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1.
Int Immunol ; 36(7): 365-371, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38442194

RESUMO

The intestinal barrier consists of mucosal, epithelial, and immunological barriers and serves as a dynamic interface between the host and its environment. Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. The homeostasis of the intestinal barrier is tightly regulated by crosstalk between gut microbes and the immune system; however, the implication of the immune system on the imbalance of gut microbes that disrupts barrier integrity remains to be fully elucidated. An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits Toll-like receptor (TLR)-2 and TLR-4 signaling in these cells. Since TLRs are major sensors of microbiota and are involved in local epithelial homeostasis, we investigated the role of Allergin-1 in maintaining intestinal homeostasis. Allergin-1-deficient (Milr1-/-) mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type (WT) mice. Milr1-/- mice showed an enhanced intestinal permeability compared with WT mice even before DSS administration. Treatment of Milr1-/- mice with neomycin, but not ampicillin, restored intestinal barrier integrity. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium pseudolongum was the dominant bacterium in Milr1-/- mice after treatment with ampicillin. Although the transfer of B. pseudolongum to germ-free WT mice had no effect on intestinal permeability, its transfer into ampicillin-treated WT mice enhanced intestinal permeability. These results demonstrated that Allergin-1 deficiency enhanced intestinal dysbiosis with expanded B. pseudolongum, which contributes to intestinal barrier dysfunction in collaboration with neomycin-sensitive and ampicillin-resistant microbiota.


Assuntos
Disbiose , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Camundongos Knockout , Animais , Disbiose/imunologia , Camundongos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Sulfato de Dextrana , Microbioma Gastrointestinal/imunologia , Colite/imunologia , Colite/microbiologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Neomicina/farmacologia , Permeabilidade
2.
Clin Immunol ; 259: 109892, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38185269

RESUMO

Radioresistance and metastasis are critical issues in managing oral squamous cell carcinoma (OSCC). Although immune checkpoint inhibitors (ICIs) has been recommended to treat OSCC, lacking useful biomarkers limited their anti-cancer effectiveness. We found that guanylate binding protein 5 (GBP5) is upregulated in primary tumors and associates with radioresistance in OSCC. GBP5 expression causally associated with cellular radioresistance and migration ability in the OSCC cell variants. GBP5 upregulation was examined to be correlated with NF-κB activation and programmed cell death-ligand 1 (PD-L1) elevation in OSCC samples. GBP5 knockdown was mitigated, but overexpression enhanced, NF-κB activity and PD-L1 expression in the OSCC cells. NF-κB inhibition by SN50 dramatically suppressed the GBP5-forested irradiation resistance, cellular migration ability and PD-L1 expression in OSCC cells. Importantly, GBP5 upregulation predicted a favorable outcome in cancer patients received ICI treatment. Our findings provide GBP5 as a useful biomarker to predict the anti-OSCC effectiveness of irradiation and ICIs.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Antígeno B7-H1 , Biomarcadores , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , NF-kappa B , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
3.
Ann Plast Surg ; 90(1 Suppl 1): S103-S110, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37075300

RESUMO

BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Géis de Silicone/uso terapêutico , Estudos Prospectivos , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/prevenção & controle , Queloide/etiologia , Queloide/prevenção & controle , Resultado do Tratamento
4.
J Immunol ; 204(4): 753-762, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31900344

RESUMO

House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1-deficient CD11b+ bone marrow-derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.


Assuntos
Asma/imunologia , Hipersensibilidade/imunologia , Pneumonia/imunologia , Pyroglyphidae/imunologia , Receptores Imunológicos/imunologia , Animais , Células Dendríticas/imunologia , Camundongos , Camundongos Endogâmicos BALB C
5.
Anal Chem ; 93(48): 15931-15940, 2021 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-34780171

RESUMO

Alterations of protein glycosylation are closely related with pathophysiological regulation. Due to the structural macro- and microheterogeneity, low stoichiometry, and low ionization efficiency of glycopeptides, high-performance tools to enrich glycopeptides, especially the negatively charged and labile sialoglycopeptides, are essential to enhance the identification of the underexplored glycoproteome. Here, we present the first implementation of zwitterionic hydrophilic interaction chromatography with the exposed choline group (ZIC-cHILIC) in StageTip for simultaneous enrichment and fractionation of intact glycopeptides. In a model study using lung cancer cells, early elution by a high percentage of acetonitrile prominently prefilters nonglycopeptides, facilitating high enrichment specificity for glycopeptides (92-96%) and sialoglycopeptides (77-89%) in the subsequent hydrophilic fractions. The stepwise elution shows a high glycopeptide fractionation efficiency by a <10% overlap of glycopeptides between adjacent fractions. Most importantly, the ZIC-cHILIC stepwise strategy demonstrated good reproducibility (>80% in triplicate analysis) as well as superior coverage of 4.6- to 12.0-fold and 2.1- to 35.6-fold more glycopeptides and sialoglycopeptides compared to conventional TiO2 and ZIC-HILIC, respectively. To the best of our knowledge, the result with 2742 sialoglycopeptides among 7367 unique glycopeptides and 166 glycans from 2434 N-glycosites of 1118 glycoproteins (Byonic score > 100) provides one of the deepest glycoproteomic profiles in single-cell type. Without the immunoprecipitation step, the large-scale glycoproteomic atlas also reveals site-specific glycosylation of many druggable receptor proteins, such as EGFR, MET, ERBB2, ERBB3, AXL, and IGF1R. The demonstrated high enrichment specificity and identification depth show that stepwise ZIC-cHILIC is an efficient method to explore the under-represented sialoglycoproteome.


Assuntos
Glicopeptídeos , Proteoma , Glicoproteínas , Glicosilação , Interações Hidrofóbicas e Hidrofílicas , Reprodutibilidade dos Testes
6.
Int Immunol ; 32(3): 213-219, 2020 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-31793637

RESUMO

Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcεRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas-TRECK mice, which had been reconstituted with either WT or Milr1-/- bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1-/- mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.


Assuntos
Anafilaxia/imunologia , Basófilos/imunologia , Receptores Imunológicos/imunologia , Animais , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Receptores Imunológicos/administração & dosagem , Receptores Imunológicos/deficiência
7.
Mol Cell Proteomics ; 18(8): 1479-1490, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31097672

RESUMO

Fetuin, also known as α-2-HS-glycoprotein (gene name: AHSG), is one of the more abundant glycoproteins secreted into the bloodstream. There are two frequently occurring alleles of human AHSG, resulting in three genotypes (AHSG*1, AHSG*2, and heterozygous AHSG1/2). The backbone amino acid sequences of fetuin coded by the AHSG*1 and AHSG*2 genes differ in two amino acids including one known O-glycosylation site (aa position 256). Although fetuin levels have been extensively studied, the originating genotype is often ignored in such analysis. As fetuin has been suggested repeatedly as a potential biomarker for several disorders, the question whether the gene polymorphism affects the fetuin profile is of great interest. In this work, we describe detailed proteoform profiles of fetuin, isolated from serum of 10 healthy and 10 septic patient individuals and investigate potential glycoproteogenomics correlations, e.g. how gene polymorphisms affect glycosylation. We established an efficient method for fetuin purification from individuals' serum using ion-exchange chromatography. Subsequently, we performed hybrid mass spectrometric approaches integrating data from native mass spectra and peptide-centric MS analysis. Our data reveal a crucial effect of the gene polymorphism on the glycosylation pattern of fetuin. Moreover, we clearly observed increased fucosylation in the samples derived from the septic patients. Our serum proteoform analysis, targeted at one protein obtained from 20 individuals, exposes the wide variability in proteoform profiles, which should be taken into consideration when using fetuin as biomarker. Importantly, focusing on a single or few proteins, the quantitative proteoform profiles can provide, as shown here, already ample data to classify individuals by genotype and disease state.


Assuntos
alfa-2-Glicoproteína-HS/genética , alfa-2-Glicoproteína-HS/metabolismo , Glicosilação , Humanos , Polimorfismo Genético , Proteogenômica , Sepse/sangue , Sepse/genética
8.
BMC Musculoskelet Disord ; 22(1): 974, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814900

RESUMO

BACKGROUND: Recent research has proposed a classification of spinopelvic stiffness according to pelvic spatial orientation for risk stratification in patients who undergo total hip arthroplasty (THA). However, the influence of global alignment was not investigated, and this study evaluated the effect of global balance (sagittal vertical axis [SVA]) on spinopelvic motion. METHODS: We conducted a retrospective review of consecutive primary THA patients. We measured SVA, spinopelvic parameters (pelvic tilt [PT], pelvic incidence, and sacral slope), thoracic kyphosis (TK), lumbar lordosis (LL), proximal femur angle (PFA), and cup version using functional radiographs of patients in the standing and upright sitting positions. Linear regression was performed to identify parameters related to global trunk alignment change (∆SVA). Spinopelvic stiffness was defined as PT position change < 10°, and a subset of patients with PT change < 0° was categorized into a paradoxical spinopelvic motion group. RESULTS: One hundred twenty-four patients were analyzed (mean age: 65 years, 61% female). In univariate regression analysis, ∆TK, ∆LL, and ∆PFA were correlated to ∆SVA. In multivariate regression analysis, ΔLL (p < 0.001) and ΔPFA (p < 0.001) were found to be correlated to ΔSVA (ΔSVA = - 11.97 + 0.05ΔTK - 0.23ΔLL - 0.17ΔPFA; adjusted R2 = 0.558). Spinopelvic stiffness was observed in 40 patients (32%), including five (4%) with paradoxical motion (∆PT = - 3° ± 1°, p < 0.001) with characteristics of balanced standing global trunk alignment (standing SVA = - 1.0 ± 5.1 cm), similar stiffness of the lumbosacral spine (∆LL = - 7° ± 5°), higher hip motion (∆PFA = - 78° ± 6°, p = 0.017), and higher anterior trunk shift (∆SVA = 6.2 ± 2.0 cm, p = 0.003) from standing to sitting as compared to the stiffness group. Two of these five patients experienced dislocation events after THA. CONCLUSIONS: The lumbosacral and hip motions were the major contributors to global alignment postural change. Paradoxical motion is a rare but dangerous clinical condition in THA that might be related to a disproportionally large trunk shift in the stiff lumbosacral spine causing excessive hip motion. In paradoxical motion, diminishing functional acetabular clearance during position change might pose the prosthesis at higher risk of impingement and instability than spinopelvic stiffness.


Assuntos
Artroplastia de Quadril , Cifose , Lordose , Equilíbrio Postural , Idoso , Artroplastia de Quadril/efeitos adversos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sacro
9.
Ann Plast Surg ; 86(2S Suppl 1): S96-S101, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33438958

RESUMO

BACKGROUND: Skin flap transfer is a commonly used technique by surgeons; however, compromised blood flow may result in flap ischemia and necrosis. We describe the use of closed incision negative pressure therapy (ciNPT) to help manage skin flap reconstructions with indocyanine green fluorescence angiography (ICG-FA) to assess perfusion of the flaps before and after ciNPT. METHODS: Three female and 5 male patients underwent various skin flap reconstructions, including local flaps, pedicled flaps, and propeller flaps, for wound defects related to trauma, infection, or cancer. After flap setting and suturing, ciNPT (-125 mm Hg) was applied to the closed incision for 7 days. Perfusion was assessed using ICG-FA before applying ciNPT and again at 24 hours later. The Shapiro-Wilk test and Wilcoxon signed rank test were used in statistical analysis. RESULTS: Initial postoperative survival was observed for all skin flaps; however, 1 flap failed after 2 weeks due to uncontrolled infection. The remaining 7 flaps healed well without any surgical revision. All patients were initially determined to have impaired flap perfusion; however, skin flap perfusion was significantly higher after ciNPT than before ciNPT in each case (P = 0.012). CONCLUSIONS: This study showed good healing outcomes for skin flap reconstructions without complications, despite the fact that each flap had compromised flap perfusion to some extent during the surgery. This case series is novel in that it used laser-assisted ICG-FA to provide a real-time assessment of skin flap perfusion before and after ciNPT.


Assuntos
Procedimentos de Cirurgia Plástica , Ferida Cirúrgica , Feminino , Fluorescência , Humanos , Verde de Indocianina , Masculino , Retalhos Cirúrgicos
10.
Sensors (Basel) ; 21(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204682

RESUMO

This study proposes the development of an underwater object-tracking control system through an image-processing technique. It is used for the close-range recognition and dynamic tracking of autonomous underwater vehicles (AUVs) with an auxiliary light source for image processing. The image-processing technique includes color space conversion, target and background separation with binarization, noise removal with image filters, and image morphology. The image-recognition results become more complete through the aforementioned process. After the image information is obtained for the underwater object, the image area and coordinates are further adopted as the input values of the fuzzy logic controller (FLC) to calculate the rudder angle of the servomotor, and the propeller revolution speed is defined using the image information. The aforementioned experiments were all conducted in a stability water tank. Subsequently, the FLC was combined with an extended Kalman filter (EKF) for further dynamic experiments in a towing tank. Specifically, the EKF predicts new coordinates according to the original coordinates of an object to resolve data insufficiency. Consequently, several tests with moving speeds from 0.2 m/s to 0.8 m/s were analyzed to observe the changes in the rudder angles and the sensitivity of the propeller revolution speed.


Assuntos
Lógica Fuzzy
11.
J Proteome Res ; 19(5): 1941-1952, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32125861

RESUMO

Protein N-glycosylation on human milk proteins assists in protecting an infant's health and functions among others as competitive inhibitors of pathogen binding and immunomodulators. Due to the individual uniqueness of each mother's milk and the overall complexity and temporal changes of protein N-glycosylation, analysis of the human milk N-glycoproteome requires longitudinal personalized approaches, providing protein- and N-site-specific quantitative information. Here, we describe an automated platform using hydrophilic-interaction chromatography (HILIC)-based cartridges enabling the proteome-wide monitoring of intact N-glycopeptides using just a digest of 150 µg of breast milk protein. We were able to map around 1700 glycopeptides from 110 glycoproteins covering 191 glycosites, of which 43 sites have not been previously reported with experimental evidence. We next quantified 287 of these glycopeptides originating from 50 glycoproteins using a targeted proteomics approach. Although each glycoprotein, N-glycosylation site, and attached glycan revealed distinct dynamic changes, we did observe a few general trends. For instance, fucosylation, especially terminal fucosylation, increased across the lactation period. Building on the improved glycoproteomics approach outlined above, future studies are warranted to reveal the potential impact of the observed glycosylation microheterogeneity on the healthy development of infants.


Assuntos
Leite Humano , Proteoma , Glicopeptídeos , Glicoproteínas , Humanos , Proteômica
12.
Toxicol Appl Pharmacol ; 402: 115115, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32634518

RESUMO

Physalin A (PA), a withanolide, was isolated from Physalis angulata L. In this study, it is shown that PA can inhibit the production of inflammatory cytokines such as PGE2, NO, IL-1ß, IL-6, and TNF-α in LPS-induced RAW 264.7 cells. Furthermore, the results indicated that PA suppressed the IκB/NF-κB and JNK/ AP-1 inflammatory signaling pathways and inhibited the levels of pro-inflammatory factors iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. In the carrageenan-induced mouse hind paw edema study, PA was shown to inhibit the production of inflammatory mediators such as NO, MDA, and TNF-α production. Conversely, the antioxidant factor levels of SOD, CAT, and GPx were all increased by the treated PA. According to the data, we are suggesting that the anti-inflammatory effects of PA may be through the suppressions of the JNK/AP-1 and IκB/NF-κB signaling pathways and up-regulation of the anti-oxidative activity.


Assuntos
Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fator de Transcrição AP-1/metabolismo , Vitanolídeos/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Carragenina/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas I-kappa B/genética , Proteínas I-kappa B/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Masculino , Malondialdeído , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Physalis/química , Células RAW 264.7 , Distribuição Aleatória , Fator de Transcrição AP-1/genética , Vitanolídeos/química
13.
Environ Toxicol ; 35(12): 1352-1363, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32677756

RESUMO

Although pipoxolan (PIPO) is a smooth muscle relaxant, its anti-inflammatory capability has not been studied. Therefore, we investigated the anti-inflammatory molecular mechanisms of PIPO in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. In this study, we used the MTT assay to evaluate the cytotoxicity, applied the enzyme-linked immunosorbent assay to determine the inflammatory cytokines, and performed Western blotting to assess protein expression. The results showed that PIPO significantly inhibited cytokine production, including nitric oxide, prostaglandin E2 , tumor necrosis factor-α, and interleukin-6. PIPO also suppressed the pro-inflammatory mediator expression with inducible nitric oxide synthase and cyclooxygenase-2. Moreover, PIPO prohibited the multiple inflammatory transcription factor pathways, including inhibitor kappa B/nuclear factor of the κ light chain enhancer of B cells (NF-κB), mitogen-activated protein kinase/activator protein-1 (AP-1), Janus kinase/signal transducer and activator of transcription (STAT), and toll-like receptor 4 (TLR4)/serine/threonine kinase (AKT). Besides, PIPO effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 antioxidative pathway. Collectively, PIPO may attenuate the inflammatory effects via influencing the LPS/TLR4 receptor binding; suppress the expression of anti-inflammatory transcription factors NF-κB, AP-1, and STAT; and activating the antioxidative transcription factor Nrf2 in LPS-stimulated mouse RAW 264.7 cells.


Assuntos
Anti-Inflamatórios/farmacologia , Dioxolanos/farmacologia , Macrófagos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição STAT/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Antioxidantes/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7
14.
J Nanosci Nanotechnol ; 19(8): 4529-4534, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30913744

RESUMO

A high-quality HfGeOx interfacial layer (IL) was formed in a HfO2/Al2O3/HfO2/GeOx gate stack through thermal annealing. The diffusing of GeO into the HfO2 layer led to the mixing of the GeOx and HfO2 layers, as identified through energy-dispersive X-ray Spectroscopy (EDX). X-ray photo-electron spectroscopy (XPS) data for HfGeOx IL confirmed the formation of Ge-O-Hf bonds owing to the induced shift of the Ge3dox spectra to lower binding energies. The electrical and reliability data indicated that the capacitor with HfGeOx IL presented not only lower interface states density (Dit, approximately 7 × 1011 eV-1cm-2) but also less Dit increment (approximately 3 × 1011 eV-1cm-2) after stressing than did the capacitor without the HfGeOx IL. Moreover, the Ge p-metal-oxide-semiconductor field-effect transistor HfGeOx IL exhibited a high effective hole mobility (approximately 704 cm2/V s).

16.
J Proteome Res ; 17(8): 2861-2869, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29966421

RESUMO

Fetuin, also known as alpha-2-Heremans Schmid glycoprotein (AHSG), belongs to some of the most abundant glycoproteins secreted into the bloodstream. In blood, fetuins exhibit functions as carriers of metals and small molecules. Bovine fetuin, which harbors 3 N-glycosylation sites and a suggested half dozen O-glycosylation sites, has been used often as a model glycoprotein to test novel analytical workflows in glycoproteomics. Here we characterize and compare fetuin in depth, using protein from three different biological sources: human serum, bovine serum, and recombinant human fetuin expressed in HEK-293 cells, with the aim to elucidate similarities and differences between these proteins and the post-translational modifications they harbor. Combining data from high-resolution native mass spectrometry and glycopeptide centric LC-MS analysis, we qualitatively and quantitatively gather information on fetuin protein maturation, N-glycosylation, O-glycosylation, and phosphorylation. We provide direct experimental evidence that both the human serum and part of the recombinant proteins are processed into two chains (A and B) connected by a single interchain disulfide bridge, whereas bovine fetuin remains a single-chain protein. Although two N-glycosylation sites, one O-glycosylation site, and a phosphorylation site are conserved from bovine to human, the stoichiometry of the modifications and the specific glycoforms they harbor are quite distinct. Comparing serum and recombinant human fetuin, we observe that the serum protein harbors a much simpler proteoform profile, indicating that the recombinant protein is not ideally engineered to mimic human serum fetuin. Comparing the proteoform profile and post-translational modifications of human and bovine serum fetuin, we observe that, although the gene structures of these two proteins are alike, they represent quite distinct proteins when their glycoproteoform profile is also taken into consideration.


Assuntos
Processamento de Proteína Pós-Traducional , alfa-2-Glicoproteína-HS/metabolismo , Animais , Sítios de Ligação , Bovinos , Glicosilação , Células HEK293 , Humanos , Espectrometria de Massas , Fosforilação , Isoformas de Proteínas , Proteínas Recombinantes/genética , alfa-2-Glicoproteína-HS/genética
17.
BMC Musculoskelet Disord ; 19(1): 411, 2018 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-30474544

RESUMO

BACKGROUND: Reasons for dissatisfaction with total knee arthroplasty (TKA) include unequal flexion or extension gap, soft tissue imbalance, and patella maltracking, which often occur with mismatch between femoral and tibial coronal bony alignment in the knee joint or extremely varus or valgus alignment. However, lower limb coronal alignment classification is based only on hip-knee-ankle angle (HKAA), leading to oversight regarding a mismatch between femoral and tibial coronal alignment. We aimed to classify alignment of the lower limbs according to the mechanical alignment of the femur and tibia in a healthy population. METHODS: All 214 normal triple films were reviewed retrospectively. HKAA, mechanical lateral distal femoral angle (mLDFA), mechanical medial proximal tibial angle (mMPTA), angle between the femoral anatomical axis and the mechanical axis (AA-MA), and knee alignment angle (KAA) were measured. Subjects were categorized into one of five types based on the mechanical alignment of femur and tibia. RESULTS: Mean HKAA, mLDFA, and mMPTA of all subjects were 1.2°, 87.3°, and 85.8°, respectively. All subjects were classified into one of five types with significant differences (p < 0.001). About 61% of subjects showed neutral alignment, of which nearly 40% were type 2 (valgus of the femur and varus of the tibia with oblique joint line: mLDFA 85.0° ± 1.4°, mMPTA 85.1° ± 1.2°, TJLA 2.7° ± 2.4°) and 60% exhibited neutral alignment with a neutral femur and tibia (type 1). In varus and valgus types, mismatch between the mechanical angle of the femur and tibia was common. Varus alignment, including types 3 (varus of the tibia: mLDFA 88.0° ± 1.4°, mMPTA 83.5° ± 1.6°) and 4 (varus of both the tibia and femur: mLDFA 91.4° ± 1.4°, mMTPA 85.2° ± 2.0°), was found in 30% of subjects. Valgus alignment (type 5 valgus of femur: mLDFA 84.6° ± 1.6°, mMPTA 88.8° ± 2.0°) accounted for 8.9% of all subjects. CONCLUSIONS: Mismatch between mechanical alignment of the femur and tibia was common in varus and valgus alignment types. Joint line obliquity was also observed in 40% of the neutral alignment population. This classification provides a quick, simple interpretation of femoral and tibial coronal alignment, and more detailed guidance for preoperative planning for TKA than the traditional varus-neutral-valgus classification.


Assuntos
Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Adulto , Idoso , Fenômenos Biomecânicos/fisiologia , Feminino , Fêmur/anormalidades , Humanos , Articulação do Joelho/anormalidades , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tíbia/anormalidades , Suporte de Carga/fisiologia , Adulto Jovem
18.
Ann Plast Surg ; 81(1): 62-67, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29762451

RESUMO

BACKGROUND: Defects after total pharyngolaryngectomy for hypopharyngeal cancer often require reconstruction via free tissue transfer. Recently, anterolateral thigh (ALT) flap has become the gold standard in many centers because of its advantages with respect to versatility, minimal donor-site morbidity, good speech quality, and relatively low fistula and anastomotic leakage rates. Moreover, ALT allows 2 surgical teams to work simultaneously. However, the height of the parallelogram in the ALT design for neoesophagus reconstruction is usually set at a minimum of 9.4 cm (circumference, 2πr) for smooth food passage. Because this height exceeds 8 cm, the donor site may not be closed primarily, which highly depends on the patient's body habitus and the skin tone or quality and requires other methods, such as local flap or skin graft for wound closure, which subsequently increase operating time and donor-site complication rate. OBJECTIVES: Thus, we aimed to construct a simple and modified ALT design that will not only include the advantages described earlier but also provide adequate donor-site primary closure without jeopardizing complication rates. METHODS: Ten patients with hypopharyngeal cancer underwent reconstructive surgery using our modified ALT design after total pharyngolaryngectomy between 2010 and 2017. Our modified ALT design converts this "classical" shape into a parallelogram so that the height of the modified design is always less than 8 cm, thus allowing for easy primary closure of the wound. RESULTS: The donor-site defects of all 10 patients were closed primarily. No donor-site complications and partial or total flap loss were observed. One patient experienced persistent wound infection with dehiscence, for which debridement was performed. The stricture and fistula rates were 10% (n = 1) and 20% (n = 2), respectively. The mean follow-up time is approximately 1 year. CONCLUSIONS: Minimizing donor-site morbidity is an important goal in reconstructive surgery. Our modified ALT flap design is simple, enabling easy primary closure of the donor-site defect, with improved results for the patient and operators. Furthermore, this design is also suitable for ALT flaps with widths larger than 8 cm.


Assuntos
Retalhos de Tecido Biológico/transplante , Faringectomia/métodos , Coxa da Perna/cirurgia , Sítio Doador de Transplante/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retalho Perfurante/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Coxa da Perna/patologia , Sítio Doador de Transplante/patologia , Resultado do Tratamento
19.
Ann Plast Surg ; 76 Suppl 1: S80-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26855168

RESUMO

PURPOSE: Refractory migraine surgery developed since 2003 has excellent results over the past 10 years. According to the pioneer of migraine surgery, Dr. Bahman Guyuron, 5 major surgical classifications of migraines are described in the field of plastic surgery, namely, frontal migraine, temporal migraine, rhinogenic migraine, occipital migraine, and auriculotemporal migraine. In this study, we present the preliminary surgical results of the occipital migraine surgery. MATERIALS AND METHODS: A total of 22 patients with simple occipital migraines came to our outpatient clinic for help from June 2014 to February 2015. Thirteen cases were excluded owing to ineligibility for operation or other reasons. The patients who concurrently experienced other types of migraines were precluded even if they received combined migraine surgery. Therefore, 9 simple occipital migraine cases were enrolled in this study. Migraine severity was evaluated by uniform questionnaires to identify the source of migraine. Neurolysis was performed under general anesthesia, with the patient in a prone position. Postoperative conditions were evaluated at the second, fourth, sixth, and eighth weeks by posttreatment questionnaires. RESULTS: Of all the 9 patients, 5 experienced single-sided migraines of greater occipital nerve origin (2 left-sided and 3 right-sided cases). Two patients had bilateral migraines of greater occipital nerve origin, and unilateral right lesser occipital nerve origin was noted in one patient. The last patient had right-sided migraines of greater and lesser occipital nerve origin. As a result in the follow-up, a response rate greater than 90% was documented, and complete resolution was observed in 2 patients. Drug doses were reduced more than 50% in the remaining patients. The overall efficacy of occipital migraine surgery in this study was 88.8% (8/9 cases). CONCLUSION: Some patients with migraine are good candidates for surgical resolution with appropriate and meticulous selection. Similar to what is observed in Western countries, the migraine surgery is promising and could provide a better quality of life to selected refractory migraine patients in Taiwan.


Assuntos
Denervação/métodos , Transtornos de Enxaqueca/cirurgia , Nervos Espinhais/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan , Resultado do Tratamento
20.
Org Biomol Chem ; 13(47): 11550-60, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26463681

RESUMO

A concise synthesis of single components of C2 sulfated oligomannans including trimers, tetramers, and pentamers is reported. The synthesis features the application of the DMF-modulation method for the participatory thiomannoside donors in 1,2-transα-glycosidic bond formation. The obtained oligomannans were fully characterized using (1)H, (13)C, COSY, and HSQC NMR spectroscopy.


Assuntos
Mananas/síntese química , Sulfatos/síntese química , Dimerização , Dissacarídeos/síntese química , Dissacarídeos/química , Espectroscopia de Ressonância Magnética , Mananas/química , Sulfatos/química
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