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1.
Gene ; 806: 145921, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454033

RESUMO

Maoto, a traditional Japanese medicine (Kampo), is widely used to treat upper respiratory tract infections, including influenza virus infection. Although maoto is known to inhibit pro-inflammatory responses in a rodent model of acute inflammation, its underlying mechanism remains to be determined. In this study, we investigated the involvement of immune responses and noradrenergic function in the inhibitory action of maoto. In a mouse model of polyI:C-induced acute inflammation, maoto was administered orally in conjunction with intraperitoneal injection of PolyI:C (6 mg/kg), and blood was collected after 2 h for measurement of plasma cytokines by ELISA. Maoto significantly decreased PolyI:C-induced TNF-α levels and increased IL-10 production. Neither pretreatment with IL-10 neutralizing antibodies nor T-cell deficiency using nude mice modified the inhibitory effect of maoto, indicating that the anti-inflammatory effects of maoto are independent of IL-10 and T cells. Furthermore, the inhibitory effects of maoto on PolyI:C-induced TNF-α production were not observed in ex vivo splenocytes, suggesting that maoto does not act directly on inflammatory cells. Lastly, pretreatment with a ß-adrenergic receptor antagonist partially cancelled the anti-inflammatory effects of maoto. Collectively, these results suggest that maoto mediates its anti-inflammatory effects via ß-adrenergic receptors in vivo.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anti-Inflamatórios/farmacologia , Inflamação/prevenção & controle , Interleucina-10/genética , Extratos Vegetais/farmacologia , Receptores Adrenérgicos beta/genética , Administração Oral , Animais , Modelos Animais de Doenças , Efedrina/farmacologia , Regulação da Expressão Gênica , Injeções Intraperitoneais , Interleucina-10/agonistas , Interleucina-10/imunologia , Japão , Masculino , Medicina Kampo/métodos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poli I-C/administração & dosagem , Poli I-C/antagonistas & inibidores , Receptores Adrenérgicos beta/imunologia , Transdução de Sinais , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
2.
Gene ; 806: 145922, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34454032

RESUMO

Gastric cancer (GC)-derived cell lines were generally used in basic cancer research and drug screening. However, it is always concerned about the difference between cultured cells and primary tumor by oncologists. To address this question, we compared differentially expressed genes (DEGs) in primary cancers, healthy tissues, and cell lines both in vitro and in silico. Seven reported genes with decreased expression in GCs by DNA methylation were analyzed in our cohort studies and experimentally validation. Selected datasets from TCGA (The Cancer Genome Atlas), CCLE (The Broad Institute Cancer Cell Line Encyclopedia), and GTEx (The Genotype-Tissue Expression project) were used to represent GCs, GC-derived cell lines, and healthy tissues respectively in the in silico analysis. Thirty gastric tissues together with six cell lines were used for validations. Unexpectedly, we experimentally found that reported cancer-related downregulated genes were only found in cancer cell lines but not in biopsies. The unchanged gene expressions in primary GCs were generally consistent with our cohort study, using information from cancerous (TCGA) and healthy tissues (GETx). Substantial differences were also found between DEGs of cancer tissues (TGCA)/ healthy tissues (GTEx) pair and cell lines (CCLE)/ healthy tissues (GTEx) pair, which confirmed the significant differences between primary cancer and cancer cell lines. Moreover, elevated expression of YWHAQ (14-3-3 δ) and THBS1 were observed in the GC biopsies, which might be potential biomarkers for GC diagnosis, considering the increased YWHAQ and THBS1 associated with poor survival rates in gastric cancer patients. In sum, it is suggested that cautions should be taken when using GC cell lines to study genes that show great differences between cell lines and tissues.


Assuntos
Proteínas 14-3-3/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Neoplasias Gástricas/genética , Trombospondinas/genética , Proteínas 14-3-3/metabolismo , Idoso , Atlas como Assunto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Metilação de DNA , Conjuntos de Dados como Assunto , Epigênese Genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Proteínas de Neoplasias/metabolismo , Cultura Primária de Células , Prognóstico , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Trombospondinas/metabolismo , Células Tumorais Cultivadas
3.
Gene ; 806: 145935, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478821

RESUMO

Soluble molecules of programmed death ligand 1 (sPD-L1) are known to modulate T-cell depletion, an important mechanism of hepatitis B virus (HBV) persistence and liver disease progression. In addition, PD-L1 polymorphisms in the 3'-UTR can influence PD-L1 expression and have been associated with cancer risk, although not definitively. The purpose of this study was to investigate the association of PD-L1 polymorphisms and circulating levels of sPD-L1 in HBV infection and live disease progression. In this study, five hundred fifty-one HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 186), liver cirrhosis (LC, n = 142) and hepatocellular carcinoma (HCC, n = 223) and 240 healthy individuals (HC) were enrolled. PD-L1 polymorphisms (rs2297136 and rs4143815) were genotyped by in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of PD-L1 polymorphisms with HBV infection as well as with progression of related liver diseases. Plasma sPD-L1 levels were quantified by ELISA assays. The PD-L1 rs2297136 AA genotype was associated with HBV infection susceptibility (HBV vs. HC: OR = 1.6; 95%CI = 1.1-2.3; p = 0.0087) and disease progression (LC vs. CHB: OR = 1.8; 95%CI = 1.1-2.9; p = 0.018). Whereas, the rs2297136 GG genotype was a protective factor for HCC development. Plasma sPD-L1 levels were significantly high in HBV patients (p < 0.0001) and higher in the LC followed by CHB and HCC groups. High sPD-L1 levels correlated with increased liver enzymes and with advanced liver disease progression (Child-pugh C > B > A, p < 0.0001) and BCLC classification (BCLC D > C > B > A, p = 0.031). We could, for the first time, conclude that PD-L1 rs2297136 polymorphism and plasma sPD-L1 protein levels associate with HBV infection and HBV-related liver disease progression.


Assuntos
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Regiões 3' não Traduzidas , Adulto , Idoso , Antígeno B7-H1/sangue , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Progressão da Doença , Feminino , Expressão Gênica , Predisposição Genética para Doença , Vírus da Hepatite B/crescimento & desenvolvimento , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/virologia , Humanos , Fígado/metabolismo , Fígado/patologia , Fígado/virologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(8): 743-747, 2021 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-34517454

RESUMO

Objective: To determine the diagnostic value of plasma heme oxygenase 1 (HO-1) in the occurrence, development, and pathological stages of chronic hepatitis B-related liver fibrosis. Methods: 211 outpatients and inpatients with chronic hepatitis B (CHB) and 57 healthy controls who visited the Third Hospital of Hebei Medical University were selected. Simultaneously, clinical data, peripheral blood routine and serum biochemical test results of the research subjects were collected. Plasma HO-1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Liver fibrosis (S1 ~ 4) was staged according to liver biopsy and liver stiffness measurement (LSM). Statistical analysis: binary logistic regression was used to analyze the independent risk factors of hepatitis B-related liver fibrosis to establish a diagnostic model, and the receiver operating characteristic curve (ROC) was used to compare and analyze the staging efficiency of HO-1, new model, FIB-4 and APRI for the diagnosis of liver fibrosis. Results: Plasma HO-1 levels were significantly higher in CHB patients than healthy controls [10.11 (7.08 ~ 13.12) ng/ml and 6.71 (5.56 ~ 8.45) ng/ml, (P < 0.001)]. There were 37, 38, 38, and 98 cases with liver fibrosis stages S1, S2, S3, and S4, respectively and plasma HO-1 level was (6.91 ± 2.80) ng/ml, (8.24 ± 2.44) ng/ml, (9.96 ± 3.46) ng/ml, (12.65 ± 3.70) ng/ml, P < 0.001. HO-1, albumin, and platelets (PLT) were independent risk factors for liver fibrosis. A HAP model was established. HAP, FIB-4 and APRI sensitivity and specificity for the diagnosis of liver fibrosis staging were as follows: ≥S2 were 84.62%, 72.35 %, 81.18% and 83.78%, 81.08%, 67.57%; ≥S3 were 80.15%, 82.09%, 85.82% and 88.64%, 76.19%, 60.32%; S4 were 90.82%, 82.29%, 86.46% and 74.37%, 65.77%, 48.65%, respectively. Conclusion: Plasma HO-1 level can reflect the severity of liver fibrosis. HAP diagnostic model can more accurately mirror the process of liver fibrosis than FIB-4 and APRI, and point clinical diagnosis and prognosis assessment.


Assuntos
Heme Oxigenase-1 , Hepatite B Crônica , Aspartato Aminotransferases , Biomarcadores , Biópsia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Curva ROC , Estudos Retrospectivos
5.
Horm Metab Res ; 53(9): 575-587, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34496408

RESUMO

Global warming and the rising prevalence of obesity are well described challenges of current mankind. Most recently, the COVID-19 pandemic arose as a new challenge. We here attempt to delineate their relationship with each other from our perspective. Global greenhouse gas emissions from the burning of fossil fuels have exponentially increased since 1950. The main contributors to such greenhouse gas emissions are manufacturing and construction, transport, residential, commercial, agriculture, and land use change and forestry, combined with an increasing global population growth from 1 billion in 1800 to 7.8 billion in 2020 along with rising obesity rates since the 1980s. The current Covid-19 pandemic has caused some decline in greenhouse gas emissions by limiting mobility globally via repetitive lockdowns. Following multiple lockdowns, there was further increase in obesity in wealthier populations, malnutrition from hunger in poor populations and death from severe infection with Covid-19 and its virus variants. There is a bidirectional relationship between adiposity and global warming. With rising atmospheric air temperatures, people typically will have less adaptive thermogenesis and become less physically active, while they are producing a higher carbon footprint. To reduce obesity rates, one should be willing to learn more about the environmental impact, how to minimize consumption of energy generating carbon dioxide and other greenhouse gas emissions, and to reduce food waste. Diets lower in meat such as a Mediterranean diet, have been estimated to reduce greenhouse gas emissions by 72%, land use by 58%, and energy consumption by 52%.


Assuntos
Mudança Climática , Obesidade/etiologia , Agricultura/economia , Agricultura/tendências , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/patologia , Mudança Climática/história , Comorbidade , Disruptores Endócrinos/toxicidade , Meio Ambiente , Exposição Ambiental/história , Exposição Ambiental/estatística & dados numéricos , Gases de Efeito Estufa/toxicidade , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Obesidade/epidemiologia , Obesidade/metabolismo , Pandemias , Fatores de Risco
6.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502340

RESUMO

The SARS-CoV-2 main protease (Mpro) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role of natural products against SARS-CoV-2 Mpro as repurposable agents in the treatment of coronavirus disease 2019 (COVID-19). Through in silico approach, selected flavonoids were docked into the active site of Mpro. The free energies of the ligands complexed with Mpro were computationally estimated using the molecular mechanics-generalized Born surface area (MM/GBSA) method. In addition, the inhibition process of SARS-CoV-2 Mpro with these ligands was simulated at 100 ns in order to uncover the dynamic behavior and complex stability. The docking results showed that the selected flavonoids exhibited good poses in the binding domain of Mpro. The amino acid residues involved in the binding of the selected ligands correlated well with the residues involved with the mechanism-based inhibitor (N3) and the docking score of Quercetin-3-O-Neohesperidoside (-16.8 Kcal/mol) ranked efficiently with this inhibitor (-16.5 Kcal/mol). In addition, single-structure MM/GBSA rescoring method showed that Quercetin-3-O-Neohesperidoside (-87.60 Kcal/mol) is more energetically favored than N3 (-80.88 Kcal/mol) and other ligands (Myricetin 3-Rutinoside (-87.50 Kcal/mol), Quercetin 3-Rhamnoside (-80.17 Kcal/mol), Rutin (-58.98 Kcal/mol), and Myricitrin (-49.22 Kcal/mol). The molecular dynamics simulation (MDs) pinpointed the stability of these complexes over the course of 100 ns with reduced RMSD and RMSF. Based on the docking results and energy calculation, together with the RMSD of 1.98 ± 0.19 Å and RMSF of 1.00 ± 0.51 Å, Quercetin-3-O-Neohesperidoside is a better inhibitor of Mpro compared to N3 and other selected ligands and can be repurposed as a drug candidate for the treatment of COVID-19. In addition, this study demonstrated that in silico docking, free energy calculations, and MDs, respectively, are applicable to estimating the interaction, energetics, and dynamic behavior of molecular targets by natural products and can be used to direct the development of novel target function modulators.


Assuntos
Produtos Biológicos/metabolismo , SARS-CoV-2/enzimologia , Proteínas da Matriz Viral/metabolismo , Sítios de Ligação , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/patologia , COVID-19/virologia , Domínio Catalítico , Desenho de Fármacos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/uso terapêutico , Quercetina/análogos & derivados , Quercetina/química , Quercetina/metabolismo , Quercetina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Proteínas da Matriz Viral/química
7.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502274

RESUMO

Heat shock proteins (HSPs) are a large group of chaperones found in most eukaryotes and bacteria. They are responsible for the correct protein folding, protection of the cell against stressors, presenting immune and inflammatory cytokines; furthermore, they are important factors in regulating cell differentiation, survival and death. Although the biological function of HSPs is to maintain cell homeostasis, some of them can be used by viruses both to fold their proteins and increase the chances of survival in unfavorable host conditions. Folding viral proteins as well as replicating many different viruses are carried out by, among others, proteins from the HSP70 and HSP90 families. In some cases, the HSP70 family proteins directly interact with viral polymerase to enhance viral replication or they can facilitate the formation of a viral replication complex and/or maintain the stability of complex proteins. It is known that HSP90 is important for the expression of viral genes at both the transcriptional and the translational levels. Both of these HSPs can form a complex with HSP90 and, consequently, facilitate the entry of the virus into the cell. Current studies have shown the biological significance of HSPs in the course of infection SARS-CoV-2. A comprehensive understanding of chaperone use during viral infection will provide new insight into viral replication mechanisms and therapeutic potential. The aim of this study is to describe the molecular basis of HSP70 and HSP90 participation in some viral infections and the potential use of these proteins in antiviral therapy.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Viroses/patologia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Vírus de DNA/fisiologia , Humanos , Isoformas de Proteínas/metabolismo , Vírus de RNA/fisiologia , SARS-CoV-2/isolamento & purificação , Viroses/metabolismo , Viroses/virologia
8.
Int J Mol Sci ; 22(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34502431

RESUMO

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can become infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.


Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Equipamento de Proteção Individual , Anti-Infecciosos/química , Bacteriófago phi 6/efeitos dos fármacos , Compostos de Benzalcônio/química , Compostos de Benzalcônio/farmacologia , COVID-19/patologia , COVID-19/virologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Polietilenotereftalatos/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/isolamento & purificação , Staphylococcus epidermidis/efeitos dos fármacos
9.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502454

RESUMO

COVID-19 is a global threat that has spread since the end of 2019, causing severe clinical sequelae and deaths, in the context of a world pandemic. The infection of the highly pathogenetic and infectious SARS-CoV-2 coronavirus has been proven to exert systemic effects impacting the metabolism. Yet, the metabolic pathways involved in the pathophysiology and progression of COVID-19 are still unclear. Here, we present the results of a mass spectrometry-based targeted metabolomic analysis on a cohort of 52 hospitalized COVID-19 patients, classified according to disease severity as mild, moderate, and severe. Our analysis defines a clear signature of COVID-19 that includes increased serum levels of lactic acid in all the forms of the disease. Pathway analysis revealed dysregulation of energy production and amino acid metabolism. Globally, the variations found in the serum metabolome of COVID-19 patients may reflect a more complex systemic perturbation induced by SARS-CoV-2, possibly affecting carbon and nitrogen liver metabolism.


Assuntos
Biomarcadores/sangue , Carbono/metabolismo , Fígado/metabolismo , Metaboloma , Nitrogênio/metabolismo , Aminoácidos/metabolismo , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , Citocinas/sangue , Análise Discriminante , Humanos , Análise dos Mínimos Quadrados , Redes e Vias Metabólicas/genética , Metabolômica/métodos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
10.
Int J Mol Sci ; 22(17)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34502487

RESUMO

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.


Assuntos
Anticonvulsivantes/uso terapêutico , COVID-19/tratamento farmacológico , Canabidiol/uso terapêutico , Interações Medicamentosas , Nutrientes/metabolismo , Anticonvulsivantes/química , Anticonvulsivantes/farmacocinética , COVID-19/virologia , Canabidiol/química , Canabidiol/farmacocinética , Carbamazepina/química , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Clobazam/química , Clobazam/farmacocinética , Clobazam/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Humanos , SARS-CoV-2/isolamento & purificação
11.
Acta Cytol ; 65(5): 385-392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34482310

RESUMO

OBJECTIVE: The objective of this study was to evaluate the application of DNA ploidy analysis in large-scale population screening for cervical cancer. METHODS: From March 2016 to March 2019, eligible subjects were enrolled and recommended to undergo DNA ploidy analysis, the ThinPrep cytology test (TCT), and high-risk human papillomavirus (hrHPV) detection concurrently. Patients with positive results were recommended for colposcopy, and biopsy diagnosis was regarded as the "gold standard." We compared the test efficiencies of the 3 methods and compared the efficiency and accuracy of the TCT in our hospital and the "2-cancer screening" project in Hubei Province during the same period. RESULTS: Among 20,574 women, the positive rates of DNA ploidy analysis, cytology, and hrHPV testing were 4.01%, 4.71%, and 16.28%, respectively. The sensitivities of these methods for screening for grade 2+ cervical intraepithelial neoplasia were 0.70, 0.68, and 0.96, and their specificities were 0.79, 0.82, and 0.45, respectively. On comparing DNA ploidy analysis with the TCT, there was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value, and missed diagnosis rate. In opportunistic screening and the 2-cancer screening project, the positive rates of cytology were 4.71% and 2.87%, respectively. And the efficiency and accuracy of the TCT in opportunistic screening were higher than in the 2-cancer screening project. CONCLUSION: Therefore, DNA ploidy analysis, which is of low-cost and does not depend on cytopathologists, can replace cytology and be applied in large-scale population screening for cervical cancer.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Programas de Rastreamento , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Adulto , Biópsia , Neoplasia Intraepitelial Cervical/diagnóstico , Neoplasia Intraepitelial Cervical/patologia , Citodiagnóstico/métodos , DNA , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Papillomaviridae/genética , Gravidez , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
12.
Hematology ; 26(1): 691-696, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34493159

RESUMO

Objective: The 8p11 myeloproliferative syndrome [EMS] is a rare myeloproliferative disorder which usually develops rapidly with chromosomal translocation of the fibroblast growth factor receptor 1 gene. The gene has 15 fusion partners, including the breakpoint cluster region (BCR) gene on chromosome 22. Of all the tests available, chromosome karyotype determination is the most important for the diagnosis of EMS. Here, we describe one case of a patient characterized by marked increase of white blood cells and thrombocytopenia and diagnosed as EMS with t(8;22)(p11;q11) by chromosome karyotype.Methods: 28-year-old man was referred to our hospital. He had a onemonth history of intermittent coughing and a small amount of expectoration after catching a cold. As an outpatient, his complete blood count showed: WBC was 130.04 × 109/L with 80.20% granulocytes.Hematologic investigations, bone marrow analysis and genomic DNA sequencing studies were performed.Results: Despite additional chromosomal abnormalities,the patient progressed rapidly with a B blast cell clone in one month. After diagnosis inthree months, the patient underwent the haplo-identical BMT of his brother, followed up for three years, and had a high rate of survival.Conclusions: Our report provides a definite conceptual framework for a better understanding of the characteristics of The 8p11 myeloproliferative syndrome [EMS].


Assuntos
Cromossomos Humanos Par 22/genética , Cromossomos Humanos Par 8/genética , Transplante de Células-Tronco Hematopoéticas , Transtornos Mieloproliferativos , Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-bcr/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Translocação Genética , Adulto , Aloenxertos , Humanos , Masculino , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Síndrome
13.
Hematology ; 26(1): 684-690, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34493173

RESUMO

BACKGROUND: Sickle cell anaemia affects about 4 million people across the globe, making it an inherited disorder of public health importance. Red cell lysis consequent upon haemoglobin crystallization and repeated sickling leads to anaemia and a baseline strain on haemopoiesis. Vaso-occlusion and haemolysis underlies majority of the chronic complications of sickle cell. We evaluated the clinical and laboratory features observed across the various clinical phenotypes in adult sickle cell disease patients. METHODS: Steady state data collected prospectively in a cohort of adult sickle cell disease patients as out-patients between July 2010 and July 2020. The information included epidemiological, clinical and laboratory data. RESULTS: About 270 patients were captured in this study (165 males and 105 females). Their ages ranged from 16 to 55 years, with a median age of 25 years. Sixty-eight had leg ulcers, 43 of the males had priapism (erectile dysfunction in 8), 42 had AVN, 31 had nephropathy, 23 had osteomyelitis, 15 had osteoarthritis, 12 had cholelithiasis, 10 had stroke or other neurological impairment, 5 had pulmonary hypertension, while 23 had other complications. Frequency of crisis ranged from 0 to >10/year median of 2. Of the 219 recorded, 148 of the patients had been transfused in the past, while 71 had not. CONCLUSION: The prevalence of SLU, AVN, priapism, nephropathy and the other complications of SCD show some variations from other studies. This variation in the clinical parameters across different clinical phenotypes indicates an interplay between age, genetic and environmental factors.


Assuntos
Anemia Falciforme , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Colelitíase/etiologia , Colelitíase/metabolismo , Colelitíase/patologia , Feminino , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Nefropatias/epidemiologia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Úlcera da Perna/epidemiologia , Úlcera da Perna/etiologia , Úlcera da Perna/metabolismo , Úlcera da Perna/patologia , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Osteoartrite/epidemiologia , Osteoartrite/etiologia , Osteoartrite/metabolismo , Osteomielite/epidemiologia , Osteomielite/etiologia , Osteomielite/metabolismo , Osteomielite/patologia , Priapismo/epidemiologia , Priapismo/etiologia , Priapismo/metabolismo , Priapismo/patologia , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia
14.
Hematology ; 26(1): 628-636, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34494505

RESUMO

Over the past 20 years, granulocyte colony-stimulating factor (G-CSF) has driven the attention of researchers as a therapeutic agent for curing patients suffering from neutropenia. Despite the successful use of G-CSF, it currently requires daily injections, which are inconvenient, expensive, and distressing for children. Therefore, an alternative strategy for using G-CSF for treatment is needed. Understanding the G-CSF structure, expression, mechanism of action, and how it induces neutrophils mobilization is crucial to producing promising cancer therapy. The ability of G-CSF to mobilize hematopoietic stem cells from the bone marrow into the blood circulation was consequently exploited and altered the practice of hematopoietic stem cell transplantation. This is the motivation for the current review, which sheds light on the history of G-CSF and then focuses on the mechanism of action upon binding to its receptor (G-CSFR) and how that had led to the stimulation of neutrophils mobilization. The findings of this review show new insight into the mechanism of G-CSF that induces neutrophils mobilization. Thus, Understanding the G-CSF will provide a more effective treatment for all neutropenia patients.


Assuntos
Fator Estimulador de Colônias de Granulócitos/metabolismo , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Neutropenia/metabolismo , Neutrófilos/metabolismo , Fator Estimulador de Colônias de Granulócitos/história , Células-Tronco Hematopoéticas/patologia , História do Século XX , História do Século XXI , Humanos , Neutropenia/patologia , Neutropenia/terapia , Neutrófilos/patologia
15.
Nature ; 597(7875): 250-255, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34497389

RESUMO

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.


Assuntos
Envelhecimento , Sistema Nervoso Entérico/citologia , Feto/citologia , Saúde , Intestinos/citologia , Intestinos/crescimento & desenvolvimento , Linfonodos/citologia , Linfonodos/crescimento & desenvolvimento , Adulto , Animais , Criança , Doença de Crohn/patologia , Conjuntos de Dados como Assunto , Sistema Nervoso Entérico/anatomia & histologia , Sistema Nervoso Entérico/embriologia , Sistema Nervoso Entérico/crescimento & desenvolvimento , Células Epiteliais/citologia , Feminino , Feto/anatomia & histologia , Feto/embriologia , Humanos , Intestinos/embriologia , Intestinos/inervação , Linfonodos/embriologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Organogênese , Receptores de IgG/metabolismo , Transdução de Sinais , Análise Espaço-Temporal , Fatores de Tempo
16.
PLoS One ; 16(9): e0257191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34499677

RESUMO

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread. Although several mRNA- and adenovirus-based vaccines are highly effective, their dependence on the "cold chain" transportation makes global vaccination a difficult task. In this context, a stable lyophilized vaccine may present certain advantages. Accordingly, establishing additional vaccine platforms remains vital to tackle SARS-CoV-2 and any future variants that may arise. Vaccinia virus (VACV) has been used to eradicate smallpox disease, and several attenuated viral strains with enhanced safety for human applications have been developed. We have generated two candidate SARS-CoV-2 vaccines based on two vaccinia viral strains, MVA and v-NY, that express full-length SARS-CoV-2 spike protein. Whereas MVA is growth-restricted in mammalian cells, the v-NY strain is replication-competent. We demonstrate that both candidate recombinant vaccines induce high titers of neutralizing antibodies in C57BL/6 mice vaccinated according to prime-boost regimens. Furthermore, our vaccination regimens generated TH1-biased immune responses in mice. Most importantly, prime-boost vaccination of a Syrian hamster infection model with MVA-S and v-NY-S protected the hamsters against SARS-CoV-2 infection, supporting that these two vaccines are promising candidates for future development. Finally, our vaccination regimens generated neutralizing antibodies that partially cross-neutralized SARS-CoV-2 variants of concern.


Assuntos
Vacinas contra COVID-19/administração & dosagem , COVID-19/imunologia , Vírus Vaccinia/genética , Animais , Anticorpos Neutralizantes/análise , Anticorpos Neutralizantes/imunologia , COVID-19/virologia , Vacinas contra COVID-19/genética , Feminino , Imunização Secundária , Pulmão/patologia , Masculino , Mesocricetus , Camundongos , Camundongos Endogâmicos C57BL , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/química
17.
Front Immunol ; 12: 709861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475873

RESUMO

Background: Immune hyperactivity is an important contributing factor to the morbidity and mortality of COVID-19 infection. Nasal administration of anti-CD3 monoclonal antibody downregulates hyperactive immune responses in animal models of autoimmunity through its immunomodulatory properties. We performed a randomized pilot study of fully-human nasal anti-CD3 (Foralumab) in patients with mild to moderate COVID-19 to determine if its immunomodulatory properties had ameliorating effects on disease. Methods: Thirty-nine outpatients with mild to moderate COVID-19 were recruited at Santa Casa de Misericordia de Santos in Sao Paulo State, Brazil. Patients were randomized to three cohorts: 1) Control, no Foralumab (n=16); 2) Nasal Foralumab (100ug/day) given for 10 consecutive days with 6 mg dexamethasone given on days 1-3 (n=11); and 3) Nasal Foralumab alone (100ug/day) given for 10 consecutive days (n=12). Patients continued standard of care medication. Results: We observed reduction of serum IL-6 and C-reactive protein in Foralumab alone vs. untreated or Foralumab/Dexa treated patients. More rapid clearance of lung infiltrates as measured by chest CT was observed in Foralumab and Foralumab/Dexa treated subjects vs. those that did not receive Foralumab. Foralumab treatment was well-tolerated with no severe adverse events. Conclusions: This pilot study suggests that nasal Foralumab is well tolerated and may be of benefit in treatment of immune hyperactivity and lung involvement in COVID-19 disease and that further studies are warranted.


Assuntos
Anticorpos Monoclonais/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , Pneumonia/terapia , Administração Intranasal , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Biomarcadores , Proteína C-Reativa/análise , COVID-19/fisiopatologia , COVID-19/terapia , Estudos de Coortes , Feminino , Humanos , Imunidade/efeitos dos fármacos , Interleucina-6/sangue , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Projetos Piloto , Pneumonia/prevenção & controle , Adulto Jovem
18.
Front Immunol ; 12: 728513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34484238

RESUMO

VITT is a rare, life-threatening syndrome characterized by thrombotic symptoms in combination with thrombocytopenia, which may occur in individuals receiving the first administration of adenoviral non replicating vectors (AVV) anti Covid19 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) is characterized by high levels of serum IgG that bind PF4/polyanion complexes, thus triggering platelet activation. Therefore, identification of the fine pathophysiological mechanism by which vaccine components trigger platelet activation is mandatory. Herein, we propose a multistep mechanism involving both the AVV and the neo-synthetized Spike protein. The former can: i) spread rapidly into blood stream, ii), promote the early production of high levels of IL-6, iii) interact with erythrocytes, platelets, mast cells and endothelia, iv) favor the presence of extracellular DNA at the site of injection, v) activate platelets and mast cells to release PF4 and heparin. Moreover, AVV infection of mast cells may trigger aberrant inflammatory and immune responses in people affected by the mast cell activation syndrome (MCAS). The pre-existence of natural antibodies binding PF4/heparin complexes may amplify platelet activation and thrombotic events. Finally, neosynthesized Covid 19 Spike protein interacting with its ACE2 receptor on endothelia, platelets and leucocyte may trigger further thrombotic events unleashing the WITT syndrome.


Assuntos
Anticorpos/efeitos adversos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Púrpura Trombocitopênica Idiopática/induzido quimicamente , Púrpura Trombocitopênica Idiopática/fisiopatologia , Adenoviridae/genética , Animais , Plaquetas/imunologia , Plaquetas/patologia , Vacinas contra COVID-19/imunologia , Modelos Animais de Doenças , Vetores Genéticos , Humanos , Camundongos , Ativação Plaquetária/imunologia , Fator Plaquetário 4 , Coelhos
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