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1.
Mol Biotechnol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38862861

RESUMO

Retinal microangiopathies, such as neovascularization and preretinal and vitreous hemorrhages, are the primary pathological features of diabetic retinopathy (DR). These conditions can worsen visual impairment and may result in blindness. Furthermore, multiple metabolic pathways are associated with microangiopathy in DR. However, the specific underlying pathological mechanisms remain unclear. Several studies have demonstrated the important role of G protein-coupled receptor 124 (Gpr124) in cerebral vascular endothelial cells, but its effect on the retinal endothelium has not been elucidated. In this study, we found that Gpr124 is expressed in both pathological retinal fibrous vascular membranes of DR patients and retinal blood vessels of mice, with elevated protein expression specifically observed in the retinas of DR model mice. Furthermore, Gpr124 expression was elevated after high-glucose treatment of human retinal microvascular endothelial cells (HRMECs). Inhibition of Gpr124 expression affected the high glucose-induced proliferation, migration, and tube-forming ability of HRMECs. We concluded that Gpr124 expression was upregulated in DR and promoted HRMECs angiogenesis in a high-glucose environment. This finding may help to elucidate the pathogenesis of DR and provide a critical research basis for identifying effective treatments.

2.
Phytochem Anal ; 35(4): 817-824, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38279571

RESUMO

METHODOLOGY: The chemical constituents of LCT were identified and quantified using high-performance liquid chromatography with a diode array detector. A characteristic fingerprint was then established and combined with multivariate statistical analysis of 16 common peaks and eight diterpenoids to identify the quality markers. INTRODUCTION: The leaves of Croton tiglium (LCT) have long been used in folk and ethnic medicine in China. Owing to the various regions, the chemical composition and content of LCT may differ, and hence, the quality of medicinal materials may be different. However, quality standards have not yet been established, although some studies have been conducted on their composition. OBJECTIVES: To quantitatively compare the chemical constituents of LCT from different areas and establish a quality evaluation of LCT based on quality markers. RESULTS: Eight quality markers selected based on 16 common peaks and three quality markers selected based on eight diterpenoids can distinguish LCT from three regions. The diterpenoids, including 12-O-acetylphorbol-13-(2-methylbutyrate) (3), 12-O-tiglyl-4-deoxy-4α-phorbol-13-acetate (6), and 12-O-(2-methyl)butyrylphorbol-13-tiglate (8), can be used as potential quality markers for the quality evaluation of LCT. CONCLUSION: Diterpenoids are highly efficient markers for quality evaluation. This study provides robust identification data and lays the foundation for formulating quality standards for LCT.


Assuntos
Croton , Folhas de Planta , Croton/química , Folhas de Planta/química , Cromatografia Líquida de Alta Pressão/métodos , Diterpenos/análise , Diterpenos/química , Controle de Qualidade , China
3.
Molecules ; 29(2)2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38257314

RESUMO

The leaves of C. tiglium have been comprehensively researched for their structurally novel bioactive natural compounds, especially those with anti-schistosomiasis liver fibrosis activity, because ethyl acetate extract, which can be extracted from the leaves of C. tiglium, has good anti-schistosomiasis liver fibrosis effects. One new tigliane-type diterpene, 20-acetyl-13-O-(2-metyl)butyryl-phorbol (1), and nine known (2-10) analogues were isolated from the leaves of C. tiglium. Their structures were elucidated on the basis of spectroscopic analysis and ECD analysis. All diterpenoids had a stronger insecticidal effect on schistosomula, and compounds 2, 4, and 10 had good anti-liver-fibrosis effects. Furthermore, compared with the model group, compound 2 significantly downregulated the protein and mRNA expression of COL-I, COL-III, α-SMA, and TGF-ß1 on TGF-ß1-induced liver fibrosis in LX-2 cells. Meanwhile, compound 2 also regulated the expression of TGF-ß/Smad-pathway-related proteins. The results suggest that diterpenoids from C. tiglium may serve as potential schistosomula-killing and anti-liver-fibrosis agents in the future.


Assuntos
Croton , Diterpenos , Fator de Crescimento Transformador beta1 , Diterpenos/farmacologia , Cirrose Hepática/tratamento farmacológico , Folhas de Planta , Antifibróticos
4.
Plast Reconstr Surg ; 153(3): 539e-548e, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-37010462

RESUMO

BACKGROUND: According to the volume restoration theory, lower facial fat compartments tend to selectively atrophy or hypertrophy with age. The aim of this study was to demonstrate age-related changes in lower facial fat compartments using computed tomography, with strict control of the body mass index and underlying diseases. METHODS: This study included 60 adult women in three age-based categories. The thicknesses of the jowl, labiomandibular, and chin fat compartments were measured using computed tomographic images. The distribution and arrangement of facial blood vessels were further analyzed to provide evidence of the safety of rejuvenation strategies based on the facial volumetric theory. RESULTS: The inferior part of the superficial jowl fat compartment and deep jowl fat compartment thickened with age. The deep layer of the labiomandibular fat compartment thinned with age, and the superficial layer thickened with age. The deep and superficial layers of the chin compartments thickened with age. The facial vein passes through the lower mandibular border at the anterior edge of the masseter muscle and moves upward, perpendicular to the lower mandibular border. The high-risk area of the facial artery had an angle of approximately 45 degrees to the lower mandibular border. CONCLUSIONS: This study suggests that with age, selective thickening or thinning occurs in different lower facial fat compartments. The mandible and masseter muscle were used as reference markers to analyze the courses of the facial artery and facial vein, which can help clinicians to reduce vascular injury.


Assuntos
Face , Mandíbula , Adulto , Humanos , Feminino , Face/diagnóstico por imagem , Queixo , Tomografia Computadorizada por Raios X , Músculo Masseter
5.
Transl Vis Sci Technol ; 12(12): 15, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38088829

RESUMO

Purpose: To use optical coherence tomography angiography (OCTA) to assess the pattern of changes in retinal and choroidal blood flow and structure in healthy volunteers who quickly went from sea level to a plateau and to determine the parameters associated with acute mountain sickness (AMS). Methods: Forty-five individuals (89 eyes) were examined by OCTA and filled out the AMS questionnaire. One baseline examination was performed on the plain, followed by examinations at days 1, 3, and 5 after entering the plateau. Parameters were self-controlled to explore patterns of change, analyzed for correlation with AMS score, and modeled as a nomogram of AMS risk. Results: On the plateau compared to the plain, vascular morphology showed dilated superficial macular retinal vessels and constricted deeper layers with increased vessel length density and fractal dimension; vessel density increased in all retinal strata and decreased in the choroidal macrovascular layer; and thickness increased except for a decrease in mean retinal thickness in the central macular sulcus. The rate of increase in retinal nerve fiber layer (RNFL) thickness in the inner and outer macular rings correlated with AMS score (r = -0.211). The nomogram showed moderate accuracy (AUC = 0.672) and consistency (C-index = 0.659) in assessing AMS risk. Conclusions: In high-altitude hypoxia, retinal vessels dilate and distort, resulting in increased blood flow density and thickness. Increased RNFL thickness in the paracentral macula may be a marker of low AMS risk. Translational Relevance: The changes in the retinal structure of the fundus can be used to assess the risk of developing AMS.


Assuntos
Doença da Altitude , Humanos , Doença da Altitude/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Fundo de Olho , Retina/diagnóstico por imagem , Doença Aguda , Angiografia
6.
Case Rep Nephrol Dial ; 13(1): 129-134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37900933

RESUMO

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with varying clinical presentations. The hereditary susceptibility to IgAN is rather complex. In this report, a Chinese case of IgAN was recruited. Renal biopsy showed the tubular atrophy and dilatation, but the glomerular lesions were rather weak except slight mesangial hyperplasia. Immunological staining of kidney tissue revealed the positive immunological staining of IgA and C3. By using whole-exome sequencing, a heterozygous variant in UMOD gene was found and was confirmed by Sanger sequencing. The variant in UMOD gene might contribute to the disease and this case helps understand the correlation of genotype and phenotypes of UMOD mutations.

7.
Neuron ; 111(12): 1898-1913.e5, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37040764

RESUMO

Aberrant low γ-secretase activity is associated with most of the presenilin mutations that underlie familial Alzheimer's disease (fAD). However, the role of γ-secretase in the more prevalent sporadic AD (sAD) remains unaddressed. Here, we report that human apolipoprotein E (ApoE), the most important genetic risk factor of sAD, interacts with γ-secretase and inhibits it with substrate specificity in cell-autonomous manners through its conserved C-terminal region (CT). This ApoE CT-mediated inhibitory activity is differentially compromised in different ApoE isoforms, resulting in an ApoE2 > ApoE3 > ApoE4 potency rank order inversely correlating to their associated AD risk. Interestingly, in an AD mouse model, neuronal ApoE CT migrates to amyloid plaques in the subiculum from other regions and alleviates the plaque burden. Together, our data reveal a hidden role of ApoE as a γ-secretase inhibitor with substrate specificity and suggest that this precision γ-inhibition by ApoE may protect against the risk of sAD.


Assuntos
Doença de Alzheimer , Apolipoproteína E4 , Camundongos , Animais , Humanos , Apolipoproteína E2/genética , Apolipoproteína E4/genética , Apolipoproteína E3/genética , Secretases da Proteína Precursora do Amiloide , Apolipoproteínas E/genética , Doença de Alzheimer/genética , Peptídeos beta-Amiloides
8.
Food Res Int ; 166: 112602, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36914326

RESUMO

Despite the widespread use of food brand logo frame in food brand logo cues, little is known about how food brand logo frame influences consumers' food preferences. Through five studies, this article explores the food brand logo frame on consumers' food preferences for different food types. For utilitarian foods, framed (vs unframed) food brand logos result in higher (lower) consumers' food preferences (Study 1), and this framing effect is driven by the psychological mechanism of food safety associations (Study 2); for hedonic foods, unframed (vs framed) food brand logos result in higher (lower) consumers' food preferences (Study 3), and this framing effect is driven by the psychological mechanism of food confinement associations (Study 4). Furthermore, this framing effect was also observed among UK consumers (Study 5). The findings contribute to the literature of brand logo and frame effect, as well as to the literature of food association, and bear important implications regarding food brand logo frame design for food marketers when developing food brand logo programs.


Assuntos
Preferências Alimentares , Alimentos , Preferências Alimentares/psicologia , Pesquisa Empírica , Comportamento do Consumidor
9.
Front Bioeng Biotechnol ; 11: 1327027, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38260747

RESUMO

Purpose: This study was aimed to examine the global research status and current research hotspots in the field of tendon stem cells. Methods: Bibliometric methods were employed to retrieve relevant data from the Web of Science Core Collection (WOSCC) database. Additionally, Citespace, Vosviewer, SCImago, and Graphad Prism were utilized to analyze the publication status in this field, identify the current research hotspots, and present a mini-review. Results: The most active countries in this field were China and the United States. Notable authors contributing significantly to this research included Lui Pauline Po Yee, Tang Kanglai, Zhang Jianying, Yin Zi, and Chen Xiao, predominantly affiliated with institutions such as the Hong Kong Hospital Authority, Third Military Medical University, University of Pittsburgh, and Zhejiang University. The most commonly published journals in this field were Stem Cells International, Journal of Orthopedic Research, and Stem Cell Research and Therapy. Moreover, the current research hotspots primarily revolved around scaffolds, molecular mechanisms, and inflammation regulation. Conclusion: Tendon stem cells hold significant potential as seed cells for tendon tissue engineering and offer promising avenues for further research Scaffolds, molecular mechanisms and inflammation regulation are currently research hotspots in this field.

10.
BMC Ophthalmol ; 22(1): 478, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36482340

RESUMO

BACKGROUND: To develop a model for predicting the risk of visual impairment in diabetic retinopathy (DR) by a nomogram. METHODS: Patients with DR who underwent both optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA) were retrospectively enrolled. FFA was conducted for DR staging, swept-source optical coherence tomography (SS-OCT) of the macula and 3*3-mm blood flow imaging by OCTA to observe retinal structure and blood flow parameters. We defined a logarithm of the minimum angle of resolution visual acuity (LogMAR VA) ≥0.5 as visual impairment, and the characteristics correlated with VA were screened using binary logistic regression. The selected factors were then entered into a multivariate binary stepwise regression, and a nomogram was developed to predict visual impairment risk. Finally, the model was validated using the area under the receiver operating characteristic (ROC) curve (AUC), calibration plots, decision curve analysis (DCA), and clinical impact curve (CIC). RESULTS: A total of 29 parameters were included in the analysis, and 13 characteristics were used to develop a nomogram model. Finally, diabetic macular ischaemia (DMI) grading, disorganization of the retinal inner layers (DRIL), outer layer disruption, and the vessel density of choriocapillaris layer inferior (SubVD) were found to be statistically significant (P < 0.05). The model was found to have good accuracy based on the ROC (AUC = 0.931) and calibration curves (C-index = 0.930). The DCA showed that risk threshold probabilities in the (3-91%) interval models can be used to guide clinical practice, and the proportion of people at risk at each threshold probability is illustrated by the CIC. CONCLUSION: The nomogram model for predicting visual impairment in DR patients demonstrated good accuracy and utility, and it can be used to guide clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200059835. Registered 12 May 2022, https://www.chictr.org.cn/edit.aspx?pid=169290&htm=4.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Estudos Retrospectivos , Transtornos da Visão
11.
Mol Cell Neurosci ; 123: 103771, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36064132

RESUMO

The precise control of proliferation and differentiation of neural progenitors is crucial for the development of the central nervous system. Fused in sarcoma (FUS) is an RNA-binding protein pathogenetically linked to Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD) disease, yet the function of FUS on neurodevelopment is remained to be defined. Here we report a pivotal role of FUS in regulating the human cortical brain and spinal cord development via the human iPSCs-derived organoids. We found that depletion of FUS via CRISPR/CAS9 leads to an enhancement of neural proliferation and differentiation in cortical brain-organoids, but intriguingly an impairment of these phenotypes in spinal cord-organoids. In addition, FUS binds to the mRNA of a Trk tyrosine kinase receptor of neurotrophin-3 (Ntrk3) and regulates the expression of the different isoforms of Ntrk3 in a tissue-specific manner. Finally, alleviated Ntrk3 level via shRNA rescued the effects of FUS-knockout on the development of the brain- and spinal cord-organoids, suggesting that Ntrk3 is involved in FUS-regulated organoids developmental changes. Our findings uncovered the role of FUS in the neurodevelopment of the human CNS.


Assuntos
Esclerose Lateral Amiotrófica , Degeneração Lobar Frontotemporal , Humanos , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Organoides/metabolismo , Corpos de Inclusão/metabolismo , Degeneração Lobar Frontotemporal/genética , Esclerose Lateral Amiotrófica/metabolismo , Medula Espinal/metabolismo , Encéfalo/metabolismo
12.
Proteomics Clin Appl ; 16(5): e2100128, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35510950

RESUMO

PURPOSE: The purpose of the present study was to characterize the idiopathic epiretinal membrane (iERM) through proteomics and phosphoproteomics analysis to facilitate the diagnosis and treatment of iERM. EXPERIMENTAL DESIGN: The vitreous of 25 patients with an iERM and 15 patients with an idiopathic macular hole were analyzed by proteomic and phosphoproteomic analysis based on tandem mass tag. PRM was used to verify the differential proteins. RESULTS: Proteomic analysis identified a total of 878 proteins, including 50 differential proteins. Tenascin-C, galectin-3-binding protein, glucose-6-phosphate isomerase, neuroserpin, collagen alpha-1(XI) chain, and collagen alpha-1(II) chain were verified to be upregulated in iERM by PRM. Phosphoproteomic analysis identified a total of 401 phosphorylation sites on 213 proteins, including 27 differential phosphorylation sites on 24 proteins. Mitogen-activated protein kinase-activated protein kinase (MAPKAPK)3 and MAPKAPK5 were predicted as the major kinases in the vitreous of iERM. Twenty-six of the differential proteins and phosphorylated proteins may be closely related to fibrosis in iERM. CONCLUSION AND CLINICAL RELEVANCE: Our results indicated the potential biomarkers or therapeutic targets for iERM, provided key kinases that may be involved in iERM. Fibrosis plays an essential role in iERM, and further exploration of related differential proteins has important clinical significance.


Assuntos
Membrana Epirretiniana , Biomarcadores , Colágeno , Membrana Epirretiniana/diagnóstico , Membrana Epirretiniana/metabolismo , Fibrose , Galectina 3 , Glucose-6-Fosfato Isomerase , Humanos , Proteínas Quinases Ativadas por Mitógeno , Proteínas Quinases , Proteômica/métodos , Tenascina
13.
Clin Chim Acta ; 529: 17-20, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35151619

RESUMO

Mesangial proliferative glomerulonephritis (MsPGN) is the most common clinicopathologic feature of the primary glomerulonephritis. The hereditary susceptibility to MsPGN is rather complex. In this report, a Chinese case of proliferative glomerulosclerosis was recruited. Renal biopsy revealed extensive glomerulosclerosis with mesangial hypertrophy, and tubular atrophy and dilatation. Whole exome sequencing (WES) revealed compound heterozygous variants in TTC21B gene, which were confirmed by Sanger sequencing. The variants in TTC21B gene were the molecular pathogenic basis of this disorder, and this case help to understand the correlation of genotype and phenotypes of TTC21B mutations.


Assuntos
Nefropatias , Proteínas Associadas aos Microtúbulos/genética , Povo Asiático , Predisposição Genética para Doença , Humanos , Mutação , Sequenciamento do Exoma
14.
BMC Ophthalmol ; 22(1): 9, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983454

RESUMO

BACKGROUND: To study the effects of aerobic exercise (AE) on tear secretion and tear film stability in dry eye patients. METHODS: This study consisted of two parts, each part included 3 groups, namely dry eye without AE group, dry eye with AE group and pre-clinical dry eye with AE group. In part 1, we studied the variations of Schirmer I test and six tear compositions before and after AE (34 eyes in each group). In part 2, we studied the variations of tear meniscus height, first and average non-invasive tear breakup time (F-NITBUT and A-NITBUT), lipid layer thickness, number of incomplete and complete blinks, partial blink rate (PBR) and visual acuity before and after AE (30 eyes in each group). RESULTS: In dry eye with AE group, Schirmer I test at 0 min after AE increased significantly compared to baseline (P < 0.001), the oxidative stress marker 8-hydroxy-2'-deoxyguanosine after AE decreased significantly compared to baseline (P = 0.035, P = 0.045), F-NITBUT and A-NITBUT after AE prolonged significantly compared to baseline (P < 0.001, P = 0.007, P = 0.036; P < 0.001, P = 0.001, P = 0.044), number of incomplete blinks and PBR at 10 min after AE decreased significantly compared to baseline (P < 0.001; P < 0.001) while number of complete blinks increased significantly (P < 0.001). Besides, significant differences were also found between dry eye with AE group and dry eye without AE group at all above corresponding time point (P < 0.05). CONCLUSION: AE promotes tear secretion and improves tear film stability in dry eye patients. AE may be a potential treatment for dry eye. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000038673 . Registered 27 September 2020.


Assuntos
Síndromes do Olho Seco , Lágrimas , Piscadela , Exercício Físico , Humanos , Acuidade Visual
15.
Cell Biosci ; 11(1): 158, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380548

RESUMO

BACKGROUND: In the central nervous system (CNS), three types of myelin-associated inhibitors (MAIs) exert major inhibitory effects on nerve regeneration: Nogo-A, myelin-associated glycoprotein (MAG), and oligodendrocyte-myelin glycoprotein (OMgp). MAIs have two co-receptors, Nogo receptor (NgR) and paired immunoglobulin-like receptor B (PirB). Existing studies confirm that inhibiting NgR only exerted a modest disinhibitory effect in CNS. However, the inhibitory effects of PirB on nerve regeneration after binding to MAIs are controversial too. We aimed to further investigate the effect of PirB knockdown on the neuroprotection and axonal regeneration of retinal ganglion cells (RGCs) after optic nerve injury in rats. METHODS: The differential expression of PirB in the retina was observed via immunofluorescence and western blotting after 1, 3, and 7 days of optic nerve injury (ONI). The retina was locally transfected with adeno-associated virus (AAV) PirB shRNA, then, the distribution of virus in tissues and cells was observed 21 days after AAV transfection to confirm the efficiency of PirB knockdown. Level of P-Stat3 and expressions of ciliary neurotrophic factor (CNTF) were detected via western blotting. RGCs were directly labeled with cholera toxin subunit B (CTB). The new axons of the optic nerve were specifically labeled with growth associated protein-43 (GAP43) via immunofluorescence. Flash visual evoked potential (FVEP) was used to detect the P1 and N1 latency, as well as N1-P1, P1-N2 amplitude to confirm visual function. RESULTS: PirB expression in the retina was significantly increased after ONI. PirB knockdown was successful and significantly promoted P-Stat3 level and CNTF expression in the retina. PirB knockdown promoted the regeneration of optic nerve axons and improved the visual function indexes such as N1-P1 and P1-N2 amplitude. CONCLUSIONS: PirB is one of the key molecules that inhibit the regeneration of the optic nerve, and inhibition of PirB has an excellent effect on promoting nerve regeneration, which allows the use of PirB as a target molecule to promote functional recovery after ONI.

16.
Stem Cell Res Ther ; 12(1): 485, 2021 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454631

RESUMO

BACKGROUND: Achondroplasia (ACH) is the most common genetic form of dwarfism and belongs to dominant monogenic disorder caused by a gain-of-function point mutation in the transmembrane region of FGFR3. There are no effective treatments for ACH. Stem cells and gene-editing technology provide us with effective methods and ideas for ACH research and treatment. METHODS: We generated non-integrated iPSCs from an ACH girl's skin and an ACH boy's urine by Sendai virus. The mutation of ACH iPSCs was precisely corrected by CRISPR-Cas9. RESULTS: Chondrogenic differentiation ability of ACH iPSCs was confined compared with that of healthy iPSCs. Chondrogenic differentiation ability of corrected ACH iPSCs could be restored. These corrected iPSCs displayed pluripotency, maintained normal karyotype, and demonstrated none of off-target indels. CONCLUSIONS: This study may provide an important theoretical and experimental basis for the ACH research and treatment.


Assuntos
Acondroplasia , Células-Tronco Pluripotentes Induzidas , Acondroplasia/genética , Acondroplasia/terapia , Diferenciação Celular , Feminino , Edição de Genes , Humanos , Masculino , Mutação , Reparo Gênico Alvo-Dirigido
17.
Nat Commun ; 12(1): 4075, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210972

RESUMO

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.


Assuntos
Oxirredutases do Álcool/metabolismo , Dano ao DNA , Instabilidade Genômica , Proteína HMGB1/metabolismo , Neurônios/metabolismo , RNA Longo não Codificante/metabolismo , Oxirredutases do Álcool/genética , Animais , Fenômenos Biológicos , Cerebelo , Cromatina , Feminino , Regulação da Expressão Gênica , Proteína HMGB1/genética , Masculino , Camundongos , Camundongos Knockout , Mutação , RNA Longo não Codificante/genética
18.
Oncol Rep ; 41(1): 15-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542733

RESUMO

Recently, LOC285194 has shown a potential tumor-suppressor function in several types of human cancers, but its function in non-small cell lung cancer (NSCLC) remains unknown. This study intended to investigate the biological role of LOC285194 and its clinical significance in NSCLC. LOC285194 was detected by qRT-PCR, and its correlation with clinicopathological features of NSCLC was analyzed. The expression of LOC285194 was knocked down or ectopically expressed in lung cancer cells (A549 and H1299) and tumor cell growth, migration and invasion in vitro were investigated. In addition, the interaction of LOC285194 and target proteins was assessed by RNA pulldown and RNA immunoprecipitation in vitro. The results revealed that the expression of LOC285194 was significantly lower in tumor tissues when compared with the corresponding non-tumor tissues (P<0.001). Its expression was correlated with the tumor size (P=0.027). Kaplan-Meier analysis revealed that patients with lower LOC285194 expression had worse disease-free survival and overall survival rates (P<0.05). RNA protein interaction analysis revealed that p53 was the direct binding target of LOC285194 in NSCLC. Bioinformatics analyses suggested that depletion of LOC285149 could affect its antitumor function through the KRAS/BRAF/SMEK pathway. Our findings indicated that LOC285194 was a novel non-coding prognostic indicator and contributed to tumor suppression by targeting p53 in NSCLC, suggesting that it may be a non-coding target for NSCLC gene therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , RNA Longo não Codificante/metabolismo , Proteína Supressora de Tumor p53/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Genes Supressores de Tumor , Humanos , Estimativa de Kaplan-Meier , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/metabolismo
19.
Turk J Pediatr ; 59(2): 1621-168, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29276869

RESUMO

Yan YM, Gong M, Chen JL, Li D, Xu TT, Zou H, Li AQ, Fan QL, Lu QF. Incidence, risk factors and treatment outcomes of drug extravasation in pediatric patients in China. Turk J Pediatr 2017; 59: 162-168. Extravasation injury is a common phenomenon in hospitals. Failure to detect and treat extravasation injury can lead to irreversible local injuries, tissue necrosis and malfunction of the affected tissue. Until now, it is largely unknown about incidence, risk factors and treatment outcomes of extravasation in Chinese pediatric patients. The aim of this study is to explore the incidence, risk factors and summarize the characteristics and treatment outcomes of extravasation injuries resulting in drug extravasation among Chinese children in our hospital. The children undergoing infusion therapy (0-18 years) were enrolled in this study between December 2014 and June 2015 in Shanghai Children`s Hospital. The patients` information including age, gender, injection site, estimated volume of solution extravasated, patient symptoms, severity of extravasation injury, treatment methods, and outcomes was collected. Multivariate logistic regression was used to identify the independent risk factors for the development of extravasation. The incidence of extravasations in pediatric patients was 1.79% (18/1,004). The severity of extravasation was labeled with grade range from Grade 1 through Grade 4: 4 cases with Grade 1, 8 cases with Grade 2, 5 cases with Grade 3, and 1 case with Grade 4. The risk factors of extravasation include infused high volume/day (≥1000 ml), received operation, infused agents with high osmolarity and poor vein condition. The severity of extravasation was related to the large volumes of drug or special drugs (high-osmolarity, high-risk, low pH, etc). All extravasations were treated with physical, pharmacological and surgical intervention according to our standard operation protocols. Systematic implementation of intervention can alleviate the extravasation injuries and improve the patients` outcome.


Assuntos
Gerenciamento Clínico , Extravasamento de Materiais Terapêuticos e Diagnósticos/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/terapia , Feminino , Hidratação , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Nurs Crit Care ; 22(6): 355-361, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27212426

RESUMO

BACKGROUND: Nursing-sensitive indicators are considered effective tools for improving the quality of care in hospitals. However, these have not been used in paediatric intensive care units (PICUs) in China. AIM: To develop nursing-sensitive indicators for PICUs and to assess the quality of nursing in PICUs in China based on the nursing-sensitive indicators. DESIGN: Multi-centre, cross-sectional study. METHODS: Structure, process and outcome indicators were developed and measured from 1 January to 31 March 2014 in seven PICUs in China. RESULTS: The structure indicators showed that one nurse cared for an average of 2·8 patients in a PICU, and 44% of nurses had a bachelor's degree. The process indicators revealed that hand-washing compliance varied across PICUs, whereas pain management and physical restraint have not been adequately addressed in China. The outcome indicators revealed that the incidence rates of ventilator-associated pneumonia and central-line-associated blood stream infections were 2·96 and 0·7, respectively, per 1000 device days. Patients were intubated for a total of 4392 mechanical ventilator days, and 32 patients (7·29‰) had an unplanned extubation. Nurses were moderately satisfied in their jobs (3·1 ± 0·3), and parents reported that nurses provide high quality of care. CONCLUSIONS: This study developed and used nursing-sensitive indicators to assess the quality of nursing in PICUs in China, which provided a reference for national and international comparisons of nursing quality in PICUs. Nursing staffing levels and education should be improved. Pain management and physical restraints should be regulated in China's PICUs. Nurse managers need to explore staff attitudes towards implementation of family-centred care. The development of a national database of nursing quality indicators can contribute to quality and safety improvement. RELEVANCE TO CLINICAL PRACTICE: This study developed a set of nursing-sensitive indicators, and these indicators were used to assess and improve the quality of nursing in PICUs.


Assuntos
Enfermagem de Cuidados Críticos/organização & administração , Cuidados Críticos/organização & administração , Unidades de Terapia Intensiva Pediátrica/organização & administração , Segurança do Paciente/estatística & dados numéricos , Melhoria de Qualidade , Atitude do Pessoal de Saúde , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hospitais Universitários , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Medição de Risco , Taiwan
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