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1.
Front Bioeng Biotechnol ; 10: 1028278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338136

RESUMO

The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration.

2.
Plant Dis ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36383997

RESUMO

Tribulus terrestris L. is an annual herbaceous medicinal plant of Zygophyllaceae, which is cultivated commercially in China. Subrotund or irregular gray, sunken, necrotic spots ranging from 2 to 9 mm were observed on diseased leaves of T. terrestris landrace in Fushun County, Liaoning Province of northeast China in July 2021, with more than 32% of the plants being infected in a 18-ha field. The symptoms first appeared on older leaves and gradually spread to younger leaves. The lesions developed a white center gradually and became perforated; multiple lesions could coalesce (Fig. 1). Ten symptomatic leaves were collected and the diseased tissues were cut into small pieces, immersed in 1% NaOCl for 2 min, rinsed three times with sterile water, and placed on acidified potato dextrose agar (PDA) in Petri dishes at 25°C in darkness. Fifteen suspected Colletotrichum single-spore fungal isolates (JL1 to JL15) with consistent morphological characteristics were obtained, and isolate JL6 was selected for identification and pathogenicity testing. Colonies on PDA were flat with an entire margin, dense and white at first, then became dark gray with numerous black microsclerotia and formed a concentric circular pattern with aging. Conidia were single-celled, sickle-curved with a tapered tip and truncate base, ranging from 16.46 to 20.26 µm in length and 2.81 to 3.96 µm in width (n=100). Setae were dark brown, septate, straight with a slightly acute tip, 75.45 to 135.63×3.19 to 4.95 µm in size. Appressoria were dark brown, round or irregular, mostly in groups. All characteristics were consistent with the descriptions of C. truncatum (Damm et al. 2009). Further confirmation of the identification was determined according to methods described previously (Damm et al. 2009). The rDNA internal transcribed spacer region (OP364400, 585 bp), and actin (OP380867, 290 bp), beta-tubulin (OP380868, 498 bp), chitin synthase 1 (OP380869, 277 bp), glyceraldehyde-3-phosphate dehydrogenase (OP380870, 280 bp), and histone (OP380871, 411 bp) genes were amplified by PCR and sequenced (Carbone and Kohn 1999; Glass and& Donaldson 1995; Guerber et al. 2003; O'Donnell and Cigelnik 1997). BLAST results showed 98-100% similarity at 85-97% coverage compared to the corresponding sequences of the type strain CBS 151.35 (GU227862, GU227960, GU228156, GU228352, GU228254, and GU228058). Phylogenetic analysis combining all loci revealed that the isolate JL6 and the type strains of C. truncatum clustered in one group (Fig. 2). One-year-old healthy seedlings of T. terrestris (cultivar: landrace) were used for pathogenicity test. Suspension (1×105 conidia/mL) of isolate JL6 was sprayed on ten seedlings, and ten seedlings sprayed with sterilized distilled water were used as the control. Three replicates were performed on each treatment. All plants were kept at 28±1°C (12 h photoperiod), and were evaluated after 7 days. The inoculated plants showed lesions on the leaf surface, similar to those in the field, and the control remained symptomless. The pathogen was successfully reisolated and identified using the methods mentioned above. To our knowledge, this is the first report of C. truncatum causing anthracnose on T. terrestris, which will provide valuable information for designing strategies to manage anthracnose on T. terrestris.

3.
J Med Chem ; 65(21): 14589-14598, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36318612

RESUMO

VSA-2 is a recently developed semisynthetic saponin immunostimulant. It is prepared by incorporating a terminal-functionalized side chain to the branched trisaccharide domain at the C3 position of Momordica saponin II (MS II) isolated from the seeds of perennial Momordica cochinchinensis Spreng. Direct comparison of VSA-2 and the clinically proven saponin adjuvant QS-21 shows that VSA-2 is comparable to QS-21 in enhancing humoral and cellular immune responses. Structure-activity relationship studies show that structural changes in the side chain have a significant impact on saponins' adjuvant activity. However, with the VSA-2 molecular framework intact, the new VSA-2 analogues with various substitution(s) at the terminal benzyl group of the side chain retain the ability of potentiating antigen-specific humoral and cellular responses.


Assuntos
Momordica , Saponinas , Momordica/química , Adjuvantes de Vacinas , Saponinas/química , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/química , Relação Estrutura-Atividade
4.
Infect Drug Resist ; 15: 6641-6650, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386413

RESUMO

Purpose: The appropriate management of spinal tuberculosis (TB) is challenging for clinicians and the key to treat spinal TB. Surgery and long course anti-TB chemotherapy may not be necessary to all situations. This study aimed to characterize the clinical features and factors affecting treatment outcomes. Patients and Methods: A retrospective study of patients with spinal TB over a 5-year period at a teaching hospital in central China was conducted. Features of patients with spinal TB who received different treatment modalities and factors associated with patient outcomes at the end of chemotherapy were analyzed. Results: Forty-five patients (21 men and 24 women) with spinal TB were available for analysis. The mean age was 55.39 ± 14.94 years. The most common vertebral area involved was the lumbar (42.2%). The mean number of vertebrae involved was 2.20 ± 0.59. 27 patients (60.0%) received surgical treatment, of which 21 (77.8%) received radical surgical treatment. Thirty-five patients (77.8%) had achieved a favorable status. Statistically, there was no significant correlation between favorable status and surgery, but among 27 surgical patients with spinal tuberculosis, patients receiving radical surgery tended to achieve good prognosis (P = 0.010; odds ratio = 0.053; 95% confidence interval 0.006-0.493). Moreover, there was no significant difference between long course and short course of anti-TB chemotherapy in prognosis in different treatment modalities. Conclusion: Although the patients with spinal TB who needed surgical treatment often got a better prognosis when they had radical surgery, surgery was not actually a factor for the favorable outcomes of patients with spinal TB. In different treatment modalities, there was no additional benefit in longer anti-TB chemotherapy periods.

5.
J Agric Food Chem ; 70(45): 14480-14487, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36321207

RESUMO

Succinate dehydrogenase (SDH) inhibitor is one of the research hotspots for the development of fungicides. Herein, we describe the design and synthesis of N-methoxy-(biphenyl-ethyl)-pyrazole-carboxamide derivatives with enhanced fungicidal activity by employing fragment combination strategy. The SDH enzymatic activity was evaluated for 24 title compounds, and compound 7s was identified as the highest activity against porcine SDH with an IC50 value of 0.014 µM, 205-fold greater than that of fluxapyroxad. Furthermore, the greenhouse experiments showed that compound 7u exhibited potent fungicidal activity against wheat powdery mildew with an EC50 value of 0.633 mg/L, higher activity than fluxapyroxad and benzovindiflupyr. The computational results showed that the fluorine atom substituted on the pyrazole ring formed an extra dipolar-dipolar interaction with C_S42 and then increased the van der Waals interaction between the compound and SDH. The structural and mechanistic insights obtained from the present work will provide a valuable clue to developing novel SDH inhibitors.


Assuntos
Fungicidas Industriais , Succinato Desidrogenase , Suínos , Animais , Relação Estrutura-Atividade , Fungicidas Industriais/química , Pirazóis/farmacologia , Pirazóis/química , Simulação de Acoplamento Molecular , Inibidores Enzimáticos/química
6.
J Org Chem ; 87(22): 15061-15070, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36321917

RESUMO

A regio- and chemoselective sulfonylation of propargyl alcohols with sulfinamides in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) was developed. It provided straightforward and mild access to multi-substituted allenyl sulfones by using sulfinamides as the sulfonyl sources. This transformation was promoted by HFIP and did not require any catalysts or oxidants, which allowed for the successful conversion of various tertiary and secondary propargyl alcohols into allenyl sulfones in high yields.

7.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362052

RESUMO

Neutrophils play a pivotal role in innate immunity by releasing neutrophils extracellular traps (NETs). Excessive NETs are detrimental to the local tissue and further exacerbate inflammation. Protein arginine deiminases (PAD) mediate histone citrullination and NET formation that, in turn, exacerbate endotoxin shock damages. In this study, we further investigated the molecular mechanism underlying PAD and NETs in endotoxic stress in mice. The control group mice were injected with solvent, the LPS endotoxic shock group mice were intraperitoneally injected with LPS at 35 mg/kg only, while the LPS and PAD inhibitor YW3-56 treatment group mice were injected with YW3-56 at 10 mg/kg prior to the LPS injection. YW3-56 significantly prolonged the survival time of the LPS-treated mice. NETs, cfDNA, and inflammatory factors were detected by ELISA in serum, paitoneal cavity, and lung at 24 h after LPS administration. Lung injuries were detected by immunostaining, and lung tissue transcriptomes were analyzed by RNA-seq at 24 h after LPS administration. We found that YW3-56 altered neutrophil tissue homeostasis, inhibited NET formation, and significantly decreased cytokines (IL-6, TNFα and IL-1ß) levels, cytokines gene expression, and lung tissue injury. In summary, NET formation inhibition offers a new avenue to manage inflammatory damages under endotoxic stress.


Assuntos
Armadilhas Extracelulares , Choque Séptico , Camundongos , Animais , Desiminases de Arginina em Proteínas/metabolismo , Choque Séptico/induzido quimicamente , Choque Séptico/tratamento farmacológico , Choque Séptico/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Citocinas/metabolismo
8.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362053

RESUMO

Coronary artery spasm (CAS) plays an important role in the pathogenesis of many ischemic heart entities; however, there are no established diagnostic biomarkers for CAS in clinical and forensic settings. This present study aimed to identify such serum biomarkers by establishing a rabbit CAS provocation model and integrating quantitative serum proteomics, parallel reaction monitoring/mass spectrometry-based targeted proteomics, and partial least-squares discriminant analysis (PLS-DA). Our results suggested that SELENBP1 and VCL were potential candidate biomarkers for CAS. In independent clinical samples, SELENBP1 and VCL were validated to be significantly lower in serum but not blood cells from CAS patients, with the reasons for this possibly due to the decreased secretion from cardiomyocytes. The areas under the curve of the receiver operating characteristics (ROC) analysis were 0.9384 for SELENBP1 and 0.9180 for VCL when diagnosing CAS. The CAS risk decreased by 32.3% and 53.6% for every 10 unit increases in the serum SELENBP1 and VCL, respectively. In forensic samples, serum SELENBP1 alone diagnosed CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, and its combination with VCL yielded a diagnostic specificity of 100.0%, which was superior to the traditional biomarkers of cTnI and CK-MB. Therefore, serum SELENBP1 and VCL could be effective biomarkers for both the clinical and forensic diagnosis of CAS.


Assuntos
Vasoespasmo Coronário , Vasos Coronários , Animais , Coelhos , Vasoespasmo Coronário/diagnóstico , Creatina Quinase Forma MB , Biomarcadores , Espasmo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36374590

RESUMO

Without external chiral intervention, it is a challenge to form homochirality from achiral molecules with conformational flexibility. We here report on a rational strategy that uses multivalent noncovalent interactions to clamp the molecular conformational of achiral D-A molecules. These interactions overcome the otherwise dominant dipole-dipole interactions and thus disfavor their symmetric antiparallel stacking. It in turn facilitates parallel packing, leading to spontaneous symmetry breaking during crystallization and thus the formation of homochiral conglomerates. When this emergent homochirality is coupled with optical gain characteristics of the molecules, the homochiral crystals are explored as excellent circularly polarized micro-lasers with low lasing threshold (16.4 µJ/cm2) and high dissymmetry factor glum (0.9). This study therefore provides a facile design strategy for supramolecular chiral materials and active laser ones without the necessity of intrinsic chiral element.

10.
Clin Otolaryngol ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36317525

RESUMO

OBJECTIVES: To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia. DESIGN: This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment. RESULTS AND CONCLUSION: CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non-eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.

11.
Front Endocrinol (Lausanne) ; 13: 1026901, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353245

RESUMO

Background and aims: Findings about the associations between transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 and nonalcoholic fatty liver disease have not been consistently replicated, particularly in steatosis and fibrosis. The present study aimed to investigate the associations between the rs58542926T allele and the spectrum of NAFLD and its related metabolic phenotypes. Methods: Systematic literature research was performed to analyse the associations between rs58542926 and the spectrum of NAFLD and its related metabolic phenotypes. A random effects meta-analysis with a dominant genetic model was applied. Results: Data from 123,800 individuals across 44 studies were included in the current meta-analysis.rs58542926 T allele was associated with an increased risk of NAFLD in both adults (OR=1.62; 95% CI: 1.40, 1.86) and children (OR=2.87; 95% CI: 1.85, 4.46). Children had a stronger association with NAFLD (P=0.01). rs58542926 T allele was also positively associated with steatosis progression (mean difference=0.22; 95% CI: 0.05, 0.39) and fibrosis stage (OR=1.50; 95% CI: 1.20, 1.88) in adults. The TM6SF2 rs58542926 T allele was positively associated with ALT in both adults and children (both P<0.01) and only with higher AST in adults (P<0.01). The rs58542926 T allele was negatively associated with serum total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TGs) in both adults and children (all P<0.01).The serum level of TG was much lower in adults than in children (P<0.01). Conclusion: TM6SF2 rs58542926 is involved in the entire spectrum of NAFLD and its related metabolic phenotype, and differences in serum lipid levels were observed between adults and children. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021288163.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Proteínas de Membrana/genética , Fibrose , Alelos , Triglicerídeos
12.
Biochem Pharmacol ; : 115343, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36370754

RESUMO

Osteoarthritis (OA) is characterized by cartilage matrix degeneration and chondrocyte apoptosis. Prolonged endoplasmic reticulum (ER) stress participates in chondrocyte apoptosis and cartilage degeneration in OA progression. miR-486-5p could suppress the apoptosis of nucleus pulposus cells and cardiomyocyte, yet whether miR-486-5p modified exosomes could modulate ER stress and apoptosis of chondrocytes remain unknown. We validated the increased inflammation and ER stress in OA synovium and cartilage, and the inhibition of ER stress could attenuate the IL-1ß induced chondrocyte apoptosis. Administration of exogenous miR-486-5p could inhibit the ER stress, alleviate chondrocytes apoptosis and promote matrix regeneration. In comparison with direct administration of miR-486-5p and miR-486-5p overexpressing ADSCs, miR-486-5p modified exosomes showed a better effect in modulating chondrocyte homeostasis. MiR-486-5p containing exosomes could also regulate macrophage polarization. Our IVIS imaging data validated that intraarticular injection of miR-486-5p containing exosomes could sustain for at least 7 days. MiR-486-5p containing exosomes showed a better effect on alleviating rats OA compared with direct administration of miR-486-5p and miR-486-5p overexpressing ADSCs. Our data demonstrated that miR-486-5p modified exosomes have a better effect on alleviating chondrocyte apoptosis and osteoarthritis. This study provides evidence of this efficient strategy of exosomal miRNA delivery and the miRNA-based therapy for OA.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36347830

RESUMO

Disclosed herein is RhCl3-catalyzed peri-selective C-H/C-H oxidative homo-coupling of 1-substituted naphthalenes, which provides a highly efficient and streamlined approach to chalcogen-embedded anthanthrenes from readily available starting materials. Introducing O, S, and Se into the anthanthrene skeleton leads to gradually increased π-π stacking distances but significantly enhanced π-π overlaps with the growth of heteroatomic radius. Moderate π-π distance, overlap area, and intermolecular S-S interactions endow S-embedded anthanthrene (PTT) with excellent 2D charge-transport properties. Moreover, the transformation of p-type to n-type S-embedded anthanthrenes is realized for the first time via the S-atom oxidation from PTT to PTT-O4. In organic field-effect transistor devices, PTT derivatives exhibit hole transport properties with mobilities up to 1.1 cm2 V-1 s-1, while PTT-O4 shows an electron transport property with a mobility of 0.022 cm2 V-1 s-1.

14.
J Am Chem Soc ; 144(46): 20979-20997, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36346429

RESUMO

Covalent modifications of DNA and histones are key cellular epigenetic marks to regulate gene functions. Most of these epigenetic marks are added or removed by corresponding enzymes known as writers and erasers, whose catalytic activities normally rely on the presence of cellular metabolites as cofactors. Epigenetic marks can either directly alter the chromatin structure and dynamics through changing the intra-/internucleosomal histone-histone and histone-DNA interactions or recruit readers that further bring in other proteins with chromatin-modifying/remodeling activities to reshape the local and regional chromatin organization. In these two ways, epigenetic modifications modulate diverse DNA-templated processes, such as gene transcription, DNA replication, and DNA damage repair. Therefore, elucidation of the regulatory mechanisms and biological significance of epigenetic marks requires the identification and characterization of the protein-protein, protein-nucleic acid, and protein-small molecule interactions that control the underlying epigenetic processes. Here, we review the recent advances in using photo-cross-linking strategies to interrogate the epigenetic interactome, focusing on the protein-protein interactions mediated by epigenetic marks in histone tails. We also discuss future directions of developing photo-cross-linking-based tools and methods toward the investigation of the binding events in nucleosomal/chromatinic contexts, and toward the in situ capture of the epigenetic interactome in live cells or even organisms.


Assuntos
Epigênese Genética , Histonas , Histonas/química , Cromatina , Nucleossomos , DNA/metabolismo , Processamento de Proteína Pós-Traducional
15.
Anal Chem ; 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416078

RESUMO

The interconnection of microRNAs (miRNAs) and metal ions governs multiple biological processes in disease development and progression. However, developing multiplexed tools for dynamic imaging of these regulators remains a significant challenge. Herein, we report a conceptual approach for the design of an optically controlled DNA nanomachine by introducing a ternary DNAzyme-based, UV light-cleavable DNA scaffold and upconversion nanoparticle to the activatable hybrid chain reaction. We demonstrate that this nanomachine is capable of being effectively operated either in the presence of an endogenous miRNA target or the coexistence of intracellular Zn2+ and external near-infrared light, resulting in enhanced fluorescence resonance energy transfer signals. With this design, the logic-gated imaging of endogenous miR-21 and Zn2+ is demonstrated in living cells. More importantly, taking advantages of photoacoustic imaging modality, a combinational logic circuit (AND/OR) is constructed for the bioorthogonal cascade imaging of miR-21 and Zn2+ in vivo, realizing dynamic monitoring of the correlation of miRNA and metal ions levels. Collectively, our results suggest that this conceptual design possesses the ability to expand the DNA nanomachine toolbox for visualizing a broad spectrum of interconnected molecules and thus provides new perspectives to improve the diagnostic and therapeutic outcomes.

16.
Front Immunol ; 13: 960094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389744

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed serious threats to global health and economy and calls for the development of safe treatments and effective vaccines. The receptor-binding domain in the spike protein (SRBD) of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2 (ACE2) receptor. It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines. Here, we showed that dimeric SRBD-Fc and tetrameric 2xSRBD-Fc fusion proteins bind ACE2 with different affinity and block SARS-CoV-2 pseudoviral infection. Immunization of mice with SRBD-Fc fusion proteins elicited high titer of RBD-specific antibodies with robust neutralizing activity against pseudoviral infections. As such, our study indicates that the polymeric SRBD-Fc fusion protein can serve as a treatment agent as well as a vaccine for fighting COVID-19.


Assuntos
Anticorpos Neutralizantes , COVID-19 , Humanos , Camundongos , Animais , Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Proteínas do Envelope Viral , Vacinas contra COVID-19 , Glicoproteínas de Membrana/metabolismo
17.
Allergy Asthma Immunol Res ; 14(6): 604-652, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36426395

RESUMO

In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.

18.
Metabolites ; 12(11)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36422284

RESUMO

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography-mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

19.
Mar Drugs ; 20(11)2022 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-36355019

RESUMO

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.


Assuntos
Heme Oxigenase-1 , Ficocianina , Humanos , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Ficocianina/metabolismo , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antioxidantes/metabolismo , Estresse Oxidativo , Inflamação/tratamento farmacológico , Bilirrubina/metabolismo , Bilirrubina/farmacologia , Bilirrubina/uso terapêutico , Anti-Inflamatórios/farmacologia , Tetrapirróis/farmacologia , Tetrapirróis/uso terapêutico , Fibrose
20.
Diagnostics (Basel) ; 12(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36359503

RESUMO

Pulmonary nodule detection with low-dose computed tomography (LDCT) is indispensable in early lung cancer screening. Although existing methods have achieved excellent detection sensitivity, nodule detection still faces challenges such as nodule size variation and uneven distribution, as well as excessive nodule-like false positive candidates in the detection results. We propose a novel two-stage nodule detection (TSND) method. In the first stage, a multi-scale feature detection network (MSFD-Net) is designed to generate nodule candidates. This includes a proposed feature extraction network to learn the multi-scale feature representation of candidates. In the second stage, a candidate scoring network (CS-Net) is built to estimate the score of candidate patches to realize false positive reduction (FPR). Finally, we develop an end-to-end nodule computer-aided detection (CAD) system based on the proposed TSND for LDCT scans. Experimental results on the LUNA16 dataset show that our proposed TSND obtained an excellent average sensitivity of 90.59% at seven predefined false positives (FPs) points: 0.125, 0.25, 0.5, 1, 2, 4, and 8 FPs per scan on the FROC curve introduced in LUNA16. Moreover, comparative experiments indicate that our CS-Net can effectively suppress false positives and improve the detection performance of TSND.

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