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1.
Cell ; 187(12): 2935-2951.e19, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38772371

RESUMO

Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Centro Germinativo , Imunidade Humoral , Baço , Animais , Masculino , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/farmacologia , AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Gânglios Espinais/metabolismo , Centro Germinativo/imunologia , Camundongos Endogâmicos C57BL , Nociceptores/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Transdução de Sinais , Baço/inervação , Baço/imunologia , Feminino
2.
Cell ; 174(5): 1200-1215.e20, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-30100187

RESUMO

Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.


Assuntos
Fator de Transcrição E2F1/metabolismo , Glicoproteínas de Membrana/metabolismo , Poro Nuclear/fisiologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição/metabolismo , Transporte Ativo do Núcleo Celular , Carcinogênese , Núcleo Celular/metabolismo , Proliferação de Células , Fator de Transcrição GATA2/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Membrana Nuclear , Complexo de Proteínas Formadoras de Poros Nucleares , Transdução de Sinais
3.
Biomacromolecules ; 25(3): 1923-1932, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38394470

RESUMO

Fatty acid cellulose esters (FACE) are common cellulose-based thermoplastics, and their thermoplasticity is determined by both the contents and the lengths of the side chains. Herein, various FACE were synthesized by the ball-milling esterification of cellulose and fatty acyl chlorides containing 10-18 carbons, and their structures and thermoplasticity were thoroughly studied. The results showed that FACE with high degrees of substitution (DS) and low melting flow temperatures (Tf) were achieved as the chain lengths of the fatty acyl chlorides were reduced. In particular, a cellulose decanoate with a DS of 1.85 and a Tf of 186 °C was achieved by feeding 3 mol of decanoyl chloride per mole anhydroglucose units of cellulose. However, cellulose stearate (DS = 1.53) synthesized by the same protocols cannot melt even at 250 °C. More interestingly, the fatty acyl chlorides with 10 and 12 carbons resulted in FACE with superior toughness (elongation at break up to 94.4%). In contrast, due to their potential crystallization of the fatty acyl groups with 14-18 carbons, the corresponding FACE showed higher tensile strength and Young's modulus than the others. This study provides some theoretical basis for the mechanochemical synthesis of thermoplastic FACE with designated properties.


Assuntos
Cloretos , Ésteres , Ésteres/química , Estudos de Viabilidade , Esterificação , Celulose/química
4.
BMC Geriatr ; 24(1): 17, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38177989

RESUMO

BACKGROUND: The ageing of the population has become an escalating problem in China, which has led to an increasing demand for healthcare throughout society. The care services of elderly institutions, as a more mature way of aging, can alleviate various social problems brought about by ageing to a certain extent. The aim of this paper is to explore the degree of acceptance of institutional care by rural elderly people in Shandong Province and the factors that influence whether rural elderly people accept institutional care services. METHODOLOGY: Based on the theory of planned behavior, an analytical framework was constructed for the willingness of rural elderly people to receive nursing services from elderly care institutions. Using survey data from 192 rural elderly people in Shandong Province, descriptive statistics, binary logistic regression, and horizontal comparative analysis methods were used to analyze the willingness of rural elderly people to provide for the elderly and its influencing factors. RESULT: Only 17.71% of respondents expressed willingness to receive services from elderly care institutions. Among them, education level, trust in elderly care institutions, and support from adult children have a significant positive impact on whether rural elderly people receive nursing services from elderly care institutions; The number of children, the level of understanding of elderly care institutions, neighbors' choices of elderly care methods, and their ability to contribute to the family have a significant negative impact on whether rural elderly people receive nursing services from elderly care institutions. There are significant differences in the willingness and influencing factors of rural elderly people to provide for the elderly among different regions. CONCLUSION: The non-acceptance of institutional care by rural older people is a general phenomenon rather than a sample characteristic, thus justifying the supplementary status of institutional care services. The pension intention of the rural elderly in Shandong Province is obviously affected by personal will factors, and the influencing factors are various. The traditional concept of old-age care in Shandong province has a strong path-dependent effect on the choice of the rural elderly. There is heterogeneity in the willingness and influencing factors of the rural elderly in different regions and countries. Based on this, this paper puts forward the following suggestions: strengthen the spiritual and cultural construction of residents; The government should pay attention to the correct guidance of public opinion; And increase pension subsidies. It is hoped that reduce the burden of national elderly care through these suggestions.


Assuntos
Envelhecimento , População Rural , Humanos , Idoso , Inquéritos e Questionários , Instalações de Saúde , China/epidemiologia
5.
Bull Entomol Res ; 114(1): 41-48, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38098270

RESUMO

Hemiptera insects exhibit a close relationship to plants and demonstrate a diverse range of dietary preferences, encompassing phytophagy as the predominant feeding habit while a minority engages in carnivorous or haematophagous behaviour. To counteract the challenges posed by phytophagous insects, plants have developed an array of toxic compounds, causing significant evolutionary selection pressure on these insects. In this study, we employed a comparative genomics approach to analyse the expansion and contraction of gene families specific to phytophagous insect lineages, along with their adaptive evolutionary traits, utilising representative species from the Hemiptera order. Our investigation revealed substantial expansions of gene families within the phytophagous lineages, especially in the Pentatomomorpha branch represented by Oncopeltus fasciatus and Riptortus pedestris. Notably, these expansions of gene families encoding enzymes are potentially involved in hemipteran-plant interactions. Moreover, the adaptive evolutionary analysis of these lineages revealed a higher prevalence of adaptively evolved genes in the Pentatomomorpha branch. The observed branch-specific gene expansions and adaptive evolution likely contribute significantly to the diversification of species within Hemiptera. These results help enhance our understanding of the genomic characteristics of the evolution of different feeding habits in hemipteran insects.


Assuntos
Hemípteros , Heterópteros , Animais , Hemípteros/genética , Insetos , Genômica , Comportamento Alimentar , Plantas , Filogenia
6.
Carcinogenesis ; 44(7): 610-625, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37235794

RESUMO

Although emerging evidence has established the roles of miRNAs in hepatocellular carcinoma (HCC), the global functional implication of miRNAs in this malignancy remains largely uncharacterized. Here, we aim to systematically identify novel miRNAs involved in HCC and clarify the function and mechanism of specific novel candidate miRNA(s) in this malignancy. Through an integrative omics approach, we identified ten HCC-associated functional modules and a collection of candidate miRNAs. Among them, we demonstrated that miR-424-3p, exhibiting strong associations with extracellular matrix (ECM), promotes HCC cells migration and invasion in vitro and facilitates HCC metastasis in vivo. We further demonstrated that SRF is a direct functional target of miR-424-3p, and is required for the oncogenic activity of miR-424-3p. Finally, we found that miR-424-3p reduces the interferon pathway by attenuating the transactivation of SRF on STAT1/2 and IRF9 genes, which in turn enhances the matrix metalloproteinases (MMPs)-mediated ECM remodeling. This study provides comprehensive functional relevance of miRNAs in HCC by an integrative omics analysis, and further clarifies that miR-424-3p in ECM functional module plays an oncogenic role via reducing the SRF-STAT1/2 axis in this malignancy.

7.
J Cell Physiol ; 238(8): 1641-1650, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37260091

RESUMO

Palmitoylation, a critical lipid modification of proteins, is involved in various physiological processes such as altering protein localization, transport, and stability, which perform essential roles in protein function. Palmitoyltransferases are specific enzymes involved in the palmitoylation modification of substrates. S-palmitoylation, as the only reversible palmitoylation modification, is able to be deacylated by deacyltransferases. As an important mode of programmed cell death, apoptosis functions in the maintenance of organismal homeostasis as well as being associated with inflammatory and immune diseases. Recently, studies have found that palmitoylation and apoptosis have been demonstrated to be related in many human diseases. In this review, we will focus on the role of palmitoylation modifications in apoptosis.


Assuntos
Lipoilação , Proteínas , Humanos , Proteínas/metabolismo , Metabolismo dos Lipídeos , Apoptose , Processamento de Proteína Pós-Traducional
8.
PLoS Comput Biol ; 18(11): e1010615, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36355750

RESUMO

The "replication crisis" is a methodological problem in which many scientific research findings have been difficult or impossible to replicate. Because the reproducibility of empirical results is an essential aspect of the scientific method, such failures endanger the credibility of theories based on them and possibly significant portions of scientific knowledge. An instance of the replication crisis, analytic replication, pertains to reproducing published results through computational reanalysis of the authors' original data. However, direct replications are costly, time-consuming, and unrewarded in today's publishing standards. We propose that bioinformatics and computational biology students replicate recent discoveries as part of their curriculum. Considering the above, we performed a pilot study in one of the graduate-level courses we developed and taught at our University. The course is entitled Intro to R Programming and is meant for students in our Master's and PhD programs who have little to no programming skills. As the course emphasized real-world data analysis, we thought it would be an appropriate setting to carry out this study. The primary objective was to expose the students to real biological data analysis problems. These include locating and downloading the needed datasets, understanding any underlying conventions and annotations, understanding the analytical methods, and regenerating multiple graphs from their assigned article. The secondary goal was to determine whether the assigned articles contained sufficient information for a graduate-level student to replicate its figures. Overall, the students successfully reproduced 39% of the figures. The main obstacles were the need for more advanced programming skills and the incomplete documentation of the applied methods. Students were engaged, enthusiastic, and focused throughout the semester. We believe that this teaching approach will allow students to make fundamental scientific contributions under appropriate supervision. It will teach them about the scientific process, the importance of reporting standards, and the importance of openness.


Assuntos
Currículo , Educação de Pós-Graduação , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Educação de Pós-Graduação/métodos , Estudantes , Ensino
9.
Clin Oral Investig ; 27(8): 4747-4755, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37316642

RESUMO

OBJECTIVES: Oncologic risk is a serious concern of submental artery island flaps. Here, we introduce the contralateral-based submental artery island flap (C-SAIF) and demonstrate its feasibility and long-term oncological safety in reconstructing oral cancer-related defects. METHODS: An anatomical study was performed concentrating on the pedicle length in seven cadavers. Then, a retrospective study was carried out on C-SAIF patients operated on by a single team. The standard surgical technique of C-SAIF was conducted. Outcomes including operative time, length of hospital stay, volume of intraoperative blood loss, and scores of the Multidisciplinary Salivary Gland Society (MSGS) questionnaire were compared with a similar cohort reconstructed with anterolateral thigh free flap (ALTF). In addition, oncological outcomes were evaluated by the 5-year cumulative survival rate between C-SAIF and ALTF patients. RESULTS: The pedicle length of C-SAIF was sufficient for the flap to be extended to the contralateral oral cavity. Fifty-two patients were included in the retrospective study, and nineteen of them underwent reconstruction with C-SAIF. The operative time of C-SAIF was shorter (p = 0.003), and the intraoperative blood loss was less (p = 0.004) than that of ALTF. There was no difference in MSGS scores. The results of survival analysis revealed comparable survival curves for the two groups in terms of overall survival, disease-specific survival, and disease-free survival. CONCLUSION: C-SAIF is a feasible and reliable flap for reconstructing oral cancer-related defects. Moreover, it is an effective island flap to preserve the perforator and pedicle without compromising oncological safety.


Assuntos
Retalhos de Tecido Biológico , Neoplasias Bucais , Procedimentos de Cirurgia Plástica , Humanos , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Estudos de Viabilidade , Neoplasias Bucais/cirurgia , Artérias/cirurgia
10.
Clin Chem ; 68(2): 332-343, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34942001

RESUMO

BACKGROUND: Although major advances have been made in the histopathological diagnosis of high-grade astrocytoma (HGA), methods for effective and noninvasive diagnosis remain largely unknown. Exosomes can cross the blood-brain barrier and are readily accessible in human biofluids, making them promising biomarkers for HGA. Circular RNAs (circRNAs) have potential as tumor biomarkers owing to their stability, conservation, and tissue specificity. However, the landscape and characteristics of exosome circRNAs in HGA remain to be studied. METHODS: CircRNA deep sequencing and bioinformatics approaches were used to generate a circRNA profiling database and analyze the features of HGA cell circRNAs and HGA cell-derived exosome circRNAs. Exosome circRNA expression in the serum and tissues of healthy individuals and patients with HGA was detected using reverse transcription-quantitative PCR. Additionally, the receiver operating characteristic curve and overall survival curves were analyzed. RESULTS: By investigating the characteristics of HGA cell-derived exosome circRNAs and HGA cell circRNAs, we observed that exosomes were more likely to enrich short-exon and suppressor circRNAs than HGA cells. Moreover, a serum exosome circRNA panel including hsa_circ_0075828, hsa_circ_0003828, and hsa_circ_0002976 could be used to screen for HGA, whereas a good prognosis panel comprised high concentrations of hsa_circ_0005019, hsa_circ_0000880, hsa_circ_0051680, and hsa_circ_0006365. CONCLUSIONS: This study revealed a comprehensive circRNA landscape in HGA exosomes and cells. The serum exosome circexosome circRNA panel and tissue circRNAs are potentially useful for HGA liquid biopsy and prognosis monitoring. Exosome circRNAs as novel targets should facilitate further biomarker discovery and aid in HGA diagnosis and therapy monitoring.


Assuntos
Astrocitoma , Exossomos , Astrocitoma/diagnóstico , Astrocitoma/genética , Biomarcadores Tumorais/genética , Exossomos/genética , Humanos , RNA/genética , RNA Circular/genética , Análise de Sequência de RNA
11.
J Environ Manage ; 322: 115989, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36055090

RESUMO

Flupyradifurone (FLU) has great application potential in agricultural production as a new generation of neonicotinoid insecticide after imidacloprid. Nevertheless, the toxic effects of FLU on non-target soil organisms remain unclear, resulting in considerable environmental risks. We evaluated the acute and subchronic toxicities of FLU to earthworms. The results of acute toxicity show that the median lethal concentration (LC50) values (14 d) of FLU were 186.9773 mg kg-1 for adult earthworms and 157.6502 mg kg-1 for juveniles, respectively. The subchronic toxicity of FLU that focused on the activities of antioxidant and detoxication enzymes showed the superoxide dismutase (SOD), catalase (CAT), and glutathione-S transferase (GST) activities in earthworms increased while the peroxidase (POD) and acetylcholinesterase (AChE) activities decreased after exposure to FLU. Oxidative damage analyses revealed that the reactive oxygen species (ROS) level and malonaldehyde (MDA) content in earthworms were increased by FLU, resulting in DNA damage. Transcriptomics and RT-qPCR confirmed that FLU influenced the expression of genes related to antioxidant response and detoxification of earthworms. Ultimately detoxification metabolism, environmental information processing, cell processes, and immune system pathways are significantly enriched to respond jointly to FLU. Our study fills the gaps in the toxicity of FLU to earthworms, providing a basis for its risk assessment of soil ecosystems and non-target biological toxicity.


Assuntos
Inseticidas , Oligoquetos , Poluentes do Solo , 4-Butirolactona/análogos & derivados , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/genética , Catalase/metabolismo , Catalase/farmacologia , Ecossistema , Glutationa/metabolismo , Glutationa/farmacologia , Inseticidas/metabolismo , Malondialdeído/metabolismo , Malondialdeído/farmacologia , Neonicotinoides/metabolismo , Neonicotinoides/toxicidade , Oligoquetos/metabolismo , Estresse Oxidativo , Piridinas , Espécies Reativas de Oxigênio , Solo , Poluentes do Solo/metabolismo , Superóxido Dismutase/metabolismo , Transferases/metabolismo , Transferases/farmacologia
12.
J Cell Mol Med ; 25(6): 2861-2871, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33512774

RESUMO

Cisplatin nephrotoxicity has been considered as serious side effect caused by cisplatin-based chemotherapy. Recent evidence indicates that renal tubular cell apoptosis and inflammation contribute to the progression of cisplatin-induced acute kidney injury (AKI). Hepatocyte nuclear factor 1ß (HNF1ß) has been reported to regulate the development of kidney cystogenesis, diabetic nephrotoxicity, etc However, the regulatory mechanism of HNF1ß in cisplatin nephrotoxicity is largely unknown. In the present study, we examined the effects of HNF1ß deficiency on the development of cisplatin-induced AKI in vitro and in vivo. HNF1ß down-regulation exacerbated cisplatin-induced RPTC apoptosis by indirectly inducing NF-κB p65 phosphorylation and nuclear translocation. HNF1ß knockdown C57BL/6 mice were constructed by injecting intravenously with HNF1ß-interfering shRNA and PEI. The HNF1ß scramble and knockdown mice were treated with 30 mg/kg cisplatin for 3 days to induce acute kidney injury. Cisplatin treatment caused increased caspase 3 cleavage and p65 phosphorylation, elevated serum urea nitrogen and creatinine, and obvious histological damage of kidney such as fractured tubules in control mice, which were enhanced in HNF1ß knockdown mice. These results suggest that HNF1ß may ameliorate cisplatin nephrotoxicity in vitro and in vivo, probably through regulating NF-κB signalling pathway.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Fator 1-beta Nuclear de Hepatócito/genética , NF-kappa B/metabolismo , Néfrons/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Modelos Animais de Doenças , Fator 1-beta Nuclear de Hepatócito/metabolismo , Túbulos Renais/efeitos dos fármacos , Camundongos , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Ratos , Fator de Transcrição RelA/metabolismo
13.
Hepatology ; 71(1): 112-129, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31148184

RESUMO

To identify hepatocellular carcinoma (HCC)-implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC-implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53-stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53-mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down-regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild-type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.


Assuntos
Carcinoma Hepatocelular/etiologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/fisiologia , Neoplasias Hepáticas/etiologia , RNA Longo não Codificante/fisiologia , Sumoilação/fisiologia , Proteína Supressora de Tumor p53/fisiologia , Humanos , Células Tumorais Cultivadas
14.
Opt Lett ; 46(21): 5485-5488, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724507

RESUMO

Anisotropic nanostructures can be generated in fused silica glass by manipulating the spatiotemporal properties of a picosecond pulse. This phenomenon is attributed to laser-induced interband self-trapped excitons. The anisotropic structures exhibit birefringent properties, and thus can be employed for multi-dimensional optical data storage applications. Data voxels generated by such short laser irradiation enable on-the-fly high-speed data recording.

15.
Virol J ; 18(1): 22, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461581

RESUMO

BACKGROUND: Oxidative stress is an important pathogenic factor in influenza A virus infection. It has been found that reactive oxygen species induced by the H9N2 influenza virus is associated with viral replication. However, the mechanisms involved remain to be elucidated. METHODS: In this study, the role of autophagy was investigated in H9N2 influenza virus-induced oxidative stress and viral replication in A549 cells. Autophagy induced by H9N2 was inhibited by an autophagy inhibitor or RNA interference, the autophagy level, viral replication and the presence of oxidative stress were detected by western blot, TCID50 assay, and Real-time PCR. Then autophagy and oxidative stress were regulated, and viral replication was determined. At last, the Akt/TSC2/mTOR signaling pathways was detected by western blot. RESULTS: Autophagy was induced by the H9N2 influenza virus and the inhibition of autophagy reduced the viral titer and the expression of nucleoprotein and matrix protein. The blockage of autophagy suppressed the H9N2 virus-induced increase in the presence of oxidative stress, as evidenced by decreased reactive oxygen species production and malonaldehyde generation, and increased superoxide dismutase 1 levels. The changes in the viral titer and NP mRNA level caused by the antioxidant, N-acetyl-cysteine (NAC), and the oxidizing agent, H2O2, confirmed the involvement of oxidative stress in the control of viral replication. NAC plus transfection with Atg5 siRNA significantly reduced the viral titer and oxidative stress compared with NAC treatment alone, which confirmed that autophagy was involved in the replication of H9N2 influenza virus by regulating oxidative stress. Our data also revealed that autophagy was induced by the H9N2 influenza virus through the Akt/TSC2/mTOR pathway. The activation of Akt or the inhibition of TSC2 suppressed the H9N2 virus-induced increase in the level of LC3-II, restored the decrease in the expression of phospho-pAkt, phospho-mTOR and phospho-pS6 caused by H9N2 infection, suppressed the H9N2-induced increase in the presence of oxidative stress, and resulted in a decrease in the viral titer. CONCLUSION: Autophagy is involved in H9N2 virus replication by regulating oxidative stress via the Akt/TSC2/mTOR signaling pathway. Thus, autophagy maybe a target which may be used to improve antiviral therapeutics.


Assuntos
Células Epiteliais Alveolares/virologia , Autofagia/genética , Regulação da Expressão Gênica , Vírus da Influenza A Subtipo H9N2/fisiologia , Infecções por Orthomyxoviridae/veterinária , Estresse Oxidativo/genética , Replicação Viral , Células A549 , Animais , Humanos , Vírus da Influenza A Subtipo H9N2/patogenicidade , Transdução de Sinais , Suínos
16.
BMC Public Health ; 21(1): 9, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397345

RESUMO

BACKGROUND: To explore the relationship between geographical differences of mortality and related risk factors in ischemic heart disease (IHD) in China. METHODS: Data were collected from the nationally representative China Mortality Surveillance System to calculate annual IHD mortality counts (2010-2015). Descriptive analysis was used to analyze the IHD mortality among Chinese population from 2010 to 2015. Negative binomial regression was used to investigate potential spatiotemporal variation and correlations with age, gender, urbanization, and region. RESULTS: The overall IHD mortality was 221.17/100,000, accounting for 1.51 million deaths in 2015. The standardized IHD mortality rate increased by 5.51% from 2010 to 2015 among people aged 40 years and older. Multilevel analysis indicated significant differences in gender, regions, and age. High urbanization rate (risk ratio [RR] = 0.728, 95% confidence interval [CI] = (0.631, 0.840)) and average high-density lipoprotein (HDL) (RR = 0.741, 95%CI: 0.616,0.891) were negatively associated with IHD mortality. IHD mortality was significantly higher in populations with a low rate of medical insurance coverage (RR = 1.218, 95%CI: 1.007, 1.473), as well as the average body mass index (BMI) (RR = 1.436, 95%CI: 1.135, 1.817) and systolic blood pressure (SBP) (RR = 1.310, 95%CI: 1.019, 1.684). While the relationship with current smoking rate, excessive intake of red meat, insufficient vegetable or fruits intake didn't show the statistical significance. The negative correlation between the average sedentary time and IHD mortality was not conclusive due to the possible deviation of the data. CONCLUSIONS: The mortality of IHD showed an upward trend for people aged 40 years and older in China during 2010-2015, which should be paid attention to. Therefore, some risk factors should be controlled, such as SBP, overweight/obesity. HDL is a protective factor, as well as higher urbanization rate, family income level, and medical insurance coverage.


Assuntos
Isquemia Miocárdica , Adulto , Índice de Massa Corporal , China/epidemiologia , Humanos , Pessoa de Meia-Idade , Análise Multinível , Fatores de Risco
17.
Microb Pathog ; 148: 104408, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32707310

RESUMO

Oxidative stress is implicated in the pathogenesis of influenza virus infection. Increasing evidences show that transient receptor potential melastatin 2 (TRPM2), a Ca2+-permeable non-selective cation channel, plays an important role in the pathomechanism of reactive oxygen species (ROS)-coupled diseases. The present study investigated the role of TRPM2 in pulmonary microvascular endothelial cells (PMVECs) during H9N2 influenza virus infection. We knocked down TRPM2 in PMVECs using TRPM2 shRNA lentiviral particles. Subsequently, we utilized enzyme-linked immunosorbent assay and flow cytometry to compare ROS levels, DNA damage, mitochondrial integrity, apoptosis, and inflammatory factors between control and TRPM2-knockdown PMVECs following H9N2 influenza virus infection. Inhibition of TRPM2 channels reduced H9N2 virus-induced intracellular ROS production, decreased DNA damage, and inhibited H9N2-induced cellular apoptosis. This study shows that the inhibition of TRPM2 channels may protect PMVECs from the damage caused by H9N2 virus infection. Our results highlight the importance of TRPM2 in modulating ROS production, apoptosis, mitochondrial dysfunction, cytokine expression, and DNA damage in H9N2 virus-infected PMVECs, and suggest that TRPM2 may be a potential antiviral target.


Assuntos
Células Endoteliais , Vírus da Influenza A Subtipo H9N2 , Infecções por Orthomyxoviridae , Canais de Cátion TRPM , Animais , Apoptose , Cálcio/metabolismo , Dano ao DNA , Células Endoteliais/metabolismo , Células Endoteliais/virologia , Técnicas de Silenciamento de Genes , Camundongos , Mitocôndrias , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo
18.
Catheter Cardiovasc Interv ; 95 Suppl 1: 606-615, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31868307

RESUMO

OBJECTIVES: This study demonstrated the prognostic value of the residual SYNTAX score (rSS) for patients with chronic renal insufficiency (CRI). BACKGROUND: The rSS has been proposed as a useful tool for quantifying and stratifying the degree and complexity of residual stenosis and predicting long-term clinical outcomes following percutaneous coronary intervention (PCI). However, it has never been validated for patients with CRI. METHODS: A total of 2,468 consecutive patients with an estimated glomerular filtration rate <90 ml/min/1.73 m2 who underwent PCI were retrospectively enrolled. Patients with rSS >0 were defined as having incomplete revascularization and were stratified into the reasonable incomplete revascularization (RICR; 0 < rSS ≤ 8) group or the incomplete revascularization (ICR; rSS >8) group. Their outcomes were compared to those of the complete revascularization (CR) group. RESULTS: During follow-up (median, 3 years; range, 1.5-5 years), the ICR group had the highest incidence of all-cause death, cardiac death, myocardial infarction (MI), unplanned revascularization, stroke, and major adverse cardiovascular and cerebrovascular events (MACCE). Despite having higher rates of unplanned revascularization and MACCE, RICR group had comparable all-cause mortality, cardiac mortality, MI, and stroke with CR group. A multivariable Cox analysis indicated that rSS was an independent predictor of cardiac death, MI, unplanned revascularization, stroke, and MACCE. Furthermore, compared with baseline SYNTAX score, rSS had stronger prognostic accuracy when predicting the risk of unplanned revascularization, stroke, and MACCE at the 3-year follow-up. CONCLUSIONS: The rSS is a powerful indicator of clinical outcomes and may help determine reasonable levels of revascularization for patients with CRI following PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Técnicas de Apoio para a Decisão , Taxa de Filtração Glomerular , Indicadores Básicos de Saúde , Rim/fisiopatologia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/fisiopatologia , Idoso , Algoritmos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
BMC Neurol ; 20(1): 6, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910808

RESUMO

OBJECTIVE: The traditional approaches for diagnosing catheter-related bloodstream infection(CRBSI) is time consuming, which could not meet the clinical requirement. Our aim was to investigate the value of serum procalcitonin(PCT) in predicting CRBSI in first-ever acute ischemic stroke patients with central venous catheters (CVCs). METHODS: This was a retrospective study. First-ever acute ischemic stroke patients hospitalized in neurological intensive care unit(NICU) of Aerospace Center Hospital and NICU of Beijing Chaoyang Hospital during January 2010 and December 2017 with clinically suspected CRBSI were enrolled. Peripheral blood white blood cell (WBC) count, neutrophils percentage(NE%), the levels of serum PCT, dwell time of catheterization and outcome of the patients were collected. According to the diagnosis of CRBSI or not, they were divided into CRBSI group and no CRBSI group. We used receiver operating characteristic curve (ROC) to evaluate the value of serum PCT levels in predicting CRBSI in patients with clinically suspected CRBSI. RESULTS: Forty-five patients with suspected CRBSI were included in this study, and 13 patients were diagnosed with CRBSI. Comparing to those in no CRBSI group, the maximum body temperature (Tmax) (p = 0.036) and the PCT levels (P = 0.013) in CRBSI group were both significantly higher. The area under ROC of the serum PCT levels and the Tmax to predict the CRBSI were 0.803 (0.95CI,0.660-0.946) and 0.680 (0.95CI,0.529-0.832) respectively. The PCT cut-off value was 0.780 ng/ml, with the sensitivity 69.23%, specificity 87.50%, positive predictive values 69.23% and negative predictive values 87.50%. CONCLUSION: It could be helpful to adopt PCT as a rapid diagnostic biomarker for first-ever acute stroke patients with suspected CRBSI.


Assuntos
Bacteriemia/diagnóstico , Isquemia Encefálica/complicações , Infecções Relacionadas a Cateter/diagnóstico , Pró-Calcitonina/sangue , Acidente Vascular Cerebral/complicações , Bacteriemia/sangue , Bacteriemia/complicações , Infecções Relacionadas a Cateter/sangue , Infecções Relacionadas a Cateter/complicações , Humanos , Curva ROC , Estudos Retrospectivos
20.
Lasers Surg Med ; 52(7): 590-596, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31820470

RESUMO

BACKGROUND AND OBJECTIVES: Although topical corticosteroids are still the first-line option for vitiligo, its efficacy is still unsatisfactory for stable vitiligo. A few studies have focused on laser-assisted drug delivery (LADD) but were limited by their sample deficiency and analyses of the influencing factors. To determine the efficacy, adverse events, and their influencing factors of fractional erbium: yttrium-aluminum-garnet (Er:YAG) laser-assisted topical delivery of corticosteroids in stable vitiligo. STUDY DESIGN/MATERIALS AND METHODS: We retrospectively reviewed 1,026 lesions in 684 patients with stable vitiligo who underwent treatment with fractional Er:YAG laser-assisted delivery of topical compound betamethasone solution between January 2014 and December 2017. Multi-factors associated with different outcomes were analyzed by logistic regression in this study. RESULTS: A total of 413 of 1,026 lesions (40.3%) were effective 12 months after the first treatment. Age (<14 years old), disease duration (<1 year), lesion location (on face and neck), hairy lesions, and drug concentration were independent factors associated with effective repigmentation. A common adverse event was hyperpigmentation (14.4%), which was highly correlated with 22% density. CONCLUSIONS: Fractional Er:YAG laser-assisted delivery of topical compound betamethasone is a good option for the management of vitiligo. The treatment may be suggested in these situations: younger patients, shorter disease duration, and lesions on the face and neck with hair. The appearance of white hair in the lesion area does not affect our confidence in vitiligo treatment. Density >22% may cause hyperpigmentation, but it does not significantly contribute to the efficacy. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.


Assuntos
Lasers de Estado Sólido , Vitiligo , Adolescente , Betametasona , Érbio , Humanos , Lasers de Estado Sólido/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Vitiligo/tratamento farmacológico
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