RESUMO
Fucosyltransferase 2 (FUT2) gene, which regulates the formation of Histoblood group antigens, could determine the human susceptibility to norovirus. This study aimed to investigate the correlation between FUT2 gene polymorphism and susceptibility to norovirus gastroenteritis in Han Chinese population. A total of 212 children patients with acute gastroenteritis were enrolled. The stool and serum samples were collected respectively. We used the qPCR method to detect the norovirus infection status from the stool samples, and we used serum samples to detect the FUT2 polymorphism. A case-control study was conducted to investigate the three common SNPs polymorphisms (rs281377, rs1047781, and rs601338) of FUT2 gene with sanger sequencing method. The results indicated that the homozygous genotypes and mutant allele of rs1047781 (A385T) would downgrade the risk of norovirus gastroenteritis in Chinese Han population (AA vs. TT, odds ratio [OR] = 0.098, 95% confidence interval [CI] = 0.026-0.370, p = 0.001; AA + AT vs. TT, OR = 0.118. 95% CI = 0.033-0.424, p = 0.001; A vs. T, OR = 0.528, 95% CI = 0.351-0.974, p = 0.002). There were no significant difference of rs281377 (C357T) and rs601338 (G428A) polymorphisms between norovirus positive and norovirus negative groups (p > 0.05). The haplotype T-T-G was less susceptible (OR = 0.49, 95% CI = 0.31-0.79, p = 0.0034) to norovirus infection compared to other haplotypes. Our results investigated the relationship between the FUT2 gene polymorphisms and norovirus susceptibility in Han Chinese population, and firstly revealed that children with homozygous genotypes and mutant alleles of FUT2 rs1047781 (A385T) were less susceptible to norovirus gastroenteritis.
Assuntos
Povo Asiático , Infecções por Caliciviridae , Fucosiltransferases , Galactosídeo 2-alfa-L-Fucosiltransferase , Gastroenterite , Predisposição Genética para Doença , Genótipo , Norovirus , Polimorfismo de Nucleotídeo Único , Humanos , Fucosiltransferases/genética , Infecções por Caliciviridae/genética , Infecções por Caliciviridae/virologia , Infecções por Caliciviridae/epidemiologia , Feminino , Masculino , Gastroenterite/virologia , Gastroenterite/genética , Estudos de Casos e Controles , Pré-Escolar , Norovirus/genética , Povo Asiático/genética , Lactente , China/epidemiologia , Criança , Fezes/virologia , Alelos , Haplótipos , População do Leste AsiáticoRESUMO
BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16. METHODS: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively. RESULTS: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes. CONCLUSION: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.
Assuntos
Variação Genética , Papillomavirus Humano 18 , Proteínas Oncogênicas Virais , Proteínas E7 de Papillomavirus , Filogenia , Proteínas Oncogênicas Virais/genética , China , Humanos , Papillomavirus Humano 18/genética , Papillomavirus Humano 18/classificação , Proteínas E7 de Papillomavirus/genética , Proteínas do Capsídeo/genética , Feminino , Epitopos de Linfócito T/genética , Infecções por Papillomavirus/virologia , Proteínas Repressoras/genética , Epitopos de Linfócito B/genética , Proteínas de Ligação a DNARESUMO
BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide with a serious threat to women's health. Persistent infection with high-risk human papillomavirus (HR-HPV) has been identified as the main cause of cervical cancer. This study aimed to evaluate the prevalence and genotype distribution of HR-HPV among women in Jingzhou, Hubei province, China, which is critical for the government to formulate the precision strategies of cervical cancer screening and HPV vaccine innoculation. METHODS: To obtain the baseline data on the population-based prevalence and genotype distribution of HR-HPV infection among age groups and different years, a total of 51,720 women from 2018 to 2022 who went to Jingzhou Hospital Affiliated to Yangtze University for physical examination or gynacological treatment and received HR-HPV DNA genotyping were included in this retrospective study. The possible cervicovaginal infection of 15 high-risk HPV genotypes were analyzed by multiplex fluorescent real-time PCR, including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 82. RESULTS: The overall high-risk HPV prevalence among 51,720 women was 18.75% (9,698/51,720), and the HPV-positive rate of physical examination group (PEG) was 13.22% (541/4,091), which was lower than the HPV-positive rate of gynacological checkup group (GCG) 19.23% (9,157/47,629), with statistical difference (χ2 = 89.069, P < 0.01). The five most common prevalent genotypes were HPV52 (6.55%), HPV58 (3.41%), HPV16 (2.58%), HPV68 (1.82%) and HPV51 (1.57%). Single HPV infection was the predominant (14.36%), which compared to double (3.34%) and multiple (1.05%) infections. The HPV-positive rate was the highest in the > 60 age group (31.73%), and the lowest in the 31-40 age group (15.46%). CONCLUSIONS: The prevalence of high-risk HPV infection among women in Jingzhou area was 18.75%. HPV52, HPV58 and HPV16 genotypes were the most common. The higher prevalence was in the > 60 and ≤ 20 age group, which showed a "U" shape curve, suggesting the necessity of screening among older women to decrease the mortality of cervical cancer.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Idoso , Prevalência , Detecção Precoce de Câncer , Estudos Retrospectivos , Genótipo , China/epidemiologia , Papillomaviridae/genética , Papillomavirus Humano 16/genéticaRESUMO
BACKGROUND: Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. METHODS: In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV-16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. RESULTS: Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). CONCLUSION: HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.
Assuntos
Papillomavirus Humano 16 , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , China/epidemiologia , Epitopos de Linfócito B/genética , Variação Genética , Papillomavirus Humano 16/genética , Papillomavirus Humano , Nucleotídeos , Infecções por Papillomavirus/epidemiologia , Filogenia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country's epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters' predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). METHODS: A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. RESULTS: Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P < 0.01). The ROC curve further demonstrated that lymphocyte (LYM) counts, neutrophil (NEU) counts, monocyte-to-lymphocyte ratios (MLR), platelet-to-lymphocyte ratios (PLR), white blood cell counts (WBC), and mean corpuscular hemoglobin concentration (MCHC) were the top 6 indicators in diagnosing Omicron infection with fever, with area under the curve (AUC) values of 0.738, 0.718, 0.713, 0.702, 0.700, and 0.687, respectively (P < 0.01). Furthermore, the mean platelet volume (MPV) with an AUC of 0.764, red blood cell count (RBC) with 0.753, hematocrit (HCT) with 0.698, MLR with 0.694, mean corpuscular hemoglobin (MCH) with 0.676, and systemic inflammation response indexes (SIRI) with 0.673 were the top 6 indicators for the diagnosis of COVID-19 patients with PI (P < 0.01). CONCLUSIONS: LYM, NEU, MLR, PLR, WBC, and MCHC can serve as potential prescreening indicators for Omicron infection in fever clinics. Additionally, MPV, RBC, HCT, MLR, MCH, and SIRI can predict the presence of PI in COVID-19 patients infected by the Omicron variant.
Assuntos
COVID-19 , Humanos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/terapia , COVID-19/virologia , População do Leste Asiático , Linfócitos , Neutrófilos , Estudos Retrospectivos , SARS-CoV-2 , China/epidemiologiaRESUMO
BACKGROUND: Toll-like receptors (TLRs) may be involved in the natural history of human papillomavirus (HPV) infection. In our study, we aimed to investigate the association of TLR4 (rs10116253, rs1927911, rs10759931) and TLR9 (rs187084, rs352140) gene polymorphisms with cervical persistent high-risk HPV (HR-HPV) infection, as well as multiple HR-HPV infections. METHODS: A total of 269 study subjects were enrolled and grouped by retrospectively analyzing the HR-HPV testing results and other clinical data of 2647 gynecological outpatients from Jingzhou Hospital Affiliated to Yangtze University. We conducted a case-control study to compare the role of TLR4/TLR9 gene polymorphisms between HR-HPV transient and persistent infections, as well as between HR-HPV single and multiple infections. HR-HPV genotypes were detected using Real-time polymerase chain reaction (RT-PCR). PCR-restriction fragment length polymorphism (PCR-RFLP) was used to determine TLR4 and TLR9 gene polymorphisms. Analyses of the different outcome variables (HR-HPV infection status and time for HR-HPV clearance) with respect to TLR4/TLR9 polymorphisms were carried out. Logistic regression analysis was used to determine the association of TLR4/TLR9 genotypes and alleles with HR-HPV infection status. The Kaplan-Meier method with the log-rank test was used to analyze the relationship between TLR4/TLR9 genotypes and the time for HR-HPV clearance. RESULTS: The mutant genotypes of TLR9 rs187084 and rs352140 were associated with persistent (rs187084: CT and CT+CC; rs352140: CT and CT+TT) and multiple (rs187084: CT and CT+CC; rs352140: CT+TT) (all P < 0.05) HR-HPV infection. However, no association was found between TLR4 polymorphisms and HR-HPV infection status. Kaplan-Meier time to HR-HPV clearance analysis demonstrated that women carrying rs187084 and rs352140 mutant genotypes take longer duration to clear HR-HPV infection compared with wild-type genotype carriers (P1 = 0.012; P2 = 0.031). CONCLUSION: Our results suggested that TLR9 polymorphisms, but not TLR4, were associated with cervical persistent and multiple HR-HPV infections, which could be useful as a potential predictor of HR-HPV infection status.
Assuntos
Infecções por Papillomavirus , Receptor 4 Toll-Like , Receptor Toll-Like 9 , Feminino , Humanos , Estudos de Casos e Controles , População do Leste Asiático , Predisposição Genética para Doença , Genótipo , Infecções por Papillomavirus/genética , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Receptor 4 Toll-Like/genética , Receptor Toll-Like 9/genéticaRESUMO
The incidence of cervical cancer is closely related to high-risk human papillomavirus (HR-HPV). Women in Jingzhou had relatively high susceptibility to HPV-51, whose ratio was 9.61% (456/4743) among HR-HPV-positive samples and ranked fifth in all analyzed HR-HPV types. In this study, variations and phylogenetic trees of HPV-51 E6-E7 and L1 sequences were analyzed by MEGA-X. The selective pressure was estimated using PAML. The B-cell epitope of L1 amino acid sequences and T-cell epitope of E6 and E7 amino acid sequences were further predicted by ABCpred server and IEDB website, respectively. In the E6-E7 sequences 14 single nucleotide variants occurred, among which 4 were nonsynonymous variants and 10 were synonymous variants. A total of 41 single nucleotide variants were identified in the L1 sequences, including 10 nonsynonymous variants and 31 synonymous variants. All the isolates of both E6-E7 and L1 were classified into the A variant lineage. In HPV-51 E6-E7 and L1 sequences, no positively selected site was found. Two nonconservative substitutions, H119Y and N176S in L1, affected multiple hypothetical B-cell epitopes. Three nonconservative substitutions, T86P, S100L in E6, and F29L in E7, affected multiple hypothetical T-cell epitopes. Elucidation of the HR-HPV prevalence characteristics and genetic variations of HPV-51 in central China may contribute to future investigations of diagnostic probes, therapeutic or preventative vaccines with wider coverage.
Assuntos
Alphapapillomavirus , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Alphapapillomavirus/genética , China/epidemiologia , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/genética , Feminino , Variação Genética , Humanos , Nucleotídeos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Filogenia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
The central control of feeding behavior and metabolic homeostasis has been proposed to involve a form of post-ingestive nutrient learning independent of the gustatory value of food. However, after such learning, it is unknown which brain regions or circuits are activated to retrieve the stored memory and whether this memory undergoes reconsolidation that depends on protein synthesis after its reactivation through retrieval. In the present study, using a conditioned-flavor-preference paradigm by associating flavors with intra-gastric infusion of glucose to minimize the evaluation of the taste of food, we show that retrieval of the post-ingestive nutrient-conditioned flavor memory stimulates multiple brain regions in mice, including the central nucleus of the amygdala (CeA). Moreover, memory retrieval activated the mammalian target of rapamycin complex 1 (mTORC1) in the CeA, while site-specific or systemic inhibition of mTORC1 immediately after retrieval prevented the subsequent expression of the post-ingestive nutrient-associated flavor memory, leading to a long-lasting suppression of reinstatement. Taken together, our findings suggest that the reconsolidation process of a post-ingestive nutrient memory modulates food preferences.
Assuntos
Núcleo Central da Amígdala , Memória , Nutrientes , Animais , Encéfalo , Núcleo Central da Amígdala/fisiologia , Condicionamento Clássico , Preferências Alimentares , Camundongos , Serina-Treonina Quinases TORRESUMO
BACKGROUND: Cervical cancer is a common malignant tumor in women, with a high mortality rate, has great harm to women's health. Long-term and persistent infection of high-risk human papillomavirus (HR-HPV) is the main reason of the occurrence and development of cervical cancer. METHODS: The infection rate of HPV-58 is higher in the Jingzhou area. In this study, 172 complete HPV-58 E6-E7 sequences were amplified by polymerase chain reaction (PCR), the amplified products were sequenced, and the gene variations of HPV-58 E6-E7 were analyzed. A Neighbor-Joining phylogenetic tree was constructed by MEGA 11. The secondary structure of E6 and E7 protein was investigated. PAML X was used to analyze the selective pressure. The B cell epitopes of E6 and E7 proteins in HPV-58 were predicted by ABCpred server. RESULTS: In E6 sequences, 10 single nucleotide variants were observed, including 7 synonymous and 3 non-synonymous variants. In E7 sequences, 12 single nucleotide variants were found, including 3 synonymous variants and 9 non-synonymous variants. There are 5 novel variants. The phylogenetic analysis showed that all the E6-E7 sequences were distributed in A lineage. No positively selected site was found in E6 sequence, but G63 in E7 sequences was identified as positively selected site. Some amino acid substitutions affected multiple B cell epitopes. CONCLUSION: Various E6 and E7 mutational data may prove useful for development of better diagnostic and vaccines for the region of Jingzhou, Hubei province of central China.
Assuntos
Alphapapillomavirus , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Alphapapillomavirus/genética , China/epidemiologia , Epitopos de Linfócito B , Feminino , Humanos , Nucleotídeos , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Proteínas E7 de Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Filogenia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
Osteoporotic fractures cause major morbidity and mortality in the aging population. Genome-wide association studies (GWAS) have identified USF3 as the novel susceptibility gene of osteoporosis. However, the functional role in bone metabolism and the target gene of the basic helix-loop-helix transcription factor USF3 are unclear. Here, we show that USF3 enhances osteoblast differentiation and suppresses osteoclastogenesis in cultured human osteoblast-like U-2OS cells. Mechanistic studies revealed that transcription factor USF3 antagonistically interacts with anti-osteogenic TWIST1/TCF12 heterodimer in the WNT16 and RUNX2 promoter, and counteracts CREB1 and JUN/FOS in the RANKL promoter. Importantly, the osteoporosis GWAS variant g.1744A>G (rs2908007A>G) located in the WNT16 promoter confers G-allele-specific transcriptional modulation by USF3, TWIST1/TCF12 and TBX5/TBX15, and USF3 transactivates the osteoclastogenesis suppressor WNT16 promoter activity and antagonizes the repression of WNT16 by TWIST1 and TCF12. The risk G allele of osteoporosis GWAS variant g.3260A>G (rs4531631A>G) in the RANKL promoter facilitates the binding of CREB1 and JUN/FOS and enhances transactivation of the osteoclastogenesis contributor RANKL that is inhibited by USF3. Our findings uncovered the functional mechanisms of osteoporosis novel GWAS-associated gene USF3 and lead single nucleotide polymorphisms rs2908007 and rs4531631 in the regulation of bone formation and resorption.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Estudo de Associação Genômica Ampla , Osteoporose , Idoso , Diferenciação Celular/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Ligante RANK/genética , Proteínas com Domínio T/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismoRESUMO
Cervical cancer is the fourth most common malignant tumor in women worldwide and is closely related to human papillomavirus (HPV). Women have the highest susceptibility to HPV-52 type in Jingzhou, China. In this study, E6-E7 sequences of 183 HPV-52 positive samples were amplified by a polymerase chain reaction and sequenced. HPV-52 E6-E7 gene variations were analyzed. The phylogenetic tree was constructed using the Kimura 2-parameter method. The secondary structure of the protein was analyzed. The selective pressure to E6-E7 genes was estimated using PAML. In addition, the B cell epitopes of the E6-E7 sequences in HPV-52 were predicted by the ABCpred server. In E6 sequences, 15 single nucleotide variants were observed, including 6 nonsynonymous variants and 9 synonymous variants. In E7 sequences, 19 single nucleotide variants occurred, including 10 nonsynonymous variants and 9 synonymous variants. Six amino acid variants, including 3 nonconservative substitutions, were found in sequences encoding the alpha helix. Eight amino acid variants, including three nonconservative substitutions, occurred in sequences encoding the strand. Through phylogenetic analysis, the E6-E7 sequences were mainly distributed in B lineage. In HPV-52 E6-E7 sequences, no positively selected site was found. The nonconservative substitutions, such as K93R, K93E in E6, T37I, and D38N in E7, affected multiple hypothetical epitopes in the B cell. This study provides information for the investigation of HPV epidemic characters. The discovery of new variants of HPV-52 may lay the basis for the development of the virus diagnosis, further study of cervical cancer, and vaccine design in Central China.
Assuntos
Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Variação Genética , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genética , Filogenia , Adolescente , Adulto , Alphapapillomavirus/isolamento & purificação , Proteínas do Capsídeo/genética , Colo do Útero/citologia , Colo do Útero/virologia , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/classificação , Proteínas E7 de Papillomavirus/química , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Análise de Sequência de DNA , Neoplasias do Colo do Útero/virologia , Adulto JovemRESUMO
Upstream transcription factor family member 3 (USF3) c.3781C>A (rs1026364) in the 3'-untranslated region (3'-UTR) has been firmly associated with bone mineral density (BMD) in genome-wide association study (GWAS). However, the molecular mechanism by which it influences BMD and osteoporosis is unknown. Bioinformatics analyses suggested that the risk c.3781A allele creates a target site for hsa-miR-345-5p binding. Luciferase assay validated that the c.3781A allele displayed significantly lower luciferase activities than the c.3781C allele in the human osteoblast cell line hFOB1.19, osteosarcoma cell lines U-2OS and Saos-2, and embryonic kidney cell line 293T. Furthermore, hsa-miR-345-5p regulated USF3 expression on both messenger RNA and protein levels in hFOB1.19 and U937 cells with heterozygous A/C genotype. Transfection of hsa-miR-345-5p antagomiR in heterozygous hFOB1.19 cells significantly increased the expression of osteogenic marker genes RUNX2, OSTERIX, COL1A1, ALP, OPN, OCN, and alkaline phosphatase activity and matrix mineralization level. Importantly, we found that hsa-miR-345-5p also inhibits osteoblast maturation in cell lines U-2OS with hsa-miR-345-5p nonbinding C/C genotype by targeting RUNX3 and SMAD1. Our findings uncovered a novel pathogenetic mechanism of osteoporosis by GWAS variant c.3781C>A-mediated disruption of hsa-miR-345-5p binding at the 3'-UTR of USF3 and the functional role of hsa-miR-345-5p in osteogenic differentiation.
Assuntos
Alelos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , MicroRNAs/genética , Osteoporose/diagnóstico , Osteoporose/genética , Regiões 3' não Traduzidas , Diferenciação Celular/genética , Linhagem Celular , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Genes Reporter , Humanos , Conformação de Ácido Nucleico , Osteoblastos/citologia , Osteoblastos/metabolismo , Interferência de RNA , RNA Mensageiro/genética , TranscriptomaRESUMO
OBJECTIVE: To explore the genetic basis for a female with a peripheral lymphocyte karyotype of trisomy 18 but normal intelligence. METHODS: G-banding karyotype analysis, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism microarray (SNP array) were employed to analyze the peripheral blood sample and buccal cells from the patient. RESULTS: Chromosomal karyotyping, SNP array and FISH analysis of the patient's peripheral blood all suggested 47,XX,+18. Interphase FISH analysis of buccal cells, however, revealed presence of 45,X and low percentage of trisomy 18 and monosomy 18. CONCLUSION: The clinical manifestation of germ layer chromosomal mosaicism is complex. The impact of the genetic disorder on the individual will depend on the structure and function derived from the affected germ layer.
Assuntos
Cariotipagem , Síndrome da Trissomía do Cromossomo 18/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Inteligência , Cariótipo , Linfócitos , Mosaicismo , Mucosa Bucal , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Previous genome-wide linkage and association studies have identified an osteoporosis-associated locus at 1p36 that harbors SNPs rs34920465 and rs6426749. The 1p36 locus also comprises the WNT4 gene with known role in bone metabolism and functionally unknown ZBTB40/lncRNA ZBTB40-IT1 genes. How these might interact to contribute to osteoporosis susceptibility is not known. In this study, we show that lncRNA ZBTB40-IT1 is able to suppress osteogenesis and promote osteoclastogenesis by regulating the expression of WNT4, RUNX2, OSX, ALP, COL1A1, OPG and RANKL in U-2OS and hFOB1.19 cell lines, whereas ZBTB40 plays an opposite role in bone metabolism. Treatment with parathyroid hormone significantly downregulates the expression of ZBTB40-IT1 in U-2OS cell lines. ZBTB40 can suppress ZBTB40-IT1 expression but has no response to parathyroid hormone treatment. Dual-luciferase assay and biotin pull-down assay demonstrate that osteoporosis GWAS lead SNPs rs34920465-G and rs6426749-C alleles can respectively bind transcription factors JUN::FOS and CREB1, and upregulate ZBTB40 and ZBTB40-IT1 expression. Our study discovers the critical role of ZBTB40 and lncRNA ZBTB40-IT1 in bone metabolism, and provides a mechanistic basis for osteoporosis GWAS lead SNPs rs34920465 and rs6426749.
Assuntos
Regulação da Expressão Gênica , Predisposição Genética para Doença , Osteogênese/genética , Osteoporose , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante , Alelos , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Estudo de Associação Genômica Ampla , Células HEK293 , Humanos , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , Hormônio Paratireóideo/metabolismo , Hormônio Paratireóideo/farmacologia , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genéticaRESUMO
Opaque2 (O2) is a transcription factor that plays important roles during maize endosperm development. Mutation of the O2 gene improves the nutritional value of maize seeds but also confers pleiotropic effects that result in reduced agronomic quality. To reveal the transcriptional regulatory framework of O2, we studied the transcriptome of o2 mutants using RNA sequencing (RNA-Seq) and determined O2 DNA binding targets using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-Seq). The RNA-Seq analysis revealed 1605 differentially expressed genes (DEGs) and 383 differentially expressed long, noncoding RNAs. The DEGs cover a wide range of functions related to nutrient reservoir activity, nitrogen metabolism, stress resistance, etc. ChIP-Seq analysis detected 1686 O2 DNA binding sites distributed over 1143 genes. Overlay of the RNA-Seq and ChIP-Seq results revealed 35 O2-modulated target genes. We identified four O2 binding motifs; among them, TGACGTGG appears to be the most conserved and strongest. We confirmed that, except for the 16- and 18-kD zeins, O2 directly regulates expression of all other zeins. O2 directly regulates two transcription factors, genes linked to carbon and amino acid metabolism and abiotic stress resistance. We built a hierarchical regulatory model for O2 that provides an understanding of its pleiotropic biological effects.
Assuntos
DNA de Plantas/genética , Regulação da Expressão Gênica de Plantas , Genoma de Planta , Proteínas de Plantas/genética , Regiões Promotoras Genéticas , Transcrição Gênica , Zea mays/genética , Sequência de Bases , Sítios de Ligação , Imunoprecipitação da Cromatina , Regulação para Baixo/genética , Ontologia Genética , Genes de Plantas , Dados de Sequência Molecular , Mutação , Nitrogênio/metabolismo , Motivos de Nucleotídeos/genética , Fases de Leitura Aberta/genética , Proteínas de Plantas/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA não Traduzido/genética , Análise de Sequência de RNA , Estresse Fisiológico/genética , Zeína/genéticaRESUMO
A novel glutamine synthetase (GS) gene DvGS1 showing highest amino acid sequence identity of 78 % with the other homologous GS proteins from green algae, was isolated and characterized from Dunaliella viridis. Phylogenetic analysis revealed that DvGS1 occupied an independent phylogenetic position which was different with the GSs from higher plants, animals and microbes. Functional complement in E. coli mutant confirmed that the DvGS1 encoded functional GS enzyme. Real-time PCR analysis of DvGS1 in D. viridis cells under nitrogen starvation revealed that the mRNA level of DvGS1 was positively up-regulated in 12 h. The DvGS1 levels at the points of 12 and 24 h were separately twofold and fourfold of the level before nitrogen starvation. In order to investigate the potential application of DvGS1 in higher plants, the transgenic study of DvGS1 in Arabidopsis thaliana was carried out. Phenotype identification demonstrated that all three transgenic lines of T3 generation showed obviously enhanced root length (26 %), fresh weight (22-46 % at two concentrations of nitrate supplies), stem length (26 %), leaf size (29 %) and silique number (30 %) compared with the wild-type Arabidopsis. Biochemical analysis confirmed that all three transgenic lines had higher total nitrogen content, soluble protein concentration, total amino acid content and the leaf GS activity than the wild type plants. The free NH4 (+) and NO3 (-) concentration in fresh leaves of three transgenic lines were reduced by 17-26 % and 14-15 % separately (at two concentrations of nitrate supplies) compared with those of the wild types. All the results indicated that over-expression of DvGS1 in Arabidopsis significantly results in the improvement of growth phenotype and the host's nitrogen use efficiency.
Assuntos
Arabidopsis/genética , Clorófitas/enzimologia , Glutamato-Amônia Ligase/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Clonagem Molecular , Glutamato-Amônia Ligase/biossíntese , Dados de Sequência Molecular , Nitrogênio/metabolismo , Fenótipo , Filogenia , Proteínas de Plantas/biossíntese , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/metabolismo , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU) are the common sexually transmitted pathogens and lead to genital diseases, highly prevalent all around the world. The objective of this study was to analyze the prevalence of NG, CT and UU among outpatients in central China. A total of 2186 urogenital swabs were collected from the patients and the NG, CT and UU pathogens were testing with RT-PCR method, meanwhile the medical records were obtained from the hospital information system. The overall infection rates of NG, CT and UU were 4.57 %, 6.63 % and 48.81 % respectively, showed the prevalence of UU was higher than NG and CT. The younger people had the highest infection rate of NG (10.81 %), CT (20.54 %) and UU (54.59 %). Single infection (89.09 %) was significant higher than co-infection (10.91 %), and the CT-UU co-infection was the prominent pattern (66.41 %). There were an obvious sex difference, the prevalence of NG and CT were significant higher in male, whereas UU was higher in female. Our study could contributed a better understanding of the prevalence of NG, CT and UU, facilitating to the development of effective screening, prevention and treatment policies.
Assuntos
Infecções por Chlamydia , Chlamydia trachomatis , Gonorreia , Neisseria gonorrhoeae , Pacientes Ambulatoriais , Infecções por Ureaplasma , Ureaplasma urealyticum , Humanos , China/epidemiologia , Feminino , Masculino , Chlamydia trachomatis/genética , Chlamydia trachomatis/isolamento & purificação , Ureaplasma urealyticum/isolamento & purificação , Ureaplasma urealyticum/genética , Adulto , Prevalência , Estudos Retrospectivos , Neisseria gonorrhoeae/isolamento & purificação , Neisseria gonorrhoeae/genética , Infecções por Ureaplasma/epidemiologia , Infecções por Ureaplasma/microbiologia , Gonorreia/epidemiologia , Gonorreia/microbiologia , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/microbiologia , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Adulto Jovem , Adolescente , Coinfecção/epidemiologia , Coinfecção/microbiologia , IdosoRESUMO
Today, with the advancement of science in nanotechnology, it is possible to remove dust nanostructures from the air breathed by humans or other fluids. In the present study, the separation of SiO2 molecules from H2O vapor is studied using molecular dynamics (MD) simulation. This research studied the effect of initial temperature, nanopore geometry, and initial pressure on the separation of SiO2 molecules. The obtained results show that by increasing the temperature to 500 K, the maximum velocity (Max-Vel) of the samples reached 2.47 Å/fs. Regarding the increasing velocity of particles, more particles pass via the nanopores. Moreover, the shape of the nanopore could affect the number of passing particles. The results show that in the samples with a cylindrical nanopore, 20 and 40% of SiO2 molecules, and with the sphere cavity, about 32 and 38% of SiO2 particles passed in the simulated structure. So, it can be concluded that the performance of carbon nanosheets with a cylindrical pore and 450 K was more optimal. Also, the results show that an increase in initial pressure leads to a decrease in the passage of SiO2 particles. The results reveal that about 14 and 54% of Silica particles passed via the carbon membrane with increasing pressure. Therefore, for use in industry, in terms of separating dust particles, in addition to applying an EF, temperature, nanopore geometry, and initial pressure should be controlled.
Assuntos
Nanoporos , Humanos , Simulação de Dinâmica Molecular , Vapor , Dióxido de Silício , Carbono , Temperatura , PoeiraRESUMO
Interest in taking advantage of the unique spectral properties of semiconductor quantum dots (QDs) has driven their widespread use in biological applications such as in vitro cellular labeling/imaging and sensing. Despite their demonstrated utility, concerns over the potential toxic effects of QD core materials on cellular proliferation and homeostasis have persisted, leaving in question the suitability of QDs as alternatives for more traditional fluorescent materials (e.g., organic dyes, fluorescent proteins) for in vitro cellular applications. Surprisingly, direct comparative studies examining the cytotoxic potential of QDs versus these more traditional cellular labeling fluorophores remain limited. Here, using CdSe/ZnS (core/shell) QDs as a prototypical assay material, we present a comprehensive study in which we characterize the influence of QD dose (concentration and incubation time), QD surface capping ligand, and delivery modality (peptide or cationic amphiphile transfection reagent) on cellular viability in three human cell lines representing various morphological lineages (epithelial, endothelial, monocytic). We further compare the effects of QD cellular labeling on cellular proliferation relative to those associated with a panel of traditionally employed organic cell labeling fluorophores that span a broad spectral range. Our results demonstrate the important role played by QD dose, capping ligand structure, and delivery agent in modulating cellular toxicity. Further, the results show that at the concentrations and time regimes required for robust QD-based cellular labeling, the impact of our in-house synthesized QD materials on cellular proliferation is comparable to that of six commercial cell labeling fluorophores. Cumulatively, our results demonstrate that the proper tuning of QD dose, surface ligand, and delivery modality can provide robust in vitro cell labeling reagents that exhibit minimal impact on cellular viability.
Assuntos
Compostos de Cádmio/toxicidade , Corantes Fluorescentes/toxicidade , Pontos Quânticos/toxicidade , Compostos de Selênio/toxicidade , Sulfetos/toxicidade , Compostos de Zinco/toxicidade , Compostos de Cádmio/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Células HEK293 , Humanos , Ligantes , Pontos Quânticos/química , Compostos de Selênio/química , Sulfetos/química , Tensoativos/química , Tensoativos/toxicidade , Compostos de Zinco/químicaRESUMO
In this article, polydopamine (Pdop) functionalized multiwalled carbon nanotubes (MWCNTs@Pdop) were firstly synthesized and employed as the template for the dispersion of Pt nanoparticles to form Pt/MWCNTs@Pdop hybrid nanocomposite. The characterizations of the Pt/MWCNTs@Pdop were investigated by SEM, transmission electron microscopy, x-ray diffraction, and voltammetry. Based upon the Pt/MWCNTs@Pdop nanocomposite, a modified carbon disk electrode was fabricated and successfully applied to the simultaneous detection of four important monoamines, including dopamine, epinephrine, norepinephrine, and serotonin, using capillary electrophoresis--amperometric detection system. Compared with the bare electrode, the four analytes at the Pt/MWCNTs@Pdop electrode exhibited higher sensitivity, broad linear responses from 0.5 to 1.0 × 10(2) nmol/L. The detection limits (S/N = 3) were lower than 9.2 × 10(-10) mol/L. More importantly, the effect of noise exposure on monoamines (MAs) in hippocampus and hypothalamus was investigated for the first time. Compared with the control group, the levels of the MAs all varied to different extents after rats receiving the same noise stimulation. The results showed that the proposed method could be applied to the determination of low levels of MAs in biological samples and screening the target molecules for the diagnosis and treatment of various related diseases.