1.Research progress on ferroptosis regulation in tumor immunity of hepatocellular carcinoma.
Yuqian MO ; Zhilin ZOU ; Erbao CHEN
Journal of Zhejiang University. Medical sciences 2024;53(6):715-725
Ferroptosis is a form of regulated cell death, which is dependent on iron metabolism imbalance and characterized by lipid peroxidation. Ferroptosis plays a crucial role in various pathological processes. Studies have shown that the occurrence of ferroptosis is closely associated with the progression of hepatocellular carcinoma (HCC). Ferroptosis is involved in regulating the lipid metabolism, iron homeostasis, mitochondrial metabolism, and redox processes in HCC. Additionally, ferroptosis plays a key role in HCC tumor immunity by modulating the phenotype and function of various immune cells in the tumor microenvironment, affecting tumor immune escape and progression. Ferroptosis-induced lipid peroxidation and oxidative stress can promote the polarization of M1 macrophages and enhance the pro-inflammatory response in tumors, inhibiting immune suppressive cells such as myeloid-derived suppressor cells and regulatory T cells to disrupt their immune suppression function. The regulation of expression of ferroptosis-related molecules such as GPX4 and SLC7A11 not only affects the sensitivity of tumor cells to immunotherapy but also directly influences the activity and survival of effector cells such as T cells and dendritic cells, further enhancing or weakening host antitumor immune response. Targeting ferroptosis has demonstrated significant clinical potential in HCC treatment. Induction of ferroptosis by nanomedicines and molecular targeting strategies can directly kill tumor cells or enhance antitumor immune responses. The integration of multimodal therapies with immunotherapy further expands the application of ferroptosis targeting as a cancer therapy. This article reviews the relationship between ferroptosis and antitumor immune responses and the role of ferroptosis in HCC progression from the perspective of tumor immune microenvironment, to provide insights for the development of antitumor immune therapies targeting ferroptosis.
Ferroptosis
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Humans
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Carcinoma, Hepatocellular/pathology*
;
Liver Neoplasms/metabolism*
;
Tumor Microenvironment/immunology*
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Lipid Peroxidation
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Immunotherapy
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Oxidative Stress
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Iron/metabolism*
;
Lipid Metabolism
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Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism*
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Macrophages/immunology*
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Amino Acid Transport System y+
2.Clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio in patients with multiple myeloma
Jingyun ZOU ; Yue LIU ; Yang CAO ; Guoqiang QIU ; Haoqing WU ; Zhilin WANG ; Xiaobao XIE
Journal of Leukemia & Lymphoma 2020;29(4):219-224
Objective:To investigate the clinical significances of CD4/CD8 ratio and neutrophil-to-lymphocyte ratio (NLR) in patients with multiple myeloma (MM).Methods:The clinical data of 124 MM patients in the Third Affiliated Hospital of Soochow University from December 2002 to April 2017 were retrospectively analyzed, and 31 healthy people were chosen as the controls. Peripheral blood T lymphocyte subsets were detected by using flow cytometry, and the correlations between CD4/CD8 ration and related clinical indicators were also investigated. All MM patients were divided into the high NLR group and the low NLR group according to the media of NLR, and the correlation of them with related clinical indicators, chromosome karyotype, overall survival (OS) and progression-free survival (PFS) was also compared.Results:Compared with the healthy control group, the proportion of CD4 + T cells [(35.28±6.58)% vs. (31.85±6.76)%, t = -2.067, P = 0.043], absolute value of NK cells [0.22×10 9/L (0.13×10 9/L-0.59×10 9/L) vs. 0.17×10 9/L (0.00×10 9/L-0.42×10 9/L), Z = -2.614, P = 0.009] and CD4/CD8 ratio [0.97 (0.50-2.69) vs. 0.81 (0.30-1.28), Z = -2.253, P = 0.024] was decreased, respectively. The proportion of CD8 + cells was increased [(36.93±7.38)% vs. (40.50±6.50)%, t = 2.074, P = 0.042] in MM group. The hemoglobin level of CD4/CD8 ratio ≥0.94 group was higher than that of CD4/CD8 ratio <0.94 [(98.89±21.35) g/L vs.(80.60±23.23) g/L, t = -2.066, P = 0.047]. Compared with the healthy control group, NLR was increased in MM group [1.54 (1.10-3.23) vs. 1.95 (0.29-12.70), Z = -2.384, P = 0.017]. Compared with the low NLR group (<1.95), serum β 2-microglobulin [4.56 mg/L (1.63-12.60 mg/L) vs. 6.17 mg/L (1.58-67.50 mg/L), Z = -2.586, P = 0.010] and serum creatinine [84.5 μmol/L (43.0-376.5 μmol/L) vs. 113.0 μmol/L (46.5-754.0 μmol/L), Z = -3.866, P < 0.001] was increased in the high NLR group for MM patients. The proportion of the male patients, β 2-microglobulin > 5.5 mg/L, serum creatinine > 177 μmol/L, stage Ⅲ of international staging system (ISS) in the high NLR group was higher than that in the low NLR group (all P < 0.05), and there was no statistically significant difference in the composition of chromosome karyotype (all P > 0.05). The median OS time in the low NLR group was longer than that in the high NLR group [30 months (20-40 months) vs. 17 months (7-27 months), χ 2 = 4.519, P = 0.034], and there was no statistically significant difference in the PFS of both groups ( P > 0.05). Multivariate Cox analysis demonstrated that the age, corrected serum calcium, serum creatinine, lactic dehydrogenase were the independent influencing factors of OS in MM (all P < 0.05), while NLR wasn′t an independent influencing factor of OS in MM ( P = 0.513). Conclusions:CD4/CD8 ratio is decreased and immune dysfunction occurs in MM patients. MM patients with high NLR have a shorter OS time.
3.Comparison of Recovery Phase CT Features between Mild/moderate and Severe/critical Coronavirus Disease 2019 Patients.
Wenbin ZOU ; Changyu LIU ; Yixin CAI ; Zhilin ZENG ; Ni ZHANG ; Xiangning FU
Acta Academiae Medicinae Sinicae 2020;42(3):370-375
To investigate the computed tomographc(CT)features of mild/moderate and severe/critical cases of coronavirus disease 2019(COVID-19)in the recovery phase. Totally 63 discharged patients in Wuhan,China,who underwent both chest CT and reverse transcription-polymerase chain reaction(RT-PCR)from February 1 to February 29,2020,were included.With RT-PCR as a gold standard,the performance of chest CT in diagnosing COVID-19 was assessed.Patients were divided into mild/moderate and severe/critical groups according to the disease conditions,and clinical features such as sex,age,symptoms,hospital stay,comorbidities,and oxygen therapy were collected.CT images in the recovery phase were reviewed in terms of time from onset,CT features,location of lesions,lobe score,and total CT score. There were 37 patients in the mild/moderate group and 26 in the severe/critical group. Compared with the mild/moderate patients,the severe/critical patients had older age [(43±16) years (52±16) years; =2.10, =0.040], longer hospital stay [(15±6)d (19±7)d; =2.70, =0.009], higher dyspnea ratio (5.41% 53.85%; =18.90, <0.001), lower nasal oxygen therapy ratio (81.08% 19.23%;=23.66, <0.001), and higher bi-level positive airway pressure ventilation ratio (0 57.69%; =25.62, <0.001). Time from onset was (23±6) days in severe/critical group, significantly longer than that in mild/moderate group [(18±7) days] (=3.40, <0.001). Severe/critical patients had significantly higher crazy-paving pattern ratio (46.15% 10.81%;=4.24, =0.039) and lower ground-glass opacities ratio (15.38% 67.57%; =16.74, <0.001) than the mild/moderate patients. The proportion of lesions in peripheral lung was significantly higher in mild/moderate group than in severe/critical group (78.38% 34.61%; =13.43, <0.001), and the proportion of diffusely distributed lesions was significantly higher in severe/critical group than in mild/moderate group (65.38% 10.81%; =20.47, <0.001). Total CT score in severe/critical group was also significantly higher in severe/critical group than in mild/moderate group [11 (8,17) points 7 (4,9) points; =3.81, <0.001]. The CT features in the recovery stage differ between mild/moderate and severe/critical COVID-19 patients.The lung infiltration is remarkably more severe in the latter.
Adult
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Aged
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Betacoronavirus
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China
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Coronavirus Infections
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diagnostic imaging
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Humans
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Middle Aged
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Pandemics
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Pneumonia, Viral
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diagnostic imaging
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Retrospective Studies
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Tomography, X-Ray Computed
4.Regulation of T cell immunity by cellular metabolism.
Zhilin HU ; Qiang ZOU ; Bing SU
Frontiers of Medicine 2018;12(4):463-472
T cells are an important adaptive immune response arm that mediates cell-mediated immunity. T cell metabolism plays a central role in T cell activation, proliferation, differentiation, and effector function. Specific metabolic programs are tightly controlled to mediate T cell immune responses, and alterations in T cell metabolism may result in many immunological disorders. In this review, we will summarize the main T cell metabolic pathways and the important factors participating in T cell metabolic programming during T cell homeostasis, differentiation, and function.
Animals
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Cell Physiological Phenomena
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Humans
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Immunity, Cellular
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physiology
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Metabolic Networks and Pathways
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immunology
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T-Lymphocytes
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immunology
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metabolism
5.The effect of drug dependence severity on the relationship between impulsivity construct and cue-elicited craving
Zhilin YANG ; Xiaodan XU ; Fuyin XIAO ; Zhiling ZOU
Chinese Journal of Behavioral Medicine and Brain Science 2015;24(7):607-610
Objective To investigate the effect of drug dependence severity on the relationship between impulsivity and craving.Methods 36 abstiuent drug-dependent individuals were recruited in the study.The participants were divided into the heavy depeudence group (HDG) or the low dependence group (LDG) according to the scores of Addiction Severity Index (ASI).The Barratt Impulsiveness Scale (BIS-11) and classical Stroop task were used to measure the trait impulsivity and state impulsivity.Block designed cue-induced craving paradigm was presented to measure cue-elicited craving.Results For the HDG,a significant positive correlation was found between trait impulsivity (the mean value of BIS-11-CI scale was (39.03± 16.50)) or state impulsivity (the difference of reaction time between congruent and incongruent situation was (87.77±36.95)ms)and cue-elicited craving (0.83± 1.91)(r=0.487,0.500,P<0.05).However,for the LDG subjects,the impulsivity was not found significantly correlated with the cue-elicited craving(r=-0.261,0.081,P>0.05).Conclusion The addiction severity influences the relationship between impulsivity and craving,and impulsivity can only be used as a predictor of relapse in HDG.The findings suggest that the drug may influence the shared brain mechanism between impulsivity and craving.
6.P53 abnormality and clinical prognosis of leukemia patients with complex chromosomal abnormalities.
Zhaoling ZOU ; Xiangshan CAO ; Zhilin WANG
Chinese Journal of Medical Genetics 2010;27(1):81-85
OBJECTIVETo investigate the p53 deletion in leukemia patients with complex chromosomal abnormalities (CCA) and the clinical significance.
METHODSThe p53 deletion status of 38 leukemia cases with CCA and 24 cases without CCA were analyzed by interphase fluorescence in situ hybridization (I-FISH).
RESULTSThe frequency of p53 deletion in the 38 patients with CCA (44.74%) was significantly higher than that in the 24 cases without CCA (4.16%) (P<0.01). The rate of complete remission in 13 cases of acute leukemia with CCA was 15.4%, with median survival time (MST) of 105 days.
CONCLUSIONI-FISH is a rapid, accurate and sensitive technique for detection of p53 deletion, patients with CCA have a higher p53 deletion and a lower complete remission rate and MST.
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; cytology ; Cells, Cultured ; Chromosome Aberrations ; Female ; Gene Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Leukemia ; diagnosis ; genetics ; mortality ; Male ; Middle Aged ; Prognosis ; Survival Analysis ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult

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