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1.
Cell ; 187(9): 2288-2304.e27, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38565142

RESUMO

Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.


Assuntos
Linfócitos T CD8-Positivos , Glicoproteínas de Membrana , Taurina , Taurina/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Estresse do Retículo Endoplasmático , Fator 4 Ativador da Transcrição/metabolismo , Transdução de Sinais , Feminino , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Fator de Transcrição STAT3/metabolismo
2.
Aging (Albany NY) ; 15(23): 14445-14456, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38095633

RESUMO

Aims to investigate the relationship between nutritional biochemical indexes and hospitalization outcomes of COVID-19 patients, 132 continuous patients with COVID-19 from December 2022 to January 2023 in Lishui hospital were retrospectively analyzed, and the nutritional biochemical indexes in peripheral blood, such as total protein, albumin, calcium, phosphorus, and magnesium, were detected. Meanwhile, the levels of several cytokines and PBMC subtypes (CD4, CD3, CD8, NK and B cells) were detected too. The Spearman correlation analysis, one-way ANOVA and multivariate logit regression were conducted. Results suggested that the levels of total protein and albumin were significantly decreased in patients with poor outcomes, and the levels of calcium, phosphorus, and magnesium were significantly correlated with hospitalization outcomes. COVID-19 patients with diabetes had higher levels of IL-6 and IFN-γ than those patients without diabetes. The levels of IL-2, IFN-γ, IL-6 and Il-10 in the dead patients were significantly higher than those in the recovery and worse patients. Total protein and albumin were significantly positively correlated with levels of NK and B, CD4, CD8, CD3 lymphocytes. The levels of CD4, CD8 and CD3 lymphocytes were significantly decreased in dead patients than other patients. Multivariate logit regression analysis suggests that lymphocyte number, albumin and IL-6 are independent risk factors to evaluate the hospitalization outcome. In summary, nutritional biochemical indexes were significantly corelated with cytokines and PBMC subsets, and had an impact on the severity of COVID-19 patients. Improvement of low protein malnutrition is broad-spectrum and basic strategy to improve the hospitalization outcome of COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus , Humanos , Estudos Retrospectivos , Leucócitos Mononucleares , Cálcio , Interleucina-6 , Magnésio , Citocinas , Hospitalização , Albuminas , Fósforo
3.
Zhongguo Zhong Yao Za Zhi ; 34(21): 2751-3, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20209907

RESUMO

OBJECTIVE: To establish a method for simultaneous determination of alpha-pinene, beta-pinene, eucalyptol and alpha-terpineolin in essential oil from Alpinia officinarum by GC. METHOD: The essential oil was extracted by steam distillation. The determination was carried on with capillary column DB-1 (0.25 mm x 30 m, 0.25 microm). Temperature programs: 50 degrees C (hold 2 min) programmed to 130 degrees C (hold 3 min) at 8 degrees C x min(-1). The detector was FID. Inlet temperature was 230 degrees C. The detector temperature was 250 degrees C. Carrying gas was nitrogen (1.2 mL x min(-1)), split injection was conducted with split ratio of 10:1. Injection volumn was 1 microL. RESULT: The linear ranges of alpha-pinene, beta-pinene, eucalyptol and alpha-terpineolin were 0.009-0.090 (r = 0.999 8), 0.009-0.091 (r = 0.999 8), 0.060 4-0.604 (r = 0.999 7) and 0.037 4-0.374 g x L(-1) (r = 0.999 5), respectively. The average recoveries (n = 9) of a-pinene, beta-pinene, eucalyptol and alpha-terpineolin were 96.2% (RSD 0.8%) and 96.7% (RSD 1.1%), 98.7% (RSD 1.1%) and 96.7% (RSD 2.2%), respectively. CONCLUSION: The developed method is simple, quick and accurate, which is helpful to control the quality of A. officinarum.


Assuntos
Alpinia/química , Compostos Bicíclicos com Pontes/análise , Cromatografia Gasosa/métodos , Cicloexanóis/análise , Medicamentos de Ervas Chinesas/análise , Monoterpenos/análise , Terpenos/análise , Monoterpenos Bicíclicos , Monoterpenos Cicloexânicos , Eucaliptol , Óleos Voláteis/análise
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