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1.
Osteoarthritis Cartilage ; 32(5): 601-611, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38049030

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and cost-effectiveness of telemonitored self-directed rehabilitation (TR) compared with hospital-based rehabilitation (HBR) for patients with total knee arthroplasty (TKA). DESIGN: In this randomized, non-inferiority clinical trial, 114 patients with primary TKA who were able to walk independently preoperatively were randomized to receive HBR (n = 58) or TR (n = 56). HBR comprised at least five physical therapy sessions over 10 weeks. TR comprised a therapist-led onboarding session, followed by a 10-week unsupervised home-based exercise program, with asynchronous monitoring of rehabilitation outcomes using a telemonitoring system. The primary outcome was fast-paced gait speed at 12 weeks, with a non-inferiority margin of 0.10 m/s. For economic analysis, quality-adjusted-life-years (QALY) was the primary economic outcome (non-inferiority margin, 0.027 points). RESULTS: In Bayesian analyses, TR had >95% posterior probability of being non-inferior to HBR in gait speed (week-12 adjusted TR-HBR difference, 0.02 m/s; 95%CrI, -0.05 to 0.10 m/s; week-24 difference, 0.01 m/s; 95%CrI, -0.07 to 0.10 m/s) and QALY (0.006 points; 95%CrI, -0.006 to 0.018 points). When evaluated from a societal perspective, TR was associated with lower mean intervention cost (adjusted TR-HBR difference, -S$227; 95%CrI, -112 to -330) after 24 weeks, with 82% probability of being cost-effective compared with HBR at a willingness to pay of S$0/unit of effect for the QALYs. CONCLUSIONS: In patients with uncomplicated TKAs and relatively good preoperative physical function, home-based, self-directed TR was non-inferior to and more cost-effective than HBR over a 24-week follow-up period. TR should be considered for this patient subgroup.

2.
Proteomics ; 23(9): e2200432, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36625413

RESUMO

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, often metastasizes to the lungs. The implications of lysine lactylation (Kla), a recently identified histone post-translational modification (PTM), in the pathology of HCC remain unclear. Here, we report the first proteomic survey of this specific modification in HCC (with no metastasis during 3 years of follow-up), normal liver tissues, and lung metastasis samples of HCC. Of the 2045 modification sites detected on 960 proteins, 1438 sites on 772 proteins contained quantitative information. Subsequently, we analyzed the differentially modified proteins among the different groups. Differentially lactylated proteins were found to be involved in several biological processes, including-but not limited to-amino acid metabolism, ribosomal protein synthesis, and fatty acid metabolism. In addition, we identified numerous highly valuable lactate-modified proteins from the literature. Among them, we verified the lactate modification levels of the following two tumor-related proteins and obtained similar results: USP14 and ABCF1. These two modified proteins will be further investigated in our future studies. This paper is the first report on the lactylome of HCC and it provides a reliable foundation for further research on Kla in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Lisina/metabolismo , Proteômica , Lactatos , Transportadores de Cassetes de Ligação de ATP , Ubiquitina Tiolesterase/metabolismo
3.
Glob Chang Biol ; 29(23): 6647-6660, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37846616

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing incidence and geographic extent. The extent to which global climate change affects the incidence of SFTS disease remains obscure. We use an integrated multi-model, multi-scenario framework to assess the impact of global climate change on SFTS disease in China. The spatial distribution of habitat suitability for the tick Haemaphysalis longicornis was predicted by applying a boosted regression tree model under four alternative climate change scenarios (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) for the periods 2030-2039, 2050-2059, and 2080-2089. We incorporate the SFTS cases in the mainland of China from 2010 to 2019 with environmental variables and the projected distribution of H. longicornis into a generalized additive model to explore the current and future spatiotemporal dynamics of SFTS. Our results demonstrate an expanded geographic distribution of H. longicornis toward Northern and Northwestern China, showing a more pronounced change under the RCP8.5 scenario. In contrast, the environmental suitability of H. longicornis is predicted to be reduced in Central and Eastern China. The SFTS incidence in three time periods (2030-2039, 2050-2059, and 2080-2089) is predicted to be increased as compared to the 2010s in the context of various RCPs. A heterogeneous trend across provinces, however, was observed, when an increased incidence in Liaoning and Shandong provinces, while decreased incidence in Henan province is predicted. Notably, we predict possible outbreaks in Xinjiang and Yunnan in the future, where only sporadic cases have been reported previously. These findings highlight the need for tick control and population awareness of SFTS in endemic regions, and enhanced monitoring in potential risk areas.


Assuntos
Ixodidae , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Animais , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , China/epidemiologia , Ecossistema
4.
Biotechnol Bioeng ; 120(12): 3427-3445, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37638646

RESUMO

Structural information can help engineer enzymes. Usually, specific amino acids in particular regions are targeted for functional reconstruction to enhance the catalytic performance, including activity, stereoselectivity, and thermostability. Appropriate selection of target sites is the key to structure-based design, which requires elucidation of the structure-function relationships. Here, we summarize the mutations of residues in different specific regions, including active center, access tunnels, and flexible loops, on fine-tuning the catalytic performance of enzymes, and discuss the effects of altering the local structural environment on the functions. In addition, we keep up with the recent progress of structure-based approaches for enzyme engineering, aiming to provide some guidance on how to take advantage of the structural information.


Assuntos
Aminoácidos , Engenharia de Proteínas , Biocatálise , Catálise , Estabilidade Enzimática
5.
Biotechnol Bioeng ; 120(6): 1521-1530, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36799475

RESUMO

Carbonyl reductase (CR)-catalyzed bioreduction in the organic phase and the neat substrate reaction system is a lasting challenge, placing higher requirements on the performance of enzymes. Protein engineering is an effective method to enhance the properties of enzymes for industrial applications. In the present work, a single point mutation E145A on our previously constructed CR mutant LsCRM3 , coevolved thermostability, and activity. Compared with LsCRM3 , the catalytic efficiency kcat /KM of LsCRM3 -E145A (LsCRM4 ) was increased from 6.6 to 21.9 s-1 mM-1 . Moreover, E145A prolonged the half-life t1/2 at 40°C from 4.1 to 117 h, T m ${T}_{m}$ was increased by 5°C, T 50 30 ${T}_{50}^{30}$ was increased by 14.6°C, and Topt was increased by 15°C. Only 1 g/L of lyophilized Escherichia coli cells expressing LsCRM4 completely reduced up to 600 g/L 2-chloro-1-(3,4-difluorophenyl)ethanone (CFPO) within 13 h at 45°C, yielding the corresponding (1S)-2-chloro-1-(3,4-difluorophenyl)ethanol ((S)-CFPL) in 99.5% eeP , with a space-time yield of 1.0 kg/L d, the substrate to catalyst ratios (S/C) of 600 g/g. Compared with LsCRM3 , the substrate loading was increased by 50%, with the S/C increased by 14 times. Compared with LsCRWT , the substrate loading was increased by 6.5 times. In contrast, LsCRM4 completely converted 600 g/L CFPO within 12 h in the neat substrate bioreaction system.


Assuntos
Mutação Puntual , Engenharia de Proteínas , Catálise , Etanol , Especificidade por Substrato
6.
Proteins ; 90(7): 1413-1424, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35171521

RESUMO

Human immunodeficiency virus (HIV) exploits the sequence variation and structural dynamics of the envelope glycoprotein gp120 to evade the immune attack of neutralization antibodies, contributing to various HIV neutralization phenotypes. Although the HIV neutralization phenotype has been experimentally characterized, the roles of rapid sequence variability and significant structural dynamics of gp120 are not well understood. Here, 45 prefusion gp120 from different HIV strains belong to three tiers of sensitive, moderate, and resistant neutralization phenotype are structurally modeled by homology modeling and then investigated by molecular dynamics (MD) simulations and graph machine learning (ML). Our results show that the structural deviations, population distribution, and conformational flexibility of gp120 are related to the HIV neutralization phenotype. Per-residue dynamics indicate the local regions especially in the second structural elements with high-flexibility, may be responsible for the HIV neutralization phenotype. Moreover, a graph ML model with the attention mechanism was trained to explore inherent representation related to the classification of the HIV neutralization phenotype, further distinguishing the strong related gp120 sequence variation together with structural dynamics in the HIV neutralization phenotype. Our study not only deciphers gp120 sequence variation and structural dynamics in the HIV neutralization phenotype but also explores complex relationships between the sequence, structure, and dynamics of protein by combining MD simulations and ML.


Assuntos
Infecções por HIV , HIV-1 , Antígenos CD4/química , Antígenos CD4/genética , Antígenos CD4/metabolismo , Anticorpos Anti-HIV/genética , Proteína gp120 do Envelope de HIV/genética , HIV-1/química , Humanos , Aprendizado de Máquina , Simulação de Dinâmica Molecular , Testes de Neutralização , Fenótipo
7.
J Viral Hepat ; 29(4): 289-296, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35152517

RESUMO

Renal safety is a critical issue in chronic hepatitis B (CHB) patients receiving long-term entecavir (ETV) or tenofovir disofuroxil fumarate (TDF) therapy. We investigated their effects on estimated glomerular filtration rate (eGFR). Treatment-naive CHB patients receiving ETV or TDF for ≥1 year were recruited. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. We calculated average annual percent change (AAPC) in eGFR using Joinpoint regression. At the beginning of the observation, the ETV group had more unfavorable conditions than the TDF group: lower eGFR and higher FIB-4 and APRI than the TDF group (all p < .001). After 6 years of antiviral therapy, the mean eGFR in the ETV group (n = 1793) was maintained (96.0 at first year to 95.6 ml/min/1.73 m2 at sixth year; AAPC -0.09%; p = .322), whereas that in the TDF group (n = 1240) significantly decreased annually (101.9 at first year to 96.9 ml/min/1.73 m2 at sixth year; AAPC -0.88%; p < .001). Notably, in the TDF group, even patients without diabetes (AAPC -0.80%; p = 0.001) or hypertension (AAPC -0.87%; p = .001) experienced significant decrease in eGFR. Expectably, accompanying diabetes (AAPC -1.59%; p = .011) or hypertension (AAPC -1.00%; p = .002) tended to accelerate eGFR decrease. TDF treatment (odds ratio 1.66, p < .001), along with eGFR<60 ml/min/1.73 m2 , serum albumin<3.5 mg/dl, and hypertension, were independently associated with ongoing renal dysfunction, defined as a negative slope of the mean eGFR change. In conclusion, compared with ETV, long-term TDF treatment induced slow, but progressive renal dysfunction. Although the annual eGFR change by TDF was small, careful monitoring is necessary, especially in patients requiring life-long therapy.


Assuntos
Hepatite B Crônica , Hipertensão , Insuficiência Renal Crônica , Antivirais/efeitos adversos , Feminino , Guanina/análogos & derivados , Vírus da Hepatite B , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Tenofovir/efeitos adversos , Resultado do Tratamento
8.
J Med Virol ; 94(12): 5933-5942, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36030552

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high case fatality rate. Few studies have been performed on bacterial or fungal coinfections or the effect of antibiotic therapy. A retrospective, observational study was performed to assess the prevalence of bacterial and fungal coinfections in patients hospitalized for SFTSV infection. The most commonly involved microorganisms and the effect of antimicrobial therapy were determined by the site and source of infection. A total of 1201 patients hospitalized with SFTSV infection were included; 359 (29.9%) had microbiologically confirmed infections, comprised of 292 with community-acquired infections (CAIs) and 67 with healthcare-associated infections (HAIs). Death was independently associated with HAIs, with a more significant effect than that observed for CAIs. For bacterial infections, only those acquired in hospitals were associated with fatal outcomes, while fungal infection, whether acquired in hospital or community, was related to an increased risk of fatal outcomes. The infections in the respiratory tract and bloodstream were associated with a higher risk of death than that in the urinary tract. Both antibiotic and antifungal treatments were associated with improved survival for CAIs, while for HAIs, only antibiotic therapy was related to improved survival, and no effect from antifungal therapy was observed. Early administration of glucocorticoids was associated with an increased risk of HAIs. The study provided novel clinical and epidemiological data and revealed risk factors, such as bacterial coinfections, fungal coinfections, infection sources, and treatment strategies associated with SFTS deaths/survival. This report might be helpful in curing SFTS and reducing fatal SFTS.


Assuntos
Infecções por Bunyaviridae , Coinfecção , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Antibacterianos/uso terapêutico , Antifúngicos/uso terapêutico , Infecções por Bunyaviridae/epidemiologia , Coinfecção/epidemiologia , Humanos , Estudos Retrospectivos
9.
BMC Geriatr ; 22(1): 384, 2022 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501716

RESUMO

BACKGROUND: Physiological deterioration (aging, poor dental status, and reduced tongue pressure) makes chewing difficult. This study aimed to investigate the chewing patterns of older people with or without dentures, evaluate the textural and masticatory properties of texture-modified radish Kimchi, and investigate the correlation between dental status and tongue pressure. Additionally, differences in the subjective-objective concordance of texture-modified Kimchi were investigated using the preference test. METHODS: This study included 32 Korean women aged between 65 and 85 years. Masticatory behavior was recorded by electromyography, and tongue pressure was measured using the Iowa Oral Performance Instrument. A preference test, with hardness as the relevant textural property, determined the participants' preferences among the test samples (food with a homogeneous structure-radish Kimchi). To assess preference differences, a questionnaire suitable for older people was designed. The preference for cooked radish Kimchi with various blanching times based on overall acceptability and self-reporting of preference was investigated to develop elderly-friendly food. The subjective scores indicated whether the sample (radish Kimchi) was hard or soft based on the chewing ability of the participants. Dental status, muscle activities, and tongue pressure were considered for the food design with optimized texture. The relationship between subject score and mastication properties were examined using multiple regression analysis. RESULTS: The number of chews and chewing time increased with hardness, significantly activating the masseter and temporalis muscles. The evaluation of masseter muscle activity, particularly for level-6 radish Kimchi, showed that older people with complete dentures chewed less actively than those with natural teeth (p < 0.05). The older people with natural teeth (18.94 ± 10.27 kPa) exhibited higher tongue pressure than those with complete dentures (10.81 ± 62.93 kPa), and the difference was statistically significant (p < 0.01). Older people preferred food with familiar tastes and textures. An association was found between the subjective hardness score and the objective hardness level. The perceived hardness intensity was linked to the chewing ability of the participant. Denture wearers exhibited a lower chewing ability, and at level 6, they perceived greater hardness of food than those with natural teeth. CONCLUSIONS: Developing food with a modified texture can bridge the gap between physiological and psychological aspects of food texture; texture-modified radish Kimchi, with limited blanching time, may be favorable for older people.


Assuntos
Mastigação , Língua , Idoso , Idoso de 80 Anos ou mais , Feminino , Alimentos , Humanos , Músculo Masseter , Mastigação/fisiologia , Pressão
10.
Mol Med ; 27(1): 137, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711178

RESUMO

BACKGROUND: Obesity-related nephropathy (ORN) has become one of the leading causes of end-stage renal disease and has tripled over the past decade. Previous studies have demonstrated that decreased reactive oxygen species production may contribute to improving ORN by ameliorating oxidative stress injury. Here, IκB kinase (IKK) was hypothesized to inactivate the deubiquitination activity of cylindromatosis (CYLD) by activating the phosphorylation of CYLD, thus promoting the ubiquitination of NF-E2-related factor 2 (Nrf2) and further aggravating oxidative stress injury of the kidney in ORN. This study was aimed to confirm this hypothesis. METHODS: Haematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Oil Red O staining were performed to assess histopathology. Dihydroethidium (DHE) staining and MDA, SOD, CAT, and GSH-PX assessments were performed to measure reactive oxygen species (ROS) production. Immunohistochemical (IHC) staining, qRT-PCR and/or western blotting were performed to assess the expression of related genes. JC-1 assays were used to measure the mitochondrial membrane potential (ΔΨm) of treated HK-2 cells. Co-immunoprecipitation experiments (Co-IP) were used to analyse the interaction between CYLD and Nrf2 in ORN. RESULTS: ORN in vivo and in vitro models were successfully constructed, and oxidative stress injury was detected in the model tissues and cells. Compared with the control groups, the phosphorylation level of CYLD increased while Nrf2 levels decreased in ORN model cells. An IKK inhibitor reduced lipid deposition, ROS production, CYLD phosphorylation levels and ΔΨm in vitro, which were reversed by knockdown of CYLD. Nrf2 directly bound to CYLD and was ubiquitinated in ORN cells. The proteasome inhibitor MG132 activated the Nrf2/ARE signalling pathway, thereby reversing the promoting effect of CYLD knockdown on oxidative stress. CONCLUSION: IKK inactivates the deubiquitination activity of CYLD by activating the phosphorylation of CYLD, thus promoting the ubiquitination of Nrf2 and further aggravating oxidative stress injury of the kidney in ORN. This observation provided a feasible basis for the treatment of kidney damage caused by ORN.


Assuntos
Enzima Desubiquitinante CYLD/metabolismo , Quinase I-kappa B/metabolismo , Nefropatias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/metabolismo , Amidas/farmacologia , Animais , Linhagem Celular , Enzima Desubiquitinante CYLD/genética , Humanos , Quinase I-kappa B/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/etiologia , Nefropatias/patologia , Metabolismo dos Lipídeos , Lipoproteínas LDL/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Obesidade/complicações , Obesidade/patologia , Estresse Oxidativo , Oxirredutases/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiofenos/farmacologia , Ubiquitinação
11.
Acta Neurol Taiwan ; 30(3): 118-122, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34841508

RESUMO

PURPOSE: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare but treatable autoimmune disorder, characterized by gastrointestinal symptoms, cognitive dysfunction, and central nervous system hyperexcitability. CASE REPORT: Herein, we report a case of an 80-year-old male patient who presented with unexplained diarrhea, weight loss, rapidly progressive dementia, tremors, and myoclonus. His serum tested positive for anti-DPPX antibodies. He was treated with plasma exchange, oral prednisolone, and azathioprine. All his symptoms improved substantially after treatment. CONCLUSION: Early recognition of anti-DPPX encephalitis is important because it can be treated with immunotherapy. To the best of our knowledge, this is the first reported case of anti-DPPX encephalitis in Taiwan.


Assuntos
Demência , Encefalite , Idoso de 80 Anos ou mais , Dipeptidil Peptidases e Tripeptidil Peptidases , Humanos , Masculino , Proteínas do Tecido Nervoso , Canais de Potássio , Taiwan
12.
Infect Immun ; 88(7)2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32284373

RESUMO

Proteus mirabilis, a frequent uropathogen, forms extensive biofilms on catheters that are infamously difficult to treat. To explore the mechanisms of biofilm formation by P. mirabilis, we performed in vivo transposon mutagenesis. A mutant with impaired biofilm formation was isolated. The mutant was found to have Tn5 inserted in the zapD gene, encoding an outer membrane protein of the putative type 1 secretion system ZapBCD. zapBCD and its upstream zapA gene, encoding a protease, constitute an operon under the control of CpxR, a two-component regulator. The cpxR mutant and zapA mutant strains also had a biofilm-forming defect. CpxR positively regulates the promoter activities of zapABCD, cpxP, and cpxR An electrophoretic mobility shift assay revealed that CpxR binds zapA promoter DNA. The loss of zapD reduced CpxR-regulated gene expression of cpxR, zapA, cpxP, and mrpA, the mannose-resistant Proteus-like (MR/P) fimbrial major subunit gene. The restoration of biofilm formation in the zapD mutant with a CpxR-expressing plasmid reinforces the idea that CpxR-mediated gene expression contributes to zapD-involved biofilm formation. In trans expression of zapBCD from a zapBCD-expressing plasmid also reestablished the biofilm formation ability of the cpxR mutant to a certain level. The zapD and cpxR mutants had significantly lower protease activity, adhesion, and autoaggregation ability and production of exopolysaccharides and extracellular DNA (eDNA) than did the wild type. Finally, we identified copper as a signal for CpxR to increase biofilm formation. The loss of cpxR or zapD abolished the copper-mediated biofilm upshift. CpxR was required for copper-induced expression of zapA and cpxR Taken together, these data highlight the important role of CpxR-regulated zapD in biofilm formation and the underlying mechanisms in P. mirabilis.


Assuntos
Proteínas de Bactérias/genética , Biofilmes , Proteínas de Ciclo Celular/genética , Regulação Bacteriana da Expressão Gênica , Infecções por Proteus/microbiologia , Proteus mirabilis/fisiologia , Cobre/metabolismo , Genes Bacterianos , Mutação , Regiões Promotoras Genéticas , Análise de Sequência de DNA
13.
Cancer Cell Int ; 20: 232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32536820

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) results in development of human diseases including hepatocellular carcinoma (HCC). Although several HCC related lncRNAs have been reported, the biological functions of many lncRNAs during the development of HCC remains unknown. METHODS: The expression of ST8SIA6-AS1 was studied by realtime PCR (RT-qPCR) and bioinformatic analysis. The biological functions of ST8SIA6-AS1 was examined by CCK-8 assay and flow cytometry analysis. The target of ST8SIA6-AS1 was analyzed by bioinformatic analysis and validated by dual luciferase reporter assay, western blotting and RT-qPCR. RESULTS: In this study we demonstrated that ST8SIA6-AS1 was an upregulated lncRNA in hepatocellular carcinoma. SiRNA-mediated knockdown of ST8SIA6-AS1 repressed cell proliferation and induced cell apoptosis in HCC cells. Bioinformatic analysis and RT-qPCR further showed that ST8SIA6-AS1 mainly located in cytoplasm. Dual luciferase reporter assay further revealed that ST8SIA6-AS1 interacted with miR-4656 in HCC cells. In addition, HDAC11 was identified as a target gene in HCC cells and ST8SIA6-AS1 could upregulate HDAC11 via sponging miR-4656. Transfection of recombinant HDAC11 partially rescued the inhibition of cell proliferation and increase of cell apoptosis inducing by knockdown of ST8SIA6-AS1. CONCLUSION: In conclusion, our findings suggested that ST8SIA6-AS1 was a novel upregulated lncRNA in HCC and could facilitate cell proliferation and resistance to cell apoptosis via sponging miR-4656 and elevation of HDAC11, which might be a promising biomarker for patients with HCC.

14.
Epilepsy Behav ; 113: 107555, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33242769

RESUMO

BACKGROUND: Long-term treatment with certain antiepileptic drugs may lead to thyroid function disturbances or alterations in bone metabolism; the data on the effects of new antiepileptic drugs on this are limited and conflicting, especially in children with epilepsy. Therefore, the aim of this study was to investigate the effects of levetiracetam and oxcarbazepine on thyroid hormone levels and bone metabolism in children with epilepsy. METHODS: A total of 51 children with new-onset partial epilepsy were selected. They were randomly treated with either levetiracetam (n = 25), or oxcarbazepine (n = 26) monotherapy. Eight of the 51 patients were excluded for failing to take the drug continuously or failing to undergo a regular review. Thus, 43 patients were finally included (levetiracetam: 23 patients, oxcarbazepine: 20 patients). A control group consisting of age- and sex-matched healthy subjects (n = 20) was included for comparison. Serum triiodothyronine, tetraiodothyronine, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, calcium, phosphorus, alkaline phosphatase, osteocalcin, parathyroid hormone, and 25-hydroxyvitamin D levels and bone mineral density values were measured before and at 6 and 12 months after therapy in all groups. RESULTS: At baseline, thyroid hormone levels, bone metabolism index, and bone mineral density values did not differ between the control group and the drug-treated groups. Levetiracetam-treated patients showed no significant changes in thyroid hormone levels, bone metabolism, and bone mineral density during the 12-month follow-up period compared with baseline values. In the oxcarbazepine group, compared to baseline values, serum free thyroxine levels decreased after 12 months of treatment (Z = -3.115, p = 0.002), and after 6 and 12 months of treatment, calcium levels decreased (Z = -3.705, p < 0.001 and Z = -3.884, p < 0.001, respectively) and parathyroid hormone levels increased (Z = -3.698, p < 0.001 and Z = -3.921, p < 0.001, respectively); however, all other parameters did not differ from baseline values. CONCLUSION: Our data show that levetiracetam treatment has no significant effect on thyroid function and bone metabolism in children with epilepsy. Long-term use of oxcarbazepine may reduce serum free thyroxine levels, resulting in impaired thyroid function, and may reduce serum calcium and increase parathyroid hormone levels, leading to bone metabolism disorders.


Assuntos
Anticonvulsivantes/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Epilepsias Parciais/tratamento farmacológico , Levetiracetam/farmacologia , Oxcarbazepina/farmacologia , Tireotropina/sangue , Carbamazepina/uso terapêutico , Criança , Feminino , Humanos , Levetiracetam/uso terapêutico , Estudos Longitudinais , Masculino , Oxcarbazepina/uso terapêutico , Hormônio Paratireóideo , Estudos Prospectivos , Hormônios Tireóideos/sangue
15.
Fish Shellfish Immunol ; 84: 1018-1029, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30395994

RESUMO

Chitinase is an important enzyme for many physiological processes. Mytichitin-1 is a chitinase-like protein in Mytilus coruscus, and its C-terminal 55-AA fragment (mytichitin-CB) is a novel antimicrobial peptide, suggesting a new immune process in which chitinase is involved; mytichtin-1 may have various forms in the different biological processes of M. coruscus. Thus, the study of mytichitin-1 will be helpful for understanding the mechanism of mussel immune biology and the functional diversity of chitinase. In this study, mytichitin-1 was recombinantly expressed with different lengths, full-length mytichtin-1 (rMchi-F) and the N-terminal region (rMchi-N) in Escherichia coli BL21 with codon optimization. The results of SDS-PAGE, Western blotting, and mass spectrometry confirmed that the two forms of mytichitin-1 had been successfully recombinant expressed with a yield of 40 mg purified enzyme per L culture. In addition, the 55-AA fragment of mytichitin-CB was chemically synthesized (sMchi-CB). After purification and oxidation, the functions of the three protein products were analysed, including chitin degradation, chitin binding, and antimicrobial activities. Both rMchi-F and rMchi-N displayed enzymatic activity with the optimum pH of 4.0 and optimum temperature of 40 °C, and rMchi-N showed a stronger activity than rMchi-F. Enzymatic activities of rMchi-F and rMchi-N were stimulated by the metal ions Fe2+, Ba2+, and Na+ and partially inhibited by Cu2+, Ni2+ and Zn2+. rMchi-F, rMchi-N, and sMchi-CB had the ability to combine with colloid chitin. The antimicrobial activities of these proteins were tested against bacteria and fungi, and the results indicated the strongest activity for sMchi-CB and the weakest activity for rMchi-N. Using a prepared anti-rMchi-F polyclonal antibody, immunohistochemistry and immunoprecipitation were performed and the results revealed the location of mytichitin-1 in mantle, digestive gland and blood cells. In addition, two forms of mytichitin-1, mytichitin-CB (6 kD) and full-length mytichitin-1 (48 kD), were detected, and a 35 kD protein was identified as the third form of mytichitin-1, existing in various tissues of M. coruscus. These findings suggest that mytichitin-1 may play different roles, with at least three forms, in different M. coruscus tissues.


Assuntos
Quitina/genética , Imunidade Inata/genética , Mytilus/genética , Mytilus/imunologia , Sequência de Aminoácidos , Animais , Antibacterianos/análise , Sequência de Bases , Quitina/química , Quitina/metabolismo , Escherichia coli/genética , Microrganismos Geneticamente Modificados/genética , Especificidade de Órgãos
17.
Sleep Breath ; 21(2): 487-495, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28210922

RESUMO

STUDY OBJECTIVES: The aim of this study is to investigate changes in regional cerebral blood flow (rCBF) in awake people with untreated severe obstructive sleep apnoea (OSAs) compared with good sleepers (GSs). DESIGN: Arterial spin labelling perfusion imaging was used to quantify cerebral perfusion based on resting-state functional magnetic resonance imaging (MRI). SETTING: Lying supine in a 3.0-T magnetic resonance imaging scanner in the night was done. PARTICIPANTS: Included in this study were 30 subjects with OSA (males; mean age 38.4 years, range 25-55) and 30 controls (males; mean age: 38.3 years, range 26-52) matched for age and years of education. RESULTS: Compared with GSs, participants with severe OSA had reduced rCBF in the left cerebellum posterior lobe, left temporal lobe, right medial frontal gyrus, and bilateral parahippocampal gyrus and increased rCBF in the bilateral superior frontal gyrus. The lower mean CBF in the right parahippocampal gyrus exhibited a significant positive correlation with arousal index (r = 0.365, P = 0.047). The increased mean CBF in the left superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.422, P = 0.020), and the increased mean CBF in the right superior frontal gyrus exhibited a significant positive correlation with the longest apnoea time (r = 0.447, P = 0.013). CONCLUSIONS: Our results show that the altered rCBF pattern in the left cerebellum posterior lobe, left temporal lobe, left medial frontal gyrus, bilateral parahippocampal gyrus and superior frontal gyrus in patients have with severe OSA. The arterial spin labelling perfusion imaging method is a useful non-invasive imaging tool for detection of early changes in the regional cerebral blood flow in patients with OSA.


Assuntos
Encéfalo/irrigação sanguínea , Espectroscopia de Ressonância de Spin Eletrônica , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Marcadores de Spin , Adulto , Dominância Cerebral/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia
18.
J Shoulder Elbow Surg ; 26(5): 895-901, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28131678

RESUMO

BACKGROUND: Range of motion (ROM) is a clinically important parameter in evaluating joint function. However, dynamic evaluation to determine the quality of the arm motion using digitized measurement is often overlooked during clinical assessment. We evaluated the accuracy of Kinect v2 (Microsoft, Redmond, WA, USA) as a digital tool for measuring shoulder ROM objectively and proposed a concept of motion smoothness reflecting the quality of arm motion. METHODS: Ten male participants were included in a 2-stage experiment. First, shoulder ROM was measured in 4 static poses (flexion, abduction, external rotation, and internal rotation) with Kinect v2, a 3-dimensional (3D) motion analysis system, and goniometry. Second, participants performed a point-to-point arm motion as naturally as possible. Kinematic data were collected with Kinect v2 and the 3D motion analysis system and then postprocessed to acquire parameters related to motion smoothness, including peak to mean velocity ratio, acceleration to movement time ratio, and number of peaks. RESULTS: Kinect v2 resulted in very good agreement of ROM measurement (r > 0.9) with the 3D motion analysis (95% limits of agreement < ±8°) compared with goniometry (95% limits of agreement < ±10°). Kinect v2 also showed a good correlation and agreement of measurement of motion quality parameters compared with the 3D motion analysis (peak to mean velocity ratio, acceleration to movement time ratio, and number of peaks: r = 0.769, discrepancy = ±0.1; r = 0.922, discrepancy = ±5%; and mean = 1 ± 0, respectively). CONCLUSIONS: We show that Kinect v2 can be used as a reliable tool to measure shoulder ROM and arm motion smoothness.


Assuntos
Artrometria Articular/instrumentação , Amplitude de Movimento Articular/fisiologia , Articulação do Ombro/fisiologia , Software , Adulto , Artrometria Articular/métodos , Fenômenos Biomecânicos/fisiologia , Humanos , Masculino
19.
World J Surg Oncol ; 14(1): 205, 2016 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-27487779

RESUMO

BACKGROUND: Extramedullary plasmacytoma is a rare plasma cell neoplasm within soft tissue and without bone marrow involvement or other systemic characteristics of multiple myeloma. Primary pulmonary plasmacytoma is a rare type of extramedullary plasmacytoma. CASE PRESENTATION: A 48-year-old male with a tumor in the right middle ear was referred to our hospital. A routine chest X-ray was arranged and showed enlargement of the left lung hilum. His bilateral breathing sounded clear. A chest CT scan revealed a well-circumscribed mass. Pathological biopsy yielded a diagnosis of isolated pulmonary plasmacytoma. CONCLUSIONS: This is the first presentation of primary pulmonary plasmacytoma with a solitary pulmonary nodule and no lymph node involvement.


Assuntos
Neoplasias Pulmonares/patologia , Plasmocitoma/patologia , Nódulo Pulmonar Solitário/patologia , Antineoplásicos/uso terapêutico , Biópsia por Agulha , Exame de Medula Óssea , Broncoscopia , Intervalo Livre de Doença , Neoplasias da Orelha/diagnóstico por imagem , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Orelha Média/diagnóstico por imagem , Orelha Média/patologia , Orelha Média/cirurgia , Seguimentos , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/tratamento farmacológico , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/tratamento farmacológico , Tomografia Computadorizada por Raios X
20.
J Assist Reprod Genet ; 33(2): 181-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26584823

RESUMO

PURPOSE: The purpose of this research was to study the association between the single nucleotide polymorphisms (SNPs) of the tektin-t gene and idiopathic asthenozoospermia. METHODS: We conducted sequence analyses of the tektin-t gene in 104 idiopathic asthenozoospermia and 102 fertile men with normospermic parameters in Sichuan, China. RESULTS: In this study, we found that allele 136 T (odds ratio [OR] 1.745, 95 % confidence interval [CI] 1.146-2.655, P = 0.009) was significantly increased in idiopathic asthenozoospermic patients compared with fertile men. This mutation substitutes a highly conserved arginine at position 46 to cysteine. Moreover, PolyPhen-2 analysis predicted that this variant was "probably damaging". In addition, a novel heterozygous mutation, R207H (c.620G >A), was detected in five asthenozoospermic patients, while there was no detection of this genotype among the fertile candidates, indicating that the mutation was located within a conserved domain predicted by PolyPhen-2 analysis as "probably damaging" to the protein. CONCLUSIONS: These results suggested that tektin-t variants (Arg/Cys + Cys/Cys) were probably one of the high risk genetic factors for idiopathic asthenozoospermia among males in Sichuan, China, while the R207H polymorphism may be associated with idiopathic asthenozoospermia risk.


Assuntos
Astenozoospermia/genética , Estudos de Associação Genética , Proteínas dos Microtúbulos/genética , Motilidade dos Espermatozoides/genética , Adulto , Alelos , Astenozoospermia/patologia , China , Genótipo , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Espermatozoides/patologia
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