RESUMEN
Porphyran possesses various activities, while the effects of the porphyran from Porphyra haitanensis (PPH) on obesity are rarely reported. In this study, C57BL/6J male mice were fed with HFD combined with PPH gavage (50 mg/kg/d) for 16 weeks, and body weight was measured once a week. After that, serum, adipose, and liver tissues were collected for physiological and biochemical analyses. Our research indicated that PPH treatment alleviated obesity in HFD-fed mice. PPH alleviated fat accumulation in serum, liver, and adipose tissues. In addition, PPH activated the AMPK-HSL/ACC pathway in epididymal adipose tissue to reduce lipid accumulation. Moreover, PPH turned white adipose into brown and activated the PGC 1α-UCP 1-mitochondrial pathway in scapular adipose tissue to generate more heat. Interestingly, PPH regulated colonic microbiota homeostasis in obese mice, including significant elevation of Roseburia and Eubacterium and marked reduction of Helicobacter. Moreover, Spearman's correlation analysis demonstrated that regulation of gut microbiota can decrease lipid accumulation. In summary, our study illustrated that PPH possesses the potential to be developed as an anti-obesity agent.
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BACKGROUND: Circadian positive feedback loop (CPFL) genes (CLOCK, BAML1, and NPAS2) have been implicated in cancer initiation and progression. The purpose of this study was to explore the effects of single-nucleotide polymorphisms (SNPs) in CPFL genes on prognosis of gastric cancer (GC) patients. METHODS: Nine functional SNPs from the three CPFL genes were genotyped in a cohort of 704 GC patients undergoing resection. Multivariate Cox regression model and Kaplan-Meier curve were used for prognosis analysis. RESULTS: Among the nine SNPs, rs11133399 in CLOCK, rs1044432 and rs2279284 in BAML1 were significantly associated with GC overall survival and recurrence-free survival. The unfavorable genotypes of these SNPs showed a cumulative effect on GC prognosis. Multivariate assessment model indicated that these SNPs, in conjunction with clinical variables, enhanced the power to predict GC prognosis. In addition, survival tree analysis revealed the genotype of rs11133399 as a primary risk factor contributing to the prognosis of GC patients. Functional assays showed that the G allele in rs11133399 significantly enhanced luciferase reporter activity than A allele. Immunohistochemical analysis further demonstrated that the genotype of rs11133399 was significantly associated with the expression level of CLOCK in GC tissues, suggesting that this SNP might affect the prognosis of GC through its influence on the expression of CLOCK gene. CONCLUSIONS: Our data indicate that SNPs in CPFL genes might contribute to the clinical outcome of GC through their impact on gene expression. Further studies are needed to elucidate its underlying molecular mechanisms.
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Péptidos y Proteínas de Señalización del Ritmo Circadiano/genética , Polimorfismo de Nucleótido Simple , Neoplasias Gástricas/genética , Factores de Transcripción ARNTL/genética , Anciano , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteínas CLOCK/genética , China/epidemiología , Relojes Circadianos/genética , Epistasis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Pronóstico , Regiones Promotoras Genéticas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugíaRESUMEN
The latent expression pattern of Epstein-Barr Virus (EBV) genes in nasopharyngeal carcinoma (NPC) has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type III latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through realtime PCR.We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type III latency and lytic genes. This study provided further insights into the potential role of EBV in the development of NPC.
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Perfilación de la Expresión Génica/métodos , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virología , Línea Celular Tumoral , Herpesvirus Humano 4/metabolismo , Humanos , Proteínas Inmediatas-Precoces/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal , Transactivadores/metabolismo , Latencia del Virus/genéticaRESUMEN
The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage-independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.
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Línea Celular Tumoral , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Adulto , Animales , Pueblo Asiatico , Transformación Celular Neoplásica , Ensayo de Unidades Formadoras de Colonias , ADN Viral/metabolismo , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Trasplante de Neoplasias , ARN Viral/metabolismo , Proteínas de la Matriz Viral/metabolismo , Proteínas Virales/metabolismoRESUMEN
BACKGROUND: The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN) is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC) is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs) in NPC susceptibility. METHODS: We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software. RESULTS: A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs) of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006) and 2.52 (1.29-4.93; P = 0.007) respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90) increased risks of developing NPC (P = 0.003). Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002) and the association was still significant when using 1000 permutation test runs (P = 0.001). CONCLUSIONS: Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.
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Moléculas de Adhesión Celular/genética , Estudios de Asociación Genética , Variación Genética , Lectinas Tipo C/genética , Regiones Promotoras Genéticas , Receptores de Superficie Celular/genética , Adulto , Carcinoma , Estudios de Casos y Controles , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/epidemiología , Neoplasias Nasofaríngeas/genética , Polimorfismo de Nucleótido Simple , RiesgoRESUMEN
BACKGROUND: Many kinetochore proteins have been shown to be associated with human cancers. The aim of the present study was to clarify the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in esophageal carcinoma and its correlation with clinicopathological features. METHODS: We examined the expression of CENP-H in immortalized esophageal epithelial cells as well as in esophageal carcinoma cells, and in 12 cases of esophageal carcinoma tissues and the paired normal esophageal tissues by RT-PCR and Western blot analysis. In addition, we analyzed CENP-H protein expression in 177 clinicopathologically characterized esophageal carcinoma cases by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. RESULTS: The level of CENP-H mRNA and protein were higher in the immortalized cells, cancer cell lines and most cancer tissues than in normal control tissues. Immunohistochemistry showed that CENP-H was expressed in 127 of 171 ESCC cases (74.3%) and in 3 of 6 esophageal adenocarcinoma cases (50%). Statistical analysis of ESCC cases showed that there was a significant difference of CENP-H expression in patients categorized according to gender (P = 0.013), stage (P = 0.023) and T classification (P = 0.019). Patients with lower CENP-H expression had longer overall survival time than those with higher CENP-H expression. Multivariate analysis suggested that CENP-H expression was an independent prognostic marker for esophageal carcinoma patients. A prognostic value of CENP-H was also found in the subgroup of T3 approximately T4 and N0 tumor classification. CONCLUSION: Our results suggest that CENP-H protein is a valuable marker of esophageal carcinoma progression. CENP-H might be used as a valuable prognostic marker for esophageal carcinoma patients.