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OBJECTIVE: To explore the potential mechanism of electroacupuncture (EA) for vascular dementia (VD) using tandem mass tag (TMT) quantitative proteomics technology. METHODS: Among 80 male SPF SD rats, 78 rats which met the selection criteria through the Morris water maze test were selected and randomly divided into a sham surgery group (18 rats) and a surgery group (60 rats). VD model was established by four-vessel occlusion (4-VO) method in the surgery group, and 36 rats with successful modeling were randomly assigned to a model group (18 rats) and an EA group (18 rats). Each group was further divided into three subgroups based on intervention duration, with each subgroup containing 6 rats. Seven days after model establishment, the EA group received EA intervention at left and right "Sishencong" (EX-HN 1) and bilateral "Fengchi" (GB 20), with continuous wave at a frequency of 2 Hz and current intensity of 1 mA, daily for 30 min, with subgroups receiving EA for 7, 14, or 21 d respectively. Cognitive function before and after interventions was assessed using Morris water maze. Proteomic analysis was conducted on the optimal EA subgroup and corresponding sham surgery and model subgroups, identifying differentially expressed proteins and analyzing them through bioinformatics. Differentially expressed target proteins was performed using parallel reaction monitoring (PRM) and Western blot techniques. RESULTS: Compared to the sham surgery group, the model group exhibited prolonged escape latency and reduced number of platform crossings (P<0.01); compared with model group, the EA group showed reductions in escape latency and increased platform crossings after 7, 14, and 21 days of intervention (P<0.01, P<0.05). Compared to the 7 and 14-day intervention, the rats in the EA group of 21-day intervention showed the most significant improvements in reductions of escape latency and increased platform crossings (P<0.01, P<0.05), and was selected for further proteomic, PRM analyses, and Western blot validation. Compared to the sham surgery group, the model group displayed 71 differentially expressed proteins, with 50 up-regulated and 21 down-regulated proteins; compared to the model group, the EA group had 54 differentially expressed proteins, with 30 up-regulated and 24 down-regulated proteins. Functional enrichment and clustering analyses indicated that these proteins were primarily associated with cellular processes, metabolic processes, phagocytosis recognition, immune response, and regulation of extracellular matrix, etc. Enrichment was observed in the mammalian target of rapamycin (mTOR) signaling pathway and neurotrophic factors signaling pathways, involving glycogen synthase kinase 3ß (GSK3ß) and mitogen-activated protein kinase kinase 2 (Map2k2), with PRM and Western blot findings consistent with the proteomic results. Which meant that compared with the model group, the protein expression of GSK3ß and Map2k2 of hippocampus was increased in the EA group (P<0.01, P<0.05). CONCLUSION: EA at "Sishencong" (EX-HN 1) and "Fengchi" (GB 20) could improve cognitive function in VD rats, with the mechanism involving multiple targets and pathways, potentially related to GSK3ß, Map2k2 proteins, and the mTOR and neurotrophic factor signaling pathways.
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Demência Vascular , Eletroacupuntura , Proteômica , Ratos Sprague-Dawley , Animais , Demência Vascular/terapia , Demência Vascular/metabolismo , Masculino , Ratos , Humanos , Aprendizagem em Labirinto , Memória , Modelos Animais de DoençasRESUMO
In response to biotic and abiotic stresses, the WRKY gene family plays a crucial role in plant growth and development. This study focused on Phoebe bournei and involved genome-wide identification of WRKY gene family members, clarification of their molecular evolutionary characteristics, and comprehensive mapping of their expression profiles under diverse abiotic stress conditions. A total of 60 WRKY gene family members were identified, and their phylogenetic classification revealed three distinct groups. A conserved motif analysis underscored the significant conservation of motif 1 and motif 2 among the majority of PbWRKY proteins, with proteins within the same class sharing analogous gene structures. Furthermore, an examination of cis-acting elements and protein interaction networks revealed several genes implicated in abiotic stress responses in P. bournei. Transcriptomic data were utilized to analyze the expression patterns of WRKY family members under drought and waterlogged conditions, with subsequent validation by quantitative real-time PCR (RT-qPCR) experiments. Notably, PbWRKY55 exhibited significant expression modulation under drought stress; PbWRKY36 responded prominently to waterlogging stress; and PbWRKY18, PbWRKY38, and PbWRKY57 demonstrated altered expression under both drought and waterlogging stresses. This study revealed the PbWRKY candidate genes that potentially play a pivotal role in enhancing abiotic stress resilience in P. bournei. The findings have provided valuable insights and knowledge that can guide further research aimed at understanding and addressing the impacts of abiotic stress within this species.
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Secas , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Proteínas de Plantas , Estresse Fisiológico , Fatores de Transcrição , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica , Evolução MolecularRESUMO
Plant growth and development are driven by intricate processes, with the cell membrane serving as a crucial interface between cells and their external environment. Maintaining balance and signal transduction across the cell membrane is essential for cellular stability and a host of life processes. Ion channels play a critical role in regulating intracellular ion concentrations and potentials. Among these, K+ channels on plant cell membranes are of paramount importance. The research of Shaker K+ channels has become a paradigm in the study of plant ion channels. This study offers a comprehensive overview of advancements in Shaker K+ channels, including insights into protein structure, function, regulatory mechanisms, and research techniques. Investigating Shaker K+ channels has enhanced our understanding of the regulatory mechanisms governing ion absorption and transport in plant cells. This knowledge offers invaluable guidance for enhancing crop yields and improving resistance to environmental stressors. Moreover, an extensive review of research methodologies in Shaker K+ channel studies provides essential reference solutions for researchers, promoting further advancements in ion channel research.
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Soil salinization poses a mounting global ecological and environmental threat. The identification of genes responsible for negative regulation of salt tolerance and their utilization in crop improvement through gene editing technologies emerges as a swift strategy for the effective utilization of saline-alkali lands. One efficient mechanism of plant salt tolerance is maintaining the proper intracellular K+/Na+ ratio. The Shaker K+ channels play a crucial role in potassium absorption, transport, and intracellular potassium homeostasis in plant cells. Here, the study presents the first genome-wide identification of Shaker K+ channels in Nicotiana tabacum L., along with a detailed bioinformatic analysis of the 20 identified members. Transcriptome analysis revealed a significant up-regulation of NtSKOR1B, an outwardly-rectifying member predominantly expressed in the root tissue of tobacco seedlings, in response to salt stress. This finding was then confirmed by GUS staining of ProNtSKOR1B::GUS transgenic lines and RT-qPCR analysis. Subsequently, NtSKOR1B knockout mutants (ntskor1) were then generated and subjected to salt conditions. It was found that ntskor1 mutants exhibit enhanced salt tolerance, characterized by increased biomass, higher K+ content and elevated K+/Na+ ratios in both leaf and root tissues, compared to wild-type plants. These results indicate that NtSKOR1B knockout inhibits K+ efflux in root and leaf tissues of tobacco seedlings under salt stress, thereby maintaining higher K+/Na+ ratios within the cells. Thus, our study identifies NtSKOR1B as a negative regulator of salt tolerance in tobacco seedlings.
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INTRODUCTION: This review is to explore the relevant experience of colorectal cancer survivors' return-to-work, reintegrating and analyzing the promoting factors and obstacles of colorectal cancer survivors' return-to-work. METHODS: This review followed PRISMA List. Databases including the Cochrane Library, PubMed, Web of Science, EM base, CINAHL, APA PsycInfo, Wangfang Database, CNKI and CBM from inception to October 2022 were searched to collect qualitative studies in the experience of colorectal cancer survivors' return-to-work. Article selection and data extraction were conducted by two researchers used the Joanna Briggs Institute Critical Appraisal Tool for qualitative researches (2016) in Australia. RESULTS: Seven studies were included, the thirty-four themes distilled from the literature were grouped into eleven new categories and summed into two integrated findings: (1) facilitators to return-to-work for colorectal cancer survivors: desire and expectation for return-to-work and social dedication, economic needs, support and tolerance from employers and colleagues, work suggestions provided by professionals, health insurance policy of the workplace. (2) obstacles to return-to-work for colorectal cancer survivors: physical problems, psychological barriers, lack of family support, negative attitudes of employers and colleagues, limited information and resources available from professionals, Imperfection of related policies. CONCLUSION: This study shows that colorectal cancer survivors' return-to-work is influenced by many factors. We should pay attention to and avoid obstacles, help colorectal cancer survivors recover their physical functions and maintain a positive psychological state, improve the social support for colorectal cancer survivors to return-to-work, so as to achieve comprehensive rehabilitation as soon as possible.
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Sobreviventes de Câncer , Neoplasias Colorretais , Humanos , Retorno ao Trabalho , Sobreviventes/psicologia , Sobreviventes de Câncer/psicologia , Pesquisa QualitativaRESUMO
Background: To identify novel clinical phenotypic signatures of congenital nephrogenic diabetes insipidus (CNDI). Methods: A Chinese family with CNDI was recruited for participation in this study. The proband and one of his uncles suffered from polydipsia and polyuria since infancy. The results of clinical testing indicated the diagnosis of CNDI. 10 family members had similar symptoms but did not seek medical advice. Genetic testing of mutations in the coding region of the aquaporin 2 (AQP2) gene and the arginine vasopressin receptor 2 (AVPR2) gene were carried out in 11 family members. Somatic DNA from 5 female family members was used to test for methylation of polymorphic CAG repeats in the human androgen receptor (AR) gene, as an index for X-chromosome inactivation pattern (XCIP). Results: AQP2 gene mutations were not found in any family members, but a novel missense mutation (814th base A>G) in exon 2 of the AVPR2 gene was identified in 10 individuals. This mutation leads to a Met 272 Val (GAT-GGT) amino acid substitution. Skewed X-chromosome inactivation patterns of the normal X allele were observed in 4 females with the AVPR2 gene mutation and symptoms of diabetes insipidus, but not in an asymptomatic female with the AVPR2 gene mutation. Conclusions: Met 272 Val mutation of the AVPR2 gene was identified as a novel genetic risk factor for CDNI. The clinical NDI phenotype of female carriers with heterozygous AVPR2 mutation may be caused by X-chromosome inactivation induced by dominant methylation of the normal allele of AVPR2 gene.
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Diabetes Insípido Nefrogênico , Diabetes Mellitus , Receptores de Vasopressinas , Aquaporina 2/genética , China , Cromossomos , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/genética , Diabetes Mellitus/genética , Feminino , Heterozigoto , Humanos , Mutação de Sentido Incorreto , Linhagem , Receptores de Vasopressinas/genéticaRESUMO
OBJECTIVES: This meta-analysis assessed the treatment effectiveness of acupuncture in patients with vascular dementia. METHODS: The PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure were searched to identify eligible randomized controlled trials (RCTs). The odds ratios (ORs) and weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the pooled effect estimates using a random-effects model for categorical and continuous outcomes, respectively. RESULTS: Thirty-four RCTs (2672 patients) were selected for the final meta-analysis. The use of acupuncture showed association with an increased incidence of effective rate (OR: 3.28; 95 % CI: 2.54-4.24; P < 0.001). The pooled WMDs revealed that acupuncture was significantly associated with an improvement in the Hasegawa dementia scale (HDS) (WMD: 4.31; 95 % CI: 3.15-5.47; P < 0.001), and Mini-Mental State Examination scores (MMSE) (WMD: 3.07; 95 % CI: 2.40-3.74; P < 0.001). However, the use of acupuncture showed no association with the level of Activities of daily living (ADL) (WMD: 1.93; 95 % CI: - 2.53 to 6.38; P = 0.397). Finally, acupuncture was associated with lower levels of Scale for the differentiation of syndromes of vascular dementia (SDSVD) (WMD: - 2.15; 95 % CI: - 4.14 to - 0.16; P = 0.034), and National Institutes of Health stroke scale (NIHSS) (WMD: - 3.90; 95 % CI: - 4.87 to - 2.94; P < 0.001). CONCLUSIONS: Acupuncture is probably helpful in vascular stroke, but strong supportive data are not yet available. Acupuncture should be used cautiously, owing to the analysis of this study based on low to moderate evidence. Further high-quality, large-scale RCTs should be conducted.
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Terapia por Acupuntura , Demência Vascular , Acidente Vascular Cerebral , China , Humanos , Resultado do TratamentoAssuntos
Neoplasias da Mama Masculina , Humanos , Masculino , Pesquisa Qualitativa , Retorno ao TrabalhoRESUMO
Background: Microribonucleic acids (miRNAs) have been shown to play important roles in hepatocellular carcinoma (HCC) progression. MiR-448 has frequently been shown to be a tumor suppressor, and is abnormally expressed in HCC tumor tissues. However, little is known about the role of miR-448 in HCC development. In this article, the regulatory role of miR-448 on insulin-like growth factor 1 receptor (IGF-1R) in modulating hepatoma cell viability and glycolysis was investigated. Methods: The expression of miR-448 profiles in clinical tumor tissues and cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). HepG2 and Huh7 cells were transfected with miR-448 mimics, inhibitors, and scramble sequences. Cell viability and apoptosis were determined by a Cell Counting Kit-8 assay and a flow cytometry analysis. IGF-1R, a potential target of miR-448, was selected following a bioinformatic analysis, and the regulatory effects of miR-448 on IGF-1R expression was confirmed by luciferase reporter assay, qRT-PCR, and western blot. Glucose uptake, lactate production, and adenosine triphosphate (ATP) generation were detected by corresponding kits. Results: Decreased miR-448 expression was observed in both HCC patients' tumor tissues and hepatoma cells in vitro. The overexpression of miR-448 in HepG2 and Huh7 cells decreased cell viability and increased apoptosis. Additionally, the overexpression of miR-448 or the knockdown of IGF-1R lowered the level of glucose uptake, lactate production, and ATP generation, while the knockdown of miR-448 increased glycolysis. Further, aberrantly expressed miR-448 downregulated IGF-1R levels, while the inhibition of miR-448 resulted in the upregulation of IGF-1R in both HepG2 and Huh7 cells. In addition, miR-448 interacted with the wild-type 3'untranslated regions (3'UTRs) of IGF-1R, but had no effect on the mutant 3'UTRs. The expression of IGF-1R was increased in HCC patients' tumor tissues and serum, and was inversely correlated with miR-448 expression. Conclusions: The increased expression of miR-448 appears to downregulate the expression of IGF-1R by interacting with the 3'UTR in HCC progression. These findings highlight its role as a potential target for HCC therapy.
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INTRODUCTION: As an autoimmune central nervous system disease characterized by inflammation and demyelination, neuromyelitis optica (NMO) has been extensively investigated. A specific antigenic target, astrocytic water channel aquaporin-4 (AQP4) has already been identified, and it can be recognized explicitly by the autoantibody marker NMO-IgG. Along with the immune attacks, clinical disabilities would gradually accumulate. As there has been no validated and well-recognized therapy for NMO till now, preventing and postponing attack using immunosuppressive therapies is the primary treatment option. METHODS: In the current retrospective study, the effect of immunosuppressive agents was investigated through a long-term follow-up. To assess the long-term effectiveness and safety of rituximab (RTX), azathioprine (AZA), and mycophenolate mofetil (MMF) therapies, all 129 patients with NMO spectrum disorders (NMOSD) who received at least one of these treatments were studied, including 55 seropositive for AQP4-Ab and 74 seronegative for AQP4-Ab. RESULTS: The median post-treatment annualized relapse rate (ARR) was lower than the pre-treatment rates in all AQP4+Ab groups (from 1.0 to 0.7 in RTX, from 0.8 to 0.3 in AZA, and from 0.85 to 0.35 in MMF). Meanwhile, the ARR also decreased in all AQP4-Ab groups (from 0.3 to 0.2 in RTX, from 0.9 to 0.5 in AZA, and from 0.9 to 0.4 in MMF). Disability condition improved in the Expanded Disability Status Scale (EDSS) in all AQP4+Ab groups (from 4.0 to 2.75 in RTX, from 3.5 to 2.5 in AZA, and from 3.0 to 2.0 in MMF) and in all AQP4-Ab groups (from 3.0 to 2.5 in RTX, from 3.0 to 2.5 in AZA, and from 3.5 to 2.0 in MMF). There was no statistically significant difference between the post-treatment and pre-treatment changes of EDSS and ARR in the RTX, AZA, and MMF groups (P > 0.05). However, according to Kaplan-Meier survival analysis, RTX-treated patients were more likely to be relapse-free after long-term follow-up than those who received AZA or MMF therapy. Meanwhile, adverse effects were noted in three out of 23 patients with RTX treatment, five of 32 with AZA treatment, and three of 21 with MMF treatment. No serious adverse events were observed in all treatment groups during the study. CONCLUSIONS: RTX, AZA, and MMF therapies efficiently lowered the relapse frequency and disability in both of the AQP4-Ab seropositive or seronegative patients with NMO. Furthermore, low dosage of RTX is recommended for the patients with NMO owing to its long-term effectiveness and safety.
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BACKGROUND: Psittacosis ranges from a mild illness to fulminant severe pneumonia with multi-organ failure. It's crucial to understand the clinical characteristics and identify risk factors for a better outcome. METHODS: We conducted a retrospective analysis designed to identify risk factors for severe Chlamydia psittaci pneumonia (C. psittaci pneumonia) by comparing the clinical characteristics of patients with severe and less severe forms of the disease. Epidemiological, clinical, laboratory, computed tomography (CT) imaging, and outcome data were collected. RESULTS: We enrolled 27 patients with C. psittaci pneumonia, with a median age of 63 (range, 47-82) years, and 23 of whom (85.2%) had a history of avian exposure. Dyspnea was seen in 15 patients with severe C. psittaci pneumonia (100%), and four in 12 non-severe patients (33.3%) (P<0.01). Compared to non-severe patients, those with severe C. psittaci pneumonia had significantly higher levels of procalcitonin, urea nitrogen, lactate dehydrogenase, creatine kinase (CK), B natriuretic peptide (BNP), myoglobin, IL-6, and IL-10, as well as lower lymphocyte and CD8+ T cell counts, and PaO2/FiO2 ratio. Among patients with severe infection, CT showed that 46.7% had multi-lobar (more than two lobes) pneumonia, whereas its incidence was 0% in non-severe patients (P=0.01). Multivariate analysis revealed that the independent risk factors associated with severe C. psittaci pneumonia were abnormal CK (OR 15.2, 95% CI: 1.1-204.8, P=0.04) and BNP (OR 22.3, 95% CI: 1.8-281.9, P=0.02). CONCLUSIONS: A history of prior avian exposure in middle-aged patients should serve as a clue in the diagnosis of C. psittaci pneumonia, and patients with its severe form are more likely to develop dyspnea and progress into respiratory failure, with involvement of multiple lung lobes. Abnormal CK and BNP levels are risk factors associated with severe C. psittaci pneumonia.
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Chlamydophila psittaci , Pneumonia , Psitacose , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world. Despite the rapid development of targeted therapy and immune checkpoint inhibitors for lung cancer in recent years, their efficacy is still unsatisfactory overall. Therefore, there is an urgent unmet clinical need for lung cancer treatment. Here, we attempted to treat lung cancer using a personalized neoantigen peptide-pulsed autologous DC vaccine and conducted a single-arm, 2 medical centers, pilot study initiated by the investigator (ChiCTR-ONC-16009100, NCT02956551). The patients enrolled were patients with heavily treated metastatic lung cancer. Candidate neoantigens were derived from whole-exome sequencing and RNA sequencing of fresh biopsy tissues as well as bioinformatics analysis. A total of 12 patients were enrolled in this study. A total of 85 vaccine treatments were administered with a median value of 5 doses/person (range: 3-14 doses/person). In total, 12-30 peptide-based neoantigens were selected for each patient. All treatment-related adverse events were grade 1-2 and there were no delays in dosing due to toxic effects. The objective effectiveness rate was 25%; the disease control rate was 75%; the median progression-free survival was 5.5 months and the median overall survival was 7.9 months. This study provides new evidence for neoantigen vaccine therapy and new therapeutic opportunities for lung cancer treatment.
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Antígenos de Neoplasias , Vacinas Anticâncer , Células Dendríticas , Imunoterapia , Neoplasias Pulmonares , Medicina de Precisão , Idoso , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Autoenxertos , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Células Dendríticas/transplante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Taxa de SobrevidaRESUMO
Abnormal B cells, which produce antibodies against self-antigens, play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). B-cell activating factor (BAFF) is closely associated with abnormal B cells and participates in B cell-mediated autoimmune diseases; thus, neutralizing BAFF is an effective method for treating these diseases. Our group designed a novel fusion protein, BAFF-Trap, that contains the BAFF-binding domains of two BAFF receptors (TACI and BAFF-R) and the Fc domain of human IgG1. In this study, we showed that BAFF-Trap significantly decreased the autoantibody levels, BAFF concentrations and B cells numbers in MRL/lpr mice. BAFF-Trap suppressed the expression of pro-inflammatory cytokines in the kidney and decreased the frequencies of T cell subsets and dendritic cells. Furthermore, BAFF-Trap reduced proteinuria and IgG deposition, relieved glomerular damage in the kidney, and markedly improved the survival rate of mice. These results indicated that BAFF-Trap may be a potential drug for the treatment of SLE.
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Fator Ativador de Células B/antagonistas & inibidores , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Animais , Autoanticorpos/metabolismo , Receptor do Fator Ativador de Células B/metabolismo , Linfócitos B/efeitos dos fármacos , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Progressão da Doença , Feminino , Humanos , Imunoglobulina G/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , Taxa de Sobrevida , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Proteína Transmembrana Ativadora e Interagente do CAML/metabolismoRESUMO
mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi-tRNA synthetase complex (MSC) component glutaminyl-tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA-like structures in mammalian cells.
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RNA Longo não Codificante , Pequeno RNA não Traduzido , Animais , Biossíntese de Proteínas , Processamento Pós-Transcricional do RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismoRESUMO
Obesity has been recognized as a low-grade, chronic inflammatory disease that leads to an increase in obesity-associated disorders, including type 2 diabetes (T2D), fatty liver diseases and cancer. Glucagon-like peptide-1 (GLP-1) is an effective drug for T2D, and it not only has glucose-regulating effects but also has anti-inflammatory effects in obesity. In our previous study, we designed a novel GLP-1 analogue, (EX-4)2-Fc, which has been shown to reduce body weight and improve glucose tolerance in vivo. In this study, we observed that (EX-4)2-Fc also has anti-inflammatory functions in adipose tissue. After the treatment of diet-induced obesity (DIO) mice with (EX-4)2-Fc, we found that the inflammatory response in adipose tissue was significantly attenuated. (Ex-4)2-Fc can reduce obesity-associated proinflammatory cytokine levels and macrophage numbers in DIO mice. In addition, (EX-4)2-Fc treatment resulted in proinflammatory M1-type macrophages beginning to transform into anti-inflammatory M2-type macrophages. The inflammatory mitogen-activated protein kinase (MAPK) signalling pathway and nuclear factor kappa B (NF-κB) were altered in adipose tissue after (EX-4)2-Fc treatment. Leptin has been proven to be closely related to immunity, and we demonstrated that the effect of (EX-4)2-Fc on adipocyte inflammation was related to leptin. The data suggested that (EX-4)2-Fc could modulate the inflammatory response by inhibiting the expression of leptin in adipose tissue.
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Tecido Adiposo/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Inflamação/prevenção & controle , Leptina/antagonistas & inibidores , Obesidade/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon/química , Inflamação/metabolismo , Leptina/metabolismo , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/classificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , NF-kappa B/metabolismo , Obesidade/etiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
The study investigated the expression of long noncoding RNA (lncRNA) MALAT1 in high glucose (HG)-induced human vascular endothelial cells (HUVECs) and the role of MALAT1 in the apoptosis of HG-induced HUVECs. The HUVECs were cultured and induced with 25 mmol/L HG. After that, the HUVECs were transfected with MALAT1 siRNA. The expression levels of MALAT1 were detected with qPCR, whereas the expression levels of Bax, Bcl-2, cleaved-caspase-3, cleaved-caspase-9, p-65, and p-p65 were detected using Western blot. The roles of MALAT1 in cell activities, including apoptosis, were evaluated using the CCK-8 assay, TUNEL staining, and flow cytometry. The expression levels of inflammatory factors (TNF-α and IL-6) were measured using ELISA. The expression levels of MALAT1, TNF-α, and IL-6 in HUVECs were increased in the HG environment; however, when MALAT1 was silenced in the HUVECs, cell proliferation increased significantly, the expression levels of TNF-α, IL-6, Bax, cleaved-caspase-3, and cleaved-caspase-9 decreased, and the rate of apoptosis also decreased. Silencing MALAT1 inhibited the expression of p-p65 in HG-induced HUVECs. In conclusion, our study demonstrated that MALAT1 is upregulated in HG-induced HUVECs, and inhibition of MALAT1 inhibits HG-induced apoptosis and inflammation in HUVECs by suppression of the NF-κB signaling pathway.
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Apoptose/efeitos dos fármacos , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismoRESUMO
The graphene-based nanomaterials have been measured as a most promising nanomaterials in the various fields. Graphene oxide having attractive and effective attention in the modified of medicine. Also, graphene oxide is one of the distinct bio-chemical properties with minimum cytotoxicity compared to the other nanomaterials. Up to till date, gastric treatments with reduced graphene oxide not studied so far. In this report, 7-ethyl- 10-hydroxycamptothecin (SN-38) coated graphene oxide synthesized (SN-rGO) effectively and are characterized using various analytical methods. The hydroxyl and carbonyl gatherings of oxidized SN38 will in general ingest onto GO by means of hydrogen bond arrangement with their leftover oxygen functionalities and offers steadiness to SN38. The morphological analyses showed the foldable fields of SN38-rGO NPs with acquire transparency, thin sheets and the crumpled structures. Further the photothermal efficiency and cytotoxicity of the SN-rGO were examined by MTT assay using two NCI-N87 and SGC-791 gastric carcinoma cells. In addition, the morphological changes were examined through the live and dead cells and nuclear staining biochemical techiniques and apoptosis were evaluated through flow cytometry analysis. Our result's suggested that the SN-38 coated reduced graphene oxide can be used for the photothermal treatment of gastric carcinoma for the future nanotechnology cancer therapies without using functionalized polymeric nanoparticles.
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Antineoplásicos Fitogênicos/biossíntese , Camptotecina/análogos & derivados , Grafite/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Camptotecina/biossíntese , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Humanos , Raios Infravermelhos , Microscopia de Fluorescência , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: The purpose of this study was to evaluate and compare the clinical outcomes of two different fixation techniques for anatomic medial patellofemoral ligament (MPFL) reconstruction. METHODS: A retrospective study was undertaken between 2012 and 2018 of 60 cases of patellar dislocation who underwent surgical reconstruction between 2007 and 2010: 30 patients were treated with modified semi-tunnel bone bridge fixation (group A) and 30 patients with suture anchor fixation (group B). All patients had computed tomography scans available to review the patellar tilt angle and lateral patellar angle (LPA). In addition, a physical examination was performed, and the patellar apprehension sign and patellar stability were evaluated. Knee function was also evaluated using the Kujala score and Lysholm score. RESULTS: At a minimum 5-year follow-up, the patellar tilt angle and LPA were restored to the normal range, and a significant difference was observed between the groups. There was a significant improvement in knee function in the Kujala and Lysholm scores after surgery in both groups. At the final follow-up, the mean Kujala and Lysholm scores in groups A and B were significantly different. CONCLUSION: Both the semi-tunnel bone bridge and suture anchor fixation for double-bundle anatomic reconstruction of the MPFL can effectively restore patellar stability and improve knee function. The semi-tunnel bone bridge technique achieved statistically better knee function than the suture anchor technique at a minimum 5-year follow-up. LEVEL OF EVIDENCE: III.
Assuntos
Artroscopia/métodos , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Âncoras de Sutura , Técnicas de Sutura , Adulto , Feminino , Humanos , Masculino , Luxação Patelar/diagnóstico por imagem , Luxação Patelar/fisiopatologia , Articulação Patelofemoral/diagnóstico por imagem , Articulação Patelofemoral/fisiologia , Exame Físico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND The flavones are considered as competent antidiabetic molecules due to their strong antioxidant activities and higher in vivo stability. The present study evaluated the antidiabetic and hypolipidemic effects of 5,7-dimethoxyflavone in streptozotocin (STZ)-induced diabetic rat models. MATERIAL AND METHODS The antidiabetic potential of 5,7-dimethoxyflavone was evaluated in streptozotocin-induced diabetic rats. The serum levels of triglyceride, total cholesterol, and high-density lipoprotein cholesterol were measured using the Randox assay kit. Histopathological examination was carried out by hematoxylin and eosin (HE) staining. RESULTS Oral administration of 5,7-dimethoxyflavone significantly reduced STZ-induced enhancement in blood sugar and glycosylated hemoglobin, as well as significant increases in C-peptide, insulin, hemoglobin, and total protein content (p<0.05). Additionally, treatment with 5,7-dimethoxyflavone resulted in a remarkable increase in non-enzymic antioxidants. Administration of 5,7-dimethoxyflavone had a hypolipidemic effect by significantly reducing levels of serum triglycerides, total cholesterol, and low-density lipoproteins. The histopathological examination of rat pancreases revealed the beneficial effect of 5,7-dimethoxyflavone and protection of ß cell integrity in STZ-induced diabetic rats. CONCLUSIONS These findings reflect the antidiabetic and hypolipidemic effects of 5,7-dimethoxyflavone, suggesting that 5,7-dimethoxyflavone may be a promising compound for use in development of new antidiabetic drugs.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Animais , Antioxidantes/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Modelos Animais de Doenças , Hemoglobinas Glicadas/metabolismo , Hipoglicemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , EstreptozocinaRESUMO
B-cell targeted therapy is effective for autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis (RA), although there are setbacks in RA clinical trials. In this study, we designed a novel B-cell activating factor (BAFF) antagonist: BAFF-Trap, a recombinant glycoprotein with BAFF-binding domains of two BAFF receptors (TACI and Br3) linked to Fc domain of human IgG1. Unlike TACI-Fc, BAFF-Trap bound BAFF but not APRIL (a proliferation-inducing ligand), and significantly suppressed the development of collagen-induced arthritis and adjuvant-induced arthritis. Furthermore, BAFF-Trap inhibited proinflammatory cytokine expression, ameliorated joint damage and suppressed B- and T-cell activation. BAFF-Trap reduced dendritic cells in joints, and increased regulatory T cell, regulatory B-cell, and M2 macrophage. The function of BAFF-Trap was related to inhibition of canonical and noncanonical NF-κB activation. Thus, BAFF-Trap may be a valuable agent for the effective treatment of RA.