期刊：
Journal of Cardiovascular Translational Research,2025年:1-15 ISSN：1937-5387
通讯作者：
Dai, Xiaoyan;Peng, Juan;Tang, Zhihan
作者机构：
[Ni Gan; Yanyu Chen; Qiong Xiang; Yuting Cui; Man Li; Yating Zhou] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Wen Zeng] Shaoyang Branch of Key Laboratory for Arteriosclerology of Hunan Province, The Central Hospital of Shaoyang, Shaoyang, 421001, China;[Xi-Long Zheng] Departments of Biochemistry & Molecular Biology and Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada;[Xiaoyan Dai] Clinical Research Center, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, China. xdai@usc.edu.cn;[Xiaoyan Dai] Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Hengyang, 421002, China. xdai@usc.edu.cn
通讯机构：
[Peng, Juan; Tang, Zhihan] I;[Dai, Xiaoyan] C;Clinical Research Center, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421002, China.;Hunan Provincial Key Laboratory of Basic and Clinical Pharmacological Research of Gastrointestinal Cancer, Hengyang, 421002, China.;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, China.
摘要：
Ferroptosis plays a key role in abdominal aortic aneurysm (AAA) development. This study explores whether and how ferroptosis regulates AAA progression. Ferroptosis was confirmed in human AAA tissue. In vitro experiments with primary mouse vascular smooth muscle cells (VSMCs) and abdominal aortic rings revealed that angiotensin II (Ang II) triggered ferroptosis in VSMCs. Ferrostatin-1 (Fer-1), a potent ferroptosis inhibitor, effectively suppressed this effect. Additionally, the ferroptosis inducer erastin and Ang II can both promoted pathological remodeling of abdominal aortic rings, but Fer-1 significantly suppressed these effects. In AAA mouse model, Fer-1 treatment reduced AAA formation. Mechanistically, RNA-sequencing analysis revealed that Fer-1 regulates VSMC contractile function, suppresses inflammation, and mitigates extracellular matrix remodeling. These findings highlight the critical role of VSMC ferroptosis in AAA pathogenesis and demonstrate that ferroptosis inhibition effectively reduces pathological vascular remodeling, making it a promising therapeutic strategy for preventing AAA.
期刊：
NEW ENGLAND JOURNAL OF MEDICINE,2025年 ISSN：0028-4793
作者机构：
[You, Feng; Zi, Wenjie; Li, Maohua; Li, Linyu; Tian, Yan; Xie, Dongjing; Long, Xingmin; Qiu, Zhongming; Tao, Jian; Jiang, Ling; Meng, Zhaoyou; Zhou, Kai; Li, Fengli] Department of Neurology, Second Affiliated Hospital of Army Medical University (Xinqiao Hospital), Chongqing, China;[Feng, Xinggang; Wu, Yuelu; Cai, Lingyu; Li, Qi; Qiu, Zhongming; Jiang, Bingwu] Department of Neurology, No. 903 Hospital of the People's Liberation Army (PLA) Joint Logistics Support Force, Hangzhou, China;[Yin, Congguo; Sang, Hongfei] Department of Neurology, Hangzhou First People's Hospital and School of Medicine of Westlake University, Hangzhou, China;[Wu, Junxiong; Long, Chen; Wu, Derong; Yuan, Guangxiong] Emergency Department, Xiangtan Central Hospital (Affiliated Hospital of Hunan University), Xiangtan, China;[Yang, Bo; Kong, Zhenyu] Department of Neurology, First Affiliated Hospital of Henan Polytechnic University (Jiaozuo Second People's Hospital), Jiaozuo, China
摘要：
BACKGROUND: The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain. METHODS: In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible for thrombolysis to receive either intravenous tenecteplase followed by endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was functional independence (a score of 0 to 2 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 90 days. Secondary outcomes included successful reperfusion before and after thrombectomy. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and death within 90 days. RESULTS: A total of 278 patients were randomly assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. Functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and in 120 patients (44.1%) in the thrombectomy-alone group (unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P = 0.04). A total of 6.1% of the patients in the tenecteplase-thrombectomy group and 1.1% of those in the thrombectomy-alone group had successful reperfusion before thrombectomy, and 91.4% and 94.1%, respectively, had successful reperfusion after thrombectomy. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the patients in the tenecteplase-thrombectomy group and in 6.7% of those in the thrombectomy-alone group; mortality at 90 days was 22.3% and 19.9%, respectively. CONCLUSIONS: Among patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, the percentage of patients with functional independence at 90 days was higher with intravenous tenecteplase plus endovascular thrombectomy than with endovascular thrombectomy alone. (Funded by the Chongqing Science and Health Joint Medical Research Project and others; BRIDGE-TNK ClinicalTrials.gov number, NCT04733742.).
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.
作者机构：
[Zhong, Jing; Zhao, Hu; Zhong, J; Xiao, Qian] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Qian] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Clin Lab Med, Hengyang 421001, Hunan, Peoples R China.;[An, Yangfang] Yiyang Cent Hosp, Yiyang 413099, Hunan, Peoples R China.;[Wang, Mu] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Clin Mass Spectrometry Lab, Hengyang, Peoples R China.;[Zhong, Jing] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhong, J ; Wang, M ] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Clin Mass Spectrometry Lab, Hengyang, Peoples R China.
摘要：
Phospholipids, complex lipids prevalent in the human body, play crucial roles in various pathophysiological processes. Beyond their synthesis and degradation, phospholipids can influence chemoresistance by participating in ferroptosis. Extensive evidence highlights the significant link between tumor drug resistance and phospholipids. Therefore, drugs targeting phospholipid metabolism itself or the synthesis of corresponding composite materials will effectively overcome the difficulties of clinical tumor treatment.
Phospholipids, complex lipids prevalent in the human body, play crucial roles in various pathophysiological processes. Beyond their synthesis and degradation, phospholipids can influence chemoresistance by participating in ferroptosis. Extensive evidence highlights the significant link between tumor drug resistance and phospholipids. Therefore, drugs targeting phospholipid metabolism itself or the synthesis of corresponding composite materials will effectively overcome the difficulties of clinical tumor treatment.
期刊：
International Journal of Surgery,2025年 ISSN：1743-9191
作者机构：
[Liao, Wei] Department of Anesthesiology, The First People's Hospital of Chenzhou, The Affiliated ChenZhou Hospital, Hengyang Medical School, University of South China, Chenzhou, Hunan, China
关键词：
cancer pain;dexmedetomidine;opioid-sparing;opioids;α-2 adrenergic receptors
摘要：
BACKGROUND AND OBJECTIVE: Cancer pain treatment faces challenges such as ineffective pain management, high-dose opioid use, and insufficient analgesia. Dexmedetomidine (DEX), a novel α2 receptor agonist, is a potential adjuvant analgesic. Its analgesic mechanism involves central coeruleus cell hyperpolarization, activation of peripheral, spinal cord, and spinal α2 receptors, and regulation of cellular signaling pathways and inflammatory factors. DEX reduces harmful neurotransmitter production and pain signal transmission and enhances opioid analgesia while decreasing opioid use and tolerance. This review introduces the main mechanisms of DEX and its potential for treating complex and refractory cancer pain. METHODS: We conducted literature searches using the terms "dexmedetomidine," "cancer pain," "opioid sparing," "analgesic mechanism," and their combinations in PubMed, Embase, Cochrane Library, and Web of Science. We systematically retrieved research articles, reviews, and editorials published in English up to mid-December 2024. All identified publications were reviewed, and their key references were cross-checked to ensure a comprehensive and high-quality review. KEY CONTENT AND FINDINGS: Preclinical and clinical studies have demonstrated the advantages and potential of DEX in cancer pain management. DEX has intrinsic analgesic properties and can significantly relieve cancer pain by interacting with opioids, thereby delaying the development of opioid tolerance. It is particularly suitable for patients with refractory cancer pain and provides effective treatment whether used as an analgesic or an anesthetic adjuvant. CONCLUSIONS: DEX is a promising adjuvant for cancer pain management, utilizing multi-mechanism analgesia and opioid-sparing effects to address unmet needs in refractory cases. Preclinical and clinical studies highlight efficacy heterogeneity across different cancer types and limited long-term safety data. High-quality, multicenter randomized controlled trials are needed to determine the optimal dose, refine dosing regimens, and verify results across diverse populations. Until further evidence is available, DEX should be considered a valuable adjunct in individualized, multimodal analgesic strategies, with careful monitoring of hemodynamic parameters and central nervous system adverse events.
通讯机构：
[Tang, BS ; Qiu, J ; Qiu, J] C;Cent South Univ, Xiangya Hosp, Dept Neurol, Dept Geriatr, Changsha 410008, Peoples R China.;Cent South Univ, Xiangya Hosp, Hunan Key Lab Mol Precis Med, Changsha 41008, Peoples R China.
摘要：
OBJECTIVE: Despite substantial advancements in uncovering the genetic basis of Parkinson's disease (PD), a significant portion of cases characterized by familial PD remain genetically elusive. Here, we reported that biallelic variants in EPG5, a key autophagy gene responsible for Vici syndrome, are associated with PD. METHODS: Whole-exome sequencing (WES) was performed in the first cohort including 171 pedigrees with autosomal recessive PD (ARPD), 1,746 cases of sporadic early-onset PD (sEOPD, age at onset ≤ 50 years) and 1,652 healthy controls. Whole-genome sequencing (WGS) was performed in the second cohort consisting of 1,947 sporadic late-onset PD (sLOPD, age at onset >50 years) and 2,478 healthy controls. RESULTS: We identified 7 participants harboring compound heterozygous variants within the EPG5 gene across 1 family with ARPD (ARPD-F1), 4 sporadic EOPD cases, and 1 sporadic LOPD individual. A total of 10 novel variants in EPG5 were discovered in the 7 individuals, comprising 3 nonsense variants and 7 missense variants. The compound heterozygous variants in the EPG5 gene led to decreased expression of EPG5 protein, and impaired autophagy-lysosome function in cells derived from EPG5-PD individuals. We also revealed several key pathological features, including abnormal accumulation of autophagic vacuoles, aggregation of α-synuclein in skin tissue from EPG5-PD individuals. In mice, EPG5 deficiency led to progressive dopaminergic neurodegeneration in the substantia nigra of the midbrain. INTERPRETATION: Our results unveil a novel association between biallelic variants in EPG5 gene and PD, providing compelling initial evidence for the involvement of EPG5 and autophagy dysregulation in the development of PD. ANN NEUROL 2025.
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
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD; Wu, GL] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Pharm & Pharmacol, Hengyang Med Sch, Sch Pharmaceut Sci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
摘要：
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
The advancement of mitochondria-targeted near-infrared-II (NIR-II) excitable phototheranostics constitutes a promising strategy for improving fluorescence-image-guided cancer phototherapy. However, developing phototheranostic agents that simultaneously combine high-contrast NIR-II fluorescence imaging with effective multimodal therapeutic techniques remains a substantial challenge. Herein, we reported a shielding-donor–acceptor–donor-shielding structured NIR-II phototheranostic (FCD-T) by a molecular engineering strategy, followed by self-assembly with glutathione-responsive copolymer to form FCD-T nanoparticles. The introduction of functional bithiophene endows FCD-T with significant electron-donating properties and reduces intermolecular π-π stacking interactions. The robust π-conjugation of fluorene with good rigidity would enhance the intramolecular charge transfer capability. Therefore, FCD-T NPs exhibited an NIR-II absorption peak at 1075 nm and an emission peak at 1280 nm. Upon NIR-II light excitation, such nanoparticles could generate excellent photothermal and photodynamic performances with good biocompatibility. Moreover, the NIR-II mitochondria-targeted phototherapy further facilitated mitochondrial apoptosis-related pathways, activating antitumor immunity and inhibiting tumor growth with single irradiation at low doses.
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摘要：
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
Early recognition is key to improving the prognosis of ischemic stroke (IS), while available imaging methods tend to target events that have already undergone ischemia. A new method to detect early IS is urgently needed, as well as further study of its mechanisms. Viscosity and cysteine (Cys) levels of mitochondria have been associated with ferroptosis and IS. It is possible to identify IS and ferroptosis accurately and early by monitoring changes in mitochondrial Cys and viscosity simultaneously. In this work, a viscosity/Cys dual-responsive mitochondrial-targeted near-infrared (NIR) fluorescent probe ( NVCP ) was constructed for the precise tracking of IS using a two-dimensional design strategy. NVCP consists of a chromophore dyad containing diethylaminostyrene quinolinium rotor and chloro‑sulfonylbenzoxadiazole (SBD-Cl) derivative with two easily distinguished emission bands (λ em = 592 and 670 nm). NVCP performs the way of killing two birds with one stone, that is, the probe exhibits excellent selectivity and sensitivity for detecting viscosity and Cys in living cells with excellent biocompatibility and accurate mitochondrial targeting capability by dual channel imaging mode. In addition, NVCP recognized that the viscosity increases and Cys level decreases in cells when undergoing ferroptosis and oxygen-glucose deprivation (OGD) stress by confocal imaging, flow cytometry, and Western blot experiments. Treatment of ferroptosis inhibitors (ferrostatin-1 (Fer-1) and deferoxamine (DFO)) could reverse the variation tendency of viscosity and Cys. This is the first time that the relationship between ferroptosis and IS was identified through an analysis of Cys and viscosity. More importantly, the ischemic area was also instantly distinguished from normal tissues through fluorescence imaging of NVCP in vivo . The developed NIR dual-responsive probe NVCP toward viscosity and Cys could serve as a sensitive and reliable tool for tracking ferroptosis-related pathological processes during IS.
通讯机构：
[Tan, XF; Yang, QL ; Wu, GL] U;Univ South China, Affiliated Hosp 1, Dept Hepatopancreatobiliary Surg, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, NHC Key Lab Birth Defect Res & Prevent, Hengyang 421001, Hunan, Peoples R China.;Univ South China, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.
关键词：
NIR-II;Phototheranostics;Endoplasmic reticulum;Triple-negative breast cancer;Intermolecular π–π stacking interaction
摘要：
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer characterized by an extremely poor prognosis. Photoimmunotherapy has emerged as a promising strategy for the treatment of TNBC. This approach works by selectively destroying tumor cells, releasing tumor-associated antigens, activating the immune system, and effectively inhibiting tumor proliferation and metastasis. However, the majority of current phototheranostic approaches are hindered by limited tissue penetration in the first near-infrared (NIR-I) and ultraviolet-visible (UV-Vis) regions. Additionally, due to the lack of specific subcellular targets, it may be difficult to effectively treat deep-seated lesions with ambiguous and extensive boundaries caused by TNBC metastases. Consequently, the development of effective, deep-penetrating, organelle-targeted phototheranostics is essential for enhancing treatment outcomes in TNBC. This work proposes a novel molecular design strategy of NIR-II phototheranostics to realize planar rigid conjugation and alkyl chain functionalization. The di-hexaalkyl chains in a vertical configuration on the donor (4H-cyclopenta[2,1-b:3,4-b'] dithiophene) and shielding units (fluorene) are introduced to construct a S-D-A-D-S type NIR-II phototheranostics (IR-FCD). The planar and rigid structure of IR-FCD exhibits a robust intramolecular charge transfer capability, a lower band gap, enhanced photon absorption properties, and significant steric hindrance from vertically arranged alkyl chains to minimize non-radiative energy loss. By incorporating N-(but-3-yn-1-yl)-4-methylbenzenesulfonamide at the terminus of an elongated alkyl chain, followed by self-assembly into DSPE-S-S-PEG2000, NIR-II excitable phototheranostics (IR-FCD-Ts NPs) with endoplasmic reticulum (ER) targeting capability were successfully synthesized for imaging-guided photoimmunotherapy of TNBC. The IR-FCD-Ts NPs demonstrate exceptional optical characteristics, with maximum absorption at 1068nm (extending to 1300nm) and emission at 1273nm (extending to 1700nm), along with a high molar absorption coefficient of 2.76*10(4)L/mol·c at 1064nm in aqueous solution. Under exposure to 1064nm laser irradiation, IR-FCD-Ts NPs exhibit superior photothermal properties and have the potential for photodynamic therapy. By targeting ER, thereby inducing ER stress and significantly enhancing immunogenic cell death (ICD) in tumor cells, it triggers a strong antitumor immune response and inhibits the proliferation and metastasis of TNBC.
期刊：
EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY,2025年37(6):683-690 ISSN：0954-691X
作者机构：
[Pan, Linghui; Yan, Fangran] Department of Anesthesiology, Guangxi Medical University Cancer Hospital;[Yan, Fangran; Du, Xueke] Department of Anesthesiology;[Zhou, Zenghua] Departments of Pain, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region;[He, Sheng] Department of Anesthesiology, The First Affiliated Hospital of Southern China University, Hengyang, Hunan Province;[Pan, Linghui] Guangxi Clinical Research Center for Anesthesiology
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.
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
摘要：
Background The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined.
The important effects of variability of some physiological/biological characteristics (such as LDL cholesterol, blood pressure) on cardiovascular outcomes have been elucidated, while the role of insulin variability is undefined.
Objectives To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age.
To investigate the associations of long-term fasting insulin variability during young adulthood before the onset of diabetes with subsequent cardiovascular outcomes in middle age.
Methods We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated.
We included 3,983 CARDIA (Coronary Artery Risk Development Study in Young Adults) participants aged 18 to 30 years with at least three fasting insulin measurements. Intra-individual fasting insulin variability was defined by the average real variability (ARV) of insulin and standard deviation (SD) of insulin during 30-year follow-up. The presence and the degree of coronary artery calcification (CAC) were assessed by computed tomography at year 25. Incident cardiovascular disease (CVD) and all-cause mortality were adjudicated.
Results After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65 % (HR, 1.65; 95 % CI, 1.13–2.39) and all-cause mortality by 97 % (HR, 1.97; 95 % CI, 1.38–2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95 % CI, 0.03–0.18) but not with the presence of CAC ( P = 0.197). Similar results were also observed in insulin SD.
After multivariable adjustment, comparing high versus low tertile of insulin ARV, the hazard of CVD increased by 65 % (HR, 1.65; 95 % CI, 1.13–2.39) and all-cause mortality by 97 % (HR, 1.97; 95 % CI, 1.38–2.82). Higher tertile of insulin ARV was associated with significantly worse degree of CAC (β =0.1; 95 % CI, 0.03–0.18) but not with the presence of CAC ( P = 0.197). Similar results were also observed in insulin SD.
Conclusion High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.
High long-term insulin variability in young adulthood before the onset of diabetes was associated with an increased risk of CVD and all-cause mortality in later life, independent of average FG, HOMA-IR and other established cardiovascular risk factors. Long-term insulin variability was associated with the degree but not the presence of CAC.
摘要：
Channel catfish ( Ictalurus punctatus ), a significant aquaculture species, occupies a prominent position in the aquaculture industry due to its rapid growth, excellent adaptability, and economic value; however, the hemorrhagic disease caused by Aeromonas hydrophila has had a substantial impact on its cultivation. Researches have indicated that cortisol, the main stress hormone, is essential for regulating immune responses. Therefore, in this study, the immune regulatory effects of cortisol on the spleen tissue under Aeromonas hydrophila stimulation were analyzed. Through transcriptomic (RNA-seq) analysis, we identified 167 differentially expressed genes (DEGs) regulated by cortisol. The KEGG enrichment analysis indicated that the DEGs were predominantly associated with various biological pathways, including antigen processing and presentation, bladder cancer, autophagy in animals, lipid metabolism, and atherosclerosis. Protein-protein interaction network analysis further indicated that these DEGs participate in key signaling pathways, including HIF, JAK-STAT, and NF-KB. Our findings demonstrate that cortisol exerts an immunoregulatory effect by modulating these key signaling pathways in the spleen tissue infected with Aeromonas hydrophila , which is of significant importance for understanding the mechanism of cortisol in fish immune responses.
Channel catfish ( Ictalurus punctatus ), a significant aquaculture species, occupies a prominent position in the aquaculture industry due to its rapid growth, excellent adaptability, and economic value; however, the hemorrhagic disease caused by Aeromonas hydrophila has had a substantial impact on its cultivation. Researches have indicated that cortisol, the main stress hormone, is essential for regulating immune responses. Therefore, in this study, the immune regulatory effects of cortisol on the spleen tissue under Aeromonas hydrophila stimulation were analyzed. Through transcriptomic (RNA-seq) analysis, we identified 167 differentially expressed genes (DEGs) regulated by cortisol. The KEGG enrichment analysis indicated that the DEGs were predominantly associated with various biological pathways, including antigen processing and presentation, bladder cancer, autophagy in animals, lipid metabolism, and atherosclerosis. Protein-protein interaction network analysis further indicated that these DEGs participate in key signaling pathways, including HIF, JAK-STAT, and NF-KB. Our findings demonstrate that cortisol exerts an immunoregulatory effect by modulating these key signaling pathways in the spleen tissue infected with Aeromonas hydrophila , which is of significant importance for understanding the mechanism of cortisol in fish immune responses.
作者机构：
[Wang, Lihua] Hengyang Maternal and Child Health Hospital, Hengyang, China;[Zheng, Qinwen; Wei, Dangheng"] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China;[Liu, Yue] Department of Neurology, the Third Xiangya Hospital, Central South University, Changsha, China;Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China;["Xia, Dexiang] Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, China
通讯机构：
[Lihua Wang] H;[Dangheng Wei] I;Hengyang Maternal and Child Health Hospital, Hengyang, China<&wdkj&>Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Recent groundbreaking preclinical and clinical research underscores the pivotal role of metabolite remodelling in the pathology of CVD. This metabolic transformation not only directly fuels the progression of CVD but also profoundly influences the immune response within the cardiovascular system. In this review, we focused on the complex interactions between cardiovascular metabolic alterations and immune responses during the course of CVD. Furthermore, we explore the potentialtherapeutic interventions that could be developed based on the understanding of metabolic alterations and immune dysregulation in CVD. By targeting these metabolic and immunological pathways, novel strategies for the prevention and treatment of CVDs might be developed to improve patient outcomes and reduce the global burden of this disease.
期刊：
Brain and Behavior,2025年15(1):e70245- ISSN：2162-3279
通讯作者：
Xiao, ZJ
作者机构：
[Deng, Limin; Lin, Shudong; Xie, Juan; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;[Deng, Limin; Lin, Shudong; Chen, Shuangxi; Liu, Guozhi; Xiao, Zijian; Wen, Xuanwei; Li, Sijing; Zhu, Guanghua; Wang, Feiyan; Xiao, ZJ] Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Xie, Juan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Emergency, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xiao, ZJ ] U;Univ South China, Affiliated Hosp 1, Multi Res Ctr Brain Disorders, Hengyang Med Sch,Dept Neurol, Hengyang, Hunan, Peoples R China.;Univ South China, Clin Res Ctr Immune Related Encephalopathy Hunan P, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.
关键词：
cerebral amyloid angiopathy (CAA);curcumin;learning and memory;necroptosis;neuroinflammation
摘要：
BACKGROUND AND PURPOSE: Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti-Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. METHOD: The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high-cholesterol diet, and copper-containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p-RIPK-1, p-RIPK-3, p-MLKL, neuronal morphology, and learning and memory abilities in mice. RESULT: The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. CONCLUSION: Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors.
摘要：
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Of mAbs, those isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but the KP.3 became susceptible to neutralization by the other mAb, SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.
作者机构：
[Li, Shuihong; Zhang, Ru; Zuo, Yingying] Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, SH ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.
关键词：
M. pneumoniae;MAPK;NF-κB;RAW264.7;rMPN606
摘要：
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
Mycoplasma pneumoniae ( M. pneumoniae ) is one of the major pathogens causing community-acquired pneumonia (CAP), and its pathogenic mechanism is not fully understood. Inflammatory response is the most basic and common pathological phenomenon of CAP, but the specific mechanism needs further investigation. In this study, the inflammatory action of M. pneumoniae MPN606 protein was confirmed and its molecular mechanism was tentatively investigated. Compared with the control group treated with PBS, stimulation of RAW264.7 cells with rMPN606 can promote the release of NO, increase the expression level of TNF-α and IL⁃6 cytokines, and up-regulate the mRNA transcription levels of iNOS, IL-6 and TNF-α in RAW264.7 cells. In addition, rMPN606 also significantly induced the expression of iNOS protein in RAW264.7 cells, resulting in increased phosphorylation levels of p65, p38 and ERK proteins. The results of cellular immunofluorescence showed that NF-κB was transferred from cytoplasm to nucleus of RAW264.7 cells after stimulation with rMPN606, and nuclear translocation of NF-κB was significantly enhanced. These results indicate that Mycoplasma pneumoniae MPN606 induces M1-type activation of macrophages and secretes pro-inflammatory factors by activating NF-κB and MAPK pathways.
