作者机构:
[Zhang, Qi; Lu, Yiming; Lu, Hao; Zhao, Xi; Hao, Rongjiao; Han, Huihui; Li, Yuanfeng; Zhou, Gangqiao; Jiang, Siao; Xing, Shuang; Quan, Cheng; Chen, Hongxia; Yu, Zuyin] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing, Beijing, Peoples R China.;[Wang, Qianqian; Yang, Wei] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Radiat Oncol, Beijing, Peoples R China.;[Zhang, Qi; Zhou, Gangqiao] Univ South China, Sch Med, Hengyang, Hunan, Peoples R China.;[Lu, Yiming; Hao, Rongjiao; Zhou, Gangqiao; Jiang, Siao] Univ Hebei, Sch Life Sci, Baoding, Hebei, Peoples R China.;[Feng, Changjiang] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Thorac Surg, Beijing, Peoples R China.
通讯机构:
[Zhou, GQ ; Lu, YM] B;Beijing Inst Radiat Med, Beijing Proteome Res Ctr, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing, Beijing, Peoples R China.;Univ South China, Sch Med, Hengyang, Hunan, Peoples R China.;Univ Hebei, Sch Life Sci, Baoding, Hebei, Peoples R China.;Nanjing Med Univ, Sch Publ Hlth, Collaborat Innovat Ctr Personalized Canc Med, Ctr Global Hlth, Nanjing, Jiangsu, Peoples R China.
摘要:
Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m(6)A) levels showed significant alteration after acute irradiation. The m(6)A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m(6)A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m(6)A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m(6)A in radiation accidents management and clinical applications. Radiation dosimetry are critical for the medical management of individuals exposed to ionizing radiation (IR). Here, authors show that the RNA m6A levels of Ncoa4, Ate1 and Fgf22 genes in peripheral blood cells could serve as dosimetry of IR exposure.
通讯作者:
Fengrui Yang<&wdkj&>Fengrui Yang Fengrui Yang Fengrui Yang
作者机构:
[Chen, Ji] First Peoples Hosp Huaihua, Dept Endocrinol, Huaihua, Peoples R China.;[Guo, Peng; Yang, Fengrui] First Peoples Hosp Huaihua, Dept Anesthesiol, Huaihua, Peoples R China.;[Han, Mingming] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Anesthesiol, Div Life Sci & Med, Hefei, Peoples R China.;[Qin, Jie; Chen, Kemin; Yang, Fengrui] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang, Peoples R China.;[Yang, Fengrui] First Peoples Hosp Huaihua, Dept Anesthesiol, 144 Jinxi South Rd, Huaihua 418000, Hunan, Peoples R China.
通讯机构:
[Fengrui Yang; Fengrui Yang Fengrui Yang Fengrui Yang] D;Department of Anesthesiology, The First People's Hospital of Huaihua, Huaihua, P.R. China<&wdkj&>Department of Anesthesiology, The First Affiliated Hospital, University of South China, Hengyang, P.R. China
摘要:
Recent years have witnessed a growing research interest in traditional Chinese medicine as a neuroprotective nutrient in the management of diabetic cognitive dysfunction. However, the underlying molecular mechanisms of sinomenine in mediating ferroptosis of hippocampal neurons have been poorly understood. This study sought to decipher the potential effect and molecular mechanism of sinomenine in the cognitive dysfunction following type 2 diabetes mellitus (T2DM). Multi-omics analysis was conducted to identify the microbiota-gut-brain axis in T2DM patient samples obtained from the publicly available database. In HT-22 cells, erastin was utilized to create a ferroptosis model, and streptozotocin was injected intraperitoneally to create a rat model of DM. It was noted that intestinal flora imbalance occurred in patients with T2DM-associated cognitive dysfunction. Sinomenine could reduce Erastin-induced hippocampus neuronal ferroptosis by increasing EGF expression. EGF protected hippocampal neurons against ferroptosis by activating the Nrf2/HO-1 signaling pathway. Furthermore, in vivo results confirmed that sinomenine blocked ferroptosis of hippocampal neurons and alleviated cognitive dysfunction in T2DM rats. Collectively, these results suggest that sinomenine confers neuroprotective effects by curtailing hippocampal neuron ferroptosis via the EGF/Nrf2/HO-1 signaling and microbiota-gut-brain axis. It may be a candidate for the treatment of diabetic cognitive dysfunction.
作者机构:
[Huang, Haoxuan; Kuang, Yirui; Zhang, Wenlong; Kuang, YR; Li, Can] Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China.;[Huang, Haoxuan; Kuang, Yirui; Zhang, Wenlong; Kuang, YR; Li, Can] Cent South Univ, Canc Res Inst, Sch Basic Med Sci, Changsha 410008, Hunan, Peoples R China.;[Cheng, Ailan; Jiang, Bincan] Univ South China, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhu, Hecheng; Li, Xuewen] Changsha Kexin Canc Hosp, Changsha 410205, Hunan, Peoples R China.
通讯机构:
[Kuang, YR ] C;Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Dept Neurosurg, Changsha 410008, Hunan, Peoples R China.;Cent South Univ, Canc Res Inst, Sch Basic Med Sci, Changsha 410008, Hunan, Peoples R China.
摘要:
The microRNAs (miRNAs), an extensive class of small noncoding RNAs (∼22 nucleotides), have been shown to have critical functions in various biological processes during development. miR-33b (or hsa-miR-33b) is down-regulated in cancer of multiple systems. Notably, at least 27 protein-coding genes can be targeted by miR-33b. miR-33b regulates the cell cycle, cell proliferation, various metabolism pathways, epithelial-mesenchymal transition (EMT), cancer cell invasion and migration, etc. In prostate cancer, Cullin 4B (CUL4B) can be recruited to the promoter to inhibit the expression of miR-33b. In gastric cancer, the hypermethylation of the CpG island regulated the expression of miR-33b. Besides, miR-33b could be negatively regulated by 7 competing-endogenous RNAs (ceRNAs), which are all long non-coding RNAs (lncRNAs). There are at least 4 signaling pathways, including NF-κB, MAP8, Notch1, and Wnt/β-catenin signaling pathways, which could be regulated partially by miR-33b. Additionally, low expression of miR-33b was associated with clinicopathology and prognosis in cancer patients. In addition, the aberrant expression of miR-33b was connected with the resistance of cancer cells to 5 anticancer drugs (cisplatin, docetaxel, bortezomib, paclitaxel, and daunorubicin). Importantly, our work systematically summarizes the aberrant expression of miR-33b in various neoplastic diseases and the effect of its downregulation on the biological behavior of cancer cells. Furthermore, this review focuses on recent advances in understanding the molecular regulation mechanisms of miR-33b. Moreso, the relationship between the miR-33b expression levels and the clinicopathological data and prognosis of tumor patients was summarized for the first time. Overall, we suggest that the current studies of miR-33b are insufficient but provide potential hints and direction for future miR-33b-related research.
通讯机构:
[Tan, SJ ; Zeng, P] U;Univ South China, Sch Basic Med, Hengyang Med Sch, Dept Histol & Embryol, Hengyang, Peoples R China.
摘要:
Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.
期刊:
Japanese Journal of Clinical Radiology,2023年79(1):e147-e155 ISSN:0009-9252
通讯作者:
Yang, Q;Fang, X
作者机构:
[Xiang, Z.; Li, Q.; Fang, X.; Liu, F.] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Radiol, Hengyang 421001, Hunan, Peoples R China.;[Zhou, J.] Jiangsu Univ, Affiliated Hosp, Zhenjiang 212001, Jiangsu, Peoples R China.;[Yang, X.] Sichuan Sci City Hosp, Mianyang 621000, Sichuan, Peoples R China.;[Lin, H.] GE Healthcare, Dept Pharmaceut Diag, Changsha 410005, Peoples R China.;[Yang, Q.] Univ South China, Ctr Mol Imaging Probe, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Fang, X ; Yang, Q ] U;Univ South China, Hengyang Med Sch, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol,Ctr, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Dept Radiol, Hengyang Med Sch, 30 Jiefang Rd, Hengyang 421001, Hunan, Peoples R China.
摘要:
AIM: To explore the value of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography (PET)/computed tomography (CT)-based radiomics model for predicting the degree of pathological differentiation in non-small-cell lung cancer (NSCLC).MATERIALS AND METHODS: Clinical characteristics of 182 NSCLC patients from four centres were collected, and radiomics features were extracted from 18F-FDG PET/CT images. Three logistic regression prediction models were established: clinical model; radiomics model; and nomogram combining radiomics signatures and clinical features. The predictive ability of the models was assessed using receiver operating characteristics curve analysis. RESULTS: Patients from centre 1 were assigned randomly to the training and internal validation cohorts (7:3 ratio); patients from centres 2-4 served as the external validation cohort. The area under the curve (AUC) values for the clinical model in the training, internal validation, and external validation cohort were 0.74 (95% confidence interval [CI] = 0.64-0.84), 0.64 (95% CI = 0.46-0.81), and 0.74 (95% CI = 0.60-0.88), respectively. In the training (AUC: 0.84 [95% CI = 0.77-0.92]), internal validation (AUC: 0.81 [95% CI = 0.67-0.95]), and external validation cohorts (AUC: 0.74 [95% CI = 0.58-0.89]), the radiomics model showed good predictive ability for differentiation. Compared to the clinical and radiomics models, the nomogram has relatively better diagnostic performance, and the AUC values for nomogram in the training, internal validation, and external validation cohort were 0.86 (95% CI = 0.78-0.93), 0.83 (95% CI = 0.70-0.96), and 0.77 (95% CI = 0.62-0.92), respectively.CONCLUSIONS: The 18F-FDG PET/CT-based radiomics model showed good ability for predicting the degree of differentiation of NSCLC. The nomogram combining the radiomics signature and clinical features has relatively better diagnostic performance. (c) 2023 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
摘要:
Treponema pallidum (T. pallidum), an obligate extracellular bacterium, is the causative agent of sexually transmitted bacterial diseases. In this study, the glycolytic enzyme enolase (Tp Eno) of T. pallidum were injected intramuscularly into C57BL/6 mice, resulting in higher levels of specific anti-Tp Eno antibodies and Tp Eno-specific splenocyte proliferation than those in the mice immunized with recombinant protein Tp Eno. Cytokine (IL-4, IL-6, IL-10, IFN-γ, and TNF-α) analysis of splenocytes showed that the Tp Eno could slightly trigger the Th1-biased immune response. Furthermore, immunization of mice with Tp Eno elicited a significant production of IFN-γ by CD4(+) T-cells in the spleen. Subsequently, mice were inoculated intradermally (between the scapulae), intraperitoneally, intrarectally and via the corpora cavernosa with 2.5×10(6) organisms per site (1×10(7) total organisms). The bacterial organ burden detected in the blood, spleen, liver, testes or brain of immunized mice suggested that Tp Eno enhances protective immunity to inhibit T. pallidum colonization in distal tissues. Therefore, Tp Eno vaccination enhances Tp Eno-specific immunogenicity and provides protection against T. pallidum dissemination.
摘要:
(+)-JQ1, a specific chemical inhibitor of bromodomain and extraterminal (BET) family protein 4 (BRD4), has been reported to inhibit smooth muscle cell (SMC) proliferation and mouse neointima formation via BRD4 regulation and modulate endothelial nitric oxide synthase (eNOS) activity. This study aimed to investigate the effects of (+)-JQ1 on smooth muscle contractility and the underlying mechanisms. Using wire myography, we discovered that (+)-JQ1 inhibited contractile responses in mouse aortas with or without functional endothelium, reducing myosin light chain 20 (LC20) phosphorylation and relying on extracellular Ca2+. In mouse aortas lacking functional endothelium, BRD4 knockout did not alter the inhibition of contractile responses by (+)-JQ1. In primary cultured SMCs, (+)-JQ1 inhibited Ca2+ influx. In aortas with intact endothelium, (+)-JQ1 inhibition of contractile responses was reversed by NOS inhibition (L-NAME) or guanylyl cyclase inhibition (ODQ) and by blocking the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. In cultured human umbilical vein endothelial cells (HUVECs), (+)-JQ1 rapidly activated AKT and eNOS, which was reversed by PI3K or ATK inhibition. Intraperitoneal injection of (+)-JQ1 reduced mouse systolic blood pressure, an effect blocked by co-treatment with L-NAME. Interestingly, (+)-JQ1 inhibition of aortic contractility and its activation of eNOS and AKT were mimicked by the (-)-JQ1 enantiomer, which is structurally incapable of inhibiting BET bromodomains. In summary, our data suggest that (+)-JQ1 directly inhibits smooth muscle contractility and indirectly activates the PI3K/AKT/eNOS cascade in endothelial cells; however, these effects appear unrelated to BET inhibition. We conclude that (+)-JQ1 exhibits an off-target effect on vascular contractility.
摘要:
Background: Ovarian cancer (OC), a serious gynecological malignant disease, remains an enormous challenge in early diagnosis and medical treatment. Based on the GEO and TCGA databases in R language, endothelial cell-specific molecule 1 (ESM1) was confirmed separately with the bioinformatic analysis tool. ESM1 has been demonstrated to be upregulated in multiple cancer types, but the oncogenic mechanism by which ESM1 promotes OC is still largely unknown. Methods: In this study, we used WGCNA and random survival forest variable screening to filter out ESM1 in OC differentially expressed genes (DEGs). Next, we confirmed the mRNA and protein levels of ESM1 in OC samples via PCR and IHC. The correlation between the ESM1 level and clinical data of OC patients was further confirmed, including FIGO stage, lymph node metastasis, and recurrence. The role of ESM1 in OC development was explored by several functional experiments in vivo and in vitro. Then, the molecular mechanisms of ESM1 were further elucidated by bioinformatic end experimental analysis. Results: ESM1 was significantly upregulated in OC and was positively correlated with PFS but negatively correlated with OS. ESM1 knockdown inhibited cell proliferation, apoptosis escape, the cell cycle, angiogenesis, migration and invasion in multiple experiments. Moreover, GSVA found that ESM1 was associated with the Akt pathway, and our results supported this prediction. Conclusion: ESM1 was closely correlated with OC development and progression, and it could be considered a novel biomarker and therapeutic target for OC patients.
摘要:
PURPOSE: Myocardial ischemic reperfusion injury (MIRI) is a crucial clinical problem globally. The molecular mechanisms of MIRI need to be fully explored to develop new therapeutic methods. Galangin (Gal), which is a natural flavonoid extracted from Alpinia Officinarum Hance and Propolis, possesses a wide range of pharmacological activities, but its effects on MIRI remain unclear. This study aimed to determine the pharmacological effects of Gal on MIRI. METHODS: C57BL/6 mice underwent reperfusion for 3 h after 45 min of ischemia, and neonatal rat cardiomyocytes (NRCs) subjected to hypoxia and reoxygenation (HR) were cultured as in vivo and in vitro models. Echocardiography and TTC-Evans Blue staining were performed to evaluate the myocardial injury. Transmission electron microscope and JC-1 staining were used to validate the mitochondrial function. Additionally, Western blot detected ferroptosis markers, including Gpx4, FTH, and xCT. RESULTS: Gal treatment alleviated cardiac myofibril damage, reduced infarction size, improved cardiac function, and prevented mitochondrial injury in mice with MIRI. Gal significantly alleviated HR-induced cell death and mitigated mitochondrial membrane potential reduction in NRCs. Furthermore, Gal significantly inhibited ferroptosis by preventing iron overload and lipid peroxidation, as well as regulating Gpx4, FTH, and xCT expression levels. Moreover, Gal up-regulated nuclear transcriptive factor Nrf2 in HR-treated NRCs. Nrf2 inhibition by Brusatol abolished the protective effect of Gal against ferroptosis. CONCLUSION: This study revealed that Gal alleviates myocardial ischemic reperfusion-induced ferroptosis by targeting Nrf2/Gpx4 signaling pathway.
期刊:
Journal of Diabetes Investigation,2023年14(3):364-375 ISSN:2040-1116
通讯作者:
Fengrui Yang<&wdkj&>Fengrui Yang Fengrui Yang Fengrui Yang
作者机构:
[Chen, Ji] First Peoples Hosp Huaihua, Dept Endocrinol, Huaihua, Peoples R China.;[Liu, Xinxin; Guo, Peng; Liao, Huizhi; Yang, Fengrui] First Peoples Hosp Huaihua, Dept Anesthesiol, Huaihua, Peoples R China.;[Qin, Jie; Chen, Kemin; Yang, Fengrui; Wang, Yuxia] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Anesthesiol, Hengyang, Peoples R China.
通讯机构:
[Fengrui Yang; Fengrui Yang Fengrui Yang Fengrui Yang] D;Department of Anesthesiology, The First People's Hospital of Huaihua, Huaihua, China<&wdkj&>Department of Anesthesiology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, China
摘要:
Molecular mechanism diagram of the role of SIN in DPNP by regulating PTGS2‐mediated IRE1α‐XBP1s pathway. SIN down‐regulates the expression of PTGS2 to inactivate IRE1α‐XBP1s signaling pathway, which inhibits microglial cell activation and the release of inflammatory factors, finally alleviating DPNP. Abstract Introduction We tried to show the effect of sinomenine (SIN) in diabetic peripheral neuropathic pain (DPNP) and the related underlying mechanism. Methods Network pharmacological analysis and bioinformatics analysis were carried out for identification of the active ingredients of Sinomenium acutum and the related genes. The DPNP rat model was constructed and primary rat spinal cord microglial cells were isolated for in vitro cell experiments. The therapeutic role of SIN in DPNP was determined in vivo and in vitro through analysis of microglial cell activation and inflammatory response. Results Therapeutic role of S. acutum in DPNP was mainly achieved by regulating 14 key genes, among which the target gene prostaglandin‐endoperoxide synthase 2 (PTGS2) of SIN might be the key gene. An in vivo experiment showed that SIN inactivated the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 pathway by downregulating PTGS2, which relieved pain symptoms in DPNP rats. It was confirmed in vivo that SIN inhibited the pathway through PTGS2 to alleviate the activation of spinal cord microglial cells and inflammatory response. Conclusion SIN decreases the expression of PTGS2 to inactivate the inositol‐requiring enzyme 1 alpha–X‐box binding protein 1 signaling pathway, which inhibits microglial activation, as well as the release of inflammatory factors, thus alleviating DPNP.
期刊:
Journal of Assisted Reproduction and Genetics,2023年40(1):3-17 ISSN:1058-0468
通讯作者:
He, Lu;Yang, Chunfen;Wang, Zuo
作者机构:
[Cao, Zitong; Chen, Yanjun; Liang, Lingli; Xia, Linzhen; Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.;[Wu, Chunyan] Univ South China, Dept Cardiovasc, Affiliated Hosp 3, Hengyang 421001, Peoples R China.;[Meng, Jun] Univ South China, Dept Funct, Affiliated Hosp 1, Hengyang 421001, Peoples R China.;[Yang, Chunfen; He, Lu] Univ South China, Dept Gynecol, Affiliated Hosp 1, Hengyang 421001, Peoples R China.
通讯机构:
[Wang, Zuo] I;[He, Lu; Yang, Chunfen] D;Department of Gynecology, The First Affiliated Hospital of University of South China, Hengyang, 421001, China.;Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, 421001, China.
摘要:
The placenta is essential for a successful pregnancy and healthy intrauterine development in mammals. During human pregnancy, the growth and development of the placenta are inseparable from the rapid proliferation, invasion, and migration of trophoblast cells. Previous reports have shown that the occurrence of many pregnancy disorders may be closely related to the dysfunction of trophoblasts. However, the function regulation of human trophoblast cells in the placenta is poorly understood. Therefore, studying the factors that regulate the function of trophoblast cells is necessary. MicroRNAs (miRNAs) are small, non-coding, single-stranded RNA molecules. Increasing evidence suggests that miRNAs play a crucial role in regulating trophoblast functions. This review outlines the role of miRNAs in regulating the function of trophoblast cells and several common signaling pathways related to miRNA regulation in pregnancy disorders.
期刊:
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY,2023年157:106376 ISSN:1357-2725
通讯作者:
Yimou Wu
作者机构:
[Wu, Yimou; Li, Yumeng; Li, Sijia; He, Siqin; Huang, Yanru] Univ South China, Inst Pathogen Biol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dru, Hengyang Med Sch,Hunan Prov Key Lab Special Preven, Hengyang 421001, Hunan, Peoples R China.;[Li, Yumeng] Univ South China, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421000, Hunan, Peoples R China.;[He, Qingzhi] Guilin Med Univ, Sch Biotechnol, Guilin 541199, Peoples R China.;[Wu, Yimou] Univ South China, Pathogen Biol Inst, Hengyang Med Sch, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Yimou Wu] I;Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, Hunan, China
摘要:
Chlamydia psittaci is a multi-host zoonotic pathogen, which mainly infects poultry and inflicts an appreciable economic burden on the livestock farming industry. C. psittaci inclusion membrane proteins are uniquely posi-tioned at the host-pathogen interface and are important virulence proteins. We have previously confirmed that Incs regulate host cell survival to help Chlamydia sp. evade host-cell-mediated defense mechanisms. However, the role of the Inc, CPSIT_0842, in the regulation of cell death following the establishment of persistent C. psittaci infection remains unknown. This study explored the effect of CPSIT_0842 on the crosstalk between the auto-phagic and apoptotic pathways in macrophages. Results showed that CPSIT_0842 initiated autophagy and blocked autophagic flux in human macrophages, as indicated by autophagy-related protein LC3-II, Beclin-1, and p62 upregulation, autophagosome accumulation, and lysosomal protein LAMP1 diminution. We also showed that the disruption of autophagic flux had a regulatory effect on CPSIT_0842-induced apoptosis. Moreover, the suppression of autophagy initiation by 3-methyladenine attenuated CPSIT_0842-induced apoptosis. By contrast, the induction of autophagic flux by rapamycin did not significantly affect CPSIT_0842-induced apoptosis. Taken together, these findings demonstrate that CPSIT_0842 induced macrophage apoptosis by initiating incomplete autophagy through the MAPK/ERK/mTOR signaling pathway, which may be instrumental to the ability of C. psittaci to evade the host innate immune response and establish persistent infection. The improved under-standing of the autophagic and cell death pathways triggered upon bacterial inclusion will likely help in the development of novel treatment strategies for chlamydia infection.
摘要:
Alzheimer's disease is the most common neurodegenerative disease. Acanthopanax senticosus, also known as Ciwujia or Siberian ginseng in Chinese, has a wide range of antioxidant and anti-inflammatory activities. The study aims to explore the action mechanism of A. senticosus against Alzheimer's disease using network pharmacology and molecular docking. The active ingredients and targets of A. senticosus were searched through the ETCM database, and Alzheimer's disease-related targets were obtained through the OMIM and GeneCards databases. The Cytoscape 3.7.2 software was used to construct a "drug-component-target " relationship network, and the target genes of A. senticosus against Alzheimer's disease were imported into the String database to establish a protein interaction (PPI) network. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes gene enrichment analyses were performed through the Metascape database to obtain potential pathways of action of A. senticosus for the treatment of Alzheimer's disease, and the ability of these active ingredients to bind to core targets was then verified by molecular docking. 51 active ingredients were screened from A. senticosus, and 88 effective targets for Alzheimer's disease were screened. Topological and pathway-enrichment analyses revealed that A. senticosus could play a beneficial role in the treatment of Alzheimer's disease by regulating apoptosis and inflammation. Molecular docking results showed that Ciwujianoside B, Chiisanoside, and Ciwujianoside D1 had strong binding abilities to key target proteins (TNF alpha, IL1 beta, and CASP3). Collectively, A. senticosus is feasible in the treatment of Alzheimer's disease. [GRAPHICS]
摘要:
Atherosclerosis (AS) is the major factor of cardiovascular disease (CVD) and is characterized by a progressive and chronic inflammatory process in the arterial wall. Recent studies have shown that disruption of the mitochondrial membrane potential (deltapsi (m)) directly affects the electron transport chain (ETC), which in turn leads to oxidative stress, and furthermore, its alteration leads to apoptosis and activation of the NLRP3 inflammasome, thereby promoting the development of AS. Here, this review describes how deltapsi (m) contributes to the development of AS by mediating oxidative stress, apoptosis, and NLRP3 inflammasome activation, and potential AS intervention strategies by targeting oxidative stress, apoptosis, and NLRP3 inflammasome activation induced by deltapsi (m).
期刊:
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY,2023年24(2):149-161 ISSN:1562-2975
通讯作者:
Deming Wang<&wdkj&>Ji Xiao
作者机构:
[Huang, Zixia; Wang, Deming; Xiao, Ji; Fan, Xuhong; Wu, Mingyue] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang, Peoples R China.;[Zhao, Zhenyu] Hunan Univ Chinese Med, Hosp 1, Dept Anesthesiol, Changsha, Peoples R China.
通讯机构:
[Deming Wang; Ji Xiao] D;Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, China<&wdkj&>Department of Anesthesiology, The Second Affiliated Hospital of University of South China, Hengyang, China
期刊:
JOURNAL OF MATERIALS CHEMISTRY B,2023年11(39):9459-9466 ISSN:2050-750X
通讯作者:
Cheng, D;Li, Songjiao;He, LW
作者机构:
[He, LW; Zeng, Jiayu; Li, Songjiao; He, Longwei; Jiang, Renfeng] Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421002, Hunan, Peoples R China.;[Cheng, Dan; Liu, Qian] Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang 421002, Hunan, Peoples R China.
通讯机构:
[He, LW ; Cheng, D ; Li, SJ] U;Univ South China, Hengyang Med Sch, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang 421002, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Sch Pharmaceut Sci, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421002, Hunan, Peoples R China.
摘要:
Hepatocellular carcinoma (HCC) is a type of cancer associated with a high rate of mortality and morbidity. In order to achieve precise HCC theranostics, it is important to develop excellent fluorescent probes. However, the existing probes are not sensitive or specific enough to accurately identify HCC margins and contours. For diagnosing HCC and identifying tumors during surgery, it is urgent to engineer highly sensitive and selective fluorescent probes. Liver tumor progression is closely associated with leucine aminopeptidase (LAP) overexpression, a biomarker of liver cancer. Herein, we have rationally designed a NIR fluorescent probe, NLAP, which is specially activated by LAP. The probe exhibited high sensitivity (detection limit = 6.8 mU L-1) and superior affinity (Km = 2.98 mu M) for LAP. With this probe, we distinguished cancer cells overexpressing LAP from normal cells and applied it intraoperatively to guide liver tumor excisions. Furthermore, NLAP was employed to successfully detect the LAP of intestinal and splenic metastatic tumors in orthotopic liver tumor mice by "in situ spraying" and good performances were demonstrated. Visualizing a LAP change in cancer cells and normal cells and guiding surgical resection of liver cancer by engineering an activated near-infrared fluorescent probe with high sensitivity and selectivity.