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Many reports have shown that stabilization of secondary structure by stapling functional peptides enhances the intracellular bioactivity. However, no report has discussed the correlation between stabilization and biological activity based on the configuration of amino acid residues used as anchors for stapling. To clarify this, we investigated the helix content and apoptotic efficiency of an apoptosis-inducing peptide, Bim, and four stapled Bim peptides containing stapling-related Cys residues introduced with different configurations within the sequence. The results demonstrated that the configuration of Cys residues in stapled Bim peptides affected the secondary structure and intracellular activity of the peptides, and furthermore, there was a correlation between these latter two variables.
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Deltamethrin is a classical pyrethroid insecticide that is frequently detected in aquatic environments and organisms. Furthermore, deltamethrin has been detected in samples related to human health and is a potential risk to public health. This study aimed to investigate the mechanism of cardiotoxicity induced by deltamethrin. Zebrafish were exposed to 0.005, 0.05, or 0.5 µg/L deltamethrin for 28 days. The results showed a significant reduction in male reproduction compared to female reproduction. Additionally, the heart rate decreased by 15.75 % in F1 after parental exposure to 0.5 µg/L deltamethrin. To evaluate cardiotoxicity, deltamethrin was administered to the zebrafish embryos. By using miRNA-Seq and bioinformatics analysis, it was discovered that miR-29b functions as a toxic regulator by targeting dnmts. The overexpression of miR-29b and inhibition of dnmts resulted in cardiac abnormalities, such as pericardial edema, bradycardia, and abnormal expression of genes related to the heart. Similar changes in the levels of miR-29b and dnmts were also detected in the gonads of F0 males and F1 embryos, confirming their effects. Overall, the results suggest that deltamethrin may have adverse effects on heart development in early-stage zebrafish and on reproduction in adult zebrafish. Furthermore, epigenetic modifications may threaten the cardiac function of offspring.
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Cardiotoxicidad , Epigénesis Genética , Insecticidas , MicroARNs , Nitrilos , Piretrinas , Pez Cebra , Animales , Femenino , Masculino , Embrión no Mamífero/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Insecticidas/toxicidad , MicroARNs/genética , Nitrilos/toxicidad , Piretrinas/toxicidad , Reproducción/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/genética , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismoRESUMEN
Cancer cells have higher heat sensitivity compared to normal cells; therefore, hyperthermia is a promising approach for cancer therapy because of its ability to selectively kill cancer cells by heating them. However, the specific and rapid heating of tumor tissues remains challenging. This study investigated the potential of magnetic nanoparticles (MNPs) modified with tumor-homing peptides (THPs), specifically PL1 and PL3, for tumor-specific magnetic hyperthermia therapy. The synthesis of THP-modified MNPs involved the attachment of PL1 and PL3 peptides to the surface of the MNPs, which facilitated enhanced tumor cell binding and internalization. Cell specificity studies revealed an increased uptake of PL1- and PL3-MNPs by tumor cells compared to unmodified MNPs, indicating their potential for targeted delivery. In vitro hyperthermia experiments demonstrated the efficacy of PL3-MNPs in inducing tumor cell death when exposed to an alternating magnetic field (AMF). Even without exposure to an AMF, an additional ferroptotic pathway was suggested to be mediated by the nanoparticles. Thus, this study suggests that THP-modified MNPs, particularly PL3-MNPs, hold promise as a targeted approach for tumor-specific magnetic hyperthermia therapy.
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Hipertermia Inducida , Nanopartículas de Magnetita , Péptidos , Hipertermia Inducida/métodos , Humanos , Nanopartículas de Magnetita/química , Péptidos/química , Péptidos/farmacología , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/patología , Campos MagnéticosRESUMEN
Background: Accurately assessing the prognosis of patient with large-scale cerebral infarction caused by acute middle cerebral artery (MCA) occlusion in the early stages of onset can help clinicians to actively and effectively intervene, thus reducing mortality and disability rates. This study set out to investigate the predictive value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) on collateral circulation and clinical prognosis. Methods: The clinical data of 70 patients admitted to The First People's Hospital of Lianyungang from January 2018 to December 2021 with acute cerebral infarction due to occlusion of the proximal end of the M1 segment in the MCA were retrospectively collected. All patients had their first onset of disease and did not receive thrombolytic therapy at the time of onset. Subsequently, they underwent endovascular thrombectomy for treatment. The FVH and collateral vessel scores were derived according to patients' fluid-attenuated in version recovery (FLAIR) sequence and time-of-flight magnetic resonance angiography images. Based on the 90-day Modified Rankin Scale (mRS), patients were allocated to a good prognosis group (mRS ≤2) and a poor prognosis group (mRS =3-6). The correlation between the FVH and collateral vessel scores was assessed using the Spearman rank correlation test. Pearson correlation coefficient analysis was used to assess the correlation between FVH and the 90-day mRS together with the infarct size. Univariate analysis, multivariate binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were adopted to identify those factors potentially. associated with the prognosis of patients with acute ischemic stroke (AIS). Results: Out of 70 patients with acute unilateral MCA occlusion (MCAO) who met the inclusion criteria, 62 showed positive FVH sign. These 62 patients were divided into a good prognosis group (n=32) and a poor prognosis group (n=30) based on the mRS score 90 days after discharge. The Spearman rank correlation test indicated that FVH was positively correlated with collateral vessel grade (Spearman rho =0.865; P<0.001); meanwhile, Pearson correlation coefficient analysis indicated that FVH score had moderate negative correlation with 90-day mRS score (r=-0.605; P<0.001). The results of multivariate binary logistic regression analysis indicated that collateral vessel grade and FVH score may be associated with the prognosis of patients with AIS, and the area under the curve (AUC) of FVH score was larger than collateral vessel grade (AUC =0.738). Conclusions: There was a positive correlation between FVH score and collateral vessel grade, and FVH score could indicate collateral circulation. FVH score was negatively correlated with 90-day mRS score and infarct volume and thus can predict clinical prognosis.
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ATP-binding cassette (ABC) transporters were crucial for various physiological processes like nutrition, development, and environmental interactions. Selenium (Se) is an essential micronutrient for humans, and its role in plants depends on applied dosage. ABC transporters are considered to participate in Se translocation in plants, but detailed studies in soybean are still lacking. We identified 196 ABC genes in soybean transcriptome under Se exposure using next-generation sequencing and single-molecule real-time sequencing technology. These proteins fell into eight subfamilies: 8 GmABCA, 51 GmABCB, 39 GmABCC, 5 GmABCD, 1 GmABCE, 10 GmABCF, 74 GmABCG, and 8 GmABCI, with amino acid length 121-3022 aa, molecular weight 13.50-341.04 kDa, and isoelectric point 4.06-9.82. We predicted a total of 15 motifs, some of which were specific to certain subfamilies (especially GmABCB, GmABCC, and GmABCG). We also found predicted alternative splicing in GmABCs: 60 events in selenium nanoparticles (SeNPs)-treated, 37 in sodium selenite (Na2SeO3)-treated samples. The GmABC genes showed differential expression in leaves and roots under different application of Se species and Se levels, most of which are belonged to GmABCB, GmABCC, and GmABCG subfamilies with functions in auxin transport, barrier formation, and detoxification. Protein-protein interaction and weighted gene co-expression network analysis suggested functional gene networks with hub ABC genes, contributing to our understanding of their biological functions. Our results illuminate the contributions of GmABC genes to Se accumulation and tolerance in soybean and provide insight for a better understanding of their roles in soybean as well as in other plants.
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Transportadoras de Casetes de Unión a ATP , Glycine max , Proteínas de Plantas , Selenio , Glycine max/metabolismo , Glycine max/genética , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Selenio/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Deltamethrin (DM) is a widely used insecticide that has demonstrated developmental toxicity in the early life stages of fish. To better characterize the underlying mechanisms, embryos from Tg(cmlc2:RFP), Tg(apo14:GFP), and Tg(mpx:GFP) transgenic strains of zebrafish were exposed to nominal DM concentrations of 0.1, 1, 10, 25, and 50 µg/L until 120 h post-fertilization (hpf). Heart size increased 56.7%, and liver size was reduced by 17.1% in zebrafish exposed to 22.7 and 24.2 µg/L DM, respectively. RNA sequencing and bioinformatic analyses predicted that key biological processes affected by DM exposure were related to inflammatory responses. Expression of IL-1 protein was increased by 69.0% in the 24.4 µg/L DM treatment, and aggregation of neutrophils in cardiac and hepatic histologic sections was also observed. Coexposure to resatorvid, an anti-inflammatory agent, mitigated inflammatory responses and cardiac toxicity induced by DM and also restored liver biomass. Our data indicated a complex proinflammatory mechanism underlying DM-induced cardiotoxicity and hepatotoxicity which may be important for key events of adverse outcomes and associated risks of DM to early life stages of fish.
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Cardiotoxicidad , Pez Cebra , Animales , Piretrinas/toxicidad , Insecticidas/toxicidad , Hígado/efectos de los fármacos , Nitrilos/toxicidad , Corazón/efectos de los fármacosRESUMEN
The exploration of antibiotic resistance genes (ARGs) in drinking water reservoirs is an emerging field. Using a curated database, we enhanced the ARG detection and conducted a comprehensive analysis using 2.2 Tb of deep metagenomic sequencing data to determine the distribution of ARGs across 16 drinking water reservoirs and associated environments. Our findings reveal a greater diversity of ARGs in sediments than in water, underscoring the importance of extensive background surveys. Crucial ARG carriers-specifically Acinetobacter, Pseudomonas, and Mycobacterium were identified in drinking water reservoirs. Extensive analysis of the data uncovered a considerable concern for drinking water safety, particularly in regions reliant on river sources. Mobile genetic elements have been found to contribute markedly to the propagation of ARGs. The results of this research suggest that the establishment of drinking water reservoirs for supplying raw water may be an effective strategy for alleviating the spread of water-mediated ARGs.
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Agua Potable , Farmacorresistencia Microbiana , Metagenómica , Agua Potable/microbiología , Farmacorresistencia Microbiana/genética , Microbiología del Agua , Farmacorresistencia Bacteriana/genética , Abastecimiento de AguaRESUMEN
BACKGROUND: Sideroflexin 1 (SFXN1), a mitochondrial serine transporter implicated in one-carbon metabolism, is a prognostic biomarker in lung adenocarcinoma (LUAD). However, its role in LUAD progression remains elusive. This study aimed to investigate the functional significance of SFXN1 in LUAD and evaluate its potential as a therapeutic target. METHODS: We analyzed SFXN1 expression and its diagnostic and prognostic value in LUAD using the Pan-cancer TCGA dataset. In vitro assays (CCK-8, cell cycle, EDU, wound-healing, and transwell) were employed to assess the role of SFXN1, complemented by in vivo experiments. RNA sequencing elucidated SFXN1-mediated cellular functions and potential mechanisms. Bulk RNA-seq and scRNA-seq data from TCGA and GEO were used to investigate the correlation between SFXN1 and the tumor immune microenvironment. RT-qPCR, Western blot, and IHC assays validated SFXN1 expression and its impact on the immune microenvironment in LUAD. RESULTS: SFXN1 was upregulated in LUAD tissues and associated with poor prognosis. RNA-seq and scRNA-seq analyses revealed increased SFXN1 expression in tumor cells, accompanied by decreased infiltration of NK and cytotoxic T cells. SFXN1 knockdown significantly reduced cell proliferation and migration, and the inhibition of ERK phosphorylation and CCL20 expression may be the molecular mechanism involved. In vivo, targeting SFXN1 decreased Tregs infiltration and inhibited tumor growth. CONCLUSIONS: Our findings suggest that SFXN1 may be a potential therapeutic target for LUAD treatment.
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Adenocarcinoma del Pulmón , Sistemas de Transporte de Aminoácidos Neutros , Neoplasias Pulmonares , Linfocitos Infiltrantes de Tumor , Microambiente Tumoral , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/inmunología , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinogénesis/genética , Carcinogénesis/inmunología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Linfocitos Infiltrantes de Tumor/inmunología , Pronóstico , Microambiente Tumoral/inmunología , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismoRESUMEN
BACKGROUND: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. MATERIALS AND METHODS: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. RESULTS: lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). CONCLUSIONS: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , Animales , Ratones , ARN Largo no Codificante/genética , Cromatografía Liquida , Hipofaringe , Proteínas Proto-Oncogénicas c-akt/genética , Espectrometría de Masas en Tándem , Carcinoma de Células Escamosas/genética , Neoplasias de la Vejiga Urinaria/genética , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Tebuconazole is a widely used fungicide for various crops that targets sterol 14-α-demethylase (CYP51) in fungi. However, attention has shifted to aromatase (CYP19) due to limited research indicating its reproductive impact on aquatic organisms. Herein, zebrafish were exposed to 0.5 mg/L tebuconazole at different developmental stages. The proportion of males increased significantly after long-term exposure during the sex differentiation phase (0-60, 5-60, and 19-60 days postfertilization (dpf)). Testosterone levels increased and 17ß-estradiol and cyp19a1a expression levels decreased during the 5-60 dpf exposure, while the sex ratio was equally distributed on coexposure with 50 ng/L 17ß-estradiol. Chemically activated luciferase gene expression bioassays determined that the male-biased sex differentiation was not caused by tebuconazole directly binding to sex hormone receptors. Protein expression and phosphorylation levels were specifically altered in the vascular endothelial growth factor signaling pathway despite excluding the possibility of tebuconazole directly interacting with kinases. Aromatase was selected for potential target analysis. Molecular docking and aromatase activity assays demonstrated the interactions between tebuconazole and aromatase, highlighting that tebuconazole poses a threat to fish populations by inducing a gender imbalance.
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Diferenciación Sexual , Pez Cebra , Masculino , Animales , Diferenciación Sexual/genética , Aromatasa/genética , Aromatasa/metabolismo , Larva/metabolismo , Simulación del Acoplamiento Molecular , Factor A de Crecimiento Endotelial Vascular/metabolismo , Estradiol/metabolismoRESUMEN
BACKGROUND: Primary malignant melanoma of the esophagus (PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival. AIM: To investigate the clinical features and survival factors in Chinese patients with PMME. METHODS: The clinicopathological findings of ten cases with PMME treated at Henan Provincial People's Hospital were summarized. Moreover, the English- and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival. RESULTS: A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients (55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients (36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis (LNM) was 51.2% (107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the pT stage [P < 0.001, odds ratio (OR): 2.47, 95% confidence interval (CI): 1.72-3.56] and larger tumor size (P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival (OS) was 11.0 mo (range: 1-204 mo). The multivariate Cox analysis showed both the pT stage [P = 0.005, hazard ratio (HR): 1.70, 95%CI: 1.17-2.47] and LNM (P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival (DFS) was 5.3 mo (range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced pT stage (P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME. CONCLUSION: The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and pT stage are independent prognosis factors for OS, and the pT stage is the prognosis factor for DFS in patients with PMME.
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Alcoholic hepatitis (AH), a kind of alcoholic liver disease, shows poor prognosis. Long noncoding RNAs (lncRNAs) exert critical role in liver diseases. Here, we intended to investigate the possible molecular mechanism that 1700020I14Rik-based regulation of microRNA (miR)-137/Aldo-keto reductase family 1 member B10 (AKR1B10) affecting the inflammatory response and hepatocyte damage in AH. AH-related genes and the down-stream regulatory pathway were screnned by bioinformatics. Mouse normal hepatocyte cell line AML12 was selected to construct an ethanol-induced hepatocyte injury model for in vitro mechanistic validation, while we also established an AH mouse model using the ethanol with gradually increased concentration of 2-4% (v/v) for in vivo study. Specific role of 1700020I14Rik/miR-137/AKR1B10 in AML12 cell viability, proliferation and apoptotic capacity as well as inflammation and liver damage in mice were analyzed following ectopic and depletion approaches. We found elevated AKR1B10 and 1700020I14Rik but reduced miR-137 in AH. 1700020I14Rik was able to elevated miR-137-mediated AKR1B10. In vitro cell experiments and in vivo animal experiments validated that 1700020I14Rik reduced ethanol-induced hepatocyte damage and inflammation in AH mice through regulation of miR-137-mediated AKR1B10/Erk axis. The current study underlied that 1700020I14Rik could activate AKR1B10/Erk signaling through inhibition of miR-137, thereby promoting the hepatocyte damage in AH mice.
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While genetic alterations in several regulators of the cell cycle have a significant impact on the gastric carcinogenesis process, the prognostic role of them remains to be further elucidated. The TCGA-STAD training set were downloaded and the mRNA expression matrix of cell cycle genes was extracted and corrected for further analysis after taking the intersection with GSE84437 dataset. Differentially expressed mRNAs were identified between tumor and normal tissue samples in TCGA-STAD. Univariate Cox regression analysis and lasso Cox regression model established a novel seven-gene cell cycle signature (including GADD45B, TFDP1, CDC6, CDC25A, CDC7, SMC1A and MCM3) for GC prognosis prediction. Patients in the high-risk group shown significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GC survival. Nomogram including the signature shown some clinical net benefit for overall survival prediction. The signature was further validated in the GSE84437 dataset. In tissue microarray, CDC6 and MCM3 protein expression were significant differences by the immunohistochemistry-based H-score between tumor tissues and adjacent tissues, and CDC6 is an independent prognostic factor for GC. Interestingly, our GSEA revealed that low-risk patients were more related to cell cycle pathways and might benefit more from therapies targeting cell cycle. Our study identified a novel robust seven-gene cell cycle signature for GC prognosis prediction that may serve as a beneficial complement to clinicopathological staging. The signature might provide potential biomarkers for the application of cell cycle regulators to therapies and treatment response prediction.
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Proteínas de Ciclo Celular , Neoplasias Gástricas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Ciclo Celular/genética , Proteínas de Ciclo Celular/genética , Humanos , Nomogramas , Pronóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
Identifying the underlying ecological drivers of macroinvertebrate community assembly is fundamental to metacommunity ecology. Comparably, determining the influence of different drivers on beta diversity patterns can provide insight into processes governing community organization. Exploring the ecological drivers of metacommunity and beta diversity are major avenues to improve bioassessment, restoration, and river management, which are still poorly explored in China, especially in subtropical highly developed river networks. To address this gap, we use a dataset (macroinvertebrate communities and environmental variables) collected from the Yangtze River Delta, China to test the above ideas. We used the K-means clustering method to divide 405 river sites into three anthropogenic impacted groups, nearly pristine sites, moderately impacted sites, and heavily impacted sites, and subsequently used partial Mantel tests to investigate how species sorting and dispersal shaped the metacommunity that varied with the levels of anthropogenic impacts and to explore the responses of different components of beta diversity to environmental and spatial distances among sites for each group. Our results revealed that both species sorting and dispersal shape communities, but the importance of species sorting and dispersal varied with the levels of anthropogenic impacts. Nearly pristine sites were mostly shaped only by species sorting, while heavily impacted sites were shaped by dispersal. We also found that turnover was by far the dominant component of beta diversity across all levels of impact. Therefore, we encourage that environmental variables and spatial processes should be considered in bioassessment approaches. In addition, it is essential to focus on maintaining habitat heterogeneity and identifying and protecting regional species pools that could improve local biodiversity through dispersal for ecosystem management of the Yangtze River Delta of China.
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Ecosistema , Ríos , Biodiversidad , ChinaRESUMEN
Objective: This study aims to explore the application value of computed tomography (CT) three-dimensional (3D) reconstruction, magnetic resonance imaging (MRI) 3D reconstruction, and conventional digital subtraction angiography (DSA) fluoroscopy in percutaneous transhepatic cholangial drainage (PTCD). Methods: The clinical data of 180 patients with obstructive jaundice requiring PTCD from December 2017 to December 2021 were retrospectively analyzed. Following PTCD, CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were conducted, after which the surgical success rates, liver function results, and postsurgical complications were compared. Results: The puncture accuracies under CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy were 90.0% (54/60), 96.7% (58/60), and 80% (48/60), respectively. The degree of jaundice and epigastric discomfort was relieved in all three groups after surgery, while a significant reduction in the levels of total bilirubin and direct bilirubin was observed relative to the levels before surgery (P < 0.05). The incidences of complications in the CT 3D reconstruction, MRI 3D reconstruction, and conventional DSA fluoroscopy groups were 6.7% (4/60), 3.3% (2/60), and 13.3% (8/60), respectively, and the differences among the three groups were statistically significant (P < 0.05). Conclusion: Conducting conventional enhanced CT and MRI scans in patients before surgery might be more practical than the conventional puncture method. Among the methods under study, MRI 3D reconstruction was found to be safer and more feasible than CT 3D reconstruction and conventional DSA fluoroscopy in PTCD. MRI 3D reconstruction could reduce the degree of jaundice, improve the success rate of surgery, reduce the incidence of complications due to surgery, and improve the patients' tolerance to surgery.
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Afatinib, a second-generation tyrosine kinase inhibitor (TKI), exerts its antitumor effects in head and neck squamous cell carcinoma (HNSCC) by inducing intrinsic apoptosis through suppression of mTORC1. However, the detailed mechanism and biological significance of afatinib-induced autophagy in HNSCC remains unclear. In the present study, we demonstrated that afatinib induced mTORC1 suppression-mediated autophagy in HNSCC cells. Further mechanistic investigation revealed that afatinib stimulated REDD1-TSC1 signaling, giving rise to mTORC1 inactivation and subsequent autophagy. Moreover, ROS generation elicited by afatinib was responsible for the induction of the REDD1-TSC1-mTORC1 axis. In addition, pharmacological or genetic inhibition of autophagy sensitized HNSCC cells to afatinib-induced apoptosis, demonstrating that afatinib activated pro-survival autophagy in HNSCC cells. Importantly, in vitro and in vivo assays showed that afatinib caused enhanced apoptosis but weaker autophagy in stem-like HNSCC cells constructed by CDH1 knockdown. This suggested that blocking autophagy has the potential to serve as a promising strategy to target HNSCC stem cells. In conclusion, our findings suggested that the combination treatment with afatinib and autophagy inhibitors has the potential to eradicate HNSCC cells, especially cancer stem cells in clinical therapy.
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Afatinib/farmacología , Apoptosis , Autofagia , Neoplasias de Cabeza y Cuello/patología , Células Madre Neoplásicas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Vasculogenic mimicry (VM) refers to vessel-like structures formed by aggressive tumor cells and is closely associated with cancer invasion and metastasis. Here, we investigated the effect of macrophage-derived MTDH on VM formation in head and neck squamous cell carcinoma (HNSCC) and its underlying mechanism. Macrophages with MTDH overexpression (Mac-MTDH) promoted cancer cell VM formation, migration, and invasion in vitro. Moreover, MTDH overexpression triggered macrophage polarization into M2 type tumor-associated macrophages. Analysis of HNSCC clinical samples revealed that MTDH+ macrophages were predominantly located in the tumor-stromal region in proximity to VM and correlated with lymph node metastasis. Mechanistically, Mac-MTDH enhanced the expression and secretion of VEGFA-165 rather than other VEGFA isoforms via ß-catenin. The VEGFA-165/Flt-1 axis was responsible for Mac-MTDH's effects in cancer cells through p-STAT3/Twist1/VE-cadherin pathway. Using mouse model, we further confirmed that Mac-MTDH increased VM formation and cancer metastasis in vivo. Furthermore, in subcutaneous xenograft mouse model, HN6 + Mac-MTDH tumor exhibited elevated expression of p-STAT3 and Twist1 than HN6 + Mac-NC tumors. This study revealed that Mac-MTDH promoted VM formation, cancer cell migration and invasion, and cancer metastasis through VEGFA-165/Flt-1 axis, and that macrophage-derived MTDH could be a potential therapeutic target in HNSCC.
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Neoplasias de Cabeza y Cuello/metabolismo , Macrófagos/metabolismo , Proteínas de la Membrana/metabolismo , Neovascularización Patológica/metabolismo , Proteínas de Unión al ARN/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Antígenos CD/metabolismo , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Activación de Macrófagos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas Nucleares/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Macrófagos Asociados a Tumores/metabolismo , Proteína 1 Relacionada con Twist/metabolismo , beta Catenina/metabolismoRESUMEN
Cisplatin is a widely used platinumbased chemotherapeutic agent for hypopharyngeal squamous cell carcinoma (HSCC). However, resistance to cisplatin limits its use for the treatment of HSCC, and the underlying molecular mechanism requires further investigation. The present study performed functional assays to determine whether the expression of plant homeodomain finger protein 20 (PHF20) may be involved in the apoptosis and cisplatin resistance of HSCC. The expression levels of PHF20 were higher in cisplatinresistant HSCC cells compared with those in cisplatinsensitive cells. The inhibition of PHF20 suppressed cell viability but did not affect the migratory and invasive abilities of HSCC cells compared with those of negative controltransfected cells. Furthermore, PHF20 inhibition reduced cell viability by enhancing apoptosis compared with those in the control cells in vitro. Notably, the inhibition of PHF20 sensitized HSCC cells to cisplatin, thus increasing apoptosis via the signal transducer and activator of transcription 3 (STAT3)myeloid cell leukemia1 (MCL1) pathway. Octamerbinding transcription factor 4 (OCT4) overexpression restored phosphorylated STAT3MCL1mediated apoptosis induced by PHF20 inhibition. In vivo experiments confirmed that PHF20 silencing induced tumor growth and increased apoptosis in HSCC cells compared with those in the control cells. Thus, PHF20 inhibition may promote apoptosis and improve cisplatin chemosensitivity via the OCT4pSTAT3MCL1 signaling pathway in HSCC.
Asunto(s)
Cisplatino/farmacología , Proteínas de Unión al ADN/genética , Resistencia a Antineoplásicos/genética , Neoplasias Hipofaríngeas/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Factores de Transcripción/genética , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hipofaríngeas/metabolismo , Neoplasias Hipofaríngeas/patología , Masculino , Ratones Endogámicos BALB C , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Renal cell carcinoma (RCC) has the highest mortality rate among urological cancers and tumor angiogenesis that plays a critical role in RCC progress. Epidermal growth factor-like domain multiple 7 (EGFL7) has been recently identified as a regulator in RCC tumor angiogenesis and progression. Long noncoding RNA (LncRNA) HOTAIR has been considered as a pro-oncogene in multiple cancers, but its precise mechanism of tumor angiogenesis has rarely been reported. MicroRNA-126 (miR-126) functions as a tumor suppressor in RCC. However, the underlying tumor angiogenesis mechanism of HOTAIR/miR-126 axis in RCC has not been studied. The proliferation, migration, angiogenesis, and expression of EGFL7 and related proteins in extracellular signal-regulated kinase (ERK)/activators of transcription 3 (STAT3) signal pathway were determined to examine the effect and mechanism of HOTAIR and miR-126 on RCC progress. The regulatory relationship of HOTAIR and miR-126, as well as miR-126 and EGFL7 were tested using dual-luciferase reporter assay. Aenograft RCC mice model was used to examine the effect of HOTAIR on RCC tumor growth and metastasis in vivo. HOTAIR knockdown and miR-126 overexpression suppressed the proliferation, migration, and angiogenesis of RCC cells. HOTAIR regulated EGFL7 expression by competitively binding to miR-126. Knockdown of HOTAIR significantly suppressed the RCC tumor progression and lung metastasis in vivo. These findings suggest that lncRNA HOTAIR regulate RCC angiogenesis through miR-126/EGFL7 axis and provide a new perspective on the molecular pathways of angiogenesis in RCC development, which might be potential therapeutic targets for RCC treatment.
Asunto(s)
Proteínas de Unión al Calcio/metabolismo , Carcinoma de Células Renales/metabolismo , Familia de Proteínas EGF/metabolismo , Neoplasias Renales/metabolismo , MicroARNs/metabolismo , Neovascularización Patológica , ARN Largo no Codificante/metabolismo , Animales , Proteínas de Unión al Calcio/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Familia de Proteínas EGF/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Ratones Endogámicos BALB C , MicroARNs/genética , Densidad Microvascular , Persona de Mediana Edad , Invasividad Neoplásica , ARN Largo no Codificante/genética , Transducción de Señal , Carga TumoralRESUMEN
Pro-apoptotic peptides may be promising agents for cancer therapy owing to their ability to induce apoptosis in cancer cells. TatBim, a fusion peptide of Tat cell-penetrating peptide (CPP) and the BH3 domain derived from Bim apoptosis-inducing protein, is a pro-apoptotic peptide. In this study, based on the TatBim sequence, we attempted to minimize the CPP-Bim peptide while retaining apoptosis-inducing activity. The CPP and Bim parts were systematically shortened, and the pro-apoptotic activities of the shortened peptides were examined. We obtained TatBim-N1C2 and R8Bim-N1C2 as minimized peptides with efficient apoptotic activity. These peptides may have potential applications in future biomedical studies, such as cancer therapeutics.