RESUMO
Neuroinflammation plays crucial role in the development and progression of depression. Large conductance calcium- and voltage-dependent potassium (BK) channels mediate the activation of microglia. Herein, we investigated whether BK channels could serve as a target for the treatment of inflammation-associated depression. Lipopolysaccharide (LPS, 0.83 mg/kg) was injected intraperitoneally (i.p.) to induce neuroinflammation and depressive-like behavior in 6-8 week ICR mice. Adeno-associated virus (AAV) constructs (AAV9-Iba1p-BK shRNA-EGFP (BK shRNA-AAV) or AAV9-Iba1p-NC shRNA-EGFP (NC shRNA-AAV)) were unilaterally injected intracerebroventricularly to selectively knock down BK channels in microglia. The tail suspension test (TST) and forced-swim test (FST) were used to evaluate depressive-like behavior in mice 24 h after LPS challenge. The morphology of microglia, expression of BK channels, levels of cytokines, and expression and activity of indoleamine 2,3-dioxygenase (IDO) were measured by immunohistochemistry, western blot, quantitative real time PCR, and enzyme-linked immunosorbent assay (ELISA), respectively. Either paxilline (i.p.), a specific BK channel blocker, or BK shRNA-AAV effectively inhibited the activation of microglia, reduced the production of IL-1ß in the hippocampus and suppressed the expression and activity of IDO in the hippocampus and prefrontal cortex, resulting in the amelioration of depressive-like behavior in mice. These data suggest for the first time that BK channels are involved in LPS-induced depressive-like behaviors. Thus, microglia BK channels may be a potential drug target for the depression treatment.
Assuntos
Canais de Potássio Ativados por Cálcio de Condutância Alta , Lipopolissacarídeos , Camundongos , Animais , Lipopolissacarídeos/toxicidade , Doenças Neuroinflamatórias , Camundongos Endogâmicos ICR , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , RNA Interferente PequenoRESUMO
AIMS: To investigate the clinical and radiographic outcomes of a chemically modified sandblasted large-grit acid-etched implant (hydrophilic) in lateral sinus floor elevation (LSFE), compared with a conventional one (hydrophobic). MATERIALS AND METHODS: A retrospective study design was adopted. Patients who received LSFE with simultaneous implant placement were recruited. According to different types of implant surfaces, patients were divided into two groups (the hydrophilic group and the hydrophobic group). Implant survival rate (SR), endo-sinus bone stability on the radiographs, mean probing depths, percentage of bleeding on probing, marginal bone loss, and patient satisfaction were evaluated. RESULTS: A total of 106 patients with 180 implants (hydrophilic:101, hydrophobic:79) in 119 maxillary sinuses were included. The follow-up period ranged from 2 to 5 years. Three hydrophobic implants and one hydrophilic implant in four different patients failed. The SR of the hydrophilic group was higher than that of the hydrophobic group but without a significant difference (p > .05). The change and change rate of endo-sinus bone height (ΔESBH and RΔESBH) and bone volume (ΔESBV and RΔESBV) in the hydrophilic group were less than those in the hydrophobic group, with a significant difference at 6 months after implantation. No other significant difference was found between the two groups. CONCLUSION: Within the limitations of this study, both hydrophilic and hydrophobic implants were suitable for LSFE with predictable clinical outcomes. Meanwhile, hydrophilic implants could contribute to the grafted endo-sinus bone stability during healing time.
Assuntos
Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Humanos , Estudos Retrospectivos , Masculino , Feminino , Levantamento do Assoalho do Seio Maxilar/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Implantação Dentária Endóssea/métodos , Idoso , Adulto , Propriedades de Superfície , Interações Hidrofóbicas e Hidrofílicas , Planejamento de Prótese DentáriaRESUMO
STATEMENT OF PROBLEM: The outcome of implant-supported fixed complete dentures in edentulous patients with a history of periodontitis is unclear. PURPOSE: The purpose of this retrospective clinical study was to assess the clinical outcomes of immediate loaded fixed complete dentures in individuals with a history of periodontitis and to analyze risk factors related to implant failure. MATERIAL AND METHODS: A total of 642 implants (146 prostheses) in 119 patients were included. The follow-up period ranged from 2 to 7 years. Implant survival rates, marginal bone loss, mechanical complications, biologic complications, and patient satisfaction were evaluated. The Pearson chi-square test, independent samples t test, and multivariate generalized estimating equation were performed for statistical analysis (α=.05). RESULTS: Eleven implants in 9 patients failed, leading to overall survival rates of 98.3% at the implant level and 92.4% at the patient level. The mean ±standard deviation marginal bone loss was 0.62 ±0.86 mm, and marginal bone loss did not differ significantly between axial and tilted implants (P>.05). Mechanical complications were detected in 55 (37.7%) definitive prostheses; biologic complications were detected in 318 (49.5%) implants. Smokers had a significantly lower survival rate than nonsmokers (odds ratio: 6.880, P=.013). Bruxers had a significantly higher incidence of mechanical complications than nonbruxers (P<.001). CONCLUSIONS: The immediate loaded fixed complete denture supported by implants is a suitable treatment option for edentulous patients with a history of periodontitis, with high survival implant rates. Smoking is a risk factor for implant failure. Bruxism may increase the incidence of mechanical complications with implant-supported fixed complete dentures, and the overall biologic complication incidence is comparatively high.
Assuntos
Perda do Osso Alveolar , Produtos Biológicos , Implantes Dentários , Carga Imediata em Implante Dentário , Periodontite , Humanos , Implantes Dentários/efeitos adversos , Estudos Retrospectivos , Perda do Osso Alveolar/etiologia , Periodontite/induzido quimicamente , Periodontite/complicações , Prótese Total Imediata , Prótese Dentária Fixada por Implante/efeitos adversos , Seguimentos , Resultado do Tratamento , Falha de Restauração DentáriaRESUMO
OBJECTIVE: To evaluate the surface topography and element proportion changes in clinically failed implants after different modalities in vitro debridement and to compare the cleaning effect of different method combinations. MATERIAL AND METHODS: Thirty clinical failed implants were treated by different debridement methods in vitro as follows: Group 1: physiologic saline irrigation; Group 2: glycine powder air polishing; Group 3: glycine powder air polishing + ethylenediaminetetraacetic acid (EDTA); Group 4: polyetheretherketone (PEEK) tip ultrasonic scaling; and Group 5: PEEK tip ultrasonic scaling + EDTA. The relative contaminated area reduction (RCAR), visual analogue scale (VAS, the higher value means, the better cleaning effect) and surface roughness were assessed using scanning electron microscopy (SEM), stereoscopic microscopy (SM) and white light interferometry (WLI). Surface chemistry was determined by energy dispersive spectroscopy (EDS). RESULTS: Group 4 and Group 5 showed higher RCARs (82.90%, 82.89%), VAS scores (2.61, 2.33) and roughness reductions (-0.85 µm, -1.80 µm). Group 3 attained the highest decrease of C% (carbon, -26.67%), O% (oxygen, -13.71%) and N% (nitrogen, -5.66%), and the highest increase of Ti% (titanium, 49.67%). PEEK remnants were detected on the implant surface of Groups 4 and 5. CONCLUSION: Within the limitation of the present in vitro design, PEEK tip ultrasonic scaling was more effective in eliminating visible contamination, while glycine powder air polishing combined with EDTA treatment was more conducive to expose the original surface element distribution. Both methods have their own advantages in decontamination, but none of them could reconstruct the surface as the pristine implant.
Assuntos
Implantes Dentários , Desbridamento , Microscopia Eletrônica de Varredura , Propriedades de Superfície , TitânioRESUMO
The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing technology has been used to inactivate viral DNA as a new strategy to eliminate chronic viral infections, including HIV-1. This utility of CRISPR-Cas9 is challenged by the high heterogeneity of HIV-1 sequences, which requires the design of the single guide RNA (sgRNA; utilized by the CRISPR-Cas9 system to recognize the target DNA) to match a specific HIV-1 strain in an HIV patient. One solution to this challenge is to target the viral primer binding site (PBS), which HIV-1 copies from cellular tRNA3Lys in each round of reverse transcription and is thus conserved in almost all HIV-1 strains. In this study, we demonstrate that PBS-targeting sgRNA directs Cas9 to cleave the PBS DNA, which evokes deletions or insertions (indels) and strongly diminishes the production of infectious HIV-1. While HIV-1 escapes from PBS-targeting Cas9/sgRNA, unique resistance mechanisms are observed that are dependent on whether the plus or the minus strand of the PBS DNA is bound by sgRNA. Characterization of these viral escape mechanisms will inform future engineering of Cas9 variants that can more potently and persistently inhibit HIV-1 infection.IMPORTANCE The results of this study demonstrate that the gene-editing complex Cas9/sgRNA can be programmed to target and cleave HIV-1 PBS DNA, and thus, inhibit HIV-1 infection. Given that almost all HIV-1 strains have the same PBS, which is copied from the cellular tRNA3Lys during reverse transcription, PBS-targeting sgRNA can be used to inactivate HIV-1 DNA of different strains. We also discovered that HIV-1 uses different mechanisms to resist Cas9/sgRNAs, depending on whether they target the plus or the minus strand of PBS DNA. These findings allow us to predict that a Cas9 variant that uses the CCA sequence as the protospacer adjacent motif (PAM) should more strongly and persistently suppress HIV-1 replication. Together, these data have identified the PBS as the target DNA of Cas9/sgRNA and have predicted how to improve Cas9/sgRNA to achieve more efficient and sustainable suppression of HIV-1 infection, therefore improving the capacity of Cas9/sgRNA in curing HIV-1 infection.
Assuntos
Proteína 9 Associada à CRISPR/metabolismo , DNA Viral/metabolismo , Edição de Genes , HIV-1/genética , RNA Guia de Cinetoplastídeos/metabolismo , Linhagem Celular , DNA Viral/genética , Humanos , Mutagênese Insercional , RNA Guia de Cinetoplastídeos/genética , Deleção de SequênciaRESUMO
We report on erbium (Er) related electroluminescence (EL) in the visible and near infrared (NIR) regions from the light-emitting device (LED) based on the Er-doped ZnO (ZnO:Er)/n-Si isotype heterostructure formed by sputtering ZnO:Er film on n-Si/n+-Si epitaxial wafer. Herein, the ZnO:Er film exhibits n-type in electrical conduction. The aforementioned LED is electroluminescent only under sufficiently high forward bias with the negative voltage connecting to n+-Si substrate. Such forward bias enables the electrons from n-Si to enter into the ultra-thin SiOx (x ≤ 2) layer inherently existing between the ZnO:Er film and n-Si via Poole-Frenkel conduction mechanism and, subsequently, to drift into the ZnO:Er film thus becoming hot electrons, which impact-excite the Er3+ ions to emit characteristic visible and NIR light. Furthermore, the Er-related EL from the aforementioned LED can be significantly enhanced through adopting the strategy of co-doping F- ions into the ZnO host, which brings about twofold primary effects. Firstly, due to the atomic size compensation between F- and Er3+ ions, the ZnO crystal grains become larger to accommodate much more optically active Er3+ ions. Secondly, the partial substitution of F- ions for O2- ions around the Er3+ ion reduces the symmetry of pseudo-octahedral crystal field of Er3+ ion, thus increasing the probabilities of intra-4f transitions of Er3+ ions. We believe that this work sheds light on developing efficient silicon-based LEDs using the Er-doped oxide semiconductors.
RESUMO
Coronary heart disease is the second highest specific cause of death. H9c2 cardiomyocytes were subjected to hypoxia (1% O2) for 0, 6, 12, 24 and 48â¯h. Cell apoptosis and the activity of caspase3/7 was detected using ELISA; western blot was applied to determine the cleaved-caspase3 (c-caspase3), cleaved-PARP (c-PARP) and cytochrome C (Cyto C) expression after the inhibitor negative control (in-NC), miR-503 inhibitor, mimic negative control (mi-NC) and miR-503 mimic were transfected into cells for 48â¯h. Moreover, flow cytometry was applied to evaluate mitochondrial membrane potential. In addition, luciferase reporter gene assay was used for detection the relationship between miR-503 and insulin-like growth-factor-1 receptor (IGF-1R). Real-time PCR showed microRNA-503 (miR-503) was elevated in a time-dependent manner under hypoxia. MiR-503 inhibition prevented cell apoptosis and reduced caspase3/7 activity and the expression of c-caspase3 and c-PARP, prevented mitochondrial membrane potential collapse and reduced the cyto C level in cytosol. While, miR-503 overexpression showed a pro-apoptotic role and resulted in mitochondrial membrane potential loss. MiR-503 directly targets IGF-1R in H9c2 cardiomyocytes. The depletion of IGF-1R using a specific IGF-1R siRNA (siIGF-1R) abolished anti-apoptotic function of miR-503 inhibitor, and LY294002 showed a similar trend. In summary, miR-503 promoted cell apoptosis, caused mitochondrial membrane potential collapse and the emancipation of cyto C from mitochondrial through PI3K/Akt pathway via targeting IGF-1R in H9c2 cardiomyocytes.
Assuntos
Apoptose/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Hipóxia Celular/genética , Linhagem Celular , Citocromos c/metabolismo , Regulação da Expressão Gênica , Potencial da Membrana Mitocondrial , MicroRNAs/genética , Ratos , Receptor IGF Tipo 1/genéticaRESUMO
To date, there have been no reports characterizing HIV-1 in the semen of Chinese men who have sex with men (MSM) with early infection. In this study, genetic diversity and viral load of HIV-1 in the seminal compartments and blood of Chinese MSM with early HIV-1 infection were examined. Viral load and genetic diversity of HIV-1 in paired samples of semen and blood were analyzed in seven MSM with early HIV-1 infection. HIV-1 RNA and DNA were quantitated by real-time PCR assays. Through sequencing the C2-V5 region of the HIV-1 env gene, the HIV-1 genotype and genetic diversity based on V3 loop amino acid sequences were determined by using Geno2pheno and PSSM programs co-receptor usage. It was found that there was more HIV-1 RNA in seminal plasma than in blood plasma and total, and more 2-LTR circular and integrated HIV-1 DNA in seminal cells than in peripheral blood mononuclear cells from all seven patients with early HIV-infection. There was also greater HIV-1 genetic diversity in seminal than in blood compartments. HIV-1 in plasma displayed higher genetic diversity than in cells from the blood and semen. In addition, V3 loop central motifs, which present some key neutralizing antibody epitopes, varied between blood and semen. Thus, virological characteristics in semen may be more representative when evaluating risk of transmission in persons with early HIV infection.
Assuntos
Variação Genética , Infecções por HIV/sangue , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/genética , Homossexualidade Masculina , Sêmen/virologia , Carga Viral , Adolescente , Adulto , Motivos de Aminoácidos , Sequência de Aminoácidos , Anticorpos Neutralizantes , Anticorpos Antivirais , Povo Asiático , Contagem de Linfócito CD4 , DNA Viral/análise , Vetores Genéticos , Genótipo , Proteína gp120 do Envelope de HIV , HIV-1/classificação , Humanos , Leucócitos Mononucleares/virologia , Masculino , Fragmentos de Peptídeos , Filogenia , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real , Infecções Sexualmente Transmissíveis/sangue , Infecções Sexualmente Transmissíveis/virologia , Sequências Repetidas Terminais/genética , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/classificação , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood.
Assuntos
Fármacos Anti-HIV/uso terapêutico , DNA Viral/análise , Infecções por HIV/virologia , HIV/isolamento & purificação , RNA Viral/análise , Sêmen/virologia , Adulto , Linfócitos T CD4-Positivos/imunologia , HIV/genética , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sêmen/química , Análise de Sequência , Produtos do Gene env do Vírus da Imunodeficiência Humana/genéticaRESUMO
BACKGROUND: Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a deadly disease to a manageable chronic illness, albeit does not provide a cure. The recently developed genome editing system called CRISPR/Cas9 offers a new tool to inactivate the integrated latent HIV-1 DNA and may serve as a new avenue toward cure. FINDINGS: We tested 10 sites in HIV-1 DNA that can be targeted by CRISPR/Cas9. The engineered CRISPR/Cas9 system was introduced into the JLat10.6 cells that are latently infected by HIV-1. The sequencing results showed that each target site in HIV-1 DNA was efficiently mutated by CRISPR/Cas9 with the target site in the second exon of Rev (called T10) exhibiting the highest degree of mutation. As a result, HIV-1 gene expression and virus production were significantly diminished with T10 causing a 20-fold reduction. CONCLUSIONS: The CRISPR/Cas9 complex efficiently mutates and deactivates HIV-1 proviral DNA in latently infected Jurkat cells. Our results also revealed a highly efficient Cas9 target site within the second exon of Rev that represents a promising target to be further explored in the CRISPR/Cas9-based cure strategy.
Assuntos
Sistemas CRISPR-Cas , DNA Viral/metabolismo , HIV-1/imunologia , Provírus/imunologia , Latência Viral , HIV-1/fisiologia , Humanos , Células Jurkat , Provírus/fisiologia , Inativação de VírusRESUMO
BACKGROUND: The effectiveness of telemedicine for the management of chronic diseases is unclear. This study examined the effectiveness of telemedicine in relieving asthma symptoms. MATERIALS AND METHODS: A systematic review of the Medline, Cochrane, EMBASE, and Google Scholar databases was conducted until December 31, 2013 using the following key words: "asthma," "telemedicine," "telehealth," "e-health," "mobile health," "Internet," "telecommunication," "telemanagement," "remote," and "short message service." Inclusion criteria were randomized controlled trial, a diagnosis of asthma, the majority of the patients were ≥18 years of age, and intervention involved any format of telemedicine. A meta-analysis of eligible studies was conducted with the primary outcome being change of asthma symptoms. RESULTS: Of 813 articles identified, 11 were included in the qualitative synthesis, and 6 were included in the meta-analysis. Among the 11 studies, there were 1,460 patients in the intervention groups and 1,349 in the control groups, and the total numbers of participants ranged from 12 to 481 in the intervention groups and from 12 to 487 in the control groups. The mean age of patients ranged in the intervention groups from 34.4 to 54.6 years and in the control groups from 30.7 to 56.4 years. The treatment duration ranged from 0.5 to 12 months. The meta-analysis of six eligible studies revealed no significant difference in asthma symptom score change between the telemedicine and control groups (pooled Hedges's g=0.34, 95% confidence interval=-0.05 to 0.74, Z=1.69, p=0.090). CONCLUSIONS: Telemedicine interventions do not appear to improve asthma function scores, but other benefits may be present.
Assuntos
Asma/tratamento farmacológico , Asma/fisiopatologia , Telemedicina , Adulto , Idoso , Doença Crônica , Gerenciamento Clínico , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Mucosal surfaces are not targeted by most human immunodeficiency virus type 1 (HIV-1) vaccines, despite being major routes for HIV-1 transmission. Here we report a novel vaccination regimen consisting of a mucosal prime with a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe)) and an intramuscular boost with a nonreplicating adenovirus strain (Ad5(SIVgpe)). This regimen elicited robust cellular immune responses with enhanced magnitudes, sustainability, and polyfunctionality, as well as higher titers of neutralizing antibodies against the simian immunodeficiency virus SIV(mac1A11) in rhesus monkeys. The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ~75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol. Our study provides a novel strategy for developing an HIV-1 vaccine by using the combination of a replicating vector and mucosal priming.
Assuntos
Portadores de Fármacos , Vetores Genéticos , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/imunologia , Vacinação/métodos , Vaccinia virus/genética , Adenoviridae/genética , Administração através da Mucosa , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Linfócitos T CD8-Positivos/imunologia , Produtos do Gene gag/imunologia , Produtos do Gene pol/imunologia , Injeções Intramusculares , Macaca mulatta , Vacinas contra a SAIDS/administração & dosagem , Vacinas contra a SAIDS/genética , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificação , Carga ViralRESUMO
PURPOSE: To evaluate the chemotherapeutic activity of temozolomide counter to mammary carcinoma. METHODS: In-vitro anticancer activity has been conducted on MCF7 cells, and mammary carcinoma has been induced in Wistar rats by introduction of 7, 12-Dimethylbenz(a)anthracene (DMBA), which was sustained for 24 weeks. Histopathology, immunohistochemistry, cell proliferation study and apoptosis assay via TUNEL method was conducted to evaluate an antineoplastic activity of temozolomide in rat breast tissue. RESULTS: IC50 value of temozolomide in MCF7 cell has been obtained as 103 µM, which demonstrated an initiation of apoptosis. The temozolomide treatment facilitated cell cycle arrest in G2/M and S phase dose dependently. The treatment with temozolomide suggested decrease of the hyperplastic abrasions and renovation of the typical histological features of mammary tissue. Moreover, temozolomide therapy caused the downregulation of epidermal growth factor receptor, extracellular signal-regulated kinase, and metalloproteinase-1 expression and upstream of p53 and caspase-3 proliferation to indicate an initiation of apoptotic events. CONCLUSIONS: The occurrence of mammary carcinoma has been significantly decreased by activation of apoptotic pathway and abrogation of cellular propagation that allowable for developing a suitable mechanistic pathway of temozolomide in order to facilitate chemotherapeutic approach.
Assuntos
Antineoplásicos Alquilantes , Apoptose , Receptores ErbB , Ratos Wistar , Temozolomida , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Feminino , Receptores ErbB/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Metaloproteinase 1 da Matriz/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , Proliferação de Células/efeitos dos fármacos , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Células MCF-7 , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , Imuno-Histoquímica , Reprodutibilidade dos Testes , Ratos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologiaRESUMO
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is a serious threat to human health; thus, early diagnosis and adequate treatment are essential. However, there are still great challenges in identifying the tipping point and detecting early warning signals of early HCC. In this study, we aimed to identify the tipping point (critical state) of and key molecules involved in hepatocarcinogenesis based on time series transcriptome expression data of HCC patients. The phase from veHCC (very early HCC) to eHCC (early HCC) was identified as the critical state in HCC progression, with 143 genes identified as key candidate molecules by combining the DDRTree (dimensionality reduction via graph structure learning) and DNB (dynamic network biomarker) methods. Then, we ranked the candidate genes to verify their mRNA levels using the diethylnitrosamine (DEN)-induced HCC mouse model and identified five early warning signals, namely, CCT3, DSTYK, EIF3E, IARS2 and TXNRD1; these signals can be regarded as the potential early warning signals for the critical state of HCC. We identified CCT3 as an independent prognostic factor for HCC, and functions of CCT3 involving in the "MYCtargets_V1" and "E2F-Targets" are closely related to the progression of HCC. The predictive method combining the DDRTree and DNB methods can not only identify the key critical state before cancer but also determine candidate molecules of critical state, thus providing new insight into the early diagnosis and preemptive treatment of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Carcinogênese/genética , Carcinogênese/patologia , Biomarcadores , Transcriptoma , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Chaperonina com TCP-1/genética , Chaperonina com TCP-1/metabolismoRESUMO
Broadly neutralizing antibodies and appropriate immunogens are critical for preexposure prophylaxis and therapeutic HIV vaccines. In this study, we aimed to explore effective antibodies against the genetically diverse HIV-1 strains by investigating the roles of human CD4 D1D2 domain and nonvariable immugens. The human CD4 D1D2 domain and the chimeric protein of mouse D1 domain/human D2 domain were expressed in Sf9 insect cells and purified by gel-filtration chromatography. The human CD4 D1D2 domain potently inhibited the infection of 77.8% HIV-1 pseudoviruses, including the clades AE, B' and BC, with less than 20 µg/mL of IC(50). pcDNA3.1-mhD1D2m and pcDNA3.1-mhD2m plasmids were used for the production of mouse anti-human CD4 polyclonal antibodies. The neutralizing activities of the polyclonal antibodies were determined by using pseudotyped HIV-1 viruses. The antibodies induced by plasmids containing human CD4 D1D2 domain were able to potently inhibit all pseudotyped HIV-1 strains. The antibodies from mhD1D2m-immunized mice also showed strong binding capacity to CD4 expressed on the surface of TZM-bl cells. The potent and broad inhibitory activity of antibodies against the human CD4 D1D2 domain may be used to develop effective passive immunization agent to control the spread of HIV infection.
Assuntos
Antígenos CD4/química , Antígenos CD4/imunologia , Anticorpos Anti-HIV/biossíntese , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Vacinas contra a AIDS/química , Vacinas contra a AIDS/genética , Vacinas contra a AIDS/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/imunologia , Antígenos CD4/genética , Antígenos CD4/metabolismo , Linhagem Celular , Células Cultivadas , Feminino , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Humanos , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Testes de Neutralização , Estrutura Terciária de Proteína , SpodopteraRESUMO
Proliferation and migration of vascular smooth muscle cells (VSMCs) are important events in the development of diabetic atherosclerosis. Previous studies have suggested that K(Ca)3.1 channels participate in atherosclerosis and coronary artery restenosis. In the present study, we attempted to clarify the roles of K(Ca)3.1 channels in the proliferation and migration of VSMCs using experimental type-2 diabetes rat serum and aortic smooth muscle cells (SMC) prepared from non-diabetic rats. mRNA and protein levels and current density of K(Ca)3.1 channels were greatly enhanced in cultured VSMCs treated with diabetic serum. In addition, diabetic serum promoted cell proliferation and migration in cultured VSMCs, and the effects were fully reversed in the cells treated with the K(Ca)3.1 channels blocker TRAM-34. In conclusion, serum from diabetic rats increases the expression of K(Ca)3.1 channels and promotes proliferation and migration of VSMCs to possibly participate in vascular remodeling in diabetes.
Assuntos
Aterosclerose/etiologia , Diabetes Mellitus Experimental/patologia , Angiopatias Diabéticas/etiologia , Canais de Potássio Ativados por Cálcio de Condutância Intermediária/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/fisiologia , Animais , Aterosclerose/sangue , Aterosclerose/patologia , Movimento Celular , Proliferação de Células , Células Cultivadas , Diabetes Mellitus Experimental/sangue , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/patologia , Masculino , Músculo Liso Vascular/citologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Soro/fisiologiaRESUMO
Compared to image-based quick response (QR) codes, acoustic QR codes have some advantages. However, an acoustic QR scanner cannot recognize an acoustic QR code at a distance of more than two meters from an acoustic QR announcer. To this end, we propose a new sort of acoustic QR code, called an audible acoustic QR code (AAQRC), which employs humanly audible sound to carry users' information directly. First, a user's string of characters is translated into a string of pitches. Then, the related algorithms convert the string of pitches into a playable audio file. As a result, an AAQRC is generated, consisting of the audio itself. AAQRC recognition is the opposite process of AAQRC generation. Compared with the existing approach for acoustic QR codes, the new method can recognize acoustic QR codes at a longer distance, even if there are obstacles between the AAQRC announcer and AAQRC scanner.
Assuntos
AcústicaRESUMO
Magic-size clusters (MSCs) are molecular materials with unique properties at the border between molecules and solids, providing important insights into the nanocrystal formation process. However, the synthesis of multicomponent alloy MSCs in a single-ensemble form remains challenging due to their tiny size and difficult doping control. Herein, for the first time, we successfully synthesized alloy ZnxCd13-xSe13 MSCs (x = 1-12) with a unique sharp absorption peak at 352 nm by cation exchange between Cd2+ ions and pre-synthesized (ZnSe)13 MSCs in a diamine solution at room temperature. The experimental results show that the use of diamines is crucial to the formation of stable ZnxCd13-xSe13 MSCs, which may be attributed to two amine groups that can coordinate to the surface of MSCs simultaneously. Limited by the robust interaction between diamine ligands and MSCs, the partial cation exchange results in the formation of alloy ZnxCd13-xSe13 MSCs. In contrast, complete cation exchange occurs in a monoamine solution, giving (CdSe)34 MSCs. Besides, a lower reaction temperature and a higher concentration of diamine favor the formation of ZnxCd13-xSe13 MSCs. Our study provides an important basis for further understanding of the transformation of MSCs and a new approach to the controllable synthesis of alloyed MSCs.
RESUMO
PURPOSE: To evaluate the in vitro cleaning effects of different decontamination methods and their impacts on surface characteristics using clinically failed TiUnite implants (Nobel Biocare, Kloten, Switzerland). MATERIALS AND METHODS: Thirty clinically failed TiUnite implants were treated using different decontamination methods. Group 1 (control group) received physiological saline irrigation; Group 2 underwent erythritol powder air polishing (AIRFLOW Master Piezon, EMS Dental, Nyon, Switzerland); Group 3 was treated with erythritol powder air polishing with ethylenediaminetetraacetic acid brushing (FileRite PRC, Pulpdent, Watertown, MA, USA); Group 4 received ultrasonic scaling with polyetheretherketone tips (EMS Dental); Group 5 underwent ultrasonic scaling with polyetheretherketone tips with ethylenediaminetetraacetic acid; and Group 6 was treated with a combination of ultrasonic scaling with polyetheretherketone tips, erythritol powder air polishing and ethylenediaminetetraacetic acid. Surface cleaning effects, quantified by relative contaminated area reduction and visual analogue scale score, as well as surface roughness and chemistry, were assessed after decontamination. The cleaning effects of each decontamination method were also compared between TiUnite and SLA (sandblasted, large-grit acid-etched; Straumann, Basel, Switzerland) implants. RESULTS: Group 6 showed the highest relative contaminated area reduction (stereoscopic microscopy 83.92%, scanning electron microscopy 96.40%), visual analogue scale score (2.83) and reduction in surface roughness (thread bottom -0.78 µm, tip -1.35 µm), as well as an almost maximal decrease in the proportion of carbon (thread bottom -12.33%, tip -8.77%) and increase in that of titanium (thread bottom 13.71%, tip 10.73%). Polyetheretherketone remnants were observed in Groups 4 and 5 but appeared to be reduced in Group 6. When comparing the outcomes with those for SLA implants, no significant differences were found. CONCLUSION: Within the limitations of the present study, the combination of ultrasonic scaling with polyetheretherketone tips, erythritol powder air polishing and ethylenediaminetetraacetic brushing achieved reasonable cleaning effects. The original surface modification did not seem to have any impact on the decontamination results for any of the methods examined.
Assuntos
Implantes Dentários , Ácido Edético/química , Eritritol/química , Descontaminação , Projetos Piloto , Pós , Propriedades de SuperfícieRESUMO
Background: Internet hospitals introduced in China have effectively reduced service time and space, promoted high-quality pediatric medical resources to grassroots areas, solved the contradiction between supply and demand of pediatric medical resources, and met patients' increasing multi-level and diversified medical service needs. However, pediatricians' attitudes toward and satisfaction with the use of internet hospitals remain unknown. Objective: This study aimed to investigate pediatricians' knowledge of, use of, and satisfaction with internet hospitals in order to identify major issues in internet hospital development, and to understand pediatricians' attitudes and opinions on the construction, development, and use of internet hospitals. Materials and methods: A total of 625 pediatricians in 17 public tertiary hospitals in Shanghai were surveyed from November 1-30, 2021. Five hundred and thirty four pediatricians completed the survey, and the response rate was 85.44%. Pediatricians' baseline demographic data were collected and information about their use of and satisfaction with internet hospitals. Results: About 70.22% (375/534) of pediatricians knew about internet hospitals and about 54.68% (292/534) use internet hospitals for patient consultation, diagnosis, and treatment. Utilized services mainly focused on online consultation (271/292, 92.81%), online follow-up consultation (174/292, 59.59%), and health sciences (111/292, 38.01%). Online services were provided by 69.18% (202/292) of pediatricians for less than 1 h a day, and 75.00% (219/292) responded to fewer than five patient consultations online every day. Pediatricians' overall satisfaction with internet hospitals was low (3.59 ± 0.92 points), user experience, systems functions, operation processes, service prices, and performance rewards of internet hospitals were main influencing factors. Pediatricians are enthusiastic about further development of internet hospitals, with 87.83% (469/534) willing to provide services on the internet hospital platform. Conclusion: Most pediatricians view internet hospitals favorably and are eager to contribute to the development of online diagnosis and treatment services. The development of internet hospitals will be more strongly supported by improving pediatricians' satisfaction and mobilizing their enthusiasm and initiative to participate in internet medical services.