ABSTRACT
MnBi2Te4 (MBT) is the first intrinsic magnetic topological insulator with the interaction of spin-momentum locked surface electrons and intrinsic magnetism, and it exhibits novel magnetic and topological phenomena. Recent studies suggested that the interaction of electrons and magnetism can be affected by the Mn-doped Bi2Te3 phase at the surface due to inevitable structural defects. Here, we report an observation of nonreciprocal transport, that is, current-direction-dependent resistance, in a bilayer composed of antiferromagnetic MBT and nonmagnetic Pt. The emergence of the nonreciprocal response below the Néel temperature confirms a correlation between nonreciprocity and intrinsic magnetism in the surface state of MBT. The angular dependence of the nonreciprocal transport indicates that nonreciprocal response originates from the asymmetry scattering of electrons at the surface of MBT mediated by magnon. Our work provides an insight into nonreciprocity arising from the correlation between magnetism and Dirac surface electrons in intrinsic magnetic topological insulators.
ABSTRACT
Galectin-10 (Gal-10) forms Charcot-Leyden crystals (CLCs), which play a key role in the symptoms of asthma and allergies and some other diseases. Gal-10 has a carbohydrate-binding site; however, neither the Gal-10 dimer nor the CLCs can bind sugars. To investigate the monomer-dimer equilibrium of Gal-10, high-performance size-exclusion chromatography (SEC) was employed to separate serial dilutions of Gal-10 with and without carbohydrates. We found that both the dimerization and crystallization of Gal-10 were promoted by lactose/galactose binding. A peak position shift for the monomer was observed after treatment with either lactose or galactose, implying that the polarity of the monomer was reduced by lactose/galactose binding. Further experiments indicated that alkaline conditions of pH 8.8 mimicked the lactose/galactose-binding environment, and the time interval between monomers and dimers in the chromatogram decreased from 0.8 min to 0.4 min. Subsequently, the electrostatic potential of the Gal-10 monomers was computed. After lactose/galactose binding, the top side of the monomer shifted from negatively charged to electrically neutral, allowing it to interact with the carbohydrate-binding site of the opposing subunit during dimerization. Since lactose/galactose promotes the crystallization of Gal-10, our findings implied that dairy-free diets (free of lactose/galactose) might be beneficial to patients with CLC-related diseases.
Subject(s)
Galactose , Lactose , Humans , Lactose/chemistry , Galactose/metabolism , Crystallization , Galectins/chemistry , Binding SitesABSTRACT
Amantadine, an antiviral drug, has been widely used in human anti-influenza treatments. However, several highly pathogenic avian influenza viruses show amantadine-resistance mutations in the viral matrix 2 (M2) protein. Here we analyzed global H5N1 sequencing data and calculate possible correlations between frequencies of key mutations in M2 and the mortality rates. We found that the frequency of L26I/V27A mutation in M2 (isolated from both human and avian hosts) is linearly correlated with the mortality rates of human H5N1 infections. The significant correlation between M2 mutations in avians and the mortality rates in humans suggests that the pre-existence of L26I/V27A in birds may determine patient fatalities after transinfections from avian to human hosts. 100% prevalence of L26I/V27A mutation increased the mortality rates from 51% (95% confidence interval [CI] 37%-65%) to 89% (95% CI 88%-90%). Mutations involving Leu26 or Val27 were identified to be the major mutations emerging from drug selection pressure. Thus the emergence of the super H5N1 virus with a fatality of over 90% may be attributed to the abuse of amantadine in poultry, especially in some southeast Asian countries. A more stringent control to antiviral veterinary drugs is imperative.
Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza in Birds , Influenza, Human , Amantadine/pharmacology , Amantadine/therapeutic use , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Birds , Drug Resistance, Viral/genetics , Humans , Influenza A Virus, H5N1 Subtype/genetics , Influenza in Birds/epidemiology , Influenza, Human/drug therapy , Influenza, Human/epidemiology , Phylogeny , Poultry , Viral Matrix Proteins/geneticsABSTRACT
BACKGROUND: At present, the gastric tube is the first choice for esophageal reconstruction after esophagectomy for various benign and malignant diseases. However, when the stomach is not available, a pedicled jejunum or colon is used to reconstruct the esophagus. The present study aimed to compare the postoperative outcomes and quality of life of patients receiving jejunal and colonic conduits. METHODS: In the present retrospective study, the clinical data of 71 patients with esophageal carcinoma, who received jejunal reconstruction (jejunum group, n = 34) and colonic reconstruction (colon group, n = 37) from 2005 to 2015, were compared. RESULTS: Compared with the colon group, the jejunum group had a lower incidence of postoperative anastomotic leakage, lesser duration of postoperative drainage, and faster recovery. Furthermore, the scores were better in the jejunum group than in the colon group, in terms of short-term overall quality of life, physical function and social relationships. Moreover, the jejunal group had a significantly lower frequency of pH < 4 simultaneous reflux time > 5 min (N45) and the longest reflux time (LT) at 24 weeks after surgery. CONCLUSION: In esophageal cancer, when gastric tube construction is not feasible, a pedicled jejunum may be preferred over a colonic conduit due to lower incidence of acid reflux, anastomotic leakage and higher postoperative short-term quality of life, and rapid postoperative recovery.
Subject(s)
Colon , Esophageal Neoplasms , Esophagectomy , Jejunum , Aged , Colon/surgery , Esophageal Neoplasms/surgery , Female , Humans , Jejunum/surgery , Male , Middle Aged , Quality of Life , Plastic Surgery Procedures , Retrospective StudiesABSTRACT
BACKGROUND: Invasion of the superior vena cava (SVC) by thoracic tumors and occurrence of SVC syndrome are often encountered in clinical practice; but the prognosis in these cases is poor. Replacement of the SVC with autologous pericardial tissue is rarely performed. In this study, we sought to investigate the postoperative outcomes of this rare procedure. METHODS: We performed a retrospective analysis of six patients who underwent SVC replacement using autologous pericardial tissue between October 2010 and November 2016. We collected data on the patients' pathological features, operative characteristics, postoperative outcomes, and survival. RESULTS: All six patients were male with an average age of 52 years (range, 18-62 years). Three of the patients had lung cancer, one had stage III thymoma, and two had germinoma. Four of the six patients had mild or moderate superior vena cava compression and no corresponding clinical symptoms. The other two patients had severe compression and obvious symptoms of SVC syndrome, with the typical swelling of the face, eyelids, and upper extremities. All six patients underwent complete tumor resection, with two of the lung cancer patients undergoing right lobectomy and one undergoing right pneumonectomy. With respect to the postoperative outcomes, one patient died, whereas the others did not develop any major complications. At the end of the follow-up period, five of the patients were alive and none of the patients had developed thrombosis in the grafts. CONCLUSIONS: Our findings indicated that SVC replacement with autologous pericardium is technically feasible and safe, with few postoperative complications and favorable long-term effects. Although it has some limitations, this method appears to be useful in achieving SVC reconstruction of moderate size. SVC replacement with autologous pericardium appears to have the potential for widespread clinical use.
Subject(s)
Blood Vessel Prosthesis Implantation/methods , Pericardium/transplantation , Thoracic Neoplasms/surgery , Vena Cava, Superior/pathology , Vena Cava, Superior/surgery , Adolescent , Adult , Blood Vessel Prosthesis Implantation/adverse effects , Humans , Male , Middle Aged , Neoplasm Invasiveness , Pericardium/pathology , Postoperative Complications/etiology , Prognosis , Retrospective Studies , Survival Rate , Thoracic Neoplasms/pathology , Transplantation, Autologous , Young AdultSubject(s)
HIV Infections , Sexual and Gender Minorities , Sexually Transmitted Diseases , Male , Humans , Homosexuality, Male , Monkeypox virus , Paris/epidemiology , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/epidemiology , France/epidemiology , HIV Infections/diagnosis , HIV Infections/epidemiologyABSTRACT
To explore the potential mechanisms of Houttuynia cordata in the treatment of CRC using network pharmacology combined with experimental validation. The major active components of Houttuynia cordata were identified using the TCMSP database, and their related targets were mined. CRC-related target genes were obtained through the Genecards and OMIM databases. The R software Ven Diagram package was used for visualization of the intersection of drug and disease targets. The intersection target genes were subjected to GO function enrichment and KEGG pathway enrichment analysis using the R software clusterProfiler package. A "Drug - active component - target - Disease" network was constructed and analyzed using Cytoscape software. Intersection target genes were uploaded to the STRING database, and the resultant data were imported into Cytoscape software to construct a PPI network and filter core target genes. Expression analysis, diagnostic efficacy, and survival analysis were used to demonstrate the function and clinical value of the core target genes. The correlation between core genes in CRC samples and immune cell infiltration was analyzed using the R software and ssGSVA algorithm. Molecular docking validation of core active components with core target genes was performed using AutodockVina 1.2.2 software. Finally, the effects of quercetin and kaempferol, core active components of Houttuynia cordata, on the growth of HCT116 cells and the regulation of core target genes were validated through CCK8 assay, flow cytometry, and RT-qPCR. Seven effective active components and 147 component-related targets were selected, along with 3806 CRC-related target genes. GO analysis mainly involved biological processes such as epithelial cell proliferation, with KEGG pathway analysis focusing on pathways including AGE-RAGE signaling. Quercetin and kaempferol were identified as two core components, with IL1B, MMP9, CXCL8, and IL6 as four core target genes. Immune infiltration analysis showed that IL1B, MMP9, CXCL8, and IL6 primarily exert anti-CRC effects by promoting neutrophil activity. Molecular docking results indicated stable binding capacities of quercetin and kaempferol with IL1B, MMP9, CXCL8, and IL6. Experimental validation showed that quercetin and kaempferol could inhibit the viability of HCT116 cells in a dose-dependent manner, promote apoptosis, and downregulate the expression of IL1B, MMP9, CXCL8, and IL6 genes. Houttuynia cordata may exert therapeutic effects on CRC by modulating the immune microenvironment and anti-inflammatory responses, providing new research directions and theoretical guidance for the treatment of CRC with Houttuynia cordata.
ABSTRACT
OBJECTIVE: To explore the value of preoperative prognostic nutritional index (PNI) and controlling nutritional status (CONUT) score in predicting response and prognosis of patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death protein 1 (PD-1) inhibitors. METHODS: A retrospective study was conducted in patients who received PD-1 inhibitors for advanced NSCLC. Patients were assigned by immunotherapy effects into response (partial and complete response, pCR) group (n=52) and non-response (non-pCR) group (n=132). The pathological and clinical data were collected for statistical analysis of factors influencing the immunotherapeutic response. The diagnostic value of PNI and CONUT score for response was assessed. The overall survival (OS) was observed over a 3-year follow-up. COX regression analysis was performed to identify risk factors affecting the survival. The effects of different PNI and CONUT scores on the survival were observed. RESULTS: Multivariate regression analysis showed that, the tumor-node-metastasis (TNM) stage (P=0.001), PNI (P<0.001), and CONUT score (P<0.001) were associated with response. The non-pCR group had a higher 3-year mortality rate and a shorter 3-year OS than the pCR group (P<0.001). COX regression analysis showed that low PNI and high CONUT score were risk factors for poor prognosis. Further analysis showed that patients with low PNI and high CONUT score had lower 3-year survival rates (P=0.005, P<0.001). CONCLUSION: High TNM stage, PNI<50, and CONUT score ≥5 are risk factors for poor response in patients with advanced NSCLC receiving PD-1 inhibitors, and low PNI and high CONUT score suggest poor prognosis.
ABSTRACT
The relapse rate of substance abusers is high, and addiction rehabilitation adjunct drugs need to be developed urgently. There have been numerous reports on blocking the formation of substance addiction, but studies on drugs that can alleviate withdrawal symptoms are very limited. Both the dopamine transporter (DAT) hypothesis and D3 dopamine receptor (D3R) hypothesis are proposed. DAT activators reduce the extracellular dopamine level, and D3R antagonists reduce the neuron's sensitivity to dopamine, both of which may exacerbate the withdrawal symptoms subsequently. The D3R partial agonist SK608 has biased signaling properties via the G-protein-dependent pathway but did not induce D3R desensitization and, thus, may be a promising drug for the withdrawal symptoms. Drugs for serotoninergic neurons or GABAergic neurons and anti-inflammatory drugs may have auxiliary effects to addiction treatments. Drugs that promote structural synaptic plasticity are also discussed.
ABSTRACT
Coronavirus Disease 2019 (COVID-19) vaccines protect the public and limit viral spread. However, inactivated viral vaccines use the whole virus particle, which contains many non-capsid proteins that may cause adverse immune responses. A report has found that the ADP-ribose-binding domains of SARS-CoV-2 non-structural protein 3 (NSP3) and human poly(ADP-ribose) polymerase family member 14 (PARP14) share a significant degree of homology. Here, we further show that antibodies against 2019 novel SARS-like coronavirus (SARS-CoV-2) NSP3 can bind human PARP14 protein. However, when G159R + G162R mutations were introduced into NSP3, the antibody titer against human PARP14 decreased 14-fold. Antibodies against SARS-CoV-2 NSP3 can cross-react with human skeletal muscle cells and astrocytes, but not human embryonic kidney 293T cells. However, when G159R + G162R mutations were introduced into NSP3, the cross-reaction was largely inhibited. The results imply that COVID-19 patients with high antibody titers against NSP3 may have high risks of muscular and/or neurological complications. And the possible strategies to improve the safety of inactivated viral vaccines are also discussed.
Subject(s)
COVID-19 , Viral Vaccines , Humans , SARS-CoV-2/genetics , Viral Nonstructural Proteins/chemistry , COVID-19 Vaccines , Antibodies , Muscle Cells/metabolism , Neuroglia/metabolismABSTRACT
Background: Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies, but studies have not fully evaluated its molecular subtypes, prognosis and response to immunotherapy of different subtypes. The purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype, prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data, and data retrieved from GEO and TCGA databases. Methods: Single-cell seq data and bioinformatics methods were used in this study. Pancreatic cancer data were retrieved from GEO and TCGA databases, the molecular subtypes of pancreatic cancer were determined using the six cGAS-STING related pathways, and the clinical phenotype, mutation, immunological characteristics and pathways related to pancreatic cancer were evaluated. Results: Pancreatic cancer was classified into 3 molecular subtypes, and survival analysis revealed that patients in Cluster3 (C3) had the worst prognosis, whereas Cluster1 (C1) had the best prognosis. The clinical phenotype and gene mutation were statistically different among the three molecular subtypes. Analysis of immunotherapy response revealed that most immune checkpoint genes were differentially expressed in the three subtypes. A lower risk of immune escape was observed in Cluster1 (C1), indicating higher sensitivity to immunotherapeutic drugs and subjects in this Cluster are more likely to benefit from immunotherapy. The pathways related to pancreatic cancer were differentially enriched among the three subtypes. Five genes, namely SFRP1, GIPR, EMP1, COL17A and CXCL11 were selected to construct a prognostic signature. Conclusions: Single-cell seq data were to classify pancreatic cancer into three molecular subtypes based on differences in clinical phenotype, mutation, immune characteristics and differentially enriched pathways. Five prognosis-related genes were identified for prediction of survival of pancreatic cancer patients and to evaluate the efficacy of immunotherapy in various subtypes.
Subject(s)
Pancreatic Neoplasms , Humans , Prognosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Computational Biology , Immunotherapy , Pancreatic NeoplasmsABSTRACT
Background: The clinical efficacy and safety of camrelizumab as a third- or later-line regimen in patients with advanced non-small cell lung cancer (NSCLC) have not been determined in large clinical trials. Objective: This study aimed to evaluate the clinical efficacy and safety of camrelizumab in combination with albumin-bound paclitaxel as a third- or later-line treatment for patients with advanced NSCLC. Methods: A total of 257 patients with advanced NSCLC who were histopathologically confirmed and failed in clinical second-line therapy regimens at Jiangxi Province Cancer hospital from January 2018 to December 2021 were retrospectively selected. Patients with advanced NSCLC were divided into the single treatment group (STG) of camrelizumab, and the combined treatment group (CTG) of camrelizumab in combination with albumin-bound paclitaxel according to the treatment regimen. The primary outcomes of interest were clinical efficacy[objective response rate (ORR) and disease control rate (DCR)], progression-free survival (PFS), and overall survival (OS). Survival data were analyzed using the Kaplan-Meier method, and the log-rank test was performed. Additionally, Cox proportional hazard regression was used to analyze the correlation of prognosis and baseline characteristics between subgroups, to identify the potential independent risk factors for PFS and OS. Furthermore, the occurrence of side effects was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03). Results: Of the 257 patients with advanced NSCLC included in the research, 135 patients received camrelizumab, and 122 patients received camrelizumab plus albumin-bound paclitaxel. The ORR of CTG and STG was 59.84% and 50.38%, and the DCR was 77.05% and 65.93%, respectively. The median PFS in CTG was higher than that in the STG (5.27 vs. 3.57 months, P = 0.0074), and the median OS was longer (7.09 vs. 6.47 months, P < 0.01). The lines of treatment, metastases, and PD-L1 expression levels were independent risk factors for the mPFS and mOS of patients with advanced NSCLC. The occurrence of adverse events was similar between camrelizumab and camrelizumab plus albumin-bound paclitaxel groups. Conclusion: Camrelizumab combined with albumin-bound paclitaxel as the third- or later-line regimen greatly prolonged PFS and OS of advanced NSCLC patients. A prospective clinical trial is warranted.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Albumin-Bound Paclitaxel , Carcinoma, Non-Small-Cell Lung/drug therapy , Prospective Studies , Retrospective Studies , Lung Neoplasms/drug therapyABSTRACT
BACKGROUND: This study aimed to identify genes related to the degree of immune cell infiltration in head and neck squamous cell carcinoma (HNSCC), explore their new biological functions, and evaluate their diagnostic and prognostic value in HNSCC. METHODS: Transcriptomic data from The Cancer Genome Atlas (TCGA) HNSCC dataset was used to screen differentially expressed genes between tumors and normal tissues, followed by weighted correlation network analysis (WGCNA) to identify immune-related modules. Differential gene expression, immune cell infiltration, and survival analyses were performed to screen key genes. The expression of these key genes was validated in Oncomine and gene expression omnibus (GEO) datasets and by immunohistochemistry (IHC). RESULTS: 1869 and 1578 genes were significantly upregulated and downregulated in HNSCC. WGCNA showed that the brown module was associated with the most significant number of immune-related genes. PPI network analysis demonstrated that PPL, SCEL, KRT4, KRT24, KRT78, KRT13, SPRR3, TGM3, CRCT1, and CRNN were key components in the brown module. Furthermore, the expression levels of KRT4, KRT78, KRT13, and SPRR3 in HNSCC correlated with infiltration levels of CD8+ T cells and macrophages. Survival analyses revealed that the expression of KRT78, KRT13, and SPRR3 in HNSCC correlated with overall survival (OS). The IHC assay indicated that KRT13 (p = .042), KRT78 (p < .001), and SPRR3 (p = .022) protein expression levels in HNSCC were significantly lower than in normal tissues. Analysis of GSE65858 and GSE41613 datasets showed that a worse OS was associated with low expression of KRT78 (p = .0086, and p = .005) and SPRR3 (p = .017, and p = .02). CONCLUSIONS: Our findings suggest that KRT4, KRT78, KRT13, and SPRR3 are related to the occurrence and development of HNSCC. Importantly, KRT78 and SPRR3 might serve as diagnostic and prognostic biomarkers of HNSCC.
Subject(s)
Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Head and Neck Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Gene Expression Profiling , Transcriptome , Transglutaminases/geneticsABSTRACT
Lung cancer is the leading cause of cancer mortality worldwide, with a median survival rate at 5 years of less than 20%. While molecular mapping aids in selecting appropriate therapies, it cannot predict personalized treatment response and long-term efficacy. For addressing these challenges, there is a great need for functional tests. Within this context, we developed patient-derived spheroids (PDS) from tumor and adjacent normal tissue to biomimic the respective tissue for assessing the personalized drug treatment response in vitro. Surgically resected lung specimens were used to generate spheroids using a two-step culture procedure. Flow cytometry and immune staining enabled the characterization of different cell populations resulting from the lung samples. PDS phenotype, cell proliferation and apoptosis were evaluated. Differential gene expression between tumor and adjacent normal tissue was analyzed via RT-qPCR. PDS drug sensitivity was assessed using a cell metabolic assay in response to two chemotherapeutic drug combinations. Cellular and molecular analysis revealed the proportion of epithelial cells, fibroblasts, and immune cells in the patients' tissue samples. Subsequently, PDS models from tumor and normal lung were successfully established using the expanded epithelial cells. As a proof of concept, an analysis of the drug treatment using PDS of lung adenoid cystic carcinoma exhibited a dose-dependent effect in response to cisplatin/etoposide and cisplatin/paclitaxel. Our spheroid model of both tumor and non-tumor lung cells holds great promise for enhancing the treatment efficacy in the cancer patients.
ABSTRACT
The perpendicular magnetic anisotropy (PMA) at ferromagnet/insulator interfaces has important technological applications, such as in the fields of magnetic recording and sensing devices. The perpendicular magnetic tunnel junctions (p-MTJs) with strong PMA have recently attracted increasing interest because they offer high stability and device performance toward low energy consumption. Heusler alloys are a large family of compounds that offer promising magnetic properties for developing p-MTJs. However, it is challenging to select appropriate combinations of Heusler ferromagnets and insulators with the desired interfacial properties. Here, we report a systematic high-throughput screening approach to search for candidate Heusler/MgO material interfaces with strong PMA and other desired material properties for spintronic technologies. On the basis of the open quantum material repositories, we developed a series of material descriptors, including formation energy, convex hull distance, magnetic ordering, lattice misfit, magnetic anisotropy constant, cleavage energy, and tunnel magnetoresistance, to filter candidate Heusler/MgO interfaces among the possible 40â¯000 ternary Heusler compounds. After a comprehensive screening, five full-Heusler compounds, including Co2CrAl, Co2FeAl, Co2HfSn, Fe2IrGa, and Mn2IrGe, and two half-Heusler compounds, PtCrSb and PtMnAs, were found to be promising for designing p-MTJs. This work demonstrates a new way for the high-throughput design of functional material interfaces for spintronic applications via exploiting the open quantum material repositories and developing effective material descriptors along with the large-scale ab initio calculations for material interfaces.
ABSTRACT
Background: To explore the changes and significance of the expression level and nutritional status of human insulin-like growth factor binding protein-2 (IGFBP2) after the treatment of esophageal cancer with left neck anastomosis combined with placement of feeding nutritional applicators carrying ^(125)I particles. Methods: A total of 110 patients with esophageal cancer (observation group: left neck anastomosis combined with placement of feeding nutritional applicators carrying ^(125)I particles) and 100 healthy people (control group) were enrolled at the same period. Then enzyme-linked immunosorbent assay (ELISA) was carried out to detect level of IGFBP-2. Lymphocyte count and serum albumin were measured by immune analyzer and automatic protein analyzer to evaluate nutritional status. Logistic regression analysis was used to analyze the relationship between serum IGFBP-2, nutritional status and prognosis of esophageal cancer after combined treatment. Results: The albumin, lymphocyte absolute value and PNI detection value of the control group were lower than those of the observation group 1 month after treatment, and the difference was statistically significant compared with the control group. The detection value of IGFBP-2 in early patients before and after treatment was lower than that in middle and late patients, and the detection values of albumin, lymphocyte absolute value and PNI were higher than those in middle and late patients, the differences were statistically significant. Serum IGFBP-2 level was negatively correlated with PNI, and albumin and lymphocyte absolute value were positively correlated with PNI. The detection value of IGFBP-2 in patients with good prognosis was significantly lower than that in patients with poor prognosis, and the detection values of albumin, lymphocyte absolute value and PNI were significantly higher than those in patients with poor prognosis. The AUC (0.887,95% CI: 0.799-0.975) of IGFBP-2, albumin, lymphocyte absolute value and PNI in predicting poor prognosis of esophageal cancer was the largest, and the sensitivity and specificity were 94.12% and 92.47%, respectively. Conclusions: Left neck anastomosis combined with ^(125)I particle application nutritional tube is helpful for the decrease of serum IGFBP-2 and the increase of various nutritional status indicators, which is beneficial for the improvement of the patient's condition.
ABSTRACT
Objective: To assess the clinical efficacy of osimertinib in patients with advanced non-small cell lung cancer and its effect on serum carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) expression. Methods: Between July 2018 and January 2020, 80 patients with advanced non-small cell lung cancer were assessed for eligibility and recruited. The patients were assigned at a ratio of 1 : 1 to receive either the PC regimen (pemetrexed + cisplatin) (conventional group) or osimertinib (experimental group). The primary endpoint was the clinical efficacy, and the secondary endpoints were the adverse events, expression of serum CEA and VEGF, and 2-year survival. Results: Osimertinib was associated with a significantly higher response rate and disease control rate versus pemetrexed plus cisplatin (P < 0.05). Osimertinib resulted in a significantly lower incidence of adverse events versus the PC regimen (P < 0.05). Patients given osimertinib had significantly lower levels of CEA and VEGF versus those given pemetrexed plus cisplatin (P < 0.05). Osimertinib was associated with a significantly higher 1-year and 2-year survival rate versus pemetrexed plus cisplatin. Conclusion: Osimertinib could inhibit the expression of serum CEA and VEGF in patients with advanced non-small cell lung cancer and reduce the adverse events with significant efficacy, so it is worthy of clinical promotion and application.
ABSTRACT
The effects of catalpol on lung cancer cell proliferation, apoptosis, migration, and oxidative stress via the Nrf2/ARE signaling pathway are investigated in this work. Catalpol-12 g/mL group, catalpol-24 g/mL group, catalpol-48 g/mL group, catalpol - 48 g/mL + vector group, catalpol - 48 g/mL + Nrf2 group, si-NC group, and si-Nrf2 group were used to split lung cancer cells A549 into control groups. Proliferation was detected using the CCK-8 assay; apoptosis was detected using flow cytometry; migration was detected using the transwell chamber; ROS was distinguished using the DCFHDA method; MDA, SOD, and GSH were detected using the microvolume method; and Cleaved Caspase-3, Cleaved Caspase-9, Nrf2, HO-1, MMP-9, and MMP-2 were detected using the Western blot method. Catalpol 12 g/mL and 24 g/mL-48 g/mL treatment decreased the proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells when compared to the control group. SOD and GSH levels of lung cancer cells were decreased, and MDA and ROS levels were increased. Cleaved caspase-3, cleaved caspase-9 protein expression levels, and apoptosis were boosted (P < 0.05). The proliferation activity, migration number, and protein levels of Nrf2, HO-1, MMP-9, and MMP-2 in the catalpol - 48 g/mL + Nrf2 group were raised compared to the catalpol - 48 g/mL + vector group, whereas there was an apparent drop in the Cleaved Caspase-3, Cleaved Caspase-9, and apoptosis rate. Similarly, SOD and GSH contents increased, whereas MDA and ROS decreased (P < 0.05). The proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells in the si-Nrf2 group were all decreased when compared to the si-NC and control groups. Cleaved Caspase-3 and Cleaved Caspase-9 protein expression, on the other hand, increased as MDA and ROS levels were raised while SOD and GSH levels dropped (P < 0.05). It reveals that catalpol inhibits the Nrf2/ARE signaling pathway, which causes antiproliferation, migration, apoptosis, and oxidative stress in cancer cells of lungs. The rate of apoptosis was also lowered.
Subject(s)
Lung Neoplasms , NF-E2-Related Factor 2 , Apoptosis , Carboxylic Ester Hydrolases/metabolism , Caspase 3/metabolism , Caspase 9/metabolism , Cell Movement , Cell Proliferation , Humans , Iridoid Glucosides , Lung/metabolism , Lung Neoplasms/drug therapy , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Signal Transduction , Superoxide Dismutase/metabolismABSTRACT
BACKGROUND: Carnosic acid (CA) is a polyphenolic diterpene extracted from rosemary. Reports have shown that CA possesses anticancer activity. However, whether CA inhibits esophageal squamous cell carcinoma, an aggressive type of esophageal cancer, remains untested. METHODS: The effects of CA on cell survival, migration, and apoptosis were evaluated by a combination of MTT, colony formation assay, flow cytometry, and Transwell assay. The potential signaling pathways involved were investigated via Western blot assay. RESULTS: CA dose-dependently inhibited cell proliferation, apoptosis, migration, and colony formation. Mechanistically, CA arrested the cell cycle at G2/M phase, promoted cell apoptosis, induced DNA damage, and inhibited the MAPK signaling pathways. CONCLUSION: Our results suggest that CA is a potential anticancer drug for esophageal squamous cell carcinoma.