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1.
Biomed Pharmacother ; 165: 115040, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37364479

RESUMO

Colorectal cancer (CRC) is one of highly prevalent cancer. Immunotherapy with immune checkpoint inhibitors (ICIs) has dramatically changed the landscape of treatment for many advanced cancers, but CRC still exhibits suboptimal response to immunotherapy. The gut microbiota can affect both anti-tumor and pro-tumor immune responses, and further modulate the efficacy of cancer immunotherapy, particularly in the context of therapy with ICIs. Therefore, a deeper understanding of how the gut microbiota modulates immune responses is crucial to improve the outcomes of CRC patients receiving immunotherapy and to overcome resistance in nonresponders. The present review aims to describe the relationship between the gut microbiota, CRC, and antitumor immune responses, with a particular focus on key studies and recent findings on the effect of the gut microbiota on the antitumor immune activity. We also discuss the potential mechanisms by which the gut microbiota influences host antitumor immune responses as well as the prospective role of intestinal flora in CRC treatment. Furthermore, the therapeutic potential and limitations of different modulation strategies for the gut microbiota are also discussed. These insights may facilitate to better comprehend the interplay between the gut microbiota and the antitumor immune responses of CRC patients and provide new research pathways to enhance immunotherapy efficacy and expand the patient population that could be benefited by immunotherapy.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Imunoterapia , Inibidores de Checkpoint Imunológico , Neoplasias Colorretais/terapia
2.
Int Immunopharmacol ; 119: 110237, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37121112

RESUMO

BACKGROUND: Impaired intestinal barrier and immune dysfunction promote the development of type 2 diabetes (T2D). Group 3 innate lymphoid cells (ILC3s), which are enriched in the intestinal lamina propria, are key for intestinal barrier integrity. However, there is a paucity of data on circulating ILC3s in patients with T2D. PURPOSE: To examine the characteristics of ILC3s in patients with T2D and identify the relationship between ILC3s and clinical indicators of T2D. METHODS: Fifty-nine patients with T2D and thirty controls were enrolled in this retrospective study. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry and plasma cytokine levels were measured by enzyme-linked immunosorbent assays. RESULTS: The proportion of circulating ILC3s in the T2D group was significantly lower than that in controls and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, the proportion of circulating integrin α4+ ILC3s was also significantly lower in the T2D group and showed a negative correlation with fasting glucose and glycated hemoglobin and a positive correlation with GM-CSF. Moreover, the level of circulating integrin α4+ ILC3s showed a positive correlation with the proportion of circulating dendritic cells (DCs), which was also decreased in patients with T2D and positively associated with GM-CSF. CONCLUSION: ILC3s, especially integrin α4+ ILC3s, were decreased in patients with T2D and showed a negative correlation with disease severity. These cell subsets may delay the progression of T2D by promoting DC differentiation via the secretion of GM-CSF.


Assuntos
Diabetes Mellitus Tipo 2 , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Linfócitos , Humanos , Hemoglobinas Glicadas , Imunidade Inata , Integrina alfa4 , Leucócitos Mononucleares , Estudos Retrospectivos
3.
Front Immunol ; 14: 1323115, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38173726

RESUMO

Background: Cancer-associated fibroblasts (CAFs) represent the predominant stromal component within the tumour microenvironment (TME), exhibiting considerable heterogeneity and plasticity that significantly impact immune response and metabolic reprogramming within the TME, thereby influencing tumour progression. Consequently, investigating CAFs is of utmost importance. The objective of this study is to employ bibliometric analysis in order to evaluate the current state of research on CAFs and predict future areas of research and emerging trends. Methods: Conduct a comprehensive search for scholarly publications within the Web of Science Core Collection database, encompassing the time period from January 1, 2001, to December 31, 2022. Apply VOSviewer, CiteSpace, R software and Microsoft Excel for bibliometric analysis and visualisation. Results: This study involved a comprehensive analysis of 5,925 publications authored by 33,628 individuals affiliated with 4,978 institutions across 79 countries/regions. These publications were published in 908 journals, covering 14,495 keywords and 203,947 references. Notably, there was a significant increase in articles published between 2019 and 2022. China had the highest count of articles, while the United States emerged as the most frequently cited country. The primary research institutions in this field were Shanghai Jiao Tong University, Harvard University, and the University of Texas MD Anderson Cancer Center. Sotgia, Federica and Lisanti, Michael P from the University of Manchester, and Martinet, Wim from the University of Antwerp were the most prolific and highly cited authors. The journal Cancers had the highest number of publications, while Cancer Research was the most frequently cited journal. Molecular, biology, immunology, medicine and genetics were the main research disciplines in the field of CAFs. Key directions in CAFs research encompassed the study of transforming growth factor-ß, Fibroblast Activation Protein, breast cancer, as well as growth and metastasis. The findings from the analysis of keyword co-occurrence and literature co-citation have revealed several emerging hotspots and trends within the field of CAFs. These include STAT3, multidrug resistance, pancreatic ductal adenocarcinoma, pan-cancer analysis, preclinical evaluation, ionizing radiation, and gold nanoparticles. Conclusion: Targeting CAFs is anticipated to be a novel and effective strategy for cancer treatment. This study provides a comprehensive overview of the existing research on CAFs from 2001 to 2022, utilizing bibliometric analysis. The study identified the prominent areas of investigation and anticipated future research directions, with the aim of providing valuable insights and recommendations for future studies in the field of CAFs.


Assuntos
Fibroblastos Associados a Câncer , Nanopartículas Metálicas , Neoplasias Pancreáticas , Humanos , China , Ouro , Bibliometria , Microambiente Tumoral
4.
J Tradit Chin Med ; 41(3): 381-389, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34114395

RESUMO

OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Triterpenos Pentacíclicos , Sirolimo , Serina-Treonina Quinases TOR/genética
5.
Cell Mol Biol (Noisy-le-grand) ; 65(3): 109-113, 2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30942163

RESUMO

With high incidence and mortality, gastric cancer seriously threatened human's life. It is arduous and necessary to investigate its pathogenesis and dig effective drugs. In this study, we explored the role of 6-Gingerol (GI), a natural active ingredient, in treating gastric cancer cells. MTT assay and colony formation assay were utilized to confirmed that GI can control the proliferation of gastric cancer cells, which is time and concentration-dependent to some extent. The Annexin V-FITC/PI staining results by flow cytometry reveal that GI induces the apoptosis of gastric cancer cells. And a study on further pathways by western blot shows that GI brings about cell apoptosis by inhibiting the activation of STAT3. GI therefore may be a good candidate for treating gastric cancer.

6.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(9): 1112-1118, 2016 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30645853

RESUMO

Objective To observe the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting a- gainst hepatoma by detecting tumor miRNAs expression profiles in H22tumor-bearing mice. Methods To- tally 50 H22tumor-bearing mice were randomly divided into the model group, the low dose XJR group, the medium dose XJR group, the high dose XJR group, the Cisplatin group, 10 in each group. Different expressions of tumor tissues in H22 tumor-bearing mice under light microscope were detected using histopathological technique. Differentially expressed miRNAs of tumor tissue in H22tumor-bearing mice were detected by using miRNA chip technique. Differentially expressed miRNAs associated with antitumor mechanism of XJR were found out by statistical analysis. Results Histopathological results showed that reduced pathologic mitosis, smaller cancer cells, and obviously enhanced anti-cancer effect along with increased XJP dose. Results of miRNA chip analyses indicated XJP could significantly up-regulate the ex- pressions of miRNAs, such as miR-1298-5p, miR-874-3p, miR-721, miR-298-5p, miR-551b-5p, miR-346- 5p, miR-105, and so on. It could also down-regulate the expressions of miR-24-3p, miR-3963, miR-127- 3p, miR-434-5p, miR-1187, miR-468-3p, miR-221-5p, and miR-6695-5p. Conclusion XJP could fight a- gainst tumor possibly by regulating expressions of multiple miRNAs.


Assuntos
Medicamentos de Ervas Chinesas , MicroRNAs , Análise de Sequência com Séries de Oligonucleotídeos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos , MicroRNAs/metabolismo
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(1): 119-24, 2013 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-23596801

RESUMO

The integration of Chinese medicine (CM) and Western medicine (WM) is the only way for the development of medicine, and it is the best form for unifying systems theory and reductionism. In this paper, systems biology and its application in medical research were discussed. The authors put forward that systems biology may possibly interpret the scientific connotation of the complex theoretic systems of CM, which will make WM to well know the human body and disease. We hold that systems biology is a bridge of integrated CM and WM.


Assuntos
Medicina Integrativa , Biologia de Sistemas , Medicina Tradicional Chinesa
8.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(7): 990-3, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-23019963

RESUMO

Pathogenesis is the core of the theoretical system in Chinese medicine (CM). Pathogenesis research is the breakthrough of the innovation and development of CM theories. Proteomics and CM pathogenesis were amazingly similar in aspects of integrity, dynamics, space, and complexity. It is of great significance using proteomics methods in studying CM pathogenesis essence and evolution laws, exploring the mechanisms of classical prescriptions or recipes with therapeutic efficacy, and promoting the modernization of CM.


Assuntos
Medicina Tradicional Chinesa , Proteômica , Pesquisa
9.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 32(6): 831-5, 2012 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-22978115

RESUMO

Metabonomics, a newly developing subject secondary to genomics, transcriptomics, and proteomics, is an important constituent part of systems biology. It is believed to be the final direction of the systems biology. It can be directly applied to understand the physiological and biochemical states by its "metabolome profile" as a whole. Therefore, it can provide a huge amount of information different from those originating from other "omics". In the modernization of Chinese materia medica research, the application of metabonomics methods and technologies has a broad potential for future development. Especially it is of important theoretical significance and application value in holistic efficacies evaluation, active ingredients studies, and safety research of Chinese materia medica.


Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Materia Medica/efeitos adversos , Materia Medica/farmacologia , Proteômica
10.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 30(8): 884-8, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21038663

RESUMO

Many Chinese drugs (CHD) have showed their significant effects of integral immune-regulation, and lots of researches have conducted in recent years for exploring their mechanism from different levels, like cytological, molecular and genetic levels. In this paper, the relation between immune-regulation of CHD and Toll-like receptors/nuclear factor-kappaB (TLRs/NF-kappaB) signaling pathway was introduced in brief based upon the achievements of previous researches. It was pointed out that the two are closely related, to explore mechanism of CHD in this way is meaningful not only for further deepening the theoretical understanding of CHD's pharmacological immunoregulation, but also be practically facilitate for enhancing therapeutic efficacy of CHD and developing new CHD.


Assuntos
Adjuvantes Imunológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , NF-kappa B/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/imunologia , Humanos
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