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2.
Nature ; 591(7848): 124-130, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33494096

RESUMO

Although infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has pleiotropic and systemic effects in some individuals1-3, many others experience milder symptoms. Here, to gain a more comprehensive understanding of the distinction between severe and mild phenotypes in the pathology of coronavirus disease 2019 (COVID-19) and its origins, we performed a whole-blood-preserving single-cell analysis protocol to integrate contributions from all major immune cell types of the blood-including neutrophils, monocytes, platelets, lymphocytes and the contents of the serum. Patients with mild COVID-19 exhibit a coordinated pattern of expression of interferon-stimulated genes (ISGs)3 across every cell population, whereas these ISG-expressing cells are systemically absent in patients with severe disease. Paradoxically, individuals with severe COVID-19 produce very high titres of anti-SARS-CoV-2 antibodies and have a lower viral load compared to individuals with mild disease. Examination of the serum from patients with severe COVID-19 shows that these patients uniquely produce antibodies that functionally block the production of the ISG-expressing cells associated with mild disease, by activating conserved signalling circuits that dampen cellular responses to interferons. Overzealous antibody responses pit the immune system against itself in many patients with COVID-19, and perhaps also in individuals with other viral infections. Our findings reveal potential targets for immunotherapies in patients with severe COVID-19 to re-engage viral defence.


Assuntos
Anticorpos Antivirais/imunologia , /fisiopatologia , Interferons/antagonistas & inibidores , Interferons/imunologia , /patogenicidade , Anticorpos Antivirais/sangue , Formação de Anticorpos , Sequência de Bases , /virologia , Feminino , Humanos , Imunoglobulina G/imunologia , Interferons/metabolismo , Masculino , Neutrófilos/imunologia , Neutrófilos/patologia , Domínios Proteicos , Receptor de Interferon alfa e beta/antagonistas & inibidores , Receptor de Interferon alfa e beta/imunologia , Receptor de Interferon alfa e beta/metabolismo , Receptores de IgG/imunologia , Análise de Célula Única , Carga Viral/imunologia
3.
Int Ophthalmol ; 41(3): 1129-1140, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33392941

RESUMO

PURPOSE: Pars plana vitrectomy is the gold standard for the treatment of idiopathic macular hole. Several chromovitrectomy dyes have been used to improve the visualization of the internal limiting membrane (ILM), including indocyanine green, trypan blue (TB), brilliant blue G (BBG), and triamcinolone acetonide (TA). We conducted a network meta-analysis (NMA) to establish the optimum concentration of chromovitrectomy dye-assisted ILM peeling for IMH. METHODS: We searched PubMed, Embase, and Cochrane Library for relevant studies before January 2020. We performed a random-effects NMA using STATA version 15.1 to assess mean difference and odds ratios with 95% confidence intervals. RESULTS: We identified twelve retrospective trails and five randomized controlled trials (RCTs), comprising 1 492 patients of IMH on stage II-IV for ILM peeling. The results of IMH closure rate show that the effect of ILM peeling without dye was better than 0.25% ICG, the effects of ILM peeling with 0.5% ICG or TA were better than without dye, and the effects of ILM peeling with 0.05% BBG, 0.15% TB, 0.5% ICG or 0.05% ICG were better than 0.25% ICG. Ranking probability analysis shows that the rates of IMH closure after ILM peeling with 0.15% TB or 0.05% BBG were better than nine other concentrations of chromovitrectomy dyes. CONCLUSION: The 0.15% TB and 0.05% BBG were recommended as the better efficient treatment-assisted ILM peeling for IMH closure. For retina specialists who prefer to use ICG to assist ILM peeling, 0.05% ICG may be a good choice. However, high-quality large-scale RCTs are recommended to confirm the NMA results.

4.
Ann Acad Med Singap ; 49(10): 829-830, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33283850
5.
Am J Cancer Res ; 10(11): 3920-3934, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33294277

RESUMO

Colorectal cancers (CRC) with microsatellite instability (MSI) or mismatch repair-deficiency (dMMR), but without detectable MMR germline mutations are termed Lynch-like syndrome (LLS). We assess the clinicopathologic and molecular characteristics of LLS tumors and the proportion in LLS, which remain poorly investigated in China. We enrolled 404 CRC patients with surgery in our institution from 2014 to 2018. LLS tumors were detected by a molecular stratification based on MMR protein expression, MLH1 methylation and MMR gene mutation. LLS tumors were profiled for germline mutations in 425 cancer-relevant genes. Among 42 MMR-deficient tumors, 7 (16.7%) were attributable to MLH1 methylation and 7 (16.7%) to germline mutations, leaving 28 LLS cases (66.6%). LLS tumors were diagnosed at a mean age of 60.7 years, had an almost equivalent ratio among rectum, left colon and right colon, and had high rates of lymph node metastases (50%, 4/28 N2). Most MMR gene mutations (88.2%, 15/17) in LLS tumors were variants of unknown significance (VUS). Two novel frameshift mutations were detected in ATM and ARID1A, which are emerging as candidate responsible genes for LLS. In this study, 28 (66.6%) MMRd tumors were classified as LLS, which were significantly higher than reports of western countries. LLS tumors were more likely to carry lymph node metastases. However, it's hard to differentiated LLS tumors from LS through family history, tumor location, histological type of tumors, immunohistochemistry (IHC) for MMR proteins and MSI analysis.

6.
Ann Hum Genet ; 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33249558

RESUMO

Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)-mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole-exome sequencing of 50 DNA samples from a healthy Korean population revealed a total of 13 single nucleotide polymorphisms including five missense variants, D12N, Y497C, H504Q, C707R, and A980V. Recombinant proteins for the five variants of PDE3A (and wild-type protein) were expressed in a FreeStyle 293 expression system with site-directed mutagenesis. The expression of the recombinant PDE3A proteins was confirmed with Western blotting. Catalytic activity of the PDE3A missense variants and wild-type enzyme was measured with a PDE-based assay. Effects of the missense variants on the inhibition of PDE3A activity by cilostazol were also investigated. All variant proteins showed reduced activity (33-53%; p < .0001) compared to the wild-type protein. In addition, PDE3A activity was inhibited by cilostazol in a dose-dependent manner and was further suppressed in the missense variants. Specifically, the PDE3A Y497C showed significantly reduced activity, consistent with the predictions of in silico analyses. The present study provides evidence that individuals carrying the PDE3A Y497C variant may have lower enzyme activity for cAMP hydrolysis, which could cause interindividual variation in cAMP-mediated physiological functions.

7.
Res Sq ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33140041

RESUMO

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a wholeblood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferonstimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and autodirected antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense.

8.
bioRxiv ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33140050

RESUMO

While SARS-CoV-2 infection has pleiotropic and systemic effects in some patients, many others experience milder symptoms. We sought a holistic understanding of the severe/mild distinction in COVID-19 pathology, and its origins. We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease. Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells. Overzealous and auto-directed antibody responses pit the immune system against itself in many COVID-19 patients and this defines targets for immunotherapies to allow immune systems to provide viral defense. One Sentence Summary: In severe COVID-19 patients, the immune system fails to generate cells that define mild disease; antibodies in their serum actively prevents the successful production of those cells.

9.
Molecules ; 25(18)2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971947

RESUMO

Because high-molecular-weight glutenin subunits (HMW-GS) are important contributors to wheat end-use quality, there is a need for high-throughput identification of HMW-GS in wheat genetic resources and breeding lines. We developed an optimized method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) to distinguish individual HMW-GS by considering the effects of the alkylating reagent in protein extraction, solvent components, dissolving volume, and matrix II components. Using the optimized method, 18 of 22 HMW-GS were successfully identified in standard wheat cultivars by differences in molecular weights or by their associations with other tightly linked subunits. Interestingly, 1Bx7 subunits were divided into 1Bx7 group 1 and 1Bx7 group 2 proteins with molecular weights of about 82,400 and 83,000 Da, respectively. Cultivars containing the 1Bx7 group 2 proteins were distinguished from those containing 1Bx7OE using well-known DNA markers. HMW-GS 1Ax2* and 1Bx6 and 1By8 and 1By8*, which are difficult to distinguish due to very similar molecular weights, were easily identified using RP-HPLC. To validate the method, HMW-GS from 38 Korean wheat varieties previously evaluated by SDS-PAGE combined with RP-HPLC were analyzed by MALDI-TOF-MS. The optimized MALDI-TOF-MS method will be a rapid, high-throughput tool for selecting lines containing desirable HMW-GS for breeding efforts.

10.
Int J Ophthalmol ; 13(8): 1272-1280, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821682

RESUMO

AIM: To investigate the affecting factors of parapapillary gamma and delta zones and other fundus morphological features in high myopia. METHODS: Seventy high myopia patients were included in this retrospective observational study and 47 patients were female. Patients were divided into three groups: no posterior staphyloma (no PS), PS with myopic traction maculopathy (PS with MTM), and PS without MTM using 3-dimensional magnetic resonance imaging and optical coherence tomography. MTM patients were further classified into three types [epiretinal membrane, macular hole, and macular retinoschisis (MRS)]. Diameters of the gamma and delta zones were measured among other morphometric variables using fundus photographs. RESULTS: Of the 70 individuals (127 eyes), the mean age was 57.46±13.56y. In univariate analysis, morphological features changed most dramatically in PS with MTM patients, who had the largest gamma zone diameters, the largest disk-fovea distance (DFD) and disk-fovea angle, and the smallest angle kappa and vertical distance of temporal arterial arcade. However, their horizontal delta zone diameter was smaller than in the patients with PS yet without MTM. In multivariate analysis, with axial length (AL) and age adjusted, the horizontal diameter in the delta zone of the PS without MTM group was still significantly larger than in the PS with MTM group (P=0.024). Comparing the three subtypes of MTM patients, the diameters of the gamma zone and DFD in MRS group were the largest. CONCLUSION: The characteristics of the gamma and delta zones change inconsistently in different stages of high myopia. These changes may be associated with anatomical changes caused by local traction. Factors such as PS, AL and age play an important role. These findings may provide a hint about the pathogenesis of traction in high myopia.

11.
Eur J Ophthalmol ; : 1120672120945901, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32757632

RESUMO

PURPOSE: To investigate associated factors with optic disc characteristics in high myopia patients. METHODS: According to the meta-analysis of pathologic myopia study, patients were divided into groups from categories 1 (C1) to C4. The diameters, tilt ratio, and rotation degree of optic disc, and the diameters of parapapillary atrophy were measured among other morphometric variables. RESULTS: Totally 147 eyes (84 patients) were included. Longer horizontal optic disc diameter was associated with smaller tilt ratio (p < 0.001, unstandardized regression coefficient B: -0.59), greater rotation degree (p < 0.001, B: 0.01), and longer horizontal delta zone diameter (p < 0.001, B: 0.09). Longer vertical optic disc diameter was associated with smaller rotation degree (p < 0.001, B: 0.01), longer vertical delta zone diameter (p < 0.001, B: 0.16), and longer disc-fovea distance (DFD; p < 0.024, B: 0.14). Generally, the horizontal optic disc diameter of C3 and C4 groups was smaller than C1 and C2, while vertical diameter and tilt ratio was greater than in C1 and C2. After setting axial length (AL) as an independent variable, horizontal diameters and tilt ratio still showed significant differences, while vertical diameters did not show significant differences. CONCLUSION: Axial elongation was associated with an increase of vertical optic disc diameter that was correlated with an reduction of optic disc rotation degree. By contrast, horizontal optic disc diameter elongation was correlated with an reduction of optic disc tilt ratio and an increase of optic disc rotation degree, which was independent of axial elongation.

12.
Clin Sci (Lond) ; 134(12): 1357-1376, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32490513

RESUMO

Non-specific inhibition of Rho-associated kinases (ROCKs) alleviated renal fibrosis in the unilateral ureteral obstruction (UUO) model, while genetic deletion of ROCK1 did not affect renal pathology in mice. Thus, whether ROCK2 plays a role in renal tubulointerstitial fibrosis needs to be clarified. In the present study, a selective inhibitor against ROCK2 or genetic approach was used to investigate the role of ROCK2 in renal tubulointerstitial fibrosis. In the fibrotic kidneys of chronic kidney diseases (CKDs) patients, we observed an enhanced expression of ROCK2 with a positive correlation with interstitial fibrosis. In mice, the ROCK2 protein level was time-dependently increased in the UUO model. By treating CKD animals with KD025 at the dosage of 50 mg/kg/day via intraperitoneal injection, the renal fibrosis shown by Masson's trichrome staining was significantly alleviated along with the reduced expression of fibrotic genes. In vitro, inhibiting ROCK2 by KD025 or ROCK2 knockdown/knockout significantly blunted the pro-fibrotic response in transforming growth factor-ß1 (TGF-ß1)-stimulated mouse renal proximal tubular epithelial cells (mPTCs). Moreover, impaired cellular metabolism was reported as a crucial pathogenic factor in CKD. By metabolomics analysis, we found that KD025 restored the metabolic disturbance, including the impaired glutathione metabolism in TGF-ß1-stimulated tubular epithelial cells. Consistently, KD025 increased antioxidative stress enzymes and nuclear erythroid 2-related factor 2 (Nrf2) in fibrotic models. In addition, KD025 decreased the infiltration of macrophages and inflammatory response in fibrotic kidneys and blunted the activation of macrophages in vitro. In conclusion, inhibition of ROCK2 may serve as a potential novel therapy for renal tubulointerstitial fibrosis in CKD.


Assuntos
Células Epiteliais/enzimologia , Túbulos Renais Proximais/patologia , Doenças Metabólicas/enzimologia , Quinases Associadas a rho/antagonistas & inibidores , Adolescente , Animais , Anti-Inflamatórios/farmacologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Feminino , Fibrose , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Lactente , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Doenças Metabólicas/patologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Células RAW 264.7 , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima/efeitos dos fármacos , Obstrução Ureteral/enzimologia , Obstrução Ureteral/patologia , Quinases Associadas a rho/metabolismo
13.
Microb Cell Fact ; 19(1): 109, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32448266

RESUMO

BACKGROUND: The biosynthesis of high value-added compounds using metabolically engineered strains has received wide attention in recent years. Myo-inositol (inositol), an important compound in the pharmaceutics, cosmetics and food industries, is usually produced from phytate via a harsh set of chemical reactions. Recombinant Escherichia coli strains have been constructed by metabolic engineering strategies to produce inositol, but with a low yield. The proper distribution of carbon flux between cell growth and inositol production is a major challenge for constructing an efficient inositol-synthesis pathway in bacteria. Construction of metabolically engineered E. coli strains with high stoichiometric yield of inositol is desirable. RESULTS: In the present study, we designed an inositol-synthesis pathway from glucose with a theoretical stoichiometric yield of 1 mol inositol/mol glucose. Recombinant E. coli strains with high stoichiometric yield (> 0.7 mol inositol/mol glucose) were obtained. Inositol was successfully biosynthesized after introducing two crucial enzymes: inositol-3-phosphate synthase (IPS) from Trypanosoma brucei, and inositol monophosphatase (IMP) from E. coli. Based on starting strains E. coli BW25113 (wild-type) and SG104 (ΔptsG::glk, ΔgalR::zglf, ΔpoxB::acs), a series of engineered strains for inositol production was constructed by deleting the key genes pgi, pfkA and pykF. Plasmid-based expression systems for IPS and IMP were optimized, and expression of the gene zwf was regulated to enhance the stoichiometric yield of inositol. The highest stoichiometric yield (0.96 mol inositol/mol glucose) was achieved from recombinant strain R15 (SG104, Δpgi, Δpgm, and RBSL5-zwf). Strain R04 (SG104 and Δpgi) reached high-density in a 1-L fermenter when using glucose and glycerol as a mixed carbon source. In scaled-up fed-batch bioconversion in situ using strain R04, 0.82 mol inositol/mol glucose was produced within 23 h, corresponding to a titer of 106.3 g/L (590.5 mM) inositol. CONCLUSIONS: The biosynthesis of inositol from glucose in recombinant E. coli was optimized by metabolic engineering strategies. The metabolically engineered E. coli strains represent a promising method for future inositol production. This study provides an essential reference to obtain a suitable distribution of carbon flux between glycolysis and inositol synthesis.

14.
Sci Transl Med ; 12(543)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404507

RESUMO

Acute kidney injury (AKI) is a worldwide public health problem with no specific and satisfactory therapies in clinic. The nuclear pregnane X receptor (PXR) is involved in the progression of multiple diseases, including metabolic diseases, atherosclerosis, hypertension, liver injury, etc. However, its role in kidney injury remains to be understood. In this study, we have investigated the role of PXR in AKI and underlying mechanism(s) involved in its function. PXR was robustly down-regulated and negatively correlated with renal dysfunction in human and animal kidneys with AKI. Silencing PXR in rats enhanced cisplatin-induced AKI and induced severe mitochondrial abnormalities, whereas activating PXR protected against AKI. Using luciferase reporter assays, genomic manipulation, and proteomics data analysis on the kidneys of PXR-/- rats, we determined that PXR targeted Aldo-keto reductase family 1, member B7 (AKR1B7) to improve mitochondrial function, thereby ameliorating AKI. We confirmed the protective role of PXR against kidney injury using genomic and pharmacologic approaches in an ischemia/reperfusion model of AKI. These findings demonstrate that disabling the PXR/AKR1B7/mitochondrial metabolism axis is an important factor that can contribute to AKI, whereas reestablishing this axis can be useful for treating AKI.

15.
Pharmacol Res ; 157: 104833, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32302706

RESUMO

The renin-angiotensin system (RAS) is crucial for the physiology and pathology of all the organs. Angiotensin-converting enzyme 2 (ACE2) maintains the homeostasis of RAS as a negative regulator. Recently, ACE2 was identified as the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that is causing the pandemic of Coronavirus disease 2019 (COVID-19). Since SARS-CoV-2 must bind with ACE2 before entering the host cells in humans, the distribution and expression of ACE2 may be critical for the target organ of the SARS-CoV-2 infection. Moreover, accumulating evidence has demonstrated the implication of ACE2 in the pathological progression in tissue injury and several chronic diseases, ACE2 may also be essential in the progression and clinical outcomes of COVID-19. Therefore, we summarized the expression and activity of ACE2 in various physiological and pathological conditions, and discussed its potential implication in the susceptibility of SARS-CoV-2 infection and the progression and prognosis of COVID-19 patients in the current review.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/patologia , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/patologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Progressão da Doença , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/diagnóstico , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Prognóstico
16.
J Zhejiang Univ Sci B ; 21(2): 172-177, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115914

RESUMO

Blakeslea trispora is a natural source of carotenoids, including ß-carotene and lycopene, which have industrial applications. Therefore, classical selective breeding techniques have been applied to generate strains with increased productivity, and microencapsulated ß-carotene preparation has been used in food industry (Li et al., 2019). In B. trispora, lycopene is synthesized via the mevalonate pathway (Venkateshwaran et al., 2015). Lycopene cyclase, which is one of the key enzymes in this pathway, is a bifunctional enzyme that can catalyze the cyclization of lycopene to produce ß-carotene and exhibit phytoene synthase activity (He et al., 2017).

17.
Autoimmunity ; 53(1): 28-34, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31790283

RESUMO

High mobility group box 1 (HMGB1) played pathogenic role in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Recent findings demonstrated that Toll-like receptor 9 (TLR9) was involved in B cell tolerance breaking of autoimmune disease, including AAV. Here, we investigated the effect of HMGB1 on TLR9 in B cells of AAV. In the present work, patients with myeloperoxidase (MPO)-AAV in active stage were recruited. Intracellular TLR9 expression in various B cell subpopulations of the whole blood was detected by flow cytometry and the correlation with clinical data was analysed. Our results showed that intracellular TLR9 expression in B cells, memory B cells and plasmablasts correlated with erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). In particular, TLR9 expression in plasma cells correlated with ESR, CRP, serum creatinine, eGFR, and Birmingham Vasculitis Activity Score. To further explore the effect of HMGB1 on B cell, peripheral blood mononuclear cells (PBMCs) from AAV patients were isolated. After stimulated with HMGB1, TLR9 expression in various B cell subpopulations and proliferation ratio of live B cells were analysed by flow cytometry. We found that TLR9 expression in plasma cells and the proliferation ratio of live B cells by HMGB1 stimulation were significantly upregulated compared with the control group. Therefore, TLR9 expression in plasma cells was associated with disease activity of MPO-AAV. HMGB1 could enhance TLR9 expression in plasma cells and B cell proliferation. These indicated a role of HMGB1 on TLR9 in B cells in MPO-AAV, which would provide potential clues for intervention strategies.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Proteína HMGB1/genética , Peroxidase/metabolismo , Receptor Toll-Like 9/metabolismo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Doenças Autoimunes , Autoimunidade , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Biomarcadores , Proteína HMGB1/metabolismo , Humanos , Imunofenotipagem , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/imunologia , Receptor Toll-Like 9/genética
18.
Int J Ophthalmol ; 12(12): 1917-1928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850178

RESUMO

AIM: To evaluate the effect of internal limiting membrane (ILM) peeling with indocyanine green (ICG), brilliant blue G (BBG), triamcinolone acetonide (TA), trypan blue (TB), or without dye for the treatment of idiopathic macular hole (IMH). METHODS: A search was conducted using PubMed, EMBASE, and CENTRAL (Cochrane Central Register of Controlled Trials) for related studies published before October 2018. RESULTS: A total of 29 studies and 2514 eyes were included in this network Meta-analysis. For IMH closure, the rank from the best to the worse treatment was: BBG, TB, TA, ICG, and no dye. There was a significant difference in postoperative IMH closure rate between BBG and no dye. The rank of the best to the worse treatment to improve visual acuity was: BBG, TB, no dye, TA, and ICG. The improvement rate of visual acuity after using BBG was significantly higher than ICG. The improvement rate of visual acuity was more favorable with TB than ICG, TA, and no dye. CONCLUSION: BBG can contribute to better anatomical and functional outcomes compared to other dyes for ILM peeling in patients with IMH. The results show that the best treatment of ILM peeling with dyes is BBG.

19.
Int J Ophthalmol ; 12(10): 1548-1554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31637189

RESUMO

AIM: To compare the differences and agreement of ocular biometric parameters in highly myopic eyes obtained by optical biometric measurement instruments, the OA-2000 and IOLMaster 500. METHODS: Totally, 90 patients (90 eyes) were included. They were divided into high myopia group and control group. Ocular parameters, including axial length (AL), mean keratometry (Km), anterior chamber depth (ACD), and white to white (WTW), were obtained from the OA-2000 and IOLMaster 500. RESULTS: For the control group, we applied Bland-Altman graphs to assess the 95% limits of agreement (LoA) for most parameters including AL, ACD, Km, and WTW (-0.24 to 0.29 mm, -0.22 to 0.45 mm, -0.39 to 0.31 D, and -0.90 to 0.86 mm, respectively). In high myopia patients, AL, ACD, Km values had wider 95% LoA (-0.34 to 0.32 mm, -0.36 to 0.34 mm, -0.57 to 0.47 D, respectively), except WTW (-0.80 to 0.68 mm). Differences were not statistically significant between these two instruments (P>0.05). CONCLUSION: Most parameters obtained by the OA-2000 and IOLMaster 500 are comparable, including the AL, ACD, and K values. Among them, the agreement of the high myopia patients is poor compared to the patients without high myopia.

20.
J Clin Invest ; 129(10): 4290-4304, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483291

RESUMO

Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Imunidade Inata/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Feminino , Homeostase , Humanos , Lipidômica , Pulmão/patologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica de Transmissão , Nicotina/administração & dosagem , Nicotina/efeitos adversos , Fosfolipídeos/metabolismo , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Fumaça/efeitos adversos , Solventes/administração & dosagem , Solventes/efeitos adversos
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