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1.
BMC Ophthalmol ; 21(1): 395, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34781914

RESUMO

BACKGROUND: To compare the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) and Kahook Dual Blade (KDB) excisional goniotomy in patients with uncontrolled juvenile open-angle glaucoma (JOAG). METHODS: Thirty-three patients (46 eyes) were included in this single-center, retrospective, comparative study and treated with GATT (36 eyes) or KDB goniotomy (13 eyes). Intraocular pressure (IOP), number of glaucoma medications, adverse events, and additional anti-glaucoma procedures were collected during pre- and postoperative visits. Surgical success was defined as 6 mmHg ≤ IOP ≤ 18 mmHg and ≥ 20% IOP reduction from baseline with (partial success) or without (complete success) IOP-lowering medications. RESULTS: The mean ± SD preoperative IOP was 30.48 ± 12.9 mmHg and 26.08 ± 13.1 mmHg (P = 0.164) on 3.71 ± 0.46 and 3.08 ± 0.86 (P = 0.023) glaucoma medications in GATT and KDB group, respectively. At 3 months, the mean ± SD IOP was 15.48 ± 5.93 mmHg and 20.0 ± 10.8 mmHg after GATT and KDB, respectively (P = 0.072). The percentage of IOP lowering from baseline was 44.4 in the GATT group and 14.1 in the KDB group (P = 0.011). The mean reduction in medications was 2.6 ± 1.7 and 0.8 ± 1.2 three months after GATT and KDB, respectively (P < 0.001). Cumulative proportion of partial and complete success were 65.6 and 44.7% in the GATT group, 30.8 and 15.4% in the KDB group at 6 months. Additional procedures were required in 13.9% of cases after GATT and in 61.5% after KDB (P = 0.001). Patients in the GATT group with prior anti-glaucoma procedures and postoperative IOP spikes were more likely to fail, while those with complete trabeculotomy had a better prognosis. CONCLUSIONS: Reduction of IOP and medications were greater after GATT in uncontrolled JOAG eyes. Whereas, more additional IOP-lowering procedures were required after KDB goniotomy. TRIAL REGISTRATION: This study was registered under the Chinese Clinical Trial Registry ( ChiCTR2000034172 , 27/06/2020).


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Trabeculectomia , Seguimentos , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Gonioscopia , Humanos , Pressão Intraocular , Estudos Retrospectivos , Resultado do Tratamento
2.
Eur J Neurol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34710256

RESUMO

BACKGROUND AND PURPOSE: The present study aimed to explore whether and how omega-3 (ω-3) supplementation could interact with genetic factors to modulate cognitive functions, amyloid pathologies, and Alzheimer's disease (AD) risk. METHODS: A total of 1,670 non-demented participants (mean age 73 years, 47% females, 41% APOE ε4 carriers) were followed up for 10 years. Hierarchical regressions, linear mixed-effects models, and Cox proportional hazards models were used to examine the interaction effects of ω-3 supplementation with APOE ε4 and polygenic hazard scores, after adjusting for age, gender, education, cognitive diagnosis, insomnia, depression, anxiety, and cardiovascular risk score. RESULTS: Individuals who progress to AD during the follow-up tend to take a shorter duration of ω-3 at baseline than those stable, for whom the difference remained significant only amongst APOE ε4 carriers (p < 0.01). The interaction term (APOE ε4 × ω-3) accounted for a significant amount of variance in cognition and cerebral amyloid burden. Long-term ω-3 use protected cognition (especially memory function) and lowered amyloid burden and AD risk only amongst APOE ε4 carriers. Mediation analysis suggested that amyloid pathologies, brain reserve capacities, and brain metabolism mediated the relationships of ω-3 use with memory and global cognition for APOE ε4 (+) carriers. Similar interaction and mediation effects were also indicated amongst high-risk subjects defined by polygenic hazard scores. CONCLUSIONS: Long-term ω-3 intake may have a role in AD prevention in genetically at-risk populations.

3.
Transpl Int ; 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34628685

RESUMO

BK polyomavirus (BKPyV) reactivation is regularly monitored after kidney transplant to prevent progression to BK associated nephropathy (BKAN). The New England BK Consortium, made up of 12 transplant centres in the northeastern United States, conducted a quality improvement project to examine adherence to an agreed upon protocol for BKPyV screening for kidney transplants performed in calendar years 2016-2017. In a total of 1047 kidney transplant recipients (KTR) from 11 transplant centres, 204 (19%) had BKPyV infection, defined as detection of BKPyV in plasma, with 41 (4%) KTR progressing to BKAN, defined by either evidence on biopsy tissues or as determined by treating nephrologists. BKPyV infection was treated with reduction of immune suppressants (RIS) in >70% of the patients in all but two centres. There was no graft loss because of BKAN during the two-year follow-up. There were nine cases of post-RIS acute rejection detected during this same period. Adherence to the protocol was low with 54% at 12 months and 38% at 24 months, reflecting challenges of managing transplant patients at all centres. The adherence rate was positively correlated to increased detection of BKPyV infection and was unexpectedly positively correlated to an increase in diagnosis of BKAN.

4.
Exp Eye Res ; 212: 108796, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34662543

RESUMO

The growing need for viewing the detailed 3D structures of various tissues and organs requires advanced tissue processing and imaging techniques. However, light scattering by tissues hinders detailed structural observations. To overcome this, the emerging technique of "tissue optical clearing" has been flourishing in recent decades, providing excellent opportunities for imaging deep, micro-scale structures of various organs, or even of the whole body. In recent years, advanced tissue clearing techniques have been optimized for specific tissues and organs. Among these tissues, the eye is unique owing to its delicate structure and pigmented retinal epithelial cells, calling for more work on making these tissues "transparent". In this review, we searched Medline and Embase for studies published between January 2006 and August 2021 using the terms "tissue optical clearing", "ophthalmology", "eye", and "optical clearing agents", and we reviewed the publications on the optical clearing techniques of eye tissue from 2006 to the present, including both the clearing procedures and the subsequent analytical processes, thus gaining more insight into the application of tissue optical clearing in basic eye research. Furthermore, we discuss the future potential of optical clearing applications in clinical ophthalmology.

5.
Infect Immun ; 89(12): e0031521, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34543119

RESUMO

Mycobacterium tuberculosis is a chronic infectious disease pathogen. To date, tuberculosis is a major infectious disease that endangers human health. To better prevent and treat tuberculosis, it is important to study the pathogenesis of M. tuberculosis. Based on early-stage laboratory research results, in this study, we verified the upregulation of sod2 in Bacillus Calmette-Guérin (BCG) and H37Rv infection. By detecting BCG/H37Rv intracellular survival in sod2-silenced and sod2-overexpressing macrophages, sod2 was found to promote the intracellular survival of BCG/H37Rv. miR-495 then was determined to be downregulated by BCG/H37Rv. BCG/H37Rv can upregulate sod2 expression by miR-495 to promote the intracellular survival of BCG/H37Rv through a decline in ROS levels. This study provides a theoretical basis for developing new drug targets and treating tuberculosis.

6.
Acta Otolaryngol ; 141(9): 860-864, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34565304

RESUMO

BACKGROUND: The incidence of local recurrence after transoral CO2 laser microsurgery for T1b-T2 glottic carcinoma is relatively low. Multiple risk factors have been described for the development of local recurrence after treatment. However, to date, there is no analysis or systematic review investigating the relationships between clinical and histopathological factors and the appearance of local recurrence after transoral CO2 laser microsurgery in T1b-T2 glottic carcinoma patients. AIMS/OBJECTIVE: To investigate risk factors for local recurrence after CO2 laser surgery in T1b-T2 glottic carcinoma involving bilateral vocal cords. MATERIAL AND METHODS: We retrospectively studied patients undergoing CO2 laser surgery for T1b-T2 glottic carcinoma involving bilateral vocal cords. Multiple follow-up laryngoscopies and computed tomographies were performed. Main outcome measures: survival rate, local recurrence rate, and independent risk factors for recurrence. RESULTS: All 85 patients (83 male; age, 63.33 ± 10.59 years; 36 T1b and 49 T2 lesions; 28 cases with and 57 without anterior commissure (AC) involvement) survived; 15 exhibited postoperative local recurrence. Recurrence rates differed between the following groups: patients without (6/57) versus patients with AC involvement (9/28) (p = .007); patients with negative (11/77) versus positive resection margins (4/8) (p = .014); p53-negative (5/51) versus p53-positive patients (10/34) (p = .0132). AC involvement, positive resection margins, and p53 expression were independent risk factors for recurrence. CONCLUSIONS: Patients with stage T1b and T2 glottic carcinoma with AC involvement, positive resection margins, and p53 expression should be followed up at shorter intervals. SIGNIFICANCE: This article provided valid clinical data for risk factors for local recurrence after CO2 laser surgery for T1b-T2 glottic carcinoma involving bilateral vocal cords.

7.
Biosci Rep ; 41(10)2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34505627

RESUMO

Inflammatory response mediated by immune cells is either directly or indirectly regulated by mesenchymal stromal cells (MSCs). Accumulating evidence suggests that thrombospondin-1 (TSP-1) is highly expressed in response to inflammation. In this work, we isolated and identified human thymic mesenchymal stromal cells (tMSCs) and detected the expression of TSP-1. We found that tMSCs expressed TSP-1 and Poly (I:C) or LPS treatment promoted the expression of TSP-1. Further, we isolated and identified exosomes originating from tMSCs (MEXs). Notably, exosomes derived from LPS-pretreated tMSCs (MEXsLPS) promoted the polarization of macrophages to M1-like phenotype and IL-6, TNF-α secretion as well as the pro-inflammatory differentiation of CD4+T cells into Th17 cells. Upon silencing the expression of TSP-1 in tMSCs, the pro-inflammatory effects of MEXsLPS were suppressed. Therefore, these findings uncovered TSP-1 as the principal factor in MEXsLPS pro-inflammatory regulation.

8.
Front Oncol ; 11: 729418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513706

RESUMO

Esophageal cancer is a common malignancy worldwide and a leading cause of cancer-related mortality. Definitive concurrent chemoradiotherapy (CCRT) has been widely used to treat locally advanced esophageal squamous cell carcinoma (ESCC). In this study, we evaluated the predictive power of a 35-gene mutation profile and radiation parameters in patients with ESCC. Data from 44 patients with ESCC who underwent definitive CCRT were retrospectively reviewed. A 35-gene mutation profile, derived from reported ESCC-specific next-generation sequencing results, and radiation dosimetry parameters were examined using the Kaplan-Meier curve and Cox proportional hazards model. All patients were native Chinese and underwent CCRT with a median follow-up time of 22.0 months. Significant prognostic factors affecting progression-free survival in the multivariable Cox regression model were clinical nodal staging ≥2 (hazard ratio, HR: 2.52, 95% CI: 1.15-5.54, p = 0.022), ≥10% lung volume receiving ≥30 Gy (V30) (HR: 2.36, 95% CI: 1.08-5.17, p = 0.032), and mutation of fibrous sheath interacting protein 2 (FSIP2) (HR: 0.08, 95% CI: 0.01-0.58, p = 0.013). For overall survival, significant prognostic factors in the multivariable Cox regression model were lung V30 ≥10% (HR: 3.71, 95% CI: 1.48-9.35, p = 0.005) and mutation of spectrin repeat containing nuclear envelope protein 1 (SYNE1) (HR: 2.95, 95% CI: 1.25-6.97, p = 0.014). Our cohort showed higher MUC17 (79.5% vs. 5.7%), FSIP2 (18.2% vs. 6.2%), and SYNE1 (38.6% vs. 11.0%) mutation rates and lower TP53 (38.6% vs. 68.7%) mutation rates than the ESCC cohorts from The Cancer Genome Atlas. In conclusion, by using a combination of a 35-gene mutation profile and radiotherapy dosimetry, mutations in FSIP2 and SYNE1 as well as lung V30 were identified as potential predictors for developing a prediction model for clinical outcomes in patients with ESCC administered definitive CCRT.

9.
Virulence ; 12(1): 2296-2313, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34482810

RESUMO

Airway epithelial cells are the first line of defense against respiratory pathogens. Porcine bacterial pathogens, such as Bordetella bronchiseptica, Actinobacillus pleuropneumoniae, Glaesserella (Haemophilus) parasuis, and Pasteurella multocida, breach this barrier to lead to local or systematic infections. Here, we demonstrated that respiratory bacterial pathogen infection disrupted the airway epithelial intercellular junction protein, E-cadherin, thus contributing to impaired epithelial cell integrity. E-cadherin knocking-out in newborn pig tracheal cells via CRISPR/Cas9 editing technology confirmed that E-cadherin was sufficient to suppress the paracellular transmigration of these porcine respiratory bacterial pathogens, including G. parasuis, A. pleuropneumoniae, P. multocida, and B. bronchiseptica. The E-cadherin ectodomain cleavage by these pathogens was probably attributed to bacterial HtrA/DegQ protease, but not host HtrA1, MMP7 and ADAM10, and the prominent proteolytic activity was further confirmed by a serine-to-alanine substitution mutation in the active center of HtrA/DegQ protein. Moreover, deletion of the htrA gene in G. parasuis led to severe defects in E-cadherin ectodomain cleavage, cell adherence and paracellular transmigration in vitro, as well as bacterial breaking through the tracheal epithelial cells, systemic invasion and dissemination in vivo. This common pathogenic mechanism shared by other porcine respiratory bacterial pathogens explains how these bacterial pathogens destroy the airway epithelial cell barriers and proliferate in respiratory mucosal surface or other systemic tissues.

10.
Arq Bras Cardiol ; 117(2): 394-403, 2021 08.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34495239

RESUMO

Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient's own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.


Assuntos
Síndrome de Brugada , COVID-19 , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/genética , Humanos , Pandemias , SARS-CoV-2
11.
Inorg Chem ; 60(17): 13080-13090, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357773

RESUMO

A series of phosphinecarbonylpalladium and -nickel catalysts bearing various substituents on the ligand backbone were prepared, characterized, and used in ethylene polymerization and copolymerization with polar monomers. The Pd and Ni catalysts can achieve high activities as well as high polymer molecular weights in both ethylene polymerization and copolymerization with polar monomers. The electron-donating group from the carbonyl side can effectively increase the polymer molecular weights. Utilization of a cyclic backbone structure can increase the catalytic activities at the expense of the polymer molecular weights. Moreover, installation of a pyridyl moiety in the ligand backbone can enable Lewis acid responsiveness and can enhance the polymerization activities. These results suggest the importance of the ligand backbone for the properties of catalysts in ethylene polymerization and copolymerization reactions.

12.
Ann Transl Med ; 9(13): 1065, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422977

RESUMO

Background: Wnt signaling pathway plays a vital role in the regulation of development. An increasing number of articles about Wnt pathway components have been published. By analyzing these studies' characteristics and qualities, we aim to reveal the current research focus and emerging trends in Wnt signaling. Methods: The databases of Web of Science Core Collection, BIOSIS Citation Index, MEDLINE, etc. were utilized to identify articles on May 23rd, 2020. Wnt signaling pathway-related articles were identified, the 100 most cited articles and articles in the last decade were selected and calculated for citations without self-citation. The subsequent analysis included citation density (citations/article age), time-related flux, authorship, institution, journal, geographic distribution, and theme. Results: These articles were published mainly from 2000 to 2009 (62%). Citations per article ranged from 599 to 3,780 with a median number of 880 times. Most studies (66%) came from the United States. Nusse Roel and Clevers Hans (15 and 13 papers) have contributed significantly to the field. The most highlighted study themes were cancer (15%), embryo development (14%), and cytoplasm signal transduction (11%). From 2011 to 2020, interest in emerging subtopics, including osteogenesis, immune, apoptosis, autophagy, microRNA, and cancer stem cell, are rising. Conclusions: Cancer, embryo development, stem cell, and signal transduction process still play a major role in the field. With multiple emerging subtopics and investigation on an integrated view of the Wnt signal network, the association of Wnt with diseases was further revealed.

13.
J Microbiol ; 59(9): 854-860, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382147

RESUMO

Extraintestinal pathogenic Escherichia coli (ExPEC) is an important zoonotic pathogen that places severe burdens on public health and animal husbandry. There are many pathogenic factors in E. coli. The type VI secretion system (T6SS) is a nano-microbial weapon that can assemble quickly and inject toxic effectors into recipient cells when danger is encountered. T6SSs are encoded in the genomes of approximately 25% of sequenced Gram-negative bacteria. When these bacteria come into contact with eukaryotic cells or prokaryotic microbes, the T6SS assembles and secretes associated effectors. In the porcine ExPEC strain PCN033, we identified four classic rearrangement hotspot (Rhs) genes. We determined the functions of the four Rhs proteins through mutant construction and protein expression. Animal infection experiments showed that the Δrhs-1CT, Δrhs-2CT, Δrhs-3CT, and Δrhs-4CT caused a significant decrease in the multiplication ability of PCN033 in vivo. Cell infection experiments showed that the Rhs protein is involved in anti-phagocytosis activities and bacterial adhesion and invasion abilities. The results of this study demonstrated that rhs1, rhs3, and rh4 plays an important role in the interaction between PCN033 and host cell. Rhs2 has contribution to cell and mice infection. This study helps to elucidate the pathogenic mechanism governing PCN033 and may help to establish a foundation for further research seeking to identify potential T6SS effectors.


Assuntos
Infecções por Escherichia coli/veterinária , Proteínas de Escherichia coli/metabolismo , Doenças dos Suínos/microbiologia , Animais , Aderência Bacteriana , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/metabolismo , Feminino , Intestinos/microbiologia , Camundongos , Família Multigênica , Suínos
14.
Arq. bras. cardiol ; 117(2): 394-403, ago. 2021. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1339157

RESUMO

Resumo Desde dezembro de 2019, observamos o rápido avanço da síndrome respiratória aguda grave causada pelo coronavírus 2019 (SARS-CoV-2). O impacto da evolução clínica de uma infecção respiratória é pouco conhecido em pacientes portadores de arritmias hereditárias, devido à baixa prevalência dessas doenças. Os pacientes que apresentam quadros infecciosos podem exacerbar arritmias primárias ocultas ou bem controladas, por diversos fatores, tais como febre, distúrbios eletrolíticos, interações medicamentosas, estresse adrenérgico e, eventualmente, o próprio dano miocárdico do paciente séptico. O objetivo desta revisão é destacar os principais desafios que podemos encontrar durante a pandemia pela Covid 19, especificamente nos pacientes com arritmias hereditárias, com destaque para a síndrome do QT longo congênito (SQTL), a síndrome de Brugada (SBr), a taquicardia ventricular polimórfica catecolaminérgica (TVPC) e a cardiomiopatia arritmogênica do ventrículo direito.


Abstract Since December 2019 we have observed the rapid advance of the severe acute respiratory syndrome caused by the new coronavirus (SARS-CoV-2). The impact of the clinical course of a respiratory infection is little known in patients with hereditary arrhythmias, due to the low prevalence of these diseases. Patients who present with infectious conditions may exacerbate hidden or well-controlled primary arrhythmias, due to several factors, such as fever, electrolyte disturbances, drug interactions, adrenergic stress and, eventually, the septic patient's own myocardial damage. The aim of this review is to highlight the main challenges we may encounter during the Covid 19 pandemic, specifically in patients with hereditary arrhythmias, with emphasis on the congenital long QT syndrome (LQTS), Brugada syndrome (SBr), ventricular tachycardia polymorphic catecholaminergic (CPVT) and arrhythmogenic right ventricular cardiomyopathy.

15.
Am J Hum Genet ; 108(8): 1466-1477, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237282

RESUMO

Multiple morphological abnormalities of the sperm flagella (MMAF)-induced asthenoteratozoospermia is a common cause of male infertility. Previous studies have identified several MMAF-associated genes, highlighting the condition's genetic heterogeneity. To further define the genetic causes underlying MMAF, we performed whole-exome sequencing in a cohort of 643 Chinese MMAF-affected men. Bi-allelic DNAH10 variants were identified in five individuals with MMAF from four unrelated families. These variants were either rare or absent in public population genome databases and were predicted to be deleterious by multiple bioinformatics tools. Morphological and ultrastructural analyses of the spermatozoa obtained from men harboring bi-allelic DNAH10 variants revealed striking flagellar defects with the absence of inner dynein arms (IDAs). DNAH10 encodes an axonemal IDA heavy chain component that is predominantly expressed in the testes. Immunostaining analysis indicated that DNAH10 localized to the entire sperm flagellum of control spermatozoa. In contrast, spermatozoa from the men harboring bi-allelic DNAH10 variants exhibited an absence or markedly reduced staining intensity of DNAH10 and other IDA components, including DNAH2 and DNAH6. Furthermore, the phenotypes were recapitulated in mouse models lacking Dnah10 or expressing a disease-associated variant, confirming the involvement of DNAH10 in human MMAF. Altogether, our findings in humans and mice demonstrate that DNAH10 is essential for sperm flagellar assembly and that deleterious bi-allelic DNAH10 variants can cause male infertility with MMAF. These findings will provide guidance for genetic counseling and insights into the diagnosis of MMAF-associated asthenoteratozoospermia.


Assuntos
Astenozoospermia/complicações , Modelos Animais de Doenças , Dineínas/genética , Infertilidade Masculina/patologia , Mutação , Fenótipo , Espermatozoides/patologia , Alelos , Animais , Homozigoto , Humanos , Infertilidade Masculina/etiologia , Infertilidade Masculina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Espermatozoides/metabolismo , Sequenciamento Completo do Exoma
16.
Int J Hematol ; 114(3): 355-362, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34302593

RESUMO

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0-122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3-4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.


Assuntos
Linfoma Cutâneo de Células T/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Terapia Combinada , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Humanos , Incidência , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/etiologia , Linfoma Cutâneo de Células T/terapia , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/epidemiologia , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vigilância em Saúde Pública , Sistema de Registros , Adulto Jovem
17.
Mol Brain ; 14(1): 116, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281571

RESUMO

Bacterial meningitis is a life-threatening infectious disease with severe neurological sequelae and a high mortality rate, in which Escherichia coli is one of the primary Gram-negative etiological bacteria. Meningitic E. coli infection is often accompanied by an elevated blood-brain barrier (BBB) permeability. BBB is the structural and functional barrier composed of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes, and we have previously shown that astrocytes-derived TGFß1 physiologically maintained the BBB permeability by triggering a non-canonical hedgehog signaling in brain microvascular endothelial cells (BMECs). Here, we subsequently demonstrated that meningitic E. coli infection could subvert this intercellular communication within BBB by attenuating TGFBRII/Gli2-mediated such signaling. By high-throughput screening, we identified E. coli α-hemolysin as the critical determinant responsible for this attenuation through Sp1-dependent TGFBRII reduction and triggering Ca2+ influx and protein kinase A activation, thus leading to Gli2 suppression. Additionally, the exogenous hedgehog agonist SAG exhibited promising protection against the infection-caused BBB dysfunction. Our work revealed a hedgehog-targeted pathogenic mechanism during meningitic E. coli-caused BBB disruption and suggested that activating hedgehog signaling within BBB could be a potential protective strategy for future therapy of bacterial meningitis.

18.
Front Vet Sci ; 8: 696262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34235206

RESUMO

Mycoplasma hyopneumoniae causes swine respiratory disease worldwide. Due to the difficulty of isolating and cultivating M. hyopneumoniae, very few attenuated strains have been successfully isolated, which hampers the development of attenuated vaccines. In order to produce an attenuated M. hyopneumoniae strain, we used the highly virulent M. hyopneumoniae strain ES-2, which was serially passaged in vitro 200 times to produce the attenuated strain ES-2L, and its virulence was evidenced to be low in an animal experiment. In order to elucidate the mechanisms underlying virulence attenuation, we performed whole-genome sequencing of both strains and conducted comparative genomic analyses of strain ES-2 and its attenuated form ES-2L. Strain ES-2L showed three large fragment deletion regions including a total of 18 deleted genes, compared with strain ES-2. Analysis of single-nucleotide polymorphisms (SNPs) and indels indicated that 22 dels were located in 19 predicted coding sequences. In addition to these indels, 348 single-nucleotide variations (SNVs) were identified between strains ES-2L and ES-2. These SNVs mapped to 99 genes where they appeared to induce amino acid substitutions and translation stops. The deleted genes and SNVs may be associated with decreased virulence of strain ES-2L. Our work provides a foundation for further examining virulence factors of M. hyopneumoniae and for the development of attenuated vaccines.

19.
Lancet Reg Health West Pac ; 10: 100126, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34327343

RESUMO

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. Interpretation: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. Funding: Samsung Biomedical Research Institute.

20.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198485

RESUMO

Brain microvascular endothelial cells (BMECs) constitute the structural and functional basis for the blood-brain barrier (BBB) and play essential roles in bacterial meningitis. Although the BBB integrity regulation has been under extensive investigation, there is little knowledge regarding the roles of long non-coding RNAs (lncRNAs) in this event. The present study aimed to investigate the roles of one potential lncRNA, lncRSPH9-4, in meningitic E. coli infection of BMECs. LncRSPH9-4 was cytoplasm located and significantly up-regulated in meningitic E. coli-infected hBMECs. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated lncRSPH9-4 overexpression in hBMECs mediated the BBB integrity disruption. By RNA-sequencing analysis, 639 mRNAs and 299 miRNAs were significantly differentiated in response to lncRSPH9-4 overexpression. We further found lncRSPH9-4 regulated the permeability in hBMECs by competitively sponging miR-17-5p, thereby increasing MMP3 expression, which targeted the intercellular tight junctions. Here we reported the infection-induced lncRSPH9-4 aggravated disruption of the tight junctions in hBMECs, probably through the miR-17-5p/MMP3 axis. This finding provides new insights into the function of lncRNAs in BBB integrity during meningitic E. coli infection and provides the novel nucleic acid targets for future treatment of bacterial meningitis.


Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Escherichia coli/fisiologia , Metaloproteinase 3 da Matriz/metabolismo , Meningites Bacterianas/genética , Meningites Bacterianas/microbiologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Sequência de Bases , Citoplasma/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Microvasos/patologia , Modelos Biológicos , Permeabilidade , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismo , Transcrição Genética , Regulação para Cima/genética
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