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1.
J Transl Med ; 20(1): 250, 2022 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-35659682

RESUMEN

Gastric cancer is a common type of gastrointestinal malignant tumor in China. The mechanism of the development and progression of gastric cancer remains the continuing research focus. The tumor microenvironment plays an important role in the development and progression of tumors. The present study used single-cell sequencing data to characterize the microenvironment of gastric cancer, investigate the effects of oxidative stress on gastric cancer microenvironmental cells through the comparison between cancer tissue and normal tissue, and identify the key genes associated with gastric cancer patients' survival. The results showed that compared with normal gastric tissue, gastric cancer tissue had a decreased oxidative stress response, weaker oxidative detoxification ability, and increased oxidative stress-induced cell death. In the different types of single cells of gastric cancer microenvironment, the oxidative stress response of T cell was increased, the ability of oxidative detoxification was enhanced, and the oxidative stress-induced cell death was exacerbate. Mucous cell showed the same trend as gastric cancer cells: decreased oxidative stress response, weak oxidative detoxification ability, and weakened oxidative stress-induced cell death. Moreover, TRIM62, MET, and HBA1, which were significantly associated with oxidative stress, may be biomarkers for the prognosis of gastric cancer. High expression of TRIM62 indicated a good prognosis, while MET and HBA1 indicated a poor prognosis, which will be confirmed by further clinical studies.


Asunto(s)
Neoplasias Gástricas , Microambiente Tumoral , Hemoglobina Glucada/metabolismo , Humanos , Estrés Oxidativo/genética , Pronóstico , Neoplasias Gástricas/patología , Microambiente Tumoral/genética
2.
J Transl Med ; 20(1): 174, 2022 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-35410343

RESUMEN

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare neurovascular disorder with highly variable manifestations and clinical courses. Animal models properly matched to the clinical form of CVST are necessary for elucidating the pathophysiology of the disease. In this study, we aimed to establish a rat model that accurately recapitulates the clinical features of CVST in human patients. METHODS: This study consisted of a clinical analysis and animal experiments. Clinical data for two centres obtained between January 2016 and May 2021 were collected and analysed retrospectively. In addition, a Sprague-Dawley rat model of CVST was established by inserting a water-swellable rubber device into the superior sagittal sinus, following which imaging, histological, haematological, and behavioural tests were used to investigate pathophysiological changes. Principal component analysis and hierarchical clustering heatmaps were used to evaluate the similarity between the animal models and human patients. RESULTS: The imaging results revealed the possibility of vasogenic oedema in animal models. Haematological analysis indicated an inflammatory and hypercoagulable state. These findings were mostly matched with the retrospective clinical data. Pathological and serological tests further revealed brain parenchymal damage related to CVST in animal models. CONCLUSIONS: We successfully established a stable and reproducible rat model of CVST. The high similarity between clinical patients and animal models was verified via cluster analysis. This model may be useful for the study of CVST pathophysiology and potential therapies.


Asunto(s)
Trombosis de los Senos Intracraneales , Animales , Humanos , Modelos Animales , Ratas , Ratas Sprague-Dawley , Estudios Retrospectivos , Trombosis de los Senos Intracraneales/diagnóstico por imagen , Trombosis de los Senos Intracraneales/patología , Seno Sagital Superior/patología
3.
Cancer Cell Int ; 22(1): 69, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144613

RESUMEN

BACKGROUND: Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC. METHODS: In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC. RESULTS: We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P < 0.05). Analysis of biological functions revealed that target genes of the lncRNAs in the IRLP signature were enriched in focal adhesion and regulation of actin cytoskeleton. Finally, as one of significant candidates of IRLP signature, overexpression of LINC01082 suppressed the invasion ability of GC cells as well as PD-L1 expression profiles. CONCLUSIONS: Our novel 18-IRLP signature provides new insights regarding immunological biomarkers, imparts a better understanding of the tumor immune microenvironment, and can be used for predicting prognosis and evaluating immune response in GC.

4.
BMC Cancer ; 21(1): 20, 2021 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-33402102

RESUMEN

BACKGROUND: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer. METHODS: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety. DISCUSSION: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer. TRIAL REGISTRATION: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Neoadyuvante , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adolescente , Adulto , Anciano , Quimioterapia Adyuvante , Ensayos Clínicos Fase III como Asunto , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Oxaliplatino/administración & dosificación , Ácido Oxónico/administración & dosificación , Pronóstico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Adulto Joven
5.
Phys Rev Lett ; 125(22): 225501, 2020 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-33315432

RESUMEN

Motivated by the recent theoretical studies on a two-dimensional (2D) chiral Hamiltonian based on the Su-Schrieffer-Heeger chains [L. Zhu, E. Prodan, and K. H. Ahn, Phys. Rev. B 99, 041117(R) (2019)PRBMDO2469-995010.1103/PhysRevB.99.041117], we experimentally and computationally demonstrate that topological flat frequency bands can occur at open edges of 2D planar metamaterials and at antiphase boundary seams of ring-shaped or tubular metamaterials. Specifically, using mechanical systems made of magnetically coupled spinners, we reveal that the presence of the edge or seam bands that are flat in the entire projected reciprocal space follows the predictions based on topological winding numbers. The edge-to-edge distance sensitively controls the flatness of the edge bands and the localization of excitations, consistent with the theoretical analysis. The analog of the fractional charge state is observed. Possible realizations of flat bands in a large class of metamaterials, including photonic crystals and electronic metamaterials, are discussed.

6.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 46(6): 600-608, 2017 May 25.
Artículo en Zh | MEDLINE | ID: mdl-29658662

RESUMEN

Objective: To evaluate the application of mechanically reinforced 45S5 Bioglass®-derived glass ceramic porous scaffolds for repair of bone defect in rabbits. Methods: The BG-ZnB powders were added into the 45S5 Bioglass® powder/paraffin microsphere mixtures and were sintered at 900℃ to obtain porous scaffolds with highly bioactive BG-ZnB of 0%, 2% or 4% of mass fraction (denoted as 45S5/ZnB0, 45S5/ZnB2, 45S5/ZnB4). Phase composition, porosity and compression properties of three kinds of as-sintered scaffolds were characterized by X-ray analysis, mercury porosimetry, and mechanical test. Thirty-six male New Zealand rabbits with critical-sized femoral bone defects were randomly divided into three groups (45S5/ZnB0 group, 45S5/ZnB2 group and 45S5/ZnB4 group, 12 for each), and were implanted with three kinds of porous scaffolds respectively. X-ray, micro-CT three-dimensional reconstruction and tissue slice staining were used to detected the efficiency of bone regeneration at 6 and 16 weeks after operation. The growth of newly formed bone was observed using HE, Masson staining and EnVision method. Results: Phase compositions of 45S5/ZnB2 and 45S5/ZnB4 were the same with 45S5/ZnB0, but the average pore size and porosity of the scaffolds were decreased with the increase of BG-ZnB content. 45S5/ZnB2 and 45S5/ZnB4 scaffolds exhibited higher compressive strength, osteogenesis and trabecular density than those of the 45S5/ZnB0 scaffold (all P<0.05). With the mechanical reinforcement of BG-ZnB increased, the content of new bone, collagen type I and osteocalcin increased. Conclusion: Low-melt BG-ZnB-assisted sintering is a promising approach to improve the mechanical strength of 45S5 Bioglass®.


Asunto(s)
Huesos/fisiología , Cerámica , Vidrio , Andamios del Tejido , Animales , Huesos/efectos de los fármacos , Cerámica/química , Masculino , Porosidad , Conejos , Andamios del Tejido/química
7.
Plant Mol Biol ; 84(3): 315-27, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24104862

RESUMEN

Transcriptomic data for Sorghum propinquum, the wild-type sorghum, are limited in public databases. S. propinquum has a subterranean rhizome and transcriptome data will help in understanding the molecular mechanisms underlying rhizome formation. We sequenced the transcriptome of S. propinquum aerial-shoot and rhizome using an Illumina platform. More than 70 % of the genes in the S. propinquum genome were expressed in aerial-shoot and rhizome. The expression patterns of 1963 and 599 genes, including transcription factors, were specific or enriched in aerial-shoot and rhizome respectively, indicating their possible roles in physiological processes in these tissues. Comparative analysis revealed several cis-elements, ACGT box, GCCAC, GATC and TGACG box, which showed significantly higher abundance in aerial-shoot-specific genes. In rhizome-specific genes MYB and ROOTMOTIFTAPOX1 motifs, and 10 promoter and cytokinin-responsive elements were highly enriched. Of the S. propinquum genes, 27.9 % were identified as alternatively spliced and about 60 % of the alternative splicing (AS) events were tissue-specific, suggesting that AS played a crucial role in determining tissue-specific cellular function. The transcriptome data, especially the co-localized rhizome-enriched expressed transcripts that mapped to the publicly available rhizome-related quantitative trait loci, will contribute to gene discovery in S. propinquum and to functional studies of the sorghum genome. Deep transcriptome sequencing revealed a clear difference in the expression patterns of genes between aerial-shoot and rhizome in S. propinquum. This data set provides essential information for future studies into the molecular genetic mechanisms involved in rhizome formation.


Asunto(s)
Genes de Plantas , Componentes Aéreos de las Plantas/metabolismo , Rizoma/metabolismo , Sorghum/genética , Transcriptoma , Regulación de la Expresión Génica de las Plantas , ARN de Planta/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa
8.
J Chem Theory Comput ; 20(6): 2390-2403, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38483826

RESUMEN

Variational quantum eigensolvers (VQEs) show promise for tackling complex quantum chemistry challenges and realizing quantum advantages. However, in VQE, the measurement step encounters difficulties due to errors in objective function evaluation, e.g., the energy of a quantum state. While increasing the number of measurement shots can mitigate measurement errors, this approach leads to higher costs. Strategies for shot assignment have been investigated, allowing for the allocation of varying shot numbers to different Hamiltonian terms and reducing measurement variance through term-specific insights. In this paper, we introduce a dynamic approach, the Variance-Preserved Shot Reduction (VPSR) method. This technique strives to minimize the total number of measurement shots while preserving the variance of measurements throughout the VQE process. Our numerical experiments on H2 and LiH molecular ground states demonstrate the effectiveness of VPSR in achieving VQE convergence with a notably lower shot count.

9.
Obes Surg ; 34(8): 2828-2834, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38981958

RESUMEN

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most popular bariatric surgery procedure in China. However, its cost-effectiveness in Chinese patients is currently unknown. OBJECTIVES: This study aims to assess the cost-effectiveness of LSG vs no surgery in Chinese patients with severe and complex obesity, taking into account both healthcare expenses and the potential improvement in health-related quality of life (HRQoL). METHODS: A retrospective cohort study was conducted, encompassing 135 Chinese patients who underwent LSG between January 3, 2022 and December 29, 2022, at a major bariatric center. The study evaluated the cost-effectiveness from a healthcare service perspective, employing the incremental cost-effectiveness ratio (ICER) for quality-adjusted life years (QALYs) gained. The analyses compared LSG with the alternative of not undergoing surgery over a 1-year period, using actual data, and extended to a lifetime horizon by projecting costs and utilities at an annual discount rate of 3.0%. Subgroup analyses were undertaken to explore cost-effectiveness variations across different sex, age and BMI categories, and diabetes status, employing a one-way analysis of variance (ANOVA). To ensure the reliability of the findings, one-way and probabilistic sensitivity analyses were executed. RESULTS: The results indicated that 1-year post-LSG, patients achieved an average total weight loss (TWL) of (32.7 ± 7.3)% and an excess weight loss (EWL) of (97.8 ± 23.1)%. The ICER for LSG compared to no surgery over a lifetime was $4,327/QALY, significantly below the willingness-to-pay (WTP) threshold for Chinese patients with severe and complex obesity. From a lifetime perspective, LSG proved to be cost-effective for all sex and age groups, across all BMI categories, and for both patients with and without diabetes. Notably, it was more cost-effective for younger patients, patients with higher BMI, and patients with diabetes. CONCLUSIONS: LSG is a highly cost-effective intervention for managing obesity in Chinese patients, delivering substantial benefits in terms of HRQoL improvement at a low cost. Its cost-effectiveness is particularly pronounced among younger individuals, those with higher BMI, and patients with diabetes.


Asunto(s)
Análisis Costo-Beneficio , Gastrectomía , Laparoscopía , Obesidad Mórbida , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Humanos , Masculino , Femenino , Estudios Retrospectivos , Laparoscopía/economía , China , Adulto , Obesidad Mórbida/cirugía , Obesidad Mórbida/economía , Persona de Mediana Edad , Gastrectomía/economía , Pérdida de Peso , Cirugía Bariátrica/economía , Cirugía Bariátrica/métodos , Resultado del Tratamiento , Pueblos del Este de Asia
10.
Heliyon ; 10(17): e37592, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39290276

RESUMEN

Metabolic enzymes play significant roles in tumor growth via nonmetabolic biological processes. However, more research is needed to understand their roles in immune modulation. This study revealed that 3-hydroxysteroid dehydrogenase (NSDHL) expression was elevated in cholangiocarcinoma. In vitro experiments demonstrated that NSDHL had no effect on the growth or invasion of cholangiocarcinoma cells in an artificial laboratory environment. However, NSDHL overexpression strongly enhanced the promotion of AKT/YAP-driven cholangiocarcinoma. NSDHL bound to STING and facilitated its degradation via ubiquitination. This inhibited the cyclic-GMP-AMP-synthase-STING signaling pathway and reduced the synthesis of IFNß. A study revealed an inverse relationship between the expression of NSDHL and the infiltration of NK cells, activated CD4+ T cells, and neutrophils in individuals who were diagnosed with cholangiocarcinoma. This study elucidates the role of NSDHL, in addition to its established metabolic functions, NSDHL regulates the cyclic-GMP-AMP-synthase signaling pathway. By exploring this interplay, this research enriches our understanding of the functions of NSDHL in terms of cellular dynamics, offering novel insights into the modulation of crucial biological pathways.

11.
Rom J Morphol Embryol ; 65(1): 107-112, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38527990

RESUMEN

Pulmonary nodules are a common complication in solid organ transplant recipients, and may have various underlying causes, with Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) being one of them. Given the rarity of this entity, we describe the diagnosis and therapeutic interventions for post-transplant EBV-SMT in two individuals. Both cases involved female patients who were diagnosed with multiple pulmonary nodules 60 months and 116 months, respectively, after receiving living-related kidney transplantation. Pathological examination revealed a spindle cell tumor, with immunophenotype and EBV in situ hybridization supporting the diagnosis of EBV-SMT. After diagnosis, these two patients underwent intervention by decreasing their intake of immunosuppressants. As of the latest follow-up, the patients' lesion size remained stable, and their overall condition was favorable. We also reviewed literature about the morphological and molecular pathological features of EBV-SMT and highlighted the diagnosis and differential diagnosis of pulmonary spindle cell lesions especially in the setting of immunosuppression.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Trasplante de Riñón , Tumor de Músculo Liso , Femenino , Humanos , Diagnóstico Diferencial , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/patología , Herpesvirus Humano 4/genética , Trasplante de Riñón/efectos adversos , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/etiología , Tumor de Músculo Liso/patología
12.
J Hematol Oncol ; 17(1): 17, 2024 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-38589926

RESUMEN

Evidence from Europe shows that perioperative chemotherapy may be beneficial for the treatment of locally advanced gastric cancer, but reliable and robust data is lacking. To rectify this, the phase 3 RESONANCE trial investigated the efficacy and safety of S-1 plus oxaliplatin (SOX) as a perioperative chemotherapy regimen for gastric cancer. This randomized, open-label trial enrolled patients from 19 medical centers with stage II/III resectable gastric cancer who were centrally randomly assigned to either perioperative chemotherapy (PC) arm or adjuvant chemotherapy (AC) arm. Patients in the PC arm received two to four cycles of SOX followed by surgery and four to six cycles of SOX. Patients in the AC arm received upfront surgery and eight cycles of SOX. 386 patients in each group were enrolled and 756 (382 in PC and 374 in AC) were included in the mITT population. The three-year DFS rate was 61.7% in the PC arm and 53.8% in the AC arm (log-rank p = 0.019). The R0 resection rate in the PC arm was significantly higher than that in the AC arm (94.9% vs. 83.7%, p < 0.0001). There was no difference between two arms in surgical outcomes or postoperative complications. Safety-related data were like the known safety profile. In conclusion, from a clinical perspective, this trial indicated a trend towards higher three-year disease-free survival rate with perioperative SOX in stage II/III resectable gastric cancer with well-tolerated toxicity compared to adjuvant SOX, which might provide a theoretical basis for applying perioperative SOX in advanced gastric cancer patients. (ClinicalTrials.gov NCT01583361).


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Oxaliplatino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Terapia Neoadyuvante
13.
Zhonghua Yi Xue Za Zhi ; 93(34): 2739-41, 2013 Sep 10.
Artículo en Zh | MEDLINE | ID: mdl-24360111

RESUMEN

OBJECTIVE: To explore the effects of gender on treatment strategies for elderly patients with acute coronary syndrome (ACS). METHODS: March 2009 to March 2012, consecutive 619 aged ACS patients undergoing coronary angiography (CA) were screened at our hospital. There were 273 females and 346 males. Risk factors, ACS diagnosis, CA results, treatments and prognosis were compared between female and male groups. RESULTS: The risk factors of body mass index, stroke history, smoking history, hemoglobin (Hb), serum cholesterol (TC), low density lipoprotein (LDL-C) and blood uric acid (UA) levels were significantly lower in female group than those in male group (P < 0.05). The morbidity of diabetes in female group was obviously higher than that in male group (27.8% vs 18.5%, P < 0.05). The prevalence of myocardial infarction history, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) history in male group were significantly greater than that in female group (48.0% vs 39.9%, P < 0.05; 30.6% vs 22.3%, P < 0.05; 19.9% vs 10.3%, P < 0.01). The rate of combined multiple risk factors (3 or higher) increased significantly in female group (41.8% vs 29.8%, P < 0.05). The incidence of unstable angina pectoris (UAP) and non-ST segment elevation myocardial infarction (NSTEMI) in female group was greater, but there was no statistical significance. The rate of 3-vessel and calcification lesions in female group was significantly elevated compared with male group (36.26% vs 28.61%, P < 0.05). Regarding the choice of treatment strategy, conservative treatment was common in females, but there was no statistical significance between them. PCI, emergency PCI and selective CABG operation were performed more frequently in female group compared with male group (26.0% vs 14.2%, P < 0.01; 14.7% vs 6.6%, P < 0.01; 19.1% vs 7.7%, P < 0.01). The prognosis had no statistical significance between two groups. CONCLUSION: The treatment strategies have certain limitations for female ACS patients. And an more aggressive treatment should be offered to improve the prognosis.


Asunto(s)
Síndrome Coronario Agudo/terapia , Factores Sexuales , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Pronóstico , Factores de Riesgo , Resultado del Tratamiento
14.
Front Pharmacol ; 14: 1267186, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908977

RESUMEN

Introduction: The 5-year survival of gastric cancer (GC) patients with advanced stage remains poor. Some evidence has indicated that tryptophan metabolism may induce cancer progression through immunosuppressive responses and promote the malignancy of cancer cells. The role of tryptophan and its metabolism should be explored for an in-depth understanding of molecular mechanisms during GC development. Material and methods: We utilized the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset to screen tryptophan metabolism-associated genes via single sample gene set enrichment analysis (ssGSEA) and correlation analysis. Consensus clustering analysis was employed to construct different molecular subtypes. Most common differentially expressed genes (DEGs) were determined from the molecular subtypes. Univariate cox analysis as well as lasso were performed to establish a tryptophan metabolism-associated gene signature. Gene Set Enrichment Analysis (GSEA) was utilized to evaluate signaling pathways. ESTIMATE, ssGSEA, and TIDE were used for the evaluation of the gastric tumor microenvironment. Results: Two tryptophan metabolism-associated gene molecular subtypes were constructed. Compared to the C2 subtype, the C1 subtype showed better prognosis with increased CD4 positive memory T cells as well as activated dendritic cells (DCs) infiltration and suppressed M2-phenotype macrophages inside the tumor microenvironment. The immune checkpoint was downregulated in the C1 subtype. A total of eight key genes, EFNA3, GPX3, RGS2, CXCR4, SGCE, ADH4, CST2, and GPC3, were screened for the establishment of a prognostic risk model. Conclusion: This study concluded that the tryptophan metabolism-associated genes can be applied in GC prognostic prediction. The risk model established in the current study was highly accurate in GC survival prediction.

15.
Stem Cells Int ; 2023: 8427767, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37274025

RESUMEN

Necroptosis, a kind of programmed necrotic cell apoptosis, is the gatekeeper for the host to defend against the invasion of pathogens. It helps to regulate different biological processes regarding human cancer. Nevertheless, studies that determine the impact of death on triple-negative breast cancer (TNBC) are scarce. Therefore, this paper has comprehensively examined the expression as well as clinical significance of necroptosis in TNBC. ConsensusClusterPlus was used to establish a stable molecular classification that used the expression regarding the necroptosis-linked genes. The clinical and immune characteristics of different subclasses were evaluated. Then, the weighted gene coexpression network analysis (WGCNA) assisted in determining key modules, and we selected the genes exhibiting obvious association with necroptosis prognosis through the relationship with prognosis. The univariate Cox regression analysis together with least absolute shrinkage and selection operator (LASSO) techniques served for the construction of the necroptosis-related prognostic risk score (NPRS) model, and the pathway characteristics of NPRS model grouping were further studied. Finally, the NPRS, taking into account the clinicopathological features, used the decision tree model for enhancing the prognostic model as well as the survival prediction. First, two stable molecular subtypes with different prognosis and immune characteristics were identified using necroptosis marker genes. Then, the key modules were identified, and 10 genes significantly related to the prognosis of necroptosis were selected. Then, the clinical prognostic model of NPRS was developed considering the prognosis-linked necroptosis genes. Finally, the NPRS model, taking into account the clinicopathological features, adopted the decision tree model for enhancing the prognostic model as well as the survival prediction. Herein, two new molecular subgroups considering necroptosis-linked genes are proposed, and an NPRS model composed of 10 genes is developed, which maybe assist in the personalized treatment and clinical treatment guidance of TNBC patients.

16.
BMC Genomics ; 13: 461, 2012 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-22953761

RESUMEN

BACKGROUND: Rice in tropical and sub-tropical areas is often subjected to cold stress at the seedling stage, resulting in poor growth and yield loss. Although japonica rice is generally more cold tolerant (CT) than indica rice, there are several favorable alleles for CT exist in indica that can be used to enhance CT in rice with a japonica background. Genome-wide gene expression profiling is an efficient way to decipher the molecular genetic mechanisms of CT enhancement and to provide valuable information for CT improvement in rice molecular breeding. In this study, the transcriptome of the CT introgression line (IL) K354 and its recurrent parent C418 under cold stress were comparatively analyzed to explore the possible CT enhancement mechanisms of K354. RESULTS: A total of 3184 differentially expressed genes (DEGs), including 195 transcription factors, were identified in both lines under cold stress. About half of these DEGs were commonly regulated and involved in major cold responsive pathways associated with OsDREB1 and OsMyb4 regulons. K354-specific cold-induced genes were functionally related to stimulus response, cellular cell wall organization, and microtubule-based movement processes that may contribute to increase CT. A set of genes encoding membrane fluidity and defensive proteins were highly enriched only in K354, suggesting that they contribute to the inherent CT of K354. Candidate gene prediction based on introgressed regions in K354 revealed genotype-dependent CT enhancement mechanisms, associated with Sir2, OsFAD7, OsWAK112d, and programmed cell death (PCD) related genes, present in CT IL K354 but absent in its recurrent parent C418. In K354, a number of DEGs were co-localized onto introgressed segments associated with CT QTLs, providing a basis for gene cloning and elucidation of molecular mechanisms responsible for CT in rice. CONCLUSIONS: Genome-wide gene expression analysis revealed that genotype-specific cold induced genes and genes with higher basal expression in the CT genotype contribute jointly to CT improvement. The molecular genetic pathways of cold stress tolerance uncovered in this study, as well as the DEGs co-localized with CT-related QTLs, will serve as useful resources for further functional dissection of the molecular mechanisms of cold stress response in rice.


Asunto(s)
Alelos , Frío , Perfilación de la Expresión Génica , Genómica , Oryza/genética , Oryza/fisiología , Plantones/fisiología , Genoma de Planta/genética , Genotipo , Hibridación Genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Plantones/genética , Estrés Fisiológico/genética , Factores de Tiempo
17.
Genome ; 55(1): 45-55, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22181322

RESUMEN

Effect of genetic background on detection of quantitative trait locus (QTL) governing salinity tolerance (ST) was studied using two sets of reciprocal introgression lines (ILs) derived from a cross between a moderately salinity tolerant japonica variety, Xiushui09 from China, and a drought tolerant but salinity susceptible indica breeding line, IR2061-520-6-9 from the Philippines. Salt toxicity symptoms (SST) on leaves, days to seedling survival (DSS), and sodium and potassium uptake by shoots were measured under salinity stress of 140 mmol/L of NaCl. A total of 47 QTLs, including 26 main-effect QTLs (M-QTLs) and 21 epistatic QTLs (E-QTLs), were identified from the two sets of reciprocal ILs. Among the 26 M-QTLs, only four (15.4%) were shared in the reciprocal backgrounds while no shared E-QTLs were detected, indicating that ST QTLs, especially E-QTLs, were very specific to the genetic background. Further, 78.6% of the M-QTLs for SST and DSS identified in the reciprocal ILs were also detected in the recombinant inbred lines (RILs) from the same cross, which clearly brings out the background effect on ST QTL detection and its utilization in ST breeding. The detection of ILs with various levels of pyramiding of nonallelic M-QTL alleles for ST from Xiushui09 into IR2061-520-6-9 allowed us to further improve the ST in rice.


Asunto(s)
Oryza/genética , Sitios de Carácter Cuantitativo , Cloruro de Sodio/farmacología , China , Cruzamientos Genéticos , Ligamiento Genético , Marcadores Genéticos , Genotipo , Filipinas , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/metabolismo
18.
Chem Pharm Bull (Tokyo) ; 60(5): 670-3, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22689406

RESUMEN

Five new indole alkaloids, alocasins A-E (3-7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1-7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.


Asunto(s)
Alocasia/química , Antineoplásicos Fitogénicos/química , Alcaloides Indólicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Alcaloides Indólicos/aislamiento & purificación , Alcaloides Indólicos/toxicidad , Espectroscopía de Resonancia Magnética , Rizoma/química
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 41(1): 81-8, 2012 01.
Artículo en Zh | MEDLINE | ID: mdl-22419469

RESUMEN

OBJECTIVE: To design and construct miRNA expression vector dual-targeting on HIF-1α and survivin genes and to investigate its effects on proliferation of human pancreatic cancer cells. METHODS: The specific pre-miRNA single strand DNA oligos for HIF-1 α and survivin genes were designed and synthesized, then via annealing and ligating with pcDNA6.2-GW/EmGFP-miR plasmids in order, two kinds (eight in total) of miRNA expression vectors for HIF-1α and survivin genes were constructed. The vectors, which were most effective to knockdown target genes, were screened with real-time RT-PCR and combined by chaining technology to construct dual-targeting plasmid. The recombined dual-targeting plasmid, mono-targeting plasmids and negative plasmid were transfected into Panc-1 cells, the suppression effect on two genes was identified by real-time RT-PCR, Western blot and MTT assays. RESULTS: The miRNA expression plasmids anti-H, anti-S and anti-H+S were successfully constructed by identification of sequencing analysis, and they were able to effectively inhibit the target genes expressing. MTT assays showed that the inhibition effect of dual-targeting vector anti-H+S was higher than that of mono-targeting vectors anti-H and anti-S 72 h after transfection (P<0.05). CONCLUSION: The effective miRNA expression vector dual-targeting on HIF-1α and survivin genes has been successfully constructed. The inhibition effect on proliferation of pancreatic cancer Panc-1 cells by dual-targeting plasmid was higher than that by mono-target plasmids.


Asunto(s)
Vectores Genéticos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Proteínas Inhibidoras de la Apoptosis/genética , MicroARNs/genética , Neoplasias Pancreáticas/patología , Línea Celular Tumoral , Proliferación Celular , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Proteínas Inhibidoras de la Apoptosis/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Plásmidos/genética , Survivin , Transfección
20.
Trials ; 23(1): 189, 2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35241130

RESUMEN

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.


Asunto(s)
Electroacupuntura , Gastroparesia , Puntos de Acupuntura , Electroacupuntura/efectos adversos , Gastrectomía/efectos adversos , Gastroparesia/etiología , Gastroparesia/terapia , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
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