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The heart is the central organ of the circulatory system, and its proper development is vital to maintain human life. As fetal heart development is complex and poorly understood, we use single-cell RNA sequencing to profile the gene expression landscapes of human fetal hearts from the four-time points: 8, 10, 11, 17 gestational weeks (GW8, GW10, GW11, GW17), and identified 11 major types of cells: erythroid cells, fibroblasts, heart endothelial cells, ventricular cardiomyocytes, atrial cardiomyocytes, macrophage, DCs, smooth muscle, pericytes, neural cells, schwann cells. In addition, we identified a series of differentially expressed genes and signaling pathways in each cell type between different gestational weeks. Notably, we found that ANNEXIN, MIF, PTN, GRN signalling pathways were simple and fewer intercellular connections in GW8, however, they were significantly more complex and had more intercellular communication in GW10, GW11, and GW17. Notably, the interaction strength of OSM signalling pathways was gradually decreased during this period of time (from GW8 to GW17). Together, in this study, we presented a comprehensive and clear description of the differentiation processes of all the main cell types in the human fetal hearts, which may provide information and reference data for heart regeneration and heart disease treatment.
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Comunicación Celular , Análisis de la Célula Individual , Transcriptoma , Humanos , Comunicación Celular/genética , Transcriptoma/genética , Análisis de Secuencia de ARN , Corazón Fetal/metabolismo , Corazón Fetal/embriología , Regulación del Desarrollo de la Expresión Génica , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Transducción de Señal/genética , Diferenciación Celular/genética , Perfilación de la Expresión Génica , Edad GestacionalRESUMEN
During the COVID-19 pandemic, an abundance of plastic face masks has been consumed and disposed of in the environment. In addition, substantial amounts of plastic mulch film have been used in intensive agriculture with low recovery. Butyl benzyl phthalate (BBP) and TiO2 nanomaterials (nTiO2) are widely applied in plastic products, leading to the inevitable release of BBP and nTiO2 into the soil system. However, the impact of co-exposure of BBP and nTiO2 at low concentrations on earthworms remains understudied. In the present study, transcriptomics was applied to reveal the effects of individual BBP and nTiO2 exposures at a concentration of 1 mg kg-1, along with the combined exposure of BBP and nTiO2 (1 mg kg-1 BBP + 1 mg kg-1 nTiO2 (anatase)) on Metaphire guillelmi. The result showed that BBP and nTiO2 exposures have the potential to induce neurodegeneration through glutamate accumulation, tau protein, and oxidative stress in the endoplasmic reticulum and mitochondria, as well as metabolism dysfunction. The present study contributes to our understanding of the toxic mechanisms of emerging contaminants at environmentally relevant levels and prompts consideration of the management of BBP and nTiO2 within the soil ecosystems.
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Nanoestructuras , Oligoquetos , Ácidos Ftálicos , Animales , Humanos , Oligoquetos/genética , Ecosistema , Pandemias , Titanio , Suelo , Perfilación de la Expresión GénicaRESUMEN
In the most primitive jawless vertebrate lamprey, the complement-dependent cytotoxicity regulated by variable lymphocyte receptors (VLRs) plays an important role in the adaptive immunity. Our previous studies have shown that the lamprey pore-forming protein (LPFP) acted as the terminal effector of VLR to lyse and kill the target cells. Here, the recombinant GST-LPFP protein was expressed and purified in prokaryotic expression system, and then used as the immunogen to produce mouse monoclonal antibody and rabbit polyclonal antibody. With these antibodies, we proved that LPFP existed as homodimers in the lamprey serum, and could be recruited to the membrane of target cells after stimulation. In conclusion, the antibodies we produced could specifically recognize the LPFP protein, which could be the useful tools to further study the pore-forming mechanism of LPFP.
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Anticuerpos Monoclonales de Origen Murino , Proteínas de Peces , Proteínas Citotóxicas Formadoras de Poros , Animales , Anticuerpos Monoclonales de Origen Murino/química , Anticuerpos Monoclonales de Origen Murino/inmunología , Anticuerpos Monoclonales de Origen Murino/aislamiento & purificación , Femenino , Proteínas de Peces/química , Proteínas de Peces/inmunología , Proteínas de Peces/aislamiento & purificación , Células HeLa , Humanos , Lampreas , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/inmunología , Proteínas Citotóxicas Formadoras de Poros/aislamiento & purificación , ConejosRESUMEN
Although some epidemiological studies have investigated the association between Hepatitis C virus (HCV) infection and the development of kidney cancer, the results are far from consistent. We conducted a systematic review and meta-analysis of observational studies to determine the association. PubMed, EMBASE and Cochrane database were searched from 1 January 1975 to 7 January 2020. Study selection, data extraction and bias assessment (using the Newcastle-Ottawa scale) were performed independently by 2 authors. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated using a random-effects model. In all, 16 studies (11 cohort studies and 5 case-control studies) involving a total of 391,071 HCV patients and 38,333,839 non-HCV controls were included. The overall analysis showed a 47% higher risk to develop kidney cancer among the patients with HCV infection (pooled OR 1.47; 95% CI 1.14-1.91), despite significant heterogeneity (I2 = 87.6%). The multivariable meta-regression showed that study design, age, sample size and HIV co-infection were significant sources of variance, and totally accounted for 82% of the I2 . The risk of KC in HCV patients was further increased in studies without HCV/HBV- and HCV/HIV- co-infection (pooled OR 1.66; 95%CI 1.23-2.24). Multiple sensitivity analyses did not change the significant association. The present meta-analysis indicated that HCV-infected patients have a significantly higher risk of developing kidney cancer. Our results highlighted the rationale for improved renal surveillance in HCV patients for the early diagnosis of kidney cancer. Further investigations for the mechanisms underlying HCV-induced kidney cancer are warranted.
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Coinfección , Infecciones por VIH , Hepatitis C , Neoplasias Renales , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Neoplasias Renales/epidemiologíaRESUMEN
BACKGROUND & AIMS: Human induced pluripotent stem cell (hiPSC)-derived liver modeling systems have the potential to overcome the shortage of donors for clinical application and become a model for drug development. Although several strategies are available to generate hepatic micro-tissues, few have succeeded in generating a liver organoid with hepatobiliary structure from hiPSCs. METHODS: At differentiation stages I and II (day 1-15), 25% of mTeSR™ culture medium was added to hepatic differentiation medium to induce endodermal and mesodermal commitment and thereafter hepatic and biliary co-differentiation. At stage III (day 15-45), 10% cholesterol+ MIX was added to the maturation medium to promote the formation and maturation of the hepatobiliary organoids. Phenotypes and functions of organoids were determined by specific markers and multiple functional assays both in vitro and in vivo. RESULTS: In this system, hiPSCs were induced to form 3D hepatobiliary organoids and to some extent recapitulated key aspects of early hepatogenesis in a parallel fashion. The organoids displayed a series of functional attributes. Specifically, the induced hepatocyte-like cells could take up indocyanine green, accumulate lipid and glycogen, and displayed appropriate secretion ability (albumin and urea) and drug metabolic ability (CYP3A4 activity and inducibility); the biliary structures in the system showed gamma glutamyltransferase activity and the ability to efflux rhodamine and store bile acids. Furthermore, after transplantation into the immune-deficient mice, the organoids survived for more than 8â¯weeks. CONCLUSION: This is the first time that functional hepatobiliary organoids have been generated from hiPSCs. The organoid model will be useful for in vitro studies of the molecular mechanisms of liver development and has important potential in the therapy of liver diseases. LAY SUMMARY: Herein, we established a system to generate human induced pluripotent stem cell-derived functional hepatobiliary organoids in vitro, without any exogenous cells or genetic manipulation. To some extent this model was able to recapitulate several key aspects of hepatobiliary organogenesis in a parallel fashion, holding great promise for drug development and liver transplantation.
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Conductos Biliares/embriología , Células Madre Pluripotentes Inducidas/citología , Hígado/embriología , Organoides/citología , Diferenciación Celular , Células Cultivadas , Humanos , OrganogénesisRESUMEN
Epileptogenesis, induced by status epilepticus (SE), is a chronic process, and intervention in this progress may prevent chronic epilepsy. It has been proposed that DNA methylation might be related with epileptogenesis. RASgrf1 has a differentially methylated region at the promoter which can silence gene expression. We have previously observed the down-regulation of RASgrf1 in epilepsy patients and proved that hypermethylation of RASgrf1 reaches maximal level at the latent period in mice after kainate-induced SE (KA mice), with corresponding alteration of RASgrf1 expression. In the present study, N-phthalyl-L-tryptophan (RG108), a DNA methyltransferase inhibitor, was applied in KA mice at latent phase and the behavior, electroencephalogram and pathological changes were observed in chronic phase. Methylation and expression of RASgrf1 were determined by polymerase chain reaction (PCR), western blotting, and bisulfite sequencing PCR. The results showed that the incidence of spontaneous recurrent seizures (SRS) was significantly lower in the RG108 group than the normal saline (NS) group. Subgroup analysis showed significant hypermethylation and lower expression of RASgrf1 in the RG108-SRS subgroup and the NS-SRS subgroup but not in the RG108-NSRS (no SRS) subgroup and the NS-NSRS subgroup compared with the control group. No significant difference was found between the RG108-SRS and NS-SRS subgroups. Meanwhile, hippocampal neuronal loss was observed in RG108-SRS and NS-SRS subgroups. We thus demonstrated that RG108 could modify the progression of epileptogenesis after KA induced SE and prevent chronic epilepsy. Meanwhile, hypermethylation of RASgrf1 after KA induced SE could be reversed with corresponding changes of RASgrf1 expression. Additionally, we speculated that RASgrf1 might be a potential epigenetic mediator in epileptogenesis and chronic epilepsy.
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Expresión Génica/efectos de los fármacos , Estado Epiléptico/metabolismo , ras-GRF1/metabolismo , Animales , Metilación de ADN/efectos de los fármacos , Modelos Animales de Enfermedad , Electroencefalografía , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ácido Kaínico/farmacología , Masculino , Ratones Endogámicos C57BL , Ftalimidas/farmacología , Regiones Promotoras Genéticas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Estado Epiléptico/inducido químicamente , Estado Epiléptico/genética , Estado Epiléptico/fisiopatología , Triptófano/análogos & derivados , Triptófano/farmacologíaRESUMEN
Dynamin 1 is a neuron-specific guanosine triphosphatase (GTPase) that is an essential component of membrane fission during synaptic vesicle recycling and endocytosis. This study evaluated the dynamin 1 expression pattern in the acute lithium-pilocarpine rat model and in patients with temporal lobe epilepsy (TLE) and investigated whether altering the dynamin 1 expression pattern affects epileptic seizures in vivo and in vitro. The immunofluorescence, western blot analysis, and reverse transcription-PCR results show that the dynamin 1 expression level increased significantly in experimental rats from day 1 to day 7 after the onset of seizures and was significantly higher in TLE patients. The behavioral study revealed that inhibiting dynamin 1 increased the latency time of the first seizure and decreased the frequency and severity of the seizures. In addition, electrophysiological recordings from brain slices showed that inhibiting dynamin 1 reduces the frequency of Mg-free induced seizure-like activity. The anticonvulsant effect of dynasore was more effective at 10 µM than at 1 µM or 160 µM. These results indicate that the altered level of dynamin 1 may contribute to the development of epileptic seizures and that the targeted regulation of dynamin 1 activity may control epileptic seizures.
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Dinamina I/metabolismo , Epilepsia del Lóbulo Temporal/metabolismo , Convulsiones/metabolismo , Regulación hacia Arriba , Adolescente , Adulto , Animales , Anticonvulsivantes/uso terapéutico , Ondas Encefálicas , Dinamina I/genética , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Humanos , Hidrazonas/uso terapéutico , Litio/toxicidad , Masculino , Pilocarpina/toxicidad , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción , Convulsiones/etiología , Convulsiones/fisiopatologíaRESUMEN
Intermedin (IMD) exerts a potent function in preventing atherosclerosis, while the mechanism remains unclear. Here we investigated the potential molecular mechanism responsible for the protective function of IMD in preventing foam cell formation in RAW264.7 cells. In our present study, IMD significantly inhibited intracellular cholesterol accumulation. Additionally, IMD dose-dependently down-regulated CD36 expression, which was confirmed by real-time quantitative reverse transcription-PCR and Western blot analysis. Our data suggest that IMD could inhibit the formation of foam cells through, at least partly, a CD36-dependent mechanism. This study suggests that IMD may be a therapeutic candidate for treating atherosclerosis.
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Antígenos CD36/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Hormonas Peptídicas/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Compuestos Azo , Western Blotting , Antígenos CD36/biosíntesis , Antígenos CD36/fisiología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Cartilla de ADN , Relación Dosis-Respuesta a Droga , Ratones , Oxidación-Reducción , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Metallic nanomaterials (MNMs) possess unique properties that have led to their widespread application in fields such as electronics and medicine. However, concerns about their interactions with environmental factors and potential toxicity to aquatic life have emerged. There is growing evidence suggesting MNMs can have detrimental effects on aquatic ecosystems, and are potential for bioaccumulation and biomagnification in the food chain, posing risks to higher trophic levels and potentially humans. While many studies have focused on the general ecotoxicity of MNMs, fewer have delved into their trophic transfer within aquatic food chains. This review highlights the ecotoxicological effects of MNMs on aquatic systems via waterborne exposure or dietary exposure, emphasizing their accumulation and transformation across the food web. Biomagnification factor (BMF), the ratio of the contaminant concentration in predator to that in prey, was used to evaluate the biomagnification due to the complex nature of aquatic food chains. However, most current studies have BMF values of less than 1 indicating no biomagnification. Factors influencing MNM toxicity in aquatic environments include nanomaterial properties, ion variations, light, dissolved oxygen, and pH. The multifaceted interactions of these variables with MNM toxicity remain to be fully elucidated. We conclude with recommendations for future research directions to mitigate the adverse effects of MNMs in aquatic ecosystems and advocate for a cautious approach to the production and application of MNMs.
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Nanoestructuras , Contaminantes Químicos del Agua , Humanos , Ecosistema , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Cadena Alimentaria , Nanoestructuras/toxicidad , Estado NutricionalRESUMEN
Mesenchymal stem cells (MSCs) are a population of multipotent cells with remarkable regenerative and immunomodulatory properties. Wharton's jelly (WJ) from the umbilical cord (UC) has gained increasing interest in the biomedical field as an outstanding source of MSCs. However, challenges such as limited supply and lack of standardization in existing methods have arisen. This article presents a novel method for enhancing MSC yield by dissecting intact WJ from the umbilical cord. The method employs blunt dissection to remove the epithelial layer, maintaining the integrity of the entire WJ and resulting in an increased quantity and viability of harvested MSCs. This approach significantly reduces WJ waste compared to conventional sharp dissection methods. To ensure the purity of WJ-MSCs and minimize external cellular influence, a procedure utilizing internal tension to peel off the endothelium after flipping the UC was conducted. Additionally, the Petri dish was inverted for a short time during explant culture to improve attachment and cell outgrowth. Comparative analysis demonstrated the superiority of the proposed method, showing a higher yield of WJ and WJ-MSCs with better viability than traditional methods. The similar morphology and expression pattern of cell surface markers in both methods confirm their characterization and purity for various applications. This method provides a high-yield and high-viability approach for WJ-MSC isolation, demonstrating great potential for the clinical application of MSCs.
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Células Madre Mesenquimatosas , Cordón Umbilical , Células Madre Mesenquimatosas/citología , Cordón Umbilical/citología , Humanos , Gelatina de Wharton/citología , Separación Celular/métodos , Técnicas Citológicas/métodos , FemeninoRESUMEN
BACKGROUND: Intermedin (IMD), a novel peptide related to calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM), may have localized actions as a modulator of cardiac function. The aim of the study is to explore the effect of IMD on angiotensin II (Ang II) and endothelin-1 (ET-1) induced hypertrophy in ventricular myocytes of neonatal rat and to try to elucidate the possible mechanism. METHODS: Neonatal rat cardiomyocytes were cultured in serum-free medium with and without AngII (1 micromol/L) or ET-1 (60 micromol/L) in the presence and absence of IMD (1 micromol/L). Hypertrophic responses (including cell surface area, alpha-actin, and beta-myosin heavy chain mRNA expression) and cardiomyocyte expression of NADPH oxidase gp91phox were determined. RESULTS: Ang II induced increases in cardiomyocyte size to 305 +/- 32 microm2 (n = 198, p < 0.05, at 48 hours), alpha-actin expression to 4 +/- 2.8-fold (n = 6, p < 0.05, at 48 hours) and beta-myosin heavy chain expression to 11 +/- 4.8-fold (n = 6, p < 0.05, at 48 hours), and expression of the gp91phox subunit of NADPH oxidase to 29.4 +/- 12.7-fold (n = 6, p < 0.05, at 48 hours). These effects were all significantly inhibited by IMD; cardiomyocyte size, alpha-actin expression, beta-myosin heavy chain expression, and gp91phox expression were reduced to 265 +/- 32 microm2 (n = 374, p < 0.05), 3.0 +/- 1.7-fold (n = 6, p < 0.05), 8.7 +/- 4.9-fold (n = 6, p < 0.05), 3.9 +/- 3-fold (n = 6, p < 0.05), respectively. IMD also significantly inhibited ET1-induced increases in cardiomyocyte size and superoxide generation. CONCLUSIONS: IMD exerts an antihypertrophic effect on neonatal cardiomyocytes by reduced levels of superoxide, suggesting that an antioxidant action contributes to the antihypertrophic actions of IMD.
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Adrenomedulina/farmacología , Angiotensina II/toxicidad , Cardiomegalia/inducido químicamente , Cardiomegalia/prevención & control , Endotelina-1/toxicidad , Miocitos Cardíacos/efectos de los fármacos , Neuropéptidos/farmacología , Actinas/biosíntesis , Actinas/genética , Actinas/metabolismo , Análisis de Varianza , Animales , Animales Recién Nacidos , Cardiomegalia/metabolismo , Cardiomegalia/patología , Tamaño de la Célula/efectos de los fármacos , Células Cultivadas , Interacciones Farmacológicas , Expresión Génica/efectos de los fármacos , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/patología , Cadenas Pesadas de Miosina/biosíntesis , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , NADPH Oxidasa 2 , NADPH Oxidasas/biosíntesis , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Sustancias Protectoras/farmacología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Nucleosides, organic acids, and amino acids separated from Morchella esculenta are well known for their nutritional value and flavor. However, how to increase their content in a better way has been a challenge. In this study, the effect of adding jujube kernel on the active components of M. esculenta was investigated by untargeted metabolomics using UPLC-MS/MS. A total of 1,243 metabolites were identified, of which 262 metabolites (21.078%) were organic acids and derivatives, 245 metabolites (19.71%) were lipids and lipid-like molecules, and 26 metabolites (2.092%) were nucleosides, nucleotides, and analogues. Subsequently, differential metabolites between groups were screened by the orthogonal partial least squares-discriminant analysis model, which showed that 256 metabolites were identified as significantly different for the positive ion model and 149 for the negative ion model. Moreover, significant differential metabolites (VIP > 1, P < 0.05) in annotation of kyoto encyclopedia of genes and genomes pathway were investigated, which showed that ABC transporters were the most commonly observed transporters, followed by pyrimidine metabolism and purine metabolism. The results indicated that the main components of jujube kernel might be conducive to the accumulation of nucleoside organic acids and amino acid metabolites in M. esculenta. These results provide important information for the understanding of more suitable way for cultivation of M. esculenta.
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Agricultural films are extensively utilized in high-intensity agriculture, with China's annual usage reaching 1.5 million tons. Unfortunately, the recovery rate is less than 60%, leading to an inevitable accumulation of plastic mulch in agricultural soils. This accumulation primarily introduces butyl benzyl phthalate (BBP) into soil ecosystems, whose specific effects remain largely unclear, thereby posing potential risks. The present study focuses on the exposure impact of BBP on earthworms, Metaphire guillelmi, a commonly found endogenic earthworm within real farmland, as it provides insight into the direct interaction between biota gut health and contaminants. Specifically, we studied the biomarkers related to oxidative stress, the digestive system, and neurotoxicity within the gut of Metaphire guillelmi, and the integrated biological response (IBR) index was utilized to track these markers at different timeframes after BBP exposures. Our findings indicate that BBP exposures lead to oxidative damage, digestive system inhibition, and neurotoxicity, with IBR indexes of 14.6 and 17.3 on the 14th and 28th days, respectively. Further, the underlying mechanisms at a molecular level through molecular docking were investigated. The results showed that the most unstable interaction was with the Na+K+-ATPase (binding energy: -2.25 kcal-1), while BBP displayed stable bonds with superoxide dismutase and 8-hydroxydeoxyguanosine via hydrogen bonds and hydrophobic interaction. These interactions resulted in changes in protein conformation and their normal physiological functions, offering new insights into the molecular mechanism underlying enzymatic activity changes. This study has significant implications for the prediction of toxicity, environmental risk assessment, and the establishment of regulations related to BBP.
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Background: Cell cycle-related genes (CDK1, CDK5, CDC20, CCNA2, CCNB1, and CCNB2) play important roles in the regulation of mitotic cell cycle in eukaryotes. However, the correlation between cell cycle-related genes and tumor-infiltrating and prognosis of hepatocellular carcinoma (HCC) needs further investigation. Methods: Two public websites, Tumor Immune Estimate Resource (TIMER) and Oncomine, were used to assess the expression levels of cycle-related genes. We also analyzed the protein expression levels of six cell cycle-related genes using the HPA database. In addition, Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) database were used to investigate the impact of cell cycle-related gene expression levels on the clinical prognosis of HCC. The correlation between cell cycle-related genes and cancer immune infiltrates was analyzed through TIMER site. Subsequently, GEPIA and TIMER database were used to assess the correlation between the expression of six cell cycle-related genes and polygenic markers in monocytes and macrophages, respectively. The cell cycle-related genes were also analyzed to find the associated genes with the highest alteration frequency, by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) approaches of Metascape and String database, respectively. Results: The expression levels of cell cycle-related genes were up-regulated in tumor tissues compared with normal tissues. Subsequently, the expression of high cell cycle-related genes was positively correlated with poor overall survival (OS) and progression-free survival (PFS) in HCC, for CDK1 (OS: HR = 2.15, P = 1.1E-05 PFS: HR = 2.03, P = 2.3E-06), CDK5 (OS: HR = 1.85, P = 0.0035 PFS: HR = 1.26, P = 0.17), CDC20 (OS: HR = 2.49, P = 5.1E-07 PFS: HR = 1.77, P = 0.00012), CCNA2 (OS: HR = 1.92, P = 0.00018 PFS: HR = 1.96, P = 5.2E-06), CCNB1 (OS: HR = 2.34, P = 3.4E-05 PFS: HR = 1.97, P = 5.3E-06), and CCNB2 (OS: HR = 1.91, P = 0.0013 PFS: HR = 1.63, P = 0.0011), respectively. Furthermore, the transcription level of cell cycle-related genes was significantly correlated with immune infiltrating levels of CD4+ T and CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs) in HCC, respectively. Amongst them, the expression levels of CDK1, CDC20, CCNA2, CCNB1 and CCNB2 manifest strongly correlated with diverse immune marker sets in HCC. Conclusions: Our results demonstrated that cell cycle-related genes played key roles in the prognosis of HCC. Meanwhile, they were significantly correlated with immune infiltrating levels of CD4+ T cells, CD8+ T cells, neutrophils, macrophages and DCs in HCC, respectively. In addition, CDK1, CDC20, CCNA2, CCNB1 and CCNB2 expressions may be involved in the regulation of monocytes and tumor-associated macrophages (TAMs) in HCC, respectively. These findings strongly suggested that cell cycle-related genes could be used as novel biomarkers for exploring the prognosis and immune cells infiltration of HCC.
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To date, hepatocytes derived from human-induced pluripotent stem cells (hiPSC) provide a potentially unlimited resource for clinical application and drug development. However, most hiPSC-derived hepatocyte-like cells initiated differentiation from highly purified definitive endoderm, which are insufficient to accurately replicate the complex regulation of signals among multiple cells and tissues during liver organogenesis, thereby displaying an immature phenotypic and short survival time in vitro. Here, we described a protocol to achieve codifferentiation of endoderm-derived hepatocytes and mesoderm-derived nonparenchymal cells by the inclusion of BMP4 into hepatic differentiation medium, which has a beneficial effect on the hepatocyte maturation and lifespan in vitro. Our codifferentiation system suggests the important role of nonparenchymal cells in liver organogenesis. Hopefully, these hepatocytes described here provide a promising approach in the therapy of liver diseases.
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OBJECTIVE: To analyze the changes in the prevalence of obesity and abdominal obesity in the middle-aged Chengdu residents during 1992 and 2007. METHODS: In 1992, a cohort of 1365 Chengdu residents were selected using a combination of nonrandom cluster sampling and intra-cluster random sampling stratified by age and gender for cardiovascular disease risk factor surveys. In 2007, 1061 of the selected residents completed a second survey. We analyzed the changes in the prevalence of obesity and abdominal obesity in the middle-aged residents using BMI and waist circumference as indicators. RESULTS: From 1992 to 2007, the BMI, waist circumference, prevalence of obesity and abdominal obesity of this cohort of respondents increased significantly (P < 0.05). The 2007 survey found significant higher BMI, waist circumference, and prevalence of obesity and abdominal obesity in the residents of 50-64 years old than those with the same age in 1992 (P < 0.05). The female respondents had consistently greater standardized prevalence of obesity and abdominal obesity than their male counterparts except for the abdominal obesity in the 2007 survey. CONCLUSION: Both prevalence of obesity and abdominal obesity are increasing in Chengdu residents, even after adjustment of age.
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Obesidad Abdominal/epidemiología , Obesidad/epidemiología , Anciano , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
The research on human hepatobiliary development and disorders has been constrained by minimal access to human fetal tissue, and low accuracy of animal models. To overcome this problem, we have established a system for the differentiation of human pluripotent stem cells (hPSCs) into functional hepatobiliary organoids (HBOs). We have previously reported that our 45-d approach closely mimics key stages of hepatobiliary development, starting with the differentiation of hiPSC into endoderm and a small part of mesoderm, and subsequently into hepatoblast-like cells, followed by the parallel generation of hepatocyte-like cells and cholangiocyte-like cells, formation of immature HBO expressing early hepatic and biliary markers, and mature HBO displaying hepatobiliary functionality. In this study, we present an updated version of our previous protocol, which only needs 35 days to achieve maturation in vitro. Furthermore, a hepatobiliary culture medium is developed to functionally maintain the HBOs for more than 1.5 months. The capacity of this approach for producing large amounts of functional HBOs and enabling long-term culture in vitro holds promise for applications on developmental research, disease modeling, as well as screening of therapeutic agents.
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OBJECTIVE: To investigate the association between serum uric acid (UA) and early kidney damage and the prevalence of early kidney damage [89 >or= GFR >or= 60 ml * min(-1) * (1.73m(2))(-1)] in the middle-aged and elders with normal serum creatinine. METHODS: A survey of cardiovascular risk factors, including serum UA and estimated glomerular filtration rate (eGFR) [according to MDRD (modification of diet in renal disease) equation], was carried out in a local general population of Chengdu. A total of 1023 subjects with normal serum creatinine [mean age: (63 +/- 6) years; male: female = 52.7%: 47.3%] were recruited by random sampling method. The subjects were divided into 4 groups (A, B, C, D) according to the quartiles of serum UA levels (A: UA < 282 micromol/L, B: 282 micromol/L
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Enfermedades Renales/fisiopatología , Riñón/fisiopatología , Ácido Úrico/sangre , Anciano , China/epidemiología , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
OBJECTIVE: To study the relationship between PPARgamma2 Pro12Ala polymorphism and cognitive function in patients with primary hypertension. METHODS: This study enrolled 502 hypertensive patients of Chinese Han population from Jan 2008 to Feb 2009 in West China Hospital of Sichuan University. We collected the general data and applied the mini mental state examination (MMSE) to test the cognitive function and computed score. Total cholesterol (TC), triglyeride (TG), fasting plasma glucose (FPG) and postprandial blood sugar (PPBS), fasting insulin (FINS) and postprandial plasma insulin (PINS) were measured. PCR-RELP method was used to analysis the PPARgamma2 Pro12Ala gene polymorphism. RESULTS: Pro12Pro genotype was present in 88.6% of the patients and Prol2Ala genotype was present in 11.4% of the population. Allele frequencies were 94.3% for Pro allele and 5.7% for Ala allele. In cognitive normal group, the frequencies of PP and PA genotype were 328 (87.2%) and 48 (12.8%), while the frequencies of PP and PA genotypes in the cognitive dysfunction group were 126 (92.9%), 9 (7.1%) respectively. Analyzed by chi2 test, both the genotype frequency and the allele frequency of PPARy2 Pro12Ala polymorphism did not display statistical variability between the cognitive normal group and the cognitive dysfunction group, even eliminating the influence of age and sexuality. CONCLUSION: Pro12Ala polymorphism in PPARgamma2 with primary hypertension may not associate with cognitive impairment.
Asunto(s)
Trastornos del Conocimiento/genética , Hipertensión/complicaciones , PPAR gamma/genética , Polimorfismo Genético , Anciano , Alanina/genética , Alelos , Trastornos del Conocimiento/complicaciones , Femenino , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Prolina/genéticaRESUMEN
OBJECTIVE: To investigate the changes of blood pressure (BP) levels of a general population in Chengdu, China from 1992 to 2007. METHODS: A baseline survey on CVD risk factors was carried out in a general population of Chengdu in 1992. A total of 1365 adults aged 35-64 years were recruited randomly. In 2007, 1061 of the participants completed a follow up survey. RESULTS: 1) The systolic blood pressure (SBP) levels increased with age in both men and women, and larger increase was found in older people. The diastolic blood pressure (DBP) levels also increased with age, however, the smallest increase was found in the age group of 45 to 54 years. 2) People of 50-64 years old in 2007 had higher SBP than those of the same age in 1992. Similar changes were also found for DBP in men, but not in women. 3) From 1992 to 2007, the prevalence of hypertension increased in all of the age groups. The greater increase occurred in the younger population. 4) During the 15 years, the prevalence of hypertension increased from 13.2% to 51.2% in men, and from 14.0% to 45.1% in women. People of 50-64 years old had higher prevalence of hypertension in 2007 than those of the same age in 1992. CONCLUSION: SBP and DBP increase with age, and younger people have larger increase than older people. The prevalence of hypertension increases with age, and the greater increase also occurred in younger people. In people with the same age of 50-64 years, the prevalence of hypertension and SBP and DBP levels are higher in 2007 than in 1992, except for DBP in women.