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1.
Brief Bioinform ; 25(4)2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38859767

RESUMEN

How to resolve the metabolic dark matter of microorganisms has long been a challenging problem in discovering active molecules. Diverse omics tools have been developed to guide the discovery and characterization of various microbial metabolites, which make it gradually possible to predict the overall metabolites for individual strains. The combinations of multi-omic analysis tools effectively compensates for the shortcomings of current studies that focus only on single omics or a broad class of metabolites. In this review, we systematically update, categorize and sort out different analysis tools for microbial metabolites prediction in the last five years to appeal for the multi-omic combination on the understanding of the metabolic nature of microbes. First, we provide the general survey on different updated prediction databases, webservers, or software that based on genomics, transcriptomics, proteomics, and metabolomics, respectively. Then, we discuss the essentiality on the integration of multi-omics data to predict metabolites of different microbial strains and communities, as well as stressing the combination of other techniques, such as systems biology methods and data-driven algorithms. Finally, we identify key challenges and trends in developing multi-omic analysis tools for more comprehensive prediction on diverse microbial metabolites that contribute to human health and disease treatment.


Asunto(s)
Metabolómica , Programas Informáticos , Metabolómica/métodos , Genómica/métodos , Proteómica/métodos , Humanos , Biología Computacional/métodos , Bacterias/metabolismo , Bacterias/genética , Bacterias/clasificación , Metaboloma , Algoritmos , Multiómica
2.
J Neurosci ; 44(26)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38664013

RESUMEN

The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7 T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.


Asunto(s)
Imagen por Resonancia Magnética , Memoria a Corto Plazo , Sustancia Gris Periacueductal , Humanos , Sustancia Gris Periacueductal/fisiología , Masculino , Femenino , Memoria a Corto Plazo/fisiología , Adulto , Imagen por Resonancia Magnética/métodos , Adulto Joven , Mapeo Encefálico
3.
J Med Virol ; 96(6): e29758, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38895781

RESUMEN

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.


Asunto(s)
Hospitales Pediátricos , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Estaciones del Año , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Masculino , Femenino , China/epidemiología , Lactante , Preescolar , Prevalencia , Hospitales Pediátricos/estadística & datos numéricos , Niño , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Recién Nacido , Nasofaringe/virología , Adolescente , Incidencia
4.
Artículo en Inglés | MEDLINE | ID: mdl-38606576

RESUMEN

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

5.
Microb Pathog ; 185: 106390, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37858633

RESUMEN

OBJECTIVES: Dental caries is a result of the ecological dysfunction of the polymicrobial community on the tooth surface, which evolves through microbial interactions. In this study, we conducted a thorough analysis of the dental plaque microbiome to comprehend its multi-microbial aetiology. MATERIALS AND METHOD: In this study, plaque was collected from healthy tooth surfaces, shallow carious teeth and deep carious teeth, and bacterial composition and abundance were assessed using 16S rRNA high-throughput sequencing. Random forest and LEfSe were used to profile various microorganisms at each stage. Additionally, we developed a molecular ecological network (MEN) based on random matrix theory (RMT) to examine microbial interactions for the first time. RESULTS: Our results reveal that Scardovia wiggsiae, Streptococcus mutans, and Propionibacterium acidifaciens may be associated with initial caries, and Propionibacterium acidifaciens differentiates between shallow and deep caries. As caries progressed, the alpha diversity index declined, indicating a decrease in microbial variety. The network topological indices such as centralization betweenness revealed that the caries network had become more complex, involving more microbial interactions. The shallow network revealed a high negative correlation ratio across nodes, indicating that microbes competed heavily. In contrast, the positive correlation ratio of deep network nodes was high, and microorganisms transitioned from a competitive to a synergistic state. CONCLUSIONS: This study suggests that microbial diversity and interactions are critical to caries progression and that future caries research should give greater consideration to the role of microbial interaction factors in caries progression.


Asunto(s)
Caries Dental , Placa Dental , Microbiota , Humanos , ARN Ribosómico 16S/genética , Streptococcus mutans , Microbiota/genética
6.
BMC Gastroenterol ; 23(1): 2, 2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36600208

RESUMEN

BACKGROUND: Emerging evidence has shown the crucial roles of pleomorphic adenoma gene (PLAG) family genes in multiple cancers. However, their functions and mechanisms in pancreatic adenocarcinoma (PAAD) remain poorly understood. METHODS: We analyzed the expression levels of PLAG family genes in both The Cancer Genome Atlas (TCGA) database and a Gene Expression Omnibus (GEO) database, and confirmed the results in our three independent cohorts of 382 PAAD tissues and 362 adjacent nontumor pancreatic tissues. Integrated analyses were carried out to explore the function, mechanism and prognostic value of the selected PLAG family gene in PAAD patients. RESULTS: By analyzing the TCGA and GEO databases, PLAGL1 was identified to be downregulated in PAAD tissues, and its decreasing levels of both mRNA and protein were verified in our three independent PAAD cohorts. PLAGL1 expression was inversely correlated with clinicopathological factors including the Ki67+ cell rate and pathologic stage. Further GSEA of the TCGA-PAAD cohort demonstrated that multiple signaling pathways implicated in cell proliferation were enriched in the lower PLAGL1 expressing PAAD group. Moreover, we demonstrated that PLAGL1 expression was obviously negatively associated with patients' overall survival outcome in both the TCGA-PAAD cohort and our verification cohorts. Additionally, through MTS and BrdU assays, we further demonstrated in vitro that PLAGL1 had the impact of preventing the proliferation of pancreatic cancer cells. CONCLUSIONS: Our present study suggested that downregulated PLAGL1 might act as a biomarker in predicts poor prognosis and one of important factors in increasing cell proliferation in PAAD. This study provides us with a novel prognostic marker and therapeutic strategy for PAAD, which deserves further study.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Factores de Transcripción , Proteínas Supresoras de Tumor , Humanos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Pronóstico , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo , Neoplasias Pancreáticas
7.
HPB (Oxford) ; 24(5): 606-615, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34872867

RESUMEN

BACKGROUND: Pancreatic fistula is a life-threatening complication of pancreaticoduodenectomy. Omega-like duct-to-mucosa pancreatojejunostomy is a novel technique which helps reduce the risk of fistulation. This study aimed to compare early postoperative outcomes of omega-like and conventional pancreatojejunostomy. METHODS: A retrospective single-centre cohort study comparing outcomes of adult patients who underwent open pancreatoduodenectomy with conventional (CDMP) or omega-like duct-to-mucosa pancreatojejunostomy (ODMP) between 1 January 2015 and 31 December 2019. The primary outcome measure was the pancreatic fistula rate. RESULTS: 440 patients were included in this study of whom 233 underwent CDMP and 207 ODMP. The rate of clinically relevant pancreatic fistula (grade B/C) was significantly higher after CDMP than ODMP (18.5% vs. 10.6%, P = 0.021). 153 patients in CDMP group and 99 patients in ODMP group developed one or more complications (65.7% vs. 47.8%, P = 0.004). The average hospitalization expenses were numerically decreased in ODMP group, although this was not statistically significant (120,000 ± 42,000 [Chinese Yuan] vs. 100,000 ± 40,000 [Chinese Yuan] or 18,581 ± 6503 [United States Dollar] vs. 15,484 ± 6194 [United States Dollar], P = 0.402). CONCLUSION: ODMP may reduce the incidence of pancreatic fistula and other early postoperative complications after pancreatoduodenectomy.


Asunto(s)
Pancreaticoduodenectomía , Pancreatoyeyunostomía , Adulto , Estudios de Cohortes , Humanos , Membrana Mucosa , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/efectos adversos , Pancreaticoduodenectomía/métodos , Pancreatoyeyunostomía/efectos adversos , Pancreatoyeyunostomía/métodos , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos
8.
Mol Cancer ; 20(1): 19, 2021 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-33468140

RESUMEN

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. METHOD: Bioinformatics methods were applied to screen for circRNAs differentially expressed in RCC. Analysis of online circRNAs microarray datasets and our own patient cohort indicated that circSDHC (hsa_circ_0015004) had a potential oncogenic role in RCC. Subsequently, circSDHC expression was measured in RCC tissues and cell lines by qPCR assay, and the prognostic value of circSDHC evaluated. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of circSDHC on RCC proliferation and metastasis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between circSDHC, miR-127-3p and its target genes. RESULTS: Clinically, high circSDHC expression was correlated with advanced TNM stage and poor survival in patients with RCC. Further, circSDHC promoted tumor cell proliferation and invasion, both in vivo and in vitro. Analysis of the mechanism underlying the effects of circSDHC in RCC demonstrated that it binds competitively to miR-127-3p and prevents its suppression of a downstream gene, CDKN3, and the E2F1 pathway, thereby leading to RCC malignant progression. Furthermore, knockdown of circSDHC caused decreased CDKN3 expression and E2F1 pathway inhibition, which could be rescued by treatment with an miR-127-3p inhibitor. CONCLUSION: Our data indicates, for the first time, an essential role for the circSDHC/miR-127-3p/CDKN3/E2F1 axis in RCC progression. Thus, circSDHC has potential to be a new therapeutic target in patients with RCC.


Asunto(s)
Carcinoma de Células Renales/genética , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina/metabolismo , Fosfatasas de Especificidad Dual/metabolismo , Factor de Transcripción E2F1/metabolismo , Neoplasias Renales/genética , MicroARNs/metabolismo , ARN Circular/metabolismo , Transducción de Señal , Animales , Secuencia de Bases , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales , ARN Circular/genética
9.
Clin Endocrinol (Oxf) ; 92(4): 312-322, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-31943312

RESUMEN

BACKGROUND: Pancreatic neuroendocrine neoplasms (pNENs) are a group of endocrine tumours arising in the pancreas and deemed to be the most common neuroendocrine tumours. The pathogenesis of pNENs remains unknown. Long noncoding RNAs (lncRNAs) are aberrantly expressed in cancers. The functional roles of lncRNAs and lncRNA-mRNA expression profiles in pNENs are undefined. The aim of this study was to identify the lncRNA and mRNA expression profiles and explore the lncRNA-mRNA co-expression networks associated with the pNENs carcinogenesis. METHOD: Differentially expressed lncRNA and mRNA in pNENs tissues from adjacent tissues were detected using human lncRNA microarray V3.0 containing 30 586 lncRNA and 26 109 coding transcripts. Probable functions for lncRNAs and mRNAs were predicted according to lncRNA-mRNA network. RESULTS: The microarray identified 2080 lncRNAs and 1771 mRNAs in pNENs tumours differentially expressed compared with the adjacent tissues. The GO terms and KEGG pathway annotation data indicated that cell projection morphogenesis, cell adhesion molecules pathway, PI3K-AKT signalling pathway, focal adhesion pathway, neuroactive ligand-receptor interaction pathways and Ras signalling pathways were significantly associated with the pNENs tumorigenesis. Co-expression network analysis revealed the differential interactions between lncRNAs and mRNAs in pNENs tumours and adjacent tissues. The genes, situated at the important nodes of the co-expression network, include ICOSLG, ENST00000512077, FGF8 and ENST00000511918. CONCLUSIONS: There were significant differences in lncRNA and mRNA expression between pNEN tumours and adjacent tissues, and these differences were associated with tumorigenesis through multiple biological processes and signalling pathways. These results provided important insights regarding lncRNA in pNENs pathogenesis and provide potential therapeutic targets.


Asunto(s)
Tumores Neuroendocrinos , ARN Largo no Codificante , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Tumores Neuroendocrinos/genética , Fosfatidilinositol 3-Quinasas , ARN Largo no Codificante/genética , ARN Mensajero/genética , Transducción de Señal/genética
10.
Mol Carcinog ; 57(10): 1358-1370, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30295962

RESUMEN

Hepatocellular Carcinoma (HCC) is a malignant tumor with high rate of relapse and metastasis. Ethanol is a well-known risk factor for HCC; it promotes the progression and aggressiveness of HCC. However, the underlying mechanism remains unclear. In clinic studies, we showed that alcohol consumption is positively correlated with TNM stage and vessel invasion; HCC patients with chronic drinking history had faster progression rate and poorer prognosis compared to non-drinkers. In experimental models, ethanol exposure enhanced the metastasis, and invasion of HCC cells. Ethanol exposure increased cancer stem cells (CSC) population and enhanced stemness of HCC cells in vitro and in vivo. Mechanically, we found that ethanol exposure induced epithelial to mesenchymal transition (EMT) through activating Wnt/ß-catenin signaling pathway in HCC cells. We further demonstrated that ß-catenin siRNA or salinomycin (an inhibitor of Wnt/ß-catenin pathway) partially rescued ethanol-induced EMT. In conclusion, this study suggested that ethanol exposure promotes the metastasis and stemness of HCC cells by inducing EMT.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Etanol/farmacología , Neoplasias Hepáticas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Consumo de Bebidas Alcohólicas , Animales , Antiinfecciosos Locales/farmacología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/patología , Masculino , Ratones Endogámicos C57BL , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Experimentales/genética , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Trasplante Heterólogo
12.
Hepatobiliary Pancreat Dis Int ; 16(5): 537-544, 2017 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-28992887

RESUMEN

BACKGROUND: Post-pancreaticoduodenectomy pancreatic fistula associated hemorrhage (PPFH) is one of the leading lethal complications. Our study was to analyze the risk factors and managements of hemorrhage associated with pancreatic fistula after pancreaticoduodenectomy, and to evaluate treatment options. METHOD: We analyzed 445 patients who underwent pancreaticoduodenectomy or pylorus-preserving pancreaticoduodenectomy and evaluated the relevance between clinical data and PPFH. RESULTS: The incidence of postoperative pancreatic fistula (POPF) was 27.42% (122/445), and the incidence of PPFH was 4.49% (20/445). Among the 20 patients with PPFH, 7 died and 13 were cured. Interventional angiographic therapy was performed for 10 patients and 5 were successfully treated. Relaparotomy was performed for 5 patients and 2 were successfully cured. Univariate logistic regression analysis indicated that several risk factors were related to PPFH: the nature of tumor (carcinoid/low-grade or high-grade malignancy), preoperative day 1 serum prealbumin, preoperative day 1 total bilirubin (TBIL), operative time, blood loss in the operation, operative method (vascular resection and revascularization), postoperative day 3 TBIL, biliary fistula, and the grade of POPF. The multivariate stepwise logistic regression analysis demonstrated that the nature of tumor and the grade of POPF were independently risk factors of PPFH. Receiver operating characteristic curve indicated that preoperative day 1 serum prealbumin level <173 mg/L and postoperative day 3 TBIL level ≥168 µmol/L were the risk factors of PPFH. CONCLUSIONS: The risk of PPFH was found to be increased with high potential malignancy and high grade of POPF. Angiography-embolization is one of the major and effective therapies for PPFH. Extraluminal-intraluminal PPFH is more serious and needs more aggressive treatments.


Asunto(s)
Hemorragia/etiología , Fístula Pancreática/complicaciones , Pancreaticoduodenectomía/efectos adversos , Adulto , Anciano , Embolización Terapéutica , Femenino , Hemorragia/terapia , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prealbúmina/análisis , Factores de Riesgo
13.
Langmuir ; 32(51): 13675-13686, 2016 12 27.
Artículo en Inglés | MEDLINE | ID: mdl-27959568

RESUMEN

Mussel-inspired polydopamine (PDA) particles with the size of ∼270 nm are used as a support of palladium (Pd) nanoparticles (NPs) for catalyst preparation. The surface morphology of the PDA particle has been modified via corrosion of CF3COOH. Surface chemistry of the obtained PDA particle has been engineered by the formation of a carboxylic acid-terminated alkanethiol monolayer. The obtained self-assembled monolayer-modified PDA (SAM-PDA) particles are used to load Pd NPs by simply adding H2PdCl4 solution to a suspension of SAM-PDA particles at room temperature. Transmission electron microscopy, energy-dispersive X-ray mapping, dynamic light scattering, X-ray diffraction, X-ray photoelectron spectroscopy, UV-vis, and Fourier transform infrared are used to characterize the catalyst and to investigate the process. Uniform Pd NPs (2-3 nm) have been well-dispersed on the SAM-PDA particles via controllable surface engineering. Surface charges and interactions with a metal ion are regulated by the monolayer of carboxylic acids. The surface chemistry of PDA particles has been finely engineered for efficient loading of noble metal NPs. The obtained Pd/SAM-PDA catalyst has shown greatly increased activity and good reusability compared with Pd/PDA in the reduction of 4-nitrophenol (4-NP) by sodium borohydride or H2. The kinetic data of 4-NP hydrogenation catalyzed by Pd/SAM-PDA are fitted to a Langmuir-Hinshelwood (L-H) model, and the calculated apparent activation energy of this process is 40.77 kJ mol-1.

14.
Mol Cancer ; 14: 190, 2015 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-26545365

RESUMEN

BACKGROUND: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms. METHODS: We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting. RESULTS: miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways. CONCLUSION: miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , MicroARNs/fisiología , Proteínas Nucleares/metabolismo , Animales , Apoptosis/genética , Apoptosis/fisiología , Ciclo Celular/genética , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Movimiento Celular/fisiología , Proliferación Celular/genética , Proliferación Celular/fisiología , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/fisiología , Células HEK293 , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Proteínas Nucleares/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
15.
Front Oncol ; 14: 1351839, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590657

RESUMEN

Purpose: Alcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38ß, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer. Methods: Female adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined. Results: Alcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population. Conclusion: PFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

16.
Comput Struct Biotechnol J ; 23: 1990-2000, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38765607

RESUMEN

Microbial communities are shaped by the complex interactions among organisms and the environment. Genome-scale metabolic models (GEMs) can provide deeper insights into the complexity and ecological properties of various microbial communities, revealing their intricate interactions. Many researchers have modified GEMs for the microbial communities based on specific needs. Thus, GEMs need to be comprehensively summarized to better understand the trends in their development. In this review, we summarized the key developments in deciphering and designing microbial communities using different GEMs. A timeline of selected highlights in GEMs indicated that this area is evolving from the single-strain level to the microbial community level. Then, we outlined a framework for constructing GEMs of microbial communities. We also summarized the models and resources of static and dynamic community-level GEMs. We focused on the role of external environmental and intracellular resources in shaping the assembly of microbial communities. Finally, we discussed the key challenges and future directions of GEMs, focusing on the integration of GEMs with quorum sensing mechanisms, microbial ecology interactions, machine learning algorithms, and automatic modeling, all of which contribute to consortia-based applications in different fields.

17.
J Clin Virol ; 172: 105679, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38677156

RESUMEN

OBJECTIVE: Norovirus (NoV) is an important human pathogen that can cause severe gastroenteritis in vulnerable populations. This study aimed to analyze the epidemiological and genetic characteristics of 2021-2023 NoV in Hangzhou, China. METHODS: This study enrolled patients aged 0-18 years who underwent NoV RNA detection in the hospital between January 2021 and October 2023 and analyzed the epidemiological characteristics of NoV. Polymerase chain reaction (PCR) was used to detect NoV RNA. Subtype classification and whole-genome sequencing were performed. RESULTS: There was a high prevalence of NoV infection in 2023, with NoV-positive samples accounting for 63.10 % of the total number of positive samples collected during the three-year period. The prevalence was abnormally high in summer, and the number of positive samples accounted for 48.20 % of the total positive samples for the whole year, which was much greater than the level in the same period in previous years (2023, 48.20% vs 2021, 13.66% vs 2022, 15.21 %). The GⅡ.4 subtype played a leading role, followed by increased mixed infection with GⅠ.5 and GⅡ.4. Whole-genome sequencing results suggested that GII.P16-GⅡ.4 had R297H and D372N key locus mutations. The evolutionary rate was 4.29 × 10-3 for the RdRp gene and 4.84 × 10-3 for the VP1 gene. The RdRp gene and VP1 gene of NoV GII.P16-GⅡ.4 have undergone rapid population evolution during the COVID-19 epidemic. CONCLUSION: In the summer of 2023, an abnormally high incidence of NoV appeared in Hangzhou, China. The major epidemic strain GII.P16-GⅡ.4 showed a certain range of gene mutations and a fast evolutionary rate.


Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Filogenia , ARN Viral , Secuenciación Completa del Genoma , Humanos , China/epidemiología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Norovirus/genética , Norovirus/clasificación , Norovirus/aislamiento & purificación , Lactante , Preescolar , Niño , Adolescente , Gastroenteritis/epidemiología , Gastroenteritis/virología , Recién Nacido , Masculino , Femenino , ARN Viral/genética , Prevalencia , Genotipo , Genoma Viral , Estaciones del Año , Heces/virología
18.
Medicine (Baltimore) ; 103(11): e37527, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489689

RESUMEN

The purpose of this study was to investigate the marital adjustment of patients with Crohn's disease and their spouses, and to analyze its influencing factors. It lays the investigation foundation for the follow-up binary study of Crohn's disease patients and their spouses. Using convenience sampling, 177 pairs of patients and their spouses from a tertiary hospital in Nanjing, China were selected. With face-to-face electronic questionnaires to survey the patient and spouse, the contents include the Lock-Wollance Marriage Adjustment Test, Subjective Well-Being Scale for Chinese Citizens, Couple Support Questionnaire, and Distress Self-Disclosure Scale. The marital adjustment score of patients was (99.03 ±â€…24.25), and the marital adjustment score of spouses was (99.61 ±â€…25.39). The proportions of patients with marital disorders and their spouses with marital disorders were 52.5% and 46.9%, respectively. Multiple linear regression showed that the spouse's age, family monthly income, time of diagnosis of Crohn's, distress self-disclosure, marital support, and subjective well-being were important factors influencing the marital adjustment of patients. Self-disclosure of spousal distress, marital support, age, and subjective well-being were important factors that influenced spouses' marital adjustment. Most couples with Crohn's disease have marital disorders, and their marital adjustment affects each other. However, the assessment results of one partner should not be limited to replacing those of the couple. In clinical practice, patient age, monthly family income, self-disclosure of distress, marital support, and subjective well-being should be considered. Spouses should be encouraged to participate in patient care and patient-spouse interventions should be implemented as a whole to improve marital stability.


Asunto(s)
Enfermedad de Crohn , Esposos , Humanos , Matrimonio , Estudios de Seguimiento , Proyectos de Investigación , Adaptación Psicológica
19.
Front Public Health ; 12: 1336077, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38389947

RESUMEN

Background: The use of nonpharmaceutical interventions (NPIs) during severe acute respiratory syndrome 2019 (COVID-19) outbreaks may influence the spread of influenza viruses. This study aimed to evaluate the impact of NPIs against SARS-CoV-2 on the epidemiological features of the influenza season in China. Methods: We conducted a retrospective observational study analyzing influenza monitoring data obtained from the China National Influenza Center between 2011 and 2023. We compared the changes in influenza-positive patients in the pre-COVID-19 epidemic, during the COVID-19 epidemic, and post-COVID-19 epidemic phases to evaluate the effect of NPIs on influenza virus transmission. Results: NPIs targeting COVID-19 significantly suppressed influenza activity in China from 2019 to 2022. In the seventh week after the implementation of the NPIs, the number of influenza-positive patients decreased by 97.46% in southern regions of China and 90.31% in northern regions of China. However, the lifting of these policies in December 2022 led to an unprecedented surge in influenza-positive cases in autumn and winter from 2022 to 2023. The percentage of positive influenza cases increased by 206.41% (p < 0.001), with high positivity rates reported in both the northern and southern regions of China. Conclusion: Our findings suggest that NPIs against SARS-CoV-2 are effective at controlling influenza epidemics but may compromise individuals' immunity to the virus.


Asunto(s)
COVID-19 , Gripe Humana , Orthomyxoviridae , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/transmisión , Brotes de Enfermedades , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Gripe Humana/transmisión , SARS-CoV-2 , China , Estudios Retrospectivos , Control de Enfermedades Transmisibles/métodos
20.
Sci Total Environ ; 912: 169141, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38072258

RESUMEN

Biomass-derived carbon materials have the characteristics of a wide range of precursor sources, controllable carbon nano-dimension, large specific surface area and abundant heteroatoms doping. At present, biomass-derived carbon materials have been widely used in electrochemical energy storage devices, especially the research and development of biomass-derived carbon materials for supercapacitors has become mature and in-depth. Therefore, it is of importance to summarize the advanced technologies and strategies for optimizing biomass-derived carbon materials for supercapacitors, which will effectively promote the further development of high-performance supercapacitors. In this review, the recent research progress of biomass-derived carbon materials is provided in detail, including the selection of biomass precursors, the design of carbon nano-dimension and the theory of heteroatom doping. Besides, the preparation methods of biomass-derived carbon materials and the related processes of optimizing the electrochemical performance are also summarized. This review ends with the perspectives for future research directions and challenges in the field of biomass-derived carbon materials for electrochemical applications. This review aims to provide helpful reference information for the nano-dimensional design and electrochemical performance optimization of biomass-derived carbon materials for the practical application of supercapacitors.

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