期刊：
EXPERIMENTAL AND THERAPEUTIC MEDICINE,2025年29(3):56 ISSN：1792-0981
通讯作者：
Tang, J
作者机构：
[Cao, Chuangjie] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Xie, Haitao] Univ South China, Affiliated Hosp 1, Inst Microbiol & Infect Dis, Dept Clin Lab Med,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Dou, Chengyun; Tang, Jian; Tang, J; Guo, Ruohan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Infect Dis, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, J ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Infect Dis, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
coronavirus disease 2019;distinction;eosinophil;influenza A;neutrophil-to-lymphocyte ratio
摘要：
Coronavirus disease 2019 (COVID-19) and influenza A outbreaks have spread rapidly in China. It is difficult to accurately differentiate these two different respiratory tract infections on the basis of their similar early-stage symptoms and lymphocytopenia. In the present study, the age, sex and white blood cell, neutrophil, lymphocyte, monocyte and eosinophil counts, as well as the neutrophil-to-lymphocyte ratio (NLR) of 201 outpatients with confirmed COVID-19 and 246 outpatients with influenza A were investigated and compared. A receiver operating characteristic curve was drawn to determine the thresholds in distinguishing COVID-19 from influenza A Our study found that the monocyte count and NLR were significantly elevated, while the eosinophil count/percentage was higher in outpatients with COVID-19 than in those with influenza A (0.06±0.07 vs. 0.04±0.09, P=0.002; 0.95±1.12 vs. 0.56±0.95, P<0.001, respectively). Logit(P)=-1.11 + 1.29 x eosinophil percentage -12.07 x eosinophil count +1.10 x monocyte count, deduced from the eosinophil count/percentage and monocyte count, had the largest area under the curve at 0.67, with high specificity (80.1%) and a sensitivity of 47.3%. The present study demonstrated that a higher eosinophil count/percentage may be a potential biomarker to significantly differentiate early COVID-19 from influenza A.
作者机构：
[He, Zhe; Tang, Huifang; Tang, Dan; Xiang, Xing; Hu, Hengjing; Cui, Jian; Mao, Jie; Huang, Hong] Hunan Provincial Key Laboratory of Multi-omics and Artificial Intelligence of Cardiovascular Diseases, University of South China, Hengyang 421001, China;[He, Zhe; Tang, Huifang; Tang, Dan; Xiang, Xing; Hu, Hengjing; Cui, Jian; Mao, Jie; Huang, Hong] Clinical Research Center for Myocardial Injury in Hunan Province, Hengyang 421001, China;[Tang, Huifang; Tang, Dan; Xiang, Xing; Cui, Jian; Mao, Jie; Huang, Hong] Institute of Cardiovascular Disease, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China;[Tang, Dan; Xiang, Xing] Department of Clinical Laboratory Medicine, Institution of Microbiology and Infectious Diseases, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China;[Mao, Jie] School of Pharmaceutical Science, Hengyang Medical College, University of South China, Hengyang 421001, China
摘要：
Atherosclerosis, a chronic inflammatory disorder, is pathophysiologically linked to endothelial cell (EC) pyroptosis. This study aims to elucidate the mechanisms by which succinate exacerbates EC pyroptosis through mitochondrial damage. Serum samples are collected from patients with coronary heart disease (CHD) and healthy controls (HCs), and the levels of succinate, interleukin (IL)-6, and IL-18 are quantified. To establish a succinate accumulation model, human umbilical vein endothelial cells (HUVECs) are treated with diethyl butyl malonate (DEBM), followed by analysis of inflammatory cytokines. The expression of pyroptosis-related proteins is assessed via western blot analysis. Morphological changes in pyroptotic vesicles and membrane pores are examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The mitochondrial membrane potential and reactive oxygen species (ROS) levels are evaluated via a JC-1 kit and MitoSOX, respectively. RNA sequencing (RNA-seq) is performed to identify potential target genes and regulatory pathways. To investigate the functional role of ATP5F1D, small interfering RNAs (siRNAs) are used to knockdown ATP5F1D, while lentiviral vectors are used to overexpress ATP5F1D in HUVECs. The results reveal significantly elevated levels of succinate, IL-6, and IL-18 in both CHD patients and DEBM-treated HUVECs. Succinate accumulation induced by DEBM triggers pyroptosis and mitochondrial damage in HUVECs, as evidenced by the upregulation of pyroptosis-related proteins and the impairment of mitochondrial structure and function. RNA sequencing analysis identifies ATP5F1D as a key downstream target of succinate accumulation. Downregulation of ATP5F1D promotes pyroptosis and mitochondrial injury in HUVECs, whereas restoration of ATP5F1D expression effectively mitigates these detrimental effects. Succinate-induced downregulation of ATP5F1D drives mitochondrial dysfunction and pyroptosis in HUVECs.
作者机构：
[Dai, Miao; Yan, Jialong; Xu, Si; Xi, Hanqing; Ou, Guifang; Li, Xiaoxue; Xue, Wen; Chen, Guang; Tang, Yonghong; Wang, Jiwu; Liu, Xuelian] Clinical Research Institute, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Dai, Miao; Xu, Si; Xi, Hanqing; Ou, Guifang; Tang, Yonghong] Department of Neurology, the Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang 421002, China;[Li, Xiaoxue] Institute of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang 421002, China;[Luo, Si; Wei, Ping] Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
作者机构：
[Tang, Ke; Shao, Xiaodan; Zhang, Yan; Wang, Na; Zhang, Y] Univ South China, Sch Nursing, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Yuting; Zhang, Yan; Wang, Kunning; Zhang, Y; Shen, Zhiwei] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Tan, Zhangyan; Xie, Jiangxiu] Univ South China, Affiliated Hosp 2, Dept Obstet, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhang, Y ] U;Univ South China, Sch Nursing, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要：
OBJECTIVE: To provide an overview of the symptom experience and interrelationships among symptoms during chemotherapy in cancer patients, as well as the state of symptom network research in this field. METHODS: This scoping review was conducted using the framework proposed by Arksey and O'Malley and the PRISMA guidelines. It included studies that focused on symptom network analysis of cancer patients currently undergoing chemotherapy treatment. A comprehensive search was conducted in both English and Chinese databases, including PubMed/MEDLINE, Cochrane, EMBASE, CINAHL (EBSCO), Web of Science, ProQuest, CNKI, VIPC, and CSPD, up to September 10, 2024.Studies were included if they involved cancer patients aged ≥ 18years undergoing chemotherapy and excluded those involving radiotherapy. Data were extracted based on study characteristics, cancer types, sample characteristics, treatment, study design, instruments, R packages used, core symptoms, and main findings. RESULTS: From 8948 initial articles, 12 studies were included. These studies varied in sample size, symptom survey instruments, and methods of symptom categorization. Six studies extracted symptom clusters, and core symptoms were identified in eight studies. Fatigue was commonly reported as a core symptom across different cancer types. The longitudinal study indicated that overall symptoms peaked after the initial chemotherapy session and gradually decreased with subsequent cycles, although some symptoms like skin changes and neuropathy worsened over time. CONCLUSIONS: Symptom network analysis offers insights into the complex interplay of symptoms during chemotherapy, highlighting fatigue as a central symptom. Future research should focus on longitudinal studies to better understand the dynamic changes in symptom networks and their implications for symptom management interventions.
摘要：
OBJECTIVE: To investigate the risk factors for all-cause mortality of previously untreated pulmonary tuberculosis patients complicated by hypertension and construct a predictive model. METHODS: We retrospectively analyzed the clinical data of inpatients with previously untreated pulmonary tuberculosis complicated by hypertension from 2019 to 2021 in Changsha Central Hospital. Patients' survival status and cardiovascular events were collected through telephone follow-up. LASSO regression was utilized to screen predictive variables, and binary logistic regression identified mortality risk factors. A predictive nomogram model was developed using R software, and its precision and reliability were verified. RESULTS: Among the 1,014 patients, there were 100 (9.86%) deaths and 82 (8.09%) cardiovascular events. LASSO regression screened out 13 predictive variables. Multivariate logistic regression analysis revealed that smoking history, sputum bacteriology, pleural effusion, coronary heart disease, and chronic kidney disease were independent risk factors. Based on the training set data, a nomogram prognostic model was developed, showing an AUC of 0.712 (95% CI: 0.777-0.847), with 50.0% sensitivity and 84.3% specificity. The model's fit was confirmed through internal and external validations. CONCLUSION: The prediction model constructed in this study has high predictive ability and satisfactory clinical efficacy, and can provide an effective individualized prediction tool for assessing all-cause mortality risk in patients with previously untreated pulmonary tuberculosis complicated by hypertension.
期刊：
Molecular and Cellular Biochemistry,2025年480(4):2143-2157 ISSN：0300-8177
通讯作者：
Wang, J
作者机构：
[Jiang, Tingting] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Dept Clin Lab, Hengyang 421000, Peoples R China.;[Zeng, Qun] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421000, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;[Wang, Jing] Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
通讯机构：
[Wang, J ] C;Changsha Med Univ, Hunan Prov Key Lab Tradit Chinese Med Agr Biogenom, Changsha 410219, Peoples R China.;Changsha Med Univ, Hunan Prov Univ Key Lab Fundamental & Clin Res Fun, Changsha 410219, Peoples R China.;Changsha Med Univ, Clin Coll 1, Changsha 410219, Peoples R China.
摘要：
FHL2 (Four-and-a-half LIM domain protein 2) is a crucial factor involved in cardiac morphogenesis, the process by which the heart develops its complex structure. It is expressed in various tissues during embryonic development, including the developing heart, and has been shown to play important roles in cell proliferation, differentiation, and migration. FHL2 interacts with multiple proteins to regulate cardiac development as a coactivator or a corepressor. It is involved in cardiac specification and determination of cell fate, cardiomyocyte growth, cardiac remodeling, myofibrillogenesis, and the regulation of HERG channels. Targeting FHL2 has therapeutic implications as it could improve cardiac function, control arrhythmias, alleviate heart failure, and maintain cardiac integrity in various pathological conditions. The identification of FHL2 as a signature gene in atrial fibrillation suggests its potential as a diagnostic marker and therapeutic target for this common arrhythmia.
关键词：
Drug reposition;Enrichment score;Immunoregulation;LINCS;Lenalidomide;Radioprotection
摘要：
Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.
摘要：
Outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa drive inflammation by metabolically reprogramming macrophages to favor aerobic glycolysis. This study shows that OMVs trigger this metabolic shift via Toll-like receptors 2 and 4 (TLR2/4)-dependent activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. OMV-stimulated macrophages exhibited increased glucose uptake, lactate production, and expression of key glycolytic enzymes, resulting in a higher extracellular acidification rate and a lower oxygen consumption rate. Inhibition of the PI3K/Akt pathway reversed these metabolic changes. Crucially, this metabolic reprogramming was required for OMV-induced secretion of pro-inflammatory cytokines, as inhibition of glycolysis via 2-deoxy-D-glucose treatment attenuated the inflammatory response both in vitro and in vivo. These findings reveal that P. aeruginosa OMVs control metabolism in macrophages through the TLR2/4-PI3K/Akt axis to promote a pro-inflammatory state and identifies glycolysis as a potential therapeutic target for bacteria-associated inflammatory diseases.
摘要：
The pathogenesis of Ureaplasma urealyticum infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the U. urealyticum GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of U. urealyticum infection.
The pathogenesis of Ureaplasma urealyticum infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the U. urealyticum GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of U. urealyticum infection.
摘要：
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine. Phase III involved 320 patients with similar groupings, including a placebo group. The primary outcome was the resting summed pain intensity difference over 24 hours (rSPID 24 ). Secondary outcomes included rSPID and active-SPID (aSPID) at other time points, rescue analgesia received, cumulative dose of analgesics, and satisfaction scores. Safety endpoints included treatment-emergent adverse events (TEAEs) and AE of special interest (AESIs). In both phases, SHR8554 demonstrated significant analgesic efficacy. In Phase II, the least squares (LS) mean differences in rSPID 24 compared to morphine for the 0.05 mg,0.1 mg, and 0.2 mg SHR8554 groups were 16.8 (p = 0.01), 7.4 (p = 0.27), and 0.2 (p = 0.98), respectively. Phase III confirmed the efficacy of the 0.05 mg and 0.1 mg SHR8554 doses compared to placebo, with LS mean differences of 15.4 (p = 0.0001) and −19.8 (p < 0.0001), respectively. Trends in other secondary outcomes mirrored these findings. Safety analysis revealed that the 0.2 mg SHR8554 group had higher incidences of TEAEs (83.3 %) and AESIs (33.3 %) compared to other groups in Phase II. Similarly, in Phase III, the incidences of TEAEs were 81.0 %, 73.4 %, and 74.1 % in the 0.05 and 0.1 mg SHR8554 and morphine groups, respectively, compared with 61.3 % in the placebo group, while the AESIs were 29.1 %, 20.3 %, and 24.7 % compared with 12.5 % in the placebo group. In conclusion, SHR8554 exhibited efficacy compared to placebo and safety comparable to morphine for patients experiencing moderate-to-severe acute pain following unilateral total knee replacement or knee ligament reconstruction surgery.
Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine. Phase III involved 320 patients with similar groupings, including a placebo group. The primary outcome was the resting summed pain intensity difference over 24 hours (rSPID 24 ). Secondary outcomes included rSPID and active-SPID (aSPID) at other time points, rescue analgesia received, cumulative dose of analgesics, and satisfaction scores. Safety endpoints included treatment-emergent adverse events (TEAEs) and AE of special interest (AESIs). In both phases, SHR8554 demonstrated significant analgesic efficacy. In Phase II, the least squares (LS) mean differences in rSPID 24 compared to morphine for the 0.05 mg,0.1 mg, and 0.2 mg SHR8554 groups were 16.8 (p = 0.01), 7.4 (p = 0.27), and 0.2 (p = 0.98), respectively. Phase III confirmed the efficacy of the 0.05 mg and 0.1 mg SHR8554 doses compared to placebo, with LS mean differences of 15.4 (p = 0.0001) and −19.8 (p < 0.0001), respectively. Trends in other secondary outcomes mirrored these findings. Safety analysis revealed that the 0.2 mg SHR8554 group had higher incidences of TEAEs (83.3 %) and AESIs (33.3 %) compared to other groups in Phase II. Similarly, in Phase III, the incidences of TEAEs were 81.0 %, 73.4 %, and 74.1 % in the 0.05 and 0.1 mg SHR8554 and morphine groups, respectively, compared with 61.3 % in the placebo group, while the AESIs were 29.1 %, 20.3 %, and 24.7 % compared with 12.5 % in the placebo group. In conclusion, SHR8554 exhibited efficacy compared to placebo and safety comparable to morphine for patients experiencing moderate-to-severe acute pain following unilateral total knee replacement or knee ligament reconstruction surgery.
Trial Registration Trial Name: Study on the Efficacy and Safety of SHR8554 Injection for Postoperative Analgesia in Orthopedics: Multicenter, Randomized, Double Blind, Dose Exploration, Placebo/Positive Control, Phase II/III Clinical Trial Registered on: chinadrugtrials.org.cn Identifier: CTR20220639.
Trial Name: Study on the Efficacy and Safety of SHR8554 Injection for Postoperative Analgesia in Orthopedics: Multicenter, Randomized, Double Blind, Dose Exploration, Placebo/Positive Control, Phase II/III Clinical Trial Registered on: chinadrugtrials.org.cn Identifier: CTR20220639.
摘要：
Acute kidney injury (AKI) is associated with poor prognosis. New biomarkers, like neutrophil gelatinase-associated lipocalin (NGAL), are helpful for early warning of AKI. This study aims to investigate the accuracy of NGAL in evaluating the perioperative AKI of liver transplantation. The four databases, PubMed, Web of Science, Embase, and Cochrane Library, were searched for relevant studies published from database inception to August 2023. Results were pooled using random-effects models, and heterogeneity was examined. A total of 16 case-control studies with 1271 patients were included. The results showed that both preoperative [standardized mean difference (SMD) = 0.53; 95% confidence interval (CI): 0.15, 0.91; P < 0.001] and postoperative NGAL levels (SMD = 0.63; 95% CI: 0.24, 1.03; P < 0.001) were higher in the AKI group compared with the non-AKI group. Subgroup analysis by continents showed higher preoperative NGAL levels in AKI patients in the European population (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.003), but no differences in Asian, African, North American, and South American. Subgroup analysis by continents revealed higher postoperative NGAL levels in the European (SMD = 1.63; 95% CI: 0.55, 0.27; P = 0.002) and Asian populations (SMD = 0.42; 95% CI: 0.04, 0.81; P = 0.039). Higher postoperative NGAL levels in plasma and urine were observed in AKI patients compared with non-AKI patients [plasma (SMD = 1.29; 95% CI: 0.21, 2.38; P = 0.011), urine (SMD = 0.88; 95% CI: 0.18, 1.59; P = 0.035)], while there was no difference in African, North American, South American, and serum NGAL. NGAL level may be an important biomarker for early detection of AKI in the perioperative period of liver transplantation.
摘要：
The recent elucidation of disulfidptosis, a unique form of cell death, has opened new paths for the development of targeted cancer therapies. However, a thorough examination of disulfidptosis-related genes (DRGs) across various cancer types has been lacking. Our extensive analysis of DRGs through genomic, transcriptional, and immune profiling has yielded substantial insights. Utilizing The Cancer Genome Atlas (TCGA), we have identified key changes in gene expression, including alterations in copy number and DNA methylation, and evaluated their impact on cancer prognosis. We constructed a disulfidptosis-related signature (DFRS) using LASSO regression and multivariate Cox regression analysis, which demonstrated a strong prognostic connection across diverse cancer types. The DFRS score is linked with poorer clinical outcomes, reflects the immune characteristics of the tumor microenvironment (TME), and predicts responsiveness to immunotherapy and other treatments. Notably, the DFRS score interacts with critical oncogenic pathways, highlighting the potential benefits of targeting disulfidptosis in cancer treatment. Our findings underscore the critical influence of disulfidptosis on cancer prognosis and therapeutic response, offering meaningful clinical insights.
作者机构：
[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Liu, Cong] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Hlth Inspect & Quarantine, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, ZK ] U;Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.
摘要：
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle, which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process. This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development, influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle, which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process. This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development, influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
期刊：
Frontiers in Pharmacology,2025年16:1648294 ISSN：1663-9812
通讯作者：
Huang, Yuanyuan;Peng, Roujun;Zhang, B
作者机构：
[Fan, Teng; Ding, Ran; Luo, Wei; Lin, Yongmiao; Liu, Zeyu; Zhang, Bei; Quan, Qi; Peng, Roujun; Huang, Yuanyuan; Su, Xin] Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, State Key Lab Oncol South China,Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China.;[Fan, Teng; Liu, Zeyu; Zhang, Bei; Quan, Qi; Huang, Yuanyuan; Su, Xin] Integrated Tradit Chinese & Western Med Res Ctr, Guangzhou, Peoples R China.;[Zhang, Sihe] Nankai Univ, Sch Med, Dept Cell Biol, Tianjin, Peoples R China.;[Lei, Mengjie] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang, Peoples R China.
通讯机构：
[Peng, RJ; Zhang, B ; Huang, YY] S;Sun Yat Sen Univ, Guangdong Prov Clin Res Ctr Canc, State Key Lab Oncol South China,Canc Ctr, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, Guangzhou 510060, Peoples R China.;Integrated Tradit Chinese & Western Med Res Ctr, Guangzhou, Peoples R China.
关键词：
Nasopharyngeal carcinoma;Qingdu Zengye Decoction;molecular networks;multi-omics;Chinese herb medicine Abbreviations NPC;Nasopharyngeal carcinoma;EBV;Epstein-Barr virus;CCRT;concurrent chemoradiotherapy;PF;Cisplatin + fluorouracil;GP;Gemcitabine + cisplatin;PD-1;programmed cell death protein 1;TCM;traditional Chinese medicine;QZD;Qingdu Zengye Decoction
摘要：
BACKGROUND: Nasopharyngeal carcinoma (NPC) remains a therapeutic challenge due to its aggressive nature and limited treatment efficacy. Traditional Chinese Medicine, particularly Qingdu Zengye Decoction (QZD), has shown clinical potential, but its mechanistic basis in NPC treatment requires elucidation. PURPOSE: This study aims to elucidate the mechanisms of action of QZD in the treatment of NPC, focusing on its multi-target regulatory effects on cell apoptosis, oncogenic signaling pathways, and tumor immune microenvironment. METHODS: An integrative approach combining computational pharmacology, functional experiments, and single-cell transcriptomic profiling was employed to dissect QZD's anti-NPC mechanisms. Network pharmacology and protein-protein interaction (PPI) analysis was used to identify potential QZD targets. Functional assays (cell proliferation, apoptosis, colony formation) and Western blotting were used to validate key pathways. Molecular docking was applied to assessed ligand-target binding affinities. Single-cell RNA sequencing (scRNA-seq) was used to analyzed spatial expression patterns in NPC tumor samples. RESULTS: QZD suppressed tumor progression by inducing apoptosis through modulating Bax in a dose-dependent manner and inhibiting the PI3K-Akt signaling pathway. Network pharmacology analysis identified AKT1, MTOR, HIF1A, SRC, and ESR1 as core regulatory genes. scRNA-seq revealed compartment-specific target localization: AKT1/ESR1 in tumor cells, SRC/IL6 in myeloid cells, and MTOR/HIF1A across stromal compartments. Molecular docking confirmed strong interactions between QZD compounds (e.g., quercetin, luteolin) and these targets. Upregulation of IL6 was observed and its dual immune-modulatory effects involving tumor suppression and microenvironment reprogramming was suggested. CONCLUSION: QZD exerts anti-tumor effects in NPC through apoptosis induction, PI3K-Akt pathway suppression, and multi-compartmental tumor microenvironment modulation. Its ability to concurrently target oncogenic signaling and immune regulation positions QZD as a promising therapeutic strategy for advanced NPC.
摘要：
Objectives Dysregulated inflammatory responses during sepsis often result in acute lung injury (ALI). Neutrophils activated at the primary site of injury can re-enter the circulation through reverse transendothelial migration (rTEM), subsequently infiltrating other organs and contributing to systemic inflammation and multi-organ damage. The specialized pro-resolving lipid mediator (SPM) maresin conjugate in tissue regeneration 1 (MCTR1) has been shown to mitigate organ injury in sepsis. This study investigated the role of neutrophil rTEM in ALI and examined whether MCTR1 can alleviate ALI by modulating neutrophil rTEM.
Dysregulated inflammatory responses during sepsis often result in acute lung injury (ALI). Neutrophils activated at the primary site of injury can re-enter the circulation through reverse transendothelial migration (rTEM), subsequently infiltrating other organs and contributing to systemic inflammation and multi-organ damage. The specialized pro-resolving lipid mediator (SPM) maresin conjugate in tissue regeneration 1 (MCTR1) has been shown to mitigate organ injury in sepsis. This study investigated the role of neutrophil rTEM in ALI and examined whether MCTR1 can alleviate ALI by modulating neutrophil rTEM.
Methods Lung injury was induced in mice by administrating lipopolysaccharide (LPS). Lung damage was assessed using H&E staining, lung wet-to-dry ratio, inflammatory mediator levels, and protein content in the bronchoalveolar lavage fluid. Neutrophil infiltration in lung tissue was evaluated by immunofluorescence, and flow cytometry was used to quantify rTEM neutrophils. Protein expression of neutrophil elastase (NE) and junctional adhesion molecule-C (JAM-C) was analyzed to assess rTEM activity. The role of CXCR4 in neutrophil rTEM was investigated using the CXCR4 inhibitor AMD3100. Additionally, bone marrow-derived neutrophils were isolated to evaluate the effects of MCTR1 on CXCR4 and GRK2 expression.
Lung injury was induced in mice by administrating lipopolysaccharide (LPS). Lung damage was assessed using H&E staining, lung wet-to-dry ratio, inflammatory mediator levels, and protein content in the bronchoalveolar lavage fluid. Neutrophil infiltration in lung tissue was evaluated by immunofluorescence, and flow cytometry was used to quantify rTEM neutrophils. Protein expression of neutrophil elastase (NE) and junctional adhesion molecule-C (JAM-C) was analyzed to assess rTEM activity. The role of CXCR4 in neutrophil rTEM was investigated using the CXCR4 inhibitor AMD3100. Additionally, bone marrow-derived neutrophils were isolated to evaluate the effects of MCTR1 on CXCR4 and GRK2 expression.
Results MCTR1 alleviated lung injury and inhibited neutrophils rTEM in LPS-induced lung injury. MCTR1 also decreased NE expression and increased JAM-C expression. The CXCR4 inhibitor AMD3100 effectively suppressed neutrophil rTEM and alleviated lung injury. Furthermore, MCTR1 inhibited CXCR4 expression and enhanced GRK2 expression.
MCTR1 alleviated lung injury and inhibited neutrophils rTEM in LPS-induced lung injury. MCTR1 also decreased NE expression and increased JAM-C expression. The CXCR4 inhibitor AMD3100 effectively suppressed neutrophil rTEM and alleviated lung injury. Furthermore, MCTR1 inhibited CXCR4 expression and enhanced GRK2 expression.
Conclusions MCTR1 reduces lung damage by upregulating GRK2 to inhibit CXCR4 expression, thereby suppressing neutrophil rTEM in LPS-induced lung injury.
MCTR1 reduces lung damage by upregulating GRK2 to inhibit CXCR4 expression, thereby suppressing neutrophil rTEM in LPS-induced lung injury.
摘要：
Sepsis-associated acute respiratory distress syndrome (ARDS) is a heterogeneous disease with high morbidity and mortality. Lactylation plays a crucial role in sepsis and sepsis-induced lung injury. This study aimed to identify distinct lactylation-based phenotypes in patients with sepsis-associated ARDS and determine relevant molecular biomarkers. We analyzed blood transcriptome and clinical data from patients with sepsis-associated ARDS and calculated the lactylation activity. KEGG pathway analysis, drug sensitivity prediction, and immune cell infiltration analysis were performed. Candidate molecular biomarkers were identified by intersecting the feature genes extracted from four machine learning models. Lactylation activity showed significant heterogeneity among patients with sepsis-associated ARDS, which enabled the classification into low- and high-lactylation activity phenotypes. Patients with high-lactylation experienced longer hospital stays and higher mortality rates, as well as distinct signaling pathways, drug responses, and circulating immune cell abundances. Six key markers (ALDOB, CCT5, EP300, PFKP, PPIA, and SIRT1) were identified to differentiate the two lactylation activity phenotypes, all significantly correlated with circulating immune cell populations. This study revealed significant heterogeneity in lactylation activity phenotypes among patients with sepsis-associated ARDS and identified potential biomarkers to facilitate the application of these phenotypes in clinical practice.
摘要：
Peptides exhibit various biological activities, including biorecognition, cell targeting, and tumor penetration, and can stimulate immune cells to elicit immune responses for tumor immunotherapy. Peptide self-assemblies and peptide-functionalized nanocarriers can reduce the effect of various biological barriers and the degradation by peptidases, enhancing the efficiency of peptide delivery and improving antitumor immune responses. To date, the design and development of peptides with various functionalities have been extensively reviewed for enhanced chemotherapy; however, peptide-mediated tumor immunotherapy using peptides acting on different immune cells, to the knowledge, has not yet been summarized. Thus, this work provides a review of this emerging subject of research, focusing on immunomodulatory anticancer peptides. This review introduces the role of peptides in the immunomodulation of innate and adaptive immune cells, followed by a link between peptides in the innate and adaptive immune systems. The peptides are discussed in detail, following a classification according to their effects on different innate and adaptive immune cells, as well as immune checkpoints. Subsequently, two delivery strategies for peptides as drugs are presented: peptide self-assemblies and peptide-functionalized nanocarriers. The concluding remarks regarding the challenges and potential solutions of peptides for tumor immunotherapy are presented. This work introduces the role of peptides in immune regulation of innate and adaptive immune cells, as well as immune checkpoints. Then this work introduces two strategies for delivering polypeptides: peptide self-assemblies, and peptide-functionalized nanocarriers. Finally, the challenges and prospects of peptides in tumor immunotherapy are summarized. image
摘要：
The major facilitator superfamily (MFS) type efflux pumps of Acinetobacter baumannii play important roles in antibiotic resistance. However, the molecular mechanism of these transporters remains poorly understood. To address the molecular basis of substrate polyspecificity mediated by multidrug MFS transporters, we compared the substrate binding modes of A. baumannii CraA with its well-studied homolog, Escherichia coli MdfA. MdfA and CraA share similar structural features, including a cavity accessible to drugs from the cytoplasm when these transporters adopt the inside-out conformation. This predominantly hydrophobic cavity contains several distinct titratable and hydrophilic residues. Through substitution analysis, we demonstrate that these polar residues within the CraA drug binding cavity contribute to the transport of all tested drugs, whereas mutations of hydrophobic residues result in altered drug recognition profiles. In addition to the known titratable residues E38 and D46, we identified E338 as the only titratable residue that plays a substrate-specific role, as it is required for efficient transport of norfloxacin, but not ethidium. Substitution of E338 with asparagine or glutamine changes substrate specificity, enabling specific recognition of phenicols and mitomycin C. Furthermore, we show that the aromaticity of Y42 is crucial for phenicol recognition, while general hydrophobicity at this position is critical for mitomycin C specificity. We propose that E338 and Y42 function as key substrate selectivity determinants in CraA. IMPORTANCE Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
The major facilitator superfamily (MFS) type efflux pumps of Acinetobacter baumannii play important roles in antibiotic resistance. However, the molecular mechanism of these transporters remains poorly understood. To address the molecular basis of substrate polyspecificity mediated by multidrug MFS transporters, we compared the substrate binding modes of A. baumannii CraA with its well-studied homolog, Escherichia coli MdfA. MdfA and CraA share similar structural features, including a cavity accessible to drugs from the cytoplasm when these transporters adopt the inside-out conformation. This predominantly hydrophobic cavity contains several distinct titratable and hydrophilic residues. Through substitution analysis, we demonstrate that these polar residues within the CraA drug binding cavity contribute to the transport of all tested drugs, whereas mutations of hydrophobic residues result in altered drug recognition profiles. In addition to the known titratable residues E38 and D46, we identified E338 as the only titratable residue that plays a substrate-specific role, as it is required for efficient transport of norfloxacin, but not ethidium. Substitution of E338 with asparagine or glutamine changes substrate specificity, enabling specific recognition of phenicols and mitomycin C. Furthermore, we show that the aromaticity of Y42 is crucial for phenicol recognition, while general hydrophobicity at this position is critical for mitomycin C specificity. We propose that E338 and Y42 function as key substrate selectivity determinants in CraA.
IMPORTANCE
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
Multidrug efflux transporters of the major facilitator superfamily (MFS) are key contributors to antibiotic resistance, mediating the export of structurally diverse compounds across bacterial membranes. While homologous transporters such as Escherichia coli MdfA and Acinetobacter baumannii CraA share high structural similarity and overlapping substrate profiles, the molecular basis of their substrate specificity remains poorly understood. In this study, we show that structural homology among MFS transporters does not inherently imply mechanistic conservation, as species-specific variations can give rise to distinct substrate recognition profiles. Our findings reveal that CraA utilizes unique residues Y42 and E338 for substrate selectivity, while R124 and Y73 contribute to its transport activity. These findings enhance our understanding of efflux pump specificity and underscore the need to consider organism-specific features when targeting multidrug transporters in antimicrobial therapy.
摘要：
Tripartite-motif protein family member 65 (TRIM65) belongs to the tripartite motif (TRIM) protein family. Its typical structure consists of the RING, B-Box motif, and coiled-coil domains, which are highly conserved at the N-terminus and the variable SPRY domain at the C-terminus. TRIM65 is an E3 ubiquitin ligase that participates in physiological and pathological processes through the ubiquitination pathway, including intracellular signal transduction, protein degradation, cell proliferation, apoptosis, carcinogenesis, autophagy, and phenotypic transformation. Evidence shows that TRIM65 plays a remarkable and obscure role in diseases, including multisystem tumours, neurodegenerative diseases, immune system diseases, and inflammatory diseases. This review is devoted to elaborating on the relationship between TRIM65 and diseases and its pathogenic mechanism, providing a theoretical basis for TRIM65 as a possible pathogenic target of diseases and exploring the possible future research direction of TRIM65 and the challenges it may face.
期刊：
Biosensors and Bioelectronics,2025年:117950 ISSN：0956-5663
通讯作者：
Yu Liu
作者机构：
[Yao Yu; Sihan Chen; Le Li] Hunan Key Laboratory of Typical Environment Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, PR China;Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China;[Qingyun Cai] State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China;[Deshuai Zhen; Qiuhui Deng] Hunan Key Laboratory of Typical Environment Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China;[Yu Liu] Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
通讯机构：
[Yu Liu] C;Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
摘要：
A highly sensitive, selective, and simple method for detecting uranyl ions (UO 2 2+ ) is crucial for human health and environmental safety. Amidoxime-based nanomaterials have been widely employed for UO 2 2+ detection, but their higher affinity for vanadium than UO 2 2+ limits their practical applications. Herein, a novel covalent organic polymer fluorescent probe (TT-COP) for UO 2 2+ detection was innovatively developed by a one-step Schiff-base condensation reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and 2,4,6-triformylphloroglucinol (Tp). TT-COP not only possesses excellent thermodynamic stability, hydrophilicity, synthetic reproducibility, and fluorescence stability but also achieves outstanding sensing performance, with its interaction with UO 2 2+ reaching equilibrium within 5 min and a detection limit of 35.75 nM. Further investigations reveal that UO 2 2+ coordinates with the imine and hydroxyl groups of TT-COP, thereby inhibiting the intramolecular charge transfer (ICT) process and leading to fluorescence quenching. Moreover, TT-COP exhibits extraordinary selectivity and biocompatibility, enabling reliable UO 2 2+ quantification in complex matrices including environmental waters, food, and biological samples, with recovery rates ranging from 94.54% to 106.43%. The detection results closely align with those obtained from high-precision ICP-MS measurements. These findings underscore the promising practical applications of TT-COP in food safety, environmental monitoring, and human health assessment.
A highly sensitive, selective, and simple method for detecting uranyl ions (UO 2 2+ ) is crucial for human health and environmental safety. Amidoxime-based nanomaterials have been widely employed for UO 2 2+ detection, but their higher affinity for vanadium than UO 2 2+ limits their practical applications. Herein, a novel covalent organic polymer fluorescent probe (TT-COP) for UO 2 2+ detection was innovatively developed by a one-step Schiff-base condensation reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and 2,4,6-triformylphloroglucinol (Tp). TT-COP not only possesses excellent thermodynamic stability, hydrophilicity, synthetic reproducibility, and fluorescence stability but also achieves outstanding sensing performance, with its interaction with UO 2 2+ reaching equilibrium within 5 min and a detection limit of 35.75 nM. Further investigations reveal that UO 2 2+ coordinates with the imine and hydroxyl groups of TT-COP, thereby inhibiting the intramolecular charge transfer (ICT) process and leading to fluorescence quenching. Moreover, TT-COP exhibits extraordinary selectivity and biocompatibility, enabling reliable UO 2 2+ quantification in complex matrices including environmental waters, food, and biological samples, with recovery rates ranging from 94.54% to 106.43%. The detection results closely align with those obtained from high-precision ICP-MS measurements. These findings underscore the promising practical applications of TT-COP in food safety, environmental monitoring, and human health assessment.
