作者机构：
[Li, Zhongyu; Zhou, Zhou; Lu, Chunxue; Bu, Jichang; Lei, Wenbo; Shu, Mingyi; Chen, Chaoqun; Chen, Lili] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hunan Prov Key Lab Special Pathogens Prevent & Con, Hengyang 421001, Peoples R China.;[Li, Zhongyu] Univ South China, Pathogen Biol Inst, Hengyang Med Sch, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhongyu Li] I;Institute of Pathogenic Biology, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
关键词：
Apoptosis;Chlamydia trachomatis;HO-1;Nrf2;PI3K/Akt pathway;Pgp3 protein
摘要：
As an obligate intracellular pathogen, Chlamydia trachomatis assumes various strategies to inhibit host cells apoptosis, thereby providing a suitable intracellular environment to ensure completion of the development cycle. In the current study, we revealed that Pgp3 protein, one of eight plasmid proteins of C. trachomatis that has been illustrated as the key virulence factor, increased HO-1 expression to suppress apoptosis, and downregulation of HO-1 with siRNA-HO-1 failed to exert anti-apoptosis activity of Pgp3 protein. Moreover, treatment of PI3K/Akt pathway inhibitor and Nrf2 inhibitor evidently reduced HO-1 expression and Nrf2 nuclear translocation was blocked by PI3K/Akt pathway inhibitor. These findings highlight that induction of HO-1 expression by Pgp3 protein is probably due to regulation of Nrf2 nuclear translocation activated by PI3K/Akt pathway, which provide clues on how C. trachomatis adjusts apoptosis.
作者机构：
[Luo, Dan; Xiao, Hua; Luo, Haodang; Liao, Yating; Ye, Youyuan; Zeng, Yanhua; Chen, Li; Lei, Aihua; Zeng, Zhuo; Yan, Xiaoliang; Peng, Kailan; Li, Xia] Univ South China, Inst Pathogen Biol, Basic Med Sch, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Luo, Dan; Xiao, Hua; Luo, Haodang; Liao, Yating; Ye, Youyuan; Zeng, Yanhua; Chen, Li; Lei, Aihua; Zeng, Zhuo; Yan, Xiaoliang; Peng, Kailan; Li, Xia] Hunan Prov Key Lab Special Pathogens Prevent & Con, Hengyang, Hunan, Peoples R China.;[Luo, Dan; Xiao, Hua; Luo, Haodang; Liao, Yating; Ye, Youyuan; Zeng, Yanhua; Chen, Li; Lei, Aihua; Zeng, Zhuo; Yan, Xiaoliang; Peng, Kailan; Li, Xia] Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang, Hunan, Peoples R China.;[Luo, Dan; Luo, Haodang; He, Jun] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang, Hunan, Peoples R China.
通讯机构：
[Yanhua Zeng] I;Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China<&wdkj&>Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, Hunan, China<&wdkj&>Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, Hunan, China
关键词：
CaN-NFAT signaling;M. genitalium protein of adhesion;T cell activation;cyclophilin A
摘要：
Mycoplasma genitalium is a sexually transmitted bacterium that can co-infect with other infections and causes nongonococcal urethritis in males, cervicitis, pelvic inflammatory disease, premature birth, and ectopic pregnancy in women. The adhesion protein of M. genitalium (MgPa) is the primary virulence factor in the complicated pathogenicity of M. genitalium. Mycoplasma genitalium is a prokaryotic microorganism that causes urogenital tract infections. M. genitalium protein of adhesion (MgPa) was essential for M. genitalium attachment and subsequent invasion into host cells. Our prior research confirmed that Cyclophilin A (CypA) was the binding receptor for MgPa and MgPa-CypA interaction can lead to the production of inflammatory cytokines. In this study, we revealed that the recombinant MgPa (rMgPa) could inhibit the CaN-NFAT signaling pathway to reduce the level of IFN-gamma, IL-2, CD25, and CD69 in Jurkat cells by binding to the CypA receptor. Moreover, rMgPa inhibited the expressions of IFN-gamma, IL-2, CD25, and CD69 in primary mouse T cells. Likewise, the expressions of these T cells activation-related molecules in CypA-siRNA-transfected cells and CypA(-/-) mouse primary T cell was strengthened by rMgPa. These findings showed that rMgPa suppressed T cell activation by downregulating the CypA-CaN-NFAT pathway, and as a result, acted as an immunosuppressive agent.IMPORTANCE Mycoplasma genitalium is a sexually transmitted bacterium that can co-infect with other infections and causes nongonococcal urethritis in males, cervicitis, pelvic inflammatory disease, premature birth, and ectopic pregnancy in women. The adhesion protein of M. genitalium (MgPa) is the primary virulence factor in the complicated pathogenicity of M. genitalium. This research proved that MgPa could interact with host cell Cyclophilin A (CypA) and prevent T cell activation by inhibiting Calcineurin (CaN) phosphorylation and NFAT nuclear translocation, which clarified the immunosuppression mechanism of M. genitalium to host T cells. Therefore, this study can provide a new idea that CypA can be used for a therapeutic or prophylactic target for M. genitalium infection.
摘要：
PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.
作者：
Liu, Shu;Shen, Ying Ying;Yin, Li Yang;Liu, Jianghua;Zu, Xuyu
期刊：
DNA AND CELL BIOLOGY,2023年42(8):445-455 ISSN：1044-5498
通讯作者：
Zu, XY;Liu, JH
作者机构：
[Yin, Li Yang; Shen, Ying Ying; Zu, Xuyu; Liu, Shu] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Liu, Jianghua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Metab & Endocrinol, Hengyang, Hunan, Peoples R China.;[Zu, Xuyu] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, 69,Chuanshan Ave, Hengyang 421001, Hunan, Peoples R China.;[Liu, Jianghua] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Metab & Endocrinol, 69,Chuanshan Ave, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zu, XY ; Liu, JH ] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, 69,Chuanshan Ave, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Metab & Endocrinol, 69,Chuanshan Ave, Hengyang 421001, Hunan, Peoples R China.
关键词：
cancer cells;lipid metabolism;targeting therapy;tumor-associated macrophages
摘要：
In the tumor microenvironment, tumor-associated macrophages (TAMs) are one of the most abundant cell populations, playing key roles in tumorigenesis, chemoresistance, immune evasion, and metastasis. There is an important interaction between TAMs and cancer cells: on the one hand, tumors control the function of infiltrating macrophages, contributing to reprogramming of TAMs, and on the other hand, TAMs affect the growth of cancer cells. This review focuses on lipid metabolism changes in the complex relationship between cancer cells and TAMs. We discuss how lipid metabolism in cancer cells affects macrophage phenotypic and metabolic changes and, subsequently, how altered lipid metabolism of TAMs influences tumor progression. Identifying the metabolic changes that influence the complex interaction between tumor cells and TAMs is also an important step in exploring new therapeutic approaches that target metabolic reprogramming of immune cells to enhance their tumoricidal potential and bypass therapy resistance. Our work may provide new targets for antitumor therapies.
通讯机构：
[Zi Wang; Xu Han; Jing Liu] D;Department of Hematology, The Second Xiangya Hospital of Central South University;Molecular Biology Research Center, Center for Medical Genetics, School of Life Sciences;Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University , Changsha 410011, China
摘要：
Normal erythropoiesis requires the precise regulation of gene expression patterns, and transcription cofactors play a vital role in this process. Deregulation of cofactors has emerged as a key mechanism contributing to erythroid disorders. Through gene expression profiling, we found HES6 as an abundant cofactor expressed at gene level during human erythropoiesis. HES6 physically interacted with GATA1 and influenced the interaction of GATA1 with FOG1. Knockdown of HES6 impaired human erythropoiesis by decreasing GATA1 expression. Chromatin immunoprecipitation and RNA sequencing revealed a rich set of HES6- and GATA1-co-regulated genes involved in erythroid-related pathways. We also discovered a positive feedback loop composed of HES6, GATA1 and STAT1 in the regulation of erythropoiesis. Notably, erythropoietin (EPO) stimulation led to up-regulation of these loop components. Increased expression levels of loop components were observed in CD34+ cells of polycythemia vera patients. Interference by either HES6 knockdown or inhibition of STAT1 activity suppressed proliferation of erythroid cells with the JAK2V617F mutation. We further explored the impact of HES6 on polycythemia vera phenotypes in mice. The identification of the HES6–GATA1 regulatory loop and its regulation by EPO provides novel insights into human erythropoiesis regulated by EPO/EPOR and a potential therapeutic target for the management of polycythemia vera.
HES6 as a GATA1 cofactor facilitated erythropoiesis. HES6, GATA1 and STAT1 formed a positive feedback loop in normal erythropoiesis. This activated loop was a potential target in polycythemia vera.
期刊：
European Journal of Preventive Cardiology,2023年30(3):e3-e3 ISSN：2047-4873
通讯作者：
Zhen Sun
作者机构：
[Liu, Mengsi; Sun, Zhen] Univ South China, Hengyang Med Sch, Dept Clin Med, 28 Changsheng West Rd, Hengyang 421001, Peoples R China.
通讯机构：
[Zhen Sun] D;Department of Clinical Medicine, Hengyang Medical School, University of South China , No. 28 Changsheng West Road, Hengyang 421001 , China
摘要：
We read with great interest and acknowledge the recent paper by Albalak et al.,1 published in European Journal of Preventive Cardiology. Based on a long-te
摘要：
The multifunctional chemotherapeutic prodrugs that possess an effective combination of tumor targeting capability, activable chemotherapeutic activity, photodynamic therapy (PDT) assistance and near‐infrared fluorescence imaging (NIRFI) guidance are desirable to be engineered for real‐time monitoring of drug delivery, distribution, and synergistic chemo‐PDT in cancer treatment. Abstract Conventional chemotherapy (CT) is associated with severe side effects and inducible resistance, making it difficult to meet clinical requirements, forcing the development of new multifunctional prodrugs for precision medicine. In recent decades, researchers and clinicians have focused on developing of multifunctional chemotherapeutic prodrugs with tumor‐targeting capability, activatable and traceable chemotherapeutic activity, as a powerful tool to improve theranostic outcomes in cancer treatment. The conjugates of near‐infrared (NIR) organic fluorophores and chemotherapy reagents create an exciting avenue for real‐time monitoring of drug delivery and distribution, as well as the combination of chemotherapy and photodynamic therapy (PDT). Therefore, there are great opportunities for researchers to conceive and exploit multifunctional prodrugs that can visualize chemo‐drugs release and tumor treatment in vivo. In this review, the design strategy and the recent progress of multifunctional organic chemotherapeutic prodrugs for activating NIR fluorescence imaging‐guided therapy are described and discussed in detail. Finally, the prospects and challenges of multifunctional chemotherapeutic prodrugs for NIR fluorescence imaging‐guided therapy are provided.
作者机构：
[Wu, Yimou; Li, Yuehua; Wu, YM] Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Lijun; Zhu, Hongbo; Li, Yuehua; Tang, Yuanbin; Feng, Wenjie; Wan, Zhixing; Qi, Xiaowen; Xie, Liming; Zhu, HB] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Baohong] Univ South China, Affiliated Hosp 1, Dept Pharm, Hengyang 421001, Hunan, Peoples R China.;[He, Rongfang] Univ South China, Affiliated Hosp 1, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Wu, YM ; Zhu, HB ] U;Univ South China, Inst Pathogen Biol, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.
关键词：
CircCRIM1;Environmental factors;Exosomes;Immune infiltration;OGA;Triple-negative breast cancer
摘要：
Triple-negative breast cancer (TNBC) has an escalating morbidity and a dismal prognosis. Obesity has been reported to be strongly linked to adverse TNBC outcomes. Exosomes (Exos) transport RNA and proteins between cells and serve as intermediaries for cell-to-cell communication. Accumulated evidence suggests that adipose-secreted circular RNAs (circRNAs) can modulate protein glycosylation in TNBC to facilitate tumor cell outgrowth. Herein, exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. Functional experiments demonstrated that by inhibiting miR-503-5p, exo-circCRIM1 enhanced TNBC evolution and metastasis while activating glycosylation hydrolase OGA. Furthermore, OGA negatively regulates FBP1 by decreasing its protein stability. Moreover, the levels of OGA and FBP1 were positively related to the infiltration level of some immune cells in TNBC. These findings indicate that exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503-5p and activating the OGA/FBP1 signaling pathway. The findings reveal a novel intercellular signaling pathway mediated by adipose-derived exosomes and suggest that treatment targeting the secreted exosome-circCRIM1 may reverse TNBC progression.
期刊：
Biochemical and Biophysical Research Communications,2023年687:149210 ISSN：0006-291X
通讯作者：
Han, HL
作者机构：
[Xu, Jing; Han, Hailong; Deng, Zhouyang; Shang, Shuai] Cent South Univ, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;[Xu, Jing; Han, Hailong; Deng, Zhouyang; Wang, Caifang] Cent South Univ, Hunan Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China.;[Wang, Caifang] Cent South Univ, Inst Mol Precis Med, Xiangya Hosp, Key Lab Mol Precis Med Hunan Prov, Changsha 410008, Hunan, Peoples R China.;[Han, Hailong] Univ South China, Dept Neurosci, Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Han, HL ] C;Cent South Univ, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Hunan Key Lab Med Genet, Changsha 410008, Hunan, Peoples R China.;Univ South China, Dept Neurosci, Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要：
Parkinson's disease is presently thought to have its molecular roots in the alteration of PINK1-mediated mitophagy and mitochondrial dynamics. Finding new suppressors of the pathway is essential for developing cutting-edge treatment approaches. Our study shows that FUNDC1 suppressed PINK1 mutant phenotypes in Drosophila. The restoration of PINK1-deficient phenotypes through FUNDC1 is not reliant on its LC3-binding motif Y (18)L (21) or autophagy-related pathway. Moreover, the absence of Drp1 affects the phenotypic restoration of PINK1 mediated by FUNDC1 in flies. In summary, our findings have unveiled a fresh mechanism through which FUNDC1 compensates for the loss of PINK1, operating independently of autophagy but exerting its influence via interaction with Drp1.
作者机构：
[Liu, Ying; Yang, Ke; He, Longwei; Wang, Peipei; Li, Songjiao] Univ South China, Canc Res Inst, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Hunan Prov Key Lab Tumor Microenv, Hengyang 421001, Peoples R China.;[Zhong, Rongbin; Cheng, Dan] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Dan Cheng] C;[Longwei He] H;Clinical Research Institute, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, PR China<&wdkj&>Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Cancer Research Institute, Department of Pharmacy and Pharmacology, Hengyang Medical School, University of South China, Hengyang, 421001, PR China
摘要：
Chlamydia psittaci is a zoonotic pathogen found in birds and humans. Macrophages, major components of the innate immune system, can resist chlamydial infections and trigger adaptive immune responses. However, the molecular mechanisms underlying the action of macrophages against C. psittaci infection are not well understood. This study investigated the roles and mechanisms of plasmid-encoded protein CPSIT_p7 of C. psittaci in regulating autophagy in RAW264.7 cells. The results demonstrated that stimulation of RAW264.7 with C. psittaci plasmid protein CPSIT_p7 induced the expressions of the autophagy signaling primary regulators LC3 and Beclin1, which could also significantly induce the phosphorylation levels of ERK, JNK, p38, and Akt. Next, siRNA knockdown of TLR2 resulted in significant downregulation of CPSIT_p7-triggered autophagy in RAW264.7 cells. Moreover, the extracellular regulated protein kinase (ERK) inhibitor PD98059 markedly reduced autophagy in CPSIT_p7-stimulated macrophages. In summary, these results indicated that TLR2 plays an essential role in the induction of autophagy through the ERK signaling pathway in CPSIT_p7-stimulated RAW264.7 cells.
期刊：
European Journal of Pharmacology,2023年939:175446 ISSN：0014-2999
通讯作者：
Zijian Xiao
作者机构：
[He, Bing; Zhou, Guijuan; Xu, Yan; Xie, Juan; Yao, Lan; Xiao, Zijian; Xiang, Tao; Zhu, Guanghua; Wu, Lin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Neurol, Hengyang 421099, Hunan, Peoples R China.;[Zhou, Guijuan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Rehabil Med, Hengyang 421099, Hunan, Peoples R China.
通讯机构：
[Zijian Xiao] D;Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421099, Hunan Province, China
关键词：
Aβ metabolism;Cerebral amyloid angiopathy (CAA);HMPL-013;Inflammation and neuron death;VEGF/VEGFR-1,-2
摘要：
Cerebral amyloid angiopathy (CAA) is characterized by the cerebrovascular amyloid-beta (A beta) accumulation, and always accompanied by Alzheimer's disease (AD). The mechanisms revealing CAA pathogenesis are still unclear, and it is challenging to develop an efficient therapeutic strategy for its treatment. Vascular endothelial growth factor (VEGF) and its receptors including VEGFR-1,-2,-3 activation are involved in A beta processing, and modulate numerous cellular events associated with central nervous system (CNS) diseases. In the present study, we attempted to explore the regulatory function of fruquintinib (also named as HMPL-013), a highly selective inhibitor of VEGFR-1,-2,-3 tyrosine kinases, on CAA progression in Tg-SwDI mice. Here, we found that HMPL-013-rich diet consumption for 12 months significantly improved the behavioral performances and cerebral blood flow (CBF) of Tg-SwDI mice compared with the vehicle group. Importantly, HMPL-013 administration considerably reduced A beta(1-40) and A beta(1-42) burden in cortex and hippocampus of Tg-SwDI mice through regulating A beta metabolism process. Congo red staining confirmed A beta deposition in vessel walls, reflecting CAA formation, which was, however, strongly ameliorated after HMPL-013 treatment. Neuron death, aberrant glial activation and pro-inflammatory response in brain tissues of Tg-SwDI mice were dramatically alleviated after HMPL-013 consumption. More studies showed that the protective effects of HMPL-013 against CAA might be partially attrib-uted to its regulation on the expression of genes associated with blood vasculature. Intriguingly, VEGF and phosphorylated VEGFR-1,-2 protein expression levels were remarkably decreased by HMPL-013 in cortex and hippocampus of Tg-SwDI mice, which were validated in HMPL-013-treated brain vascular endothelial cells (BVECs) under hypoxia. Finally, we found that VEGF-induced human umbilical vein endothelial cells (HUVEC) proliferation and tube formation were strongly abolished upon HMPL-013 exposure. Collectively, all these findings demonstrated that oral administration of HMPL-013 had therapeutic potential against CAA by reducing A beta deposition, inflammation and neuron death via suppressing VEGF/VEGFR-1,-2 signaling.
期刊：
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023年19(15):4915-4930 ISSN：1449-2288
通讯作者：
Shen, YY
作者机构：
[Chen, Xiguang; Yin, Liyang; Yuan, Qiong; Liang, Yuxin; Zeng, Qiting; Zu, Xuyu; Shen, Yingying] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Yuan, Qiong; Liang, Yuxin; Zeng, Qiting] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Clin Lab Med, Hengyang 421001, Hunan, Peoples R China.;[He, Jun] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Dept Spine Surg, Hengyang, Peoples R China.
通讯机构：
[Shen, YY ] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
关键词：
breast cancer;crosstalk;metabolism;targeted therapy;tumor-associated macrophages
摘要：
Breast cancer is the most common cancer affecting women worldwide. Investigating metabolism in breast cancer may accelerate the exploitation of new therapeutic options for immunotherapies. Metabolic reprogramming can confer breast cancer cells (BCCs) with a survival advantage in the tumor microenvironment (TME) and metabolic alterations in breast cancer, and the corresponding metabolic byproducts can affect the function of tumor-associated macrophages (TAMs). Additionally, TAMs undergo metabolic reprogramming in response to signals present in the TME, which can affect their function and breast cancer progression. Here, we review the metabolic crosstalk between BCCs and TAMs in terms of glucose, lipids, amino acids, iron, and adenosine metabolism. Summaries of inhibitors that target metabolism-related processes in BCCs or TAMs within breast cancer have also served as valuable inspiration for novel therapeutic approaches in the fight against this disease. This review provides new perspectives on targeted anticancer therapies for breast cancer that combine immunity with metabolism.
作者机构：
[Yang, Qinglai; Li, Na; Wu, Gui-Long; Tan, Xiaofeng; Wang, Minghui; Wu, Peixian; Yang, Sha] Univ South China, Canc Res Inst, Ctr Mol Imaging Probe, Hengyang Med Sch,Hunan Province Key Lab Tumor Cell, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xiaofeng Tan; Qinglai Yang] C;Center for Molecular Imaging Probe, Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Center for Molecular Imaging Probe, Hunan Province Key Laboratory of Tumor Cellular and Molecular Pathology, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Metallic aerogels (MAs) are self-supported porous nanomaterials with excellent catalytic activity, which could be a promising candidate for high-performance nanozymes. The interface regulation by heteroatom and vacancies is an effective strategy for boosting the enzyme-mimicking activity. Herein, magnetic RuCo aerogels with doping of boron and oxygen vacancies were prepared by a one-pot spontaneous NaBH(4) gelation method under a low temperature. The three-dimensional network structure with high specific surface area and interlinked pores of RuCo aerogels afford abundant active sites to facilitate the interaction with substrates. Moreover, the monolithic structure avoided conventional aggregation, thus enhancing stability during catalysis. Introducing elemtalboron and oxygen vacancies adjusted the electronic structure of RuCo aerogels to achieve enhanced enzyme-like performances. It is found that the RuCo aerogel nanozyme can mimic nature peroxidase, demonstrating their viable applications in the bioassay of H(2)O(2) and glucose. The constructed glucose sensor possesses acceptable sensitivity and stability with a linear range of 0.002 ~ 5mM and a low detection limit (1.66μM). This work provides insights into the rational design of advanced nanozymes and paves the avenue for the applications of metallic aerogels in the bioassay field. A boron-doped RuCo bimetallic aerogel with rich oxygen vacancies was prepared by a facile self-assembly method under an ice bath. The unique physical and electronic structure of RuCo aerogel results in the improvement of the intrinsic peroxidaselike activity, and thus, a sensitive and robust colorimetric glucose sensor could be developed.
期刊：
Brain and Behavior,2023年13(12):e3305- ISSN：2162-3279
通讯作者：
Zhou, HM;Li, SY
作者机构：
[Xiang, Yuyan; Li, Cai; Cao, Wenyu; Peng, Lixuan; Li, Suyun; Tang, Xiaohan] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Xu, Yang] Univ South China, Hengyang Med Sch, Inst Neurosci, Hengyang, Hunan, Peoples R China.;[Zhou, Huamao] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Zhou, Huamao] Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.;[Li, Suyun] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, SY ; Zhou, HM ] U;Univ South China, Nanhua Affiliated Hosp, Hengyang Med Sch, Hengyang 421000, Hunan, Peoples R China.;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
摘要：
A schematic illustration of the proposed mechanism for YKL‐06‐061 prevents PTZ‐induced seizures in mice. PTZ induces high expression of SIK1, leading IEGs overexpression and appearing seizure behavior in mice. SIKs inhibitors (YKL‐06‐061) reduce the expression of IEGs, thereby improving epilepsy of mice. Abstract Introduction Epilepsy is one of the most common neurological diseases, while over one third of adults with epilepsy still have inadequate seizure control. Although mutations in salt‐inducible kinases (SIKs) have been identified in epileptic encephalopathy, it is not known whether blocking SIKs can prevent pentylenetetrazole (PTZ)‐induced seizures. Methods We first determined the time course of SIKs (including SIK 1, 2, and 3) in the hippocampus of PTZ treated mice. And then, we evaluated the effects of anti‐epilepsy drug valproate acid (VPA) on the expression of SIK 1, 2, and 3 in the hippocampus of PTZ treated mice. Next, we investigated the effect of different dose of SIKs inhibitor YKL‐06‐061 on the epileptic seizures and neuronal activation by determining the expression of immediate early genes (IEGs) in the PTZ treated mice. Results We found that PTZ selectively induced enhanced expression of SIK1 in the hippocampus, which was blocked by VPA treatment. Notably, YKL‐06‐061 decreased seizure activity and prevented neuronal overactivity, as indicated by the reduced expression of IEGs in the hippocampus and prefrontal cortex. Conclusion Our findings provide the first evidence that SIK1 affects gene regulation in neuronal hyperactivity, which is involved in seizure behavior. Targeting SIK1 through the development of selective inhibitors may lead to disease‐modifying therapies that reduce epilepsy progression.
摘要：
Diallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria-dependent pathway and increases the levels of γ-H2AX, a DNA damage marker. Combination index (CI) measurements indicated that the combination of DADS with melphalan has a significant synergistic effect on MM cells. This was further confirmed by the increases in apoptotic cells and DNA damage in MM cells treated with the two drug combinations compared with those cells treated with a single drug alone. The synergy between DADS and melphalan was also observed in primary MM cells. Furthermore, mechanistic investigations showed that DADS decreases reduced glutathione (GSH) levels and increases reactive oxygen species (ROS) production in MM cells. The addition of GSH is effective in neutralizing DADS cytotoxicity and inhibiting the synergy between DADS and melphalan in MM cells. Taken together, our study highlights the effectiveness of DADS in treating MM cells and the promising therapeutic potential of combining DADS and melphalan for MM treatment.
作者机构：
[Liu, Zhiqiang; Song, Mengwen; Liao, Yajin] Univ South China, Sch Pharmaceut Sci, Hengyang 421001, Peoples R China.;[Liu, Zhiqiang; Song, Mengwen; Liao, Yajin] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang 42100, Hunan, Peoples R China.;[Liu, Zhiqiang; Song, Mengwen; Liao, Yajin; Xing, Xiaowen; Wang, Cui] Beijing Inst Basic Med Sci, Beijing 100850, Peoples R China.;[Zhong, Wu; Cao, Ruiyuan; Li, Wei; Li, Yuexiang; Chen, Xingjuan] Beijing Inst Pharmacol & Toxicol, Natl Engn Res Ctr Emergency Drug, Beijing 100850, Peoples R China.;[Chen, Xingjuan] Northwestern Polytech Univ, Inst Med Res, Xian 710072, Peoples R China.
通讯机构：
[Zhong, W ] B;[Liu, ZQ ] U;[Li, QH ] C;Univ South China, Sch Pharmaceut Sci, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang 42100, Hunan, Peoples R China.
关键词：
targeted drug delivery;NPs;aptamer;doxorubicin;pharmacotherapy
摘要：
Targeting nanoparticles (NPs) based on the specific binding of ligands with molecular targets provides a promising tool for tissue-selective drug delivery. However, the number of molecular targets on the cell surface is limited, hindering the number of NPs that can bind and, thus, limiting the therapeutic outcome. Although several strategies have been developed to enhance drug delivery, such as enhancing drug loading and circulation time or increasing the enhanced permeability and retention effect of nanocarriers, none have resolved this issue. Herein, we designed a simple method for amplified and targeted drug delivery using two matched NPs. One NP was aptamer-functionalized to specifically bind to target cells, while the other was aptamer-complementary DNA-functionalized to specifically bind to aptamer-NPs. Alternate administration of the two matched NPs enables their continuous accumulation in the disease site despite their limited molecular targets. As a proof of concept, the method was tested in a breast cancer model and significantly enhanced chemotherapy of tumor cells in vitro and in vivo. The potential applications of this method in a brain injury model were also demonstrated. Overall, the study describes a method for amplified targeted drug delivery independent of the target number.
作者机构：
[Qian, Feng-Cui; Li, Chun-Quan; Yu, Zheng-Min; Wang, Qiu-Yu; Xu, Ming-Cong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.;[Qian, Feng-Cui; Li, Chun-Quan; Wang, Qiu-Yu] Univ South China, Affiliated Hosp 1, Inst Cardiovasc Dis, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Qian, Feng-Cui; Li, Chun-Quan; Wang, Qiu-Yu] Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Changsha 410008, Hunan, Peoples R China.;[Qian, Feng-Cui; Li, Chun-Quan; Wang, Qiu-Yu; Li, Li-Dong] Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.;[Qian, Feng-Cui; Li, Chun-Quan; Wang, Qiu-Yu] Univ South China, Hengyang Med Coll, Insititute Biochem & Mol Biol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, CQ ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Cardiovasc Lab Big Data & Imaging Artificial Intel, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Inst Cardiovasc Dis, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Natl Hlth Commiss Key Lab Birth Defect Res & Preve, Changsha 410008, Hunan, Peoples R China.;Univ South China, Sch Comp, Hengyang 421001, Hunan, Peoples R China.
摘要：
Super-enhancers (SEs) play an essential regulatory role in various biological processes and diseases through their specific interaction with transcription factors (TFs). Here, we present the release of SEanal-ysis 2.0 (http://licpathway.net/SEanalysis), an up-dated version of the SEanalysis web server for the comprehensive analyses of transcriptional regula-tory networks formed by SEs, pathways, TFs, and genes. The current version added mouse SEs and further expanded the scale of human SEs, docu-menting 1 167 518 human SEs from 1739 samples and 550 226 mouse SEs from 931 samples. The SE-related samples in SEanalysis 2.0 were more than five times that in version 1.0, which significantly im-proved the ability of original SE-related network anal-yses (pathway downstream analysis', upstream reg-ulatory analysis' and genomic region annotation') for understanding context-specific gene regulation. Furthermore, we designed two novel analysis mod-els, TF regulatory analysis' and Sample compara-tive analysis' for supporting more comprehensive analyses of SE regulatory networks driven by TFs. Further, the risk SNPs were annotated to the SE re-gions to provide potential SE-related disease/trait in-formation. Hence, we believe that SEanalysis 2.0 has significantly expanded the data and analytical capa-bilities of SEs, which helps researchers in an in-depth understanding of the regulatory mechanisms of SEs. [GRAPHICS] .
