摘要：
Transcription factors, as the convergence points of multiple signaling pathways in eukaryotic cells, are closely involved in disease development. Pax-8, an important transcription factor belonging to the Pax family, exerts a crucial influence on the regulation of gene expression required for both physiological conditions and pathological processes. Pax-8 contributes to the pathogenesis of many human diseases, ranging from cardiovascular disease to many cancers, and therefore, it can be imagined that Pax-8 holds great therapeutic potential. In this review, we summarize the structure, distribution, function, and regulatory mechanisms of Pax-8 to provide a new research direction for Pax-8. 1. Pax-8, as an important transcription factor, has been described as a distinct temporal and spatial expression pattern and tissue-specific manner during growth and differentiation in the developing embryo. 2. The up-regulation or down-regulation of Pax-8 is involved in many pathological processes, including cell apoptosis, ventricular septum defect formation, adipocyte-like cell differentiation, angiogenesis, and tumor progression. 3. PPFP is a Pax-8-PPAR gamma fusion protein produced by a specific gene fusion, participating in adipocyte-like cell differentiation and tumor progression. 4. Pax-8 may be an attractive therapeutic target for atherosclerotic diseases.image
通讯机构：
[Chongjian Wang] D;Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
Diet frequency may potentially influence metabolic health. However, general population-based evidence on the association between meal frequency and type 2 diabetes mellitus (T2DM) remains limited and inconclusive. Thus, this study aimed to investigate the association between meal frequency and T2DM in resource limited area. A total of 29,405 qualified participants were enrolled from the Henan rural cohort study. Data on meal frequency were collected through a validated face-to-face questionnaire survey. Logistic regression models were utilized to explore the association between meal frequency and T2DM. Compared with 21 times per week meal frequency group, the adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) were 0.75 (0.58, 0.95) and 0.70 (0.54, 0.90) for 16–20 times/week group and 14–15 times/week group, respectively. For the analysis of the three meals, significant associations were only found between dinner frequency and T2DM. Compared with seven times per week dinner group, the ORs (95%CIs) were 0.66 (0.42, 0.99) and 0.51 (0.29, 0.82) for the group with three to six times/week and zero to two times/week. Reduced meal frequency, especially dinner frequency, was associated with lower prevalence of T2DM, which suggests that an appropriate reduction in meal frequency per week may have a role in decreasing the risk of T2DM.
作者机构：
[Fu, Yuting; Jiang, Binyuan; Yuan, Yeqin] Univ South China, Affiliated Changsha Cent Hosp, Med Res Ctr, Hengyang Med Sch, Changsha 410004, Peoples R China.;[Zhou, Ziwei; Long, Huizhi] Univ South China, Sch Pharm, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Jiang, Binyuan] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Peoples R China.
通讯机构：
[Binyuan Jiang] M;Medical Research Center, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China<&wdkj&>Department of Clinical Laboratory, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha 410004, China<&wdkj&>Author to whom correspondence should be addressed.
关键词：
breast cancer;clinical trial drugs;natural products;PI3K–AKT pathway
摘要：
BackgroundTraditional emulsion adjuvants are limited in clinical application because of their surfactant dependence. Graphene oxide (GO) has unique amphiphilic properties and therefore has potential to be used as a surfactant substitute to stabilize Pickering emulsions. MethodsIn this study, GO-stabilized Pickering emulsion (GPE) was prepared and used as an adjuvant to facilitate an enhanced immune response to the Chlamydia trachomatis (Ct) Pgp3 recombinant vaccine. Firstly, GPE was prepared by optimizing the sonication conditions, pH, salinity, GO concentration, and water/oil ratio. GPE with small-size droplets was characterized and chosen as the candidate. Subsequently, controlled-release antigen delivery by GPE was explored. Cellular uptake behaviors, M1 polarization, and cytokine stimulation by GPE + Pgp3 was considered in terms of the production of macrophages. Finally, GPE's adjuvant effect was evaluated by vaccination with Pgp3 recombinant in BALB/c mouse models. ResultsGPE with the smallest droplet sizes was prepared by sonication under 163 W for 2 min at 1 mg/mL GO in natural salinity with a pH of 2 when the water/oil ratio was 10:1 (w/w). The optimized average GPE droplet size was 1.8 mu m and the zeta potential was -25.0 +/- 1.3 mv. GPE delivered antigens by adsorption onto the droplet surface, demonstrating the controlled release of antigens both in vitro and in vivo. In addition, GPE promoted antigen uptake, which stimulated proinflammatory tumor necrosis factor alpha (TNF-alpha), enhancing the M1 polarization of macrophages in vitro. Macrophage recruitment was also significantly promoted by GPE at the injection site. In the GPE + Pgp3 treatment group, higher levels of immunoglobin (IgG), immunoglobin G1 (IgG1), immunoglobin G2a (IgG2a) sera, and immunoglobin A (IgA) were detected in vaginal fluid, and higher levels of IFN-gamma and IL-2 secretion were stimulated, than in the Pgp3 group, showing a significant type 1 T helper (Th1)-type cellular immune response. Chlamydia muridarum challenging showed that GPE enhanced Pgp3's immunoprotection through its advanced clearance of bacterial burden and alleviation of chronic pathological damage in the genital tract. ConclusionThis study enabled the rational design of small-size GPE, shedding light on antigen adsorption and control release, macrophage uptake, polarization and recruitment, which enhanced augmented humoral and cellular immunity and ameliorated chlamydial-induced tissue damage in the genital tract.
摘要：
BACKGROUND: Recent clinical evidences show that caspase-1 inhibitor-VX-765 attenuates atherosclerosis in ApoE deficient mice. However, there is rarely information about the effect of VX-765 on hyperphosphatemia-induced vascular smooth muscle cells (VSMCs) calcification or vascular calcification in chronic kidney disease (CKD) rats. Here we investigate the effect of VX-765 on vascular calcification in uremia circumstances. METHODS: Hyperphosphatemia-induced VSMC calcification were evaluated by Alizarin Red S. Aortas from CKD rats which were gavaged with VX-765 were examined for calcification signal using micro-CT. Levels of NLRP3, caspase-1, and GSDMD were measured by quantitative real-time PCR, western blotting, immunofluorescence assay, and immunohistochemistry. RESULTS: We demonstrated for the first time that the levels of NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 were up-regulated in hyperphosphatemia-induced calcifying VSMCs. Blockade of caspase-1 activation by VX-765 inhibited pyroptosis-related molecules and VSMC calcification in a concentration-dependent manner in vitro. Further analysis of aortas from calcified CKD rats showed an up-regulation of caspase-1 and GSDMD expression compared with those non-calcified vascular tissue from control rats or with those decreased-calcified vascular tissue from CKD rats treated with 50mg/kg/d, which indicated that pyroptotic indicators were tightly correlated with CKD arterial calcification. In vitro studies further demonstrated that VX-765 ameliorated hyperphosphatemia-induced VSMCs calcification through inhibiting the STAT3 activation. CONCLUSIONS: Our findings indicated that VX-765 could inhibit hyperphosphatemia-induced calcifying VSMCs and ameliorate vascular calcification in CKD rats. VX-765 might be a potential treatment strategy for CKD vascular calcification.
作者：
Li, Yong-Zhen;Chao, Ru;Qu, Shun-Lin;Huang, Liang;Zhang, Chi
期刊：
CURRENT PHARMACEUTICAL DESIGN,2023年29(17):1361-1369 ISSN：1381-6128
通讯作者：
Zhang, C;Huang, L
作者机构：
[Li, Yong-Zhen; Qu, Shun-Lin; Chao, Ru; Zhang, Chi] Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;[Huang, Liang; Huang, L] Univ South China, Hengyang Med Sch, Res Lab Clin & Translat Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhang, C ; Huang, L ] U;Univ South China, Inst Cardiovasc Dis, Hengyang Med Sch, Key Lab Arteriosclerol Hunan Prov, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Res Lab Clin & Translat Med, Hengyang 421001, Hunan, Peoples R China.
关键词：
aerobic glycolysis;inflammation;lipopolysaccharide;macrophages;mammalian target of rapamycin;zinc finger protein 667
摘要：
Background Macrophages participate in all stages of the inflammatory response, and the excessive release of inflammatory mediators and other cytokines synthesized and secreted by macrophages is fundamentally linked to an uncontrolled inflammatory response. The zinc finger 667 (ZNF667) protein, a novel DNA-binding protein, has been shown to play a vital role in oxidative stress. However, none of the target genes in macrophages or the potential roles of ZNF667 have been elucidated to date. Objectives The present study was designed to investigate the effects of ZNF667 on LPS-induced inflammation in macrophages. Methods The RAW264.7 macrophage cell line was selected as a model system. Inflammatory response-related gene expression levels and phosphorylation levels of PI3K, AKT, and mTOR were detected in LPS-treated macrophages via RT-PCR and western blotting, respectively. Results We found that LPS resulted in the up-regulation of ZNF667 in macrophages and a peak response in ZNF667 protein expression levels when used at a concentration of 100 ng/mL. ZNF667 overexpression significantly inhibited the LPS-induced up-regulation of iNOS, and IL-1 & beta; mRNA and protein expression levels, together with the secretion of IL-1 & beta;, IL-6, and TNF-& alpha;. ZNF667 overexpression also inhibited PI3K, AKT, and mTOR hyperphosphorylation and had no effect on the phosphorylation of NF-& kappa;B p65, ERK1/2, MAPK p38, and the transcriptional activity of NF-& kappa;B in macrophages. The up-regulation of ZNF667 inhibited the levels of expression of HK2 and PFKFB3, glucose consumption, and lactate production in LPS-stimulated macrophages. The up-regulation of mRNA levels of LPS-induced glycolytic genes HK2 and PFKFB3 and the increased mRNA expression of pro-inflammatory cytokines (IL-1 & beta; and iNOS) were abolished by hexokinase inhibitor 2-DG in ZNF667-deficient macrophages. Meanwhile, glucose consumption and lactate production were abrogated in macrophages when cells were treated with the specific mTOR inhibitor RPM. Conclusion Our results demonstrate that ZNF667 suppressed LPS-stimulated RAW264.7 macrophage inflammation by regulating mTOR-dependent aerobic glycolysis.
作者机构：
[Liu, Li; Xiao, Lu-shan; Xiao, LS; Liu, L; Hu, Cheng-yi; Hong, Chang] Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou, Peoples R China.;[Liu, Li; Xiao, Lu-shan; Xiao, LS; Huang, Chao-yi; Zou, Xue-jing; Liu, L; Zou, Xue-Jing; Li, Rui-ning; Hong, Chang; Cui, Hao; Li, Qi-mei] Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.;[Dong, Han-zhi] Jiangxi Canc Hosp, Nanchang Med Coll, Jiangxi Clin Res Ctr Canc, Dept Med Oncol,Affiliated Hosp 2, Nanchang, Jiangxi, Peoples R China.;[Zhu, Hong-bo] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Med Oncol, Hengyang, Peoples R China.;[Peng, Jie; Hu, Cheng-yi] Guangzhou First Peoples Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
通讯机构：
[Xiao, LS ; Zou, XJ; Liu, L] S;Southern Med Univ, Nanfang Hosp, Big Data Ctr, Guangzhou, Peoples R China.;Southern Med Univ, Nanfang Hosp, Dept Infect Dis, Guangzhou, Peoples R China.
关键词：
Alpha-fetoprotein;Hepatic immune predictive index;Immune checkpoint inhibitors;Neutrophil-lymphocyte ratio;Primary liver cancer
摘要：
BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved survival outcomes and resulted in long-term responses in primary liver cancer in some patients. However, its efficacy is limited by the risk of tumor recurrence, resulting in rapid death and graft loss if patients are not selected appropriately. Therefore, it is necessary to identify patients suitable for such therapy. METHODS: 215 patients with primary liver cancer with immunotherapy were screened between August 2018 and October 2020 as a training set and our validation set were included 71 patients of hepatocellular carcinoma from Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College from May 2019 to July 2021. The primary endpoint was the disease control rate (DCR), and the secondary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: In the traing set, Neutrophil-leukocyte ratio (NLR) >3, Alpha-fetoprotein (AFP) level >20 ng/ml, distant metastasis at baseline, and absence of combination with targeted therapy were associated with non-DCR in the training set. Moreover, NLR >3 and AFP level >20 ng/ml were also independently associated with OS. Furthermore, a hepatic immune predictive index (HIPI) based on NLR >3 and AFP level >20 ng/mL was developed and associated with worse clinical outcomes. In validation set, HIPI was associated with overall survival. CONCLUSION: Baseline hepatic immune predictive index based on NLR and AFP level is an effective indicator in ICI-treated patients with primary liver cancer. Our findings may help guide the selection and on-treatment strategies for immunotherapies for primary liver cancer patients.
摘要：
MALT1 (mucosa-associated lymphoid tissue lymphoma translocation protein 1) is a human paracaspase protein with proteolytic activity via its caspase-like domain. The pharmacological inhibition of MALT1 by MI-2, a specific chemical inhibitor, diminishes the response of endothelial cells to inflammatory stimuli. However, it is largely unknown how MALT1 regulates the functions of vascular smooth muscle cells (SMCs). This study aims to investigate the impact of MALT1 inhibition by MI-2 on the functions of vascular SMCs, both in vitro and in vivo. MI-2 treatment led to concentration- and time-dependent cell death of cultured aortic SMCs, which was rescued by the iron chelator deferoxamine (DFO) or ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, but not by inhibitors of apoptosis (Z-VAD-fmk), pyroptosis (Z-YVAD-fmk), or necrosis (Necrostatin-1, Nec-1). MI-2 treatment downregulated the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy polypeptide 1 (FTH1), which was prevented by pre-treatment with DFO or Fer-1. MI-2 treatment also activated autophagy, which was inhibited by Atg7 deficiency or bafilomycin A1 preventing MI-2-induced ferroptosis. MI-2 treatment reduced the cleavage of cylindromatosis (CYLD), a specific substrate of MALT1. Notably, MI-2 treatment led to a rapid loss of contractility in mouse aortas, which was prevented by co-incubation with Fer-1. Moreover, local application of MI-2 significantly reduced carotid neointima lesions and atherosclerosis in C57BL/6J mice and apolipoprotein-E knockout (ApoE(-/-)) mice, respectively, which were both ameliorated by co-treatment with Fer-1. In conclusion, the present study demonstrated that MALT1 inhibition induces ferroptosis of vascular SMCs, likely contributing to its amelioration of proliferative vascular diseases.
摘要：
Human papillomavirus (HPV) E7 protein as an important viral factor was involved in the progression of cervical cancer by mediating the cellular signaling pathways. Daxx (Death domain-associated protein) can interact with a variety of proteins to affect the viral infection process. However, the interaction and its related function between HPV16 E7 and Daxx have not been adequately investigated. Here, it was found that HPV16 E7 can interact with Daxx in HeLa or C33A cells by co-immunoprecipitation. HPV16 E7 protein treatment can up-regulate Daxx protein expression, while the interference in Daxx expression and the agonists for JNK can both reduce the antagonistic effects of HPV16 E7 on TNF-α-induced apoptosis, suggesting that Daxx/JNK pathway may be involved in the anti-apoptotic activity of HPV16 E7.
作者机构：
[Shi, Meng Meng; Xu, Xiao Fan; Guo, Dong Min; Cao, Wen Yu] Univ South China, Hengyang Med Sch, Clin Anat & Reprod Med Applicat Inst, Hengyang, Hunan, Peoples R China.;[Sun, Qiu Min] Yiyang Med Coll, Dept Nursing, Yiyang, Hunan, Peoples R China.;[Luo, Mingying] Kunming Med Univ, Dept Anat & Histol & Embryol, Kunming, Yunnan, Peoples R China.;[Zhong, Xiao Lin; Liu, Dan Dan; Chen, Ling] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang, Hunan, Peoples R China.;[Xu, Yang] Univ South China, Hengyang Med Sch, Inst Neurosci, Hengyang, Hunan, Peoples R China.
通讯机构：
[Xu, Y ; Cao, WY ] U;Univ South China, Hengyang Med Sch, Inst Neurosci, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Clin Anat & Reprod Med Applicat Inst, Hengyang 421001, Hunan, Peoples R China.
摘要：
Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.
期刊：
CURRENT NEUROPHARMACOLOGY,2023年21(11):2251-2265 ISSN：1570-159X
通讯作者：
Tang, XQ
作者机构：
[Wang, Chun-Yan; Qiu, Zheng-Jie] Univ South China, Hengyang Med Coll,Key Lab Arteriosclerol Hunan Pr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hunan Int Sci & Technol Cooperat Base Arterioscle, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Ping] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Xiao-Qing] Univ South China, Hengyang Med Coll, Inst Neurosci, Hengyang Key Lab Neurodegenerat & Cognit Impairme, Hengyang 421001, Hunan, Peoples R China.;[Tang, XQ] Univ South China, Dept Physiol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Tang, XQ] Univ South China, Hengyang Med Sch, Inst Neurosci, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Tang, XQ ] U;Univ South China, Dept Physiol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Inst Neurosci, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Central nervous system;DEC1;Neurodegenerative disease;Parkinson's disease;Pathogenesis;Transcription factor
摘要：
Differentiated embryo-chondrocyte expressed gene1 (DEC1), an important transcription factor with a basic helix-loop-helix domain, is ubiquitously expressed in both human embryonic and adult tissues. DEC1 is involved in neural differentiation and neural maturation in the central nervous system (CNS). Recent studies suggest that DEC1 protects against Parkinson's disease (PD) by regulating apoptosis, oxidative stress, lipid metabolism, immune system, and glucose metabolism disorders. In this review, we summarize the recent progress on the role of DEC1 in the pathogenesis of PD and provide new insights into the prevention and treatment of PD and neurodegenerative diseases.
作者：
Chen, Li-jun;Tan, Feng-hua;Li, Zhe-zhi;Liu, Wei;Lyu, Bo
期刊：
Ecotoxicology and Environmental Safety,2023年255:114832 ISSN：0147-6513
通讯作者：
Li-jun Chen<&wdkj&>Bo Lyu
作者机构：
[Chen, Li-jun; Li, Zhe-zhi] Shaoyang Univ, Coll Urban & Rural Construction, Shaoyang 422099, Peoples R China.;[Tan, Feng-hua] Univ South China, Peoples Hosp ChenZhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou 423000, Hunan, Peoples R China.;[Liu, Wei] Hunan Univ Technol, Coll Urban & Environm Sci, Zhuzhou 412007, Peoples R China.;[Lyu, Bo] Univ Missouri, Div Plant Sci & Technol, Columbia, MO 65211 USA.
通讯机构：
[Li-jun Chen] C;[Bo Lyu] D;Division of Plant Science and Technology, University of Missouri, Columbia, MO 65211, USA<&wdkj&>College of Urban and Rural Construction, Shaoyang University, 422099 Shaoyang, China
摘要：
Although research into how spiders respond to cadmium (Cd)-induced toxicity is ongoing, little is known about the effects of Cd contamination on the exogenous microorganisms of spiders. The current study used 16S rRNA gene sequencing to evaluate the richness and structure of external bacterial communities in the wolf spider Pardosa pseudoannulata under long- and short-term Cd stress. Our results showed that Proteobacteria and Acidibacter were the dominating bacterial phylum and genus. The alpha diversity analysis showed that the high background of Cd concentration (Cd) reduced bacterial alpha diversity, and short-term Cd (SCd) stress elevated bacterial richness and diversity. Hub bacterial genera, including Stenotrophobacter, Hymenobacter, Chitinophaga, and Bryobacter, were identified by co-occurrence network analysis and showed high connectance with other bacterial genera. Further investigation revealed 15 and 14 bacterial taxa that were classified distinctively under SCd and Cd stresses. Interestingly, functional prediction analysis showed that Cd stress enhanced some crucial pathways involved in specialized functions, including manganese oxidation and aromatic compound degradation. Random forest and correlation analyses found that the spider's molting time was the dominant driver affecting bacterial phyla (i.e., Proteobacteria and Planctomycetes) and genera (e.g., Acidibacter, Reyranella, and Haliangium). Collectively, this comprehensive analysis creates new perspectives to investigate the divergent responses of microbial communities in the spiders' external habitat under Cd stress, and provides valuable viewpoints for Cd pollution evaluation and control.
作者机构：
[Yang, Qinglai; He, Yuxuan] Univ South China, Hengyang Med Sch, Dept Biochem & Mol Biol, Hengyang 421001, Peoples R China.;[Tang, Li; Yang, Qinglai; Li, Na; Tan, Xiaofeng; He, Yuxuan; Yang, Sha] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang Med Sch,Ctr Mol Imaging Probe, Hengyang 421001, Peoples R China.;[Tang, Li] Hainan Normal Univ, Coll Chem & Chem Engn, Key Lab Trop Med Plant Chem, Minist Educ, Haikou 571158, Peoples R China.
通讯机构：
[Qinglai Yang] D;Department of Biochemistry and Molecular Biology, Hengyang Medica School, University of South China, Hengyang 421001, 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 421001, China<&wdkj&>Author to whom correspondence should be addressed.
摘要：
In recent years, pathogenic infections have been a growing health threat due to the proliferation of drug-resistant bacteria, so photothermal therapy (PTT) has gained considerable interest in biological and medical fields, owing to its noninvasive and highly effective properties. However, it is hard to achieve selective bacteria targeting while generating a large amount of heat at infected sites. Cationic electrostatic interaction is considered to be a common antimicrobial strategy. Herein, an organic molecule named RT-MN was synthesized with four positively charged quaternary ammonium salts that can bind to negatively charged bacteria. Under near-infrared 808 nm laser irradiation, RT-MN could be efficiently converted into a large amount of heat to eradicate bacteria. In addition, its good water solubility and biological safety proved that RT-MN has excellent biological application prospects. Overall, four such positively charged photosensitizer RT-MN, as a non-antibiotic treatment for resistant bacteria, could be promising for the exploration of highly effective antibacterial agents.
期刊：
Research Reviews in Pharmacology,2023年108(4):311-319 ISSN：0031-7012
通讯作者：
Chen, MH;Peng, JY
作者机构：
[Shi, Tonghuan] Wuhan Univ, Dept Cardiol, Renmin Hosp, Wuhan, Peoples R China.;[Shi, Tonghuan] Wuhan Univ, Hubei Key Lab Cardiol, Cardiovasc Res Inst, Wuhan, Peoples R China.;[Wang, Guangji; Chen, MH; Chen, Manhua] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Cardiol, Wuhan, Peoples R China.;[Wang, Guangji; Chen, MH; Chen, Manhua] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Key Lab Mol Diag Hubei Prov, Wuhan, Peoples R China.;[Peng, Jianye; Peng, JY] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Peoples R China.
通讯机构：
[Chen, MH ] H;[Peng, JY ] U;Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Cardiol, Wuhan, Peoples R China.;Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Key Lab Mol Diag Hubei Prov, Wuhan, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Cardiovasc Med, Hengyang, Peoples R China.
关键词：
Diabetic cardiomyopathy;Myeloid differentiation protein 1;Toll-like receptor 4;Atrial remodelling
摘要：
Introduction: Myeloid differentiation protein 1 (MD1), a negative regulator of toll-like receptor 4 (TLR4), is widely expressed in the heart. Recent studies have shown that MD1 plays an important role in cardiac remodelling. However, the effects and potential mechanisms underlying MD1-mediated atrial remodelling in diabetic cardiomyopathy (DCM) remain unclear. Therefore, this study was designed to explore the role of MD1 in DCM-related atrial remodelling. Methods: MD1 knockout (MD1-KO) mice and wild-type (WT) littermates were injected with streptozotocin (STZ) to establish a diabetic mouse model. These mice were then used to evaluate MD1 expression and its effects on atrial remodelling in vivo. Results: MD1 expression was significantly decreased in STZ-induced diabetic mice. The loss of MD1 aggravated atrial fibrosis, inflammation, and apoptosis in DCM mice and promoted atrial remodelling. MD1-KO diabetic mice also showed higher susceptibility to atrial fibrillation (AF) and worse cardiac function. Mechanistically, the deletion of MD1 promoted the activation of the TLR4/NF-& kappa;B signalling pathway, resulting in atrial remodelling in DCM mice via increased p65 phosphorylation. Conclusions: The deletion of MD1 plays an important role in inflammatory and apoptotic atrial remodelling and increases susceptibility to AF in DCM mice, providing a new target for the preventive treatment of DCM-related atrial remodelling.
作者机构：
[Peng, Jie; Jiang, Yuyang; Gao, Dan; Chen, Yulin] Tsinghua Univ, Tsinghua Shenzhen Int Grad Sch, State Key Lab Chem Oncogen, Guangdong Prov Key Lab Chem Biol, Shenzhen 518055, Guangdong, Peoples R China.;[Zhu, Qingyun] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Chu, Bizhu] Shenzhen Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Shenzhen 518060, Peoples R China.;[Wang, Jian] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Thorac Surg, Shenzhen 518020, Guangdong, Peoples R China.;[Wang, Jian; Liu, Liping] Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China.
通讯机构：
[Dan Gao] S;State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong, China
