作者机构：
[Zhou, Jie; Xie, Bibo; Zhao, Feijun; Zhao, FJ; Duan, Junxia; Zhao, Sisi; Liu, Peng; Liu, P; Zhang, Xiaohong] Univ South China, Inst Pathogen Biol, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;[Zhou, Jie; Xie, Bibo; Zhao, Feijun; Zhao, FJ; Duan, Junxia; Zhao, Sisi; Liu, Peng; Liu, P; Zhang, Xiaohong] Univ South China, Key Lab Special Pathogen Prevent & Control Hunan, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;[Wang, Yali] Univ South China, Hengyang Med Coll, Dept Clin Med Undergrad, Hengyang, Peoples R China.;[Yin, Weiguo] Qingyuan Peoples Hosp, Dept Lab, Qingyuan, Peoples R China.
通讯机构：
[Zhao, FJ ; Liu, P] U;Univ South China, Inst Pathogen Biol, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.;Univ South China, Key Lab Special Pathogen Prevent & Control Hunan, Affiliated Hosp 1, Dept Clin Lab Med,Hengyang Med Coll, Hengyang, Peoples R China.
关键词：
Tp0971;Treponema pallidum;immune-protective effect;invasion process
摘要：
Treponema pallidum (T. pallidum), the pathogen of syphilis, can invade organisms through mucous membranes or broken skin and proliferate in the host. It spreads rapidly and causes chronic systemic multi-organ damage. Currently, the invasion and pathogenesis of T. pallidum remain a mystery. In this study, we established a T. pallidum infection model in New Zealand rabbits, and the T. pallidum burden in various tissues and organs was detected to investigate the dynamic spread of T. pallidum in different organs. Our results indicated that the T. pallidum burden in rabbits was in a cyclic and repeated dynamic process of decreasing and increasing after infection. In addition, the localization of lipoprotein Tp0971 was confirmed by using the gel microdroplet method. We found that Tp0971 might be a membrane lipoprotein that exists in the inner and outer membranes of T. pallidum. The immune-protective effect of the T. pallidum infection-dependent antigen Tp0971 was evaluated. Tp0971/CpG can induce high levels of Tp0971-specific antibodies, delay skin damage, and promote healing at the infected sites of T. pallidum in New Zealand rabbits. This indicated that Tp0971 may serve as a vaccine antigen candidate. Our results provide new ideas for future research on the proliferation, spread mechanism, and vaccine development of T. pallidum. IMPORTANCE The past two decades have seen a worldwide resurgence in infections caused by Treponema pallidum (T. pallidum) subsp. pallidum, the syphilis spirochete. The well-recognized capacity of the syphilis spirochete for early dissemination and immune evasion has earned it the designation '' the stealth pathogen.'' There are many hurdles to studying syphilis pathogenesis, most notably the difficulty of culturing and genetically manipulating T. pallidum, as well as the absence of an effective vaccine for T. pallidum prevention. T. pallidum infection in humans is a complex and lengthy process. In this study, we investigated the invasion process and the function of the infection-dependent antigen Tp0971 as an immunogen to inhibit the dissemination of T. pallidum in an animal infection model. This enables a better understanding of the specific pathogenic mechanism of this pathogen, syphilis pathogenesis, and vaccine research.
期刊：
European Journal of Pharmacology,2023年953:175537 ISSN：0014-2999
通讯作者：
Hu, JY
作者机构：
[Wang, Yu-Fei] Univ South China, Hengyang Med Sch, Affiliated Changsha Cent Hosp, Dept Clin Lab, Changsha 410004, Peoples R China.;[Hu, Jin-Yue] Univ South China, Hengyang Med Sch, Affiliated Changsha Cent Hosp, Med Res Ctr, Changsha 410004, Peoples R China.
通讯机构：
[Hu, JY ] U;Univ South China, Hengyang Med Sch, Affiliated Changsha Cent Hosp, Med Res Ctr, Changsha 410004, Peoples R China.
摘要：
Glioma is the most frequent and most malignant tumor of the central nervous system (CNS)，accounting for about 50% of all CNS tumor and approximately 80% of the malignant primary tumors in the CNS. Patients with glioma benefit from surgical resection, chemo- and radio-therapy. However these therapeutical strategies do not significantly improve the prognosis, nor increase survival rates owing to restricted drug contribution in the CNS and to the malignant characteristics of glioma. Reactive oxygen species (ROS) are important oxygen-containing molecules that regulate tumorigenesis and tumor progression. When ROS accumulates to cytotoxic levels, this can lead to anti-tumor effects. Multiple chemicals used as therapeutic strategies are based on this mechanism. They regulate intracellular ROS levels directly or indirectly, resulting in the inability of glioma cells to adapt to the damage induced by these substances. In the current review, we summarize the natural products, synthetic compounds and interdisciplinary techniques used for the treatment of glioma. Their possible molecular mechanisms are also presented. Some of them are also used as sensitizers: they modulate ROS levels to improve the outcomes of chemo- and radio-therapy. In addition, we summarize some new targets upstream or downstream of ROS to provide ideas for developing new anti-glioma therapies.
通讯机构：
[Xiao, ZJ ] U;Univ South China, Affiliated Hosp 1, Dept Neurol, 69 Chuanshan Rd, Hengyang, Hunan, Peoples R China.
关键词：
Aβ deposition;Cerebral amyloid angiopathy (CAA);MICU3;Mitochondrial impairment and dysfunction;PINK1
摘要：
Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-β (Aβ) accumulation, and always accompanied by Alzheimer's disease (AD). Mitochondrial dysfunction-associated cellular events including cell death, inflammation and oxidative stress are implicated in the progression of CAA. Unfortunately, the molecular mechanisms revealing CAA pathogenesis are still obscure, thus requiring further studies. Mitochondrial calcium uptake 3 (MICU3), a regulator of the mitochondrial Ca(2+) uniporter (MCU), mediates various biological functions, but its expression and influence on CAA are largely unknown. In the present study, we found that MICU3 expression was gradually declined in cortex and hippocampus of Tg-SwDI transgenic mice. Using stereotaxic operation with AAV9 encoding MICU3, we showed that AAV-MICU3 improved the behavioral performances and cerebral blood flow (CBF) in Tg-SwDI mice, along with markedly reduced Aβ deposition through mediating Aβ metabolism process. Importantly, we found that AAV-MICU3 remarkably improved neuronal death and mitigated glial activation and neuroinflammation in cortex and hippocampus of Tg-SwDI mice. Furthermore, excessive oxidative stress, mitochondrial impairment and dysfunction, decreased ATP and mitochondrial DNA (mtDNA) were detected in Tg-SwDI mice, while being considerably ameliorated upon MICU3 over-expression. More importantly, our in vitro experiments suggested that MICU3-attenuated neuronal death, activation of glial cells and oxidative stress were completely abrogated upon PTEN induced putative kinase 1 (PINK1) knockdown, indicating that PINK1 was required for MICU3 to perform its protective effects against CAA. Mechanistic experiment confirmed an interaction between MICU3 and PINK1. Together, these findings demonstrated that MICU3-PINK1 axis may serve as a key target for CAA treatment mainly through improving mitochondrial dysfunction.
作者机构：
[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru] Univ South China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.;[Zhong, Jing; Zhong, J] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhong, J ; Wang, M ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
摘要：
The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.
期刊：
Japanese Journal of Clinical Radiology,2023年78(2):e37-e44 ISSN：0009-9252
通讯作者：
Liu, L.;Xiao, L;Zou, X.
作者机构：
[Liu, L.; Xiao, L.; Liu, L; Cui, H.] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;[Li, R.; Li, Q.; Hong, C.; Zou, X.; Liu, L.; Xiao, L.; Liu, L; Zeng, L.; Cui, H.] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.;[Zhu, H.] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang 421001, Peoples R China.;[Chen, L.] Southern Med Univ, Nanfang Hosp, Dept Med Qual Management, Guangzhou 510515, Peoples R China.
通讯机构：
[Zou, X; Xiao, L ; Liu, L] S;Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.
摘要：
PURPOSE: This study aimed to develop a radiomics signature (RS) based on contrast -enhanced computed tomography (CECT) and evaluate its potential predictive value in hepa-tocellular carcinoma (HCC) patients receiving anti-PD-1 therapy. METHOD: CECT scans of 76 HCC patients who received anti-PD-1 therapy were obtained in this study (training group = 53 and validation group = 23). The least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics features of primary and metastatic lesions and establish a RS to predict lesion-level response. Then, a nomogram com-bined the mean RS (MRS) and clinical variables with patient-level response as the end point. RESULTS: In the lesion-level analysis, the area under the curves (AUCs) of RS in the training and validation groups were 0.751 (95% CI, 0.668-0.835) and 0.734 (95% CI, 0.604-0.864), respectively. In the patient-level analysis, the AUCs of the nomogram in the training and validation groups were 0.897 (95% CI, 0.798-0.996) and 0.889 (95% CI, 0.748-1.00 0), respectively. The nomogram stratified patients into low-and high-risk groups, which showed a significant difference in progression-free survival (PFS) (p<0.05). CONCLUSIONS: The RS is a noninvasive biomarker for predicting anti-PD-1 therapy response in patients with HCC. The nomogram may be of clinical use for identifying high-risk patients and formulating individualised treatments. (c) 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
作者机构：
[Wu, Yimou; Shi, Zhisheng; Lei, Aihua; Xiang, Lin; Wu, YM; Ding, Nan] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hunan Prov Key Lab Special Pathogens Prevent & Con, Inst Pathogen Biol,Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Wei, Bo] Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang 421001, Peoples R China.
通讯机构：
[Wu, YM ; Wei, B ] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hunan Prov Key Lab Special Pathogens Prevent & Con, Inst Pathogen Biol,Hengyang Med Coll, Hengyang 421001, Peoples R China.;Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang 421001, Peoples R China.
摘要：
Mycoplasma pneumoniae (M. pneumoniae) is an atypical bacterial pathogen responsible for community-acquired pneumonia primarily among school-aged children and young adults. Camellia oleifera (C. oleifera) has been used as a medicinal and edible plant in China for centuries, the constituents from which possessed various bioactivities. Notably, flavonoids existing in residues of C. oleifera defatted seeds exhibited significant anti-inflammatory activities. In the present study, we investigated the impact of total flavonoids from C. oleifera (TFCO) seed extract on M. pneumoniae pneumonia. TFCO was obtained using multiple column chromatography methods and identified as kaempferol glycosides via UPLC-HRESIMS. In a M. pneumoniae pneumonia mouse model, TFCO significantly reduced the lung damage, suppressed IL-1 beta, IL-6, and TNF-alpha production, and curbed TLR2 activation triggered by M. pneumoniae. Similarly, in RAW264.7 macrophage cells stimulated by lipid-associated membrane proteins (LAMPs), TFCO suppressed the generation of proinflammatory cytokines and TLR2 expression. Moreover, TFCO diminished the phosphorylation of I kappa B alpha, JNK, ERK, p38, and p65 nuclear translocation in vitro. In conclusion, TFCO alleviated M. pneumoniae-induced lung damage via inhibition of TLR2-mediated NF-kappa B and MAPK pathways, suggesting its potential therapeutic application in M. pneumoniae-triggered lung inflammation.
作者机构：
[Li, Ao; He, Longwei; Liu, Yalan; Chen, Zhe; Li, Songjiao; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Sch Pharm, Hengyang Med Sch,Hunan Prov Key Lab Tumor Microen, Hengyang 421001, Peoples R China.;[Zhong, Rongbin; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang 421002, Peoples R China.
通讯机构：
[Linxi Chen; Longwei He] S;School of Pharmacy, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
摘要：
OBJECTIVE: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, with high morbidity and mortality. N6-methyladenosine (m6A) is an important regulator of LUAD progression. Here, we investigated the potential biological functions of ALKBH5 (a m6A demethylated enzyme) and cell division cycle associated protein 4 (CDCA4) in the progression of LUAD. METHODS: The expressions of CDCA4, METTL3, ALKBH5, FTO, YTHDC2 and YTHDC1 mRNA and proteins in LUAD and adjacent tissues, as well as NCI-H1299 and NCI-H157 cells were detected by RT-qPCR and western blot. Meanwhile, the role of ALKBH5 and CDCA4 in macrophage polarization was explored through tumor formation in Lewis lung carcinoma (LLC) mice and the co-culture system of NCI-H1299 and NCI-H157/THP-1 cells. Cell characterization was further analyzed. The expression of Ki-67 in tumor tissue was tested by immunohistochemistry. The scale of M1 and M2 macrophages was determined by flow cytometry. RESULTS: CDCA4 was significantly overexpressed in NCI-H1299 and NCI-H157 cell lines compared with BEAS-2B cells. The fold enrichment of CDCA4 (m6A) level in the overexpression (oe)-METTL3 or short hairpin (sh)-ALKBH5 cells was enhanced. Overexpression of CDCA4 promoted the cell viability, proliferation and migration, and inhibited apoptosis, which was reversed by sh-ALKBH5 intervention. Overexpression of YTHDC2 (not YTHDC1) inhibited the effect of CDCA4 on sh-ALKBH5 cells. sh-CDCA4 inhibited tumor growth and weight of LLC cells in mice, and promoted M1/M2 ratio in LLC mice and NCI-H1299/THP-1 and NCI-H157/THP-1 co-culture systems. Oe-CDCA4 promoted the volume and weight of tumor and inhibited the M1/M2 ratio of tumor tissue in LLC mice, but was reversed by sh-ALKBH5 intervention. CONCLUSION: m6A demethylase ALKBH5 promotes the development of LUAD through CDCA4 regulation of malignant characterization and M1/M2 macrophage polarization.
期刊：
Clinical and Translational Oncology,2023年25(10):2852-2860 ISSN：1699-048X
通讯作者：
Yunlian Tang
作者机构：
[Liu, Changqing; Li, Shan; Tang, Yunlian] Univ South China, Canc Res Inst, Key Lab Canc Cellular & Mol Pathol Hunan Prov, Hengyang Med Coll, 28 Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Yunlian Tang] K;Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Cancer Research Institute of Hengyang Medical College, University of South China, Hunan Province, Hengyang, People’s Republic of China
关键词：
Fyn;SRC;Oncogene;Cancers;Gene regulation
摘要：
The tyrosine kinase Fyn is a member of the SRC family of kinases, and its sustained activation is closely linked to tumor cell migration, proliferation, and cell metabolism. Recently, Fyn has been found to be expressed in various tumor tissues, and the expression and function of Fyn vary between tumors, with Fyn acting as an oncogene to promote proliferation and metastasis in some tumors. This article summarizes the recent studies on the role of Fyn in different human tumors, focusing on the role of Fyn in melanoma, breast cancer, glioma, lung cancer, and peripheral T-cell lymphoma in order to provide a basis for future research and targeted therapy in different human tumors.
摘要：
With the continuous cognition of the relationship between tumor cells and tumor immune microenvironment, immunotherapy based on the immune checkpoint blockade has achieved great breakthroughs, led to improved clinical outcomes, and prolonged survival for cancer patients in recent years. Nevertheless, the de novo or acquired resistance to immunotherapy has greatly counteracted the efficacy, leading to a 20%-40% overall response rate. Thus, further in-depth understanding of the regulation of the tumor microenvironment and antitumor immunity is urgently warranted. Ubiquitination-mediated protein degradation plays vital roles in protein stabilization, activation, and dynamics as well as in cellular homeostasis modulation. The dysregulated ubiquitination and deubiquitination are closely related to the changes in physiological and pathological processes, which subsequently result in a variety of diseases including cancer. In this review, the authors first summarize the current knowledge about the involvement of the ubiquitin-proteasome system in tumor development with the ubiquitin conjugation-regulated stability of p53, phosphatase and tensin homolog, and Myc protein as examples, then dissect the potential implications of ubiquitination-mediated immune checkpoints degradation in tumor microenvironment and immune responses, and finally discuss the effects of therapeutically targeting the ubiquitin-proteasome pathway on immunotherapy, with the goal of providing deep insights into the exploitation of more precise and effective combinational therapy against cancer.
作者机构：
[Zhang, Tianqing] First Peoples Hosp Changde City, Dept Cardiol, Changde 415003, Hunan, Peoples R China.;[Deng, Wenxu] Cent Hosp Hengyang, Hengyang 421001, Hunan, Peoples R China.;[Deng, Ying; He, Qi] Peoples Hosp Ningxiang City, Ningxiang, Hunan, Peoples R China.;[Liu, Yao] Univ South China, Affiliated Hosp 2, Hengyang Medcial Sch, Dept Cardiovasc Med, Hunan 421001, Peoples R China.;[Xiao, Sijie] First Peoples Hosp Changde City, Dept Ultrasound, Changde 415003, Peoples R China.
通讯机构：
[Liu, Y ] U;Univ South China, Affiliated Hosp 2, Hengyang Medcial Sch, Dept Cardiovasc Med, Hunan 421001, Peoples R China.
关键词：
Myocardial ischemia-reperfusion injury;Programmed cell death;Traditional Chinese medicine
摘要：
Acute myocardial infarction remains the leading cause of death in humans. Timely restoration of blood perfusion to ischemic myocardium remains the most effective strategy in the treatment of acute myocardial infarction, which can significantly reduce morbidity and mortality. However, after restoration of blood flow and reperfusion, myocardial injury will aggravate and induce apoptosis of cardiomyocytes, a process called myocardial ischemia-reperfusion injury. Studies have shown that the loss and death of cardiomyocytes caused by oxidative stress, iron load, increased lipid peroxidation, inflammation and mitochondrial dysfunction, etc., are involved in myocardial ischemia-reperfusion injury. In recent years, with the in-depth research on the pathology of myocardial ischemia-reperfusion injury, people have gradually realized that there is a new form of cell death in the pathological process of myocardial ischemia-reperfusion injury, namely ferroptosis. A number of studies have found that in the myocardial tissue of patients with acute myocardial infarction, there are pathological changes closely related to ferroptosis, such as iron metabolism disorder, lipid peroxidation, and increased reactive oxygen species free radicals. Natural plant products such as resveratrol, baicalin, cyanidin-3-O-glucoside, naringenin, and astragaloside IV can also exert therapeutic effects by correcting the imbalance of these ferroptosis-related factors and expression levels. Combining with our previous studies, this review summarizes the regulatory mechanism of natural plant products intervening ferroptosis in myocardial ischemia-reperfusion injury in recent years, in order to provide reference information for the development of targeted ferroptosis inhibitor drugs for the treatment of cardiovascular diseases.
期刊：
Cancer Immunology, Immunotherapy,2023年72(7):2299-2308 ISSN：0340-7004
通讯作者：
Cui, H.;Liu, L.;Dong, H.;Zeng, L.
作者机构：
[Liu, Li; Wang, Jiaren; Liao, Yanxia; Li, Qimei; Cui, Hao; Zeng, Lin; Xiao, Lushan] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou 510515, Peoples R China.;[Liu, Li; He, Jingzhe; Wang, Jiaren; Liao, Yanxia; Li, Ruining; Li, Qimei; Hong, Chang; Cui, Hao; Zeng, Lin; Xiao, Lushan] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou 510515, Peoples R China.;[Zhu, Hongbo] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Dong, Hanzhi] Jiangxi Canc Hosp, Affiliated Hosp 2, Jiangxi Clin Res Ctr Canc, Dept Med Oncol,Nanchang Med Coll, Nanchang 330029, Peoples R China.
通讯机构：
[Hao Cui; Lin Zeng; Li Liu] B;[Hanzhi Dong] D;Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Medical Oncology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, China<&wdkj&>Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, China<&wdkj&>Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
通讯机构：
[Tan, XF; Yang, QL ; Chen, GD] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, 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, Hengyang Med Sch, MOE Key Lab Rare Pediat Dis, Hengyang 421001, Hunan, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Key Lab Birth Defect Res & Prevent, Natl Hlth Commiss, Changsha 410008, Hunan, Peoples R China.
摘要：
The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H(2)S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm(2). H(2)S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.
作者机构：
[Chen, Guangqun; He, Jie; Jiang, Yiling; Yi, Lan; Tan, Hui; Liu, Ran; Ling, Hui; Qi, Su] Univ South China, Canc Res Inst, Hunan Prov Key Lab Canc Cellular & Mol Pathol, Hengyang, Peoples R China.;[Jiang, Yiling; Qi, Su] Univ South China, Affiliated Hosp 1, Dept Oncol, Hengyang, Peoples R China.;[Chen, Guangqun] Loudi Cent Hosp, Dept Oncol, Loudi, Peoples R China.;[Liu, Ran] First Hosp Changsha, Dept Pathol, Changsha, Peoples R China.;[Qi, Su] Univ South China, Canc Res Inst, Coll Hunan Prov, Key Lab Tumor Cellular & Mol Pathol,Hengyang Med C, 28 Changsheng Xi Rd, Hengyang 421001, Peoples R China.
通讯机构：
[Qi Su; Qi Su Qi Su Qi Su] H;Hunan Province Key Laboratory of Cancer Cellular and Molecular Pathology, Cancer Research Institute, University of South China, Hengyang, China<&wdkj&>Department of Oncology, First Affiliated Hospital, University of South China, Hengyang, China
摘要：
OBJECTIVE: Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether Thapsigargin (TG) -induced ER protein expression levels contributed to TLR2-mediated inflammatory response. METHODS: The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer Thapsigargin (TG) or inhibitor (TUDCA). The mRNA expressions of TLR1-TLR10 were detected by qPCR. The production and secretion of inflammatory factors were detected by PCR and ELISA. Immunohistochemistry was used to detect the expressions of GRP78 and TLR2 in the intestinal mucosa of patients with Crohn's disease (CD). The IBD mouse model was established by TNBS in the modeling group. ERS inhibitor (TUDCA) was used in the treatment group. RESULTS: The expression of TLRs was detected via polymerase chain reaction (PCR) in THP-1 cells treated by ERS agonist Thapsigargin (TG). According to the findings, TG could promote TLR2 and TLR5 expression. Subsequently, in TLR2 agonist Pam3CSK4 induced THP-1 cells, TG could lead to increased expression of the inflammatory factors such as TNF-α, IL-1β and IL-8, and ERS inhibitor (TUDCA) could block this effect. However, Pam3CSK4 did not significantly impact the GRP78 and CHOP expression. Based upon the immunohistochemical results, TLR2 and GRP78 expression were significantly increased in the intestinal mucosa of patients with Crohn's disease (CD). For in vivo experiments, TUDCA displayed the ability to inhibit intestinal mucosal inflammation and reduce GRP78 and TLR2 proteins. CONCLUSIONS: ERS and TLR2 is upregulated in inflammatory bowel disease, ERS may promote TLR2 pathway-mediated inflammatory response. Moreover, ERS and TLR2 signaling could be novel therapeutic targets for IBD.
摘要：
Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC. Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin–eosin staining. The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48 h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues. Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC.
