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We give exact and asymptotic counting results for the number of galled networks and reticulation-visible networks with few reticulation vertices. Our results are obtained with the component graph method, which was introduced by L. Zhang and his coauthors, and generating function techniques. For galled networks, we in addition use analytic combinatorics. Moreover, in an appendix, we consider maximally reticulated reticulation-visible networks and derive their number, too.
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Modelos Genéticos , Filogenia , Conceitos Matemáticos , AnimaisRESUMO
OBJECTIVES: RA damages the joints and increases the risks of total knee replacement (TKR) and total hip replacement (THR). However, the benefits of biologics in preventing TKR or THR remain unclear. METHODS: This retrospective nationwide study used the 2000-2013 claims-based National Health Insurance dataset. Biologics are reimbursed for refractory cases. The risks of TKR and THR in the biologic cohort were compared with those of an age- and sex-matched csDMARD cohort. A multivariate Cox regression model was used to investigate the benefits of bDMARDs for TKR and THR. RESULTS: TKR was performed in 5979 biologic cases and 11 958 matched controls, of which 249 (4.16%) and 871 (7.28%) cases received TKR, respectively. THR was performed in 6245 biologic cases and 12 490 matched controls, of which 159 (2.55%) and 516 (4.13%) cases had THR, respectively. The biologic cohort had significantly lower incidence rates of TKR (11.73 vs 16.33/1000 person-years, P < 0.001) and THR (7.09 vs 9.16/1000 person-years, P < 0.001). After adjustment for confounding factors, the regular bDMARD subgroup (average dose >0.95 defined daily dose/day) had significantly lower risks of TKR (aHR: 0.55, 95% CI: 0.38, 0.81) and THR (aHR: 0.63, 95% CI: 0.40, 0.98). Those without MTX use, with steroid use, with biologic switch, and overlapping antiphospholipid syndrome had significantly higher risks of TKR and THR. CONCLUSIONS: Compared with the csDMARD cohort, the risks of TKR and THR in the bDMARD cohort were the same as those in the low-to-moderate dose subgroups and significantly lower in those with regular bDMARD use.
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Artrite Reumatoide , Artroplastia de Quadril , Artroplastia do Joelho , Produtos Biológicos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/cirurgia , Produtos Biológicos/uso terapêutico , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder with systemic inflammation and may be induced by oxidative stress that affects an inflamed joint. Our objectives were to examine isotypes of autoantibodies against 4-hydroxy-2-nonenal (HNE) modifications in RA and associate them with increased levels of autoantibodies in RA patients. METHODS: Serum samples from 155 female patients [60 with RA, 35 with osteoarthritis (OA), and 60 healthy controls (HCs)] were obtained. Four novel differential HNE-modified peptide adducts, complement factor H (CFAH)1211-1230, haptoglobin (HPT)78-108, immunoglobulin (Ig) kappa chain C region (IGKC)2-19, and prothrombin (THRB)328-345, were re-analyzed using tandem mass spectrometric (MS/MS) spectra (ProteomeXchange: PXD004546) from RA patients vs. HCs. Further, we determined serum protein levels of CFAH, HPT, IGKC and THRB, HNE-protein adducts, and autoantibodies against unmodified and HNE-modified peptides. Significant correlations and odds ratios (ORs) were calculated. RESULTS: Levels of HPT in RA patients were greatly higher than the levels in HCs. Levels of HNE-protein adducts and autoantibodies in RA patients were significantly greater than those of HCs. IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgM anti-IGKC2-19 HNE may be considered as diagnostic biomarkers for RA. Importantly, elevated levels of IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 were positively correlated with the disease activity score in 28 joints for C-reactive protein (DAS28-CRP). Further, the ORs of RA development through IgM anti-HPT78-108 HNE (OR 5.235, p < 0.001), IgM anti-IGKC2-19 (OR 12.655, p < 0.001), and IgG anti-THRB328-345 (OR 5.761, p < 0.001) showed an increased risk. Lastly, we incorporated three machine learning models to differentiate RA from HC and OA, and performed feature selection to determine discriminative features. Experimental results showed that our proposed method achieved an area under the receiver operating characteristic curve of 0.92, which demonstrated that our selected autoantibodies combined with machine learning can efficiently detect RA. CONCLUSIONS: This study discovered that some IgG- and IgM-NAAs and anti-HNE M-NAAs may be correlated with inflammation and disease activity in RA. Moreover, our findings suggested that IgM anti-HPT78-108 HNE, IgM anti-IGKC2-19, and IgG anti-THRB328-345 may play heavy roles in RA development.
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Artrite Reumatoide , Autoanticorpos , Aldeídos , Artrite Reumatoide/diagnóstico , Feminino , Humanos , Peptídeos , Espectrometria de Massas em TandemRESUMO
PURPOSE: Patients with obstructive sleep apnea (OSA) have a higher risk of Behçet's disease (BD) and Sjögren syndrome (SS). However, the bidirectional relationship between these autoimmune diseases and OSA is unclear. We investigated the relationship between autoimmune diseases (SS and BD) and OSA. METHODS: SS and BD patients were identified through the Taiwan National Health Insurance Research Database from 2002 to 2012. Patients with SS or BD were matched according to age and sex with a control group in a ratio of 1:4. The study included 12,926 patients with SS and 51,704 non-SS controls. Similarly, 1221 patients with BD were matched with 4884 non-BD controls. We used a Cox regression model, stratified by age, gender, and comorbidities, to assess the risk of OSA. RESULTS: OSA was diagnosed in 0.61% of the SS cohort and 1.23% of the BD cohort. The higher overall risk for OSA was observed significantly in patients with SS than in controls (adjusted hazard ratio [HR] = 2.48, 95% confidence interval [CI] = 1.89-3.24). The higher risk was also observed significantly in BD patients than in controls (HR = 1.99, 95% CI = 1.06-3.72). Furthermore, men with SS or BD exhibited HR of 2.62 (95% CI 1.89 to 3.62) and 6.40 (95% CI 2.96 to 13.84) for developing OSA, respectively. CONCLUSION: Risk of OSA was significantly elevated in SS or BD patients compared with controls. Further study is warranted to elucidate underlying mechanisms.
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Síndrome de Behçet/epidemiologia , Síndrome de Sjogren/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan/epidemiologiaRESUMO
OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are susceptible to herpes simplex virus (HSV) infection, which occasionally leads to severe complications including meningoencephalitis and keratitis. However, few attempts to analyse the associated incidence and risk factors have been made. METHODS: We enrolled patients with SLE recorded between 1997 and 2012 and compared the incidence rate (IR) of severe HSV infection, including meningoencephalitis, septicaemia, ocular and visceral involvement, and other specific complications demanding hospitalisation, with that of a non-SLE cohort. A Cox multivariate proportional hazards model was applied to analyse the risk factors of severe HSV infection in patients with SLE. RESULTS: A total of 122 520 subjects (24 504 patients with SLE and 98 016 age-matched and sex-matched non-SLE controls) were included, and a higher IR of severe HSV infection was revealed in the SLE group (IR ratio=3.93, p<0.001). In patients with SLE, previous oral and genital infection (HR=2.29, p=0.049), intravenous steroid pulse therapy (HR=5.32, p<0.001) and daily oral dose of over 7.5 mg of prednisolone (HR=1.59, p=0.024) were independent risk factors for severe HSV infection, whereas age of ≤18 (HR=0.45, p=0.029) was a protective factor. CONCLUSIONS: Patients with SLE are at higher risk of severe HSV infection, and related risk factors include being older than 18 years, having a history of HSV mucocutaneous infection, recent receipt of steroid pulse therapy and a daily oral dose of steroid over 7.5 mg prednisolone.
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Herpes Simples/epidemiologia , Lúpus Eritematoso Sistêmico/virologia , Simplexvirus , Adulto , Anti-Inflamatórios/efeitos adversos , Feminino , Herpes Simples/etiologia , Humanos , Incidência , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
Objectives: Previous studies have shown myasthenia gravis (MG) and autoimmune rheumatic diseases (ARDs) share common pathogenetic mechanisms. Therefore, the present study investigated the possible relationship between MG and ARDs. Methods: We analysed Taiwanese medical data from the Registry of Catastrophic Illness and identified patients with MG. From the entire general population data of the National Health Insurance Research Database, we randomly selected a comparison cohort that was frequency-matched by age (in 5-year increments), sex, and index date. We analysed the risk of ARDs by using a Cox proportional hazards regression model stratified by sex, age and treatment. Results: In the present study, we enrolled 6478 patients with MG (58.03% women; mean age, 50.55 years) and 25 912 age- and sex-matched controls. The risk of total ARDs was 6.25 times higher in the MG cohort than in the non-MG cohort after adjustment for age and sex. Furthermore, the MG cohort was associated with a significantly higher risk of primary SS (pSS), SLE and other ARD types (adjusted hazard ratios: 15.84 [95% CI: 8.39, 23.91]; 11.32 [95% CI: 5.04, 25.429]; and 4.07 [95% CI: 1.31, 12.62], respectively). The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE (adjusted hazard ratios: 4.41; 15.06; and 23.68, respectively). Conclusion: The present nationwide cohort study revealed an association between MG and incident ARDs. The MG cohort who underwent thymectomy had an increased risk of RA, pSS and SLE. Future studies are needed to elucidate the underlying pathogenesis and to translate this into clinical therapeutic options.
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Doenças Autoimunes/epidemiologia , Miastenia Gravis/cirurgia , Complicações Pós-Operatórias/epidemiologia , Doenças Reumáticas/epidemiologia , Timectomia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/etiologia , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Modelos de Riscos Proporcionais , Sistema de Registros , Doenças Reumáticas/etiologia , Fatores de Risco , Taiwan/epidemiologia , Adulto JovemRESUMO
The objective of this study was to identify novel acetylation (Ac) modifications of the C1-inhibitor (C1-INH) and explain the association of the levels of autoantibodies against acetylated C1-INH peptides with the risk of developing systemic lupus erythematosus (SLE). Ac modifications of the C1-INH were identified and validated through in-gel digestion, nano-liquid chromatography-tandem mass spectrometry, immunoprecipitation, and Western blotting by using serum protein samples obtained from patients with SLE and age-matched healthy controls (HCs). In addition, the levels of serum C1-INH, Ac-protein adducts, and autoantibodies against unmodified and acetylated C1-INH peptides were measured. C1-INH levels in patients with SLE were significantly lower than those in HCs by 1.53-fold (p = 0.0008); however, Ac-protein adduct concentrations in patients with SLE were significantly higher than those in HCs by 1.35-fold (p = 0.0009). Moreover, immunoglobulin M (IgM) anti-C1-INH367-385 Ac and IgA anti-C1-INH367-385 Ac levels in patients with SLE were significantly lower than those in HCs. The low levels of IgM anti-C1-INH367-385 (odds ratio [OR] = 4.725, p < 0.001), IgM anti-C1-INH367-385 Ac (OR = 4.089, p = 0.001), and IgA anti-C1-INH367-385 Ac (OR = 5.566, p < 0.001) indicated increased risks for the development of SLE compared with HCs.
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Proteína Inibidora do Complemento C1/imunologia , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Peptídeos/imunologia , Acetilação , Sequência de Aminoácidos , Autoanticorpos/imunologia , Autoantígenos/imunologia , Proteína Inibidora do Complemento C1/química , Proteína Inibidora do Complemento C1/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/sangue , Peso Molecular , Peptídeos/química , Ligação Proteica/imunologia , Curva ROC , TaiwanRESUMO
BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is a valuable life support in acute respiratory distress syndrome (ARDS) in adult patients. However, the success of VV-ECMO is known to be influenced by the baseline settings of mechanical ventilation (MV) before its institution. This study was aimed at identifying the baseline ventilator parameters which were independently associated with hospital mortality in non-trauma patients receiving VV-ECMO for severe ARDS. METHODS: This retrospective study included 106 non-trauma patients (mean age: 53 years) who received VV-ECMO for ARDS in a single medical center from 2007 to 2016. The indication of VV-ECMO was severe hypoxemia (PaO2/ FiO2 ratio < 70 mmHg) under pressure-controlled MV with peak inspiratory pressure (PIP) > 35 cmH2O, positive end-expiratory pressure (PEEP) > 5 cmH2O, and FiO2 > 0.8. Important demographic and clinical data before and during VV-ECMO were collected for analysis of hospital mortality. RESULTS: The causes of ARDS were bacterial pneumonia (n = 41), viral pneumonia (n = 24), aspiration pneumonitis (n = 3), and others (n = 38). The median duration of MV before ECMO institution was 3 days and the overall hospital mortality was 53% (n = 56). The medians of PaO2/ FiO2 ratio, PIP, PEEP, and dynamic pulmonary compliance (PCdyn) at the beginning of MV were 84 mmHg, 32 cmH2O, 10 cmH2O, and 21 mL/cmH2O, respectively. However, before the beginning of VV-ECMO, the medians of PaO2/ FiO2 ratio, PIP, PEEP, and PCdyn became 69 mmHg, 36 cmH2O, 14 cmH2O, and 19 mL/cmH2O, respectively. The escalation of PIP and the declines in PaO2/ FiO2 ratio and PCdyn were significantly correlated with the duration of MV before ECMO institution. Finally, the duration of MV (OR: 1.184, 95% CI: 1.079-1.565, p < 0.001) was found to be the only baseline ventilator parameter that independently affected the hospital mortality in these ECMO-treated patients. CONCLUSION: Since the duration of MV before ECMO institution was strongly correlated to the outcome of adult respiratory ECMO, medical centers are suggested to find a suitable prognosticating tool to determine the starting point of respiratory ECMO among their candidates with different duration of MV. TRIAL REGISTRATION: This study reported a health care intervention on human participants and was retrospectively registered. The Chang Gung Medical Foundation Institutional Review Board approved the study (no. 201601483B0 ) on November 23, 2016. All of the data were extracted from December 1, 2016, to January 31, 2017.
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Oxigenação por Membrana Extracorpórea , Mortalidade Hospitalar , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório/terapia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/complicações , Pneumonia Aspirativa/terapia , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Respiração com Pressão Positiva , Prognóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/mortalidade , Estudos RetrospectivosRESUMO
The aim of this study was to examine oxidative stress and low level of α-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, α-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Our study suggests that elevated HNE-protein adduct, oxidative stress, level (odds ratio (OR) 4.877, p = 0.003), lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.
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Imunoglobulina G/metabolismo , Síndrome de Sjogren/metabolismo , alfa 1-Antitripsina/metabolismo , Aldeídos/metabolismo , Autoanticorpos/metabolismo , Feminino , Humanos , Estresse Oxidativo/fisiologiaRESUMO
OBJECTIVES: To identify the incidence rate (IR) and risk factors of osteoporotic fractures (OFs) among systemic sclerosis (SSc) patients. METHODS: A cohort study was conducted using the Taiwan National Health Insurance database. Patients with SSc and respective age- and gender-matched controls without SSc were enrolled. The primary endpoint was the first occurrence of OF. The Cox proportional hazard model was used to investigate the risk factor of OFs in the SSc cohort. RESULTS: Among 1712 SSc patients (77.8% female, mean age 50.3â years) with a median follow-up of 5.2â years, 54 patients developed vertebral fractures, 17 patients developed hip fractures, and 7 patients developed radius fractures (IR: 6.99, 2.18 and 0.90 per 1000 person-years, respectively). Compared with the controls, the incidence rate ratios (IRRs) (95% CIs) among SSc patients were 1.78 (1.30 to 2.39, p<0.001) for vertebral fractures and 1.89 (1.05 to 3.22, p=0.026) for hip fractures. The IRRs for overall OFs were 1.74 (1.32 to 2.27, p<0.001) for women and 1.06 (0.33 to 2.66, p=0.856) for men. The SSc patients experienced hip fractures at a younger age (67.2 vs 75.2 years, p=0.005), and had a higher 1-year mortality rate (13% vs 3%, p=0.006) of vertebral fractures than did the controls. Multivariable Cox regression analyses indicated that older age, being female, using daily prednisolone equivalent to >7.5â mg, and bowel dysmotility treated with intravenous metoclopramide are associated with OF. CONCLUSIONS: SSc patients had a high IR of vertebral and hip fractures, especially those who were female, older, used a high dose of corticosteroid or experienced bowel dysmotility.
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Fraturas do Quadril/epidemiologia , Fraturas por Osteoporose/epidemiologia , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Taiwan/epidemiologiaRESUMO
UNLABELLED: This is a prospective study using non-invasive electrical cardiometry to measure hemodynamic changes during surgical ligation of patent ductus arteriosus (PDA) in very low birth weight (VLBW, ≤1500 g) infants. The aims of this study were to examine hemodynamic aberration caused by abrupt closure of a ductal shunting and to define factors that affect hemodynamic changes. Simultaneous measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) were collected at ten time points: 1 h prior to anesthesia, at the beginning of anesthesia, starting of surgery, immediately after PDA being ligated, and 1 h followed by 6, 12, 18, 24, and 48 h after the surgery. Thirty infants with gestational age of 27.7 ± 2.0 weeks and birth weight of 929 ± 280 g were studied. Upon sudden termination of ductal shunting, there was a significant decline in CO to 73 % of presurgery baseline. The deterioration in CO was associated with a decreased SV rather than HR. At the same time, there was an increase of SVR following ductal ligation. Magnitude of CO and SV reduction were higher in smaller infants (≤1 kg), and recovery was to a lesser degree in infants with more severe PDA. CONCLUSION: Reduced stroke volume and elevated vascular resistance contribute to the major hemodynamic aberrations in VLBW infants receiving PDA ligation surgery.
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Cardiografia de Impedância/métodos , Permeabilidade do Canal Arterial/fisiopatologia , Hemodinâmica/fisiologia , Procedimentos Cirúrgicos Cardíacos , Permeabilidade do Canal Arterial/cirurgia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Ligadura , Masculino , Estudos ProspectivosRESUMO
BACKGROUND: Orthoses play an important role in the conservative treatment of hallux valgus (HV) with different therapeutic effects. In this study, a new HV orthosis was developed using three-dimensional (3D) printing technology. In addition, its kinematic effect was evaluated using motion analysis. METHODS: Seventeen participants with an HV angle of >20° were included in the study. The first metatarsophalangeal abduction angle before and after the orthosis was measured statically. Subsequently, dynamic first metatarsophalangeal abduction, dorsiflexion angle and ground reaction force with and without the orthosis were recorded and calculated during walking using a Vicon motion analysis system and force plates. The patients' comfort scales were determined after the motion analysis. RESULTS: The angular corrections of the orthosis in the first metatarsophalangeal abduction were 14.6° and 6.3° under static and dynamic conditions, respectively. Reduced hallux dorsiflexion was observed with the orthosis in the early stance phase. However, no significant changes in ground reaction forces were observed. CONCLUSION: The results of our study confirm the potential of the 3D-printed HV orthosis in the static and dynamic correction of deformities while ensuring patient comfort with minimal impact on hallux kinematics, suggesting the potential of our design for long-term use.
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Hallux Valgus , Impressão Tridimensional , Humanos , Hallux Valgus/terapia , Hallux Valgus/fisiopatologia , Fenômenos Biomecânicos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Órtoses do Pé , Aparelhos OrtopédicosRESUMO
The discovery of SARS-CoV-2 RNA in the periodontal tissues of patients who tested positive for COVID-19, 24 days post the initial symptom onset, indicates the oral cavity could serve as a viral reservoir. This research aims to investigate the antiviral capabilities of Ovatodiolide, introducing a novel periodontal ligament organoid model for the study of SARS-CoV-2. We have successfully established a reliable and expandable organoid culture from the human periodontal ligament, showcasing characteristics typical of epithelial stem cells. This organoid model enables us to delve into the lesser-known aspects of dental epithelial stem cell biology and their interactions with viruses and oral tissues. We conducted a series of in vitro and ex vivo studies to examine the inhibitory impacts of Ova on SARS-CoV-2. Our findings indicate that Ovatodiolide molecules can bind effectively to the NRP1 active domain. Our study identifies potential interaction sites for Ovatodiolide (OVA) within the b1 domain of the NRP1 receptor. We generated point mutations at this site, resulting in three variants: Y25A, T44A, and a double mutation Y25A/T44A. While these mutations did not alter the binding activity of the spike protein, they did impact the concentration of OVA required for inhibition. The inhibitory concentrations for these variants are 15 µM for Y25A, 15.2 µM for T44A, and 25 µM for the double mutant Y25A/T44A. In addition, in vitro inhibition experiments demonstrate that the EC50 of Ova against the main protease (Mpro) of the SARS-CoV-2 virus is 7.316 µM. Our in vitro studies and the use of the periodontal ligament organoid model highlight Ovatodiolide's potential as a small molecule therapeutic agent that impedes the virus's ability to bind to the Neuropilin-1 receptor on host cells. The research uncovers various pathways and biochemical strategies through which Ovatodiolide may function as an effective antiviral small molecule drug.
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Tratamento Farmacológico da COVID-19 , Neuropilina-1 , Organoides , Ligamento Periodontal , SARS-CoV-2 , Ligamento Periodontal/metabolismo , Ligamento Periodontal/citologia , Ligamento Periodontal/virologia , Humanos , Organoides/virologia , Organoides/metabolismo , Organoides/efeitos dos fármacos , Neuropilina-1/metabolismo , SARS-CoV-2/efeitos dos fármacos , Antivirais/farmacologia , COVID-19/metabolismo , COVID-19/virologia , Diterpenos/farmacologiaRESUMO
Metal nanoparticles (M-NPs) have garnered significant attention due to their unique properties, driving diverse applications across packaging, biomedicine, electronics, and environmental remediation. However, the potential health risks associated with M-NPs must not be disregarded. M-NPs' ability to accumulate in organs and traverse the blood-brain barrier poses potential health threats to animals, humans, and the environment. The interaction between M-NPs and various cellular components, including DNA, multiple proteins, and mitochondria, triggers the production of reactive oxygen species (ROS), influencing several cellular activities. These interactions have been linked to various effects, such as protein alterations, the buildup of M-NPs in the Golgi apparatus, heightened lysosomal hydrolases, mitochondrial dysfunction, apoptosis, cell membrane impairment, cytoplasmic disruption, and fluctuations in ATP levels. Despite the evident advantages M-NPs offer in diverse applications, gaps in understanding their biocompatibility and toxicity necessitate further research. This review provides an updated assessment of M-NPs' pros and cons across different applications, emphasizing associated hazards and potential toxicity. To ensure the responsible and safe use of M-NPs, comprehensive research is conducted to fully grasp the potential impact of these nanoparticles on both human health and the environment. By delving into their intricate interactions with biological systems, we can navigate the delicate balance between harnessing the benefits of M-NPs and minimizing potential risks. Further exploration will pave the way for informed decision-making, leading to the conscientious development of these nanomaterials and safeguarding the well-being of society and the environment.
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Nanopartículas Metálicas , Nanopartículas , Animais , Humanos , Estresse Oxidativo , Nanopartículas Metálicas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismoRESUMO
Rheumatoid arthritis (RA), a chronic inflammatory condition that affects persons between the ages of 20 and 40, causes synovium inflammation, cartilage loss, and joint discomfort as some of its symptoms. Diagnostic techniques for RA have traditionally been split into two main categories: imaging and serological tests. However, significant issues are associated with both of these methods. Imaging methods are costly and only helpful in people with obvious symptoms, while serological assays are time-consuming and require specialist knowledge. The drawbacks of these traditional techniques have led to the development of novel diagnostic approaches. The unique properties of nanomaterials make them well-suited as biosensors. Their compact dimensions are frequently cited for their outstanding performance, and their positive impact on the signal-to-noise ratio accounts for their capacity to detect biomarkers at low detection limits, with excellent repeatability and a robust dynamic range. In this review, we discuss the use of nanomaterials in RA theranostics. Scientists have recently synthesized, characterized, and modified nanomaterials and biomarkers commonly used to enhance RA diagnosis and therapy capabilities. We hope to provide scientists with the promising potential that nanomaterials hold for future theranostics and offer suggestions on further improving nanomaterials as biosensors, particularly for detecting autoimmune disorders.
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OBJECTIVES: This study aimed to identify the risk factors for mortality and the impact of dialysis modalities on the survival in SLE patients with end-stage renal disease (ESRD). METHODS: This retrospective nationwide population-based study using the National Health Insurance Research Database in Taiwan collected data from 1073 SLE ESRD patients starting maintenance dialysis between March 1997 and December 2006. A multivariate Cox regression hazard model was applied to identify factors predicting mortality in cohorts using different dialysis modalities and the impact of dialysis modalities on the survival outcome of these patients of both genders. RESULTS: The major threat to SLE patients on maintenance dialysis was infections. For SLE patients undergoing regular haemodialysis (HD), age, male sex, and high or absence of daily steroid dosing were predictive of higher mortality. For those undergoing regular peritoneal dialysis (PD), age and high daily steroid dosing were the predictive factors. After adjusting confounding factors, male patients with HD had a significantly poorer outcome than the counterpart with PD or female patients with HD. There was no survival difference among female SLE patients with different dialysis modalities. CONCLUSION: No underlying comorbidities were identified to increase the mortality of patients receiving particular dialysis modalities after correcting for age and steroid factors. There was no impact of different dialysis modalities on survival of female SLE patients. However, male SLE patients seemed susceptible to fatal events complicated by HD, which led to an inferior survival rate.
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Falência Renal Crônica/mortalidade , Lúpus Eritematoso Sistêmico/mortalidade , Diálise Renal/mortalidade , Adulto , Idoso , Bases de Dados Factuais , Feminino , Humanos , Falência Renal Crônica/terapia , Lúpus Eritematoso Sistêmico/terapia , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida , Taiwan/epidemiologia , Resultado do TratamentoRESUMO
An effective early diagnosis is important for rheumatoid arthritis (RA) management. This study reveals a novel RA detection method using bacteriorhodopsin as a photoelectric transducer, a light-driven proton pump in purple membranes (PMs). It was devised by covalently conjugating a PM monolayer-coated electrode with a citrullinated-inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3)542-556 peptide that recognizes the serum RA-associated autoantibodies. The direct serum coating decreased the photocurrents in the biosensor, with the reduction in the photocurrent caused by coating with an RA-patient serum that is significantly larger than that with a healthy-control serum (38.1% vs. 20.2%). The difference in the reduction in the photocurrent between those two serum groups widened after the serum-coated biosensor was further labeled with gold nanoparticle (AuNP)-conjugated anti-IgA (anti-IgA-AuNP) (53.6% vs. 30.6%). Both atomic force microscopic (AFM) and Raman analyses confirmed the sequential peptide, serum, and anti-IgA-AuNP coatings on the PM-coated substrates. The reductions in the photocurrent measured in both the serum and anti-IgA-AuNPs coating steps correlated well with the results using commercial enzyme-linked immunosorbent assay kits (Spearman rho = 0.805 and 0.787, respectively), with both a sensitivity and specificity close to 100% in both steps. It was shown that an RA diagnosis can be performed in either a single- or two-step mode using the developed biosensor.
Assuntos
Artrite Reumatoide , Bacteriorodopsinas , Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Ouro , Artrite Reumatoide/diagnóstico , Peptídeos , Ensaio de Imunoadsorção EnzimáticaRESUMO
BACKGROUD/AIM: Ocular involvement in systemic lupus erythematosus (SLE) is often primarily recognised by ophthalmologists rather than internists. This study aims to investigate the incidence and risk factors for the occurrence of posterior ocular ischaemic events (OIE), including retinal vein occlusion (RVO), retinal artery occlusion (RAO) and ischaemic optic neuropathy (ION), in patients with SLE. METHODS: A national database in Taiwan was used to identify 24 472 patients newly diagnosed with SLE and 244 720 age-matched and sex-matched controls between 1997 and 2012. New occurrences of OIE and confounding factors were recorded. The Kaplan-Meier method was used to compare the risk of OIE between the two groups. Fixed effect models were applied to evaluate the risk factors for OIE. RESULTS: The mean age was 36.24±15.82 years and women accounted for 88.4%. Patients with SLE had significantly increased risk of overall OIE (HR 3.89, 95% CI 3.36 to 4.50, p<0.001) as well as each OIE subtype. End-stage renal disease (ESRD; HR 2.91, 95% CI 2.05 to 4.14, p<0.001), hypertension (HR 1.77, 95% CI 1.21 to 2.58, p=0.003) and congestive heart failure (HR 1.67, 95% CI 1.12 to 2.48, p=0.01) were associated with RVO development. Hypertension (HR 2.89, 95% CI 1.10 to 3.96, p=0.02) and ischaemic stroke (HR 3.58, 95% CI 1.97 to 6.48, p<0.001) had increased risk of RAO. ESRD was associated with ION (HR 3.03, 95% CI 1.41 to 6.51, p=0.004). Intravenous steroid was associated with RVO development (HR 2.54, 95% CI 1.67 to 3.84, p<0.001). CONCLUSIONS: SLE increases the risk of developing OIE. Systemic comorbidities and higher dosage of steroid in patients with SLE are associated with severe ocular ischaemic complications.