摘要:
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide, and recent studies have found that CRC patients are at increased risk for cardiovascular disease (CVD). This study aimed to investigate competing causes of death and prognostic factors among a large cohort of CRC patients and to describe cardiovascular-specific mortality in relation to the US standard population. METHODS: This registry-based cohort study identified patients diagnosed with CRC between 1973 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database in the US. Cumulative mortality functions, conditional standardized mortality ratios, and cause-specific hazard ratios were calculated. RESULTS: Of the 563,298 eligible CRC patients included in this study, 407,545 died during the follow-up period. CRC was the leading cause of death, accounting for 49.8% of all possible competing causes of death. CVD was the most common non-cancer cause of death, accounting for 17.8% of total mortality. This study found that CRC patients have a significantly increased risk of cardiovascular-specific mortality compared to the US standard population, with the risk increasing with age and extended survival time. CONCLUSION: This study highlights the need to develop multidisciplinary prevention and management strategies for CRC and CVD to improve CRC patients' survival and quality of life.
摘要:
Cardiovascular disease is the leading cause of death worldwide, and it's of great importance to understand its underlying mechanisms and find new treatments. Sphingosine 1-phosphate (S1P) is an active lipid that exerts its effects through S1P receptors on the cell surface or intracellular signal, and regulates many cellular processes such as cell growth, cell proliferation, cell migration, cell survival, and so on. S1PR modulators are a class of modulators that can interact with S1PR subtypes to activate receptors or block their activity, exerting either agonist or functional antagonist effects. Many studies have shown that S1P plays a protective role in the cardiovascular system and regulates cardiac physiological functions mainly through interaction with cell surface S1P receptors (S1PRs). Therefore, S1PR modulators may play a therapeutic role in cardiovascular diseases. Here, we review five S1PRs and their functions and the progress of S1PR modulators. In addition, we focus on the effects of S1PR modulators on atherosclerosis, myocardial infarction, myocardial ischaemia/reperfusion injury, diabetic cardiovascular diseases, and myocarditis, which may provide valuable insights into potential therapeutic strategies for cardiovascular disease.
摘要:
Gram-negative Bartonella species are facultative intracellular bacteria that can survive in the harsh intracellular milieu of host cells. They have evolved strategies to evade detection and degradation by the host immune system, which ensures their proliferation in the host. Following infection, Bartonella alters the initial immunogenic surface-exposed proteins to evade immune recognition via antigen or phase variation. The diverse lipopolysaccharide structures of certain Bartonella species allow them to escape recognition by the host pattern recognition receptors. Additionally, the survival of mature erythrocytes and their resistance to lysosomal fusion further complicate the immune clearance of this species. Certain Bartonella species also evade immune attacks by producing biofilms and anti-inflammatory cytokines and decreasing endothelial cell apoptosis. Overall, these factors create a challenging landscape for the host immune system to rapidly and effectively eradicate the Bartonella species, thereby facilitating the persistence of Bartonella infections and creating a substantial obstacle for therapeutic interventions. This review focuses on the effects of three human-specific Bartonella species, particularly their mechanisms of host invasion and immune escape, to gain new perspectives in the development of effective diagnostic tools, prophylactic measures, and treatment options for Bartonella infections.
期刊:
Annals of Clinical and Translational Neurology,2024年11(1):57-66 ISSN:2328-9503
通讯作者:
Zhou, HC
作者机构:
[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha 410013, Peoples R China.;[Li, Kuankuan; Guo, Gangwen; Zhang, Zhen; Zhou, Haocheng; Huang, Dong; Han, Rui; Chen, Li] Cent South Univ, Inst Pain Med, Changsha 410013, Peoples R China.;[Chen, Li] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Anesthesiol, Changsha 410028, Peoples R China.;[Zhou, Haocheng; Huang, Dong] Cent South Univ, Hunan Key Lab Brain Homeostasis, Changsha 410013, Peoples R China.;[Huang, Yuzhao] Cent South Univ, Xiangya Hosp 3, Dept Orthopaed, Changsha 410013, Hunan, Peoples R China.
通讯机构:
[Zhou, HC ] C;Cent South Univ, Xiangya Hosp 3, Dept Pain, Changsha, Peoples R China.;Cent South Univ, Inst Pain Med, Changsha, Peoples R China.
摘要:
AIM: Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain. It is necessary to identify the responders of SCS analgesia before implantation. The aim of this study is to investigate the relationship between the cortical dynamics and SCS analgesia responders in pain management. METHODS: Resting-state EEG recording was performed in patients who underwent short-term implantation of spinal cord stimulation for pain therapy. We then did spectral analysis to capture the pattern of cortical oscillation between neuromodulation therapy analgesia responders and nonresponders. RESULTS: About 58.3% (14 out of 24) of participants were considered as analgesia responders, with average visual analogue scores reduction of 4.8 ± 1.0 after surgery, and 2.1 ± 0.7 for the nonresponder subgroup, respectively. The alpha oscillation was significantly enhanced in responder cohort compared with nonresponders. We also observed an increasing spectral power of gamma band in responders. Furthermore, the attenuation of pain severity was significantly correlated with the global alpha oscillation activity (r = 0.60, P = 0.002). Likely, positive and significant correlation was found between the pain relief and gamma activity (r = 0.58, P = 0.003). CONCLUSIONS: Distinct pattern of neural oscillation is associated with the analgesic effect of spinal cord stimulation in pain management, enhancement of cortical alpha and gamma oscillation may be a predictor of analgesia responders.
摘要:
In heat shock, various enzyme activities are clearly altered due to high body temperature. Evidence accumulated in the last few years indicates that endogenous carboxylesterase (CE) can be regarded as a biomarker of heat shock due to its close relationship to heat shock. To monitor CE activity, this study aims to develop excellent fluorescent probe for CE detection. Fluorescent probe DCM-Br-CE with a NIR turn-on signal at 660 nm and a large Stokes shift of 160 nm, as well as high sensitivity (0.117 x 10-4 U/mL) and good detection capability (30 min) for CE. DCM-Br-CE also has excellent subcellular localization for endoplasmic reticulum (ER). Furthermore, DCM-Br-CE has been shown to effectively visualize endogenous CE in PC12 or HT22 cells, can also monitor changes in CE activity during heat shock in cells and in living mice. This suggests that the probe has potential to be used for CE studies across a variety of pathological conditions, making it a promising tool for heat shock research.
摘要:
Coronary atherosclerotic disease (CAD) is a common cardiovascular disease and an important cause of death. Moreover, endothelial cells (ECs) injury is an early pathophysiological feature of CAD, and long noncoding RNAs (lncRNAs) can modulate gene expression. Recent studies have shown that lncRNAs are involved in the pathogenesis of CAD, especially by regulating ECs. In this review, we summarize the novel progress of lncRNA-modulated ECs in the pathogenesis of CAD, including ECs proliferation, migration, adhesion, angiogenesis, inflammation, apoptosis, autophagy, and pyroptosis. Thus, as lncRNAs regulate ECs in CAD, lncRNAs will provide ideal and novel targets for the diagnosis and drug therapy of CAD.
期刊:
FRONTIERS IN IMMUNOLOGY,2024年15:1355949 ISSN:1664-3224
通讯作者:
Liu, Wenpei;Qu, XW
作者机构:
[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Xie, Tianyi] Univ South China, Hengyang Med Sch, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Li, Yi-Ping; Xie, Tianyi] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Hengyang, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Qu, Xiaowang; Liu, Wenpei; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Li, Yi-Ping; Xie, Tianyi] Univ South China, Minist Educ Key Lab Rare Pediat Dis, Hengyang, Peoples R China.;[Zheng, Xingyu; Wang, You; Liu, Fen; Pan, Dong; Tang, Yinggen; Teng, Shishan; Wu, Chanfeng; Lu, Rui; Hu, Yabin; Xie, Tianyi] Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Hengyang Med Sch, Chenzhou, Peoples R China.;[Wu, Qian; Li, Yi-Ping] Sun Yat sen Univ, Inst Human Virol, Zhongshan Sch Med, Guangzhou, Peoples R China.
通讯机构:
[Qu, XW ; Liu, WP] U;Univ South China, Hengyang Med Sch, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Hengyang, Peoples R China.;Univ South China, Minist Educ Key Lab Rare Pediat Dis, Hengyang, Peoples R China.
关键词:
SARS-CoV-2;monoclonal antibody;naïve B cell;preexisting memory B cell;vaccination
摘要:
INTRODUCTION: Since December 2019, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has presented considerable public health challenges. Multiple vaccines have been used to induce neutralizing antibodies (nAbs) and memory B-cell responses against the viral spike (S) glycoprotein, and many essential epitopes have been defined. Previous reports have identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike-reactive naïve B cells and preexisting memory B cells in unexposed individuals. However, the role of these spike-reactive B cells in vaccine-induced immunity remains unknown. METHODS: To elucidate the characteristics of preexisting SARS-CoV-2 S-reactive B cells as well as their maturation after antigen encounter, we assessed the relationship of spike-reactive B cells before and after vaccination in unexposed human individuals. We further characterized the sequence identity, targeting domain, broad-spectrum binding activity and neutralizing activity of these SARS-CoV-2 S-reactive B cells by isolating monoclonal antibodies (mAbs) from these B cells. RESULTS: The frequencies of both spike-reactive naïve B cells and preexisting memory B cells before vaccination correlated with the frequencies of spike-reactive memory B cells after vaccination. Isolated mAbs from spike-reactive naïve B cells before vaccination had fewer somatic hypermutations (SHMs) than mAbs isolated from spike-reactive memory B cells before and after vaccination, but bound SARS-CoV-2 spike in vitro. Intriguingly, these germline-like mAbs possessed broad binding profiles for SARS-CoV-2 and its variants, although with low or no neutralizing capacity. According to tracking of the evolution of IGHV4-4/IGKV3-20 lineage antibodies from a single donor, the lineage underwent SHMs and developed increased binding activity after vaccination. DISCUSSION: Our findings suggest that spike-reactive naïve B cells can be expanded and matured by vaccination and cocontribute to vaccine-elicited antibody responses with preexisting memory B cells. Selectively and precisely targeting spike-reactive B cells by rational antigen design may provide a novel strategy for next-generation SARS-CoV-2 vaccine development.
摘要:
BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.
摘要:
The Pgp3 subunit vaccine elicits immune protection against Chlamydia trachomatis infection, but additional adjuvants are still required to enhance its immunoprotective efficacy. Flagellin can selectively stimulate immunity and act as an adjuvant. In this research, the FliC-Pgp3 recombinant was successfully expressed and purified. Tri-immunization with the FliC-Pgp3 vaccine in Balb/C mice induced rapid and persistent germinal center B-cell response and Tfh differentiation, promoting a significantly higher IgG antibody titer compared to the Pgp3 group. FliC-Pgp3 immunization primarily induced Th1-type cellular immunity, leading to higher levels of IFN-γ, TNF-α, and IL-2 secreted by CD4(+) T cells than in Pgp3-vaccinated mice. Chlamydia muridarum challenge results showed that FliC-Pgp3-vaccinated mice exhibited more rapid clearance of Chlamydia muridarum colonization in the lower genital tract, ensuring a lower hydrosalpinx rate and cumulative score. Histological analysis showed reduced dilation and inflammatory infiltration in the oviduct and uterine horn of FliC-Pgp3-vaccinated mice compared to the PBS and Pgp3 control. Importantly, tri-immunization with FliC-Pgp3 effectively activated CD4(+) T cells and dendritic cells, as confirmed by the adoptive transfer, resulting in better immune protection in recipient mice. In summary, the novel FliC-Pgp3 chimeric is hoped to be a novel vaccine with improved immunoprotection against Chlamydia muridarum.
摘要:
Scavenger Receptor Class B Type 1 (SR-B1), a receptor protein expressed on the cell membrane, plays a crucial role in the metabolism and transport of cholesterol and other lipids, contributing significantly to the homeostasis of lipid levels within the body. Bibliometric analysis involves the application of mathematical and statistical methods to quantitatively analyze different types of documents. It involves the analysis of structural and temporal trends in scholarly articles, coupled with the identification of subject emphasis and variations. Through a bibliometric analysis, this study examines the historical background, current research trends, and future directions in the exploration of SR-B1. By offering insights into the research status and development of SR-B1, this paper aims to assist researchers in identifying novel pathways and areas of investigation in this field of study. Following the screening process, it can be concluded that research on SR-B1 has consistently remained a topic of significant interest over the past 17 years. Interestingly, SR-B1 has recently garnered attention in areas beyond its traditional research focus, including the field of cancer. The primary objective of this review is to provide a concise and accessible overview of the development process of SR-B1 that can help readers who are not well-versed in SR-B1 research quickly grasp its key aspects. Furthermore, this review aims to offer insights and suggestions to researchers regarding potential future research directions and areas of emphasis relating to SR-B1.
作者机构:
[Zhong, Jing; Zhao, Hu; Zhong, J; Xia, Min; Xiao, Qian] Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Xiao, Qian] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Clin Lab Med, Hengyang 421001, Hunan, Peoples R China.;[Tang, Weijian] Nanchang Univ, Queen Mary Sch, Nanchang 330031, Peoples R China.;[Chen, Yajun] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.;[Zhong, Jing] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Chen, YJ ; Zhong, J ] U;Univ South China, Affiliated Hosp 1, Canc Res Inst, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Metab & Endocrinol, Hengyang 421001, Hunan, Peoples R China.
关键词:
Breast cancer;Lipid metabolism;Targeting therapy;Therapy resistance
摘要:
Lipids, as one of the three primary energy sources, provide energy for all cellular life activities. Lipids are also known to be involved in the formation of cell membranes and play an important role as signaling molecules in the intracellular and microenvironment. Tumor cells actively or passively remodel lipid metabolism, using the function of lipids in various important cellular life activities to evade therapeutic attack. Breast cancer has become the leading cause of cancer-related deaths in women, which is partly due to therapeutic resistance. It is necessary to fully elucidate the formation and mechanisms of chemoresistance to improve breast cancer patient survival rates. Altered lipid metabolism has been observed in breast cancer with therapeutic resistance, indicating that targeting lipid reprogramming is a promising anticancer strategy.
摘要:
Ferroptosis plays an important role in the early stage of myocardial ischemia/reperfusion (MI/R) injury, which is closely associated with the antioxidant damage of mitochondrial cysteine (Cys)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis. Visualization of Cys and GSH in mitochondria is meaningful to value ferroptosis and further contributes to understanding and preventing MI/R injury. Herein a mitochondria-targetable thiols fluorescent probe (MTTP) was designed and synthesized based on sulfonyl benzoxadiazole (SBD) chromophore with a triphenylphosphine unit as the mitochondria-targeted functional group. Cys and GSH can be differentiated by MTTP with two distinguishable emission bands (583 nm and 520 nm) through the controllable aromatic substitution-rearrangement reaction. Importantly, MTTP is capable of monitoring ferroptosis and its inhibition by measuring mitochondrial Cys and GSH. MTTP was also employed to non-invasively detect ferroptosis during oxygen and glucose deprivation/reoxygenation (OGD/R)-induced MI/R injury in H9C2 cells. In a word, MTTP provides a visual tool that can simultaneously detect Cys and GSH to monitor ferroptosis processes during MI/R injury, which helps for more deeper understanding of the role of ferroptosis in MI/R injury-related diseases.
作者机构:
[Feng, Wen-Jie; Wu, Xiao-Ping; Zhu, Hong -Bo; He, Zhi-Long; Tan, Ye-Ru; Xun, Yi; Li, Yue-Hua; Jiang, Yi-Ling; Zhu, HB] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.;[Jiang, Bao-Hong] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Pharm, Hengyang, Hunan, Peoples R China.
通讯机构:
[Zhu, HB ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Med Oncol, Hengyang, Hunan, Peoples R China.
关键词:
AIFM2;GPX4;circRNAs;hepatocellular cancer (HCC);miR-6085
摘要:
BACKGROUND: Circular RNAs (circRNAs) represent a subset of non-coding RNAs implicated in the regulation of diverse biological processes, including tumorigenesis. However, the expression and functional implications of circ0060467 in hepatocellular carcinoma (HCC) remain elusive. In this study, we aimed to elucidate the role of circ0060467 in modulating the progression of HCC. METHODS: Differentially expressed circRNAs in HCC tissues were identified through circRNA microarray assays. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays revealed the upregulation of circ0060467 in both HCC cell lines and tissues. Various assays were conducted to investigate the roles of circ0060467 in HCC progression. Additionally, RNA immunoprecipitation (RIP) assays and luciferase assays were carried out to assess the interactions between circ0060467, microRNA-6085 (miR-6085), apoptosis-inducing factor mitochondria-associated 2 (AIFM2), and glutathione peroxidase 4 (GPX4) in HCC. RESULTS: Microarray and qRT-PCR analyses demonstrated a marked elevation of circ0060467 in HCC tissues and cell lines. Knockdown of circ0060467 suppressed HCC cell proliferation. Luciferase reporter and RIP assays confirmed the binding of circ0060467, AIFM2, and GPX4 to miR-6805. Subsequent experiments revealed that circ0060467 competes with AIFM2 and GPX4, thereby inhibiting cancer cell ferroptosis by binding to miR-6085 and promoting hepatocellular carcinoma progression. CONCLUSIONS: Collectively, circ0060467 modulates the levels of AIFM2 and GPX4, crucial regulators of tumor cell ferroptosis, by acting as a sponge for miR-6085 in HCC. Thus, circ0060467 may represent a novel diagnostic marker and therapeutic target for HCC.
摘要:
Tumor protein 53 (P53), as an intracellular regulator of antioxidant responses, participates in the expression of antioxidant defense and lipid metabolism as well as the synthesis of genes in cells. The balance of oxidation and reduction can be disrupted by many pathological conditions, and the role of the antioxidant system in protecting the equilibrium state from pathological effects, such as reactive lipids, is crucial. In particular, the excessive accumulation of lipid peroxidation products is a key factor driving the occurrence and development of various diseases. Ferroptosis is an iron-dependent, lipid peroxidation-driven cell death cascade reaction, which has become a key research area in cardiovascular diseases. Atherosclerosis (AS) is a pathological change caused by lipid metabolic disorder, inflammatory response, and endothelial cell injury, and is the most common cause of cardiovascular disease. This review briefly outlines lipid peroxidation and key components involving ferroptosis cascade reactions, summarizes and emphasizes the role of P53-related signaling pathways in mediating lipid peroxidation and ferroptosis, and focuses on the known P53 target genes that regulate these pathways, as well as explores the possibility of P53 intervention in the treatment of AS by regulating lipid peroxidation and ferroptosis processes.
摘要:
Research on venous thromboembolism (VTE) in nursing has garnered significant attention. This study aimed to examine the characteristics of VTE nursing publications, offering valuable insights into the current state of the field and forecasting future trends. A comprehensive screening of global publications up to 2022 was conducted using the Web of Science Core Collection database to investigate VTE nursing. The search incorporated keywords such as 'venous thromboembolism', 'deep vein thrombosis', and 'pulmonary embolism' to identify relevant studies. A bibliometric analysis of these publications was performed using various visualisation tools such as VOSviewer and R software. A total of 675 papers on VTE nursing were identified, with the earliest publication dating back to 1999. The research involved 971 institutions from 43 countries, with the United States leading by contributing to 261 articles. Harvard University emerged as the most productive institution, and Heit, with 17 publications, was the most cited author. The journal Thrombosis Research published the highest number of papers (11). The frontiers of VTE nursing research are anticipated to continue focusing on topics such as epidemiology, risk factors, and VTE prevention and management.
摘要:
Circ_0032704 was overexpressed in sorafenib‐resistant tumor tissues and cells of HCC. The knockdown of circ_0032704 reduced sorafenib resistance, inhibited cell proliferation, migration, and invasion, and enhanced the function of CD8+ T cells. Our study proposed a novel mechanism that circ_032704 exerted these effects by positively regulating PD‐L1 via competitively targeting miR‐514a‐3p. In addition, exosomal circ_0032704 was a promising biomarker in the prediction of sorafenib resistance in HCC development. Abstract Purpose This study aims to explore the role of circ_0032704 in sorafenib‐resistant hepatocellular carcinoma (HCC). Methods The expression of circ_0032704, miR‐514a‐3p, and programmed death‐ligand 1 (PD‐L1) mRNA was detected by quantitative real‐time PCR (qPCR). The expression of multidrug resistant‐related proteins, migration/invasion‐related proteins, exosome‐related proteins, and PD‐L1 protein was detected by western blot. Cell viability was detected by CCK‐8 assay. Cell proliferation, migration, and invasion were assessed by EdU assay, wound healing assay, and transwell assay. The binding between miR‐514a‐3p and circ_0032704 or PD‐L1 was verified by RIP assay, pull‐down assay, and dual‐luciferase reporter assay. Cell‐ or serum‐derived exosomes were isolated and identified by TEM and NTA. Xenograft models were established to determine the effect of circ_0032704 on drug resistance in vivo. Results Circ_0032704 was overexpressed in sorafenib‐resistant HCC tissues and cells. Circ_0032704 knockdown reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib‐resistant HCC cells, while these effects were reversed by PD‐L1 overexpression. We found that circ_0032704 positively regulated PD‐L1 expression via targeting miR‐514a‐3p. Exosomes with circ_0032704 inhibition reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib‐resistant HCC cells. Exosomes with circ_0032704 inhibition also inhibited tumor growth in vivo. The expression of circ_0032704 in exosomes was stable and possessed diagnostic value. Conclusion Circ_0032704 enhanced sorafenib resistance in HCC and promoted the malignant development of sorafenib‐resistant HCC. Circ_0032704 could be transported by exosomes, and exosomal circ_0032704 had diagnostic value.
摘要:
Tumori Journal, Ahead of Print. <br/>Prostate cancer is the second most common malignancy among men in the world, posing a serious threat to men's health and lives. RB1 is the first human tumor suppressor gene to be described, and it is closely associated with the development, progression, and suppression of a variety of tumors. It was found that the loss of RB1 is an early event in prostate cancer development and is closely related to prostate cancer development, progression and treatment resistance. This paper reviews the current status of research on the relationship between RB1 and prostate cancer from three aspects: RB1 and prostate cell lineage plasticity; biological behavior; and therapeutic resistance. Providing a novel perspective for developing new therapeutic strategies for RB1-loss prostate cancer.
摘要:
Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1β and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.
摘要:
Laccase-catalyzed oxidative reactions are increasingly examined as a reliable approach to environmental analysis and remediation, and it is urgent to widen metal category to compensate huge gap in the number of studies on copper- and non-copper laccase mimics. Herein, two-dimensional ultrathin MnO2 nanofilm (Mn-uNF) was designed via a chemical deposition and alkali etching process. Similar to Cu-laccase, Mn-uNF can oxidize phenols via a one-electron-transfer reaction of Mn(III) and accelerate the MnIII/MnIV state cycle through an unconventional oxygen reduction process. The excellent laccase-like performance of Mn-uNF can be ascribed to the abundant atomically dispersed Vo-assisted Mn(III) and surface -OH species, which was confirmed by characterizations and DFT calculation. Further, a facile dual-function colorimetric platform was designed for array sensing of o-, m-, and p-dihydroxybenzene isomers and one-step discrimination of tetracyclines containing phenol groups. These findings provide reasonable guidance for the design of a nanozyme with active Mn sites as a new family member of highly efficient copper-free laccase mimics.
作者机构:
[Peng, Tong; Huang, Li-li; Yue, Qian-qian; Feng, Ge-hui; Tang, Tian; Zeng, Ying; Meng, Xin-ru; Zhao, Ke-hao; Sun, Ying-xue] Univ South China, Sch Nursing, Hengyang Med Sch, Dept Int & Human Nursing Hunan Sci Popularizat Edu, Hengyang, Peoples R China.;[Zeng, Ying; Zeng, Xi] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.;[Zeng, Ying; Zeng, Xi] Univ South China, Hengyang Med Sch, Hengyang, Peoples R China.;[Zeng, Ying] Univ South China, Sch Nursing, Dept Int & Humanist Nursing, Hengyang, Peoples R China.;[Zeng, Ying] Canc Res Inst Univ South China, Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.
通讯机构:
[Zeng, Y ] U;Univ South China, Hengyang Med Sch, Hengyang, Peoples R China.;Univ South China, Sch Nursing, Dept Int & Humanist Nursing, Hengyang, Peoples R China.;Canc Res Inst Univ South China, Key Lab Tumor Cellular & Mol Pathol, Hengyang, Peoples R China.
摘要:
BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer mortality. HCC has high morbidity, high mortality, and low survival rates. Screening is one of the most significant methods of lowering incidence and death while also increasing survival. OBJECTIVES: The aim of this study was to identify the facilitators and barriers to participation in HCC screening among high-risk populations. METHODS: A comprehensive and systematic search was undertaken in PubMed, Web of Science, MEDLINE, EMBACE, EBSCOhost and the Cochrane Library. A combination of synonyms of the keywords including HCC, screening, factors and adherence were used for searching. Studies addressing the facilitators and barriers to HCC screening compliance in at-risk individuals were included. Data were synthesized using Review Manager version 5.4. A random/fixed effects model meta-analysis was performed to estimate the pooled data and expressed with odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of seven articles met the inclusion criteria. Qualitative (n=1) and quantitative (n=6) studies using various types of surgery were conducted. The most commonly mentioned barriers were insufficient knowledge and awareness of HCC screening, unawareness of the necessity for early detection of HCC and lack of physician recommendation. A meta-analysis of seven studies showed that individuals with a family history of HCC increased screening uptake by nearly three times (OR: 2.69, 95% CI: 1.93, 3.75). Other most frequently reported facilitators include age, education level, and perceived risk etal. CONCLUSIONS: Many barriers to HCC screening were found. Meanwhile, this review points out that improving the awareness of high-risk populations toward HCC screening is expected to enhance compliance, thereby promoting early diagnosis of liver cancer, reducing mortality, and alleviating the burden of HCC.