ABSTRACT
The consensus has been reached on the benefits of surgical drainage. However, catheter-related blockage and retrograde infection remain bottleneck problems in the treatment process. To this end, with Huashan Hospital, Fudan University, as the main inventors, a drainage tube dredging umbrella and anti-retrograde infection kit have been designed and applied for the national utility model patent (patent number: ZL 2023 2 1300036.2). The main body of the kit consists of a catheter dredging umbrella, drainage tube, and drainage bag. Several isolation layers are installed in the drainage bag to form a maze structure and a reflux valve is added, thereby increasing the distance and resistance of liquid reflux, greatly reducing the possibility of liquid reflux entering the drainage tube, so as to reduce the risk of retrograde infection through physical means. When the drainage tube is blocked, the drainage tube and joint tube of the drainage bag can be separated, the unblocking umbrella can be inserted into the blockage through the guide wire, the cannula can be inserted along the guide wire, the guide wire is pulled to release the dredging umbrella in the contraction state, and the dredging umbrella can be pulled back in the expansion state until the blockage is removed from the drainage tube. The operating procedure is standardized and simple. While preventing retrograde infection (anti-retrograde infection kit), the catheter dredging umbrella could effectively address the issue of catheter blockage. It has certain clinical promotion and application value.
Subject(s)
Anti-Infective Agents , Drainage , Humans , Cannula , Consensus , HospitalsABSTRACT
Given the threat of ever-growing cancer morbidity, it is a cutting-edge frontier for multiple disciplines to apply nanotechnology in cancer therapy. Nanomedicine is now perpetually influencing the diagnosis and treatment of cancer. Meanwhile, tumorigenesis and cancer progression are intimately associated with inflammation. Inflammation can implicate in various tumor progression via the same or different pathways. Therefore, current nanomedicines exhibit tumor-suppressing function through inflammatory pathways. At present, the comprehensive understanding and research on the mechanism of various nanoparticles in cancer treatment are still in progress. In this review, we summarized the applications of nanomedicine in tumor-targeting inflammatory pathways, suggesting that nanoparticles could be a budding star for cancer therapy.
ABSTRACT
BACKGROUND: Hospital-acquired multidrug-resistant (MDR) bacterial meningitis and/or ventriculitis (MEN) is a severe condition associated with high mortality. The risk factors related to in-hospital mortality of patients with MDR bacterial MEN are unknown. We aimed to examine factors related to in-hospital mortality and evaluate their prognostic value in patients with MDR bacterial MEN treated in the neurointensive care unit. METHODS: This was a single-center retrospective cohort study of critically ill neurosurgical patients with MDR bacterial MEN admitted to our hospital between January 2003 and March 2021. Data on demographics, admission variables, treatment, time to start of intraventricular (IVT) therapy, and in-hospital mortality were analyzed. Both univariate and multivariable analyses were performed to identify determinants of in-hospital mortality. RESULTS: All 142 included patients received systemic antibiotic therapy, and 102 of them received concomitant IVT treatment. The median time to start of IVT treatment was 2 days (interquartile range 1-5 days). The time to start of IVT treatment had an effect on in-hospital mortality (hazard ratio 1.17; 95% confidence interval 1.02-1.34; adjusted p = 0.030). The cutoff time to initiate IVT treatment was identified at 3 days: patients treated within 3 days had a higher cerebrospinal fluid (CSF) sterilization rate (81.5%) and a shorter median time to CSF sterilization (7 days) compared with patients who received delayed IVT treatment (> 3 days) (48.6% and 11.5 days, respectively) and those who received intravenous antibiotics alone (42.5% and 10 days, respectively). CONCLUSIONS: Early IVT antibiotics were associated with superior outcomes in terms of the in-hospital mortality rate, time to CSF sterilization, and CSF sterilization rate compared with delayed IVT antibiotics and intravenous antibiotics alone.
Subject(s)
Cerebral Ventriculitis , Cross Infection , Meningitis, Bacterial , Meningitis , Humans , Anti-Bacterial Agents , Cerebral Ventriculitis/drug therapy , Retrospective Studies , Hospital Mortality , Cross Infection/drug therapy , Meningitis/drug therapy , Hospitals , Meningitis, Bacterial/drug therapyABSTRACT
OBJECTIVE: To date, there is no consensus on the surgery strategies of cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. This meta-analysis aimed to investigate the safety of staged and simultaneous operation in patients with comorbid cranial defects with hydrocephalus to inform future surgery protocols. METHODS: A meta-analysis of PubMed, Ovid, Web of Science, and Cochrane Library databases from the inception dates to February 8, 2023 adherent to PRISMA guidelines was conducted. The pooled analyses were conducted using RevMan 5.3 software. The outcomes included postoperative infection, reoperation, shunt obstruction, hematoma, and subdural effusion. RESULTS: Of the 956 studies initially retrieved, 10 articles encompassing 515 patients were included. Among the total patients, 193 (37.48%) and 322 (62.52%), respectively, underwent simultaneous and staged surgeries. The finding of pooled analysis indicated that staged surgery was associated with lower rate of subdural effusion (14% in the simultaneous groups vs. 5.4% in the staged groups; OR = 2.39, 95% CI: 1.04-5.49, p = 0.04). However, there were no significant differences in overall infection (OR = 1.92, 95% CI: 0.74-4.97, p = 0.18), central nervous system infection (OR = 1.50, 95% CI: 0.68-3.31, p = 0.31), cranioplasty infection (OR = 1.58, 95% CI: 0.50-5.00, p = 0.44), shunt infection (OR = 1.30, 95% CI: 0.38-4.52, p = 0.67), reoperation (OR = 1.51, 95% CI: 0.38-6.00, p = 0.55), shunt obstruction (OR = 0.73, 95% CI: 0.25-2.16, p = 0.57), epidural hematoma (OR = 2.20, 95% CI: 0.62-7.86, p = 0.22), subdural hematoma (OR = 1.20, 95% CI: 0.10-14.19, p = 0.88), and intracranial hematoma (OR = 1.31, 95% CI: 0.42-4.07, p = 0.64). Moreover, subgroup analysis failed to yield new insights. CONCLUSIONS: Staged surgery is associated with a lower rate of postoperative subdural effusion. However, from the evidence of sensitivity analysis, this result is not stable. Therefore, our conclusion should be viewed with caution, and neurosurgeons in practice should make individualized decisions based on each patient's condition and cerebrospinal fluid tap test.
Subject(s)
Hydrocephalus , Subdural Effusion , Humans , Ventriculoperitoneal Shunt/adverse effects , Ventriculoperitoneal Shunt/methods , Subdural Effusion/surgery , Postoperative Complications/epidemiology , Hydrocephalus/surgery , Hematoma , Retrospective StudiesABSTRACT
Ferroptosis is a newly discovered form of regulated cell death that is triggered primarily by lipid peroxidation. A growing body of evidence has implicated ferroptosis in the pathophysiology of traumatic brain injury (TBI). However, none of these studies focused its role on TBI-induced hippocampal injury. Here, we demonstrated that the distinct ferroptotic signature was detected in the injured hippocampus at the early stage of TBI. Besides, a prominent pro-ferroptosis environment was detected in the ipsilateral hippocampus after TBI, including elevated levels of arachidonic acid (AA), ACLS4, and ALXO15, and deficiency of GPX4. Subsequently, we used AAV-mediated Gpx4 overexpression to counteract ferroptosis in the hippocampus, and found that TBI-induced cognitive deficits were significantly alleviated after Gpx4 overexpression. Biochemical results also confirmed that TBI-induced hippocampal ferroptosis and synaptic damage were partially reversed by Gpx4 overexpression. In addition, Gpx4 overexpression inhibited TBI-induced neuroinflammation and peripheral macrophage infiltration. Interestingly, the results of transwell migration assay showed that ferroptotic neurons increased CCL2 expression and promoted iBMDM cell migration. However, this effect was inhibited by CCL2 antagonist, RS102895. These data suggested that inhibition of ferroptosis may be as a potential strategy to ameliorate TBI-induced cognitive deficits through blockade of hippocampal ferroptosis and neuroinflammation.
Subject(s)
Brain Injuries, Traumatic , Cognitive Dysfunction , Ferroptosis , Humans , Ferroptosis/genetics , Neuroinflammatory Diseases , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/genetics , Brain Injuries, Traumatic/metabolism , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Hippocampus/metabolismABSTRACT
As a member of long non-coding RNAs (lncRNAs), LncRNA HLA complex group 18 (HCG18) has recently become the focus of cancer research. As outlined in this review, LncRNA HCG18 has been reported to be dysregulated in various cancers development and appears to be activated in a variety of tumors, including clear cell renal cell carcinoma (ccRCC), colorectal cancer (CRC), gastric cancer (GC), hepatocellular carcinoma (HCC), laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), lung adenocarcinoma (LUAD), nasopharyngeal cancer (NPC), osteosarcoma (OS), and prostate cancer (PCa). Furthermore, the expression of lncRNA HCG18 decreased in bladder cancer (BC) and papillary thyroid cancer (PTC). Overall, the presence of these differential expressions suggests the clinical value of HCG18 in cancer therapy. Additionally, lncRNA HCG18 influences various biological processes of cancer cells. This review summarizes the molecular mechanisms of HCG18 in cancer development, highlights reported the abnormal expression of HCG18 found in various cancer types, and aims to discuss the potential of HCG18 as a target for cancer therapy.
Subject(s)
Bone Neoplasms , Carcinoma, Hepatocellular , Head and Neck Neoplasms , Liver Neoplasms , Nasopharyngeal Neoplasms , RNA, Long Noncoding , Thyroid Neoplasms , Male , Humans , RNA, Long Noncoding/genetics , Squamous Cell Carcinoma of Head and NeckABSTRACT
Circular RNAs (circRNAs) are a new class of non-coding RNAs (ncRNAs) with a closed-loop structure that is highly stable and widely present in the eukaryotic cytoplasm. In recent years, circRNA has played a non-negligible role in the occurrence and development of a variety of diseases, which has attracted the research attention of many scholars. Circular RNA nuclear receptor interacting protein 1 (circNRIP1), a newly discovered circRNA, has been confirmed to be closely associated with cervical carcinoma (CC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), nasopharyngeal carcinoma (NPC), non-small cell lung cancer (NSCLC), osteosarcoma (OS), ovarian cancer (OC) and papillary thyroid carcinoma (PTC). CircNRIP1 can regulate the activity of ERK1/2, PI3K/AKT, and AKT/mTOR signaling pathways. In this review, the author summarizes the biological functions and target molecular mechanisms in carcinogenesis, to point out the potential clinical values and applications of circNRIP1 in diagnosing and treating cancer.
Subject(s)
Bone Neoplasms , Carcinoma, Non-Small-Cell Lung , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Lung Neoplasms , Thyroid Neoplasms , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Esophageal Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases , Esophageal Squamous Cell Carcinoma/pathology , Thyroid Neoplasms/geneticsABSTRACT
BACKGROUND: The change of lncRNA expression is known to affect the progression of tumors. This has fueled numerous investigations aiming at the mystery of lncRNA. Clear lncRNA has been the hotspot of antisense RNAs research. More and more lncRNAs have been proven to take effect as oncogenes of multitudinous cancers and accelerate tumor progression. This review elucidates the pathophysiological functions of lncRNA DLGAP1-AS1 and lncRNA DLGAP1-AS2 in a variety of tumors. METHODS: Via systematic analysis and in-depth study about relevant articles in PubMed, this article analyzes and summarizes the mechanism of antisense transcripts DLGAP1- AS1 and DLGAP1-AS2 in tumor development. RESULTS: DLGAP1-AS1 and DLGAP1-AS2 can exert their effect as oncogenes on various cancers. The expression of DLGAP1-AS1 is aberrantly high in various tumors, including GC, BC, HCC, glioblastoma and CRC. Concurrently, in LC, RC, HCC, GC, glioma and CCA, DLGAP1-AS2 is also discovered to be highly expressed. And they have a strong pertinence with a poor prognosis. The disorder of DLGAP1-AS1 and DLGAP1- AS2 in different tumors has different malignant impacts on tumors, not only to invasion, apoptosis, multiplication and EMT of tumor cells but also to drug resistance and radioresistance. In addition, DLGAP1-AS2 was revealed to have the ability to predict the prognosis of WT and RCC. CONCLUSION: The regulatory effects of DLGAP1-AS1 and DLGAP1-AS2 on tumors make them possible to be clinical markers for the early diagnosis of tumors and effective therapeutic targets.
Subject(s)
Carcinoma, Hepatocellular , Glioma , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Oncogenes/genetics , Gene Expression Regulation, Neoplastic , Cell Proliferation , Cell Line, TumorABSTRACT
BACKGROUND: Eph receptors tyrosine kinase (RTK) were identified in 1987 from hepatocellular carcinoma cell lines and were the largest known subfamily of RTK. Eph receptors can be divided into two categories, EphA and EphB, based on their structure and receptor-ligand specificity. EphA can be divided into 10 species (EphA 1-10) and EphB into 6 species (EphB1-6). Similarly, the ligands of Eph receptors are Ephrins. Ephrins also can be divided into Ephrin A and Ephrin B, of which there are five species(Ephrin-A1-5) and three species(Ephrin-B1-3). Among the Eph receptors, EphA1 has been the least studied so far. As far as we know, Eph receptors are involved in multiple pathologies, including cancer progression, tumor angiogenesis, intestinal environmental stability, the lymph node system, neurological disease, and inhibition of nerve regeneration after injury. There is a link between EphA1, integrin and ECM- related signal pathways. Ephrin-A1 is a ligand of the EphA1 receptor. EphA1 and ephrin-A1 functions are related to tumor angiogenesis. EphA1 and ephrin-A1 also play roles in gynecological diseases. Ephrin-A1 and EphA1 receptors regulate the follicular formation, ovulation, embryo transport, implantation and placental formation, which are of great significance for the occurrence of gynecological tumor diseases. EphA1 has been identified as an oncoprotein in various tumors and has been associated with the prognosis of various tumors in recent years. EphA1 is considered a driver gene in tumor genomics. There are significant differences in EphA1 expression levels in different types of normal tissues and tumors and even in different stages of tumor development, suggesting its functional diversity. Changes at the gene level in cell biology are often used as biological indicators of cancer, known as biomarkers, which can be used to provide diagnostic or prognostic information and are valuable for improving the detection, monitoring and treatment of tumors. However, few prognostic markers can selectively predict clinically significant tumors with poor prognosis. These malignancies are more likely to progress and lead to death, requiring more aggressive treatment. Currently available treatments for advanced cancer are often ineffective, and treatment options are mainly palliative. Therefore, early identification and treatment of those at risk of developing malignant tumors are crucial. Although pieces of evidence have shown the role of EphA1 in tumorigenesis and development, its specific mechanism is still unknown to a great extent. OBJECTIVE: This review reveals the changes and roles of EphA1 in many tumors and cancers. The change of EphA1 expression can be used as a biological marker of cancer, which is valuable for improving tumor detection, monitoring and treatment and can be applied to imaging. Studies have shown that structural modification of EphA1 could make it an effective new drug. EphA1 is unique in that it can be considered a prognostic marker in many tumors and is of important meaning for clinical diagnosis and operative treatment. At the same time, the study of the specific mechanism of EphA1 in tumors can provide a new way for targeted therapy. METHODS: Relevant studies were retrieved and collected through the PubMed system. After determining EphA1 as the research object, by analyzing research articles on EphA1 in the PubMed system in recent 10 years, we found that EphA1 was closely connected with the occurrence and development of tumors and further determined the references according to the influencing factors for review and analysis. RESULTS: EphA1 has been identified as a cancer protein in various tumors, such as hepatocellular carcinoma, nasopharyngeal carcinoma, ovarian cancer, gastric cancer, colorectal cancer, clear cell renal cell carcinoma, esophageal squamous cell carcinoma, breast cancer, prostate cancer and uveal melanoma. EphA1 is abnormally expressed in these tumor cells, which mainly plays a role in cancer progression, tumor angiogenesis, intestinal environmental stability, the lymph node system, nervous system diseases and gynecological diseases. In a narrow sense, EphA1 is especially effective in breast cancer in terms of gynecological diseases. However, the specific mechanism of EphA1 leading to the change of cancer cells in some tumors is not clear, which needs further research and exploration. CONCLUSION: RTK EphA1 can be used as a biomarker for tumor diagnosis (especially a prognostic marker), an indispensable therapeutic target for new anti-tumor therapies, and a novel anti-tumor drug.
Subject(s)
Breast Neoplasms , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptor, EphA2 , Pregnancy , Male , Humans , Female , Receptor, EphA1/genetics , Receptor, EphA1/analysis , Receptor, EphA1/metabolism , Ephrin-A1/metabolism , Ligands , Placenta/chemistry , Placenta/metabolism , Ephrins/genetics , Ephrins/analysis , Ephrins/metabolism , Receptors, Eph Family/genetics , Receptors, Eph Family/metabolism , Biomarkers , Receptor, EphA2/metabolismABSTRACT
OBJECTIVE: The aim of this study was to describe the clinical and procedural risk factors associated with the unplanned neurosurgical intensive care unit (NICU) readmission of patients after elective supratentorial brain tumor resection and serves as an exploratory analysis toward the development of a risk stratification tool that may be prospectively applied to this patient population. METHODS: This was a retrospective observational cohort study. The electronic medical records of patients admitted to an institutional NICU between September 2018 and November 2021 after elective supratentorial brain tumor resection were reviewed. Demographic and perioperative clinical factors were recorded. A prognostic model was derived from the data of 4892 patients recruited between September 2018 and May 2021 (development cohort). A nomogram was created to display these predictor variables and their corresponding points and risks of readmission. External validation was evaluated using a series of 1118 patients recruited between June 2021 and November 2021 (validation cohort). Finally, a decision curve analysis was performed to determine the clinical usefulness of the prognostic model. RESULTS: Of the 4892 patients in the development cohort, 220 (4.5%) had an unplanned NICU readmission. Older age, lesion type, Karnofsky Performance Status (KPS) < 70 at admission, longer duration of surgery, retention of endotracheal intubation on NICU entry, and longer NICU length of stay (LOS) after surgery were independently associated with an unplanned NICU readmission. A total of 1118 patients recruited between June 2021 and November 2021 were included for external validation, and the model's discrimination remained acceptable (C-statistic = 0.744, 95% CI 0.675-0.814). The decision curve analysis for the prognostic model in the development and validation cohorts showed that at a threshold probability between 0.05 and 0.8, the prognostic model showed a positive net benefit. CONCLUSIONS: A predictive model that included age, lesion type, KPS < 70 at admission, duration of surgery, retention of endotracheal intubation on NICU entry, and NICU LOS after surgery had an acceptable ability to identify elective supratentorial brain tumor resection patients at high risk for an unplanned NICU readmission. These risk factors and this prediction model may facilitate better resource allocation in the NICU and improve patient outcomes.
ABSTRACT
BACKGROUND: Decompressive craniectomy (DC) and intracranial pressure (ICP) monitoring are common approaches to reduce the death rate of Traumatic brain injury (TBI) patients, but the outcomes of these patients are unfavorable, particularly those who receive bilateral DC. The authors discuss their experience using ICP and other potential methods to improve the outcomes of TBI patients who receive bilateral DC. METHODS: Data from TBI patients receiving bilateral DC from Jan. 2008 to Jan. 2022 were collected via a retrospective chart review. Included patients who received unplanned contralateral DC after initial surgery were identified as unplanned secondary surgery (USS) patients. Patients' demographics and baseline medical status; pre-, intra-, and postoperative events; and follow-up visit outcome data were analyzed. RESULTS: A total of 151 TBI patients were included. Patients who underwent USS experienced more severe outcomes as assessed using the 3-month modified Rankin Scale score (P = 0.024). In bilateral DC TBI patients, USS were associated with worsen outcomes, moreover, ICP monitoring was able to lower their death rate and was associated with a lower USS incidence. In USS patients, ICP monitoring was not associated with improved outcomes but was able to lower their mortality rate (2/19, 10.5%, vs. 10/25, 40.0%; P = 0.042). CONCLUSION: The avoidance of USS may be associated with improved outcomes of TBI patients who underwent bilateral DC. ICP monitoring was a potential approach to lower USS rate in TBI patients, but its specific benefits were uncertain.
Subject(s)
Brain Injuries, Traumatic , Brain Injuries , Decompressive Craniectomy , Humans , Decompressive Craniectomy/methods , Intracranial Pressure , Retrospective Studies , Treatment Outcome , Brain Injuries, Traumatic/surgeryABSTRACT
Enterobacteriaceae are often found in the lungs of patients with severe Traumatic Brain Injury (sTBI). However, it is unknown whether these bacteria come from the gut microbiota. To investigate this hypothesis, the mice model of sTBI was used in this study. After sTBI, Chao1 and Simpson index peaking at 7 d in the lungs (p < 0.05). The relative abundance of Acinetobacter in the lungs increased to 16.26% at 7 d after sTBI. The chao1 index of gut microbiota increased after sTBI and peaked at 7 d (p < 0.05). Three hours after sTBI, the conditional pathogens such as Lachnoclostridium, Acinetobacter, Bacteroides and Streptococcus grew significantly. At 7 d and 14 d, the histology scores in the sTBI group were significantly higher than the control group (p < 0.05). The myeloperoxidase (MPO) activity increased at all-time points after sTBI and peaked at 7 d (p < 0.05). The LBP and sCD14 peaking 7 d after sTBI (p < 0.05). The Zonulin increased significantly at 3 d after sTBI and maintained the high level (p < 0.05). SourceTracker identified that the lung tissue microbiota reflects 49.69% gut source at 7 d after sTBI. In the small intestine, sTBI induced gastrointestinal dysfunction with increased apoptosis and decreasing antimicrobial peptides. There was a negative correlation between gut conditional pathogens and the expression level of antimicrobial peptides in Paneth cells. Our data indicate that gut bacteria translocated to the lungs after sTBI, and Paneth cells may regulate gut microbiota stability and translocation.
ABSTRACT
BACKGROUND: Our aim of this study was to identify risk factors and develop a prediction model for unplanned neurological intensive care unit (NICU) events after elective infratentorial brain tumor resection in order to propose an individualized admission to the NICU tailored to patient needs. METHODS: Patients admitted to our NICU between September 2018 and May 2021 after elective infratentorial brain tumor resection were reviewed. Prolonged NICU stays and unplanned NICU admissions were defined as unplanned NICU events. The prognostic model of unplanned NICU events was developed using a forward stepwise logistic regression analysis, and external validation was evaluated. The C-statistic was used to assess discrimination, and a smooth, nonparametric calibration line was used to assess calibration graphically in the model. RESULTS: Of the 1,710 patients in the development cohort, unplanned NICU events occurred in 162 (9.5%). Based on the lesion type, a Karnofsky Performance Status score <70 at admission, longer duration of surgery, bleeding in the operative area evident on postoperative computed tomography, higher fibrinogen and blood glucose levels at admission, and more intraoperative blood loss were independently associated with unplanned NICU events. The external validation test showed good discrimination (C-statistic = 0.811) and calibration (Hosmer-Lemeshow P = 0.141) for unplanned NICU events. CONCLUSIONS: Several patient and operative characteristics are associated with a greater likelihood of the occurrence of unplanned NICU events. In the future, we may be able to provide better help for the resource allocation of NICUs according to these risk factors and prediction models.
Subject(s)
Blood Glucose , Brain Neoplasms , Brain Neoplasms/surgery , Fibrinogen , Humans , Intensive Care Units , Retrospective Studies , Risk FactorsABSTRACT
This study reports the identification of the rice open reading frame Semi-Dwarf in chr8 (SD8) that encodes a putative ortholog of Arabidopsis thaliana ABCB1. Genome editing of SD8 leads to optimized rice architecture by reducing plant height and flag-leaf angle without yield penalty. Rice SD8 knockouts may also have the potential for increased yield under high density planting.
Subject(s)
Arabidopsis , Oryza , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Adenosine Triphosphate/metabolism , Arabidopsis/genetics , Oryza/genetics , Oryza/metabolism , Plant Leaves/geneticsABSTRACT
Ferroptosis is a newly recognized form of regulated cell death. Recently, growing evidence has shown that ferroptosis is involved in the pathogenesis of traumatic brain injury (TBI). However, less attention has been paid to its role in brain microvascular endothelial cells (BMVECs) and blood-brain barrier (BBB) damage, the central pathological process in secondary brain injury of TBI. Here, we established a mechanical stretch injury bEnd.3 model and a Controlled Cortical Impact (CCI) mouse model to explore the ferroptosis-related markers in brain endothelial cells after TBI in vitro and in vivo. From the results of RNA-seq analysis, RT-qPCR and immunostaining, glutathione peroxidase 4 (GPX4) downregulation, Cyclooxygenase-2 (COX-2) upregulation, and iron accumulation were observed in brain endothelial cells after TBI both in vitro and in vivo. Furthermore, we utilized Ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, to investigate the protective effects of ferroptosis inhibition on BBB disruption and neurological deficits. From the results of immunostaining, transmission electron microscopy (TEM), and western blotting, we demonstrated that Fer-1 significantly reduced BMVECs death, BBB permeability, and tight junction loss at 3 days after TBI. The neurological tests including grid walking, rotarod test, and wire-hanging test showed that Fer-1 administration exerted neuroprotective effects in the early stage of TBI. Our findings provided evidences for inhibition of BMVECs ferroptosis as a promising therapeutic target against TBI-induced BBB disruption.
Subject(s)
Brain Injuries, Traumatic , Ferroptosis , Animals , Blood-Brain Barrier/metabolism , Brain/metabolism , Brain Injuries, Traumatic/pathology , Endothelial Cells/metabolism , Mice , Mice, Inbred C57BLABSTRACT
BACKGROUND: It is well known that the changes in the expression level of LncRNA can affect the progression of tumors, which has caused a great upsurge of research in recent years. Several LncRNAs have been identified to affect a series of cancers and can promote tumor growth, migration, and invasion. In this review, we aim to clarify the pathophysiological functions of LncRNA MIR4435-2 HG in multiple tumors. METHODS: By searching the literature through PubMed, this paper summarizes the relationship between MIR4435-2HG and tumor and its role in the occurrence and development of cancer and also explains the specific molecular mechanism of the effect of MIR4435-2HG on cancer. RESULTS: MIR4435-2HG can function as an oncogene in a variety of cancers. The expression level was reported to be abnormally elevated in a series of cancers, consisting of melanoma, gastric cancer, head and neck squamous cell carcinoma, oral squamous cell carcinoma, lung cancer, cervical cancer, prostate carcinoma, ovarian cancer, breast cancer, hepatocellular carcinoma, clear cell renal cell carcinoma malignant, glioma, and colorectal cancer. Moreover, MIR4435-2HG is related to the poor prognosis of a variety of cancers. MIR4435-2HG can also affect tumor proliferation, invasion, and apoptosis. In addition, MIR4435-2HG can also enhance the metabolic function of myeloid dendritic cells of elite HIV-1 controllers. CONCLUSION: MIR4435-2HG affects the development of a variety of cancers. It can act as a clinical marker for early tumor diagnosis and affects tumor-targeted therapy.
Subject(s)
Carcinoma, Squamous Cell , Glioma , Liver Neoplasms , Mouth Neoplasms , RNA, Long Noncoding , Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Male , Mouth Neoplasms/genetics , RNA, Long Noncoding/geneticsABSTRACT
BACKGROUND: Hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is a Long non-coding RNA (LncRNA) that participates in the occurrence and development of lots of tumors and is supposed to be a new biomarker. The text aims to illustrate the biological effect, specific mechanism and clinical significance of HNF1A-AS1 in various tumors. METHODS: Via consulting the literature, analyze and summarize the relationship between HNF1A-AS1 and all kinds of tumors and the specific mechanism. RESULTS: This is a review paper about the tumor-associated long non-coding RNA HNF1A-AS1. Many researches show that LncRNA HNF1A-AS1 is related to the development of tumorous tumors. Its expression is up-regulated in numerous tumors, such as oral squamous cell carcinoma, hepatocellular carcinoma, breast cancer, osteosarcoma, lung cancer, cervical cancer, bladder cancer, colon cancer, colorectal cancer, oesophageal adenocarcinoma and laryngeal squamous cell carcinoma. However, HNF1A-AS1 is down-regulated in gastroenteropancreatic, neuroendocrine neoplasms, oral squamous cell carcinoma. Furthermore, HNF1A-AS1 can affect tumor proliferation, invasion, migration and apoptosis by targeting some microRNAs-miR-661 and miR-124. HNF1A-AS1 can also influence the development of tumors by regulating EMT. CONCLUSION: These studies show that LncRNA-HNF1A-AS1 is closely related to the occurrence development of numerous cancers. Through various molecular mechanisms to regulate tumor growth, HNF1A-AS1 can possibly become the new biological biomarker and therapeutic target for many kinds of tumors.
Subject(s)
MicroRNAs , Neoplasms , RNA, Long Noncoding , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 1-alpha/genetics , Hepatocyte Nuclear Factor 1-alpha/metabolism , Humans , MicroRNAs/genetics , Neoplasms/genetics , RNA, Long Noncoding/geneticsABSTRACT
BACKGROUND: As a member of long non-coding RNAs (lncRNAs), maternally expressed gene 8 (MEG8) has been found involving in the progression of a variety of cancers and playing a regulatory role. Therefore, MEG8 may turn into a new therapeutic target for cancer in the future. The purpose of this review is to illustrate the molecular mechanism and physiological function of MEG8 in various cancers. METHODS: We retrieved and analyzed related articles about MEG8, lncRNAs, and cancers, and then summarize the pathophysiological mechanisms of MEG8 in cancer development. RESULTS: LncRNA MEG8 participates in various cancers progression, thus influencing the proliferation, migration, and invasion of cancers. However, the expression of MEG8 is abnormally upregulated in non-small cell lung cancer (NSCLC), pancreatic cancer (PC), liver cancer (HCC), pituitary adenoma (PA) and hemangioma (HA), and inhibited in colorectal cancer (CRC), ovarian cancer (OC) and giant cell tumor (GCT), suggesting its clinical value in cancer therapy. CONCLUSION: LncRNA MEG8 is expected to be a new therapeutic target or biomarker for a wide range of cancers in the future.
Subject(s)
Neoplasms/metabolism , RNA, Long Noncoding , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolismABSTRACT
Long non-coding RNA (lncRNA) is a new kind of RNA with a length of over 200 nucleotides. Current frontiers revealed that lncRNAs implicate in various tumor progression, including tumorigenesis, proliferation, migration, invasion, metastasis, and angiogenesis. Recently discovered long non-coding RNA SETbinding factor 2 antisense RNA 1 (lncRNA SBF2-AS1), an oncogenic antisense RNA to SBF2, locates at 11p15.1 locus and is 2708 nt long. Accumulating evidence has demonstrated that lncRNA SBF2-AS1 participates in the progression of the various tumor, including pathogenesis, diagnosis, treatment, and prognosis of acute myeloid leukemia (AML), breast cancer (BC), cervical cancer (CC), clear cell renal cell carcinoma (ccRCC), colorectal cancer (CRC), diffuse large B-cell lymphoma (DLBCL), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), glioma, glioblastoma (GBM), hepatocellular carcinoma (HCC), lung cancer (LC), lung adenocarcinoma (LUAD), non-small cell lung cancer (NSCLC), osteosarcoma (OS), pancreatic cancer (PC), papillary thyroid cancer (PTC), small cell lung cancer (SCLC). Therefore, we summarized the underlying mechanisms of lncRNA SBF2-AS1 in various cancers to utilize its therapeutic function in target-selective treatment modalities.
Subject(s)
Carcinoma, Hepatocellular , Carcinoma, Non-Small-Cell Lung , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Liver Neoplasms , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Carcinogenesis/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Lung Neoplasms/pathology , MicroRNAs/genetics , RNA, Antisense , RNA, Long Noncoding/geneticsABSTRACT
OBJECTIVE: The current meta-analysis aimed to investigate the efficacy and safety of direct endovascular treatment (EVT) and bridging therapy (EVT with prior intravenous thrombolysis (IVT)) in patients with acute anterior circulation large vessel occlusion (LVO) stroke. METHODS: This meta-analysis followed PRISMA guidelines. Eligible RCTs were identified through a systemic search of electronic databases (PubMed, Ovid, Web of Science, and Cochrane Library) from the inception dates to January 10, 2022. The pooled analyses were performed using RevMan 5.3 software. The primary outcome was functional outcome on the modified Rankin Scale (mRS) (range 0 to 5) at 90 days. The secondary outcomes included successful reperfusion, intracranial hemorrhage, and mortality (mRS 6) within 90 days. RESULTS: A total of 4 RCTs involving 1633 patients were finally included. Findings of pooled analyses indicated that neither the primary outcomes (no disability (mRS 0), no significant disability despite some symptoms (mRS 1), slight disability (mRS 2), moderate disability (mRS 3), moderately severe disability (mRS 4), severe disability (mRS 5), excellent outcome (mRS 0-1), functional independence outcome (mRS 0-2), and poor outcome (mRS 3-5)) nor the secondary outcomes (successful reperfusion, intracranial hemorrhage, and mortality) in the EVT groups were not statistically significant compared with the IVT plus EVT groups (P > 0.05). In addition, the outcomes of sensitivity analysis implied that the findings of meta-analysis were credible. CONCLUSIONS: Among patients with acute ischemic stroke due to LVO of anterior circulation, EVT alone yielded efficacy and safety outcomes similar to IVT plus EVT.