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.
期刊:
DNA AND CELL BIOLOGY,2024年43(10):492-509 ISSN:1044-5498
通讯作者:
Wang, Z
作者机构:
[Liu, Yiman; Wang, Jingjing; Wang, Zuo] Univ South China, Hengyang Med Coll, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Chengsheng rd 28, Hengyang 421001, Peoples R China.;[Peng, Wu; Yang, Peijuan] Hengyang Maternal & Child Hlth Hosp, Hengyang, Peoples R China.;[Zhao, Jinli] Univ South China, Affiliated Hosp 1, Emergency Dept, Hengyang, Peoples R China.
通讯机构:
[Wang, Z ] U;Univ South China, Hengyang Med Coll, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Chengsheng rd 28, Hengyang 421001, Peoples R China.
关键词:
cardiovascular and cerebrovascular diseases;ferroptosis;microRNA
摘要:
Cardiovascular and cerebrovascular diseases (CCVDs) significantly contribute to global mortality and morbidity due to their complex pathogenesis involving multiple biological processes. Ferroptosis is an important physiological process in CCVDs, manifested by an abnormal increase in intracellular iron concentration. MiRNAs, a key class of noncoding RNA molecules, are crucial in regulating CCVDs through pathways like glutathione-glutathione peroxidase 4, glutamate/cystine transport, iron metabolism, lipid metabolism, and other oxidative stress pathways. This article summarizes the progress of miRNAs' regulation on CCVDs, aiming to provide insights for the diagnosis and treatment of CCVDs.
摘要:
Pyroptosis, a programmed cell death marked by lytic and inflammatory characteristics, plays a crucial role in non‑infectious inflammation‑related diseases but can lead to detrimental outcomes when dysregulated. Stem cells have emerged as key players in modulating pyroptosis through paracrine signaling, offering a novel avenue for tissue repair and regeneration. The present review delved into previous studies elucidating the intricate interplay between stem cells and pyroptosis, emphasizing the potential of stem cell‑based therapies in regulating pyroptotic pathways. The exploration of this dynamic interaction holds promise for developing strategies to harness stem cells for effective tissue repair and regeneration in the context of inflammation‑related diseases.
作者机构:
[Shiqi Yang; Qing Yuan; Zhaolin Zeng; Qian Chen] Department of Metabolism and Endocrinology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China;[Shiqi Yang; Qing Yuan] Department of Clinical Laboratory Medicine, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China;[Zuo Wang] Institute of Cardiovascular Disease, Key Lab for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China;[Hui Xie] Department of Orthopaedics, Movement System Injury and Repair Research Centre, Xiangya Hospital, Central South University, Changsha, Hunan Province, China. huixie@csu.edu.cn;[Jianghua Liu] Department of Metabolism and Endocrinology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China. jianghua990@126.com
通讯机构:
[Xie, Hui; Liu, Jianghua] D;Department of Orthopaedics, Movement System Injury and Repair Research Centre, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.;Department of Metabolism and Endocrinology, Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China.
摘要:
<jats:p><jats:bold>Background:</jats:bold> Gastric cancer is one of the cancers with wide incidence, difficult treatment and high mortality in the world, especially in Asia and Africa. In our previous work, a novel <jats:italic>o</jats:italic>-aminobenzamide analogue <jats:bold>F8</jats:bold> was identified as an early preclinical candidate for treatment of undifferentiated gastric cancer (IC<jats:sub>50</jats:sub> of 0.26μM for HGC-27). However, the poor water solubility of compound <jats:bold>F8</jats:bold> prevents its further progress in preclinical studies.</jats:p><jats:p><jats:bold>Aim:</jats:bold> To improve the water solubility and drug-likeness of <jats:bold>F8</jats:bold> via salt formation.</jats:p><jats:p><jats:bold>Method:</jats:bold> Different acids and <jats:bold>F8</jats:bold> were reacted to obtain different salt forms. Physicochemical property screening, pharmacokinetic property research, and antitumor biological activity evaluation <jats:italic>in vitro</jats:italic> and<jats:italic> in vivo</jats:italic> were used to obtain the optimal salt form with the best druggability.</jats:p><jats:p><jats:bold>Results:</jats:bold> our continuous efforts have finally confirmed <jats:bold>F8·2HCl</jats:bold> as the optimal salt form with maintained <jats:italic>in vitro</jats:italic> antitumor activity, improved water solubility and pharmacokinetic properties. Importantly, the <jats:bold>F8·2HCl</jats:bold> displayed superior<jats:italic> in vivo</jats:italic> antitumor efficacy (TGI of 70.1% in 75mg/kg) in HGC-27 xenograft model. The further immunohistochemical analysis revealed that <jats:bold>F8·2HCl</jats:bold> exerts an antitumor effect through the regulation of cell cycle-related protein (CDK2 and p21), apoptosis-related protein Cleaved Caspase-3, proliferation marker Ki67, and cell adhesion molecule E-cadherin. In addition, <jats:bold>F8·2HCl</jats:bold> showed acceptable safety in the<jats:italic> in vivo</jats:italic> acute toxicity assay.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> Salting is an effective means to improve the drug-like properties of compound <jats:bold>F8</jats:bold>, and <jats:bold>F8·2HCl</jats:bold> can serve as a promising therapeutic agent against undifferentiated gastric cancer.</jats:p>
期刊:
Journal of Surgical Research,2023年284:280-289 ISSN:0022-4804
通讯作者:
Kexuan Liu<&wdkj&>Bingcheng Zhao
作者机构:
[Zhu, Lin] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Anesthesiol, Hengyang, Hunan, Peoples R China.;[Lai, Yupei; Zhu, Lin; Xu, Shiting; Zhao, Bingcheng; Liu, Kexuan; Yao, Zhiwen; Yang, Xiao; Wang, Ziyi] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, Guangzhou, Guangdong, Peoples R China.;[Zhao, Bingcheng; Liu, Kexuan] Southern Med Univ, Nanfang Hosp, Dept Anesthesiol, Guangzhou 510515, Guangdong, Peoples R China.
通讯机构:
[Kexuan Liu; Bingcheng Zhao] D;Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
关键词:
competing endogenous RNA;complementary DNA;kruppel like factor 4;long untranslated RNA;messenger RNA;microRNA;transcription factor;long untranslated RNA;messenger RNA;microRNA;animal experiment;animal model;animal tissue;Article;bioinformatics;biotechnology;controlled study;differential expression analysis;DNA binding;gene expression;gene ontology;intestine ischemia;male;mouse;nonhuman;protein expression;protein function;protein protein interaction;real time polymerase chain reaction;real time reverse transcription polymerase chain reaction;reperfusion injury;animal;biology;gene regulatory network;genetics;intestine;ischemia;metabolism;reperfusion injury;Animals;Computational Biology;Gene Regulatory Networks;Intestines;Ischemia;Mice;MicroRNAs;Reperfusion Injury;RNA, Long Noncoding;RNA, Messenger
摘要:
Introduction: Recently, accumulating studies have reported the roles of competitive endogenous RNA (ceRNA) networks in ischemia/reperfusion (I/R) injury in several organs, including the liver, kidney, heart, brain, and intestine. However, the functions and mechanisms of long noncoding RNAs (lncRNAs)dwhich serve as ceRNA networks in in-testinal I/R injurydremain elusive.Methods: RNA expression data were retrieved from the National Center for Biotechnology Information-Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs) (miDEGs) were explored between the sham and intestinal I/R injury samples. Next, targeted lncRNAs and messenger RNAs in the database were matched based on miDEGs. Hub ceRNA networks were constructed and visualized via Cytoscape. Intersection analysis was performed to screen mDEGs between two datasets. Finally, the vital nodes of the ceRNA networks were validated by quantitative PCR.Results: A total of 189 miDEGs were identified. Forty miRNAs were found to be associated with 240 predicted target genes from miRWalk 3.0. The ceRNA network was constructed with 10 miRNAs, including the 1700020114Rik/mmu-miR-7a-5p/Klf4 axis. Furthermore, the expression of lncRNA 1700020114Rik (P < 0.05) and messenger RNA Klf4 (P < 0.01) was markedly decreased in mouse models of intestinal I/R injury, whereas the expression level of mmu-miR-7a-5p was significantly increased (P < 0.05).Conclusions: The results provide novel insights into the molecular mechanism of ceRNA networks in intestinal I/R injury and highlight the potential of the 170002700020114Rik/ mmu-miR-7a-5p/Klf4 axis in the prevention and treatment of intestinal I/R injury.(c) 2022 Elsevier Inc. All rights reserved.
期刊:
Computer Methods in Biomechanics and Biomedical Engineering,2023年27(6):700-716 ISSN:1025-5842
通讯作者:
Haohua Wang
作者机构:
[Wang, Haohua; Wang, Zhigang; Zhang, Jingwen] Hainan Univ, Sch Sci, Haikou, Peoples R China.;[Wang, Haohua; Wang, Zhigang] Key Lab Engn Modeling & Stat Computat Hainan Prov, Haikou, Peoples R China.;[Wang, Yan] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang, Peoples R China.;[Wang, Haohua] Minist Educ, Key Lab Genet & Germplasm Innovat Trop Special Fo, Haikou, Peoples R China.
通讯机构:
[Haohua Wang] S;School of Sciences, Hainan University, Haikou, China<&wdkj&>Key Laboratory of Engineering Modeling and Statistical Computation of Hainan Province, Haikou, China<&wdkj&>Key Laboratory of Genetics & Germplasm Innovation Tropical Special Fo, Ministry of Education, Haikou, China
关键词:
Stochastic analysis;optimal control;time-delay;Hepatitis B epidemic model
摘要:
Considering the time delay originating from a certain incubation period or asymptomatic state, we propose a delayed epidemic system within the noisy environment of the hepatitis B virus to analyze the mechanism of disease transmission and elucidate how to control it by applying the strategy of vaccinating and treatment. Applying stochastic Lyapunov functional theory, we first construct an integral Lyapunov function coupling the time delay and stochastic fluctuation to investigate whether there exists a unique global solution to the model. Next, we yield the threshold condition for controlling disease extinction, and persistence, as well as its stationary distribution. Governed by these sufficient conditions, we study the existence of optimal control solutions in deterministic and stochastic scenarios to uncover how to accelerate disease extinction through vaccination and treatment. The results indicate that the time delay will prolong the duration of the disease for the original system but suppress the peak value of HBV in the controlled system. Finally, we verify the versatility of theoretical results by numerical simulations. These results will effectively decipher the importance of the time delay in the control of hepatitis B.
作者机构:
[Wang, Zi; Xiao, Xiaojuan; Liu, Jing; Zhu, Yu; Peng, Hongling; Li, Yanan] Cent South Univ, Xiangya Hosp 2, Mol Biol Res Ctr, Sch Life Sci,Hunan Prov Key Lab Basic & Appl Hemat, Changsha 410011, Peoples R China.;[Zhang, Ji] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Clin Lab, Hengyang 421001, Peoples R China.
通讯机构:
[Xiaojuan Xiao; Ji Zhang] A;Authors to whom correspondence should be addressed.<&wdkj&>Department of Hematology, The Second Xiangya Hospital, Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha 410011, China<&wdkj&>Authors to whom correspondence should be addressed.<&wdkj&>The Affiliated Nanhua Hospital, Department of Clinical Laboratory, Hengyang Medical School, University of South China, Hengyang 421001, China
摘要:
Simple Summary Through their regulatory effects on gene expression, histone acetyltransferases have been implicated in the normal physiological activities and genesis of cancer. Genetic aberrations of CREBBP/EP300 have been observed in various types of solid tumors and hematologic malignancies, making them serve as promising therapeutic targets. Here, this review discusses the critical role of CREBBP/EP300 in normal hematopoiesis and also provides a comprehensive overview of how they contribute to the genesis and progression of hematologic malignancies. The impact of different CREBBP/EP300 inhibitors and histone deacetylase inhibitors on targeting therapeutic potential, alleviating chemotherapy resistance, and enhancing immunotherapeutic potential has also been reviewed. Disordered histone acetylation has emerged as a key mechanism in promoting hematological malignancies. CREB-binding protein (CREBBP) and E1A-binding protein P300 (EP300) are two key acetyltransferases and transcriptional cofactors that regulate gene expression by regulating the acetylation levels of histone proteins and non-histone proteins. CREBBP/EP300 dysregulation and CREBBP/EP300-containing complexes are critical for the initiation, progression, and chemoresistance of hematological malignancies. CREBBP/EP300 also participate in tumor immune responses by regulating the differentiation and function of multiple immune cells. Currently, CREBBP/EP300 are attractive targets for drug development and are increasingly used as favorable tools in preclinical studies of hematological malignancies. In this review, we summarize the role of CREBBP/EP300 in normal hematopoiesis and highlight the pathogenic mechanisms of CREBBP/EP300 in hematological malignancies. Moreover, the research basis and potential future therapeutic implications of related inhibitors were also discussed from several aspects. This review represents an in-depth insight into the physiological and pathological significance of CREBBP/EP300 in hematology.
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.
摘要:
<jats:sec><jats:title>Background</jats:title><jats:p>Minimally invasive techniques, such as percutaneous low-power laser discectomy (PLLD) and low-temperature plasma radiofrequency ablation (coblation) can be applied to treat degenerative cervical radiculopathy. However, less evidence supports the superiority of distinct minimally-invasive therapy. Our study aimed to evaluate the clinical and radiological characteristics of the PLLD and coblation for cervical radiculopathy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This was a prospective, multicenter, cohort study (ChiCTR-ONC-17010356). The modified Macnab criteria was performed to assess the clinical improvement pre- and post-surgery. To evaluate the radiological effect, the Pfirrmann grading system and disk herniation index were applied with MRI.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In this study, 28 patients were enrolled in the coblation group and 30 patients in the PLLD group. The mean good-excellent rate at 3-month follow-up was 82.1% for PLLD group, and 66.7% for coblation group, respectively (<jats:italic>p</jats:italic> = 0.179). The PLLD group achieved higher good-excellent rate 6 and 12 months after discharge (92.9 vs. 70.0%, <jats:italic>p</jats:italic> = 0.026). Radiological data revealed that PLLD but not coblation treatment achieved significant reduction of disk herniation index (<jats:italic>p</jats:italic> &lt; 0.0001). Coblation treatment did not change the Pfirrmann grades of cervical radiculopathy patients (<jats:italic>n</jats:italic> = 18), and 7 out of 17 (41.2%) patients achieved improvement after PLLD therapy. None obvious adverse event was observed in this study.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Both PLLD and coblation are effective and safe option for patients with cervical radiculopathy. Better long-term clinical outcomes may be potentially associated with the improvement of disk degeneration after PLLD treatment.</jats:p></jats:sec>
期刊:
CURRENT NEUROVASCULAR RESEARCH,2022年19(5):495-504 ISSN:1567-2026
通讯作者:
Liu, X.;Wang, Z.
作者机构:
[Li, Huiping] Department of Rehabilitation, Hunan Provincial
People's Hospital (The First-Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, China;[Wang, Zhen; Song, Kangping; Li, Fangyi] Department of Neurology, The Affiliated Changsha Central Hospital, Hengyang Medical
School, University of South China, Changsha, Hunan, 410004, China;[Liu, Xinfeng; Guo, Hongquan] Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing,
Jiangsu, 210002, China;[Xu, Wei] Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing,
Jiangsu, 210002, China<&wdkj&>Department of Neurology, The Affiliated Changsha Central Hospital, Hengyang Medical
School, University of South China, Changsha, Hunan, 410004, China
通讯机构:
[Wang, Z.; Liu, X.] D;Department of Neurology, No. 161 Shaoshan South Road, Hunan Province, China;Department of Neurology, No. 305 East Zhongshan Road, Jiangsu Prov-ince, China
摘要:
<jats:sec>
<jats:title>Objective:</jats:title>
<jats:p>The objective of this study is to investigate the relationship between mean
platelet volume (MPV)/platelet count (PC) ratio and post-thrombolytic early neurological deterioration
(END) in patients with mild and moderate stroke.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>Mild and moderate stroke patients treated with intravenous thrombolysis (IVT) at the
Affiliated Changsha Central Hospital of the University of South China between January 2016 and
March 2022 were prospectively and consecutively enrolled. END was defined as an increase in the
total National Institutes of Health Stroke Scale (NIHSS) score of ≥4 points or an increase in the
motor items of ≥1 point within 24 hours after IVT treatment. Logistic regression and restricted cubic
spline models were used to estimate the relationship between the MPV/PC ratio and postthrombolytic
END.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>Among the 406 patients recruited, 64 (15.8%) patients developed END. Patients in the first
quintile of MPV/PC ratio (adjusted OR = 0.27, 95% CI = 0.11-0.66, p = 0.004) and the fifth quintile
(adjusted OR = 0.26, 95% CI = 0.10-0.69, p = 0.007) had a significantly lower risk of END compared
with those in the third quintile. Restricted cubic spline analysis revealed an inverted U-shaped
relationship between the MPV/PC ratio and END (p for nonlinearity = 0.016). MPV/PC ratio cut-off
value associated with the highest END risk was 51.0. An MPV/PC ratio ≤ 51.0 was shown to be
positively associated with END (adjusted OR = 1.07, 95% CI = 1.02-1.14, p = 0.012), while an
MPV/PC ratio >51.0 was negatively associated with END (adjusted OR = 0.94, 95% CI = 0.88-1.00,
p = 0.040). A significant interaction existed between the MPV/PC ratio and age in the low MPV/PC
ratio group (p = 0.012). MPV/PC ratio was positively associated with END only in patients ≥ 60
years, whereas this association was insignificant in patients < 60 years.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusion:</jats:title>
<jats:p>An inverted U-shaped relationship between the MPV/PC ratio on admission and postthrombolytic
END was identified in patients with mild and moderate stroke, with a threshold
MPV/PC ratio of 51.0. The MPV/PC ratio closer to the threshold was associated with a higher risk
of post-thrombolytic END.</jats:p>
</jats:sec>
摘要:
<jats:sec><jats:title>Background and purpose</jats:title><jats:p>Hematoma expansion (HE) is a critical event following acute intracerebral hemorrhage (ICH). We aimed to construct a non-contrast computed tomography (NCCT) model combining clinical characteristics, radiological signs, and radiomics features to predict HE in patients with spontaneous ICH and to develop a nomogram to assess the risk of early HE.</jats:p></jats:sec><jats:sec><jats:title>Materials and methods</jats:title><jats:p>We retrospectively reviewed 388 patients with ICH who underwent initial NCCT within 6 h after onset and follow-up CT within 24 h after initial NCCT, between January 2015 and December 2021. Using the LASSO algorithm or stepwise logistic regression analysis, five models (clinical model, radiological model, clinical-radiological model, radiomics model, and combined model) were developed to predict HE in the training cohort (<jats:italic>n</jats:italic> = 235) and independently verified in the test cohort (<jats:italic>n</jats:italic> = 153). The Akaike information criterion (AIC) and the likelihood ratio test (LRT) were used for comparing the goodness of fit of the five models, and the AUC was used to evaluate their ability in discriminating HE. A nomogram was developed based on the model with the best performance.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The combined model (AIC = 202.599, χ2 = 80.6) was the best fitting model with the lowest AIC and the highest LRT chi-square value compared to the clinical model (AIC = 232.263, χ2 = 46.940), radiological model (AIC = 227.932, χ2 = 51.270), clinical-radiological model (AIC = 212.711, χ2 = 55.490) or radiomics model (AIC = 217.647, χ2 = 57.550). In both cohorts, the nomogram derived from the combined model showed satisfactory discrimination and calibration for predicting HE (AUC = 0.900, sensitivity = 83.87%; AUC = 0.850, sensitivity = 80.10%, respectively).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>The NCCT-based model combining clinical characteristics, radiological signs, and radiomics features could efficiently discriminate early HE, and the nomogram derived from the combined model, as a non-invasive tool, exhibited satisfactory performance in stratifying HE risks.</jats:p></jats:sec>
作者机构:
[Gong, Haoli; Wang, Zhijun; He, Pan; Jia, Zhen] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Orthoped, Affiliated Hosp 1, Changsha 410005, Peoples R China.;[Zhang, Meilan; Liu, Feng] Univ South China, Canc Res Inst, Hengyang Med Sch, Hengyang, Peoples R China.;[Zhai, Xiaohui] Sun Yat Sen Univ, Dept Med Oncol, Affiliated Hosp 6, Guangzhou 510655, Peoples R China.
通讯机构:
[Jia, Zhen; Zhai, Xiaohui] D;Department of Orthopedics, Hunan Provincial People's Hospital, The First-Affiliated Hospital of Hunan Normal University, Changsha, 410005, China.;Department of Medical Oncology, The Sixth Affiliated Hospital of Sun-Yat Sen University, Guangzhou, 510655, China.
摘要:
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Circular RNAs (circRNAs) are forms of non-coding RNAs that have crucial roles in regulation of various biological processes of several malignant tumors. circKIF4A is closely associated with malignant progression of a variety of cancers. However, the molecular mechanisms as well as roles of circKIF4A in osteosarcoma (OS) have not yet been clearly elucidated.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>We evaluated the expression of circKIF4A in OS. Colony-formation, cell counting kit-8 (CCK-8), transwell and mice metastasis model assays were done to explore the roles of circKIF4A in vitro and in vivo. TargetScan database, double luciferase, quantitative reverse transcription polymerase chain reaction analysis (RT-qPCR), and RNA immunoprecipitation (RIP) were done to investigate the associated molecular mechanisms.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>In both OS cells and tissues, circKIF4A (hsa_circ_0007255) was found to be upregulated. In vitro and in vivo, circKIF4A knockdown markedly suppressed OS proliferation as well as metastasis. circKIF4A enhanced OS growth as well as metastasis by sponging miR-515-5p and by upregulating SLC7A11.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>We identified the biological significance of the circKIF4A-miR-515-5p-SLC7A11 axis in OS cell proliferation and metastasis, which is important in OS monitoring and treatment. More studies on circKIF4A will inform on the diagnostic markers for early OS screening.</jats:p>
</jats:sec><jats:sec>
<jats:title>Graphical abstract</jats:title>
</jats:sec>
期刊:
DNA AND CELL BIOLOGY,2022年41(9):824-837 ISSN:1044-5498
通讯作者:
Jun Meng<&wdkj&>Zuo Wang
作者机构:
[Cao, Zitong; Chen, Yanjun; Liang, Lingli; Xia, Linzhen; Wang, Zuo] Univ South China, Hengyang Med Sch, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.;[Wu, Chunyan] Univ South China, Affiliated Hosp 3, Hengyang, Peoples R China.;[Meng, Jun] Univ South China, Affiliated Hosp 1, Funct Dept, Hengyang 421001, Peoples R China.
通讯机构:
[Jun Meng] F;[Zuo Wang] K;Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, China.<&wdkj&>Functional Department, The First Affiliated Hospital of University of South China, Hengyang, China.
摘要:
Atherosclerosis is a complex vascular inflammatory disease in which multiple cell types are involved, including vascular smooth muscle cells (VSMCs). In response to vascular injury and inflammatory stimuli, VSMCs undergo a “phenotypic switching” characterized by extracellular matrix secretion, loss of contractility, and abnormal proliferation and migration, which play a key role in the progression of atherosclerosis. DNA methylation modification is an important epigenetic mechanism that plays an important role in atherosclerosis. Studies investigating abnormal DNA methylation in patients with atherosclerosis have determined a specific DNA methylation profile, and proposed multiple pathways and genes involved in the etiopathogenesis of atherosclerosis. Recent studies have also revealed that DNA methylation modification controls VSMC function by regulating gene expression involved in atherosclerosis. In this review, we summarize the recent advances regarding the epigenetic control of VSMC function by DNA methylation in atherosclerosis and provide insights into the development of VSMC-centered therapeutic strategies.
摘要:
Inflammation is a double-edged sword. The moderate inflammatory response is a fundamental defense mechanism produced by the body's resistance to dangerous stimuli and a repair process of the body itself. Increasing studies have confirmed that the overactivation of the inflammasome is involved in the occurrence and development of inflammatory diseases. Strictly controlling the overactivation of the inflammasome and preventing excessive inflammatory response have always been the research focus on inflammatory diseases. However, the endogenous regulatory mechanism of inflammasome is not completely clear. The tripartite motif (TRIM) protein is one of the members of E3 ligases in the process of ubiquitination. The universality and importance of the functions of TRIM members are recognized, including the regulation of inflammatory response. This article will focus on research on the relationship between TRIMs and NLRP3 Inflammasome, which may help us make some references for future related research and the discovery of treatment methods.