RESUMO
Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-ß, IL-6, and IL-1ß. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.
Assuntos
Peptídeo 1 Semelhante ao Glucagon/farmacologia , Mediadores da Inflamação/farmacologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Macrófagos/efeitos dos fármacos , Peptídeos/farmacologia , Peçonhas/farmacologia , Tecido Adiposo/metabolismo , Animais , Ensaios de Migração Celular , Exenatida , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo , CamundongosRESUMO
Glucagon-like peptide 1 (GLP-1), a kind of gut hormone, is used in the treatment of type 2 diabetes (T2D). Emerging evidence indicates that GLP-1 has anti-inflammatory activity. Chronic inflammation in the adipose tissue of obese individuals is a cause of insulin resistance and T2D. We hypothesized that GLP-1 analogue therapy in patients with T2D could suppress the inflammatory response of macrophages, and therefore inhibit insulin resistance. Our results showed that GLP-1 agonist (exendin-4) not only attenuated macrophage infiltration, but also inhibited the macrophage secretion of inflammatory cytokines including TNF-β, IL-6, and IL-1β. Furthermore, we observed that lipopolysaccharide (LPS)-induced macrophage conditioned media could impair insulin-stimulated glucose uptake. This effect was compensated by treatment with the conditioned media from macrophages treated with the combination of LPS and exendin-4. It was also observed that exendin-4 directly inhibited the activation of NF-κB in macrophages. In conclusion, our results indicated that GLP-1 improved inflammatory macrophage-derived insulin resistance by inhibiting NF-κB pathway and secretion of inflammatory cytokines in macrophages. Furthermore, our observations suggested that the anti-inflammatory effect of GLP-1 on macrophages can contribute to GLP-1 analogue therapy of T2D.
Assuntos
Humanos , Animais , Camundongos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Mediadores da Inflamação/farmacologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Macrófagos/efeitos dos fármacos , Peptídeos/farmacologia , Peçonhas/farmacologia , Tecido Adiposo/metabolismo , Ensaios de Migração Celular , Inflamação/metabolismo , Macrófagos/metabolismoRESUMO
We isolated and characterized microsatellite loci for the red-crowned crane (Grus japonensis) from a microsatellite-enriched database, which was obtained using high-throughput sequencing technology. We designed primer sets for 445 microsatellite loci and after initial screening, 34 loci were genotyped in 31 red-crowned cranes. The number of observed alleles ranged from 3 to 10. Observed and expected heterozygosities ranged from 0.197 to 0.935 and 0.453 to 0.887, respectively; the mean polymorphic information content was 0.663. Loci Lia10943, Lia60455, Lia48514, Lia62171, Lia1059, and Lia5286 deviated from expectation of the Hardy-Weinberg equilibrium; however, significant linkage disequilibrium was not observed among the 34 loci. Using these 34 markers, we successfully completed parental identification for 19 cranes. The probability of exclusion for 7 selected loci (Lia271333, Lia3745, Lia11091, Lia45761, Lia16468, Lia21909, and Lia22355) was >0.9977 and analyses with more loci increased the combination efficiency. These 34 markers were also proven to be efficient for individual identification. We recommend that this marker system be used in the systematic control of pedigree management and future genetic variation studies of red-crowned cranes.
Assuntos
Aves/genética , Loci Gênicos/genética , Repetições de Microssatélites/genética , Polimorfismo Genético/genética , Alelos , Animais , Biomarcadores/metabolismo , Aves/metabolismo , Feminino , Genótipo , Desequilíbrio de Ligação/genéticaRESUMO
The mite (Varroa destructor) has become the greatest threat to apiculture worldwide. As the original host of the mite, Apis cerana can effectively resist the mite. An increased understanding of the resistance mechanisms of Eastern honeybees against V. destructor may help researchers to protect other species against these parasites. In this study, the proteomes of 4 Apis cerana colonies were analyzed using an isobaric tag for relative and absolute quantitation technology. We determined the differences in gene and protein expression between susceptible and resistant colonies that were either unchallenged or challenged by V. destructor. The results showed that a total of 1532 proteins were identified. Gene Ontology enrichment analysis suggested that the transcription factors and basic metabolic and respiratory processes were efficient and feasible factors controlling this resistance, and 12 differentially expressed proteins were identified in Venn analysis. The results were validated by quantitative polymerase chain reaction. This study may provide insight into the genetic mechanisms underlying the resistance of honeybee to mites.
Assuntos
Abelhas/metabolismo , Abelhas/parasitologia , Proteínas de Insetos/metabolismo , Proteômica/métodos , Varroidae/fisiologia , Animais , Eletroforese em Gel de Poliacrilamida , Ontologia Genética , Cabeça , Proteínas de Insetos/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Short tandem repeats (STRs) are highly polymorphic sequences and have been extensively used as genetic markers in mapping studies, disease diagnosis, and human identity testing. In this study, 11 STR markers on chromosome 21, including D21S1432, D21S11, D21S1246, D21S1412, D21S1437, D21S1442, D21S2039, D21S1270, D21S1435, D21S1409, and D21S1446, were analyzed in 740 unrelated Han individuals from southeast China. A total of 132 alleles, ranging from 7-21 for each locus, were named according to the guidelines of the International Society for Forensic Haemogenetics. The distributions of allelic frequencies for the 11 STRs and population genetic parameters were determined. All 11 STR markers showed high polymorphism and heterogeneity in the southeast Han population, with polymorphism information content of 0.61-0.87, heterogeneity of 64.5-86.1%, and power of discrimination of 0.835-0.973. Among the 11 STR markers, D21S1412, D21S1270, D21S11, and D21S1442 showed relatively higher heterogeneity. Their combination was relatively informative and was used in a quantitative fluorescence-polymerase chain reaction assay to diagnose Down syndrome (trisomy 21) in a southeast Chinese Han population. The genetic information and population data for these 11 STRs may be used not only in quantitative fluorescence-polymerase chain reaction assays but also in forensic studies and other genetic tests.
Assuntos
Cromossomos Humanos Par 21/genética , Marcadores Genéticos , Repetições de Microssatélites , Alelos , Povo Asiático/genética , China , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Frequência do Gene , Testes Genéticos , Humanos , Filogeografia , Polimorfismo GenéticoRESUMO
Pituitary abscess is a rare intrasellar infectious disease. It is usually treated with a combination of surgical drainage and intravenous antibiotics. We describe the case of a 38-year-old man with headache, fever, left earache, subsequent diabetes insipidus, and anterior pituitary insufficiency due to pituitary abscess, which was confirmed on the basis of clinical symptoms, laboratory examination results, and magnetic resonance imaging features. He was treated nonsurgically with intravenous antibiotics, with complete resolution of the pituitary abscess and recovery of pituitary function. Nonsurgical treatment may be an option for pituitary abscess.
Assuntos
Abscesso/tratamento farmacológico , Antibacterianos/administração & dosagem , Hipófise/efeitos dos fármacos , Abscesso/patologia , Administração Intravenosa , Adulto , Dor de Orelha/tratamento farmacológico , Febre/tratamento farmacológico , Cefaleia/tratamento farmacológico , Humanos , Masculino , Hipófise/fisiopatologiaRESUMO
The Varroa destructor mite has become the greatest threat to Apis mellifera health worldwide, but rarely causes serious damage to its native host Apis cerana. Understanding the resistance mechanisms of eastern bees against Varroa mites will help researchers determine how to protect other species from this organism. The A. cerana genome has not been previously sequenced; hence, here we sequenced the A. cerana nurse workers transcriptome and monitored the differential gene expression of A. cerana bees challenged by V. destructor. Using de novo transcriptome assembly, we obtained 91,172 unigenes (transcripts) for A. cerana. Differences in gene expression levels between the unchallenged (Con) and challenged (Con2) samples were estimated, and a total of 36,691 transcripts showed a 2-fold difference (at least) between the 2 libraries. A total of 272 differentially expressed genes showed differences greater than 15-fold, and 265 unigenes were present at higher levels in Con2 than in Con. Among the upregulated unigenes in the Con2 colony, genes related to skeletal muscle movement (troponin and calcium-transporting ATPase), olfactory sensitivity (odorant binding proteins, and Down syndrome cell adhesion molecule gene) and transcription factors (cyclic adenosine monophosphate-responsive element-binding protein and transcription factor mblk-1) appeared to be involved in Varroa resistance. Real-time polymerase chain reaction was performed to validate these differentially expressed genes screened by the sequencing approach, and sufficient consistency was observed between the two methods. These findings strongly support that hygienic and grooming behaviors play important roles in Varroa resistance.
Assuntos
Abelhas/genética , Abelhas/parasitologia , Transcriptoma , Varroidae/fisiologia , Animais , Resistência à Doença/genética , Ontologia Genética , Interações Hospedeiro-Parasita , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNARESUMO
Varroa destructor is the greatest threat to the honeybee Apis mellifera worldwide, while it rarely causes serious harm to its native host, the Eastern honeybee Apis cerana. The genetic mechanisms underlying the resistance of A. cerana to Varroa remain unclear. Thus, understanding the molecular mechanism of resistance to Varroa may provide useful insights for reducing this disease in other organisms. In this study, the transcriptomes of two A. cerana colonies were sequenced using the Illumina Solexa sequencing method. One colony was highly affected by mites, whereas the other colony displayed strong resistance to V. destructor. We determined differences in gene expression in the two colonies after challenging the colonies with V. destructor. After de novo transcriptome assembly, we obtained 91,172 unigenes for A. cerana and found that 288 differentially expressed genes varied by more than 15-fold. A total of 277 unigenes were present at higher levels in the non-affected colony. Genes involved in resistance to Varroa included unigenes related to skeletal muscle movement, olfactory sensitivity, and transcription factors. This suggests that hygienic behavior and grooming behavior may play important roles in the resistance to Varroa.
Assuntos
Abelhas/genética , Abelhas/parasitologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Varroidae/fisiologia , Animais , Abelhas/classificação , Resistência à Doença/genética , Feminino , Ontologia Genética , Genes de Insetos/genética , Genética Populacional/métodos , Genótipo , Interações Hospedeiro-Patógeno , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TranscriptomaRESUMO
Prostate cancer is one of the most common malignancies in men. The multidrug resistance 1 gene (MDR1) is an important candidate gene for prostate cancer. The aim of this study was to evaluate the association between MDR1 gene polymorphisms and the risk of prostate cancer. MDR1 gene polymorphism and its association with the risk of prostate cancer were investigated in 357 Chinese men. A novel c.1465C>T polymorphism was detected with created restriction site-polymerase chain reaction and DNA sequencing. We found a significantly increased risk of prostate cancer in the homozygote comparison [TT vs CC: odds ratio (OR) = 2.300, 95% confidence interval (95%CI) = 1.261-4.196, chi-square = 7.53, P = 0.007], heterozygote comparison (TC vs CC: OR = 1.667, 95%CI = 1.049-2.648, chi-square = 4.71, P = 0.030), dominant model (TT/TC vs CC: OR = 1.835, 95%CI = 1.197-2.815, chi-square = 7.81, P = 0.005), recessive model (TT vs TC/CC: OR = 1.776, 95%CI = 1.023- 3.085, chi-square = 4.23, P = 0.041), and allele contrast (T vs C: OR = 1.625, 95%CI = 1.199-2.202, chi-square = 9.87, P = 0.002). These findings suggested that the c.1465C>T polymorphism of MDR1 may be risk factors for prostate cancer in Chinese men.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Povo Asiático/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Razão de Chances , Fatores de Risco , Análise de Sequência de DNARESUMO
MicroRNAs (miRNAs) are non-coding small RNAs that regulate gene expression by translational repression or transcript degradation. A large number of miRNAs have been identified from model plant species; however, the character of conserved miRNAs is poorly understood. We studied 42 miRNA families that are conserved within the plant kingdom, using the miRBase database. Some conserved miRNA families were found to be preferentially expressed in dicots relative to monocots, especially miR403, miR472 and miR479. Using an improved homology search-based approach and the conserved miRNAs as the query set, 34 conserved miRNAs and the miR482 family were identified in wheat. Forty-six wheat mRNAs were predicted as their putative target genes. Most conserved wheat miRNAs were found to retain homologous target interactions and have analogous molecular functions. The miR172 displayed a wheat-specific function and was found to have an additional target interaction with succinyl-CoA ligase. We concluded that although miRNAs are conserved, the expression and function of some have drifted during long periods of plant evolution.