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1.
Cell Rep ; 39(3): 110700, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35443175

RESUMO

In Arabidopsis, GIGANTEA (GI), together with the blue-light receptors ZTL, LKP2, and FKF1, regulates degradation of the core clock protein TOC1 and the flowering repressor CDFs, thereby controlling circadian oscillation and flowering. Despite the significance of GI in diverse plant physiology, its molecular function is not much understood because of technical problems in protein preparation and a lack of structural information. Here, we report the purification of the GI monomer and the crystal structure of the GI/LKP2 complex. The crystal structure reveals that residues 1-813 of GI possess an elongated rigid structure formed by stacking hydrophobic α-helices and that the LOV domain of LKP2 binds to the middle region of the GI (residues 563-789). Interaction analysis further shows that LOV homodimers are converted to monomers by GI binding. Our results provide structural insights into the regulation of the circadian clock and photoperiodic flowering by GI and ZTL/LKP2/FKF1.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Relógios Circadianos , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Relógios Circadianos/fisiologia , Ritmo Circadiano , Flores/metabolismo , Regulação da Expressão Gênica de Plantas , Luz
3.
Sleep Breath ; 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-35122605

RESUMO

BACKGROUND: Excessive collapse of the soft palate and lateral pharyngeal wall narrowing are established causes of loud snoring and sleep apnea in subjects with obstructive sleep apnea (OSA). Therefore, delicate surgical techniques are needed to reshape the soft palate and create sufficient tension in the lateral pharyngeal wall. This study aimed to determine the therapeutic outcome and favorable indications of soft-palate webbing flap pharyngoplasty in subjects with OSA and primary snoring. METHODS: A total of 174 subjects who underwent soft-palate webbing flap pharyngoplasty combined with uvulopalatal flap and septoturbinoplasty from August 2015 to February 2020 were included in this study. Medical records, including pre- and postoperative sleep parameters, were retrospectively reviewed. The primary outcome measure was the degree of improvement in AHI after surgery. Other outcomes were differences in surgical response rates, subjective visual analog score (VAS) for snoring, sleep quality, and complications. RESULTS: Polysomnographic results showed that apnea-hypopnea index (AHI) scores were significantly reduced from 39.6 ± 6.1 to 22.9 ± 3.6 following soft-palate webbing flap pharyngoplasty in 59 subjects, and overall success and response rates of this technique were analyzed with 71%. We found that the successful outcomes were observed in 50% of mild (n = 12) and 56% of moderate (n = 16) subjects with OSA subjects due to lateral pharyngeal wall collapse. The success rate of soft-palate webbing flap pharyngoplasty was relatively higher in subjects with mild and moderate OSA than those with severe OSA. Additionally, the mean VAS snoring scale was 4.7 and subjects' primary snoring intensity significantly improved to 2.9 after soft-palate webbing flap pharyngoplasty. Subjective symptoms such as daytime sleepiness and sleep quality also showed improvement. Most complications were found to be minimal and improved by 1 month after the operation. CONCLUSION: Our data demonstrate that soft-palate webbing flap pharyngoplasty is an effective treatment for OSA and primary snoring and may be a promising technique to reduce lateral pharyngeal wall collapse.

4.
BMC Biol ; 20(1): 41, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35144597

RESUMO

BACKGROUND: In sprouting angiogenesis, VEGFR2 level is regulated via a fine-tuned process involving various signaling pathways. Other than VEGF/VEGFR2 signaling pathway, Wnt/ ß-catenin signaling is also important in vascular development. However, the crosstalk between these two signaling pathways is still unknown to date. In this study, we aimed to investigate the role of DIX domain containing 1 (DIXDC1) in vasculature, facilitating the crosstalk between VEGF/VEGFR2 and Wnt/ ß-catenin signaling pathways. RESULTS: In mice, DIXDC1 deficiency delayed angiogenesis at the embryonic stage and suppressed neovascularization at the neonatal stage. DIXDC1 knockdown inhibited VEGF-induced angiogenesis in endothelial cells in vitro by downregulating VEGFR2 expression. DIXDC1 bound Dishevelled Segment Polarity Protein 2 (Dvl2) and polymerized Dvl2 stabilizing VEGFR2 protein via its direct interaction. The complex formation and stability of VEGFR2 was potentiated by Wnt signaling. Moreover, hypoxia elevated DIXDC1 expression and likely modulated both canonical Wnt/ß-catenin signaling and VEGFR2 stability in vasculatures. Pathological angiogenesis in DIXDC1 knockout mice was decreased significantly in oxygen-induced retinopathy (OIR) and in wound healing models. These results suggest that DIXDC1 is an important factor in developmental and pathological angiogenesis. CONCLUSION: We have identified DIXDC1 as an important factor in early vascular development. These results suggest that DIXDC1 represents a novel regulator of sprouting angiogenesis that links Wnt signaling and VEGFR2 stability and may have a potential role in pathological neovascularization.


Assuntos
Fator A de Crescimento do Endotélio Vascular , beta Catenina , Animais , Células Endoteliais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos , Neovascularização Patológica/metabolismo , Retina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
5.
Biochem Biophys Res Commun ; 599: 38-42, 2022 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-35168062

RESUMO

CONSTANS is a central protein in the regulation of photoperiodic flowering, which is expressed in response to day length and promotes the expression of Flowering Locus T. The tandem B-box domain in CONSTANS mediates interactions with various proteins to regulate the expression of Flowering Locus T. Although most plants, including Arabidopsis, have multiple B-box proteins, their B-box structures have not been elucidated. Here, we report the crystal structure of a tandem B-box domain from Arabidopsis CONSTANS. The crystal structure shows that each B-box adopts a canonical B-box fold and coordinates two zinc atoms. Furthermore, the crystal structure reveals that the B-box domain has a unique structure that distinguishes it from animal B-boxes at the monomer and dimer level.


Assuntos
Proteínas de Arabidopsis/química , Proteínas de Ligação a DNA/química , Fatores de Transcrição/química , Proteínas de Arabidopsis/metabolismo , Cristalografia por Raios X , Proteínas de Ligação a DNA/metabolismo , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Multimerização Proteica , Fatores de Transcrição/metabolismo , Zinco/metabolismo
6.
Materials (Basel) ; 15(3)2022 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-35161157

RESUMO

Polymer composites containing conductive fillers that utilize the piezoresistive effect can be employed in flexible pressure sensors. Depending on the filler used, different characteristics of a pressure sensor such as repeatability, sensitivity, and hysteresis can be determined. To confirm the variation of the pressure sensing tendency in accordance with the dimensions of the filler, carbon black (CB) and carbon nanotubes (CNTs) were used as representative 0-dimension and 1-dimension conductive fillers, respectively. The piezoresistive effect was exploited to analyze the process of resistance change according to pressure using CB/PDMS (polydimethylsiloxane) and CNT/PDMS composites. The electrical characteristics observed for each filler were confirmed to be in accordance with its content. The pressure sensitivity of each composite was optimized, and the pressure-sensing mechanism that explains the difference in sensitivity is presented. Through repeated compression experiments, the hysteresis and repeatability of the pressure-sensing properties were examined.

7.
J Allergy Clin Immunol ; 149(1): 340-357, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957165

RESUMO

BACKGROUND: Diesel exhaust particles (DEPs) are associated with the prevalence and exacerbation of allergic respiratory diseases, including allergic rhinitis and allergic asthma. However, DEP-induced mechanistic pathways promoting upper airway disease and their clinical implications remain unclear. OBJECTIVE: We sought to investigate the mechanisms by which DEP exposure contributes to nasal polyposis using human-derived epithelial cells and a murine nasal polyp (NP) model. METHODS: Gene set enrichment and weighted gene coexpression network analyses were performed. Cytotoxicity, epithelial-to-mesenchymal transition (EMT) markers, and nasal polyposis were assessed. Effects of DEP exposure on EMT were determined using epithelial cells from normal people or patients with chronic rhinosinusitis with or without NPs. BALB/c mice were exposed to DEP through either a nose-only exposure system or nasal instillation, with or without house dust mite, followed by zinc finger E-box-binding homeobox (ZEB)2 small hairpin RNA delivery. RESULTS: Bioinformatics analyses revealed that DEP exposure triggered EMT features in airway epithelial cells. Similarly, DEP-exposed human nasal epithelial cells exhibited EMT characteristics, which were dependent on ZEB2 expression. Human nasal epithelial cells derived from patients with chronic rhinosinusitis presented more prominent EMT features after DEP treatment, when compared with those from control subjects and patients with NPs. Coexposure to DEP and house dust mite synergistically increased the number of NPs, epithelial disruptions, and ZEB2 expression. Most importantly, ZEB2 inhibition prevented DEP-induced EMT, thereby alleviating NP formation in mice. CONCLUSIONS: Our data show that DEP facilitated NP formation, possibly via the promotion of ZEB2-induced EMT. ZEB2 may be a therapeutic target for DEP-induced epithelial damage and related airway diseases, including NPs.


Assuntos
Poluentes Atmosféricos/toxicidade , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pólipos Nasais , Emissões de Veículos/toxicidade , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Adulto , Idoso , Alérgenos/administração & dosagem , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Doença Crônica , Células Epiteliais/fisiologia , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Pólipos Nasais/genética , Pyroglyphidae/imunologia , RNA Interferente Pequeno/administração & dosagem , Rinite/genética , Sinusite/genética , Adulto Jovem
9.
J Clin Sleep Med ; 18(2): 505-515, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34463248

RESUMO

STUDY OBJECTIVES: Although the airway mucosal system plays a pivotal role in the pathogenesis of obstructive sleep apnea (OSA), the underlying disease mechanism remains unclear. The microbiome greatly impacts human health and disease, particularly in the mucosa, where it can have direct interactions. In this study, we aimed to analyze the microbiome composition in the upper airway mucosa of individuals with and without OSA to identify potential disease severity-related microbial signatures. METHODS: This population-based cohort study involved 92 participants (mean age = 62.7 ± 5.8 years; male-to-female ratio = 0.74) who underwent a physical examination and sleep study. Upper airway swab samples were collected from the nasopharyngeal mucosa to evaluate the microbiome based on 16S rRNA gene pyrosequencing. The relationship between microbiome composition and sleep parameters was explored through bioinformatics analysis. RESULTS: The average apnea-hypopnea index was 7.75 ± 6.5 events/h. Proteobacteria, Firmicutes, and Actinobacteria were the predominant phyla in the nasopharyngeal microbiota in all participants. Simpson diversity indexes were higher in patients with OSA (0.6435 ± 0.2827) than in the control patients (0.6095 ± 0.2683); however, the difference was not significant (P = .1155). Specific anaerobes negatively correlated with the lowest oxygen saturation level during sleep (sum of powered score (1) = -117.47; P = .0052). CONCLUSIONS: The upper airway microbiome of older patients with mild-moderate OSA exhibited minor differences in composition compared with that of individuals without OSA, possibly owing to environmental changes in the upper airway mucosa resulting from recurrent airway obstruction and intermittent hypoxia in patients with OSA. CITATION: Hong S-N, Kim KJ, Baek M-G, et al. Association of obstructive sleep apnea severity with the composition of the upper airway microbiome. J Clin Sleep Med. 2022;18(2):505-515.


Assuntos
Microbiota , Apneia Obstrutiva do Sono , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Microbiota/genética , Pessoa de Meia-Idade , Polissonografia , RNA Ribossômico 16S/genética , Apneia Obstrutiva do Sono/microbiologia
10.
Sci Rep ; 11(1): 21963, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34754001

RESUMO

We investigated the thermographic findings of carpal tunnel syndrome (CTS). We enrolled 304 hands with electrodiagnostically identified CTS and 88 control hands. CTS hands were assigned to duration groups (D1, < 3 months; D2, 3‒6 months; D3, 6‒12 months; D4, ≥ 12 months) and severity groups (S1, very mild; S2, mild; S3, moderate; S4, severe). The temperature difference between the median and ulnar nerve territories (ΔM-U territories) decreased as CTS duration and severity increased. Significant differences in ΔM-U territories between the D1 and D3, D1 and D4, D2 and D4, and S1 and S4 groups (P = 0.003, 0.001, 0.001, and < 0.001, respectively) were observed. Thermal anisometry increased as CTS duration and severity increased. Significant differences in thermal anisometry between the D1 and D4 as well as the D2 and D4 groups (P = 0.005 and 0.04, respectively) were noted. Thermal anisometry was higher in the S4 group than in the S1, S2, and S3 groups (P = 0.009, < 0.001, and 0.003, respectively). As CTS progresses, skin temperature tends to decrease and thermal variation tends to increase in the median nerve-innervated area. Thermographic findings reflect the physiological changes of the entrapped median nerve.


Assuntos
Síndrome do Túnel Carpal/diagnóstico , Termografia/métodos , Idoso , Síndrome do Túnel Carpal/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Raios Infravermelhos , Masculino , Nervo Mediano/fisiopatologia , Pessoa de Meia-Idade , Nervo Ulnar/fisiopatologia
11.
12.
Cells ; 10(10)2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34685714

RESUMO

Pancreatic cancer is characterized by late detection, frequent drug resistance, and a highly metastatic nature, leading to poor prognosis. Antibody-based immunotherapy showed limited success for pancreatic cancer, partly owing to the low delivery rate of the drug into the tumor. Herein, we describe a poly(lactic-co-glycolic acid;PLGA)-based siRNA nanoparticle targeting PD-L1 (siPD-L1@PLGA). The siPD-L1@PLGA exhibited efficient knockdown of PD-L1 in cancer cells, without affecting the cell viability up to 6 mg/mL. Further, 99.2% of PDAC cells uptake the nanoparticle and successfully blocked the IFN-gamma-mediated PD-L1 induction. Consistently, the siPD-L1@PLGA sensitized cancer cells to antigen-specific immune cells, as exemplified by Ovalbumin-targeting T cells. To evaluate its efficacy in vivo, we adopted a pancreatic PDX model in humanized mice, generated by grafting CD34+ hematopoeitic stem cells onto NSG mice. The siPD-L1@PLGA significantly suppressed pancreatic tumor growth in this model with upregulated IFN-gamma positive CD8 T cells, leading to more apoptotic tumor cells. Multiplex immunofluorescence analysis exhibited comparable immune cell compositions in control and siPD-L1@PLGA-treated tumors. However, we found higher Granzyme B expression in the siPD-L1@PLGA-treated tumors, suggesting higher activity of NK or cytotoxic T cells. Based on these results, we propose the application of siPD-L1@PLGA as an immunotherapeutic agent for pancreatic cancer.


Assuntos
Antígeno B7-H1/metabolismo , Imunidade , Nanopartículas/química , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/metabolismo , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Animais , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células , Granzimas/metabolismo , Humanos , Evasão da Resposta Imune , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Microambiente Tumoral/imunologia , Regulação para Cima
13.
J Phys Chem Lett ; 12(40): 9955-9962, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34617766

RESUMO

Identifying pentagons and heptagons in graphene nanoflake (GNF) structures at the atomic scale is important to completely understand the chemical and physical properties of these materials. Herein, we used X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy to analyze the spectral features of GNFs according to the position of pentagons and heptagons introduced onto their zigzag and armchair edges. The XPS peak maxima were shifted to higher binding energies by introducing the pentagons or heptagons on armchair rather than zigzag edges, and the structures could be distinguished depending on the positions of the introduced pentagons or heptagons. Raman spectroscopic analyses also revealed that the position of edges with introduced pentagons or heptagons could also be identified using Raman spectroscopy, with characteristic bands appearing at 800-1200 cm-1, following the introduction of either pentagons or heptagons on armchair edges. This precise spectroscopic identification of pentagons and heptagons in GNFs provides the groundwork for the analysis of graphene-related materials.

14.
Nat Commun ; 12(1): 5617, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556671

RESUMO

Although prime editing is a promising genome editing method, the efficiency of prime editor 2 (PE2) is often insufficient. Here we generate a more efficient variant of PE2, named hyPE2, by adding the Rad51 DNA-binding domain. When tested at endogenous sites, hyPE2 shows a median of 1.5- or 1.4- fold (range, 0.99- to 2.6-fold) higher efficiencies than PE2; furthermore, at sites where PE2-induced prime editing is very inefficient (efficiency < 1%), hyPE2 enables prime editing with efficiencies ranging from 1.1% to 2.9% at up to 34% of target sequences, potentially facilitating prime editing applications.


Assuntos
Algoritmos , Sistemas CRISPR-Cas , DNA/metabolismo , Edição de Genes/métodos , Modelos Genéticos , Rad51 Recombinase/metabolismo , Sequência de Aminoácidos , Sítios de Ligação/genética , DNA/genética , Células HCT116 , Células HEK293 , Humanos , Rad51 Recombinase/genética , Reprodutibilidade dos Testes
16.
Sci Rep ; 11(1): 17464, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465860

RESUMO

Identifying the severity of carpal tunnel syndrome (CTS) is essential to providing appropriate therapeutic interventions. We developed and validated machine-learning (ML) models for classifying CTS severity. Here, 1037 CTS hands with 11 variables each were retrospectively analyzed. CTS was confirmed using electrodiagnosis, and its severity was classified into three grades: mild, moderate, and severe. The dataset was randomly split into a training (70%) and test (30%) set. A total of 507 mild, 276 moderate, and 254 severe CTS hands were included. Extreme gradient boosting (XGB) showed the highest external validation accuracy in the multi-class classification at 76.6% (95% confidence interval [CI] 71.2-81.5). XGB also had an optimal model training accuracy of 76.1%. Random forest (RF) and k-nearest neighbors had the second-highest external validation accuracy of 75.6% (95% CI 70.0-80.5). For the RF and XGB models, the numeric rating scale of pain was the most important variable, and body mass index was the second most important. The one-versus-rest classification yielded improved external validation accuracies for each severity grade compared with the multi-class classification (mild, 83.6%; moderate, 78.8%; severe, 90.9%). The CTS severity classification based on the ML model was validated and is readily applicable to aiding clinical evaluations.


Assuntos
Índice de Massa Corporal , Síndrome do Túnel Carpal/classificação , Eletrodiagnóstico/métodos , Aprendizado de Máquina , Medição da Dor/métodos , Índice de Gravidade de Doença , Síndrome do Túnel Carpal/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Estudos Retrospectivos
17.
Sci Rep ; 11(1): 16300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381060

RESUMO

Diesel exhaust particles (DEPs), traffic-related air pollutants, are considered environmental factors adversely affecting allergic diseases. However, the immunological basis for the adjuvant effects of DEP in allergic rhinitis (AR) remains unclear. Therefore, this study aimed to investigate the effect of DEP exposure on AR using a mouse model. BALB/c mice sensitized to house dust mite (HDM) were intranasally challenged with HDM in the presence and absence of DEP. Allergic symptom scores, serum total and HDM-specific immunoglobulins (Igs), eosinophil infiltration in the nasal mucosa, cytological profiles in bronchoalveolar lavage fluid (BALF), and cytokine levels in the nasal mucosa and spleen cell culture were analyzed. Mice co-exposed to HDM and DEP showed increased allergic symptom scores compared with mice exposed to HDM alone. Reduced total IgE and HDM-specific IgE and IgG1 levels, decreased eosinophil infiltration in the nasal mucosa, and increased proportion of neutrophils in BALF were found in mice co-exposed to HDM and DEP. Interleukin (IL)-17A level was found to be increased in the nasal mucosa of the co-exposure group compared with that in the HDM-exposed group. The levels of IL-4, IL-13, interferon-γ, IL-25, IL-33, and TSLP expression showed no difference between the groups with and without DEP treatment. Increased expression of IL-17A in the nasal mucosa may contribute to DEP-mediated exacerbation of AR in HDM-sensitized murine AR model.


Assuntos
Alérgenos/imunologia , Interleucina-17/imunologia , Mucosa Nasal/imunologia , Material Particulado/imunologia , Pyroglyphidae/imunologia , Rinite Alérgica/imunologia , Poluentes Atmosféricos/imunologia , Animais , Asma/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Hipersensibilidade Respiratória/imunologia
18.
Ear Nose Throat J ; : 1455613211036236, 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427151

RESUMO

OBJECTIVE: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. METHODS: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology-Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. RESULTS: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. CONCLUSIONS: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

19.
Sci Rep ; 11(1): 15953, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354168

RESUMO

Given the fact that threatened species are often composed of isolated small populations, spatial continuity or demography of the populations may be major factors that have shaped the species' genetic diversity. Thus, neutral loci have been the most commonly-used markers in conservation genetics. However, the populations under the influence of different environmental factors may have evolved in response to different selective pressures, which cannot be fully reflected in neutral genetic variation. Rhodeus pseudosericeus, a bitterling species (Acheilognathidae; Cypriniformes) endemic to the Korean Peninsula, are only found in some limited areas of three rivers, Daecheon, Han and Muhan, that flow into the west coast. Here, we genotyped 24 microsatellite loci and two loci (DAB1 and DAB3) of MHC class II peptide-binding ß1 domain for 222 individuals collected from seven populations. Our microsatellite analysis revealed distinctive differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, and populations were structured into two subgroups within the Han River. Apparent positive selection signatures were found in the peptide-binding residues (PBRs) of the MHC loci. The allelic distribution of MHC showed a degree of differentiation between the populations of Daecheon and Muhan Rivers and the Han River populations, partially similar to the results obtained for microsatellites, however showed rather complex patterns among populations in the Han River. Considering the apparent differences in the distribution of supertypes obtained based on the physicochemical differences induced by the polymorphisms of these PBRs, the differentiation in DAB1 between the two regional groups may result in the differences in immune function. No differentiation between these two regions was observed in the supertyping of DAB3, probably indicating that only DAB1 was associated with the response to locally specialized antigenic peptides.


Assuntos
Cyprinidae/genética , Variação Genética/genética , Repetições de Microssatélites/genética , Alelos , Animais , Espécies em Perigo de Extinção , Genética Populacional/métodos , Antígenos de Histocompatibilidade Classe II/genética , Filogenia , Polimorfismo Genético/genética , Seleção Genética/genética
20.
J Allergy Clin Immunol Pract ; 9(12): 4450-4458.e6, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34464748

RESUMO

BACKGROUND: Meta-analyses comparing the efficacy of sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) for house dust mite allergy are lacking. OBJECTIVE: To compare the efficacy of SLIT drops, SLIT tablets, and SCIT in patients with perennial allergic rhinitis through network analysis. METHODS: Frequentist network meta-analyses estimated the standardized mean difference (SMD) across the three immunotherapy modalities on allergic rhinitis symptom and medication score data from double-blind randomized clinical trials. Random effects models were investigated. RESULTS: We included 26 double-blind randomized clinical trials in this meta-analysis for the symptom score and 18 for the medication score. In the direct pairwise meta-analysis, a significant reduction of the symptom score was observed for all immunotherapy modalities compared with the placebo: pooled SMDs of -0.461 (95% confidence interval [CI], -0.795 to -0.127) for SLIT drop, -0.329 (95% CI, -0.426 to -0.231) for SLIT tablet, and -1.669 (95% CI, -2.753 to -0.585) for SCIT. For the medication score, a significant reduction was observed for all modalities. In network meta-analysis, the clinical efficacy of SCIT based on the symptom score was greater than for SLIT drop or SLIT tablet (SMD: -0.697, 95% CI, -1.105 to -0.288; and SMD: -0.819, 95% CI, -1.242 to -0.397). However, there was no significant difference in the symptom score between SLIT drop and SLIT tablet. CONCLUSIONS: This study demonstrated the clinical efficacy of all house dust mite immunotherapy modalities and suggests that SCIT may be more effective than SLIT drops or tablets in controlling symptoms of allergic rhinitis.


Assuntos
Rinite Alérgica Perene , Rinite Alérgica , Imunoterapia Sublingual , Alérgenos , Animais , Dessensibilização Imunológica , Humanos , Injeções Subcutâneas , Metanálise em Rede , Pyroglyphidae , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite Alérgica/terapia , Resultado do Tratamento
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