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1.
Vet Sci ; 11(9)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39330793

RESUMO

The pathogens responsible for porcine viral diarrhea are diverse, causing significant economic losses to the pig industry. PEDV and TGEV are well-known pathogens causing diarrheal diseases in pigs, leading to significant economic losses in the breeding industry. In contrast, the newly identified diarrhea virus, PKV, has not garnered as much attention. However, co-infection of PKV with PEDV results in more severe symptoms in piglets, such as acute gastroenteritis, and promotes increased replication of PEDV. Rapid and accurate diagnosis of viral diarrhea is essential for farms to identify pathogens early and mitigate economic losses. This study describes the development of a triplex real-time fluorescent quantitative RT-qPCR technique that can simultaneously detect three RNA viruses associated with porcine viral diarrhea: PEDV, TGEV, and PKV. To establish the triplex RT-qPCR method for the simultaneous detection and identification of the above three diarrhea viruses, conserved regions of the M gene of TGEV, the N gene of PEDV, and the 3D gene of PKV were selected to design specific primers and probes. After optimizing the reaction conditions, the method's specificity, sensitivity, and reproducibility were evaluated. The triplex RT-qPCR method did not show a significant difference in PCR efficiency compared to the single RT-qPCR method. The method is specific to TGEV, PKV, and PEDV, exhibits no cross-reactivity with other pathogens, and demonstrates satisfactory sensitivity and reproducibility; the limit of detection (LOD) of PEDV, TGEV, and PKV is 11.42 copies/µL. Furthermore, the performance of the triplex RT-qPCR assay was compared with the Chinese standard single-assay method for detecting TGEV, PKV, and PEDV, showing complete consistency between the two methods (100% compliant). Subsequently, 1502 clinical diarrhea samples were collected from the Guangxi Zhuang Autonomous Region to investigate the local prevalence of TGEV, PKV, and PEDV and the positive rates were 16.38% (246/1502), 1.46% (22/1502), and 45.14% (678/1502), respectively. Co-infection of PEDV and PKV were most common, with a rate of 12.12% (182/1502). This study presents a valuable method for the rapid and simultaneous identification of PEDV, TGEV, and PKV in clinical animal farming practices, and provides a reassessment of the epidemiology of these diarrhea-causing viral pathogens in the Guangxi Zhuang Autonomous Region.

2.
Emerg Microbes Infect ; 13(1): 2400559, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39222358

RESUMO

Porcine deltacoronavirus (PDCoV) is an emerging pathogen that can cause severe diarrhoea and high mortality in suckling piglets. Moreover, evidence of PDCoV infection in humans has raised concerns regarding potential public health risks. To identify potential therapeutic targets for PDCoV, we performed a genome-wide CRISPR/Cas9 library screening to find key host factors important to PDCoV infection. Several host genes in this screen were enriched, including ANPEP, which encodes the PDCoV receptor aminopeptidase N (APN). Furthermore, we discovered C16orf62, also known as the VPS35 endosomal protein sorting factor like (VPS35L), as an important host factor required for PDCoV infection. C16orf62 is an important component of the multiprotein retriever complex involved in protein recycling in the endosomal compartment and its gene knockout led to a remarkable decrease in the binding and internalization of PDCoV into host cells. While we did not find evidence for direct interaction between C16orf62 and the viral s (spike) protein, C16orf62 gene knockout was shown to downregulate APN expression at the cell surface. This study marks the first instance of a genome-wide CRISPR/Cas9-based screen tailored for PDCoV, revealing C16orf62 as a host factor required for PDCoV replication. These insights may provide promising avenues for the development of antiviral drugs against PDCoV infection.


Assuntos
Sistemas CRISPR-Cas , Infecções por Coronavirus , Deltacoronavirus , Doenças dos Suínos , Animais , Suínos , Doenças dos Suínos/virologia , Deltacoronavirus/genética , Infecções por Coronavirus/virologia , Infecções por Coronavirus/veterinária , Humanos , Antígenos CD13/metabolismo , Antígenos CD13/genética , Técnicas de Inativação de Genes , Interações Hospedeiro-Patógeno , Internalização do Vírus
3.
Sheng Wu Gong Cheng Xue Bao ; 40(7): 1981-1996, 2024 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-39044570

RESUMO

Proteins serve as the primary executors of cellular activities in organisms, and thus investigating the subcellular localization and interactions of proteins is crucial for understanding protein functions and elucidating the molecular mechanisms in organisms. Proximity labeling is a recently developed effective method for detecting protein-protein interactions in live cells. Compared with the conventional methods for studying protein-protein interactions, proximity labeling demonstrates high sensitivity, strong specificity, and low background and is widely employed in the research of protein-protein interactions between pathogens and hosts. This article reviews the recent progress in the development and applications of the biotin ligase BirA and its mutants and elucidates the functioning principles of several classical biotin ligases. This review aims to clarify the role of proximity labeling based on BirA and its mutants in identifying protein-protein interactions between pathogens and hosts.


Assuntos
Carbono-Nitrogênio Ligases , Interações Hospedeiro-Patógeno , Mutação , Carbono-Nitrogênio Ligases/metabolismo , Carbono-Nitrogênio Ligases/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Biotina/metabolismo , Humanos , Mapeamento de Interação de Proteínas , Escherichia coli/genética , Escherichia coli/metabolismo
4.
Psychol Rep ; : 332941241258922, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842056

RESUMO

This study investigated gender differences in health-risk behaviour patterns among young adults and assessed the associations of anxiety and depression with these patterns. A cross-sectional survey was conducted with 1740 young Chinese adults aged 18-24 years. Latent class analysis (LCA) and multinomial logistic regression were conducted to identify the clusters of health-risk behaviours and their associations with anxiety and depression. Three common patterns were found for both genders: physical inactivity, substance use, and insufficient fruit intake (5.7% for males [M] and 11.6% for females [F]); a sedentary lifestyle only (48.4% for M and 48.9% for F); and a sedentary lifestyle, substance use, and an unhealthy diet (7.6% for M and 20.0% for F). Additionally, two additional unique patterns were found: physical inactivity and unhealthy diet in males (38.3%) and physical inactivity and insufficient fruit intake in females (19.6%). Sociodemographic variables exert different effects on health-risk behaviour patterns as a function of gender. Lower anxiety levels (odds ratio [OR]: 0.892; 95% confidence interval [CI]: 0.823-0.966) and greater depression levels (OR: 1.074; 95% CI: 1.008-1.143) were associated with a sedentary lifestyle, substance use, and unhealthy diet class only in female young adults compared with a sedentary-only class. These findings underscore the need for the implementation of targeted interventions based on gender differences.

5.
Int J Mol Sci ; 25(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38612855

RESUMO

Odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs) is crucial for continued root development and dentin formation in immature teeth with apical periodontitis (AP). Fat mass and obesity-associated protein (FTO) has been reported to regulate bone regeneration and osteogenic differentiation profoundly. However, the effect of FTO on hSCAPs remains unknown. This study aimed to identify the potential function of FTO in hSCAPs' odontoblastic differentiation under normal and inflammatory conditions and to investigate its underlying mechanism preliminarily. Histological staining and micro-computed tomography were used to evaluate root development and FTO expression in SD rats with induced AP. The odontoblastic differentiation ability of hSCAPs was assessed via alkaline phosphatase and alizarin red S staining, qRT-PCR, and Western blotting. Gain- and loss-of-function assays and online bioinformatics tools were conducted to explore the function of FTO and its potential mechanism in modulating hSCAPs differentiation. Significantly downregulated FTO expression and root developmental defects were observed in rats with AP. FTO expression notably increased during in vitro odontoblastic differentiation of hSCAPs, while lipopolysaccharide (LPS) inhibited FTO expression and odontoblastic differentiation. Knockdown of FTO impaired odontoblastic differentiation, whereas FTO overexpression alleviated the inhibitory effects of LPS on differentiation. Furthermore, FTO promoted the expression of secreted modular calcium-binding protein 2 (SMOC2), and the knockdown of SMOC2 in hSCAPs partially attenuated the promotion of odontoblastic differentiation mediated by FTO overexpression under LPS-induced inflammation. This study revealed that FTO positively regulates the odontoblastic differentiation ability of hSCAPs by promoting SMOC2 expression. Furthermore, LPS-induced inflammation compromises the odontoblastic differentiation of hSCAPs by downregulating FTO, highlighting the promising role of FTO in regulating hSCAPs differentiation under the inflammatory microenvironment.


Assuntos
Lipopolissacarídeos , Osteogênese , Humanos , Animais , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-X , Inflamação/genética , Proteínas de Ligação ao Cálcio , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética
6.
Int J Biol Macromol ; 268(Pt 2): 131839, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38663699

RESUMO

Streptococcus suis (S. suis) is a significant zoonotic microorganism that causes a severe illness in both pigs and humans and is characterized by severe meningitis and septicemia. Suilysin (SLY), which is secreted by S. suis, plays a crucial role as a virulence factor in the disease. To date, the interaction between SLY and host cells is not fully understood. In this study, we identified the interacting proteins between SLY and human brain microvascular endothelial cells (HBMECs) using the TurboID-mediated proximity labeling method. 251 unique proteins were identified in TurboID-SLY treated group, of which six plasma membrane proteins including ARF6, GRK6, EPB41L5, DSC1, TJP2, and PNN were identified. We found that the proteins capable of interacting with SLY are ARF6 and PNN. Subsequent investigations revealed that ARF6 substantially increased the invasive ability of S. suis in HBMECs. Furthermore, ARF6 promoted SLY-induced the activation of p38 MAPK signaling pathway in HBMECs. Moreover, ARF6 promoted the apoptosis in HBMECs through the activation of p38 MAPK signaling pathway induced by SLY. Finally, we confirmed that ARF6 could increase the virulence of SLY in C57BL/6 mice. These findings offer valuable insights that contribute to a deeper understanding of the pathogenic mechanism of SLY.


Assuntos
Fator 6 de Ribosilação do ADP , Fatores de Ribosilação do ADP , Apoptose , Células Endoteliais , Proteínas Hemolisinas , Streptococcus suis , Streptococcus suis/patogenicidade , Streptococcus suis/metabolismo , Humanos , Animais , Apoptose/efeitos dos fármacos , Camundongos , Fatores de Ribosilação do ADP/metabolismo , Fatores de Ribosilação do ADP/genética , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/microbiologia , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/metabolismo , Virulência , Encéfalo/metabolismo
7.
Geriatr Nurs ; 56: 312-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422626

RESUMO

The purpose of this study was to identify latent classes of chronic pain in older adults based on perceptual, cognitive, behavioral, emotional and social factors, and to explore the associations between each class of chronic pain and different cognitive domains. A total of 629 participants were included. Three classes of chronic pain were identified: "episodic recurrent mild pain with good psychosocial state" (class 1), "episodic recurrent moderate pain with general psychosocial state" (class 2) and "continuous multilocational severe pain with attacks accompanied by poor psychosocial state and avoidance of activity" (class 3). After adjusting for relevant confounders, chronic pain presenting as class 1 was associated with worse memory; class 2 was associated with worse global cognitive function, memory, information processing speed, and executive function; and class 3 was additionally associated with worse attention compared to class 2. The findings contribute to the development of targeted programs for treating pain and improving cognitive functioning.


Assuntos
Dor Crônica , Disfunção Cognitiva , Humanos , Idoso , Dor Crônica/psicologia , Estudos Transversais , Análise de Classes Latentes , Cognição , Função Executiva
8.
J Affect Disord ; 352: 410-418, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38367710

RESUMO

BACKGROUND: Cognitive frailty (CF) is an important geriatric syndrome and is reversible. It is crucial to develop preventive interventions for CF. We aimed to explore the associations between CF and its associated factors in Chinese aged 45 years and above. METHODS: Based on the available data of 3 waves in China Health and Retirement Longitudinal Study from 2011 to 2015, 16,071 individuals aged 45 years and above from 3 waves were included. Based on the health ecology model, the associated factors were classified as downstream, midstream and upstream factors. Generalized hierarchical linear model including time level, individual level, and province level was applied to analyze the associations between factors and CF. RESULTS: Multilevel factors have different effects on physical and cognitive function. In the downstream, old age, female, underweight, chronic diseases, and depression were risk factors of reversible CF and potentially reversible CF, and overweight was their protective factor. In the midstream, short or long night sleep duration was their risk factor, and > 30 and ≤ 60 min afternoon naps, alcohol drinking, and participation in social activities were their protective factors. In the upstream, living in rural areas was their risk factor, and high educational level, household consumption and GDP per capita were their protective factors. CONCLUSIONS: Physical function and cognitive function are affected differently by multiple factors. The occurrence and development of physical frailty and cognitive impairment may have some common mechanisms. CF can be influenced by multilevel factors, and multilevel and comprehensive management of CF should be achieved. KEY POINTS: Cognitive frailty was correlated with multilevel factors, including downstream, midstream, and upstream factors. It is crucial to focus on individual interventions such as physiological factors, psychological factors and health behaviors, especially the elderly, women and those with depression. Socioeconomic status was associated with the lower prevalence of cognitive frailty.


Assuntos
Disfunção Cognitiva , Fragilidade , Pessoa de Meia-Idade , Idoso , Humanos , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Longitudinais , Disfunção Cognitiva/epidemiologia , Cognição , Avaliação Geriátrica
9.
Virus Res ; 340: 199303, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38145807

RESUMO

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1ß and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.


Assuntos
Benzodioxóis , Benzilisoquinolinas , Infecções por Coronavirus , Coronavirus , Deltacoronavirus , Doenças dos Suínos , Animais , Suínos , Coronavirus/genética , Antígenos CD13/metabolismo
10.
Environ Sci Pollut Res Int ; 30(54): 116266-116278, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37910359

RESUMO

Antenatal exposure to air pollutants is thought to be associated with a variety of maternal blood markers as well as adverse birth outcomes. However, the dysgenic influence of air pollutants on the antiphospholipid syndrome (APS) in mothers and their pregnancy outcomes remains unclear. In the current study, 371 mother-infant pairs (189 healthy: 182 APS) from Nanjing Maternal and Child Health Hospital as well as air pollutants concentration from their living environment were used to investigate correlations between air pollution with maternal blood indicators and fetal birth weight in the groups of APS and healthy mothers. Generalized linear model was used to evaluate the contributions of air pollutant exposure during pregnancy to the blood indicators variation. The relationships between birth weight with specific air pollutant and blood index were analyzed using ridge regression. Results showed that APS fetal birth weight was significantly impacted by air pollutant exposure during pregnancy, in particular, the birth weight decreased significantly along with increasing fine particulate matter 2.5 (PM2.5) and fine particulate matter 10 (PM10) exposure concentrations throughout pregnancy. In contrast, birth weight increased significantly with sulfur dioxide (SO2) exposure. In addition, APS-related blood indicators comprised of platelet distribution width (PDW), total bilirubin (TBIL), mean platelet volume (MPV), platelet-larger cell ratio (P_LCR), homocysteine (HCY), alkaline phosphatase (ALP), direct bilirubin (DBIL), basophilic granulocyte (BAS), platelet thrombocytocrit (PCT), preprandial glucose levels (OGTT0), monocytes (MON), and monocytes ratio (MON_ratio) were also strongly related with prenatal exposure to PM2.5 and PM10, in which PDW levels showed most strongly negative impaction on fetal birth weight. Together, we showed that prenatal exposure to air pollutant (PM2.5 and PM10) may exacerbate the poor birth outcomes of low birth weight by impacting APS maternal blood indicators especially for PDW.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Síndrome Antifosfolipídica , Efeitos Tardios da Exposição Pré-Natal , Lactente , Criança , Humanos , Feminino , Gravidez , Gestantes , Peso ao Nascer , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Síndrome Antifosfolipídica/induzido quimicamente , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Resultado da Gravidez , Bilirrubina , China , Exposição Materna
11.
BMJ Open ; 13(9): e068554, 2023 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-37739471

RESUMO

OBJECTIVE: To determine the relationship of napping with incident diabetes risk and glycaemic control in people with diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (PubMed), EMBASE, Web of Science and the Cochrane Library were searched for studies published from database inception to 9 May 2023. ELIGIBILITY CRITERIA: Observational studies reporting the relationship of napping with diabetes or glycaemic control in patients with diabetes in adult populations were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the literature, extracted data and assessed the quality of the included studies. The results were reported as ORs and 95% CIs, which were pooled by using fixed and random effects models, and subgroup analyses were performed. The Grading of Recommendations Assessment, Development and Evaluation method was used to assess the quality of the evidence. RESULTS: Forty studies were included in our review. Habitual napping was associated with an increased diabetes risk (OR 1.20, 95% CI 1.14 to 1.27) and poor glycaemic control in patients with diabetes (OR 2.05, 95% CI 1.55 to 2.73). Nap durations less than 30 min were unrelated to diabetes (OR 1.05, 95% CI 0.97 to 1.14). Nap durations of 30-60 min were associated with diabetes risk (OR 1.09, 95% CI 1.02 to 1.17), but there were differences in the subgroup analysis results. Nap durations of more than 60 min significantly increased the risk of diabetes (OR 1.31, 95% CI 1.20 to 1.44). CONCLUSIONS: Napping is associated with increased diabetes risk and poor glycaemic control, and future research will need to confirm whether there are sex and regional differences. Nap durations of more than 60 min significantly increases the risk of diabetes, and the relationship between nap duration and glycaemic control in patients with diabetes needs to be further explored in the future. PROSPERO REGISTRATION NUMBER: CRD42021292103.


Assuntos
Diabetes Mellitus , Adulto , Humanos , Diabetes Mellitus/epidemiologia , Bases de Dados Factuais , Controle Glicêmico , MEDLINE , PubMed
12.
Ecol Lett ; 26(9): 1584-1596, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37387416

RESUMO

Non-native plants are typically released from specialist enemies but continue to be attacked by generalists, albeit at lower intensities. This reduced herbivory may lead to less investment in constitutive defences and greater investment in induced defences, potentially reducing defence costs. We compared herbivory on 27 non-native and 59 native species in the field and conducted bioassays and chemical analyses on 12 pairs of non-native and native congeners. Non-natives suffered less damage and had weaker constitutive defences, but stronger induced defences than natives. For non-natives, the strength of constitutive defences was correlated with the intensity of herbivory experienced, whereas induced defences showed the reverse. Investment in induced defences correlated positively with growth, suggesting a novel mechanism for the evolution of increased competitive ability. To our knowledge, these are the first linkages reported among trade-offs in plant defences related to the intensity of herbivory, allocation to constitutive versus induced defences, and growth.


Assuntos
Herbivoria , Fenômenos Fisiológicos Vegetais , Plantas
13.
Nurs Open ; 10(8): 5117-5128, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37071702

RESUMO

AIM: To explore the physical and mental health status of community residents and to identify the risk factors of chronic diseases. DESIGN: A cross-sectional, descriptive correlational study was conducted. METHODS: A total of 579 participants were recruited from 15 communities in Tianjin. The demographic information sheet, 7-item Generalized Anxiety Disorder scale (GAD-7) and Patient Health Questionnaire (PHQ-9) were used. Data collection was undertaken based on the health management system on mobile phones from April to May 2019. RESULTS: Eighty-four participants of the total number of surveyed were with chronic disease. The incidence of depression and anxiety in participants was 44.2% and 41.3%. Logistic regression analysis showed that age (OR = 4.905, 95%CI: 2.619-9.187), religious belief (OR = 0.445, 95%CI: 1.510-11.181) and working condition (OR = 0.161, 95%CI: 0.299-0.664) entered the regression equation. Old age is a risk factor for chronic diseases. No religious belief and working condition are protective factors for chronic diseases.


Assuntos
Telefone Celular , Depressão , Humanos , Depressão/epidemiologia , Depressão/psicologia , Estudos Transversais , Fatores de Risco , Doença Crônica , Inquéritos e Questionários
14.
Oral Dis ; 2023 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-37026687

RESUMO

OBJECTIVE: Runt-related transcription factor 2 (Runx2) plays an important role in bone metabolism; however, the relationship between Runx2 and periodontitis remains unclear. We investigated Runx2 expression in the gingiva of patients to explore its role in periodontitis. METHODS: Gingival samples of patients were collected, including healthy samples (control group) and periodontitis samples (P group). Periodontitis samples were divided into three groups based on the periodontitis stage. Samples with stage I and grade B periodontitis were in the P1 group, stage II and grade B in the P2 group, and stage III or IV and grade B in the P3 group. Immunohistochemistry and western blotting were performed to detect Runx2 levels. The probing (PD) and clinical attachment loss (CAL) were recorded. RESULTS: Runx2 expression levels in the P and P3 groups were higher than those in the control group. In addition, Runx2 expression was positively correlated with CAL and PD (r1 = 0.435, r2 = 0.396). CONCLUSION: The high expression level of Runx2 in the gingiva of patients with periodontitis may be correlated with the pathogenesis of periodontitis.

15.
Indian J Cancer ; 60(4): 562-569, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36861729

RESUMO

BACKGROUND: Apatinib exhibits a synergistic effect with transarterial chemoembolization (TACE) by inhibiting TACE-induced neoangiogenic reaction in hepatocellular carcinoma (HCC) patients. But apatinib plus drug-eluting bead TACE (DEB-TACE) is rarely reported as a bridging therapy to surgery. This study aimed to evaluate the efficacy and safety of apatinib plus DEB-TACE as a bridge to surgical resection in intermediate-stage HCC patients. MATERIALS AND METHODS: Thirty-one intermediate-stage HCC patients who received apatinib plus DEB-TACE as a bridging therapy to surgery were enrolled. After the bridging therapy, complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and objective response rate (ORR) were evaluated; meanwhile, relapse-free survival (RFS) and overall survival (OS) were determined. RESULTS: After the bridging therapy, three (9.7%), twenty one (67.7%), seven (22.6%), and twenty four (77.4%) patients achieved CR, PR, SD, and ORR, respectively; besides, PD did not occur. The successful downstaging rate was 18 (58.1%). The median (95% confidence interval [CI]) accumulating RFS was 33.0 (19.6 - 46.6) months. Besides, the median (95% CI) accumulating OS was 37.0 (24.8 - 49.2) months. HCC patients with successful downstaging showed a higher accumulating RFS rate ( P = 0.038) and similar accumulating OS rate ( P = 0.073) compared to those without successful downstaging. The overall incidence of adverse events was relatively low. Besides, all the adverse events were mild and controllable. The most frequent adverse events included pain (14 [45.2%]) and fever (9 [29.0%]). CONCLUSION: Apatinib plus DEB-TACE as a bridging therapy to surgical resection displays good efficacy and safety profile in intermediate-stage HCC patients.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Resultado do Tratamento
16.
Protein Cell ; 14(2): 105-122, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36929001

RESUMO

Glioblastoma multiforme (GBM), a highly malignant and heterogeneous brain tumor, contains various types of tumor and non-tumor cells. Whether GBM cells can trans-differentiate into non-neural cell types, including mural cells or endothelial cells (ECs), to support tumor growth and invasion remains controversial. Here we generated two genetic GBM models de novo in immunocompetent mouse brains, mimicking essential pathological and molecular features of human GBMs. Lineage-tracing and transplantation studies demonstrated that, although blood vessels in GBM brains underwent drastic remodeling, evidence of trans-differentiation of GBM cells into vascular cells was barely detected. Intriguingly, GBM cells could promiscuously express markers for mural cells during gliomagenesis. Furthermore, single-cell RNA sequencing showed that patterns of copy number variations (CNVs) of mural cells and ECs were distinct from those of GBM cells, indicating discrete origins of GBM cells and vascular components. Importantly, single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages. Rather than expansion owing to trans-differentiation, vascular cell expanded by proliferation during tumorigenesis. Therefore, cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis. Our findings advance understanding of cell lineage dynamics during gliomagenesis, and have implications for targeted treatment of GBMs.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Camundongos , Animais , Humanos , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Células Endoteliais/patologia , Variações do Número de Cópias de DNA , Encéfalo/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia
17.
Bioconjug Chem ; 34(2): 326-332, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36629744

RESUMO

We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.


Assuntos
Herpesvirus Suídeo 1 , Nanopartículas , Animais , Herpesvirus Suídeo 1/genética , Sistemas CRISPR-Cas/genética , Replicação Viral , Antivirais/farmacologia
18.
J Nurs Res ; 30(6): e243, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36201603

RESUMO

BACKGROUND: Little is known about how health behaviors cluster to form meaningful patterns that influence health outcomes in young adult nursing students. PURPOSE: The purpose of this study was to identify the unique health behavior patterns among young adult nursing students in China and examine the associations between health behaviors and chronic diseases. METHODS: Using an electronic app, the achievements of an exercise target, sedentary behavior, smoking and drinking, and dietary patterns were assessed in 1,480 nursing student participants aged 18-24 years from two medical universities in Eastern China. RESULTS: A four-class model was developed using latent class analysis that included the "failure to achieve exercise target, alcohol-drinking, and insufficient fruit and vegetable group" (Group 1, n = 187, 12.6%), the "alcohol-drinking and sedentary behavior group" (Group 2, n = 290, 19.6%), the "sedentary behavior only group" (Group 3, n = 721, 48.7%), and the "failure to achieve exercise target only group" (Group 4, n = 282, 19.1%). Logistic regressions indicated that nursing students in Group 2 (odds ratio [ OR ] = 0.42), Group 3 ( OR = 0.51), and Group 4 ( OR = 0.30) were less likely to have chronic diseases than those in Group 1 after adjusting for sociodemographic variables. CONCLUSIONS: The health behaviors were clustered in different patterns among young adult nursing students. Tailoring interventions to specific groups is suggested to improve health outcomes.


Assuntos
Estudantes de Enfermagem , Adulto Jovem , Humanos , Comportamentos de Risco à Saúde , Análise de Classes Latentes , Universidades , Consumo de Bebidas Alcoólicas , Doença Crônica
19.
Biomed Res Int ; 2022: 2938015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158888

RESUMO

Objective: This work is aimed at revealing the role and the molecular mechanism of connective tissue growth factor 2 (CTGF) in the osteoblast differentiation of periodontal ligament stem cells (PDLSCs). Methods: The osteogenic differentiation of PDLSCs was induced by osteogenic induction medium (OM), and the expression level of osteogenic related proteins ALP, RUNX2, OCN, and CTGF was estimated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis. We constructed cell lines with CTGF overexpression or knockdown to verify the role of CTGF in the osteoblast differentiation of PDLSCs. Alkaline phosphatase (ALP) staining was introduced to measure the osteoblasts activity, and alizarin red S (ARS) staining was employed to test matrix mineralization. The interaction between CTGF and bone morphogenetic protein-2 (BMP-2) was determined by endogenous coimmunoprecipitation (Co-IP). Results: The expression level of CTGF was increased during the osteogenic induction of PDLSCs. Additionally, CTGF overexpression effectively maintained the stemness and facilitated the osteoblast differentiation in PDLSCs, and CTGF knockdown exerted opposite effects. Moreover, at molecular mechanism, CTGF increased the activity of BMP-2/Smad signaling pathway. Conclusion: This investigation verified that CTGF promotes the osteoblast differentiation in PDLSCs at least partly by activating BMP-2/Smad cascade signal.


Assuntos
Osteogênese , Ligamento Periodontal , Fosfatase Alcalina/metabolismo , Proteína Morfogenética Óssea 2/metabolismo , Diferenciação Celular , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , Osteoblastos/metabolismo , Transdução de Sinais , Células-Tronco/metabolismo
20.
Commun Biol ; 5(1): 761, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35902771

RESUMO

Temperature has a large influence on insect abundances, thus under climate change, identifying major drivers affecting pest insect populations is critical to world food security and agricultural ecosystem health. Here, we conducted a meta-analysis with data obtained from 120 studies across China and Europe from 1970 to 2017 to reveal how climate and agricultural practices affect populations of wheat aphids. Here we showed that aphid loads on wheat had distinct patterns between these two regions, with a significant increase in China but a decrease in Europe over this time period. Although temperature increased over this period in both regions, we found no evidence showing climate warming affected aphid loads. Rather, differences in pesticide use, fertilization, land use, and natural enemies between China and Europe may be key factors accounting for differences in aphid pest populations. These long-term data suggest that agricultural practices impact wheat aphid loads more than climate warming.


Assuntos
Afídeos , Agricultura , Animais , Mudança Climática , Ecossistema , Temperatura
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