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In higher plants, fertilization induces many structural and physiological changes in the fertilized egg that reflect the transition from the haploid female gamete to the diploid zygote - the first cell of the sporophyte. After fusion of the egg nucleus with the sperm nucleus, many molecular changes occur in the zygote during the process of zygote activation during embryogenesis. The zygote originates from the egg, from which some pre-stored translation initiation factors transfer into the zygote and function during zygote activation. This indicates that the control of zygote activation is pre-set in the egg. After the egg and sperm nuclei fuse, gene expression is activated in the zygote, and paternal and maternal gene expression patterns are displayed. This highlights the diversity of zygotic genome activation in higher plants. In addition to new gene expression in the zygote, some genes show quantitative changes in expression. The asymmetrical division of the zygote produces an apical cell and a basal cell that have different destinies during plant reconstruction; these destinies are determined in the zygote. This review describes significant advances in research on the mechanisms controlling zygote activation in higher plants.
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Oryza , Zigoto , Diploide , Haploidia , SementesRESUMO
Cadmium (Cd) is one of the major transitional metals that have toxic effects on aquatic organisms. To investigate the effects of dietary cadmium on growth, salinity stress, hepatotoxicity in juvenile Pacific white shrimp (L. vannamei) and potential protective effect of Zn(II)-curcumin, five experimental diets (control, 100mg/kg Zn(II)-curcumin, 30mg/kg Cd, 30mg/kg Cd+100mg/kg Zn(II)-curcumin, 30mg/kg Cd+200mg/kg Zn(II)-curcumin) were formulated. The results showed that Cd at 30mg/kg induced significant increase in weight gain, specific growth rate and visible alterations to the hepatopancreas structures of L. vannamei. Compared with control diet, 100mg/kg Zn(II)-curcumin added diet had no effect on growth performance or feed utilization, while healthier hepatopancreas and less plasma ALT, AST production was found. Moreover, 200mg/kg dietary Zn(II)-curcumin significantly ameliorated the Cd induced hepatotoxicity while 100mg/kg dietary Zn(II)-curcumin slightly ameliorated. Cd accumulation in the whole body was decreasing and Metallothioneins like was increasing in hepatopancreas with increasing dietary Zn(II)-curcumin level. The shrimp fed with dietary Zn(II)-curcumin showed higher survival rate after acute salinity change. Therefore, it can be demonstrated that hepatotoxicity and hormesis could be induced by Cd when Cd levels were 30mg/kg, Zn(II)-curcumin could mitigate the effects of dietary Cd on L. vannamei.
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Cádmio/toxicidade , Curcumina/farmacologia , Fígado/efeitos dos fármacos , Penaeidae/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Zinco/farmacologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Cádmio/administração & dosagem , Curcumina/química , Dieta , Monitoramento Ambiental , Hepatopâncreas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Metalotioneína/metabolismo , Penaeidae/crescimento & desenvolvimento , Salinidade , Zinco/químicaRESUMO
UNLABELLED: Identifying biological functions and molecular networks in a gene list and how the genes may relate to various topics is of considerable value to biomedical researchers. Here, we present a web-based text-mining server, GenCLiP 2.0, which can analyze human genes with enriched keywords and molecular interactions. Compared with other similar tools, GenCLiP 2.0 offers two unique features: (i) analysis of gene functions with free terms (i.e. any terms in the literature) generated by literature mining or provided by the user and (ii) accurate identification and integration of comprehensive molecular interactions from Medline abstracts, to construct molecular networks and subnetworks related to the free terms. AVAILABILITY AND IMPLEMENTATION: http://ci.smu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Mineração de Dados/métodos , Redes Reguladoras de Genes , Genes , Software , Análise por Conglomerados , Humanos , Internet , MEDLINERESUMO
Increasing evidence suggests that body composition is associated with the development of acute pancreatitis (AP). This study aimed to investigate the applicability of body composition in predicting AP severity. Data of 213 patients with AP from Affiliated Hospital of Putian University (AHOPTU) were included in this study, whilst data of 173 patients with AP from Fujian Medical University Union Hospital (FMUUH) were used for external validation. Patients were classified into the non-severe and severe groups according to AP severity. After seven days of treatment, in patients from AHOPTU, the difference in skeletal muscle index before and after treatment (ΔSMI) was significantly higher (P = 0.002), while the skeletal muscle radiodensity before treatment (PreSMR) was significantly lower (P = 0.042) in the non-severe group than in the severe group. The multivariate logistic regression model also revealed that the ΔSMI and PreSMR were independent risk factors for AP severity. The optimal cut-off values of ΔSMI and PreSMR were 1.0 and 43.7, respectively. The following metabolic score (SMS) was established to predict AP severity: 0: ΔSMI < 1.0 and PreSMR < 43.7; 1: ΔSMI ≥ 1.0 and PreSMR < 43.7 or ΔSMI < 1.0 and PreSMR ≥ 43.7; 3: ΔSMI ≥ 1.0 and PreSMR ≥ 43.7. In patients from AHOPTU and FMUUH, the areas under the curves (AUC) for this model were 0.764 and 0.741, respectively. ΔSMI and PreSMR can accurately predict AP severity. It is recommended to routinely evaluate the statuses of patients with AP using the predictive model presented in this study for individualized treatment.
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Pancreatite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Pancreatite/diagnóstico , Pancreatite/metabolismo , Índice de Gravidade de Doença , Adulto , Composição Corporal , Medicina de Precisão/métodos , Idoso , Músculo Esquelético/metabolismo , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Doença Aguda , Fatores de RiscoRESUMO
BACKGROUND: The autologous anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy LCAR-B38M has been approved for the treatment of relapsed and refractory multiple myeloma in many countries across the world under the name ciltacabtagene autoleucel. LEGEND-2 was the first-in-human trial of LCAR-B38M and yielded deep and durable therapeutic responses. Here, we reported the outcomes in LEGEND-2 after a minimal 5-year follow-up. METHODS: Participants received an average dose of 0.5 × 106 cells/kg LCAR-B38M in split or single unfractionated infusions after cyclophosphamide-based lymphodepletion therapy. Investigator-assessed response, survival, safety and pharmacokinetics were evaluated. RESULTS: Seventy-four participants enrolled and had a median follow-up of 65.4 months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 21.0% and 49.1%, with progressive flattening of the survival curves over time. Patients with complete response (CR) had longer PFS and OS, with 5-year rates of 28.4% and 65.7%, respectively. Twelve patients (16.2%) remained relapse-free irrespective of baseline high-risk cytogenetic abnormality and all had normal humoral immunity reconstituted. An ongoing CR closely correlated with several prognostic baseline indices including favorable performance status, immunoglobulin G subtype, and absence of extramedullary disease, as well as a combination cyclophosphamide and fludarabine preconditioning strategy. Sixty-two (83.8%) suffered progressive disease (PD) and/or death; however, 61.1% of PD patients could well respond to subsequent therapies, among which, the proteasome inhibitor-based regimens benefited the most. Concerning the safety, hematologic and hepatic function recovery were not significantly different between non-PD and PD/Death groups. A low rate of second primary malignancy (5.4%) and no severe virus infection were observed. The patients who tested positive for COVID-19 merely presented self-limiting symptoms. In addition, a sustainable CAR T population of one case with persistent remission was delineated, which was enriched with indolently proliferative and lowly cytotoxic CD4/CD8 double-negative functional T lymphocytes. CONCLUSIONS: These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma. TRIAL REGISTRATION: LEGEND-2 was registered under the trial numbers NCT03090659, ChiCTRONH-17012285.
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Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno de Maturação de Linfócitos B/imunologia , Seguimentos , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/mortalidade , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão , Taxa de SobrevidaRESUMO
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV) with an average fatality rate of 12%. The clinical factors for death in SFTS patients remain unclear. METHODS: Clinical features and laboratory parameters were dynamically collected for 11 fatal and 48 non-fatal SFTS cases. Univariate logistic regression was used to evaluate the risk factors associated with death. RESULTS: Dynamic tracking of laboratory parameters revealed that during the initial fever stage, the viral load was comparable for the patients who survived as well as the ones that died. Then in the second stage when multi-organ dysfunction occurred, from 7-13 days after disease onset, the viral load decreased in survivors but it remained high in the patients that died. The key risk factors that contributed to patient death were elevated serum aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatine kinase fraction, as well as the appearance of CNS (central nervous system) symptoms, hemorrhagic manifestation, disseminated intravascular coagulation, and multi-organ failure. All clinical markers reverted to normal in the convalescent stage for SFTS patients who survived. CONCLUSIONS: We identified a period of 7-13 days after the onset of illness as the critical stage in SFTS progression. A sustained serum viral load may indicate that disease conditions will worsen and lead to death.
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Infecções por Bunyaviridae/mortalidade , Phlebovirus/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de Células Sanguíneas , Infecções por Bunyaviridae/sangue , Infecções por Bunyaviridae/patologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Fatores de Risco , Carga ViralRESUMO
Type 2 diabetes has been suggested as an independent risk factor for the development of hepatocellular carcinoma (HCC). However, the role of Type 2 diabetes on the development of HCC in the presence of chronic hepatitis B (CHB) remains inconclusive. We conducted this hospital-based case-control study to evaluate the roles of Type 2 diabetes in HCC development in patients with CHB. From January 2004 to December 2008, a total of 6,275 eligible consecutive patients with chronic hepatitis B virus (HBV) infection were recruited. A total of 1,105 of them were patients with HBV-related HCC and 5,170 patients were CHB but without HCC. We used multivariate logistic regression models to investigate the association between Type 2 diabetes and HCC risk. The prevalence of Type 2 diabetes is higher among HCC patients without cirrhosis than among those with cirrhosis (12.1% vs. 6.7%, p=0.003). Type 2 diabetes was associated with a significantly high risk of HCC in female patients after adjusting for age, family history of HCC, city of residence, hepatitis B e antigen and cirrhosis with an odds ratio (95% confidence interval, CI) of 1.9 (1.1-3.4). Restricted analyses among female patients without cirrhosis indicated that Type 2 diabetes was strongly associated with HCC risk with adjusted odds ratio (95% CI) of 5.6 (2.2-14.1). In conclusion, Type 2 diabetes is independently associated with the increased risk of HCC in female CHB patients. Female CHB patients with Type 2 diabetes are of a high HCC risk population and should be considered for HCC close surveillance program.
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Carcinoma Hepatocelular/etiologia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Neoplasias Hepáticas/etiologia , Adulto , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Complicações do Diabetes/epidemiologia , Feminino , Antígenos E da Hepatite B/metabolismo , Humanos , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
The COVID-19 pandemic has caused many medical issues. It has tested the impact of healthcare providers' job demands, emotional exhaustion, and other pressures related to the impact on organizational leave intention. Accordingly, the purpose of this study was to verify the relationship between healthcare providers' job demands, leisure involvement, emotional exhaustion, and leave intention under the COVID-19 pandemic. The questionnaire survey was used to address the issue of the present study. Convenience sampling was utilized to recruit 440 healthcare providers with a validity rate of 95%. Collected data were analyzed by structural equation modelling. Results indicated that healthcare providers' job demands do not significantly influence leisure involvement. Job demands significantly influence emotional exhaustion. Job demands significantly influence leave intention. Emotional exhaustion significantly influences leave intention. Emotional exhaustion has a significant mediating effect between job demands and leave intention. Finally, relevant practical suggestions are provided based on the study results.
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Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.
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Doenças dos Bovinos , Orquite , Doenças dos Roedores , Animais , Peptídeos Antimicrobianos , Barreira Hematotesticular/metabolismo , Bovinos , Doenças dos Bovinos/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Orquite/tratamento farmacológico , Orquite/metabolismo , Orquite/veterinária , Doenças dos Roedores/metabolismo , Células de Sertoli/metabolismo , Testículo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Macrophagecapping protein (CapG) is a newly characterized oncogene involved in several types of cancer. However, the expression patterns and biological mechanisms of CapG in clear cell renal cell carcinoma (ccRCC) are unclear. The present study aimed to investigate the roles of CapG in the prognosis, proliferation and metastasis of ccRCC. In the present study, the expression of CapG was analyzed by western blotting in 24 paired ccRCC and adjacent normal tissue samples. Another 152 tissue samples from 152 patients with ccRCC were examined by immunohistochemistry. Compared with normal tissue, CapG expression was significantly increased in ccRCC tissue, and high CapG expression was associated with advanced tumor stage, histological grade, lymph node metastasis, and poor overall survival. Moreover, CapG was an independent predictor of survival. Lentivirusmediated CapG knockdown significantly inhibited 786O cell proliferation, migration, and invasion, induced cell cycle arrest at the G2/M phase, and increased apoptosis in vitro. Microarray analysis indicated that RAC, CDC42 and ERK/MAPK signaling were disrupted by CapG knockdown in 786O cells. In conclusion, the present findings indicate that CapG plays an oncogenic role in ccRCC and may represent a potential therapeutic target for this disease.
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Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteínas dos Microfilamentos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Oncogênicas/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular , Pontos de Checagem da Fase G2 do Ciclo Celular , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Pontos de Checagem da Fase M do Ciclo Celular , Sistema de Sinalização das MAP Quinases , Proteínas dos Microfilamentos/genética , Proteínas Nucleares/genética , Proteínas Oncogênicas/genéticaRESUMO
This study aimed to investigate if myo-inositol (MI) supplementation could alleviate adverse effects caused by aflatoxin B1 (AFB1) with respect to growth performance, AFB1 residues, immune response and antioxidant status of Litopenaeus vannamei. 800 shrimp (initial weight: 1.1 g) were divided into five groups: MI0 (basal diet); MI0 + LA, MI0 + HA, MI200 + LA and MI200 + HA fed with AFB1-contaminated diets (LA, low concentration AFB1; HA, high concentration AFB1; MI200, adding 200 mg MI kg-1 diet). The results showed that HA significantly decreased growth performance, systemic inositol content and lipid content. AFB1 residues were detected in the hepatopancreas of shrimp, but not the muscle. Histological lesions were observed in MI0 + LA and MI0 + HA groups. HA supplementation raised malondialdehyde and protein carbonyl content and reduced some antioxidant enzyme activities and immune-related genes expression, which was slightly ameliorated by MI supplementation. Our results suggest that myo-inositol may slightly mitigate negative impacts caused by AFB1 in L. vannamei.
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Aflatoxina B1/análise , Antioxidantes/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inositol/farmacologia , Penaeidae/crescimento & desenvolvimento , Aflatoxina B1/administração & dosagem , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Dieta , Suplementos Nutricionais , Hepatopâncreas/enzimologia , Hepatopâncreas/metabolismo , Malondialdeído/metabolismo , Penaeidae/imunologia , Penaeidae/metabolismo , Carbonilação Proteica/efeitos dos fármacosRESUMO
BACKGROUND: To explore the risk factors and prognostic factors related to the acute-on-chronic liver failure (ACLF) occurrence and adverse outcome after withdrawal of nucleos(t)ide analogs (NAs) in chronic hepatitis B (CHB) patients. METHODS: Hospitalized CHB patients with relapse after NAs withdrawal at our medical center were retrospectively included in the present study from January 2011 to May 2018. Logistic regression, Cox regression analysis, Kaplan-Meier log-rank test, and area under the receiver operating characteristic curves (AUROC) were used. RESULTS: A total of 389 CHB patients (including 46 ACLF patients) were included. Their median age was 48.0 years; 315 patients were male and 74 were female. The age ≥30 years and HBVDNA ≤1000 copies at admission in logistic regression were the independent risk factors for ACLF after NAs withdrawal in CHB patients. In patients who developed ACLF, only the model of end-stage liver disease combining serum natrium concentration (MELD-Na) score and relapse after Lamivudine (LAM) cessation in the Cox multivariate regression analysis were independent predictors for 12-week mortality. The artificial liver support system (ALSS) showed no improvement in the 12-week survival of ACLF patients. We further defined 22.35 as the optimal cutoff value of MELD-Na score to predict 12-week mortality for ACLF patients, with the AUROC of 0.817, a sensitivity of 76.5%, and a specificity of 75.9%. CONCLUSION: The age ≥30 years and HBVDNA ≤1000 copies at admission strongly correlate with occurrence of ACLF, and higher MELD-Na score and relapse after LAM withdrawal are closely related with 12-week mortality among patients with ACLF after NAs withdrawal.
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Insuficiência Hepática Crônica Agudizada , Hepatite B Crônica , Hepatite B , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Feminino , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
An 8-week feeding trial and transcriptome analysis were conducted to investigate the potential mechanism of muscle-hardening caused by faba bean in grass carp (Ctenopharyngodon idellus). Ordinary grass carp (fed with practical diet) and crisp grass carp (fed with faba bean meal) groups were designed. Lower water holding capacity and higher some texture parameters were observed in the muscle of crisp grass carp compared with another group. 19.62 GB clean reads were generated, and total 1354 genes exhibiting differentially expression were identified (FDR < 0.05). Genes function enrichment revealed up-regulated genes in crisp grass carp mainly in response to myofibroblast proliferation, while down-regulated genes in response to immune regulation. Consistent with this, the tight junction pathway and the NF-κB signaling pathway were likewise significantly enriched. In summary, this study identified several candidate genes and putative signaling pathways deserving further investigation to the mechanism of muscle-hardening in fish fed with faba bean.
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Ração Animal , Carpas/genética , Animais , Carpas/metabolismo , Proteínas de Peixes/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Músculos/metabolismo , Análise de Sequência de RNA , Vicia fabaRESUMO
BACKGROUND: A liver support therapy, named molecular adsorbents recirculating system (MARS), has been used for more than 700 liver failure patients in China. We made here a summary to evaluate the effects of MARS treatment in different applications with emphasis on hepatitis B virus (HBV) based liver failure. METHODS: This report analyzed data of 252 patients (mean age (44.9+/- 12.7) years) in three groups: acute severe hepatitis (ASH), subacute severe hepatitis (SSH) and chronic severe hepatitis (CSH). The largest group was CSH (156 patients, 61.9%), and 188 patients (74.6%, 188/252) were infected with HBV. RESULTS: MARS treatments were associated with significant reduction of albumin bound toxins and water-soluble toxins. Most of the patients showed a positive response with a significant improvement of multiple organ function substantiated by a significant increase in prothrombin time activity (PTA) and median arterial pressure (MAP). There was a decrease in hepatic encephalopathy (HE) grade and Child-Turcotte-Pugh (CTP) scale. Thirty-nine of 188 HBV patients (20.7%) dropped out of the commendatory consecutive therapy ending with lower survival of 43.6% while the rest of the 149 patients had a survival rate of 62.4%. Survival within the ASH and SSH groups were 81.2% and 75.0%, respectively. In the CSH group, end stage patients were predominant (65/151, 43%), whereas the early and middle stage patients had a better prognosis: early stage survival, including orthotopic liver transplantation (OLT) survival of 91.7%, middle stage survival of 75%, end stage survival of 33.8%. CONCLUSIONS: MARS continues to be the most favorable extracorporeal treatment for liver support therapy in China for a wide range of conditions, including the majority of hepatitis B related liver failure conditions. The appropriate application of MARS for the right indications and stage of hepatic failure, as well as the fulfillment of prescribed treatments, will lead to the optimal therapeutic result.
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Falência Hepática/terapia , Diálise Renal , Desintoxicação por Sorção/métodos , Humanos , Falência Hepática/mortalidade , Desintoxicação por Sorção/efeitos adversosRESUMO
Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships.
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DNA Mitocondrial/genética , Ixodidae/genética , Animais , Genoma/genética , Filogenia , Análise de Sequência de DNARESUMO
The complete mitochondrial genome (15,573 bp) of an understudied sheep parasite Melophagus ovinus was sequenced and characterized. Its organization and characteristics, including the size, structure, gene order, start/stop codon usage and gene overlaps, are largely typical for Diptera. It exhibits very high A + T bias (81%). Posterior probability values in the inferred phylogenetic dendrogram were very high, but Oestroidea and Muscoidea superfamilies were both paraphyletic. The sequence was nested within the Oestridae clade, thus also rendering the family paraphyletic. A larger number of Hippoboscoidea mitogenomes will have to be available to achieve a better phylogenetic resolution.
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AIM: To assess the efficacy and safety of in vivo electroporation (EP)-mediated dual-plasmid hepatitis B virus (HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine (LAM) in patients with chronic hepatitis B. METHODS: Two hundred and twenty-five patients were randomized to receive either LAM + vaccine (vaccine group, n = 109) or LAM + placebo (control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12 (start of treatment with vaccine or placebo, SOT), 16, 24, and 36 (end of treatment with vaccine or placebo, EOT). RESULTS: In the modified intent-to-treat population, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir (ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeAg seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION: The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.
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DNA Viral/uso terapêutico , Eletroporação/métodos , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Vacinas de DNA/uso terapêutico , Adulto , DNA Viral/administração & dosagem , DNA Viral/efeitos adversos , DNA Viral/isolamento & purificação , Método Duplo-Cego , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/efeitos adversos , Vírus da Hepatite B/isolamento & purificação , Humanos , Injeções Intramusculares , Lamivudina/administração & dosagem , Masculino , Plasmídeos , Inibidores da Transcriptase Reversa/administração & dosagem , Resultado do Tratamento , Vacinas de DNA/administração & dosagem , Vacinas de DNA/efeitos adversos , Carga Viral , Adulto JovemAssuntos
Adenina/análogos & derivados , Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Qualidade de Vida , Adenina/uso terapêutico , Adulto , Idoso , Guanina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effect of control integrative measures which persist in snail eradication and chemotherapy on schistosomiasis transmission-interruption in hilly areas. METHODS: The data of integrated control and endemic situation of schistosomiasis from 2004 to 2014 were collected, and the control effect of integrated measures was evaluated. RESULTS: From 2004 to 2014, both the Oncomelania hupensis snail area and density of living snails of Jurong City were reduced from 43.13 hm2 and 1.48 snails/0.1 m2 to 0; the residents' seropositive rate declined continuously; the residents' and students' awareness rates on schistosomiasis control were increased from 88.43% and 82.04% to 92.56% and 95.74% respectively; the snail area was significantly negatively correlated with the coverage rate of snail control (r = -0.864, P < 0.05). CONCLUSIONS: In the hilly areas, the schistosomiasis control integrated measures which persist in snail eradication and chemotherapy could control the endemic situation rapidly and steadily, accelerating to achieve the goal of schistosomiasis transmission-interruption.