1.Nanomedicine-driven tumor glucose metabolic reprogramming for enhanced cancer immunotherapy.
Chenwei JIANG ; Minglu TANG ; Yun SU ; Junjie XIE ; Qi SHANG ; Mingmei GUO ; Xiaoran AN ; Longfei LIN ; Ruibin WANG ; Qian HUANG ; Guangji ZHANG ; Hui LI ; Feihu WANG
Acta Pharmaceutica Sinica B 2025;15(6):2845-2866
Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.
2.G protein-coupled estrogen receptor alleviates lung injury in mice with exertional heat stroke by inhibiting ferroptosis.
Ziwei HAN ; Jiansong GUO ; Xiaochen WANG ; Zhi DAI ; Chao LIU ; Feihu ZHOU
Chinese Critical Care Medicine 2025;37(3):268-274
OBJECTIVE:
To investigate whether the G protein-coupled estrogen receptor (GPER) can attenuates acute lung injury in mice with exertional heat stroke (EHS) by inhibiting ferroptosis.
METHODS:
Sixty SPF-grade male C57BL/6 mice were randomly divided into four groups: normal control group (control group), EHS model group (EHS group), dimethyl sulfoxide (DMSO) solvent group (EHS+DMSO group), and GPER-specific agonist G1 group (EHS+G1 group), with 15 mice in each group. All mice underwent 14 days of adaptive training at 24-26 centigrade before modeling, and the EHS model was established using a high-temperature treadmill device. After successful modeling, the mice were allowed to cool naturally at room temperature. In the EHS+G1 group, 40 μg/kg of the GPER-specific agonist G1 was slowly injected intraperitoneally immediately after modeling. In the EHS+DMSO group, 40 μg/kg of DMSO was slowly injected intraperitoneally immediately after modeling. The control group received no treatment. Five hours after modeling, abdominal aortic blood was collected, and lung tissues were harvested after euthanasia. The lung coefficient was calculated to evaluate lung injury. Lung histopathological changes were observed under a light microscope after hematoxylin-eosin (HE) staining, and a lung histopathological score was assigned. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), malondialdehyde (MDA), and Fe2+ in lung tissue. Immunofluorescence was used to detect the expression of glutathione peroxidase 4 (GPX4). Real-time polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of GPX4, ferroportin 1 (FPN1), and ferritin heavy chain 1 (FTH1). Western blotting was performed to detect the protein expression of GPX4, FPN1, and FTH1.
RESULTS:
Compared with the control group, the lung coefficient and lung histopathological score were significantly increased in the EHS group. HE staining showed significant thickening and unevenness of the alveolar septa and alveolar walls, partial alveolar collapse, and extensive erythrocyte, inflammatory cell, and plasma-like material extravasation in the alveolar spaces. Serum levels of TNF-α, IL-1β, MDA, and Fe2+ were significantly elevated. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue. Western blotting and RT-PCR showed significantly reduced protein and mRNA expression of GPX4, FPN1, and FTH1 in lung tissue. Compared with the EHS group, the EHS+G1 group showed a significant reduction in lung coefficient and lung histopathological score [lung coefficient (mg/g): 3.9±0.1 vs. 4.6±0.3, lung histopathological score: 4.2±0.2 vs. 6.9±0.2, both P < 0.05]. HE staining revealed reduced severity of lung tissue fluid extravasation, inflammatory infiltration, decreased hemorrhage, and less severe alveolar structural damage. Serum levels of TNF-α, IL-1β, MDA, and Fe2+ were significantly reduced [TNF-α (ng/L): 44.3±0.2 vs. 64.6±0.3, IL-1β (ng/L): 69.3±0.4 vs. 97.8±0.2, MDA (nmol/L): 2.8±0.3 vs. 3.6±0.5, Fe2+ (nmol/L): 0.021±0.004 vs. 0.028±0.004, all P < 0.05]. Immunofluorescence staining showed a significant decrease in GPX4-positive expression in lung tissue (fluorescence intensity: 35.53±2.41 vs. 16.45±0.31, P < 0.05). RT-PCR and Western blotting showed significantly increased mRNA and protein expression of GPX4, FPN1, and FTH1 in lung tissue [mRNA expression: GPX4 mRNA (2-ΔΔCt): 0.44±0.05 vs. 0.09±0.01, FPN1 mRNA (2-ΔΔCt): 0.77±0.17 vs. 0.42±0.14, FTH1 mRNA (2-ΔΔCt): 0.75±0.04 vs. 0.58±0.01; protein expression: GPX4/β-actin: 0.96±0.11 vs. 0.24±0.04, FPN1/β-actin: 1.26±0.21 vs. 0.44±0.14, FTH1/β-actin: 0.27±0.12 vs. 0.15±0.07; all P < 0.05]. However, there were no statistically significant differences in any of the above indicators between the EHS+DMSO group and the EHS group.
CONCLUSION
Activation of GPER can attenuate EHS-related lung injury in mice, and its mechanism may be related to the activation of the GPX4 signaling pathway and inhibition of ferroptosis.
Animals
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Mice, Inbred C57BL
;
Male
;
Mice
;
Heat Stroke/metabolism*
;
Receptors, G-Protein-Coupled
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Ferroptosis
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Receptors, Estrogen
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Acute Lung Injury/metabolism*
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Tumor Necrosis Factor-alpha/metabolism*
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Interleukin-1beta/metabolism*
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Lung Injury
;
Lung/metabolism*
3.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
4.Influence of online and offline Satir family therapy on emotions of adolescents with depressive disorder and their parents
Heli LU ; Feng CAI ; Yun LIU ; Ming GUO ; Xiaoqin HUANG ; Yipin XIONG ; Xi XU ; Feihu HU ; Biyi WANG ; Guanhua LI ; Xiangli DONG
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(10):893-898
Objective:To explore the influence of online and offline family therapy based on the Satir model on emotions of adolescents with depressive disorder and their parents in remote areas.Methods:A total of 98 cases adolescents with depressive disorder treated in the psychosomatic medicine of the Second Affiliated Hospital of Nanchang University from January 2021 to June 2021 and their parents were selected as the objects. The adolescents with depressive disorder and their parents were randomly divided into the control group (49 parents and 49 adolescents) and the observation group (49 parents and 49 adolescents). The control group received the medical treatment (sertraline 100 mg/d) and the routine health education, while the observation group received the online and offline Satir family therapy on the basis of the intervention of the control group. Generalized anxiety disorder-7 (GAD-7) and patient health questionnaire-9 (PHQ-9) were used to investigate the negative emotions of the parents of the two groups before and 12 weeks after the intervention. The screen for child anxiety related emotional disorders (SCARED) and depression self-rating scale for childhood (DSRS) were used to investigate the negative emotions of the adolescents before and 12 weeks after the intervention.The SPSS 20.0 software was used for statistical analysis. t test was used to compare the SCARED scale score and DSRS score changes of the adolescents in the two groups, and χ 2 test was used to compare the proportional changes of parents' anxiety and depression. Results:The scores of SCARED (51.55±12.69 vs 36.82±7.69, t=15.839) and DSRS (25.08±4.81 vs 16.88±2.16, t=13.047) of adolescents in the control group were significantly different before and after the intervention (both P<0.05). The scores of SCARED (51.16±15.84 vs 31.31±7.72, t=14.385) and DSRS (24.12±4.81 vs 14.08±2.03, t=14.723) of adolescents in the observation group were significantly different before and after the intervention (both P<0.05). After the intervention, the scores of SCARED and DSRS in the observation group were lower than those in the control group ( t=3.540, 6.609, both P<0.05). Before intervention, there was no significant difference in the proportion of anxiety and depression between the parents of the two groups (χ 2=1.837, 3.547, both P>0.05). After 12 weeks of intervention, there was a statistically significant difference in the proportion of anxiety and depression between the two groups, which were lower in the observation group than those in the control group (χ 2=5.995, 4.009, both P<0.05). Conclusion:Online + offline family therapy based on the Satir model can not only effectively reduce anxiety and depression of adolescents, but also effectively reduce anxiety and depression of their parents.It is especially suitable for outpatient management of children with depressive disorder in remote areas.
5.Research progress of synthetic methods of [18F]F-DOPA
Weihua CHENG ; Feihu GUO ; Xuesong DENG ; Xiangyu QIN ; Hongqiang FAN ; Ji HU
Journal of China Pharmaceutical University 2019;50(3):357-363
[18F]6-fluoro-3, 4-dihydroxy-L-phenylalanine([18F]F-DOPA)has been used as a radiotracer for Parkinson′s disease over 30 years. The previously reported electrophilic synthesis method has low radiochemical yield(RCY), low specific activity(SA)and other defects. Recent reported nucleophilic synthesis of [18F]F-DOPA could overcome the disadvantages. In this paper, the nucleophilic synthetic methods for [18F]F-DOPA are reviewed.
6.Preparation and biological application of carbon nanotube atomic force microscope probe.
Tieqiang ZHAO ; Liqiu GUO ; Shen DONG ; Feihu ZHANG
Journal of Biomedical Engineering 2003;20(2):352-355
The atomic force microscope (AFM) with an atomic resolution is a powerful tool for biological structure. The probe is an important part that determines the resolution of AFM. Carbon nanotube is becoming an ideal AFM probe due to its unique structure physical and chemical properties. Carbon nanotube AFM probes can be made by manual assembly or chemical vapor deposition. Several proteins, nucleic acids and cells have been investigated with carbon nanotube probes. Not only the high-resolution images but also the determination of specific DNA sequence and haplotype were acquired. Carbon nanotube AFM probe will increasingly play an important role in biological studies.
Carbon
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Cells, Cultured
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Equipment Design
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Erythrocytes
;
parasitology
;
ultrastructure
;
Microscopy, Atomic Force
;
instrumentation
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Proteins
;
ultrastructure
;
Sequence Analysis, DNA
;
methods

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