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Bidirectional regulation of the cyclic guanosine monophosphateadenosine monophosphate synthase-stimulator of interferon gene pathway and its impact on hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 246-261页

作者： Ai-Yu Nie Zhong-Hui Xiao Jia-Li Deng Na Li Li-Yuan Hao Sheng-Hao Li Xiao-Yu Hu College of Clinical Medicine Chengdu University of Traditional Chinese MedicineChengdu 610075Sichuan ProvinceChina department of infection Affiliated Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)ranks as the fourth leading cause of cancerrelated deaths in China,and the treatment options are *** cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)activates the stimulator of interferon gene(STING)signaling pathway as a crucial immune response pathway in the cytoplasm,which detects cytoplasmic DNA to regulate innate and adaptive immune *** a potential therapeutic target,cGASSTING pathway markedly inhibits tumor cell proliferation and metastasis,with its activation being particularly relevant in ***,prolonged pathway activation may lead to an immunosuppressive tumor microenvironment,which fostering the invasion or metastasis of liver tumor *** To investigate the dual-regulation mechanism of cGAS-STING in *** This review was conducted according to the PRISMA *** study conducted a comprehensive search for articles related to HCC on PubMed and Web of Science *** rigorous screening and meticulous analysis of the retrieved literature,the research aimed to summarize and elucidate the impact of the cGAS-STING pathway on HCC *** All authors collaboratively selected studies for inclusion,extracted data,and the initial search of online databases yielded 1445 *** removing duplicates,remaining 964 records were ***,55 articles met the inclusion criteria and were included in this *** Acute inflammation can have a few inhibitory effects on cancer,while chronic inflammation generally promotes its *** cGAS-STING pathway activation will result in a suppressive tumor microenvironment.

关键词： Hepatocellular carcinoma Cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene Interferon genes The metastasis of a tumor Immunology

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Effect of dietary fibre on the gastrointestinal microbiota during critical illness:A scoping review

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World Journal of Critical Care Medicine 2025年第1期14卷 49-59页

作者： Angajendra N Ghosh Calum J Walsh Matthew J Maiden Tim P Stinear Adam M Deane department of Intensive Care The Northern HospitalEpping 3076VictoriaAustralia department of Microbiology and Immunology The Peter Doherty Institute for Infection and ImmunityMelbourne 3052VictoriaAustralia department of Intensive Care The Royal Melbourne HospitalThe University of MelbourneParkville 3050VictoriaAustralia department of Intensive Care Medicine The Royal Melbourne HospitalParkville 3050VictoriaAustralia

The systemic effects of gastrointestinal(GI)microbiota in health and during chronic diseases is increasingly *** strategies to modulate the GI microbiota during chronic diseases have demonstrated *** changes in dietary intake can rapidly change the GI microbiota,the impact of dietary changes during acute critical illness on the microbiota remain *** fibre is metabolised by carbohydrate-active enzymes and,in health,can alter GI *** aim of this scoping review was to describe the effects of dietary fibre supplementation in health and disease states,specifically during critical *** controlled trials and prospective cohort studies that include adults(>18 years age)and reported changes to GI microbiota as one of the study outcomes using non-culture methods,were *** show dietary fibres have an impact on faecal microbiota in health and *** fibre,inulin,has a marked and specific effect on increasing the abundance of faecal *** chain fatty acids produced by Bifidobacteria have been shown to be beneficial in other patient *** few trials have evaluated the effect of dietary fibre on the GI microbiota during critical *** research is necessary to establish optimal fibre type,doses,duration of intervention in critical illness.

关键词： Gastrointestinal microbiota Dietary fibre Health Critical illness Short chain fatty acids

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Immunological roulette: Luck or something more? Considering the connections between host and environment in TB

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Cellular & Molecular Immunology 2018年第3期15卷 226-232页

作者： John E Pearl Mrinal Das Andrea M Cooper department of infection immunity and inflammation Leicester Tuberculosis Research Group(LTBRG)University of LeicesterUniversity RoadLeicesterLE17RHUK

Accurate prediction of which patient will progress from a sub-clinical Mycobacterium tuberculosis infection to active tuberculosis represents an elusive,yet critical,clinical research *** the individual perspective,progression can be considered to be the product of a series of unfortunate events or even a run of bad ***,we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated *** infected individuals who progress to disease have apparently good immune responses,but these responses are,at times,compromised by either local or systemic environmental *** disease promoting processes,such as tissue-damaging granulomata,usually manifest in the lung,but illness is *** apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological *** discuss aspects of the host environment that can impact expression of immunity,including the microbiome,glucocorticoid-mediated regulation,catecholamines and interaction between the gut,liver and *** suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious,but rather reflect the impact of these subtle relationships with our environment and microbiota.

关键词： gut-liver-lung axis microbiome tuberculosis

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Repeatability of two-dimensional chemical shift imaging multivoxel proton magnetic resonance spectroscopy for measuring human cerebral choline-containing compounds

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World Journal of Psychiatry 2018年第1期8卷 20-26页

作者： Basant K Puri Mary Egan Fintan Wallis Philip Jakeman department of Medicine Hammersmith HospitalImperial College London department of Radiology University Hospital Limerick Centre for Interventions in infection Inflammation and Immunity University of Limerick

AIM To investigate the repeatability of proton magnetic resonance spectroscopy in the in vivo measurement of human cerebral levels of choline-containing compounds(Cho).METHODS Two consecutive scans were carried out in six healthy resting subjects at a magnetic field strength of 1.5 T. On each occasion, neurospectroscopy data were collected from 64 voxels using the same 2 D chemical shift imaging(CSI) sequence. The data were analyzed in the same way, using the same software, to obtain the values for each voxel of the ratio of Cho to creatine. The Wilcoxon related-samples signed-rank test, coefficient of variation(CV), repeatability coefficient(RC), and intraclass correlation coefficient(ICC) were used to assess the repeatability. RESULTS The CV ranged from 2.75% to 33.99%, while the minimum RC was 5.68%. There was excellent reproducibility, as judged by significant ICC values, in 26 voxels. Just three voxels showed significant differences according to the Wilcoxon related-samples signed-rank test. CONCLUSION It is therefore concluded that when CSI multivoxel proton neurospectroscopy is used to measure cerebral choline-containing compounds at 1.5 T, the reproducibility is highly acceptable.

关键词： Cerebral metabolites Chemical shift imaging Choline Neurospectroscopy Neuropsychiatric disorders

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Laparoscopic hepatectomy using indocyanine green attenuates postoperative inflammatory response for hepatocellular carcinoma:A propensity score matching analysis

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World Journal of Gastrointestinal Surgery 2025年第1期17卷 193-202页

作者： Wei-Xun Wu Ming-Bin Huang Mei-Xia Wang Li-Hua Chen Bo Hu Zhen-Bin Ding department of Liver Surgery Zhongshan Hospital(Xiamen)Fudan UniversityXiamen 361006Fujian ProvinceChina department of infection Management Zhongshan Hospital(Xiamen)Fudan UniversityXiamen 361015Fujian ProvinceChina department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China Key Laboratory of Carcinogenesis and Cancer Invasion(Ministry of Education) Fudan UniversityShanghai 200032China

BACKGROUND Improving the intraoperative and postoperative performance of laparoscopic hepatectomy was quite a challenge for liver *** To determine the benefits of indocyanine green(ICG)fluorescence imaging in patients with hepatocellular carcinoma(HCC)who underwent laparoscopic hepatectomy during and after *** We retrospectively collected the clinicopathological data of 107 patients who successfully underwent laparoscopic hepatectomy at Zhongshan Hospital(Xiamen),Fudan University from June 2022 to June *** using the ICG fluorescence imaging technique,we divided them into the ICG and non-ICG *** eliminate statistical bias,a 1:1 propensity score matching analysis was *** comparison of perioperative outcomes,including inflammationrelated markers and progression-free survival,was analyzed *** Intraoperatively,the ICG group exhibited lower blood loss,a shorter surgical time,lower hepatic inflow occlusion(HIO)frequency,and a shorter total HIO ***,the participation of ICG resulted in a shorter duration of hospitalization(6.5 vs 7.6 days,P=0.03)and postoperative inflammatory response attenuation(lower neutrophil-lymphocyte ratio on the first day after surgery and platelet-lymphocyte ratio on the third day,Pinflammation-related markers were lower in the ICG *** rates of postoperative complications and the survival analyses,including progression-free and overall survivals showed no significant difference between the *** The involvement of ICG fluorescence imaging may lead to improved perioperative outcomes,especially postoperative inflammatory response attenuation,and ultimately improve HCC patients’recovery after surgery.

关键词： Hepatocellular carcinoma Laparoscopic hepatectomy Indocyanine green fluorescence Postoperative inflammatory response attenuation Propensity score matching analysis

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Intestine-derived fibroblast growth factor 19 alleviates lipopolysaccharide-induced liver injury by regulating bile acid homeostasis and directly improving oxidative stress

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重症医学（英文） 2025年第1期5卷 79-88页

作者： Tang Xiaomeng Ning Jingjing Zhao Yilin Feng Shuyun Shao Lujing Liu Tiantian Miao Huijie Zhang Yucai Wang Chunxia department of Critical Care Medicine Shanghai Children’s Hospital School of Medicine Shanghai Jiao Tong University Shanghai China Laboratory of Critical Care Translational Medicine Institute of Pediatric Infection Immunity and Critical Care Medicine Shanghai Children’s Hospital Shanghai Jiao Tong University School of Medicine Shanghai China Institute of Pediatric Critical Care Shanghai Jiao Tong University Shanghai China

Background::Cholestasis plays a critical role in sepsis-associated liver injury (SALI). Intestine-derived fibroblast growth factor 19 (FGF19) is a key regulator for bile acid homeostasis. However, the roles and underlying mechanisms of FGF19 in SALI are still ***::We conducted a case-control study that included 58 pediatric patients aged from 1 month to 14-years-old diagnosed with sepsis at Shanghai Children’s Hospital from January to December 2018 and 30 healthy individuals. The serum FGF19 levels of these patients with sepsis were analyzed and compared with those of healthy controls. Recombinant human FGF19 was intravenously injected in mice once a day for 7 days at a dose of 0.1 mg/kg body weight before lipopolysaccharide (LPS) treatment. Liver bile acid profiles and the gene expression involved in bile acid homeostasis were investigated in the mice groups. Metabolomic data were further integrated and analyzed using Ingenuity Pathways Analysis (IPA) software. In the in vitro analysis using HepG2 cells, the influence of FGF19 pretreatment on reactive oxygen species (ROS) production and mitochondrial dysfunction was analyzed. Compound C (CC), an inhibitor of AMP-activated protein kinase (AMPK) activation, was used to confirm the roles of AMPK activation in FGF19-mediated hepatoprotective effects. Results::Serum FGF19 levels were significantly lower in children with sepsis than in healthy controls (115 pg/mL vs. 79 pg/mL, P=0.03). Pre-administration of recombinant human FGF19 alleviated LPS-induced acute liver injury (ALI) and improved LPS-induced cholestasis in mice. Moreover, FGF19 directly reversed LPS-induced intracellular ROS generation and LPS-decreased mitochondrial membrane potential in vitro and in vivo, resulting in hepatoprotection against LPS-induced apoptosis. More importantly, the inhibition of AMPK activity partially blocked the protective effects of FGF19 against LPS-induced oxidative stress and mit

关键词： FGF19 Bile acid Oxidative stress Mitochondria dysfunction Acute liver injury Sepsis

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Myeloid derived suppressor cells in breast cancer:A novel therapeutic target?

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World Journal of Immunology 2016年第3期6卷 119-125页

作者： Rebekah M Weston Cordula M Stover department of infection Immunity and Inflammation College of Medicine Biological Sciences and Psychology University of Leicester department of infection Immunity and Inflammation University of Leicester

The relationship of the immune system and tumour cells is complex; although recognised that the immune system can protect the host against tumour development, the immune system also facilitates tumour progression through immune suppression. Pro-inflammatory mediators associated with chronic inflammation are responsible for the expansion and activation of myeloid derived suppressor cells(MDSCs); a heterogeneous group of cells that originates from myeloid progenitor cells but does not complete the final stages of differentiation. A causal relationship between chronic inflammation and tumour progression relies on the accumulation and maintenance of MDSCs as its linchpin; responsible for immunosuppression through the down-regulation of antitumour responses. MDSCs cause immunosuppression through a number of mechanisms; inhibiting the proliferation of CD4^+ and CD8^+ T cells, blocking natural killer cell activation and limiting dendritic cell maturation and function. As well as using various mechanisms to inhibit adaptive and immune responses, MDSCs also have non-immunological functions that aid tumour spread; including directly promoting tumour proliferation and metastasis by having an important role in tumour angiogenesis, secretion of matrix metalloproteinases and induction of epithelial-mesenchymal transition. Breast cancer is the most common cancer among women in the United Kingdom with 44540 new cases of invasive carcinoma in 2013 and results in the second highest cancer mortality rate in women, with 11600 deaths in 2012. Considering this, the need for novel therapeutic interventions is higher than ever. This review summarises the rationale for the targeting of MDSCs in breast cancer as a realistic avenue to increase survival from breast cancer.

关键词： Breast cancer Immune cells Treatment Suppression Survival

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Identification of a CD4 T-cell epitope in the hemagglutinin stalk domain of pandemic H 1N 1 influenza virus and its antigen-driven TCR usage signature in BALB/c mice

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Cellular & Molecular Immunology 2017年第6期14卷 511-520页

作者： I-Na Lu Sophie Farinelle Aurelie Sausy Claude P Muller department of infection and immunity Luxembourg Institute of Health Esch-sur-Alzette L-4354 Luxembourg

The stalk region of the influenza virus hemagglutinin is relatively well conserved compared with the globular head domain, which makes it a potential target for use as a universal vaccine against influenza. However, the role of CD4 T cells in the hemagglutinin stalk-specific immune response is not clear. Here we identified a mouse CD4 T-cell epitope that encompasses residues HA2113-131 from the hemagglutinin stalk domain after a sub-lethal infection of influenza. In response to stimulation with the identified epitope, splenocytes derived from the infected mice showed significant polyfunctionality as shown by IL-2, TNF-a and IFN-7 production as well as degranulation. Moreover, mice immunized with the peptide corresponding to this CD4 T-cell epitope exhibited interindividual sharing of the CD4 T-cell receptor I~ sequences, and they had a higher survival rate following a challenge with a lethal dose of pandemic H IN 1 influenza virus. Thus, our data demonstrated a crucial role of hemagglutinin stalk-specific CD4 T cells in the host immune resoonse a^ainst influenza virus infection.

关键词： H1N1 hemagglutinin influenza T-cell receptor

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The TNFα/TNFR2 axis mediates natural killer cell proliferation by promoting aerobic glycolysis

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Cellular & Molecular Immunology 2023年第10期20卷 1140-1155页

作者： Abrar Ul Haq Khan Alaa Kassim Ali Bryan Marr Donghyeon Jo Simin Ahmadvand Claire Fong-McMaster Saeedah Musaed Almutairi Lisheng Wang Subash Sad Mary-Ellen Harper Seung-Hwan Lee department of Biochemistry Microbiologyand ImmunologyFaculty of MedicineUniversity of OttawaOttawaONCanada The University of Ottawa Centre for infection Immunityand InflammationOttawaONCanada Botany and Microbiology department College of SciencesKing Saud UniversityRiyadhSaudi Arabia

Natural killer(NK)cells are predominant innate lymphocytes that initiate the early immune response during *** cells undergo a metabolic switch to fuel augmented proliferation and activation following *** necrosis factor-alpha(TNFα)is a well-known inflammatory cytokine that enhances NK cell function;however,the mechanism underlying NK cell proliferation in response to TNFαis not well ***,we demonstrated that upon infection/inflammation,NK cells upregulate the expression of TNF receptor 2(TNFR2),which is associated with increased proliferation,metabolic activity,and effector ***,IL-18 can induce TNFR2 expression in NK cells,augmenting their sensitivity toward TNFα.Mechanistically,TNFα-TNFR2 signaling upregulates the expression of CD25(IL-2Rα)and nutrient transporters in NK cells,leading to a metabolic switch toward aerobic *** analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO ***,our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis,leading to impaired NK cell proliferation and antiviral function during MCMV infection in ***,our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation,glycolysis,and effector function.

关键词： Natural killer cells TNFa TNFR2 Glycolysis Proliferation Murine cytomegalovirus

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Innate and adaptive T cells in influenza disease

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Frontiers of Medicine 2018年第1期12卷 34-47页

作者： Simone Nfissing Sneha Sant Marios Koutsakos Kanta Subbarao Thi H.O. Nguyen Katherine Kedzierska department of Microbiology and Immunology University of Melbourne at the Peter Doherty Institute for Infection and Immunity Parkville 3010 Victoria Australia World Health Organisation (WHO) Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity Melbourne 3000 Victoria Australia

Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza- specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses （T cells and antibody-producing B cells） achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T- cells （MAIT cells, y~ T cells, and NKT cells） in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8＋ and CD4＋ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.

关键词： influenza innate T cells CD4+ and CD8+ T cells vaccination

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