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Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require to multiply, once thought to be a characteristic of tumor cells known as the "Warburg effect". In fact, throughout the process of carcinogenesis, immune cells and stromal cells, two major cellular constituents of the tumor microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. In this review, we provide a full-scale review of the glycolytic remodeling of several types of TME cells and show how these TME cells behave in the acidic milieu created by glucose shortage and lactate accumulation as a result of increased tumor glycolysis. Notably, we provide an overview of putative targets and inhibitors of glycolysis along with the viability of using glycolysis inhibitors in combination with immunotherapy and chemotherapy. Understanding the glycolytic situations in diverse cells within the tumor immunological milieu will aid in the creation of subsequent treatment plans.
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Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log2fold change) > log21.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.
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Proliferación Celular , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Perfilación de la Expresión Génica , Hipertensión Pulmonar , Monocrotalina , Animales , Ratas , Hipertensión Pulmonar/inducido químicamente , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/patología , Masculino , Ratas Sprague-Dawley , Transcriptoma , Pulmón/patología , Pulmón/metabolismoRESUMEN
BACKGROUND: Sepsis is a common syndrome of multiorgan system dysfunction secondary to the dysregulated inflammatory response to infection. The role of pancreatic stone protein (PSP) in diagnosing sepsis has been investigated in previous studies. The meta-analysis aimed to comprehensively investigate the diagnostic value of PSP in identifying sepsis. METHODS: PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI), were systematically searched. Studies investigating the diagnostic performance of PSP were included. Pooled sensitivity, specificity, positive Likelihood Ratio (+ LR) and negative Likelihood Ratio (-LR), diagnostic odds ratio (DOR), and area under the curve (AUC) of summary receiver operating characteristic (SROC) were calculated. RESULTS: The sensitivity of PSP was 0.88 (95% CI: 0.77-0.94), and the pooled specificity was 0.78 (95% CI: 0.65-0.87). Pooled + LR, -LR, and DOR were 4.1 (2.3, 7.3), 0.16 (0.07, 0.34), and 26 (7, 98). The AUC value for the SROC of PSP was 0.90 (0.87, 0.92). The pooled sensitivity, specificity, + LR and - LR, and DOR for PSP among neonates were 0.91 (95% CI: 0.84, 0.96), 0.66 (95% CI: 0.58, 0.74), 3.97 (95% CI: 0.53, 29.58), 0.13 (95% CI: 0.02, 1.00), and 31.27 (95% CI: 0.97, 1004.60). CONCLUSIONS: This study indicates that PSP demonstrated favorable diagnostic accuracy in detecting sepsis. Well-designed studies are warranted to ascertain the value of PSP measurement to guide early empirical antibiotic treatment, particularly in neonates.
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Biomarcadores , Litostatina , Sepsis , Humanos , Biomarcadores/sangre , Litostatina/sangre , Curva ROC , Sensibilidad y Especificidad , Sepsis/diagnósticoRESUMEN
Starch and plant fibers are abundant natural polymers that offer biodegradability, making them potential substitutes for plastics in certain applications, but are usually limited by its high hydrophilicity, and low mechanical performance. To address this issue, polylactic acid (PLA) is blended with cellulose and chitosan to create a waterproof film that can be applied to starch-fiber foaming biodegradable composites to enhance their water resistance properties. Here, plant fibers as a reinforcement is incorporated to the modified starch by foaming mold at 260 °C, and PLA based hydrophobic film is coated onto the surface to prepare the novel hydrophobic bio-composites. The developed bio-composite exhibits comprehensive water barrier properties, which is significantly better than that of traditional starch and cellulose based materials. Introducing PLA films decreases water vapor permeability from 766.83 g/m2·24h to 664.89 g/m2·24h, and reduce hysteresis angles from 15.57° to 8.59° within the first five minutes after exposure to moisture. The water absorption rate of PLA films also decreases significantly from 12.3 % to 7.9 %. Additionally, incorporating hydrophobic films not only enhances overall waterproof performance but also improves mechanical properties of the bio-composites. The fabricated bio-composite demonstrates improved tensile strength from 2.09 MPa to 3.53 MPa.
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Interacciones Hidrofóbicas e Hidrofílicas , Poliésteres , Almidón , Resistencia a la Tracción , Agua , Poliésteres/química , Almidón/química , Agua/química , Permeabilidad , Quitosano/química , Celulosa/química , Vapor , Propiedades de SuperficieRESUMEN
OBJECTIVE: Our study aims to head to head compare the application of gallium-68-fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT in primary and metastatic lesions of gastric tumor to determine the superior diagnostic tool. MATERIALS AND METHODS: A systematic search, up to March 31, 2023, across PubMed, Embase, and Cochrane Library databases utilized a data-specific Boolean logic strategy. Sensitivity (SEN) and specificity (SPE) evaluations of 68Ga-FAPI and 18F-FDG PET/CT in gastric cancer lesions were conducted. The quality of the studies was assessed using QUADAS-2, and publication bias was examined through Begg and Egger tests. RESULTS: Analysis involved 141 gastric tumor patients and 2753 metastatic lesions in five studies, with overall satisfactory study quality and no apparent publication bias. Patient-level data showed a combined SEN of 0.95 (95% CI: 0.90-0.98) for 68Ga-FAPI and 0.84 (95% CI: 0.77-0.89) for 18F-FDG. At the lesion level, combined SEN were 0.91 (95% CI: 0.84-0.96) for 68Ga-FAPI and 0.72 (95% CI: 0.63-0.80) for 18F-FDG. The pooled SEN for detecting lymph node metastases was 0.78 (95% CI: 0.74-0.82) for 68Ga-FAPI and 0.35 (95% CI: 0.30-0.39) for 18F-FDG, with pooled SPE values of 0.99 (95% CI: 0.98-0.99) and 0.97 (95% CI: 0.96-0.98), respectively. For detecting distant metastases, pooled SEN values were 0.97 (95% CI: 0.96-0.98) and 0.69 (95% CI: 0.66-0.72) for 68Ga-FAPI and 18F-FDG, with pooled SPE values of 0.86 (95% CI: 0.82-0.89) and 0.64 (95% CI: 0.59-0.68), respectively. CONCLUSION: This meta-analysis concluded that 68Ga-FAPI PET/CT was significantly more sensitive than 18F-FDG PET/CT in assessing primary gastric tumors, lymph nodes, and distant metastases, but the difference in the specificity of lymph node metastasis was not significant.
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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Quinolinas , Neoplasias Gástricas , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Humanos , Metástasis de la Neoplasia , Sensibilidad y EspecificidadRESUMEN
Papillary thyroid carcinoma (PTC) is a prevalent histological subtype of thyroid cancer, whose occurrence and development may be related to circRNA dysregulation. This research proposed to unravel circ-LDLRAD3-related mechanisms in PTC. First, circ-LDLRAD3, miR-655-3p .and MAPK1 levels in PTC were quantitatively measured. Then, plasmid vectors or oligonucleotides that interfere with circ-LDLRAD3, miR-655-3p, or MAPK1 were transfected into PTC cells, followed by the analysis of proliferation, apoptosis, migration, and invasion. Finally, the targeted binding sites between miR-655-3p and circ-LDLRAD3 or MAPK1 were predicted by starBase and experimentally verified. Statistically, PTC samples expressed high circ-LDLRAD3 and MAPK1 and low miR-655-3p. Knocking down circ-LDLRAD3 or enhancing miR-655-3p hindered PTC cell proliferation, migration, and invasion, and forced apoptosis. circ-LDLRAD3 bound to miR-655-3p to affect MAPK1 expression. Elevating MAPK1 rescued circ-LDLRAD3 knockdown-allowed obstruction of PTC cell growth. In conclusion, circ-LDLRAD3 stimulates PTC development by releasing miR-655-3p-targeted MAPK1.
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Movimiento Celular , MicroARNs , ARN Circular , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , ARN Circular/genética , ARN Circular/metabolismoRESUMEN
Importance: Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts. Objectives: To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups. Design, Setting, and Participants: This survey study included 20â¯430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022. Exposures: National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018. Main Outcomes and Measures: Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis. Results: This study included 20â¯430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend). Conclusions and Relevance: The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.
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Obesidad Metabólica Benigna , Masculino , Adulto , Humanos , Femenino , Obesidad Metabólica Benigna/epidemiología , Encuestas Nutricionales , Estudios Transversales , Prevalencia , Obesidad/epidemiología , TriglicéridosRESUMEN
BACKGROUND AND AIMS: Very high levels of high-density lipoprotein cholesterol (HDL-C) have been paradoxically linked to increased mortality risk. The present study aimed to examine associations of HDL-C and varied sizes of the HDL particle (HDL-P) with mortality risk stratified by hypertension. METHODS AND RESULTS: This prospective cohort study included 429 792 participants (244 866 with hypertension and 184 926 without hypertension) from the UK Biobank. During a median follow-up of 12.7 years, 23 993 (9.8%) and 8142 (4.4%) deaths occurred among individuals with and without hypertension, respectively. A U-shaped association of HDL-C with all-cause mortality was observed in individuals with hypertension after multivariable adjustment, whereas an L-shape was observed in individuals without hypertension. Compared with individuals with normal HDL-C of 50-70 mg/dL, those with very high HDL-C levels (>90 mg/dL) had a significantly higher risk of all-cause mortality among individuals with hypertension (hazard ratio, 1.47; 95% confidence interval, 1.35-1.61), but not among those without hypertension (1.05, 0.91-1.22). As for HDL-P, among individuals with hypertension, a larger size of HDL-P was positively whereas smaller HDL-P was negatively associated with all-cause mortality. After additional adjustment for larger HDL-P in the model, the U-shaped association between HDL-C and mortality risk was altered to an L-shape among individuals with hypertension. CONCLUSIONS: The increased risk of mortality associated with very high HDL-C existed only in individuals with hypertension, but not in those without hypertension. Moreover, the increased risk at high HDL-C levels in hypertension was likely driven by larger HDL-P.
This study examined the potential modification of hypertension on associations of high-density lipoprotein cholesterol (HDL-C), especially at a very high level, and varied sizes of HDL particle (HDL-P) with the risk of mortality.Very high HDL-C levels were associated with increased risk of mortality in individuals with hypertension, but not in those without hypertension.In individuals with hypertension, the increased risk at a high HDL-C level was attributed to a larger size of HDL-P, which was directly associated with mortality risk. An inverse association with mortality was observed for a smaller size of HDL-P.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Causas de Muerte , Factores de Riesgo , Estudios Prospectivos , Bancos de Muestras Biológicas , HDL-Colesterol , Hipertensión/diagnóstico , Reino Unido/epidemiologíaRESUMEN
Discovery of disease biomarker based on untargeted metabolomics is informative for pathological mechanism studies and facilitates disease early diagnosis. Numerous of metabolomic strategies emerge due to different sample properties or experimental purposes, thus, methodological evaluation before sample analysis is essential and necessary. In this study, sample preparation, data processing procedure and metabolite identification strategy were assessed aiming at the discovery of biomarker of breast cancer. First, metabolite extraction by different solvents, as well as the necessity of vacuum-dried and re-dissolution, was investigated. The extraction efficiency was assessed based on the number of eligible components (components with MS/MS data acquired), which was more reasonable for metabolite identification. In addition, a simplified data processing procedure was proposed involving the OPLS-DA, primary screening for eligible components, and secondary screening with constraints including VIP, fold change and p value. Such procedure ensured that only differential candidates were subjected to data interpretation, which greatly reduced the data volume for database search and improved analysis efficiency. Furthermore, metabolite identification and annotation confidence were enhanced by comprehensive consideration of mass and MS/MS errors, isotope similarity, fragmentation match, and biological source confirmation. On this basis, the optimized strategy was applied for the analysis of serum samples of breast cancer, according to which the discovery of differential metabolites highly encouraged the independent biomarkers/indicators used for disease diagnosis and chemotherapy evaluation clinically. Therefore, the optimized strategy simplified the process of differential metabolite exploration, which laid a foundation for biomarker discovery and studies of disease mechanism.
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Dryopteris crassirhizoma Nakai is a fern plant with important evolutionary and medicinal values. Herein, we assembled the complete chloroplast genome of D. crassirhizoma by next-generation sequencing technology. The complete chloroplast genome of D. crassirhizoma was 153,355 bp in length, and the GC content was 42.86%; the genome consisted of a pair of inverted repeats (IRs, 23,470 bp), a small single copy region (SSC, 21,570 bp) and a large single copy region (LSC, 84,854 bp). The genome contained 111 genes, namely, 73 protein-coding genes, 34 tRNA genes and four rRNA genes. The phylogenetic analysis suggested that both D. crassirhizoma and D. decipiens from Dryopteridaceae were most closely related to Lepisorus clathratus from Polypodiaceae.
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Corydalis bungeana Turcz. is a perennial herb belonging to the family Papaveraceae. Its chloroplast genome was sequenced and characterized. The cp genome of C. bungeana is 167,629 bp long with a GC content of 36.52%. A total of 144 genes were identified in this cp genome, including 79 protein-coding genes, 31 tRNAs and four rRNAs. A phylogenetic tree based on the complete nucleic acid sequence indicated that C. bungeana was classified into Corydaleae and had a close relationship with Lamprocapnos spectabilis.
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In this study, the effect of leachate seepage on the strength properties of a landfill temporary cover material: sewage sludge solidified with soda residue, ground granulated blast furnace slag, and quicklime, was investigated using small-scale column tests. The strength of the solidified sludge was reflected by penetration resistance with a micro penetrometer. The results showed that the penetration resistance increased at first, but then decreased with the increase in duration. The peak value for penetration resistance appeared at around the 75th day under the effect of leachate seepage. In contrast, without leachate seepage, penetration resistance increased at first as duration increased and then remained stable. The main hydration products were calcium silicate hydrate, ettringite and hydrocalumite. Some pollutants, such as copper, chromium, and arsenic, were also stabilized by the solidified sludge. The nuclear magnetic resonance results showed that the sample with highest penetration resistance had a reduced pore volume, especially macropore volume. Furthermore, leachate corrosion and the removal of some substances contributed to the decrease in penetration resistance after long-term seepage. The strength performance of temporary cover in laboratory short-term seepage and leachate soaking environments might be different from that in a landfill leachate seepage environment. This study improves understanding about the performance of temporary cover materials in landfill.
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Arsénico , Contaminantes Químicos del Agua , Cromo , Aguas del Alcantarillado , Instalaciones de Eliminación de ResiduosRESUMEN
AWPPH is a newly discovered long noncoding (lnc)RNA that serves an oncogenic role in the development of several types of cancer; however, its involvement in nonsmall cell lung cancer (NSCLC) is unknown. Therefore, the aim of the present study was to investigate the function of AWPPH in NSCLC. The results demonstrated that AWPPH expression levels were significantly upregulated in the lung tissues and serum samples of patients with NSCLC compared with in healthy controls. High expression levels of AWPPH effectively distinguished NSCLC patients from healthy controls. In addition, patients with high expression levels of AWPPH had significantly shorter survival time. AWPPH overexpression in NSCLC cells promoted proliferation and inhibited apoptosis, and activated the Wnt/ßcatenin signaling pathway, which is a classic signaling pathway involved in the development and progression of different types of cancers. Treatment with a Wnt/ßcatenin signaling pathway activator produced no significant effect on AWPPH expression. Therefore, it was concluded that lcRNA AWPPH could promote the growth of NSCLCs by activating the Wnt/ßcatenin signaling pathway.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Proliferación Celular , Neoplasias Pulmonares/diagnóstico , ARN Largo no Codificante/metabolismo , Vía de Señalización Wnt , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , ARN Largo no Codificante/genética , Tasa de Supervivencia , Adulto JovenRESUMEN
Pulmonary fibrosis (PF) is a chronic, fibrosing interstitial pneumonia and devastating disease. Here we investigated the potential roles of Kruppel-like factor 2 (KLF2) on pulmonary fibrosis and inflammation response. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM). The mRNA and protein levels of KLF2 were assayed by RT-PCR and Western blotting respectively. The extent of lung fibrosis was determined using hematoxylin and eosin (HE) staining and Masson's trichrome staining, and the hydroxyproline content was quantified. RT-PCR was used to evaluate the mRNA expression of collagen type 1a1 (col1a1), col3a1, α-SMA, TNF-α, IL-1ß and IL-6. The concentrations of TNF-α, IL-1ß, and IL-6 in bronchoalveolar lavage fluid (BALF) and lung tissue were examined by ELISA. Also, the effects of KLF2 on activator protein-1 (AP-1) were evaluated by measuring the c-Jun and c-Fos protein levels. We found that KLF2 was remarkably downregulated in BLM-treated rats, both in mRNA and protein levels. Additionally, overexpression of KLF2 attenuated the destruction of the alveolar space and pulmonary interstitial collagen hyperplasia, and deposition reduced the expression of col1a1, col3a1, and α-SMA, and blocked the production of TNF-α, IL-1ß, and IL-6 in BALF and lung tissue in vivo. Moreover, adenoviral transduction of KLF2 inhibited TGF-ß1-induced expression of col1a1, col3a1, and α-SMA in vitro. Mechanically, BLM up-regulated c-Jun and c-Fos expression, which was impeded by KLF2 overexpression. Taken together, our data indicate that KLF2 attenuates pulmonary fibrosis and inflammation, possibly through the regulation of AP-1.
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Factores de Transcripción de Tipo Kruppel/metabolismo , Fibrosis Pulmonar/metabolismo , Factor de Transcripción AP-1/metabolismo , Actinas/genética , Animales , Bleomicina/toxicidad , Línea Celular , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Colágeno Tipo III/genética , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Mediadores de Inflamación/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
BACKGROUND: Obesity is characterized by the excess accumulation of adipose tissues, mainly composed of adipocytes. The differentiation of adipocytes is one of the major events in the process of adipogenesis. Among various adipogenic transcription factors, CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferators-activated receptor γ (PPARγ) have been identified as essential regulators of adipocyte differentiation. METHODS: RT-qPCR assay was conducted to detect the expression of microRNA-142a-3p (miR-142a-3p), high-mobility group AT-hook 1 (HMGA1) mRNA, C/EBPα mRNA, and PPARγ mRNA. Western blot assay was performed to measure the protein levels of HMGA1, C/EBPα and PPARγ. Bioinformatics analysis and luciferase reporter assay were carried out to explore the interaction between miR-142a-3p and HMGA1. RESULTS: miR-142a-3p expression was notably increased and HMGA1 expression was markedly reduced during 3T3-L1 preadipocyte differentiation. Functional analysis revealed that miR-142a-3p overexpression promoted 3T3-L1 preadipocyte differentiation. Further investigations on molecular mechanisms showed that HMGA1 was a target of miR-142a-3p in 3T3-L1 preadipocytes. Moreover, the knockdown of HMGA1 induced 3T3-L1 preadipocyte differentiation. Additionally, HMGA1 silencing abolished miR-142a-3p deficiency-mediated inhibitory effect on 3T3-L1 preadipocyte differentiation. CONCLUSION: MiR-142a-3p overexpression facilitated 3T3-L1 preadipocyte differentiation by targeting HMGA1, highlighting the importance of miR-142a-3p, HMGA1 and the miR-142a-3p/HMGA1 axis in adipogenesis.
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The present study aimed to investigate the roles of the hydrolytic process of N-cadherin by A disintegrin and metalloproteases 10 (ADAM10) in sustaining myocardial structure and integrity, and discuss the mechanisms of ventricular remodeling in dilated cardiomyopathy (DCM). Single chain variable fragment antibody (ScFv) with the ability to specifically block the ADAM10 hydrolysis site of N-cadherin was designed and constructed. Western blot analysis and flow cytometry were used to detect the expression of N-cadherin and its C-terminal fragment 1 (CTF1) on cardiomyocytes, and cells were also subjected to a cell adhesion assay. Furthermore, in a rat model of dilated cardiomyopathy (DCM), the effects of intracardiac injection of the recombinant adenovirus on cardiac structure and contractile function were observed by hematoxylin and eosin staining and color Doppler echocardiography. The recombinant ScFv-expressing adenoviral plasmid with the ability to block the ADAM10 hydrolysis site on N-cadherin was successfully constructed and efficiently transfected into H9C2 cells. After transfection, N-cadherin protein expression was significantly increased, CTF1 protein was significantly decreased and the adhesion capability of myocardial cells was significantly improved. In the in vivo experiment, N-cadherin expression was significantly increased in the treatment group compared with that in the model group, and the structure and function of the heart were significantly improved. In conclusion, blocking of the ADAM10 hydrolysis site on N-cadherin by ScFv increased N-cadherin expression and improved ventricular remodeling. The present study provided experimental evidence for a novel approach for the treatment and prevention of DCM.
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We studied the relationship between the polymorphisms of -800G/A and +915G/C in transforming growth factor-ß1 (TGF-ß1) gene and lung cancer susceptibility. The sequence-specific primer polymerase chain reaction (PCR-SSP) technique was used to test 156 non-small cell lung cancer (NSCLC) patients that were selected as the observation group and 156 patients with pneumonia and tuberculosis that were selected as the control group (age and gender 1:1 proximal matching principle) and the polymorphisms of the first exon -800G/A and +915G/C TGF-ß1 genes. The expression of TGF-ß1 levels in peripheral blood was detected using ELISA. The proportion of -800G/A gene AA subtype and A allelic gene in the observation group was significantly higher than that in the control group, while the proportion of +915G/C gene CC subtype and C allelic gene was also significantly higher than that in the control group (P<0.05). The cancer risk [odds ratio (OR)] of patients with A allelic gene in -800G/A gene was 4.8 (95% CI=2.563-6.537, P<0.05), while the cancer risk (OR) of patients with C allelic gene in +915G/C gene was 4.7 (95% CI=2.317-5.864, P<0.05). The serum TGF-ß1 expression levels of -800G/A gene AA subtype in the observation group was significantly higher than the GG type, GA type and the control group, while the TGF-ß1 level of +915G/C gene CC subtype was significantly higher than the GG type, GC type and the control group (P<0.05). Therefore, the polymorphisms of -800G/A and +915G/C in TGF-ß1 gene are closely related to the lung cancer susceptibility.
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OBJECTIVE: To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of ß1 adrenergic receptor G1165C in children with enterovirus 71 (EV71) infection in hand foot and mouth disease (HFMD). METHODS: The polymerase chain reaction (PCR) was used to detect the expression of gene polymorphism of ß1 adrenergic receptor G1165C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD (P < 0.05); however, the levels of plasma adrenaline in two groups had no statistical differences (P > 0.05); There was no significant difference in the distribution of ß1 adrenergic receptor G1165C genotype and allele between EV71 infection group and healthy control group (P > 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well (P > 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group (P > 0.05), and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups (P > 0.05). CONCLUSIONS: As the disease gets worse, the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD, which is an important indicator to evaluate the progress of the disease. However, the gene polymorphism of ß1 adrenergic receptor G1165C have no significant correlation, not only with the susceptibility and severity of EV71 infection in hand, foot and mouth disease, but also with the levels of catecholamine.
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Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder of women, with complex pathogenesis and heterogeneous manifestations. Professor Jin Yu recently wrote an article entitled "Proposal of Diagnosis and Diagnostic Classification of PCOS in Integrated Traditional Chinese and Western Medicine."From this, the Obstetrics and Gynecology branches of the Chinese Association of Integrative Medicine and the China Association of Chinese Medicine collaborated with the Gynecology branch of the Chinese Association for Research and Advancement of Chinese Medicine to draft a report on the consensus of criteria for the diagnosis and classification of PCOS in integrated traditional Chinese and Western medicine. The diagnosis for PCOS includes all three features: (1) oligo-ovulation or anovulation; (2) clinical and/or laboratory evidence of hyperandrogenism;(3) PCOS is classified into four types: types Ia,Ib, IIa, and IIb. Syndrome differentiation types for PCOS in traditional Chinese medicine are as follows: Kidney deficiency with phlegm blockage syndrome, Kidney Yin deficiency with phlegm blockage and blood stasis syndrome, and Kidney deficiency with Liver Qi stagnation syndrome.
Asunto(s)
Medicina Tradicional China , Síndrome del Ovario Poliquístico/clasificación , Consenso , Prestación Integrada de Atención de Salud , Femenino , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Qi , Deficiencia YinRESUMEN
NSCLC accounts for over 80% of all lung cancers and is associated with poor prognosis. Human nuclear distribution C (hNUDC) was predicted to be the target gene of microRNA-194 (miR-194). The present study was designed to demonstrate the mechanism of miR-194 in the regulation of non-small cell lung cancer (NSCLC) via targeting the hNUDC. The hNUDC expression was found to strongly be increased while the miR-194 decreased significantly in the NSCLC cell lines when compared with the healthy controls. Moreover, the luciferase report confirmed the targeting reaction between miR-194 and hNUDC. After transfection with miR-194 mimic into NSCLC cells, we found that the miR-194 overexpression resulted in abnormal nuclear division, decreased cell proliferation and inhibited the expression of hNUDC and Mpl/ERK pathway proteins. Furthermore, the hNUDC overexpression affected the suppression effect of miR-194 in 95D cells, indicating that miR-194 suppresses tumor cell process by inhibiting the hNUDC expression. In brief, the present study suggests that the upregulation of miR-194 affects the hNUDC expression, leading to a downregulated expression of Mpl/ERK pathway proteins, and suppresses the mitosis and proliferation of NSCLC cells. These results offer a potential therapeutic strategy for the treatment of lung cancer.