RESUMO
Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs' maturation and migration, as well as CD4+ and CD8+ T cells' proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF-κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.
Assuntos
Células Dendríticas/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Polissacarídeos/farmacologia , Undaria , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/metabolismo , Fatores Imunológicos/química , Subunidade p40 da Interleucina-12/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Peso Molecular , NF-kappa B/metabolismo , Nova Zelândia , Polissacarídeos/química , Baço/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.
Assuntos
Aterosclerose/prevenção & controle , Cafeína/farmacologia , Catequina/farmacologia , Animais , Aorta/efeitos dos fármacos , Aterosclerose/sangue , Aterosclerose/genética , Aterosclerose/metabolismo , Peso Corporal/efeitos dos fármacos , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Receptores Depuradores Classe E/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Acute-on-chronic liver failure (ACLF) implies high short-term mortality rates and usually requires intensive care unit (ICU) admission. Proper prognosis for these patients is crucial for early referral for liver transplantation. The superiority of CLIF-C ACLF score in Asian patients with ACLF admitted to an ICU remains inconclusive when compared to other scoring systems. The purpose of the study is (i) to compare the predictive performance of original MELD, MELD-Lactate, CLIF-C ACLF, CLIF-C ACLF-Lactate, and APACHE-II scores for short-term mortality assessment. (ii) to build and validate a novel scoring system and to compare its predictive performance to that of the original five scores. Two hundred sixty-five consecutive cirrhotic patients with ACLF who were admitted to our ICU were enrolled. The prognostic values for mortality were assessed by ROC analysis. A novel model was developed and internally validated using fivefold cross-validation. Alcohol abuse was identified as the primary etiology of cirrhosis. The AUROC of the five prognostic scores were not significantly superior to each other in predicting 1-month and 3-month mortality. The newly developed prognostic model, incorporating age, alveolar-arterial gradient (A-a gradient), BUN, total bilirubin level, INR, and HE grades, exhibited significantly improved performance in predicting 1-month and 3-month mortality with AUROC of 0.863 and 0.829, respectively, as compared to the original five prognostic scores. The novel ACLF model seems to be superior to the original five scores in predicting short-term mortality in ACLF patients admitted to an ICU. Further rigorous validation is required.
Assuntos
Insuficiência Hepática Crônica Agudizada , Unidades de Terapia Intensiva , Humanos , Insuficiência Hepática Crônica Agudizada/mortalidade , Masculino , Feminino , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Curva ROC , Índice de Gravidade de Doença , Valor Preditivo dos Testes , APACHERESUMO
To maintain or adjust posture under the challenges of gravity and increased self-weight, or the effects of light, snow, and slope, plants have the ability to develop a special type of tissue called reaction tissue. The formation of reaction tissue is a result of plant evolution and adaptation. The identification and study of plant reaction tissue are of great significance for understanding the systematics and evolution of plants, the processing and utilization of plant-based materials, and the exploration of new biomimetic materials and biological templates. Trees' reaction tissues have been studied for many years, and recently, many new findings regarding these tissues have been reported. However, reaction tissue requires further detailed exploration, particularly due to their complex and diverse nature. Moreover, the reaction tissues in gymnosperms, vines, herbs, etc., which display unique biomechanical behavior, have also garnered the attention of research. After summarizing the existing literature, this paper provides an outline of the reaction tissues in woody plants and non-woody plants, and lays emphasis on alternations in the cell wall structure of the xylem in softwood and hardwood. The purpose of this paper is to provide a reference for the further exploration and study of reaction tissues with great diversity.
RESUMO
We previously demonstrated that Pleurotus ferulae polysaccharide (PFPS) promoted dendritic cell (DC) maturation through the TLR4 signaling pathway. To improve PFPS activity and bioavailability, gold nanoparticles with PFPS (PFPS-Au NPs) were synthesized. Of note, although the polysaccharide content of PFPS-Au NPs was only one tenth of PFPS, PFPS-Au NPs enhanced the immunostimulatory activities of PFPS in the maturation and function of dendritic cells (DCs) by TLR4 and NLRP3 signaling pathways, evidenced by stronger activation of the down-stream MAPK and NF-κB pathways and NLRP3 inflammasome pathway. More importantly, PFPS-Au NPs enhanced DC migration and murine immunity, particularly in type 1 T-helper cell responses. Moreover, the half-life of PFPS-Au NPs (2.217 ± 0.187 h) was longer than that of PFPS (1.39 ± 0.257 h) in the blood and the distribution of PFPS-Au NPs (19.8 %) in the spleen was significantly increased compared with PFPS (13.3 %), indicating the improved bioavailability in vivo. PFPS-Au NPs as an adjuvant promoted antigen-specific cellular immune responses to an HPV DC-based vaccine, which significantly inhibited the growth of TC-1 tumors in mice. All results suggest that the prepared Au NPs could enhance PFPS-immunostimulatory activity, which will pave the way for PFPS-Au NPs to be applied in clinical trials.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Pleurotus , Animais , Camundongos , Pleurotus/metabolismo , Ouro/farmacologia , Ouro/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/metabolismo , Células DendríticasRESUMO
TRAIP, as a 53 kDa E3 ubiquitin protein ligase, is involved in various cellular processes and closely related to the occurrence and development of tumors. At present, few studies on the relationship between TRAIP and triple negative breast cancer (TNBC) were reported. Bioinformatic analysis and Western blot, immunohistochemistry (IHC), CCK-8, colony formation, flow cytometry, wound healing, Transwell, and dual-luciferase reporter assays were performed, and xenograft mouse models were established to explore the role of TRAIP in TNBC. This study showed that the expression of TRAIP protein was upregulated in TNBC tissues and cell lines. Silencing of TRAIP significantly inhibited the proliferation, migration, and invasion of TNBC cells, whereas opposite results were observed in the TRAIP overexpression. In addition, TRAIP regulated cell proliferation, migration, and invasion through RB-E2F signaling and epithelial mesenchymal transformation (EMT). MiR-590-3p directly targeted the TRAIP 3'-UTR, and its expression were lower in TNBC tissues. Its mimic significantly downregulated the expression of TRAIP and subsequently suppressed cell proliferation, migration, and invasion. Rescue experiments indicated that TRAIP silencing reversed the promotion of miR-590-3p inhibitor on cell proliferation, migration, and invasion. TRAIP overexpression could also reverse the inhibition of miR-590-3p mimic on tumorigenesis. Finally, TRAIP knockdown significantly inhibited tumor growth and metastasis in animal experiments. In conclusion, TRAIP is an oncogene that influences the proliferation, migration, and invasion of TNBC cells through RB-E2F signaling and EMT. Therefore, TRAIP may be a potential therapeutic target for TNBC.
Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication in cirrhosis patients with ascites, leading to high mortality rates if not promptly treated. However, specific prediction models for SBP are lacking. AIMS: This study aimed to compare commonly used cirrhotic prediction models (CTP score, MELD, MELD-Na, iMELD, and MELD 3.0) for short-term mortality prediction and develop a novel model to improve mortality prediction. METHODS: Patients with the first episode of SBP were included. Prognostic values for mortality were assessed using AUROC analysis. A novel prediction model was developed and validated. RESULTS: In total, 327 SBP patients were analyzed, with HBV infection as the main etiologies. MELD 3.0 demonstrated the highest AUROC among the traditional models. The novel model, incorporating HRS, exhibited superior predictive accuracy for in-hospital in all patients and 3-month mortality in HBV-cirrhosis, with AUROC values of 0.827 and 0.813 respectively, surpassing 0.8. CONCLUSIONS: MELD 3.0 score outperformed the CTP score and showed a non-significant improvement compared to other MELD-based scores, while the novel SBP model demonstrated impressive accuracy. Internal validation and an HBV-related cirrhosis subgroup sensitivity analysis supported these findings, highlighting the need for a specific prognostic model for SBP and the importance of preventing HRS development to improve SBP prognosis.
RESUMO
Hepatocellular carcinoma (HCC) is associated with high mortality, especially in Asian populations where chronic HBV infection is a major cause. Accurate prediction of mortality can assist clinical decision-making. We aim to (i) compare the predicting ability of Barcelona Clinic Liver Cancer classification (BCLC) stage, neutrophil-to-lymphocyte ratio (NLR), and Albumin-Bilirubin (ALBI) score in predicting short-term mortality (one- and two-year) and (ii) develop a novel model with improved accuracy compared to the conventional models. This study enrolled 298 consecutive HCC patients from our hepatology department. The prognostic values for mortality were assessed by area under the receiver operating characteristic curve (AUROC) analysis. A novel model was established and internally validated using 5-fold cross-validation, followed by external validation in a cohort of 100 patients. The primary etiology of cirrhosis was hepatitis B virus (HBV), with 81.2% of HCC patients having preserved liver function. Significant differences were observed in hemoglobin (Hb) and serum albumin levels, which reflect patients' nutrition status, between patients who survived for one year and those who died. BCLC exhibited superior predictive accuracy compared to NLR but had borderline superiority to the ALBI score. Therefore, a novel model incorporating BCLC, Hb, and serum albumin was developed, internally and externally validated, as well as subgroup sensitivity analysis. The model exhibited significantly higher predictive accuracy for one- and two-year mortality than conventional prognostic predictors, with AUROC values of 0.841 and 0.805, respectively. The novel "BCLC-Nutrition Model", which incorporates BCLC, Hb, and serum albumin, may provide improved predictive accuracy for short-term mortality in HCC patients compared to commonly used prognostic scores. This emphasizes the importance of nutrition in the management of HCC patients.
RESUMO
In order to focus on the degree of adaptation and resilience of residents of tourist destinations to the changes caused by the COVID-19 pandemic, and to explore how the psychological resilience of residents affects their attitudes and behavioral intentions toward destination brand development, this study constructs a structural equation model guided by positive organizational behavior and uses a questionnaire method to conduct the research. The results show that (1) residents' psychological resilience has a positive effect on brand ambassador behavioral intentions; (2) residents' psychological resilience has a positive effect on resident-tourist interaction; (3) resident-tourist interaction has a positive effect on brand ambassador behavioral intentions; (4) resident-tourist interaction plays a mediating role between psychological resilience and brand ambassador behavioral intentions; and (5) cognitive reappraisal plays a moderating role between psychological resilience and resident-tourist interaction. The findings not only fill the deficiency of positive organizational behavior in tourism research, but also provide a theoretical basis for developing residents as destination brand ambassadors in the context of the COVID-19 pandemic according to destination branding. In fact, destination managers not only need to strengthen residents' behaviors to participate in destination brand development, but also should care about the psychological state and emotional events of residents who are negatively affected by the COVID-19 pandemic.
RESUMO
To explore the relationship between community support in tourist destinations and residents' psychological well-being in the post-COVID-19 pandemic period, this study adopts the questionnaire survey method and draws the following conclusions by constructing a structural equation model: (1) perceived community support is very helpful for the psychological well-being of residents, (2) psychological resilience significantly mediates the relationship between perceived community support and residents' psychological well-being, (3) the resident-tourist interaction mediates the relationship between perceived community support and residents' psychological well-being, and (4) the resident-tourist interaction and psychological resilience play an ordered chain-mediating role between perceived community support and residents' psychological well-being. These findings not only fill the gap in tourism research regarding destination-based community support studies but also provide a theoretical basis for maintaining residents' psychological well-being in a given destination in the context of the COVID-19 pandemic. To a certain extent, improving residents' well-being is helpful for promoting the healthy and sustainable development of tourism activities and realizing a "win-win" situation in which tourist destinations develop economically while promoting their residents' living standards.
Assuntos
COVID-19 , Apoio Comunitário , Humanos , COVID-19/epidemiologia , Pandemias , Inquéritos e Questionários , Nível de SaúdeRESUMO
To elucidate effects of catechins and caffeine on lipid metabolism in adipocytes and identify the mechanism of action, differentiated 3T3-L1 adipocytes were incubated in culture media containing catechins at 1, 2.5, 5, and 10 µg/mL and caffeine at 50 and 100 µg/mL, singly or in combination, for 8 days. Intracellular lipid accumulation and glycerol-3-phosphate dehydrogenase activity were strongly suppressed by catechins and caffeine combination treatment. The mRNA expression of PPARɤ, GLUT4, HSL, UCP-1, and TMEM26 were significantly increased in the combined groups. These findings suggest that the combined treatment inhibited lipid synthesis and improved lipid metabolism in adipocytes. Moreover, it was indicated that the differentiated 3T3-L1 adipocytes could be transformed from white adipocytes to beige-like adipocytes by catechins and caffeine, and accordingly that this transformation could promote calorigenic action. PRACTICAL APPLICATION: In this study, we revealed that the combined treatment of catechins and caffeine inhibited lipid synthesis and improved lipid metabolism in adipocytes. Moreover, the treatment may contribute to the transforming from white adipocytes to beige-like adipocytes, which could strongly promote calorigenic action.