RESUMEN

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Asunto(s)

Osteogénesis , Ligamento Periodontal , Células Madre , Diente Primario , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Humanos , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Diente Primario/citología , Células Madre/efectos de los fármacos , Lipopolisacáridos/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inflamación , Transducción de Señal/efectos de los fármacos , Células Cultivadas , Reacción en Cadena en Tiempo Real de la Polimerasa , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/análisis

RESUMEN

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

RESUMEN

Background: Previous studies demonstrated that induction chemotherapy (IC) followed by de-escalated chemoradiotherapy adapted to tumor response was effective in treating childhood nasopharyngeal carcinoma (NPC), but the toxicity profile of this treatment strategy, and whether childhood patients with advanced stages can obtain enough benefits from it requires further investigation. Methods: We conducted a single-center phase II trial (NCT03020329). All participants received 3 cycles of paclitaxel liposome, cisplatin and 5-fluorouracil (TPF)-based IC. Patients who showed complete or partial response received de-escalated radiotherapy of 60 Gy with 3 cycles of concurrent cisplatin, and those who showed stable or progressive disease received standard-dose radiotherapy of 70 Gy with concurrent cisplatin. The primary endpoint was the complete response (CR) rate at the end of concurrent chemoradiotherapy (CCRT). Findings: From November 2016 to March 2021, 44 patients were recruited in the cohort. The CR rate was 80% (35/44, 95% CI, 65-90) of the whole cohort. All patients achieved CR 3 months after CCRT. By the last follow-up, the 3-year progression-free survival and overall survival were 91% (95% CI, 82-99) and 100% respectively. Dry mouth was the most common late toxicity, with an incidence of 41% (18/44), followed by skin fibrosis and hearing impairment. No patient suffered from severe late toxicity and growth retardation. Interpretation: Our results proved the efficacy and safety of TPF regimen followed by de-escalated radiotherapy with concurrent cisplatin in treating stage IVa-b childhood NPC patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

RESUMEN

OBJECTIVE This study aimed to propose a co-expression-network (CEN) based gene functional inference by extending the "Guilt by Association" (GBA) principle to predict candidate gene functions for type 1 diabetes mellitus (T1DM). METHODS Firstly, transcriptome data of T1DM were retrieved from the genomics data repository for differentially expressed gene (DEGs) analysis, and a weighted differential CEN was generated. The area under the receiver operating characteristics curve (AUC) was chosen to determine the performance metric for each Gene Ontology (GO) term. Differential expression analysis identified 325 DEGs in T1DM, and co-expression analysis generated a differential CEN of edge weight > 0.8. RESULTS A total of 282 GO annotations with DEGs > 20 remained for functional inference. By calculating the multifunctionality score of genes, gene function inference was performed to identify the optimal gene functions for T1DM based on the optimal ranking gene list. Considering an AUC > 0.7, six optimal gene functions for T1DM were identified, such as regulation of immune system process and receptor activity. CONCLUSIONS CEN-based gene functional inference by extending the GBA principle predicted 6 optimal gene functions for T1DM. The results may be potential paths for therapeutic or preventive treatments of T1DM.

Asunto(s)

Diabetes Mellitus Tipo 1/genética , Biomarcadores , Perfilación de la Expresión Génica , Humanos , Curva ROC , Transcriptoma

RESUMEN

SUMMARY OBJECTIVE This study aimed to propose a co-expression-network (CEN) based gene functional inference by extending the "Guilt by Association" (GBA) principle to predict candidate gene functions for type 1 diabetes mellitus (T1DM). METHODS Firstly, transcriptome data of T1DM were retrieved from the genomics data repository for differentially expressed gene (DEGs) analysis, and a weighted differential CEN was generated. The area under the receiver operating characteristics curve (AUC) was chosen to determine the performance metric for each Gene Ontology (GO) term. Differential expression analysis identified 325 DEGs in T1DM, and co-expression analysis generated a differential CEN of edge weight > 0.8. RESULTS A total of 282 GO annotations with DEGs > 20 remained for functional inference. By calculating the multifunctionality score of genes, gene function inference was performed to identify the optimal gene functions for T1DM based on the optimal ranking gene list. Considering an AUC > 0.7, six optimal gene functions for T1DM were identified, such as regulation of immune system process and receptor activity. CONCLUSIONS CEN-based gene functional inference by extending the GBA principle predicted 6 optimal gene functions for T1DM. The results may be potential paths for therapeutic or preventive treatments of T1DM.

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RESUMO OBJETIVO O objetivo deste estudo é realizar uma inferência funcional genética baseada na rede de coexpressão (CEN), expandindo o escopo do princípio de "Culpa por Associação" (GBA - Guilt by Association) para prever as funções genéticas do diabetes mellitus tipo 1 (T1DM). MÉTODOS Primeiro, os dados transcritos do T1DM foram recuperados do repositório de dados genômicos para a análise dos genes diferenciais (DEGs), e foi gerada uma CEN diferencial ponderada. A área sob a curva ROC (AUC) foi escolhida para determinar a métrica de desempenho para cada termo de Ontologia Genética (GO). A análise da expressão diferencial identificou 325 DEGs no T1DM, e a análise de coexpressão gerou uma CEN diferencial com aresta de peso >0,8. RESULTADOS Um total de 282 anotações de GO com DEGs >20 foram mantidas para inferência funcional. Ao calcular a pontuação de multifuncionalidade dos genes, a inferência da função genética foi realizada para identificar as funções genéticas ideais para T1DM com base na lista de classificação genética ideal. Considerando um valor de AUC >0,7, foram identificadas seis funções genéticas ideais para a T1DM, tais como a regulação do processo imunológico e da atividade dos receptores. CONCLUSÕES A inferência funcional genética baseada em CEN, ao expandir o princípio de GBA, previu seis funções genéticas ideais para o T1DM. Os resultados podem ser caminhos potenciais para tratamentos terapêuticos ou preventivos do T1DM.

Asunto(s)

Humanos , Diabetes Mellitus Tipo 1/genética , Biomarcadores , Curva ROC , Perfilación de la Expresión Génica , Transcriptoma

RESUMEN

4-Coumaric acid: coenzyme A ligase (4CL) is a key enzyme in the phenylpropanoid metabolic pathway that regulates the biosynthesis of lignin and flavonoids. Therefore, the study of 4CL is important to explore the accumulation and regulation of metabolites. This study investigated the role that the 4CL2 gene from Dryopteris fragrans (Df4CL2) plays in the metabolite synthesis. Changes in gene expression, enzyme activity, and the content of lignin and flavonoids were measured in different tissues of tobacco as model plant that was successfully transferred with Df4CL2. Tobacco plants with Df4CL2 (transgenic tobacco, TT) were successfully obtained via the Agrobacterium-transformation method. This TT tended to be thicker and had an earlier flowering period than wild type tobacco (WT). The expression levels of Df4CL2 were higher in the stem, leaf, and root in TT compared to WT. In addition, compared to WT, TT had higher 4CL enzyme activity and higher lignin and flavonoids contents. This suggests that Df4CL2 is involved in the synthesis of lignin and flavonoids in D. fragrans. This research provides important evidence toward understanding the phenylpropanoid metabolic pathway in ferns.

RESUMEN

PURPOSE: Hepatitis B core antibody (HBcAb) positivity is regarded as a sensitive marker for occult and prior hepatitis B virus (HBV) infection. However, the prognosis of patients with HBcAb-positive in non-B, non-C hepatocellular carcinoma (NBNC-HCC) remains unclear. The study aimed to compare the clinicopathological characteristics of patients with HBcAb-positive NBNC-HCC to those with overt HBV (hepatitis B surface antigen positive) HCC. METHODS: 306 HCC patients underwent hepatectomy were divided into two groups: an overt HBV-HCC group and HBcAb-positive NBNC-HCC group. Then patients were analyzed using propensity score matching (PSM) to reduce selection bias. Clinicopathological characteristics and survival outcomes were compared between the two groups. Univariate and multivariate analysis for risk factors were also evaluated. RESULTS: HBcAb-positive NBNC-HCC group showed comparable survival outcomes to the overt HBV-HCC group (3-year overall survival rates 66% vs 62%, 69% vs 53%; 3-year recurrence-free survival rates 49% vs 40%, 47% vs 37%; P > 0.05) before and after PSM. Patients with HBcAb-positive NBNC-HCC were older, had more complications, higher proportions of vascular invasion, and larger tumor sizes but lower proportions of cirrhosis, elevated alanine aminotransferase and prothrombin time. CONCLUSIONS: HBcAb-positive NBNC-HCC group had more advanced tumors, but their prognosis was relatively comparable to that of the other group. Therefore, we believe that screening is also necessary in HBcAb-positive patients for early detection of HCC, especially in the elderly.

Asunto(s)

Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Virus de la Hepatitis B/aislamiento & purificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Femenino , Hepatectomía , Hepatitis B/complicaciones , Anticuerpos contra la Hepatitis B/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Resultado del Tratamiento

RESUMEN

In the present study, the repellent activities of the leaf and/or stem crude extracts of Glycosmis lucida Wall. ex Huang, G. craibii var. glabra, G. craibii Tanaka, G. oligantha Huang, G. pentaphylla (Retz) Correa. and G. esquirolii (Levl.) Tanaka were analyzed by using assays on petri dishes against Tribolium castaneum and Liposcelis bostrychophila. The leaf and stem extracts of G. lucida, G. craibii var. glabra, G. craibii Tanaka, G. oligantha and G. esquirolii possessed significant repellent activities against T. castaneum, the same level repellent with the positive control, DEET. However, the extracts of G. pentaphylla, no repellency but some insect attractant was observed. Moreover, they also showed repellent activities against L. bostrychophila. These results indicate that extracts from G. lucida and G. oligantha leaf could be a source of novel repellent against insects.

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En el presente estudio, las actividades repelentes de la hoja y/o tronco de los extractos crudos de Glycosmis lucida Wall. ex Huang, G. craibii var. glabra, G. craibii Tanaka, G. oligantha Huang, G. pentaphylla (Retz) Correa y G. esquirolii (Levl.) Tanaka se analizaron mediante el uso de ensayos en placas de Petri contra Tribolium castaneum y Liposcelis bostrychophila. Los extractos de las hojas y tallo de G. lucida, G. craibii var. glabra, G. craibii Tanaka, G. oligantha y G. esquirolii poseían actividades repelentes significativas contra T. castaneum, el mismo nivel repelente del control positivo, el DEET. Sin embargo, los extractos de G. pentaphylla, no se observó la repelencia pero sí actividad atrayente de insectos. Por otra parte, también se mostraron las actividades repelentes contra L. bostrychophila. Estos resultados indican que los extractos de hojas de G. lucida y G. oligantha podrían ser una fuente de repelente contra los insectos.

Asunto(s)

Insectos , Repelentes de Insectos/farmacología , Extractos Vegetales/farmacología , Hojas de la Planta/química , Rutaceae/química , Tribolium

Asunto(s)

Femenino , Humanos , Masculino , Diabetes Mellitus Tipo 1/genética , Población Blanca/genética , Polimorfismo de Nucleótido Simple/genética , /genética

Asunto(s)

Diabetes Mellitus Tipo 1/genética , Polimorfismo de Nucleótido Simple/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 2/genética , Población Blanca/genética , Femenino , Humanos , Masculino

RESUMEN

The aim of the present study was to determine whether dietary Bacillus subtilis natto could affect growth performance of Muscovy ducks. A total of 120 hundred Muscovy ducks at the age of 1 day were randomly assigned to four groups (30 Muscovy ducks/group), and fed with diets supplemented with 0% (control group), 0.1%, 0.2%, and 0.4% Bacillus subtilis natto, respectively during the 6-week feeding period. Weight gain, feed intake and feed conversion efficiency of Muscovy ducks were significantly improved by the dietary addition of Bacillus subtilis natto, and the results were more significant in 0.4% dietary Bacillus subtilis natto treatment group; Also, Bacillus subtilis natto reduced Escherichia coli and Salmonella colonies, and increased lactobacilli population in the ileum and the cecum. Biochemical parameters, including total protein, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), AKP (alkaline phosphatase), triiodothyronine (T3) and tetraiodothyronine (T4) contents (pBacillus subtilis natto was added to the diets (p 0.05), and improved duodenum and immune functions. However, the results above were not significantly different between birds fed 0.1% Bacillus subtilis natto supplemented diets and the control group (p>0.05). The results of the present study indicate that diets with 0.4% Bacillus subtilis natto improved the growth performance of Muscovy ducks by increasing the absorption of protein, simulating hormone secretion, suppressing harmful microflora, and improving the duodenal structure and immune functions of Muscovy ducks. It is suggested that Bacillus subtilis natto is a potential candidate to be used use as a probiotic to improve the growth performance of Muscovy ducks.

Asunto(s)

Animales , Bacillus subtilis/patogenicidad , Patos/crecimiento & desarrollo , Patos/microbiología

RESUMEN

The aim of the present study was to determine whether dietary Bacillus subtilis natto could affect growth performance of Muscovy ducks. A total of 120 hundred Muscovy ducks at the age of 1 day were randomly assigned to four groups (30 Muscovy ducks/group), and fed with diets supplemented with 0% (control group), 0.1%, 0.2%, and 0.4% Bacillus subtilis natto, respectively during the 6-week feeding period. Weight gain, feed intake and feed conversion efficiency of Muscovy ducks were significantly improved by the dietary addition of Bacillus subtilis natto, and the results were more significant in 0.4% dietary Bacillus subtilis natto treatment group; Also, Bacillus subtilis natto reduced Escherichia coli and Salmonella colonies, and increased lactobacilli population in the ileum and the cecum. Biochemical parameters, including total protein, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), AKP (alkaline phosphatase), triiodothyronine (T3) and tetraiodothyronine (T4) contents (pBacillus subtilis natto was added to the diets (p 0.05), and improved duodenum and immune functions. However, the results above were not significantly different between birds fed 0.1% Bacillus subtilis natto supplemented diets and the control group (p>0.05). The results of the present study indicate that diets with 0.4% Bacillus subtilis natto improved the growth performance of Muscovy ducks by increasing the absorption of protein, simulating hormone secretion, suppressing harmful microflora, and improving the duodenal structure and immune functions of Muscovy ducks. It is suggested that Bacillus subtilis natto is a potential candidate to be used use as a probiotic to improve the growth performance of Muscovy ducks.(AU)

Asunto(s)

Animales , Patos/crecimiento & desarrollo , Patos/microbiología , Bacillus subtilis/patogenicidad

RESUMEN

The aim of the present study was to determine whether dietary Bacillus subtilis natto could affect growth performance of Muscovy ducks. A total of 120 hundred Muscovy ducks at the age of 1 day were randomly assigned to four groups (30 Muscovy ducks/group), and fed with diets supplemented with 0% (control group), 0.1%, 0.2%, and 0.4% Bacillus subtilis natto, respectively during the 6-week feeding period. Weight gain, feed intake and feed conversion efficiency of Muscovy ducks were significantly improved by the dietary addition of Bacillus subtilis natto, and the results were more significant in 0.4% dietary Bacillus subtilis natto treatment group; Also, Bacillus subtilis natto reduced Escherichia coli and Salmonella colonies, and increased lactobacilli population in the ileum and the cecum. Biochemical parameters, including total protein, GOT (glutamic oxaloacetic transaminase), GPT (glutamic pyruvic transaminase), AKP (alkaline phosphatase), triiodothyronine (T3) and tetraiodothyronine (T4) contents (pBacillus subtilis natto was added to the diets (p 0.05), and improved duodenum and immune functions. However, the results above were not significantly different between birds fed 0.1% Bacillus subtilis natto supplemented diets and the control group (p>0.05). The results of the present study indicate that diets with 0.4% Bacillus subtilis natto improved the growth performance of Muscovy ducks by increasing the absorption of protein, simulating hormone secretion, suppressing harmful microflora, and improving the duodenal structure and immune functions of Muscovy ducks. It is suggested that Bacillus subtilis natto is a potential candidate to be used use as a probiotic to improve the growth performance of Muscovy ducks.