1.Tumor Microenvironment Polyamines Inhibit T Cell Antitumor Activity
Yuan-Bao AI ; Xue-Mei HUANG ; Sen LIU
Progress in Biochemistry and Biophysics 2025;52(8):1986-1997
Tumor immunotherapy has emerged as the fourth major therapeutic modality, following surgery, radiotherapy, and chemotherapy. Unlike traditional treatments that primarily target tumor cells directly, immunotherapy harnesses the body’s immune system to recognize and eliminate cancer cells. Over the past decade, various immunotherapeutic strategies have been developed, including immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T cell therapy, cancer vaccines, and cytokine-based therapies. However, the immunosuppressive tumor microenvironment (TME) poses a significant obstacle to the effectiveness of these treatments. Polyamines—including putrescine, spermidine, and spermine—are polycationic metabolites that often accumulate abnormally in the TME and act as critical immunoregulatory molecules. T cells play a central role in antitumor immunity, yet their function is frequently influenced by immunoregulatory factors within the TME. Elevated polyamine levels in the TME have been implicated in dampening antitumor T cell responses, thereby facilitating tumor immune evasion. Polyamines in the TME originate from both tumor cells and tumor-associated immune cells. Tumor cells often overexpress the oncogene Myc, which drives the upregulation of polyamine biosynthetic enzymes, resulting in excessive intracellular polyamine production. Additionally, M2-polarized tumor-associated macrophages (M2-TAMs) contribute to polyamine accumulation by upregulating arginase-I (Arg-I), an enzyme that catalyzes the conversion of arginine into ornithine—a key precursor in the polyamine biosynthetic pathway. These combined sources lead to sustained polyamine enrichment in the TME, contributing to immune dysfunction and supporting tumor progression. Moreover, polyamines indirectly affect T cell activity by modulating macrophage polarization and directly suppress tumor cell apoptosis, further promoting an immunosuppressive environment. This review highlights the multifaceted roles of polyamines in modulating tumor-infiltrating T cell function, with a particular focus on their influence on CD4+ T cell differentiation,CD8+ T cell cytotoxicity, and immune checkpoint molecule expression. Recent studies suggest that polyamines suppress CD4+ T cell activation and differentiation by modulating the MAPK/ERK signaling pathway. Additionally, polyamines can impair T cell receptor (TCR) signaling and promote immune evasion through the upregulation of PD-L1 expression on tumor cells. These effects collectively contribute to weakened antitumor T cell responses. Polyamine blocking therapy (PBT), which primarily targets polyamine biosynthesis and transport, has emerged as a novel adjunctive immunotherapeutic strategy in cancer treatment. By reducing polyamine levels in the TME, PBT restores T cell effector functions and alleviates immunosuppression. Notably, studies have demonstrated that combining PBT with ICIs produces synergistic antitumor effects and may overcome resistance to ICI monotherapy. Although research has revealed the inhibitory effects of polyamines on T cell immune function, the underlying regulatory mechanisms remain to be fully elucidated. Moreover, due to compensatory mechanisms employed by tumor cells to maintain polyamine homeostasis, multi-targeted approaches may be necessary to achieve safe and effective therapeutic outcomes. Future PBT strategies may benefit from the integration of multi-omics technologies and the development of nanocarrier-based drug delivery systems, which could collectively enhance their specificity, efficacy, and applicability in cancer immunotherapy. This review systematically elucidates the immunomodulatory effects of polyamines on T cell function within the TME and provides theoretical support and novel insights for the advancement of tumor immunotherapeutic strategies.
2.Human Cytomegalovirus Infection and Embryonic Malformations: The Role of the Wnt Signaling Pathway and Management Strategies.
Xiao Mei HAN ; Bao Yi ZHENG ; Zhi Cui LIU ; Jun Bing CHEN ; Shu Ting HUANG ; Lin XIAO ; Dong Feng WANG ; Zhi Jun LIU
Biomedical and Environmental Sciences 2025;38(9):1142-1149
Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans
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Cytomegalovirus Infections/virology*
;
Wnt Signaling Pathway
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Pregnancy
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Female
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Cytomegalovirus/physiology*
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Pregnancy Complications, Infectious/virology*
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Congenital Abnormalities/virology*
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Animals
3.Identification and anti-inflammatory activity of chemical constituents and a pair of new monoterpenoid enantiomers from the fruits of Litsea cubeba
Mei-lin LU ; Wan-feng HUANG ; Yu-ming HE ; Bao-lin WANG ; Fu-hong YUAN ; Ting ZHANG ; Qi-ming PAN ; Xin-ya XU ; Jia HE ; Shan HAN ; Qin-qin WANG ; Shi-lin YANG ; Hong-wei GAO
Acta Pharmaceutica Sinica 2024;59(5):1348-1356
Eighteen compounds were isolated from the methanol extract of the fruits of
4.Design and application of portable intelligent cleaner for medical lumen instruments
Mei-Hua YU ; Chen-Yang ZHAN ; Li-Yun HE ; Cai-Hong LIU ; Bao-Xiu HUANG ; Yan-Min YAN ; Xiang-Dong HUANG
Chinese Medical Equipment Journal 2024;45(10):114-117
Objective To design a portable intelligent cleaner for medical lumen instruments to enhance cleaning efficiency.Methods The portable intelligent cleaner had a box-body shape and a shell made of 304 stainless steel,which was composed of a circuit control board,a micro pump,lithium batteries,a charging interface,a rinse tube and connectors.The circuit control board used a STM32G030C8T6 integraged circuit,which was equipped with a countdown digital tube to display the time left for cleaning;the micro pump and lithium batteries were placed at the inner wall of the box bottom,the charging interface and water inlet/outlet inteface were put on the outside of the front wall of the box bottom,the water inlet/outlet interface was connected with a silicon rinse tube linked to an adapter at its distal end,and the adapters with different calibers were compatible with sizes of medical lumen instruments.Totally 9 672 pieces of lumen instruments received by some hospital's disinfection supply center from May to October 2021 were divided into 2 groups with the convenience sampling method,with 4 836 pieces in each group.The odd-numbered instruments were enrolled into a control group and cleaned with an ultrasonic cleaner and a lumen brush,and the even-numbered instruments were included into an experimental group and cleaned conventionally after pretreatment by the intelligent cleaner.The two groups were compared in terms of eaning efficiency and satisfaction.Results Testing by visual inspection,magnifying glass with light source and white stripe method showed that the experimental group behaved better than the control group in the cleaning qualification rate,whose satisfaction rate(100%)was also higher than that of the control group(86.53%),with all the differences being statistically significant(P<0.05).Conclusion The portable cleaner with easy operation enhances the cleaning quality and efficiency for medical lumen instruments.[Chinese Medical Equipment Journal,2024,45(10):114-117]
5.Systematic identification of chemical forms of key terpene synthase in Cinnamomum camphora.
Qing MA ; Rui MA ; Ping SU ; Ye SHEN ; Mei-Lan CHEN ; Bao-Long JIN ; Shao-Lin OUYANG ; Juan GUO ; Guang-Hong CUI ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2023;48(9):2307-2315
Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.
Cinnamomum camphora/enzymology*
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Alkyl and Aryl Transferases/chemistry*
6.Clinical and genetic characteristics of young patients with myeloproliferative neoplasms
Mengyu ZHANG ; Mei BAO ; Dayu SHI ; Hongxia SHI ; Xiaoli LIU ; Na XU ; Minghui DUAN ; Junling ZHUANG ; Xin DU ; Ling QIN ; Wuhan HUI ; Rong LIANG ; Meifang WANG ; Ye CHEN ; Dongyun LI ; Wei YANG ; Gusheng TANG ; Weihua ZHANG ; Xia KUANG ; Wei SU ; Yanqiu HAN ; Limei CHEN ; Jihong XU ; Zhuogang LIU ; Jian HUANG ; Chunting ZHAO ; Hongyan TONG ; Jianda HU ; Chunyan CHEN ; Xiequn CHEN ; Zhijian XIAO ; Qian JIANG
Chinese Journal of Hematology 2023;44(3):193-201
Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.
7.Application study of stool-based methylated SDC2 test in the screening of colorectal neoplasms for physical examination population.
Li WANG ; Zhan Mei HUANG ; Yan Ying JIANG ; Min ZHU ; Nian ZHANG ; Feng Bao XIONG ; Hong Zhi ZOU ; Xiao Hui XU
Chinese Journal of Preventive Medicine 2022;56(12):1767-1773
Objective: To investigate the value of stool-based methylated SDC2 test in physical examination population for the screening of colorectal neoplasms. Methods: Using the prospective cohort study method, from December 2020 to November 2021, 2 107 participants from the First People's Hospital of Xiushui County, Jiangxi Province were enrolled, consisted of 1 012 males and 1 094 females, aged 20-90 years with the median age of 49 years old. Fresh stool samples were collected and SDC2 DNA methylation tests were carried out as the primary screening method. The participants with positive results were recommended to undergo colonoscopy, and those who were negative were followed up by telephone. The positive rate of screening, the compliance of colonoscopy, and the detection of colorectal lesions were analyzed by chi-square test. Combined the follow-up results of negative subjects, the value of SDC2 DNA methylation test for the screening of colorectal neoplasms was evaluated. Results: Among the 2 107 participants, 2 106 completed the SDC2 methylation test. 113 participants (5.4%) were positive. The positive rate of primary screening increased with age significantly (χ2=32.135, P<0.001). Out of 113 cases, 72 (63.7%) underwent colonoscopy examinations. Finally, 3 (4.2%) cases of colorectal cancer, 12 (16.7%) cases of advanced adenoma, 31 (43.1%) cases of non-advanced adenoma, and 16 (22.2%) cases of non-adenomatous polyp were detected. The positive predictive value (PPV) of stool-based SDC2 DNA methylation test for intestinal lesions and colorectal neoplasms were 86.1% and 63.9%, respectively. Among the 1 374 follow-up participants, the negative predictive value (NPV) of this test for intestinal lesions and colorectal neoplasms were 97.7% and 99.4%, respectively. Conclusion: Primary stool-based SDC2 DNA methylation test and subsequent colonoscopy examination can effectively find colorectal neoplasms. This strategy may be a potential tool for the screening of colorectal neoplasms in general risk population.
Male
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Female
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Humans
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Middle Aged
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Sensitivity and Specificity
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Prospective Studies
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Early Detection of Cancer/methods*
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Colorectal Neoplasms/diagnosis*
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Mass Screening/methods*
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Feces
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DNA Methylation
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Colonoscopy
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Physical Examination
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Syndecan-2/genetics*
8.Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma.
Meng ZHANG ; Pan WU ; Yan Long DUAN ; Ling JIN ; Jing YANG ; Shuang HUANG ; Ying LIU ; Bo HU ; Xiao Wen ZHAI ; Hong Sheng WANG ; Yang FU ; Fu LI ; Xiao Mei YANG ; An Sheng LIU ; Shuang QIN ; Xiao Jun YUAN ; Yu Shuang DONG ; Wei LIU ; Jian Wen ZHOU ; Le Ping ZHANG ; Yue Ping JIA ; Jian WANG ; Li Jun QU ; Yun Peng DAI ; Guo Tao GUAN ; Li Rong SUN ; Jian JIANG ; Rong LIU ; Run Ming JIN ; Zhu Jun WANG ; Xi Ge WANG ; Bao Xi ZHANG ; Kai Lan CHEN ; Shu Quan ZHUANG ; Jing ZHANG ; Chun Ju ZHOU ; Zi Fen GAO ; Min Cui ZHENG ; Yonghong ZHANG
Chinese Journal of Pediatrics 2022;60(10):1011-1018
Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Burkitt Lymphoma/drug therapy*
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Child
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Disease-Free Survival
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Female
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Humans
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Lactate Dehydrogenases
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Lymphoma, B-Cell/drug therapy*
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Male
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Prognosis
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Retrospective Studies
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Rituximab/therapeutic use*
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Treatment Outcome
9.Effects of curcumin on memory follicular T cells in obese mice with colitis
Zeng-ping KANG ; Hai-mei ZHAO ; Meng-xue WANG ; Jia-qi HUANG ; You-bao ZHONG ; Duan-yong LIU
Acta Pharmaceutica Sinica 2022;57(7):2068-2076
This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (
10.Strengthening the treatment of SARS-CoV-2 infection in children with underlying diseases.
Hong Bao LIU ; Xiao Bo ZHANG ; Lin YUAN ; Xiao Wen ZHAI ; Wen Hao ZHOU ; Mei ZENG ; Guo Ying HUANG
Chinese Journal of Pediatrics 2022;60(11):1100-1102
Child
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Humans
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COVID-19
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SARS-CoV-2
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COVID-19 Testing

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