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Melioidosis is a zoonotic disease, with its outbreaks being rare and indicative of an unusual concurrence of extreme climate and natural environmental factors. An outbreak of melioidosis cases emerged in Hainan following Typhoon "Dianmu" from October to December 2021, presenting an opportunity to identify the environmental sources of infection for these cases due to its nature as a well-defined point-source cluster. To investigate the relationship between the occurrence of these melioidosis cases and the environment, we extracted the entire genome of 25 clinical strains and conducted MLST typing, followed by whole genome sequencing and analysis of molecular genetic information for four ST46 genotypes from these strains. Phylogenetic and evolutionary relationships between Hainan sequence types (STs) and those found in other endemic regions were analyzed using IslandPath-DIMO, PHASTER, e-BURST, PHYLOViZ, and the maximum likelihood method. Notably, a total of 25 clinical strains were identified, encompassing 12 STs (ST46, ST1105, ST1991, ST30, ST1992, ST50, ST164, ST55, ST70, ST1993, ST1545, and ST58), with ST1991, ST1992, and ST1993 being newly discovered subtypes. PHYLOViZ clustering analysis divided the strains into two groups (A and B), both closely related to the Asian region. Phylogenetic tree analysis further revealed that most of the strains in this study were closely related to those found in Australia and Thailand. Analysis of patient information and visits to their residences suggested that contaminated water sources might be the primary source of infection during this outbreak. Our findings underscore that extreme weather events, such as typhoons, significantly increase the infection rate of B. pseudomallei, along with its genetic diversity, necessitating additional prevention strategies to control these B. pseudomallei infections.
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In a clinical isolate of Burkholderia pseudomallei from Hainan, the association between the emergence of ceftazidime resistance and a novel PenA P174L allele was identified for the first time, providing an understanding of one mechanism by which ceftazidime resistance arises in B. pseudomallei.
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Histone lysine lactylation (Kla) has emerged as a distinct epigenetic modification that differs markedly from established acylation modifications through the unique addition of a lactyl group to a lysine residue. Such modifications not only alter nucleosome structure but also significantly impact chromatin dynamics and gene expression, thus playing a crucial role in cellular metabolism, inflammatory responses, and embryonic development. The association of histone Kla with various metabolic processes, particularly glycolysis and glutamine metabolism, underscores its pivotal role in metabolic reprogramming, including in cancerous tissues, where it contributes to tumorigenesis, immune evasion, and angiogenesis. In addition, histone Kla is involved in the pathogenesis of various diseases, particularly several cancers and neurodegenerative diseases. The identification of histone Kla opens new avenues for therapeutic interventions targeting specific Kla sites. In this review, we summarize the differences between histone Kla modifications and other acylation modifications, discuss the mechanisms and roles of histone Kla in disease, and conclude by describing existing drugs and potential targets. This study provides new insights into the mechanisms linking histone Kla to diseases and into the discovery of new drugs and targets.
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Histonas , Animales , Humanos , Epigénesis Genética/fisiología , Histonas/metabolismo , Lisina/metabolismo , Lisina/química , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Procesamiento Proteico-Postraduccional/fisiología , Código de HistonasRESUMEN
TssJ-3 is an outer-membrane lipoprotein and is one of the key components of the type VI secretion system in Burkholderia pseudomallei. TssJ translocates effector proteins to target cells to induce innate immune response in the host. However, the tssJ gene has not been identified in B. pseudomallei and its function in this bacterium has not yet been characterized. tssJ-3 knockout and tssJ-3-complemented B. pseudomallei strains were constructed to determine the effects of tssJ-3 on bacterial growth, biofilm formation, flagellum synthesis, motility, host cell infection, and gene expression in B. pseudomallei. We found that the ΔtssJ-3 mutant strain of B. pseudomallei showed significantly suppressed biofilm formation, flagellum synthesis, bacterial growth, motility, and bacterial invasion into host cells (A549 cells). Furthermore, the ΔtssJ-3 mutation downregulated multiple key genes, including biofilm and flagellum-related genes in B. pseudomallei and induced interleukin-8 gene expression in host cells. These results suggest that tssJ-3, an important gene controlling TssJ-3 protein expression, has regulatory effects on biofilm formation and flagellum synthesis in B. pseudomallei. In addition, B. pseudomallei-derived tssJ-3 contributes to cell infiltration and intracellular replication. This study provides a molecular basis of tssJ-3 for developing therapeutic strategies against B. pseudomallei infections.
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Burkholderia pseudomallei , Melioidosis , Sistemas de Secreción Tipo VI , Humanos , Burkholderia pseudomallei/genética , Virulencia/genética , Melioidosis/microbiología , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismoRESUMEN
The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan-cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan-cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour-infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.
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Adenocarcinoma , Neoplasias del Colon , Humanos , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Proliferación Celular/genética , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/genética , Bases de Datos Factuales , Redes Reguladoras de Genes , Inestabilidad de Microsatélites , Microambiente Tumoral/genéticaRESUMEN
BACKGROUND: Lumbar spinal stenosis (LSS) is a prevalent and disabling cause of low back and leg pain in elderly people and nerve root sedimentation sign (NRSS) has been demonstrated to have high sensitivity and specificity in diagnosing LSS in selected patients. The purpose of this study was to investigate the diagnosis of LSS and the predictive value of NRSS. METHODS: The clinical and imaging data of 176 patients diagnosed with LSS and 156 patients with non-specific low back pain (LBP) were analyzed retrospectively. Transverse magnetic resonance images (MRI) of the narrowest spinal canal in all patients were acquired and graded by two experienced doctors using the Braz classification, Schizas classification and Chen Jia classification. Receiver operating curve (ROC) was used to compare the diagnostic efficacy of the three classifications. Univariate and multivariate logistic regression models were established to predict the surgical indications of LSS patients. RESULT: The diagnostic efficacy of Schizas classification (AUC:0.943; 95%CI:0.918,0.969) and Chen Jia classification (AUC:0.942; 95%CI:0.918,0.966) was significantly higher than that of Braz classification (AUC:0.853; 95%CI:0.808,0.898). Chen Jia classification had the highest correlation with the degree of dural sac cross-sectional area (DCSA) stenosis. In the multivariate analysis of LSS surgical indications, Chen Jia classification (odds ratio [OR], 2.127; 95%CI:1.596,2.835), DCSA (OR,0.398; 95%CI:0.169,0.802) and intermittent claudication (OR,9.481; 95%CI:3.439,26.142) were associated with surgical indications. CONCLUSION: Among the three types, it is found that Chen Jia classification has better diagnostic efficacy in differentiating LSS from LBP. In addition, Chen Jia classification is simple to be implemented in clinical practice and has high clinical application value. Hence, Chen Jia classification can be used as an effective surgical treatment indicator for LSS patients.
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Estenosis Espinal , Humanos , Anciano , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Vértebras Lumbares/patología , Dolor/patología , Imagen por Resonancia Magnética/métodosRESUMEN
@#Abstract: Objective To analyze the characteristics and corresponding drug resistance of pathogenic bacterial spectrum in eight major infection sites of hospitalized patients, and to provide epidemiological data for the rational selection of antibiotics in clinical practice. Methods A total of 396 bacterial strains isolated from clinical specimens of hospitalized patients in member institutions of the Hainan Provincial Bacterial Resistance Monitoring Network from September 1, 2020, to September 30, 2022, were included in this study. Data were screened and filtered from the database of MH120 Microbial Identification and Drug Sensitivity Analysis System based on the technical scheme of the National Bacterial Drug Resistance Surveillance Network and Science and Technology Basic Resources Investigation Project research plan in 2020. The testing data were integrated, summarized, and analyzed using EXCEL and WHONET 5.6 software, and statistical analysis was conducted using SPSS 26.0 software. Results Among of 396 strains of bacteria, 78 (19.7%) were isolated from respiratory tract specimens, 74 (18.7%) from urinary tract specimens, 72 (18.2%) from blood specimens, 54 (13.6%) from abdominal cavity specimens, 48 (12.1%) from skin and soft tissue specimens 48 strains (12.1%), 30 (7.6%) from reproductive tract specimens, 22 (5.6%) from central nervous system specimens, 18 (4.5%) from digestive tract specimens. Gram-negative bacteria accounted for 69.4% of the isolates, while gram-positive bacteria accounted for 30.6%. The top five gram-negative bacteria isolated were Klebsiella pneumoniae (14.9%), Escherichia coli (14.4%), Pseudomonas aeruginosa (10.4%), Acinetobacter baumannii (5.3%), and Salmonella species (4.5%). The top five gram-positive bacteria were Staphylococcus aureus (11.1%), Streptococcus agalactis (7.8%), Enterococcus faecalis (3.0%), Enterococcus faecium (2.8%), and Streptococcus suis (1.8%). Respiratory failure and bloodstream infection were independent influencing factors of treatment response (P<0.01). The resistance rate of Escherichia coli to ampicillin was 81.4%, and the resistance rate of Staphylococcus aureus to gentamicin and levofloxacin were both below 7%. Conclusions The pathogen spectra vary with different infection sites of patients, and rational selection of antibiotics based on drug susceptibility testing is crucial to shorten the treatment time of patients and avoid the unnecessary emergence of drug-resistant strains caused by drug abuse.
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A multifunctional catalytic nanomaterial (Co-MOF@AuNP@ABEI) composed of cobalt-doped metal-organic frameworks (Co-MOF), gold nanoparticles (AuNP), and N-(4-aminobutyl)-N-(ethylisoluminol) (ABEI) is reported. Co-MOF@AuNP@ABEI exhibits high synergistic and zero-distance catalytic properties, which are beneficial to the improvement of the detection sensitivity of an electrochemiluminescent (ECL) biosensor. After coupling with the ECL system and 3D magnetic walking nanomachine amplification strategy, the Co-MOF@AuNP@ABEI can achieve an ultrasensitive ECL assay of Burkholderia pseudomallei with the limit of detection (LOD) of 60.3 aM, which is 2 and 4 orders of magnitude lower than individual ECL system without the nanomachine (4.97 fM) and individual walking nanomachine (340 fM), and superior to the pathogenic bacteria analyses in the previous report. Moreover, the LOD of the proposed ECL detection system for the determination of B. pseudomallei in serum sample was as low as 9.0 CFU mL-1. The relative standard deviations (RSD) of ECL intensity for the detection of five B. pseudomallei-spiked serum samples were 4.02%, 0.84%, 0.84%, 1.55%, and 0.21%, respectively. The recoveries of the ECL biosensor for the detection of B. pseudomallei DNA-spiked serum samples were 93.63 ~ 107.83%. Therefore, this work demonstrated that the developed multifunctional catalytic nanomaterial with synergistic and zero-distance catalytic properties can be used as excellent ECL signal reporter to improve the detection sensitivity of ECL biosensor.
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Técnicas Biosensibles , Burkholderia pseudomallei , Luminol/análogos & derivados , Nanopartículas del Metal , Estructuras Metalorgánicas , Cobalto , Técnicas Electroquímicas , Oro , Mediciones Luminiscentes , Luminol/químicaRESUMEN
BACKGROUND: Burkholderia pseudomallei is a tropical pathogen that causes melioidosis. Its intrinsic drug-resistance is a leading cause of treatment failure, and the few available antibiotics require prolonged use to be effective. This study aimed to assess the clinical potential of B. pseudomallei phages isolated from Hainan, China. METHODS: Burkholderia pseudomallei strain (HNBP001) was used as the isolation host, and phages were recovered from domestic environmental sources, which were submitted to the host range determination, lytic property assays, and stability tests. The best candidate was examined via the transmission electron microscope for classification. With its genome sequenced and analyzed, its protective efficacy against B. pseudomallei infection in A549 cells and Caenorhabditis elegans was evaluated, in which cell viability and survival rates were compared using the one-way ANOVA method and the log-rank test. RESULTS: A phage able to lyse 24/25 clinical isolates was recovered. It was classified in the Podoviridae family and was found to be amenable to propagation. Under the optimal multiplicity of infection (MOI) of 0.1, an eclipse period of around 20 min and a high titer (1012 PFU/ml) produced within 1 h were demonstrated. This phage was found stabile at a wide range of temperatures (24, 37, 40, 50, and 60 °C) and pH values (3-12). After being designated as vB_BpP_HN01, it was fully sequenced, and the 71,398 bp linear genome, containing 93 open reading frames and a tRNA-Asn, displayed a low sequence similarity with known viruses. Additionally, protective effects of applications of vB_BpP_HN01 (MOI = 0.1 and MOI = 1) alone or in combination with antibiotics were found to improve viability of infected cells (70.6 ± 6.8%, 85.8 ± 5.7%, 91.9 ± 1.8%, and 96.8 ± 1.8%, respectively). A significantly reduced mortality (10%) and a decreased pathogen load were demonstrated in infected C. elegans following the addition of this phage. CONCLUSIONS: As the first B. pseudomallei phage was isolated in Hainan, China, phage vB_BpP_HN01 was characterized by promising lytic property, stability, and efficiency of bacterial elimination during the in vitro/vivo experiments. Therefore, we can conclude that it is a potential alternative agent for combating melioidosis.
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Bacteriófagos , Burkholderia pseudomallei , Melioidosis , Terapia de Fagos , Animales , Antibacterianos , Bacteriófagos/genética , Caenorhabditis elegans , Melioidosis/microbiología , Melioidosis/terapia , Terapia de Fagos/métodosRESUMEN
OBJECTIVE: This study investigates the differences and changing trend of posterior circulation blood perfusion between different levels of vertebrobasilar dolichoectasia(VBD) patients. The relationship between the deviation of the basilar artery(BA) in different directions and the location of pontine infarction are also investigated. METHODS: A cohort of 106 patients(74 males and 32 females) who satisfied the diagnostic criteria for VBD were recruited for this study and classified according to the bifurcation height and the deviation position of the BA, as well as the measured blood perfusion value of the pontine, which includes rCBF, rCBV, MTT, and TTP. RESULTS: Out of the 106 patients, 19 cases were classified as Level 1, 74 cases were classified as Level 2, and 13 cases were classified as Level 3. The different levels between the VBD groups were statistically significant (P<0.05, P<0.01), and it was found that as the level increases, rCBF and rCBV gradually decreased, while MTT and TTP gradually increased. The statistic results of different perfusion parameters were also significant, when pairwise comparisons between Level 1 and Level 3, and Level 2 and Level 3 were performed. However, when comparing Level 1 and Level 2, only the TTP showed significant result. Among 106 patients, 22 cases had brainstem infarction, 13 cases had left brainstem infarction, 8 cases had right brainstem infarction, and 1 case had brainstem infarction on both sides. Brainstem infarction generally occurs on the opposite side of the direction of BA deviation(P<0.05). Regardless of the BA was deviated to the left or right, perfusion analysis showed that there was significant difference in blood perfusion on both sides of the pontine when BA is deviated(P<0.05, P<0.01). The rCBF and rCBV on the contralateral side of deviation were lower than those on the same side, and the MTT and TTP were longer than those on the same side. There were 37 cases with vertebral artery dominance(VAD), 16 cases with left VAD, and 21 cases with right VAD. Statistical analysis showed that BA was more likely to deflect to the opposite side of the dominant artery(P<0.05), and compared with non-VAD, there was no significant difference in pontine blood perfusion (p>0.05). CONCLUSION: As VBD level increases, rCBF and rCBV will gradually decreases while MTT and TTP showed sign of increasing. The location of brainstem infarction is opposite to the direction of the BA deviation, and BA is more likely to deviate to the opposite side of the dominant artery.
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Infartos del Tronco Encefálico , Insuficiencia Vertebrobasilar , Arteria Basilar/diagnóstico por imagen , Infartos del Tronco Encefálico/diagnóstico por imagen , Femenino , Humanos , Masculino , Perfusión , Arteria Vertebral/diagnóstico por imagen , Insuficiencia Vertebrobasilar/diagnóstico por imagenRESUMEN
OBJECTIVE: To investigate the effect of lncRNA-CASC2 (CASC2) /miR-155-5p/APC axis to the progression of non-Hodgikn lymphoma (NHL). METHODS: The expression level of CASC2 and miR-155-5p in NHL cell lines were examined by qRT-PCR. Dual-luciferase reporter gene assay was used to verify the relationship between miR-155-5p, CASC2 and APC. The effects of CASC/miR-155-5p/APC axis to the proliferation, invasion and apoptosis of NK-92 cells were detected by MTT, Transwell assay and flow cytometry assay, respectively. RESULTS: CASC2 was downregulated in NHL cell lines. Overexpression of CASC2 could inhibit the proliferation and invasion of NK-92 cells, and promote its apoptosis. Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between miR-155-5p, CASC2 and APC. The restoration experiments proved that knockdown of both miR-155-5p and CASC2 or APC could restore the inhibitory effect of miR-155-5p silencing to the biological behavior of NK-92 cells. CONCLUSION: Overexpression of CASC2 suppresses the proliferation and invasion of NK-92 cells, promote the apoptosis of NK-92 cells via targeting miR-155-5p and upregulating APC expression.
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Linfoma no Hodgkin , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Linfoma no Hodgkin/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Proteínas Supresoras de Tumor/genéticaRESUMEN
Fibronectin type III domain containing 4 (FNDC4) belongs to the fibronectin type III domain containing protein family. FNDC5, which is highly homologous to FNDC4, can promote the differentiation of cardiac cells. We aimed to investigate the role of FNDC4 in the differentiation of C2C12 mouse skeletal muscle cells. Western blotting and immunofluorescence analysis showed that FNDC4 gradually increased with the differentiation of C2C12. Muscle injury repair experiments indicated that FNDC4 may promote the repair of injured muscles. When FNDC4 was either overexpressed or knocked down, the expression of desmin and myogenin myogenic marker molecules followed that of FNDC4, suggesting that FNDC4 can influence the differentiation of C2C12. In addition, immunoprecipitation results showed that FNDC4 can interact with the Wnt/ß-catenin signaling pathway receptor low-density lipoprotein receptor-related protein 6 (LRP6), and that ß-catenin levels in the nucleus decreased after knocking down FNDC4. Exogenous addition of FNDC4 protein could not restore the blocking of differentiation due to inhibition of both Wnt/ß-catenin signal transduction and LRP6 activity via the ß-catenin inhibitor XAV-939. Overall, our findings indicate that FDNC4 can influence the differentiation of C2C12 by activating Wnt/ß-catenin signal transduction.
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Diferenciación Celular/fisiología , Dominio de Fibronectina del Tipo III/fisiología , Proteínas de la Membrana/metabolismo , Vía de Señalización Wnt/fisiología , beta Catenina/metabolismo , Animales , Línea Celular , Ratones , Células Musculares/metabolismo , Desarrollo de Músculos/fisiología , Músculo Esquelético/metabolismo , Mioblastos/metabolismoRESUMEN
BACKGROUND: To compare the application and efficacy of ropivacaine combined with sufentanil for continuous epidural anesthesia (CEA) and combined spinal-epidural anesthesia (CSEA) in labor analgesia. METHODS: Three hundred sixty pregnant women requesting labor analgesia from October 2017 to August 2018 were selected retrospectively. According to the anesthetic method, subjects were divided into CSEA group and CEA group. Ropivacaine combined with sufentanil were used in all subjects. The labor time, visual analogue scale (VAS), Apgar score of newborn, adverse pregnancy outcomes and adverse drug reactions were observed. RESULTS: There was no significant difference in pre-analgesia (T0) VAS scores between the two groups (P > 0.05). VAS scores of first stage of labor (T1), second stage of labor (T2) and third stage of labor (T3) in CSEA group were significantly lower than CEA group (P < 0.01). The onset time, T1 and total labor time in CSEA group were significantly shorter than CEA group (P < 0.01). There were no significant differences between T2 and T3 (P > 0.05). There were no significant differences in adverse pregnancy outcomes and Apgar scores at 1, 5 and 10 min after birth between the two groups (P > 0.05). The incidence of adverse drug outcomes in CSEA group was significantly lower than CEA group (P < 0.01). Maternal satisfaction in CSEA group was significantly higher than CEA group (P < 0.01). CONCLUSION: Considering ropivacaine combined with sufentanil for CSEA achieved a shorter onset time and labor period, significant analgesic effect, lower adverse drug reactions rates and higher subject satisfaction than CEA, it may be worthy of clinical promotion and application.
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Anestesia Epidural/métodos , Anestesia Obstétrica/métodos , Anestesia Raquidea , Anestésicos Intravenosos , Anestésicos Locales , Ropivacaína , Sufentanilo , Adulto , Analgesia Obstétrica , Puntaje de Apgar , Estudios de Casos y Controles , Femenino , Humanos , Recién Nacido , Segundo Periodo del Trabajo de Parto , Tercer Periodo del Trabajo de Parto , Dimensión del Dolor , Satisfacción del Paciente , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , Ropivacaína/efectos adversos , Sufentanilo/efectos adversos , Adulto JovenRESUMEN
Objective: This study aimed to analyze the perinatal changes of plasma estradiol (E2) and angiotensin II (Ang II) in pregnant women with pulmonary arterial hypertension before and after cesarean section. Methods: Depending on pulmonary arterial pressure, the subjects were divided into two groups, moderate group, and severe group. Plasma concentrations of E2 and Ang II were determined at different time points using electrochemiluminescence immunoassay and ELISA, respectively. The correlation between E2 and Ang II concentrations was analyzed. Results: Intragroup comparison indicated that E2 levels at different time points after surgery decreased in the two groups than before, with a greater reduction in the severe group. Besides, both groups showed a reduction in Ang II concentrations after surgery. As indicated by intragroup comparison, there was a significant difference at each time point in the two groups. The reduction in Ang II concentrations was more conspicuous at 48 h and 72 h after surgery (cesarean section) than before for the two groups. Moreover, E2 concentrations were correlated positively with AngII concentrations. Conclusion: Plasma concentrations of E2 and Ang II decreased after delivery. The plasma concentrations of E2 and Ang II were correlated with each other.
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Angiotensina II/sangre , Estradiol/sangre , Parto/sangre , Complicaciones Cardiovasculares del Embarazo/sangre , Hipertensión Arterial Pulmonar/sangre , Adolescente , Adulto , Presión Sanguínea/fisiología , Femenino , Humanos , Embarazo , Adulto JovenRESUMEN
PURPOSE: The work outlined herein investigated the prognosis value and the potential role son of sevenless homolog 1 (SOS1) played in uveal melanoma (UM). METHODS: We analyzed the mRNA expression level of SOS1 in primary UM cells based on the GSE44295 dataset obtained from the Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/ ) database. The correlation between SOS1 expression and clinical characteristics were analyzed by Chi-squared (χ2) test. Then we used SOS1 siRNA to downregulate SOS1 expression in M23 cells. The effect of knockdown SOS1 on cell proliferation was studied using the Cell-Counting Kit-8 and colony formation assays. The influence of silencing SOS1 on cell motility was explored using wound-healing assays and transwell assays. In addition, the relationship between SOS1 and the MAPK signaling pathway was analyzed by western blot. RESULTS: Our results demonstrated that the mRNA expression level of SOS1 was markedly upregulated in UM cells (p < 0.001) and correlated with poor prognosis in UM patients (p = 0.015). Moreover, SOS1 mRNA expression level was found to be positively associated with histological-type (p = 0.043) and death (p = 0.012). Knockdown of SOS1 caused an inhibition on M23 cell proliferation, migration, and invasion. Moreover, the phosphorylation levels of MEK and ERK were reduced in UM cells after downregulating SOS1 expression (p < 0.010). CONCLUSION: Our data demonstrated that SOS1 might play a facilitating role in M23 cell growth and motility by regulating the MAPK signaling pathway. Furthermore, the data suggested that SOS1 may serve as an UM predictor of prognosis as well as a therapeutic target.
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Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Melanoma/patología , Proteína SOS1/metabolismo , Neoplasias de la Úvea/patología , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Masculino , Melanoma/genética , Melanoma/metabolismo , Persona de Mediana Edad , Pronóstico , ARN Interferente Pequeño/genética , Proteína SOS1/antagonistas & inhibidores , Proteína SOS1/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/metabolismoRESUMEN
CONTEXT: Sika pilose antler type I collagen (SPC-I) have been reported to promote bone marrow mesenchymal stem cell (BMSC) proliferation and differentiation. However, the underlying mechanism is still unclear. OBJECTIVE: This study investigates the molecular mechanisms of SPC-I on the BMSC proliferation and differentiation of osteoblast (OB) in vitro. MATERIAL AND METHODS: The primary rat BMSC was cultured and exposed to SPC-I at different concentrations (2.5, 5.0 and 10.0 mg/mL) for 20 days. The effect of SPC-I on the differentiation of BMSCs was evaluated through detecting the activity of alkaline phosphatase (ALP), ALP staining, collagen I (Col-I) content, and calcified nodules. The markers of osteoblastic differentiation were evaluated using RT-PCR and Western-blot analysis. RESULTS: SPC-I treatment (2.5 mg/mL) significantly increased the proliferation of BMSCs (p < 0.01), whereas, SPC-I (5.0 and 10.0 mg/mL) significantly inhibited the proliferation of BMSCs (p < 0.01). SPC-I (2.5 mg/mL) significantly increased ALP activity and Col-I content (p < 0.01), and increased positive cells in ALP staining and the formation of calcified nodules. Additionally, the gene expression of ALP, Col-I, Osteocalcin (OC), Runx2, Osterix (Osx), ERK1/2, BMP2 and p38-MAPK, along with the protein expression of ERK1/2, p-ERK1/2, p-p38 MAPK were markedly increased in the SPC-I (5.0 mg/mL) treatment group (p < 0.01) compared to the control group. DISCUSSION AND CONCLUSIONS: SPC-I can induce BMSC differentiation into OBs and enhance the function of osteogenesis through ERK1/2 and p38-MAPK signal transduction pathways and regulating the gene expression of osteogenesis-specific transcription factors.
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Cuernos de Venado/química , Diferenciación Celular/efectos de los fármacos , Colágeno Tipo I/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Animales , Western Blotting , Proliferación Celular/efectos de los fármacos , Colágeno Tipo I/administración & dosificación , Colágeno Tipo I/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Células Madre Mesenquimatosas/citología , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Factores de Transcripción/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
In this paper, effect and molecular mechanism of sika pilose antler type I collagen(SPC-I) of ROS1728 cell were explored. For the SPC-I provides the theory basis for the treatment of osteoporosis. The adherent method was used to cultivate rat osteosarcoma osteogenesis sample cell line ROS1728. The effect of SPC-I on ROS1728 cells proliferation was tested by CCK-8 method. Runx2, osernix, ALP, Coll-I, OC osteogenesis related genes expression was tested by RT-PCR, and Runx2 protein expression was tested by Western-bolt. Results showed that 5 gâ¢L ⻹ SPC-I could inhibit ROS1728 cell proliferation, and significantly promote the expression of ROS1728 cell specific transcription factor Runx2 and osterix mRNA, Runx2 protein and marker gene ALP, Coll-I, OC mRNA expression(P<0.01). 2.5 gâ¢L ⻹ and 10 gâ¢L ⻹ SPC-I could significantly inhibit the ROS1728 cell proliferation(P<0.01), and inhibit the expression of related genes. In conclusion, 5 gâ¢L ⻹ SPC-I could inhibit ROS1728 cell proliferation, obviously enhance ROS1728 cell function, promote ROS1728 cell differentiation, maturation.
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Cuernos de Venado/química , Colágeno/farmacología , Osteoblastos/efectos de los fármacos , Osteogénesis , Animales , Diferenciación Celular , Línea Celular Tumoral , Proliferación Celular , RatasRESUMEN
This paper presents the fabrication and characterization of a resonant pressure microsensor based on SOI-glass wafer-level vacuum packaging. The SOI-based pressure microsensor consists of a pressure-sensitive diaphragm at the handle layer and two lateral resonators (electrostatic excitation and capacitive detection) on the device layer as a differential setup. The resonators were vacuum packaged with a glass cap using anodic bonding and the wire interconnection was realized using a mask-free electrochemical etching approach by selectively patterning an Au film on highly topographic surfaces. The fabricated resonant pressure microsensor with dual resonators was characterized in a systematic manner, producing a quality factor higher than 10,000 (~6 months), a sensitivity of about 166 Hz/kPa and a reduced nonlinear error of 0.033% F.S. Based on the differential output, the sensitivity was increased to two times and the temperature-caused frequency drift was decreased to 25%.
Asunto(s)
Vidrio/química , Microtecnología/instrumentación , Presión , Silicio/química , Vacio , Técnicas Electroquímicas , Electrodos , Diseño de Equipo , Metales/química , TemperaturaRESUMEN
In this work, TiO2(B) nanoparticle (NP)-functionalized WO3 nanorods (NRs) were synthesized by a two-step solution strategy, with a hydrothermal process for WO3 NRs and hydrolyzation of Ti(OBu)4 for the functionalization of TiO2(B) NPs. Various techniques, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS), were employed to investigate the morphology, microstructure, crystalline nature and chemical composition of the prepared TiO2(B) NP-functionalized WO3 NRs. SEM and TEM results revealed that the TiO2(B)-WO3 composite showed a rod-like nanostructure with a diameter in the range from 93 to 154 nm and a rough surface, which could increase the accessible surface area and the amount of surface active sites, thus improving the properties or performance of the as-prepared composite NRs. XRD and XPS analysis clearly verified that monoclinic TiO2(B) NPs, a metastable polymorph of TiO2, were successfully supported on the WO3 NRs. Gas sensing measurement results for several common reductive organic gases such as acetone, ethanol, ether, methanol and formaldehyde demonstrated that the sensor based on the as-obtained TiO2(B) NP-functionalized WO3 NRs exhibited obviously enhanced responses compared with a pure WO3 NR based sensor, as well as fast response-recovery speeds, good reproducibility and good stability, indicating their promising application in gas sensors. The excellent gas sensing performance could be attributed to the unique 1D rod-like nanostructure with a rough surface, the existence of TiO2-WO3 heterojunctions and the catalytic effect of the TiO2(B) NPs. The as-prepared TiO2(B) NP-functionalized WO3 NRs will also have very good prospects in electrochromic devices and catalysis applications.
RESUMEN
A novel sensing hybrid-material of Au nanoparticles (Au NPs)-functionalized ZnO nanowires (Au-ZnO NWs) was successfully synthesized by a two-stage solution process. First, ZnO NWs were fabricated via a low-temperature one-pot hydrothermal method with SDSN introduced as a structure-directing agent. Afterward, the as-prepared ZnO NWs were used as supports to load Au NPs with small sizes via precipitating HAuCl4 aqueous solution with ammonia. The obtained samples were characterized by means of XRD, SEM, TEM and EDX. Both pristine and Au-ZnO NWs were practically applied as gas sensors to compare the effect of Au NPs on the sensing performances and the obtained results demonstrated that after functionalization by catalytic Au NPs, the hybrid sensor exhibited not only faster response and recovery speeds but also a higher response to benzene and toluene than the pristine ZnO sensor at 340 °C, especially showing high selectivity and long-term stability for low concentration toluene, which is rarely reported with this method, indicating its original sensor application in detecting benzene and toluene. To interpret the enhanced gas sensing mechanism, the strong spillover effect of the Au NPs and the increased Schottky barriers caused by the electronic interaction between Au NPs and ZnO NW support are believed to contribute to the improved sensor performance.