepatosplenic candidiasis had been previously reported in literature. All the cases showed either resistance or unimproved to initial antifungal therapies. Splenectomy provided salvage therapeutic value in all cases. Conclusion: Splenectomy has therapeutic effect and may change the traditional concept in most surgeons. The present study may expand an alternative strategy in clinical practice guideline for the management of hepatosplenic candidiasis.
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Obesity-induced adipose chronic inflammation is closely related to the development of insulin resistance and T2DM. Tripeptides l-valyl-l-prolyl-l-proline (VPP) and l-isoleucyl-l-prolyl-L-proline (IPP) derived from bovine casein have been reported to prevent inflammatory changes and mitigate insulin resistance in adipocytes. In this study, we aimed to investigate the influence of casein hydrolysates (CH) containing VPP and IPP on a high fat diet (HFD)-induced obese mice and cytokine TNF-α-induced adipocytes. Our data showed that CH alleviated chronic inflammation both in vivo and in vitro. 4% CH suppressed HFD-induced systemic inflammatory factors, hypertrophic white adipocytes, and macrophage infiltration. More importantly, CH was able to improve adipocyte dysfunction induced by TNF-α by increasing the expression of CCAAT/enhancer binding protein α (C/EBP-α) rather than peroxisome proliferator-activated receptor γ (PPAR-γ). Furthermore, CH also dose-dependently suppressed mitogen-activated protein kinase (MAPK)-c-Jun N-terminal kinase (JNK) phosphorylation and enhanced the phosphorylation of Erk 1/2, but not nuclear factor-kappa B (NF-κB) p65 phosphorylation, in TNF-α-induced 3T3-L1 cells. These results indicated that CH could ameliorate adipose chronic inflammation through the MAPK pathway. Altogether, our findings suggested that 4% CH supplementation for 6 weeks exerted a protective role in preventing obesity-related inflammation and adipose dysfunction.
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Resistencia a la Insulina , Proteínas Quinasas Activadas por Mitógenos , Ratones , Animales , Bovinos , Caseínas/farmacología , Ratones Obesos , Factor de Necrosis Tumoral alfa , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Células 3T3-L1RESUMEN
SCOPE: Two peptides VY (Val-Tyr) and SFLLR (Ser-Phe-Leu-Leu-Arg) are recently identified from soy-fermented douchi with hypoglycemic activity in cells. The study aims to understand their potential effects on glucose metabolism and insulin sensitivity as well as their mechanisms of action in a high-fat diet (HFD) induced insulin resistant model. METHODS AND RESULTS: C57BL/6 mice are fed HFD for 8 weeks, followed by peptide supplementation (doses: 10 and 50 mg kg-1 body weight) for 8 weeks. Peptides supplementation, especially SFLLR, reduces body weight gain, insulin resistance, hyperglycemia, inflammation, liver injury, and lipid accumulation. In both muscle and liver, both peptides activate glycogen synthase (GS), the key enzyme for glycogen synthesis, and also inhibit phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6PC), two rate-limiting enzymes for gluconeogenesis, via insulin and AMPK (5'-adenosine monophosphate-activated protein kinase) signaling pathways. Furthermore, VY and SFLLR supplementation reverse HFD-induced gut dysbacteriosis by decreasing the abundance of Enterococcus, Oscillibacter, and Deferribacter, and also increase the abundances of Alistipes, Lactobacillus, Faecalibaculum, Akkermansia, and Bifidobacterium (usually beneficial in the intestine). CONCLUSION: The study reveals the potential applications of peptides VY and SFLLR as a diet-based strategy for the prevention of type 2 diabetes.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Ratones , Insulina/metabolismo , Dieta Alta en Grasa/efectos adversos , Diabetes Mellitus Tipo 2/metabolismo , Disbiosis/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Peso Corporal , Glucosa/metabolismo , HomeostasisRESUMEN
Two novel hypoglycemic peptides VY and SFLLR were identified from douchi as the major peptides responsible for the glucose uptake activity. The present work aimed to elucidate their digestion, absorption and transport properties using simulated digestion and Caco-2 cell monolayers transport models. Besides, the effects of digestion and absorption on the structure and activity were also studied. The results showed that VY was resistant to gastrointestinal tract digestion and could cross Caco-2 cell monolayers intactly via both TJs-mediated passive paracellular pathway and PepT1-mediated active route. In comparison, SFLLR was partially degraded into small fragments of SFLL, SFL, and SF by the digestive system, leading to increased glucose uptake activity. Notably, SFLLR, SFLL, and SFL were partly hydrolyzed by aminopeptidase N or dipeptidyl peptidase IV during transport, but they were transported intact. SFL was transported via both paracellular diffusion and PepT1-mediated routes, while SFLLR and SFLL were via paracellular route only.
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Digestión , Péptidos , Humanos , Células CACO-2 , Péptidos/química , Transporte Biológico , GlucosaRESUMEN
PURPOSE: Cutaneous metastases as an extrahepatic metastasis from hepatomas (HCC) is extremely rare and always carry a poor prognosis and less survival time. Previously, there has been a limited number of literature that reported skin metastasis in a large number of cases, which has rarely been discussed in the empirical treatment and therapy of cutaneous metastasis, especially for non-iatrogenic implantation. It is necessary to discuss this kind of metastasis. PATIENTS AND METHODS: We summarize cases from our medical center from 2013 to 2021, there are 12 patients diagnosed with non-iatrogenic implantation of cutaneous metastasis after HCC. We conducted the investigation of the clinical prognosis, pathological characteristics, and treatment of those patients. RESULTS: All patients were male, the age ranged from 21 to 71 years old, the average size of primary HCC was over 5 cm, there was four patient's cutaneous metastasis from the skin of head (including scalp and occipital region), followed by right abdominal (2 patients), right chest wall (2 patients), back (2 patients), umbilical (1 patient), gluteal region (1 patient). The cutaneous metastases presented as solitary or multiple nodules, papules, and erythema without ulcers with sizes between 0.5 cm and 5 cm. 7 patients died after being diagnosed with cutaneous metastasis within 2-19 months. CONCLUSIONS: The rate of non-iatrogenic implantation cutaneous metastasis is low, but the prognosis is poor, combining with histopathological analysis and history of diseases can be helpful in diagnosis. For large HCC (> 5 cm), systematic treatment is recommended to prevent the occurrence of cutaneous metastasis and improve the prognosis after hepatectomy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Cutáneas , Humanos , Masculino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Femenino , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Pronóstico , HepatectomíaRESUMEN
A phenylalanine (Phe)-restricted diet is indispensable for individuals suffering from phenylketonuria (PKU). Our previous study reported a low-Phe-containing whey protein hydrolysate (LPH) prepared from a selected whey protein hydrolysate (TA2H). This study aimed to investigate the osteogenic activity of LPH and TA2H in MC3T3-E1 preosteoblast cells and explore the underlying mechanism. Results showed that the treatment of TA2H and LPH (at the final concentrations of 100-1000 µg/mL) had a stimulatory effect on the proliferation, differentiation, and mineralization of MC3T3-E1 cells. The LPH of 1000 µg/mL significantly increased cell proliferation (2.15- ± 0.11-fold) and alkaline phosphatase activity (1.22- ± 0.07-fold), promoted the protein and mRNA levels of runt-related transcription factor 2 (Runx2, 2.50- ± 0.14-fold and 2.97- ± 0.23-fold, respectively), enhanced the expression of differentiation biomarkers (type-I collagen, osteocalcin, and osteopontin), increased calcium deposition (1.56- ± 0.08-fold), and upregulated the ratio of osteoprotegerin/receptor activator of nuclear factor-κB ligand. The exploration of signaling pathways indicated that the activated p38-dependent Runx2 signaling contributed to the LPH-induced osteogenesis. These results provided evidence, for the first time, that a prepared low-Phe whey protein hydrolysate positively modulated the activity of osteoblasts through the p38/Runx2 pathway, thereby providing a new osteoinductive protein substitute to make functional PKU food.
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Subunidad alfa 1 del Factor de Unión al Sitio Principal , Osteogénesis , Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Humanos , Osteoblastos , Fenilalanina/metabolismo , Fenilalanina/farmacología , Hidrolisados de Proteína/metabolismo , Hidrolisados de Proteína/farmacología , Suero Lácteo/metabolismoRESUMEN
A phenylalanine (Phe)-restricted diet is indispensable to control the blood Phe for individuals with phenylketonuria (PKU), who are also confronted with progressive bone impairment. Thus, the development of a low-Phe protein substitute that could positively regulate bone metabolism is desired for their bone health. Our previous study reported the preparation of a low-Phe containing whey hydrolysate (LPH) from a selected whey protein hydrolysate (TAH). However, the effect of LPH on the bone status is unknown. In this study, we used an ovariectomized (OVX) mice model to evaluate the anti-osteoporotic potential of oral administration of whey protein concentrate (WPC, protein control), TAH, and LPH on bone physiology and bone metabolism. The results showed that after 12 weeks of treatment, the decreased bone mineral density, the deteriorated trabecular microarchitecture, and the reduced ultimate load due to ovariectomy were significantly attenuated by two whey protein hydrolysates (TAH and LPH); meanwhile, the body weight, uterine weight, bone composition, and the femoral elastic load of OVX mice had not been significantly affected by whey samples. In addition, LPH and TAH dual-regulated bone remodeling in OVX mice through triggering osteogenesis (promoted the expression of runt-related protein 2 (Runx2) and osteoformation markers) and inhibiting osteoresorption as well as inflammation. The modulated mitogen-activated protein kinase signaling and the inhibited nuclear factor κB signaling by LPH and TAH might relate to the dual-regulatory activities on bone. Overall, in the OVX mice model, LPH exerted higher osteoprotective potential than TAH of the same dose by activating the bone formation markers and inhibiting the inflammatory status. The current study demonstrated for the first time the potential use of a low-Phe whey hydrolysate, a protein substitute for PKU individuals, in the prevention of osteoporosis.
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Osteoporosis , Hidrolisados de Proteína , Animales , Densidad Ósea , Femenino , Humanos , Ratones , Osteogénesis , Osteoporosis/tratamiento farmacológico , Ovariectomía , Fenilalanina/farmacología , Hidrolisados de Proteína/farmacología , Hidrolisados de Proteína/uso terapéutico , Suero LácteoRESUMEN
BACKGROUND AND AIM: Donor shortage has become worldwide limitation in liver transplantation (LT). Use of hepatitis B virus surface antigen positive (HBsAg+) donors could be an alternative source of donor organs. This study aims to investigate the safety and efficacy of LT using HBsAg+ liver grafts and associated long-term outcome. METHODS: This was a retrospective study of adults LT registered in the database of the China Liver Transplant Registry between January 2015 and September 2018. By propensity score matching (1:1), 503 eligible patients who received HBsAg+ liver grafts were compared with 503 matched patients who received HBsAg- liver grafts. RESULTS: The 1-, 3-, and 5-year patient survival rates were 81.52%, 72.04%, and 66.65% in HBsAg+ donor group, which were comparable with 83.93%, 77.27%, and 65.73% in HBsAg- donor group (P = 0.222). The 1-, 3-, and 5-year graft survival rates were also comparable between the two groups (81.49%, 71.45%, and 67.26% vs 83.62%, 77.11%, and 65.81%, respectively, P = 0.243). Most main complications were not increased in HBsAg+ donor group except for the retaining of HBsAg positivity after LT. Furthermore, transplanting HBsAg+ liver grafts did not result in inferior outcomes either in HBsAg+ or HBsAg- recipients. The risk of tumor recurrence after LT was not increased in hepatocellular carcinoma patients. CONCLUSIONS: The outcomes of using HBsAg+ liver grafts were comparable with those of HBsAg- liver grafts. Our study provided strong evidence for the safe use of HBsAg+ grafts in LT to expand the donor liver pool.
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Hepatitis B , Neoplasias Hepáticas , Trasplante de Hígado , Adulto , Antígenos de Superficie , Antígenos de Superficie de la Hepatitis B , Virus de la Hepatitis B , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Donadores Vivos , Recurrencia Local de Neoplasia/etiología , Sistema de Registros , Estudios Retrospectivos , Donantes de Tejidos , Resultado del TratamientoRESUMEN
Douchi is a popular soy-fermented food that originated in China with documented hypoglycemic effects. However, the responsible molecules and the mechanism underlying their beneficial effects remain unclear. Therefore, in this study, we aimed to identify the responsible peptide(s) in douchi. A peptide extract of douchi was isolated step-wise by the C18 Sep-Pak technique, size exclusion chromatography, and semi-preparative liquid chromatography, and then the peptides were sequenced by UPLC-MS/MS. A total of 21 peptides were identified, of which three peptides, P3 (HPFR), P5 (VY), and P7 (SFLLR), were shown to improve glucose uptake in L6 cells. Both P5 and P7 increased glucose transporter 4 (GLUT4) translocation via the activation of AMPK and MAPK signaling pathways, but not the insulin-signaling pathway; adding an AMPK or an MAPK inhibitor prevented P5 or P7-induced glucose uptake as well as AMPK and MAPK activation. Our study showed that P5 and P7 could promote glucose uptake via AMPK and MAPK signaling pathways. In this study, two hypoglycemic peptides from douchi have been characterized for the first time.
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Alimentos Fermentados , Glucosa/metabolismo , Hipoglucemiantes/aislamiento & purificación , Mioblastos/metabolismo , Péptidos/aislamiento & purificación , Proteínas Quinasas Activadas por AMP/metabolismo , Secuencia de Aminoácidos , Animales , Línea Celular , Transportador de Glucosa de Tipo 4/metabolismo , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Insulina/metabolismo , Sistema de Señalización de MAP Quinasas , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/efectos de los fármacos , Péptidos/química , Péptidos/farmacología , Ratas , Transducción de SeñalRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a public health challenge and significant cause of morbidity and mortality worldwide. Early identification is crucial for disease intervention. We recently proposed a nomogram-based NAFLD prediction model from a large population cohort. We aimed to explore machine learning tools in predicting NAFLD. METHODS: A retrospective cross-sectional study was performed on 15 315 Chinese subjects (10 373 training and 4942 testing sets). Selected clinical and biochemical factors were evaluated by different types of machine learning algorithms to develop and validate seven predictive models. Nine evaluation indicators including area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, positive predictive value, sensitivity, F1 score, Matthews correlation coefficient (MCC), specificity and negative prognostic value were applied to compare the performance among the models. The selected clinical and biochemical factors were ranked according to the importance in prediction ability. RESULTS: Totally 4018/10 373 (38.74%) and 1860/4942 (37.64%) subjects had ultrasound-proven NAFLD in the training and testing sets, respectively. Seven machine learning based models were developed and demonstrated good performance in predicting NAFLD. Among these models, the XGBoost model revealed the highest AUROC (0.873), AUPRC (0.810), accuracy (0.795), positive predictive value (0.806), F1 score (0.695), MCC (0.557), specificity (0.909), demonstrating the best prediction ability among the built models. Body mass index was the most valuable indicator to predict NAFLD according to the feature ranking scores. CONCLUSIONS: The XGBoost model has the best overall prediction ability for diagnosing NAFLD. The novel machine learning tools provide considerable beneficial potential in NAFLD screening.
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Enfermedad del Hígado Graso no Alcohólico , Estudios Transversales , Humanos , Aprendizaje Automático , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudios Retrospectivos , UltrasonografíaRESUMEN
The traditional low-alcoholic beverages, such as grape wine, sake, and rice wine, have been consumed all over the world for thousands of years, each with their unique methods of production that have been practiced for centuries. Moderate consumption of wine is generally touted as beneficial for health, although there is ongoing debate for the responsible components in wine. In this review, the structural and functional characteristics, the formation mechanisms, and their health-promoting activities of peptides in three brewed wines, grape wine, Chinese rice wine (also called Chinese Huangjiu or Chinese yellow wine), and Japanese sake, are discussed. The formation of peptides in wine imparts sensorial, technological, and biological attributes. Prospects on future research, with an emphasis on the peptide characterization, formation mechanism, physiological activity, and molecular mechanisms of action, are presented.
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Vino , Bebidas Alcohólicas , Fermentación , Péptidos , Vino/análisisRESUMEN
BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease in China. The early identification and management of patients at risk are essential. We aimed to develop a novel clinical and laboratory-based nomogram (CLN) model to predict NAFLD with high accuracy. METHODS: We designed a retrospective cross-sectional study and enrolled 21,468 participants (16,468 testing and 5000 validation). Clinical information and laboratory/imaging results were retrieved. Significant variables independently associated with NAFLD were identified by a logistic regression model, and a NAFLD prediction CLN was constructed. The CLN was then compared with four existing NAFLD-related prediction models: the fatty liver index (FLI), the hepatic steatosis index (HSI), the visceral adiposity index (VAI) and the triglycerides and glucose (TyG) index. Area under the receiver operator characteristic curve (AUROC) and decision curve analysis (DCA) were performed. RESULTS: A total of 6261/16,468 (38.02%) and 1759/5000 (35.18%) participants in the testing and validation datasets, respectively, had ultrasound-proven NAFLD. Six variables were selected to build the CLN: body mass index (BMI), diastolic blood pressure (DBP), uric acid (UA), fasting blood glucose (FBG), triglyceride (TG), and alanine aminotransferase (ALT). The diagnostic accuracy of the CLN for NAFLD (AUROC 0.857, 95% CI 0.852-0.863) was significantly superior to that of the FLI (AUROC 0.849, 95% CI 0.843-0.855), the VAI (AUROC 0.752, 95% CI 0.745-0.760), the HSI (AUROC 0.828, 95% CI 0.822-0.834), and the TyG index (AUROC 0.774, 95% CI 0.767-0.781) (all p < 0.001). DCA confirmed the clinical utility of the CLN. CONCLUSIONS: This physical examination and laboratory test-based, nonimage-assisted novel nomogram has better performance in predicting NAFLD than the FLI, the VAI, the HSI and the TyG index alone. This model can be used as a quick screening tool to assess NAFLD in the general population.
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Pruebas de Función Hepática , Hígado , Nomogramas , Enfermedad del Hígado Graso no Alcohólico , Ultrasonografía , Biopsia/métodos , Biopsia/estadística & datos numéricos , Glucemia/análisis , China/epidemiología , Estudios Transversales , Diagnóstico Precoz , Femenino , Humanos , Grasa Intraabdominal , Hígado/diagnóstico por imagen , Hígado/patología , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Reproducibilidad de los Resultados , Estudios Retrospectivos , Triglicéridos/sangre , Ultrasonografía/métodos , Ultrasonografía/estadística & datos numéricosRESUMEN
BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a primary cause of organ dysfunction occurring during liver resection surgery and transplantation. Galectin-1, an endogenous lectin expressed on lymphoid organs, plays an important role in governing innate and adaptive immunity. This study was designed to determine the therapeutic role of galectin-1 and underlying mechanism in hepatic IRI. METHODS: Male C57BL/6 mice were subjected to 90â¯min of partial hepatic ischemia followed by reperfusion with or without treatment with recombinant galectin-1 (rGal-1) or neutralizing anti-IL-10 antibody. Mice were sacrificed at 6 and 24â¯h following reperfusion. Liver damage related enzymes were determined and cytokines/chemokines were measured by qPCR and ELISA. RESULTS: Administration of rGal-1 significantly attenuated hepatic IRI, including a remarkable reduction in serum ALT/AST levels and an improved liver histology score compared to controls. rGal-1 treatment reduced TUNEL positive apoptotic hepatocytes, attenuated proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-12, IFN-γ, IL-17) and chemokines (CXCL-1, CXCL-10) levels, but upregulated IL-10 expression, compared with controls. In addition, rGal-1 increased the production of IL-10 in hepatic macrophages in vivo and in vitro. Blockade of IL-10 using neutralizing anti-IL-10 antibody reversed the protection of galectin-1 in hepatic IRI in mice. CONCLUSION: These data suggest that galectin-1 may attenuate hepatic IRI via an IL-10-dependent mechanism, which is a promising therapeutic target.
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Galectina 1/metabolismo , Hepatopatías/metabolismo , Hígado/metabolismo , Daño por Reperfusión/metabolismo , Animales , Citocinas/metabolismo , Femenino , Hepatocitos/metabolismo , Inflamación/metabolismo , Interleucina-10/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BLRESUMEN
CD8+CD28-T cells (CD8Ts) exert immunosuppressive effects in various autoimmune diseases. The current study was designed to investigate the role of defects in CD8Ts in liver transplantation (LT). The proportion of CD8Ts in peripheral blood was determined by flow cytometry. The mean proportion of CD8Ts was 23.39% in recipients with stable graft function and 16.64% in those with graft dysfunction following LT compared with 19.86% in the healthy cohort. After receiving enhanced immunosuppressive therapy, patients in the rejection group who achieved recovery of graft function showed an increase in the proportion of CD8Ts (from 17.39% to 25.55%), but those in the group with refractory graft dysfunction showed no significant change (12.49% to 10.30%). Furthermore, in the first year after LT, recipients longer removed in time from the LT date exhibited a higher proportion of CD8Ts. Patients benefited most from tacrolimus concentrations of 5-10 ng/ml in the first year after LT and 0-5 ng/ml thereafter. Moreover, the change in the proportion of CD8Ts (ΔCD8Ts) was significantly higher in recipients with stable graft function than in those with graft dysfunction. These results suggest that a high frequency of CD8Ts prevents rejection and contributes to reduce immunosuppressant dosage and even induces tolerance.
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Antígenos CD28 , Linfocitos T CD8-positivos , Rechazo de Injerto/inmunología , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Adulto , Linfocitos T CD4-Positivos , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
One of the most famous Chinese vinegars, Shanxi aged vinegar (SAV), is produced with solid-state fermentation technology. Total antioxidant activity (TAC) is a special property for SAV. In this study, we investigate correlations between total antioxidant activity (TAC) and total polyphenol (TP) and total flavonoid (TF) contents of SAV, especially during the brewing process. For SAV, TAC, TP, and TF increased with the increase of aging time. The correlation coefficients between TAC and TP were 0.869 and 0.934, respectively, when analyzed with the method of ABTS and FRAP. They were 0.828 (ABTS) and 0.877 (FRAP) between the TAC and TF. In smoking pei stage that is a special technique for SAV different from other Chinese cereal vinegars, TAC increased by 120% (ABTS) and 111% (FRAP) mainly due to the increase of TP (89%) and TF (75%), which was more obvious than that during alcohol fermentation and acetic acid fermentation stages. Moreover, variation during brewing process of 8 main polyphenol compounds that were proved responsible for the TAC of SAV was analyzed. In addition to catechins and chlorogenic acid, gallic acid serves as one of the principal antioxidant ingredients in SAV. PRACTICAL APPLICATION: Total antioxidant activity (TAC) of Shanxi aged vinegar (SAV), which is highly correlated with total polyphenol and total flavonoid, increased with aging time, however, there is a little loss of total antioxidant after more than 8 y. During the brewing process smoking pei technique is important for enhancing the TAC of SAV suggesting critical controlled and thoroughly study of smoking pei stage are needed to improve the quality of SAV.
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Ácido Acético/análisis , Antioxidantes/análisis , Flavonoides/análisis , Polifenoles/análisis , Catequina/análisis , China , FermentaciónRESUMEN
BACKGROUND: Ischemia-reperfusion injury after liver transplantation (LT) impairs graft function and affects prognosis of recipients. Isoglycyrrhizinate magnesium (Iso) is a hepatoprotective drug usually used after liver injury. In this study, we intended to explore whether Iso alone have protective effect after ischemia-reperfusion injury in a rat model of liver transplantation. We also aimed to study whether Iso could enhance the hepatoprotective effect of FK506 (tacrolimus) and underlying mechanism. METHODS: Rats after LT were treated with different concentration of FK506 with or without, Iso or lower-dose FK506 plus Iso. Alanine transaminase, aspartate transaminase, and albumin level were measured after 48 hours, 72 hours, and 7 days. A cell ischemic/reperfusion model was established to further study the mechanism of hepatoprotective effect of FK506 and Iso. RESULTS: Iso treatment alone had no effect on liver grafts after LT, but lower-dose FK506 + Iso was better for maintenance of liver function than lower-dose FK506 alone at 48 hours, 72 hours, and 7 days after LT. In terms of mechanism, FK506 induced autophagy which resulted in significantly reduced apoptosis and maintained proliferative potential. However, autophagy induced by FK506 also lead to high-mobility group box (HMGB) 1 release from nuclei, resulting in hepatocyte injury through triggering of p38 phosphorylation and chemokine release. Iso effectively inhibited the release of HMGB1 and downstream inflammatory cytokines. CONCLUSIONS: Iso could inhibit release of HMGB1 by FK506 and enhance the hepatoprotective effect of FK506 in rat LT. Combining Iso with FK506 would be promising for the patients after LT.