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Phenotypic variation among species is a product of evolutionary changes to developmental programs1,2. However, how these changes generate novel morphological traits remains largely unclear. Here we studied the genomic and developmental basis of the mammalian gliding membrane, or patagium-an adaptative trait that has repeatedly evolved in different lineages, including in closely related marsupial species. Through comparative genomic analysis of 15 marsupial genomes, both from gliding and non-gliding species, we find that the Emx2 locus experienced lineage-specific patterns of accelerated cis-regulatory evolution in gliding species. By combining epigenomics, transcriptomics and in-pouch marsupial transgenics, we show that Emx2 is a critical upstream regulator of patagium development. Moreover, we identify different cis-regulatory elements that may be responsible for driving increased Emx2 expression levels in gliding species. Lastly, using mouse functional experiments, we find evidence that Emx2 expression patterns in gliders may have been modified from a pre-existing program found in all mammals. Together, our results suggest that patagia repeatedly originated through a process of convergent genomic evolution, whereby regulation of Emx2 was altered by distinct cis-regulatory elements in independently evolved species. Thus, different regulatory elements targeting the same key developmental gene may constitute an effective strategy by which natural selection has harnessed regulatory evolution in marsupial genomes to generate phenotypic novelty.
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Evolución Molecular , Proteínas de Homeodominio , Locomoción , Marsupiales , Factores de Transcripción , Animales , Femenino , Masculino , Ratones , Epigenómica , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Genoma/genética , Genómica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Locomoción/genética , Marsupiales/anatomía & histología , Marsupiales/clasificación , Marsupiales/genética , Marsupiales/crecimiento & desarrollo , Filogenia , Secuencias Reguladoras de Ácidos Nucleicos/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Fenotipo , HumanosRESUMEN
BACKGROUND: Microsatellite instability (MSI) indicates DNA mismatch repair deficiency in certain types of cancer, such as colorectal cancer. The current gold standard technique, PCR-capillary electrophoresis (CE), requires matching normal samples and specialized instrumentation. We developed VarTrace, a rapid and low-cost quantitative PCR (qPCR) assay, to evaluate MSI using solely the tumor sample DNA, obviating the requirement for matching normal samples. METHODS: One hundred and one formalin-fixed paraffin-embedded (FFPE) tumor samples were tested using VarTrace and compared with the Promega OncoMate assay utilizing PCR-CE. Tumor percentage limit of detection was evaluated on contrived samples derived from clinical high MSI (MSI-H) samples. Analytical sensitivity, specificity, limit of detection, and input requirements were assessed using synthetic commercial reference standards. RESULTS: VarTrace successfully analyzed all 101 clinical FFPE samples, demonstrating 100% sensitivity and 98% specificity compared to OncoMate. It detected MSI-H with 97% accuracy down to 10% tumor. Analytical studies using synthetic samples showed a limit of detection of 5% variant allele frequency and a limit of input of 0.5 ng. CONCLUSIONS: This study validates VarTrace as a swift, accurate, and economical assay for MSI detection in samples with low tumor percentages without the need for matching normal DNA. VarTrace's capacity for highly sensitive MSI analysis holds potential for enhancing the efficiency of clinical work flows and broadening the availability of this test.
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Inestabilidad de Microsatélites , Humanos , Adhesión en Parafina , Neoplasias/genética , Neoplasias/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/diagnóstico , Sensibilidad y Especificidad , Electroforesis Capilar/métodos , Formaldehído , ADN de Neoplasias/genética , Límite de Detección , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We developed a single-particle optical particle counter with polarization detection (SOPC) for the real-time measurement of the optical size and depolarization ratio (defined as the ratio of the vertical component to the parallel component of backward scattering) of atmospheric particles, the polarization ratio (DR) value can reflect the irregularity of the particles. The SOPC can detect aerosol particles with size larger than 500 nm and the maximum particle count rate reaches â¼1.8 × 105 particles per liter. The SOPC uses a modulated polarization laser to measure the optical size of particles according to forward scattering signal and the DR value of the particles by backward S and P signal components. The sampling rate of the SOPC was 106 #/(sec·channel), and all the raw data were processed online. The calibration curve was obtained by polystyrene latex spheres with sizes of 0.5-10 µm, and the average relative deviation of measurement was 3.96% for sub 3 µm particles. T-matrix method calculations showed that the DR value of backscatter light at 120° could describe the variations in the aspect ratio of particles in the above size range. We performed insitu observations for the evaluation of the SOPC, the mass concentration constructed by the SOPC showed good agreement with the PM2.5 measurements in a nearby state-controlled monitoring site. This instrument could provide useful data for source appointment and regulations against air pollution.
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Contaminación del Aire , Monitoreo del Ambiente , Monitoreo del Ambiente/métodos , Tamaño de la Partícula , Luz , MicroesferasRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern, necessitating a deeper understanding of its prognosis and underlying mechanisms. This study aimed to investigate the mechanism and prognostic value of CD8+ T Cell exhaustion (CD8+ TEX)-related genes in HCC and construct a survival prognosis prediction model for patients with HCC. METHODS: CD8+ TEX-related genes associated with HCC prognosis were analysed and identified, and a prognostic prediction model was constructed using the 'least absolute shrinkage and selection operator' Cox regression model. Immunohistochemistry was used to verify the expression of the model genes in HCC tissues. A nomogram was constructed based on risk scores and clinical features, and its predictive efficacy was verified. The expression of STAM, ANXA5, and MAD2L2 in HCC cell lines was detected by western blotting; subsequently, these genes were knocked down in HCC cell lines by small interfering RNA, and their effects on the proliferation and migration of HCC cell lines were detected by colony formation assay, cck8, wound healing, and transwell assays. RESULTS: Six genes related to CD8+ TEX were included in the risk-prediction model. The prognosis of patients with HCC in the low-risk group was significantly better than that of those in the high-risk group. Cox regression analysis revealed that the risk score was an independent risk factor for the prognosis of patients with HCC. The differentially expressed genes in patients with high-risk HCC were mainly enriched in the nucleotide-binding oligomerization domain-containing protein-like receptor, hypoxia-inducible factor-1, and tumour programmed cell death protein (PD)-1/PD-L1 immune checkpoint pathways. The CD8+ TEX-related genes STAM, ANXA5, and MAD2L2 were knocked down in HCC cell lines to significantly inhibit cell proliferation and migration. The prediction results of the nomogram based on the risk score showed a good fit and application value. CONCLUSION: The prediction model based on CD8+ TEX-related genes can predict the prognosis of HCC and provide a theoretical basis for the early identification of patients with poor HCC prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Agotamiento de Células T , Neoplasias Hepáticas/genética , Genes cdc , Anexina A5 , Linfocitos T CD8-positivos , Pronóstico , Proteínas Mad2RESUMEN
Black carbon (BC) aerosols in the atmosphere play a significant role in climate systems due to their strong ability to absorb solar radiation. The lifetime of BC depends on atmospheric transport, aging and consequently on wet scavenging processes (in-cloud and below-cloud scavenging). In this study, sequential rainwater samples in eight rainfall events collected in 2 mm interval were measured by a tandem system including a single particle soot photometer (SP2) and a nebulizer. The results showed that the volume-weighted average (VWA) mass concentrations of refractory black carbon (rBC) in each rainfall event varied, ranging from 10.8 to 78.9 µg/L. The highest rBC concentrations in the rainwater samples typically occurred in the first fraction from individual rainfall events. The geometric mean median mass-equivalent diameter (MMD) decreased under precipitation, indicating that rBC with larger sizes was relatively aged and preferentially removed by wet scavenging. A positive correlation (R2 = 0.73) between the VWA mass concentrations of rBC in rainwater and that in ambient air suggested the important contribution of scavenging process. Additionally, the contributions of in-cloud and below-cloud scavenging were distinguished and accounted for 74% and 26% to wet scavenging, respectively. The scavenging ratio of rBC particles was estimated to be 0.06 on average. This study provides helpful information for better understanding the mechanism of rBC wet scavenging and reducing the uncertainty of numerical simulations of the climate effects of rBC.
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Contaminantes Atmosféricos , Contaminantes Atmosféricos/análisis , Beijing , Hollín/análisis , Aerosoles/análisis , Carbono , Monitoreo del Ambiente/métodosRESUMEN
BACKGROUND: The effectiveness of pancreatic duct (PD) stenting in the early stages of acute pancreatitis (AP) remains controversial. This study aimed to investigate the efficacy and safety of PD stenting in the early stages of AP. METHODS: This is a retrospective cohort study. The clinical data of 131 patients with AP from 2018 to 2019 were analysed and divided into two groups: the study group (n = 46, PD stenting) and the control group (n = 85, standard treatment). RESULTS: There was a statistically significant reduction in pain relief, oral refeeding, hospitalization, and intensive care unit (ICU) stay in the study group compared with that of the control group (P < 0.05). There were no significant differences in the incidence of complications between the two groups. Further multivariate analysis of risk factors for new-onset organ failure showed that the control group (odds ratio [OR] (95% confidence interval [CI]): 6.533 (1.104-70.181)) and a higher level of haematocrit (HCT) at admission (HCT > 46.1%, OR (95%CI): 8.728 (1.264-116.767)) were independent risk factors. CONCLUSIONS: In the early phase of AP, PD stenting has the potential to reduce pain relief time, oral refeeding time, ICU stay time, and overall hospital stay time. This finding highlights a new route for the treatment of AP.
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Pancreatitis , Enfermedad Aguda , Humanos , Conductos Pancreáticos/cirugía , Pancreatitis/complicaciones , Estudios Retrospectivos , Stents/efectos adversosRESUMEN
BACKGROUND: Naringenin, a natural resource-derived flavanone, exhibits a plethora of pharmacological properties. The present study aimed to investigate the effects of naringenin on obesity-associated hypertension and its underlying mechanism. METHODS: Obesity-associated hypertension rat model was established with a high-fat diet (HFD) and was administrated with naringenin (25, 50, 100 mg/kg). Body and fat weights were recorded and blood pressure was measured. Serum lipid parameters (cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides), oxidative stress biomarkers (malondialdehyde [MDA], superoxide dismutase [SOD], nitrite oxide [NO], and glutathione [GSH]), and adipocytokines (leptin and adiponectin) were determined. The expressions of signal transducer and activator of transcription (STAT) 3 were determined by using Western blotting. RESULTS: Treatment with naringenin (100 mg/kg) reduced body and fat weight in HFD-induced rats. Besides, treatment with naringenin (50 and 100 mg/kg) reduced blood pressure and regulated lipid parameters by decreasing cholesterol, triglycerides, and LDL and increasing HDL. Treatment with naringenin (50 and 100 mg/kg) reduced serum MDA and NO, whereas it increased serum SOD and GSH. Furthermore, treatment with naringenin (50 and 100 mg/kg) regulated adipocytokines and decreased the phosphorylation of STAT3. CONCLUSION: Naringenin ameliorates obesity-associated hypertension by regulating lipid disorder and oxidative stress.
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Flavanonas , Hipertensión , Adipoquinas/metabolismo , Adipoquinas/farmacología , Animales , Colesterol , Flavanonas/farmacología , Flavanonas/uso terapéutico , Hipertensión/tratamiento farmacológico , Lipoproteínas HDL/farmacología , Obesidad/complicaciones , Obesidad/metabolismo , Estrés Oxidativo , Ratas , Superóxido Dismutasa , TriglicéridosRESUMEN
Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes with limited therapies. Tang Luo Ning (TLN), a traditional Chinese medicine compound, has been proved to be effective in the treatment of DPN in clinical and experimental studies. However, the potential metabolic mechanism of TLN for the treatment of DPN is still unclear. Here the therapeutic effect of TLN on DPN was studied, and HPLC-IT-TOF/MS was used to explore the metabolic changes related to DPN and to explore the mechanism of TLN on DPN induced by high glucose. Furthermore, metabolic pathway analysis was used to explore the metabolic changes induced by DPN and TLN. As a result, TLN could improve the peripheral nerve function of DPN rats, and TLN could reduce the demyelination of the sciatic nerve in DPN rats. Metabolomics analysis showed that 14 potential biomarkers (citrate, creatine, fumarate, glyceric acid, glycine, succinate, etc.) of both DPN and TLN treatment were identified. Pathway analysis showed that the changes in these metabolites were mainly related to the citrate cycle (TCA cycle); glycine, serine, and threonine metabolism; and glyoxylate and dicarboxylate metabolism.
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Diabetes Mellitus , Neuropatías Diabéticas , Animales , Ratas , Cromatografía Liquida , Citratos , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/metabolismo , Glicina , Metabolómica , Ratas Sprague-Dawley , Espectrometría de Masas en TándemRESUMEN
The attainment of suitable ambient air quality standards is a matter of great concern for successfully hosting the XXIV Olympic Winter Games (OWG). Transport patterns and potential sources of pollutants in Zhangjiakou (ZJK) were investigated using pollutant monitoring datasets and a dispersion model. The PM2.5 concentration during February in ZJK has increased slightly (28%) from 2018 to 2021, mostly owing to the shift of main potential source regions of west-central Inner Mongolia and Mongolian areas (2015-18) to the North China Plain and northern Shanxi Province (NCPS) after 2018. Using CO as an indicator, the relative contributions of the different regions to the receptor site (ZJK) were evaluated based on the source-receptor-relationship method (SRR) and an emission inventory. We found that the relative contribution of pollutants from NCPS increased from 33% to 68% during 2019-21. Central Inner Mongolia (CIM) also has an important impact on ZJK under unfavorable weather conditions. This study demonstrated that the effect of pollution control measures in the NCPS and CIM should be strengthened to ensure that the air quality meets the standard during the XXIV OWG.
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Cross-boundary transport of air pollution is a difficult issue in pollution control for the North China Plain. In this study, an industrial district (Shahe City) with a large glass manufacturing sector was investigated to clarify the relative contribution of fine particulate matter (PM2.5) to the city's high levels of pollution. The Nest Air Quality Prediction Model System (NAQPMS), paired with Weather Research and Forecasting (WRF), was adopted and applied with a spatial resolution of 5 km. During the study period, the mean mass concentrations of PM2.5, SO2, and NO2 were observed to be 132.0, 76.1, and 55.5 µg/m3, respectively. The model reproduced the variations in pollutant concentrations in Shahe at an acceptable level. The simulation of online source-tagging revealed that pollutants emitted within a 50-km radius of downtown Shahe contributed 63.4% of the city's total PM2.5 concentration. This contribution increased to 73.9±21.2% when unfavorable meteorological conditions (high relative humidity, weak wind, and low planetary boundary layer height) were present; such conditions are more frequently associated with severe pollution (PM2.5 ≥ 250 µg/m3). The contribution from Shahe was 52.3±21.6%. The source apportionment results showed that industry (47%), transportation (10%), power (17%), and residential (26%) sectors were the most important sources of PM2.5 in Shahe. The glass factories (where chimney stack heights were normally < 70 m) in Shahe contributed 32.1% of the total PM2.5 concentration in Shahe. With an increase in PM2.5 concentration, the emissions from glass factories accumulated vertically and narrowed horizontally. At times when pollution levels were severe, the horizontally influenced area mainly covered Shahe. Furthermore, sensitivity tests indicated that reducing emissions by 20%, 40%, and 60% could lead to a decrease in the mass concentration of PM2.5 of of 12.0%, 23.8%, and 35.5%, respectively.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Ciudades , Monitoreo del Ambiente , Material Particulado/análisis , Estaciones del AñoRESUMEN
BACKGROUND: Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN). METHODS: DPN was induced in male Wistar rats by intraperitoneal administration of streptozocin (STZ) (60 mg/kg.b.w) for 8 weeks. Fasting blood glucose (FBG) levels were measured in the blood obtained by clipping the tails of the rats. Tail-flick tests were conducted with a tail-flick analgesic meter. Motor and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured directly at two sites using a Functional Experiment System. Oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD) and glutathione peroxidase (GSH-Px), inflammatory cytokines such as interleukin (IL)-6, and tumour necrosis factor (TNF)-α were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis of variance (ANOVA), followed by least-significant difference post hoc with SPSS. RESULTS: The administration of TBK for 4 weeks in DPN rats resulted in a significant decrease in FBG levels compared to untreated DPN rats. There was a significant increase in MNCV and SNCV in the DPN rats compared to untreated DPN rats. Serum level of MDA was significantly reduced while the activities of SOD and GSH-pX were significantly increased in the TBK treated DPN rats. TBK prevented DPN-induced increase in the serum levels of IL-6 and TNF-α. CONCLUSION: The results of this study demonstrate that the therapeutic effect of TBK on DPN rats may be associated with the antioxidative and anti-inflammatory responses.
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Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Fitoterapia , Nervio Ciático/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Glucemia/metabolismo , Citocinas/sangre , Neuropatías Diabéticas/sangre , Neuropatías Diabéticas/inducido químicamente , Neuropatías Diabéticas/fisiopatología , Medicamentos Herbarios Chinos/farmacología , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Masculino , Malondialdehído/sangre , Conducción Nerviosa/efectos de los fármacos , Ratas Wistar , Nervio Ciático/fisiología , Estreptozocina , Superóxido Dismutasa/metabolismoRESUMEN
OBJECTIVE: To assese the healing of stoma after magnetic anastomosis for the reconstruction of biliary-enteric continuity under severe inflammation. METHODS: Acute bile duct injury was constructed as a bile peritonitis model in mongrel dogs (n=32). Magnetic anastomosis (group A, n=16) and traditional suture anastomosis (group B, n=16) were performed to reconstruct the biliary-enteric continuity in one stage. Half of the dogs in each group were euthanized on the 30th postoperative day, and the other half on the 90th postoperative day to harvest the stoma region. The healing conditions of the stoma after the 2 anastomotic approaches were observed with naked eyes, under light microscope and scanning electron microscope. RESULTS: The stoma leakage rate (50% versus 0% on the 30th postoperative day, 37.5% versus 12.5% on the 90th postoperative day, both P<0.05) and stenosis degree (13.9%±0.3% versus 7.1%±0.3% on the 30th postoperative day, 17.2%±0.4% versus 9.4%±0.4% on the 90th postoperative day, both P<0.01) were significantly higher in group B than in group A. Compared with traditional manual anastomoses, the histological analysis under light and electron microscope showed a more continuous stoma with more regular epithelium proliferation and collagen arrangement, less inflammation in group A. CONCLUSIONS: Magnetic anastomosis stent ensures better healing of the stoma even under the circumstance of severe inflammation.
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Anastomosis Quirúrgica , Conductos Biliares/cirugía , Modelos Animales de Enfermedad , Intestinos/cirugía , Magnetismo , Peritonitis/cirugía , Estomas Quirúrgicos , Cicatrización de Heridas , Animales , Perros , Femenino , Masculino , Microscopía Electrónica de RastreoRESUMEN
BACKGROUND: This study aimed to construct an enteral nutrition evaluation system for critically ill patients using the Delphi method to direct the formulation of enteral nutrition support strategies and reduce interruption to enteral feeding. METHODS: We used domestic and foreign databases to obtain and analyze the literature and form "The Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients." The Delphi method was used to conduct two rounds of expert opinion consultation, combined with the suggestions from the research group to finalize the nutrition evaluation content of the system. RESULTS: After two rounds of expert consultation, a nutrition evaluation system was formed around three dimensions: before the start, during, and after the end of nutritional support. The effective recovery rates of the two rounds of expert consultation were 90.0% (18/20) and 100.0% (18/18), respectively. Authority coefficients were 0.865 and 0.908, while Kendall coordination coefficients were 0.108 ( P < 0.05) and 0.115 ( P < 0.001), respectively. Finally, the full enteral nutrition evaluation system for critically ill patients was constructed based on the Delphi method, including three primary items and seven secondary and 28 tertiary indicators. CONCLUSION: The established "Whole-Proceeding Enteral Nutrition Evaluation System for Critically Ill Patients" has high consistency from expert opinions and reliability, which can provide a practical evaluation tool for the process of enteral nutrition for severe patients.
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Enfermedad Crítica , Nutrición Enteral , Humanos , Nutrición Enteral/métodos , Enfermedad Crítica/terapia , Técnica Delphi , Reproducibilidad de los Resultados , Derivación y ConsultaRESUMEN
Background: There were bacteria in the early pancreatic juice culture of severe acute pancreatitis (SAP) patients, but during the clinical time, some patients showed more positive bacteria and some patients showed more negative bacteria. Many scholars have different test results, and further clinical research needs to be carried out to clarify this fact. To determine evidence of infection in the early stage of acute pancreatitis (AP) by pancreatic juice bacterial culture and provide a reference for the anti-infective therapy of AP. Methods: Patients with AP who underwent pancreatic juice bacterial culture in the Department of hepatobiliary surgery of the General Hospital of Ningxia Medical University from January 1, 2019 to June 30, 2020were reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) was used to collect pancreatic juice, which was sent to the laboratory for culturing. The clinical data and bacterial culture results of the patients were then recorded and analyzed. According to the results of the pancreatic juice culture, the patients were divided into a positive bacterial culture group (n=64) and a negative bacterial culture group (n=92). It was compared the data results of two groups [age, gender, etiology, acute physiology and chronic health evaluation (APACHE) II score, cultured bacteria, complications, local complications, Balthazar computed tomography (CT) score, inflammatory factors, the use of antibiotics, drug sensitivity analysis results, and the patient's co-infection] and performed multivariate analysis to identify the clinically valuable indicators. Moreover, a receiver operating characteristic (ROC) curve was drawn to predict the model of positive pancreatic juice culture in AP. Results: The patients in the positive bacterial culture group and the negative bacterial culture group had statistically significant differences in gender, age, body mass index (BMI), amylase, white blood cell count and the two groups of patients were comparable. A total of 156 patients were included in the study and pathogenic bacteria were cultured in the pancreatic juice of 64 patients (41.03%) and 94 strains of bacteria were found (Gram-positive bacteria, 38.30%; Gram-negative bacteria, 58.51%; fungi, 3.19%). A history of ERCP and early pancreatic necrosis were independent influencing factors of positive pancreatic juice culture. The incidence of complications, APACHE II, and inflammatory factor levels of patients with positive pancreatic juice bacterial culture were significantly higher than those of negative pancreatic juice bacterial culture (P<0.05). Multivariate regression and the ROC curve of pancreatic infection showed that positive pancreatic and Balthazar CT score >7 on admission were independent risk factors of pancreatic. The area under the ROC curve of patients with later pancreatic infection was 0.863 [95% confidence interval (CI): 0.769-0.957], specificity was 65.30%, sensitivity was 90.50%, and the Youden index was 0.603. Conclusions: Bacterial culturing of pancreatic juice provides evidence of infection in the early stage of AP, which has certain significance for the anti-infective therapy of AP.
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BACKGROUND: The expression of cytoplasmic poly (A) binding protein-1 (PABPC1) has been reported in multiple cancer types. This protein is known to modulate cancer progression. However, the effects of PABPC1 expression in pancreatic adenocarcinoma (PAAD) have not been investigated. Here, we investigate the regulatory targets and molecular mechanisms of PABPC1 in PAAD. METHODS: PABPC1 and collagen type XII α1 chain (COL12A1) expression in PAAD and their role in tumor prognosis and tumor stage were investigated using The Cancer Genome Atlas database analysis. After silencing PABPC1, messenger RNA sequencing and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The expression of differentially expressed genes (DEGs), cell viability, apoptosis, and cell migration and invasion were explored using reverse transcription-quantitative polymerase chain reaction, Cell Counting Kit-8 assay, flow cytometry assay, and transwell assay, respectively. The relationship between PABPC1 and COL12A1 expression was assessed by Pearson's correlation analysis. The regulatory function of COL12A1 in PABPC1-affected BXPC3 cell behavior was studied after COL12A1 was overexpressed. RESULTS: PABPC1 and COL12A1 expression was upregulated in patients with PAAD and was linked to poor prognosis. Four hundred and seventy-four DEGs were observed in BXPC3 cells after PABPC1 silencing. GO and KEGG analyses revealed that the top 10 DEGs were enriched in cell adhesion pathways. Additionally, PABPC1 silencing inhibited cell viability, migration, and invasion and accelerated apoptosis in BXPC3 cells. PABPC1 silencing increased AZGP1 and ARHGAP30 expression and decreased CAV1 and COL12A1 expression in BXPC3 cells. PABPC1 positively mediated COL12A1 expression, whereas PABPC1 knockdown induced the inhibition of BXPC3 cell proliferation, migration, and invasion. CONCLUSION: The results of this study indicate that PABPC1 may function as a tumor promoter in PAAD, accelerating BXPC3 cell proliferation and metastasis by regulating COL12A1 expression.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Adenocarcinoma/patología , Proliferación Celular/genética , Colágeno Tipo XII/genética , Colágeno Tipo XII/metabolismo , Proteínas Activadoras de GTPasa , Neoplasias Pancreáticas/genética , Pronóstico , Proteína I de Unión a Poli(A)/metabolismo , Neoplasias PancreáticasRESUMEN
BACKGROUND: This study aimed to investigate the feasibility, effectiveness, and safety of pancreatic duct stenting in managing acute biliary pancreatitis (ABP) necessitating endoscopic retrograde cholangiopancreatography (ERCP). It further aimed to provide valuable insights for subsequent clinical diagnosis and treatment. METHODS: This research employs an observational retrospective case-control study design, encompassing patients with ABP who underwent ERCP at the hepatobiliary surgery department of the General Hospital of Ningxia Medical University between August 1, 2018, and December 31, 2020. A total of 229 cases were screened based on inclusion and exclusion criteria. Regardless of ABP severity, patients were categorized into the stent group (141) and the non-stent group (88). Changes in blood amylase (Amy), lipase (LIP), leukocyte count (WBC), total bilirubin (TBIL), alanine aminotransferase (ALT), hematocrit (HCT), and creatinine (CR) were compared between the two groups. Moreover, variables such as recovery time for oral feeding, hospitalization duration, hospitalization costs, local complications, systemic complications, and new organ failure were recorded to assess the therapeutic effect of pancreatic duct stenting. RESULTS: No significant differences were observed in gender, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, ABP severity grade, organ failure (OF), cholangitis, or biliary obstruction between the pancreatic stent and non-stent groups (P > 0.05). There was no significant difference in the incidence of complications related to acute pancreatitis between the two groups (P > 0.05). The median fasting and hospitalization times of patients in the stent group were significantly shorter than those in the non-stent group (P < 0.05). No significant differences between the groups were observed in hospitalization costs and in-hospital mortality (P > 0.05). There were no significant variations in white blood cell (WBC) count, TBIL, ALT, and creatinine (Cr) at admission, 72 h, and in the differences between the two groups (P > 0.05). The levels of Amy at admission and 72 h in the stent group were significantly higher than those in the non-stent group (P < 0.05). The differences in LIP and HCT in the stent group were considerably higher than in the non-stent group (P < 0.05). Although no significant differences were observed in mean Amy and LIP between the two groups (P > 0.05), the mean 72-h HCT in the stent group was 38.39% (95% confidence interval [CI] 37.82%-38.96%) was lower than that in the non-stent group (39.44%, 95% CI 38.70-40.17%) (P < 0.05). CONCLUSION: In the stent group, feeding time and hospital stay were significantly shorter than those in the non-stent group. No significant differences were observed between the two groups in the incidence of complications and mortality. The HCT value decreased more rapidly in the stent group. Early pancreatic stent implantation demonstrated the potential to shorten the eating and hospitalization duration of patients with ABP, facilitating their prompt recovery. TRIAL REGISTRATION: This study was registered as a single-center, retrospective case series (ChiCTR1800019734) at chictr.org.cn.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Pancreatitis/cirugía , Pancreatitis/etiología , Estudios Retrospectivos , Enfermedad Aguda , Estudios de Casos y Controles , Creatinina , Conductos Pancreáticos/cirugía , Resultado del Tratamiento , Stents/efectos adversosRESUMEN
Background: Acute pancreatitis (AP) is one of the most common gastrointestinal disorders, which causes death with a high mortality rate of about 30%. The study aims to identify whether the nonalcoholic fatty liver disease (NAFLD)-derived lncRNA MALAT1 participates in the inflammation of pancreatic cell and its potential mechanism. Methods: The NAFLD cell model was constructed by treating HepG2 cells with FFA. The in vitro model of acute pancreatitis (AP) was established by the administration of caerulein on AR42J cells. MALAT1 and si-MALAT1 were transfected into pancreatic cells, and then exosomes were collected from the NAFLD cell model and then were cocultured with AR42J cells. Transmission electron microscopy was used to observe the morphology of exosomes. Oil Red O staining was applied to reveal the lipid deposition. The triglyceride, IL-6, and TNF-α levels were detected using ELISA. The MALAT1 level in exosomes was detected by qRT-PCR. The CD9, CD63, CD81, and CYP2E1, LC3II, and LC3I levels were detected by western blot. Results: MALAT1 was upregulated in NAFLD-derived exosomes and increased the levels of IL-6 and TNF-α in pancreatic cells. NAFLD-derived exosomes inhibited YAP phosphorylation, decreased the levels of IL-6 and TNF-α, and reduced the ratio of LC3II/LC3I protein in pancreatic cells. Silencing MALAT1 significantly returned the inhibitory effect of NAFLD on hippo-YAP pathway. YAP1 signal transduction inhibitor CA3 reversed the decrease of LC3II/LC3I expression and the increase of IL-6 and TNF-α levels induced by MALAT1 in the AP cell model. Conclusions: NAFLD-derived MALAT1 exacerbates pancreatic cell inflammation via inhibiting autophagy by upregulating YAP.
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Enfermedad del Hígado Graso no Alcohólico , Pancreatitis , ARN Largo no Codificante , Enfermedad Aguda , Autofagia , Hepatocitos/metabolismo , Humanos , Inflamación , Interleucina-6/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor de Necrosis Tumoral alfaRESUMEN
Background: To explore the feasibility, safety, and efficacy of endoscopic transpapillary drainage through the minor papilla in the treatment of acute pancreatitis (AP). Methods: We retrospectively evaluated the safety and efficacy of endoscopic transpapillary drainage via the minor papilla among AP patients who were treated in our hospital from September 2018 to March 2020. Results: The present study included 18 patients (12 males and 6 females). All patients successfully received endoscopic transpapillary drainage via the minor papilla and were discharged upon recovery. No patient died, received ICU treatment, or had endoscopic operation-related complications. Two patients (11.11%) received additional abdominal paracentesis due to local complications. Fifteen patients (83.33%) resumed oral feeding within 3 days. The postoperative 24-hour leukocyte level, APACHE II score, serum amylase level, and lipase level significantly decreased compared with those at admission. The median hospitalization stay was 5 (3.75-9) days. The median hospitalization cost was 25,123.82 (22,942.50-43,874.68) RMB. The patients were followed up at 6-24 months, during which 4 patients (22.22%) had recurrence. Two patients had recurrence after pancreatic duct removal and other 2 patients in the period of carrying ducts. Conclusions: Early endoscopic transpapillary drainage via the minor papilla in cases of difficult cannulation or stenting via the major papilla is safe and effective in the treatment of AP, and is worthy of further popularization.
RESUMEN
GC-SAW was used to carry out online sampling analysis of the main business sources, residential sources, and roads in Rizhao City from August 22 to 29 in 2020. The spatial distribution characteristics of various volatile organic compounds (VOCs) in the atmosphere were obtained, and the chemical reactivity of the main components was studied. The results showed that the VOCs with carbon atoms greater than 5 (VOCC>5) were mainly toluene propylbenzene and n-octane, and the spatial distribution was significant; the average ρ(TVOCC>5) in the port area, downtown area, and industrial area were 80.5, 115.3, and 118.1 µg·m-3, respectively. Combined with road traffic impact and industrial production emissions, the maximum ρ(TVOCC>5) on the main roads in Rizhao City appeared near the Yingbin Road; the concentration value was 164.37 µg·m-3; the ρ(BTEX) in adhesive processing, painting, and glass factories reached 432.34, 1010.84, and 1989.85 µg·m-3, respectively. The chemical reactivity analysis of the main components of VOCC>5 showed that BTEX and n-octane were the important active components of ozone formation in Rizhao City.
Asunto(s)
Contaminantes Atmosféricos , Ozono , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Ciudades , Monitoreo del Ambiente , Ozono/análisis , Compuestos Orgánicos Volátiles/análisisRESUMEN
Pancreatic adenocarcinoma (PAAD) is one of the most fatal types of cancer in humans. However, the molecular mechanisms underlying the migration and invasion abilities of PAAD cells remain unclear. The aim of the present study was to explore the regulatory roles of microRNA (miR)325p in PAAD cells. miR325p mimic and inhibitor were used to transfect the human PAAD AsPC1 cell line to determine the role of miR325p in cell proliferation and metastasis. The starBase database predicted the binding of miR325p to the target gene TBC/LysMassociated domain containing 1 (TLDC1). Further analyses were performed to assess miR325p and TLDC1 expression levels in healthy and PAAD tissues, as well as the association between miR325p or TLDC1 expression and the prognosis of patients with PAAD. The interaction between miR325p and TLDC1 was verified using the dualluciferase reporter assay. miR325p and TLDC1 expression levels were detected by reverse transcriptionquantitative PCR and western blotting, respectively. The Cell Counting Kit8 assay was utilised to assess cell proliferation, whereas the woundhealing and Transwell assays were conducted to assess cell migration and invasion, respectively. miR325p expression levels were markedly lower in PAAD tissue compared with those in healthy tissue, and were significantly lower in PAAD cell lines compared with those in the human pancreatic duct cell line HPDE6, which corresponded with poor prognosis. miR325p significantly inhibited the proliferation of PAAD cells and markedly reduced migration and invasion compared with the negative controls. miR325p was shown to target TLDC1, with miR325p expression in PAAD being negatively correlated with TLDC1 expression. High TLDC1 expression levels were associated with a poorer prognosis compared with low TLDC1 expression levels. Cotransfection of miR325p mimic and pcDNA/TLDC1 demonstrated that TLDC1 significantly reversed miR325pmediated inhibition of the proliferation, migration and invasion of PAAD cells. Overall, the present study demonstrated that miR325p may serve as a tumorsuppressor gene by inhibiting the proliferation and migration and invasion of PAAD cells via the downregulation of TLDC1. Therefore, miR325p may serve as a potential diagnostic or prognostic marker for PAAD.