Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 246
Filtrar
1.
Neural Regen Res ; 17(3): 477-481, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34380874

RESUMO

SRY-related HMG-box (Sox) transcription factors are known to regulate central nervous system development and are involved in several neurological diseases. Post-translational modification of Sox proteins is known to alter their functions in the central nervous system. Among the different types of post-translational modification, small ubiquitin-like modifier (SUMO) modification of Sox proteins has been shown to modify their transcriptional activity. Here, we review the mechanisms of three Sox proteins in neuronal development and disease, along with their transcriptional changes under SUMOylation. Across three species, lysine is the conserved residue for SUMOylation. In Drosophila, SUMOylation of SoxN plays a repressive role in transcriptional activity, which impairs central nervous system development. However, deSUMOylation of SoxE and Sox11 plays neuroprotective roles, which promote neural crest precursor formation in Xenopus and retinal ganglion cell differentiation as well as axon regeneration in the rodent. We further discuss a potential translational therapy by SUMO site modification using AAV gene transduction and Clustered regularly interspaced short palindromic repeats-Cas9 technology. Understanding the underlying mechanisms of Sox SUMOylation, especially in the rodent system, may provide a therapeutic strategy to address issues associated with neuronal development and neurodegeneration.

2.
Asian J Androl ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34755700

RESUMO

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 616-621, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821094

RESUMO

Objective: To investigate the effects and mechanisms of taurine up-regulated gene 1 (TUG1) in hepatic fibrosis. Methods: According to the literature, the classic hepatic fibrosis model of rats induced by 1%DMN(1ml/kg/d) was established. The rats with hepatic fibrosis and activated hepatic stellate cells (HSC) were divided into model control group, negative control group (transfected with siRNA negative control), siRNA interference group (transfected with TUG1). At the end of the experiment, hematoxylin eosin (HE) staining was used to detect the pathological changes of liver tissue; reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to determine the expression levels of α-smooth muscle actin (α-SMA), TUG1, collagen I, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), Smad2 and Smad3 in rat liver tissue and activated hepatic stellate cells. Results: Compared with the model control group, the protein and gene levels of TUG1 and α-SMA in the negative control group were increased significantly(P<0.05). The protein and gene levels of TUG1, α-SMA, collagen I, MMP-2, TIMP-1, Smad2 and Smad3 in the liver tissue and activated hepatic stellate cells in the siRNA interference group were decreased (P<0.05) while compared with the blank control group and the negative control group. There were no significant differences in the levels of TUG1, α-SMA, collagen I, MMP-2, TIMP-1, Smad2 and Smad3 in the liver tissue and activated hepatic stellate cells between the control group and the negative control group (P>0.05). Conclusion: TUG1 level is elevated in hepatic fibrosis tissue and activated hepatic stellate cells. Silencing TUG1 may improve the pathological damage of hepatic fibrosis induced by 1% DMN by inhibiting the transforming growth factor(TGF-ß1)/ Smad signaling pathway.


Assuntos
Metaloproteinase 2 da Matriz , Inibidor Tecidual de Metaloproteinase-1 , Actinas/genética , Animais , Células Estreladas do Fígado , Cirrose Hepática/patologia , Metaloproteinase 2 da Matriz/genética , Ratos , Inibidor Tecidual de Metaloproteinase-1/genética , Fator de Crescimento Transformador beta1/genética
4.
PhytoKeys ; 182: 83-91, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629929

RESUMO

A revision of Nertera (Rubiaceae) in Taiwan was carried out by classical taxonomic methods and the presence of two endemic species was confirmed. Only one species, misapplied as N.granadensis, had been reported in the second edition of "Flora of Taiwan", but there were two additional endemic species in this genus: N.nigricarpa and N.taiwaniana confirmed. Nerteranigricarpa is characterised by the entire leaf, purple-black petals, black fruits and dark-purple seeds with raised striate. Nerterataiwaniana has leaves with undulated margins, yellowish-green petals, red fruits and yellow-white seeds without striate. N.granadensis is excluded from the flora of this Island.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34453870

RESUMO

WHAT IS KNOWN ON THE SUBJECT?: Individuals diagnosed with substance use disorders may perceive stigma and suffer from mental health problems. Perceived stigma is related to poor mental health among individuals diagnosed with substance use disorders. The social support deterioration deterrence model proposes that stressors (e.g. perceived stigma) negatively affect mental health via reduced perceived social support. To the best of the present authors' knowledge, the model has never been tested in the context of perceived stigma among individuals diagnosed with substance use disorders. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The paper used structural equation modelling to show that the social support deterioration deterrence model could explain the relationship between perceived stigma and depression among individuals diagnosed with substance use disorders. Perceived support from family and perceived support from friends are mediators in the association between perceived stigma and depression among individuals diagnosed with substance use disorders. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Psychosocial interventions to increase perceived support from family and friends would be helpful in addressing perceived stigma effects on mental health. ABSTRACT: Introduction Although the relationship between perceived stigma and mental health outcomes is documented in the existing literature, very few studies have investigated the mechanism linking perceived stigma and mental health outcomes among individuals diagnosed with substance use disorders. To the best of the present authors' knowledge, the social support deterioration deterrence model has never been tested in the context of perceived stigma among individuals diagnosed with substance use disorders. Aim/Question Guided by the social support deterioration deterrence model, the present study investigated the mediating role of perceived support from three types of social network members (i.e. significant others, family members, and friends) in the association between perceived stigma and depression in individuals diagnosed with substance use disorders. Method The study employed a cross-sectional survey design comprising 300 participants diagnosed with substance use disorders in Taiwan. Results Results of a structural equation modelling analysis indicated that perceived stigma was significantly associated with depression. The relationship between perceived stigma and depression was partially mediated by perceived family support and perceived friend support. Discussion Consistent with the prediction of the social support deterioration deterrence model, the negative effect of perceived stigma on depression for individuals diagnosed with substance use disorders is through the mediating effect of social support. Implications for practices Based on the present study's results, psychosocial interventions to increase perceived support from family and friends would be helpful in addressing negative effects of perceived stigma on mental health among individuals diagnosed with substance use disorders.

6.
Biomed Pharmacother ; 139: 111665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243607

RESUMO

Multicomponent herbal formulas (MCHFs) have earned a wide reputation for their definite efficacy in preventing or treating chronic complex diseases. However, holistic elucidation of the causal relationship between the bioavailable ingredients of MCHFs and their multitarget interactions is very challenging. To solve this problem, pharmacokinetics/pharmacometabolomics-pharmacodynamics (PK/PM-PD) combined with a multivariate biological correlation-network strategy was developed and applied to a classic MCHF, Baoyuan decoction (BYD), to clarify its active components and synergistic mechanism against cardiac hypertrophy (CH). First, multiple plasma metabolic biomarkers for ß-adrenergic agonist-induced CH rats were identified by using untargeted metabolomic profiling, and then, these CH-associated endogenous metabolites and the absorbed BYD-compounds in plasma at different treatment stages after oral administration of BYD were analyzed by using targeted PK and PM. Second, the dynamic relationship of BYD-related compounds and CH-associated endogenous metabolites and signaling pathways was built by using multivariate and bioinformatic correlation analysis. Finally, metabolic-related PD indicators were predicted and further verified by biological tests. The results demonstrated that the bioavailable BYD-compounds, such as saponins and flavonoids, presented differentiated and distinctive metabolic features and showed positive or negative correlations with various CH-altered metabolites and PD-indicators related to gut microbiota metabolism, amino acid metabolism, lipid metabolism, energy homeostasis, and oxidative stress at different treatment stages. This study provides a novel strategy for investigating the dynamic interaction between BYD and the biosystem, providing unique insight for disclosing the active components and synergistic mechanisms of BYD against CH, which also supplies a reference for other MCHF related research.


Assuntos
Cardiomegalia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/farmacocinética , Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Aminoácidos/metabolismo , Animais , Biomarcadores/metabolismo , Cardiomegalia/metabolismo , Sinergismo Farmacológico , Flavonoides/farmacocinética , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Saponinas/farmacocinética , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos
7.
J Pharm Biomed Anal ; 204: 114229, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252820

RESUMO

Quinoline alkaloids are the main bioactive and potentially toxic constituents in the root bark of Dictamnus dasycarpus Turcz. (BXP), a widely used traditional Chinese medicine for the treatment of skin inflammation, eczema and rubella. However, the comprehensive analysis of the chemical components and metabolites of quinoline alkaloids remain unclear. In this study, an integrated strategy by combining UPLC/Q-TOF-MS and UPLC/Qtrap-MS was established to comprehensively profile the quinoline alkaloids from BXP and their metabolites in rat plasma, urine and feces. Q-TOF-MS (MSE mode), Qtrap-MS (EMS, MIM, pMRM and NL mode) were performed for acquiring more precursor ions and clearer precursor product ions. A step-by-step manner based on the diagnostic fragment ions (DFIs), in-house database, ClogP value and dipole moment (µ) was proposed to overcome the complexities due to the similar fragmentation behaviors of the quinoline alkaloids. As a result, a total of 73 quinoline alkaloids were unambiguously or tentatively identified. Among them, 4 furoquinolines, 10 dihydrofuroquinolines, 2 pyranoquinolinones, 4 dihydropyranoquinolinones and 9 quinol-2-ones were characterized in BXP for the first time. Moreover, a total of 98 BXP-related constituents (including 57 prototypes and 41 metabolites) were detected in rat plasma, urine and feces. The metabolic pathways included phase I reactions (O-demethylation, hydroxylation and 2,3-olefinic epoxidation) and phase II reactions (conjugation with glucuronide, sulfate and N-acetylcysteine). In conclusion, the integrated strategy with the proposed stepwise manner is suitable for rapid identifying and characterizing more extensive quinoline alkaloids of BXP in vitro and in vivo. Moreover, the results will be helpful for revealing the pharmacological effective substances or toxic substances of BXP and provide a solid basis for further research.


Assuntos
Alcaloides , Dictamnus , Medicamentos de Ervas Chinesas , Quinolinas , Animais , Cromatografia Líquida de Alta Pressão , Fezes , Casca de Planta , Ratos , Espectrometria de Massas em Tandem
8.
Medicine (Baltimore) ; 100(24): e26307, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128868

RESUMO

INTRODUCTION: 22q13.3 deletion syndrome is a well-known syndrome characterized by typical clinical findings including neonatal hypotonia, absent or severely delayed speech, intellectual disability, and other various features, and detection of a heterozygous deletion of chromosome 22q13.3 with the involvement of at least part of SHANK3. It is reported that 10% to 29% of patients with 22q13.3 deletion syndrome present lymphedema. Protein-losing enteropathy (PLE) has never been reported in 22q13.3 deletion syndrome. PATIENT CONCERNS: The patient presented to our institution for refractory hypoalbuminemia and chronic lymphedema in both legs. DIAGNOSIS: The patient manifested intellectual disability, absent speech, tooth grinding, dysmorphic face, and abnormal hands and toenails. Copy-number variation sequencing confirmed the maternal deletion in 22q13.31-q13.33 (chr22:46285592-51244566, hg19). The patient was genetically diagnosed with 22q13.3 deletion syndrome. INTERVENTIONS: Low-fat diets and medium-chain triglycerides supplements were prescribed. The patient was recommended to wear compression garments and elevate legs. OUTCOMES: The symptom of diarrhea was resolved, but hypoalbuminemia persisted. Lower extremities lymphedema was gradually becoming severe. CONCLUSIONS: Primary lymphedema and PLE can occur simultaneously in a patient with 22q13.3 deletion syndrome. The 2 phenotypes could share the same genetic etiology of congenital lymphatic abnormalities. CELSR1 deletion may play a role in lymphatic dysplasia. The case also provides additional proof of the pathogenic effect of CELSR1 on hereditary lymphedema.


Assuntos
Caderinas/genética , Transtornos Cromossômicos/genética , Linfedema/genética , Enteropatias Perdedoras de Proteínas/genética , Deleção Cromossômica , Cromossomos Humanos Par 22/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Hipoalbuminemia/genética , Deficiência Intelectual/genética , Perna (Membro)/patologia , Adulto Jovem
9.
Opt Express ; 29(11): 16362-16376, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154201

RESUMO

In passively mode-locked fiber lasers (PMLFLs), the dissipative solitons (DSs) can self-organize to form complex structures through delicate interactions. However, it is still elusive to control these soliton structures by external influences. We here find that at a certain critical power, the location between two soliton molecules can be controlled by a slow modulated pump power. After applying the pump power with periodic fluctuation, two soliton molecules oscillate from the state of soliton molecular complex to stable distribution with maximum inter-molecular separation. During this process, the internal structure of each soliton molecule keeps steady. The slow gain depletion and recovery mechanism which plays a dominant role affects the motion of soliton molecules. These results could further expand the molecular analogy of spectroscopy and stimulate the development of optical information storage and processing.

10.
Nature ; 594(7862): 277-282, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34040258

RESUMO

Neurons have recently emerged as essential cellular constituents of the tumour microenvironment, and their activity has been shown to increase the growth of a diverse number of solid tumours1. Although the role of neurons in tumour progression has previously been demonstrated2, the importance of neuronal activity to tumour initiation is less clear-particularly in the setting of cancer predisposition syndromes. Fifteen per cent of individuals with the neurofibromatosis 1 (NF1) cancer predisposition syndrome (in which tumours arise in close association with nerves) develop low-grade neoplasms of the optic pathway (known as optic pathway gliomas (OPGs)) during early childhood3,4, raising  the possibility that postnatal light-induced activity of the optic nerve drives tumour initiation. Here we use an authenticated mouse model of OPG driven by mutations in the neurofibromatosis 1 tumour suppressor gene (Nf1)5 to demonstrate that stimulation of optic nerve activity increases optic glioma growth, and that decreasing visual experience via light deprivation prevents tumour formation and maintenance. We show that the initiation of Nf1-driven OPGs (Nf1-OPGs) depends on visual experience during a developmental period in which Nf1-mutant mice are susceptible to tumorigenesis. Germline Nf1 mutation in retinal neurons results in aberrantly increased shedding of neuroligin 3 (NLGN3) within the optic nerve in response to retinal neuronal activity. Moreover, genetic Nlgn3 loss or pharmacological inhibition of NLGN3 shedding blocks the formation and progression of Nf1-OPGs. Collectively, our studies establish an obligate role for neuronal activity in the development of some types of brain tumours, elucidate a therapeutic strategy to reduce OPG incidence or mitigate tumour progression, and underscore the role of Nf1mutation-mediated dysregulation of neuronal signalling pathways in mouse models of the NF1 cancer predisposition syndrome.


Assuntos
Transformação Celular Neoplásica/genética , Genes da Neurofibromatose 1 , Mutação , Neurofibromina 1/genética , Neurônios/metabolismo , Glioma do Nervo Óptico/genética , Glioma do Nervo Óptico/patologia , Animais , Astrocitoma/genética , Astrocitoma/patologia , Moléculas de Adesão Celular Neuronais/deficiência , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Transformação Celular Neoplásica/efeitos da radiação , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Proteínas do Tecido Nervoso/deficiência , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos da radiação , Nervo Óptico/citologia , Nervo Óptico/efeitos da radiação , Estimulação Luminosa , Retina/citologia , Retina/efeitos da radiação
11.
Ann Palliat Med ; 10(4): 4768-4776, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33894723

RESUMO

BACKGROUND: Chylothorax is caused by accumulation of chylous fluid in the thoracic cavity following injury to the thoracic duct or its tributaries. It is a rare but relatively severe complication of lung cancer surgery, especially after lung resection and mediastinal lymph node dissection. If chylothorax is not treated promptly and effectively, it may result in relatively high mortality rate. Although the majority of patients with chylothorax secondary to lung cancer surgery can be treated with conservative measures, there are still some patients who fail to respond to conservative treatment or suffer from recurrent episodes. This study aims to explore the causes of postoperative chylothorax and how targeted treatment can help achieve better outcomes. METHODS: Four cases of chylothorax secondary to lung cancer surgery are reported in which patients underwent direct lymphangiography (DLG) after failed conservative treatment. RESULTS: Thoracic duct obstruction was found in all patients on DLG, as well as dilated intrathoracic part of the thoracic duct. Thoracic duct reconstruction was performed to successfully treat 3 of the 4 patients. CONCLUSIONS: DLG is of great value in the diagnosis of chylothorax secondary to lung cancer surgery, for which thoracic duct reconstruction proves to be an effective procedure. DLG provides a new objective basis for the diagnosis and treatment of chylothorax. It is our best wish to help more patients with chylothorax secondary to lung cancer surgery.


Assuntos
Quilotórax , Neoplasias Pulmonares , Quilotórax/diagnóstico por imagem , Quilotórax/etiologia , Quilotórax/terapia , Humanos , Linfografia , Complicações Pós-Operatórias , Ducto Torácico/diagnóstico por imagem , Ducto Torácico/cirurgia
12.
Sensors (Basel) ; 21(5)2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33802432

RESUMO

Super-resolution (SR) algorithms based on deep learning have dominated in various tasks, including medical imaging, street view surveillance and face recognition. In the remote sensing field, most of the current SR methods utilize the low-resolution (LR) images that directly bicubic downsampled the high-resolution (HR) images as not only train set but also test set, thus achieving high PSNR/SSIM scores but showing performance drop in application because the degradation model in remote sensing images is subjected to Gaussian blur with unknown parameters. Inspired by multi-task learning strategy, we propose a multiple-blur-kernel super-resolution framework (MSF), in which a multiple-blur-kernel learning module (MLM) optimizes the parameters of the network transferable and sensitive for SR procedures with different blur kernels. Besides, to simultaneously exploit the prior of the large-scale remote sensing images and recurrent information in a single test image, a class-feature capture module (CCM) and an unsupervised learning module (ULM) are leveraged in our framework. Extensive experiments show that our framework outperforms the current state-of-the-art SR algorithms in remotely sensed imagery SR with unknown Gaussian blur kernel.

13.
Nurs Open ; 8(4): 1892-1908, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33745219

RESUMO

AIM: The threats of novel coronavirus disease 2019 (COVID-19) have caused fears worldwide. The Fear of COVID-19 Scale (FCV-19S) was recently developed to assess the fear of COVID-19. Although many studies found that the FCV-19S is psychometrically sound, it is unclear whether the FCV-19S is invariant across countries. The present study aimed to examine the measurement invariance of the FCV-19S across eleven countries. DESIGN: Cross-sectional study. METHODS: Using data collected from prior research on Bangladesh (N = 8,550), United Kingdom (N = 344), Brazil (N = 1,843), Taiwan (N = 539), Italy (N = 249), New Zealand (N = 317), Iran (N = 717), Cuba (N = 772), Pakistan (N = 937), Japan (N = 1,079) and France (N = 316), comprising a total 15,663 participants, the present study used the multigroup confirmatory factor analysis (CFA) and Rasch differential item functioning (DIF) to examine the measurement invariance of the FCV-19S across country, gender and age (children aged below 18 years, young to middle-aged adults aged between 18 and 60 years, and older people aged above 60 years). RESULTS: The unidimensional structure of the FCV-19S was confirmed. Multigroup CFA showed that FCV-19S was partially invariant across country and fully invariant across gender and age. DIF findings were consistent with the findings from multigroup CFA. Many DIF items were displayed for country, few DIF items were displayed for age, and no DIF items were displayed for gender. CONCLUSION: Based on the results of the present study, the FCV-19S is a good psychometric instrument to assess fear of COVID-19 during the pandemic period. Moreover, the use of FCV-19S is supported in at least ten countries with satisfactory psychometric properties.


Assuntos
COVID-19 , Adolescente , Adulto , Idoso , Ansiedade , Bangladesh , Brasil , Criança , Estudos Transversais , Cuba , Medo , França , Humanos , Irã (Geográfico) , Itália , Japão/epidemiologia , Pessoa de Meia-Idade , Nova Zelândia , Paquistão , Reprodutibilidade dos Testes , SARS-CoV-2 , Taiwan , Reino Unido , Adulto Jovem
14.
Int Urogynecol J ; 32(5): 1307-1312, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33620539

RESUMO

INTRODUCTION AND HYPOTHESIS: Interstitial cystitis/bladder pain syndrome (IC/BPS) and irritable bowel syndrome (IBS) often occur concomitantly without an obvious reason. It is important to determine the relationship between these related diseases. We aimed to determine whether IBS increase the risk of IC/BPS. METHODS: We identified newly diagnosed IBS patients between 2002 and 2013 from a nationwide database as the IBS cohort. Subjects diagnosed with IC/BPS before IBS were excluded. Cox's regression analysis with a hazard ratio (HR) of IC/BPS between IBS and the non-IBS cohort was applied to unmatched and matched (16 confounders of propensity scores) models. The time from diagnosis of IBS to IC/BPS was also calculated. RESULTS: In the unmatched group, which included 100,124 IBS (55% female) and 874,048 non-IBS patients, the IC/BPS adjusted HR was 1.292 (95% confidence interval [CI], 1.131-1.476;p < 0.0001) in the IBS cohort compared with the non-IBS cohort. In the matched group, there were 85,359 patients in each cohort, and the IC/BPS HR was 1.599 (95% CI, 1.344-1.903; p < 0.0001). The average numbers of years until the development of IC/BPS in the IBS cohort and non-IBS cohort were 4.60 ± 2.58 (n = 253) and 5.99 ± 3.49 (n = 295) years, respectively. CONCLUSIONS: IBS was shown to increase the risk of IC/BPS in this 12-year cohort study. The time from the diagnosis of IBS to IC/BPS was 5.35 ± 3.18 years. A common pathophysiology of IBS and IC/BPS is possible. Clinicians should be mindful of the association and promote collaborative care of these two elusive diseases.


Assuntos
Cistite Intersticial , Síndrome do Intestino Irritável , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos
15.
eNeuro ; 8(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33441400

RESUMO

The failure of adult CNS neurons to survive and regenerate their axons after injury or in neurodegenerative disease remains a major target for basic and clinical neuroscience. Recent data demonstrated in the adult mouse that exogenous expression of Sry-related high-mobility-box 11 (Sox11) promotes optic nerve regeneration after optic nerve injury but exacerbates the death of a subset of retinal ganglion cells (RGCs), α-RGCs. During development, Sox11 is required for RGC differentiation from retinal progenitor cells (RPCs), and we found that mutation of a single residue to prevent SUMOylation at lysine 91 (K91) increased Sox11 nuclear localization and RGC differentiation in vitro Here, we explored whether this Sox11 manipulation similarly has stronger effects on RGC survival and optic nerve regeneration. In vitro, we found that non-SUMOylatable Sox11K91A leads to RGC death and suppresses axon outgrowth in primary neurons. We furthermore found that Sox11K91A more strongly promotes axon regeneration but also increases RGC death after optic nerve injury in vivo in the adult mouse. RNA sequence (RNA-seq) data showed that Sox11 and Sox11K91A increase the expression of key signaling pathway genes associated with axon growth and regeneration but downregulated Spp1 and Opn4 expression in RGC cultures, consistent with negatively regulating the survival of α-RGCs and ipRGCs. Thus, Sox11 and its SUMOylation site at K91 regulate gene expression, survival and axon growth in RGCs, and may be explored further as potential regenerative therapies for optic neuropathy.


Assuntos
Doenças Neurodegenerativas , Traumatismos do Nervo Óptico , Animais , Axônios/metabolismo , Sobrevivência Celular , Camundongos , Regeneração Nervosa , Doenças Neurodegenerativas/metabolismo , Traumatismos do Nervo Óptico/metabolismo , Processamento de Proteína Pós-Traducional , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo
16.
Toxins (Basel) ; 13(1)2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466634

RESUMO

Protobothrops mucrosquamatus poses a serious medical threat to humans in Southern and Southeastern Asia. Hemorrhage is one of the conspicuous toxicities related to the pathology of P. mucrosquamatus envenoming. Previous in vitro and in vivo studies showed that a silica-derived reagent, sodium silicate complex (SSC), was able to neutralize hemorrhagic and proteolytic activities induced by pit viper venoms, including Crotalus atrox, Agkistrodon contortrix contortrix and Agkistrodon piscivorus leucostoma. In this study, we validated that SSC could neutralize enzymatic and toxic effects caused by the venom of P. mucrosquamatus. We found that SSC inhibited the hemolytic and proteolytic activities induced by P. mucrosquamatus venom in vitro. In addition, we demonstrated that SSC could block intradermal hemorrhage caused by P. mucrosquamatus venom in a mouse model. Finally, SSC could neutralize lethal effects of P. mucrosquamatus venom in the mice. Therefore, SSC is a candidate for further development as a potential onsite first-aid treatment for P. mucrosquamatus envenoming.


Assuntos
Venenos de Crotalídeos/toxicidade , Hemólise/efeitos dos fármacos , Hemorragia/tratamento farmacológico , Silicatos/uso terapêutico , Mordeduras de Serpentes/tratamento farmacológico , Animais , Modelos Animais de Doenças , Hemorragia/induzido quimicamente , Injeções Intradérmicas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Viperidae
17.
Ecol Evol ; 11(1): 376-389, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33437436

RESUMO

Diet analysis of potential small mammals pest species is important for understanding feeding ecology and evaluating their impact on crops and stored foods. Chinese mole shrew (Anourosorex squamipes), distributed in Southwest China, has previously been reported as a farmland pest. Effective population management of this species requires a better understanding of its diet, which can be difficult to determine with high taxonomic resolution using conventional microhistological methods. In this study, we used two DNA metabarcoding assays to identify 38 animal species and 65 plant genera from shrew stomach contents, which suggest that A. squamipes is an omnivorous generalist. Earthworms are the most prevalent (>90%) and abundant (>80%) food items in the diverse diet of A. squamipes. Species of the Fabaceae (frequency of occurrence [FO]: 88%; such as peanuts) and Poaceae (FO: 71%; such as rice) families were the most common plant foods identified in the diet of A. squamipes. Additionally, we found a seasonal decrease in the diversity and abundance of invertebrate foods from spring and summer to winter. Chinese mole shrew has a diverse and flexible diet throughout the year to adapt to seasonal variations in food availability, contributing to its survival even when food resources are limited. This study provides a higher resolution identification of the diet of A. squamipes than has been previously described and is valuable for understanding shrew feeding ecology as well as evaluating possible species impacts on crops.

18.
Mol Genet Genomic Med ; 9(1): e1566, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306870

RESUMO

BACKGROUND: Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia. METHODS: We report a 9-year-old Senior-Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H&E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1. RESULTS: Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5-phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration. CONCLUSION: The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Ciliopatias/genética , Proteínas do Citoesqueleto/genética , Doenças Renais Císticas/genética , Amaurose Congênita de Leber/genética , Atrofias Ópticas Hereditárias/genética , Monoéster Fosfórico Hidrolases/metabolismo , Criança , Cílios/metabolismo , Ciliopatias/metabolismo , Ciliopatias/patologia , Deleção de Genes , Humanos , Rim/metabolismo , Rim/patologia , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/patologia , Amaurose Congênita de Leber/metabolismo , Amaurose Congênita de Leber/patologia , Masculino , Atrofias Ópticas Hereditárias/metabolismo , Atrofias Ópticas Hereditárias/patologia , Monoéster Fosfórico Hidrolases/genética
19.
PLoS One ; 15(12): e0242884, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33315889

RESUMO

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies.


Assuntos
Fatores de Transcrição MEF2/metabolismo , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/patologia , Células Ganglionares da Retina/patologia , Alelos , Animais , Contagem de Células , Humanos , Fatores de Transcrição MEF2/deficiência , Fatores de Transcrição MEF2/genética , Camundongos , Traumatismos do Nervo Óptico/genética , Mutação Puntual , Transdução de Sinais
20.
Medicine (Baltimore) ; 99(47): e23413, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217887

RESUMO

This study aims to explore effect of initiation of renal replacement therapy (RRT) on mortality in acute pancreatitis (AP) patients. In this study, a total of 92 patients from the surgical intensive care unit (SICU) of the Second Affiliated Hospital of Harbin Medical University who were diagnosed with AP and underwent RRT or not between January 2014 and December 2018 were included in this retrospective study. Demographic and clinical data were obtained on admission to SICU. Patients were divided into early initiation of RRT group (n = 44) and delayed initiation of RRT group (n = 48). Duration of mechanical ventilation (MV), intra-peritoneal pressure, vasopressors infusion, body temperature, procalcitonin, creatinine, platelet counts, length of hospital stay and prognosis were recorded during hospitalization, and then compared between groups. Patients with delayed initiation of RRT exhibited significantly higher APACHE II score, SOFA score and lower GCS score than those with early initiation of RRT (P < 0.001, <0.001,  = 0.04, respectively). No difference in the rest of the baseline data and vasopressors infusion was found. Dose of Norepinephrine, maximum and mean PCT, maximum and mean creatinine, maximum and mean intra-peritoneal pressure, length of hospital stay, prognosis of ICU and hospitalization showed significant difference between groups. Early initiation of RRT may be beneficial for AP patients, which can provide some insight and support for patients' treatment in clinic.


Assuntos
Pancreatite/mortalidade , Pancreatite/terapia , Terapia de Substituição Renal , APACHE , Adulto , Biomarcadores/sangue , China , Feminino , Escala de Coma de Glasgow , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos Retrospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...