期刊：
Journal of Cardiovascular Translational Research,2024年17(6):1219-1228 ISSN：1937-5387
通讯作者：
Li, L
作者机构：
[Xie, Yushu] Univ South China, Hengyang Med Sch, Class Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Xie, Jie] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, L ] U;Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
关键词：
DNA methylation;Histone methylation;RNA methylation;Ferroptosis
摘要：
Methylation modification is a crucial epigenetic alteration encompassing RNA methylation, DNA methylation, and histone methylation. Ferroptosis represents a newly discovered form of programmed cell death (PCD) in 2012, which is characterized by iron-dependent lipid peroxidation. The comprehensive investigation of ferroptosis is therefore imperative for a more profound comprehension of the pathological and pathophysiological mechanisms implicated in a wide array of diseases. Researches show that methylation modifications can exert either promotive or inhibitory effects on cell ferroptosis. Consequently, this review offers a comprehensive overview of the pivotal role played by methylation in ferroptosis, elucidating its associated factors and underlying mechanisms.
期刊：
Journal of Cardiovascular Translational Research,2024年17(5):1067-1082 ISSN：1937-5387
通讯作者：
Peng, Tianhong;Xie, W;Li, L
作者机构：
[Hou, Qin] Univ South China, Inst Cardiovasc Res,Key Lab Atherosclerol Hunan Pr, Med Res Ctr,Hunan Prov Cooperat Innovat Ctr Mol Ta, Key Lab Atherosclerol Hunan Prov,Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Deng, Yunong; Guo, Jiamin; Li, Pin; Yu, Panpan; Xie, Zhongcheng; He, Yinling; Ma, Wentao; Ouyang, Siyu; Tan, Xiaoqian; Lin, Xiaoyan; Liu, Zhiyang] Univ South China, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Zhixia; Mo, Qinger; Yu, Jiang; Chen, Dandan] Univ South China, Hengyang Med Sch, Class Clin Med, Hengyang 421001, Hunan, Peoples R China.;[Chen, Xi; Xie, Wei; Peng, Tianhong; Peng, TH] Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Li, Liang] Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Xie, W ; Li, L ; Peng, TH] U;Univ South China, Clin Anat & Reprod Med Applicat Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Hengyang Med Sch, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
摘要：
Exosomes, nano-sized small extracellular vesicles, have been shown to serve as mediators between intercellular communications by transferring bioactive molecules, such as non-coding RNA, proteins, and lipids from secretory to recipient cells, modulating a variety of physiological and pathophysiological processes. Recent studies have gradually demonstrated that altered exosome charges may represent a key mechanism driving the pathological process of ferroptosis. This review summarizes the potential mechanisms and signal pathways relevant to ferroptosis and then discusses the roles of exosome in ferroptosis. As well as transporting iron, exosomes may also indirectly convey factors related to ferroptosis. Furthermore, ferroptosis may be transmitted to adjacent cells through exosomes, resulting in cascading effects. It is expected that further research on exosomes will be conducted to explore their potential in ferroptosis and will lead to the creation of new therapeutic avenues for clinical diseases.
摘要：
Acute monocytic leukemia-M5 (AML-M5) remains a challenging disease due to its high morbidity and poor prognosis. In addition to the evidence mentioned earlier, several studies have shown that programmed cell death (PCD) serves a critical function in treatment of AML-M5. However, the role and relationship between ferroptosis and necroptosis in AML-M5 remains unclear. THP-1 cells were mainly treated with Erastin and IMP-366. The changes of ferroptosis and necroptosis levels were detected by CCK-8, western blot, quantitative real-time PCR, and electron microscopy. Flow cytometry was applied to detect the ROS and lipid ROS levels. MDA, 4-HNE, GSH and GSSG were assessed by ELISA kits. Intracellular distribution of FSP1 was studied by immunofluorescent staining and western blot. The addition of the myristoylation inhibitor IMP-366 to erastin-treated acute monocytic leukemia cell line THP-1 cell not only resulted in greater susceptibility to ferroptosis characterized by lipid peroxidation, glutathione (GSH) depletion and mitochondrial shrinkage, as the FSP1 position on membrane was inhibited, but also increased p-RIPK1 and p-MLKL protein expression, as well as a decrease in caspase-8 expression, and triggered the characteristic necroptosis phenomena, including cytoplasmic translucency, mitochondrial swelling, membranous fractures by FSP1 migration into the nucleus via binding importin α2. It is interesting to note that ferroptosis inhibitor fer-1 reversed necroptosis. We demonstrated that inhibition of myristoylation by IMP-366 is capable of switching ferroptosis and ferroptosis-dependent necroptosis in THP-1 cells. In these findings, FSP1-mediated ferroptosis and necroptosis are described as alternative mechanisms of PCD of THP-1 cells, providing potential therapeutic strategies and targets for AML-M5.
作者：
Gan, Tian;Yu, Jianwei;Deng, Zhongliang;He, Jun
期刊：
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,2024年14:1454076 ISSN：2235-2988
通讯作者：
He, J
作者机构：
[Gan, Tian; He, Jun; He, J] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang, Peoples R China.;[Deng, Zhongliang; Yu, Jianwei] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Publ Hlth,Lab Sci, Hengyang, Hunan, Peoples R China.
通讯机构：
[He, J ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang, Peoples R China.
关键词：
CRISPR/Cas12a;Mycobacterium tuberculosis;enzymatic recombinant isothermal amplification;fluorescence detection;lateral flow test
摘要：
INTRODUCTION: Mycobacterium tuberculosis, the causative agent of human tuberculosis, poses a significant threat to global public health and imposes a considerable burden on the economy. However, existing laboratory diagnostic methods for M. tuberculosis are time-consuming and have limited sensitivity levels. METHODS: The CRISPR/Cas system, commonly known as the "gene scissors", demonstrates remarkable specificity and efficient signal amplification capabilities. Enzymatic recombinase amplification (ERA) was utilized to rapidly amplify trace DNA fragments at a consistent temperature without relying on thermal cyclers. By integrating of CRISPR/Cas12a with ERA, we successfully developed an ERA-CRISPR/Cas12a detection system that enables rapid identification of M. tuberculosis. RESULTS: The sensitivity of the ERA-CRISPR/Cas12a fluorescence and lateral flow systems was 9 copies/μL and 90 copies/μL, respectively. Simultaneously, the detection system exhibited no cross-reactivity with various of respiratory pathogens and non-tuberculosis mycobacteria, demonstrating a specificity of 100%. The positive concordance rate between the ERA-CRISPR/Cas12a fluorescence system and commercial qPCR was 100% in 60 clinical samples. Meanwhile, the lateral flow system showed a positive concordance rate of 93.8% when compared to commercial qPCR. Both methods demonstrated a negative concordance rate of 100%, and the test results can be obtained in 50 min at the earliest. DISCUSSION: The ERA-CRISPR/Cas12a system offers a rapid, sensitive, and specific method that presents a novel approach to laboratory diagnosis of M. tuberculosis.
作者机构：
[Qin, Qin; Zhong, Li-Yuan; Zeng, Xi; Weng, Xin; Cao, De-Liang; Xie, Li-Hua; Ge, Wen-Jun] Univ South China, Canc Res Inst, Hunan Engn Res Ctr Early Diag & Treatment Liver Ca, Hengyang Med Sch,Hunan Prov Key Lab Tumor Cellular, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Wei-Hong] Hunan Normal Univ, Coll Life Sci, Lab Mol & Stat Genet, Changsha 410081, Hunan, Peoples R China.;[Lai, Zhen] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pathol, Hengyang 421001, Hunan, Peoples R China.;[Liu, Peng] Hunan Normal Univ, Affiliated Hosp 1, Peoples Hosp, Dept Gastroenterol, Changsha 410005, Hunan, Peoples R China.
通讯机构：
[Zeng, X ] U;Univ South China, Canc Res Inst, Hunan Engn Res Ctr Early Diag & Treatment Liver Ca, Hengyang Med Sch,Hunan Prov Key Lab Tumor Cellular, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.
摘要：
Chemotherapy remains a prevalent treatment for a wide range of tumors; however, the majority of patients undergoing conventional chemotherapy experience varying levels of chemoresistance, ultimately leading to suboptimal outcomes. The present article provided an in‑depth review of chemotherapy resistance in tumors, emphasizing the underlying factors contributing to this resistance in tumor cells. It also explored recent advancements in the identification of key molecules and molecular mechanisms within the primary chemoresistant pathways.
作者机构：
[Zhu, Lin; Tan, Xian; He, Yechuan; Wu, Xiaoqi; Wang, Danling] Univ South China, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Zhu, Lin; Tan, Xian; He, Yechuan; Wu, Xiaoqi; Wang, Danling] Univ South China, Inst Future Sci, Changsha 410008, Peoples R China.;[Jiang, Binyuan] Univ South China, Affiliated Changsha Cent Hosp, Med Res Ctr, Hengyang Med Sch, Changsha 410004, Peoples R China.;[Jiang, Binyuan; Yuan, Yeqin; Wang, Danling] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Peoples R China.
通讯机构：
[Jiang, BY ] U;Univ South China, Affiliated Changsha Cent Hosp, Med Res Ctr, Hengyang Med Sch, Changsha 410004, Peoples R China.;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Clin Lab, Changsha 410004, Peoples R China.
摘要：
Background: Nasopharyngeal carcinoma (NPC) exhibits a significant prevalence in the southern regions of China, and paclitaxel (PTX) is frequently employed as a medication for managing advanced NPC. However, drug resistance is typically accompanied by a poor prognosis. Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy. Methods: This study investigated whether 3-Methyladenine (3 -MA) could potentiated the effect of PTX and its potential molecular mechanism. Samples were divided into the following categories: Negative control (NC) with the solvent dimethyl sulfoxide (DMSO, 0.5% v/v), PTX (400 nM), 3 -MA (4 mM), and PTX (400 nM) + 3 -MA (4 mM). The viability of NPC cells was assessed using both the cell counting kit-8 (CCK-8) assay and the colony formation assay. Microscopic observation was performed to identify morphological cell changes. Flow cytometry was used to assess cell cycle status, mitochondrial membrane potential (MMP), and apoptotic cells. Western blotting was conducted to quantify the protein expression. Results: 3 -MA enhanced PTX-specific inhibition of NPC cell proliferation. PTX, either alone or in combination with 3 -MA, caused cell cycle halt at the G2/M phase in the majority of NPC cells, and the combination treatment of PTX with 3 -MA induced a higher rate of NPC cell death compared to PTX alone. Western blotting results revealed the combination of PTX with 3 -MA heightened activation of cyclin-dependent kinase 1 (CDK1), a key molecule in shifting cells from mitotic arrest to apoptosis, led to a reduction in Myeloid Cell Leukemia 1 (MCL-1) expression and an increase in Poly (ADP-ribose) polymerase (PARP) cleavage. Conclusion: The concurrent administration of PTX with 3 -MA effectively enhances PTX's inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
期刊：
Clinical and Translational Medicine,2024年14(8):e1784- ISSN：2001-1326
通讯作者：
Xia, XM;Huang, W
作者机构：
[Xia, XM; Yuan, Xiaorui; Xia, Xiaomeng; Li, Fenghe] Cent South Univ, Xiangya Hosp 2, Dept Gynaecol & Obstet, Changsha, Peoples R China.;[Zeng, Chong] Univ South China, Affiliated Hosp 7, Hengyang Med Sch, Dept Resp & Crit Care Med, Changsha, Hunan, Peoples R China.;[Liu, Jie] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Pathol, Changsha, Hunan, Peoples R China.;[Wang, Lei] Cent South Univ, Canc Res Inst, Sch Basic Med Sci, NHC Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China.;[Wang, Lei] Cent South Univ, Sch Basic Med Sci, Key Lab Carcinogenesis & Canc Invas, Chinese Minist Educ,Canc Res Inst, Changsha, Hunan, Peoples R China.
通讯机构：
[Xia, XM ; Huang, W ] C;Cent South Univ, Xiangya Hosp 2, Dept Gynaecol & Obstet, Changsha, Peoples R China.;Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha, Peoples R China.
关键词：
anti-tumour immunity;immunoregulation;m6A methylation;YTH domain-containing protein family
摘要：
The YTH domain protein family regulates innate and adaptive immunity through regulating multiple immune cells and plays a role in anti‐tumour immunity. The YTH domain protein family influences the tumour immune microenvironment by targeting YAP and metabolic mechanisms, promoting immune escape and metastasis. The YTH domain protein family is a potential target for immune‐related diseases and tumour immunotherapy. Abstract Background The modification of N6‐methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as “readers” of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. Conclusion This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune‐related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. Key points This review provides an in‐depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases. These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications.
期刊：
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH,2024年50(10):1813-1829 ISSN：1341-8076
通讯作者：
Wang, Z
作者机构：
[Cao, Zitong; Wang, Jingjing; Tan, Shiming; Rao, Yuzhu; Tao, Jun; Wang, Zuo] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang, Peoples R China.;[Zhao, Jinli] Univ South China, Affiliated Hosp 1, Emergency Dept, Hengyang, Peoples R China.;[He, Lu] Univ South China, Affiliated Hosp 1, Dept Obstet & Gynecol, Hengyang, Peoples R China.;[Meng, Jun] Univ South China, Affiliated Hosp 1, Funct Dept, Hengyang, Peoples R China.;[Wu, Peng] Hengyang Maternal & Child Hlth Hosp, Hengyang, Peoples R China.
通讯机构：
[Wang, Z ] U;Univ South China, Inst Cardiovasc Dis, Heng Yang Med Sch, Key Lab Arteriosclerol Hunan Prov, Hengyang, Peoples R China.
关键词：
autophagy;gestational diabetes mellitus;pyroptosis;recombinant human placenta growth factor;trophoblast cells
摘要：
INTRODUCTION: Hyperglycemia is closely related to trophoblast dysfunction during pregnancy and results in suppressed invasion, migration, and pro-inflammatory cell death of trophoblasts. Hyperglycemia is a dependent risk factor for gestational hypertension accompanied by decreased placental growth factor (PLGF), which is important for maternal and fetal development. However, there is currently a lack of evidence to support whether PLGF can alleviate trophoblast cell dysfunction caused by high blood sugar. Here, we aim to clarify the effect of hyperglycemia on trophoblast dysfunction and determine how PLGF affects this process. METHODS: The changes in placental tissue histomorphology from gestational diabetes mellitus (GDM) patients were compared with those of normal placentas. HTR8/SVneo cells were cultured in different amounts of glucose to examine cellular pyroptosis, migration, and invasion as well as PLGF levels. Furthermore, the levels of pyroptosis-related proteins (NLRP3, pro-caspase1, caspase1, IL-1β, and Gasdermin D [GSDMD]) as well as autophagy-related proteins (LC3-II, Beclin1, and p62) were examined by Western blotting. The GFP-mRFP-LC3-II system and transmission electron microscopy were used to detect mitophagy levels, and small interfering RNAs targeting BCL2 Interacting Protein 3 (siBNIP3) and PTEN-induced kinase 1 (siPINK1) were used to determine the role of mitophagy in pyroptotic death of HTR-8/SVneo cells. RESULTS: Our results show that hyperglycemia upregulates NLRP3, pro-caspase1, caspase1, IL-1β at the protein level in GDM patients. High glucose (HG, 25 mM) inhibits viability, invasion, and migration of trophoblast cells while suppressing superoxide dismutase levels and promoting malondialdehyde production, thus leading to a senescence associated beta-gal-positive cell burst. PLGF levels in nucleus and the cytosol are also inhibited by HG, whereas PLGF treatment inhibited pyroptosis-related protein levels of NLRP3, pro-caspase1, caspase1, IL-1β, and GSDMD, Gasdermin D N-terminal domain (GSDMD-N). HG-induced mitochondrial dysfunction and BNIP3 and PINK1/Parkin expression. Knocking down BINP3 and PINK1 abolished the protective role of PLGF by preventing mitophagy. CONCLUSION: PLGF inhibited hyperglycemia, while PLGF reversed hyperglycemic injury by promoting mitophagy via the BNIP3/PINK1/Parkin pathway. Altogether, these results suggest that PLGF may protect against trophoblast dysfunction in diabetes.
