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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
Cell Physiol Biochem ; 35(2): 616-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25612921

RESUMO

BACKGROUND: Nogo-A, a major myelin-associated inhibitor, can inhibit injured optic nerve regeneration. However, whether Amino-Nogo is the most important functional domain of Nogo-A remains unknown. This study aimed to identify the role of Amino-Nogo following optic nerve injury, and the mechanism of the Amino-Nogo-integrin αv signaling pathway in vivo. METHODS: Sprague-Dawley rats with optic nerve crush injury were injected with Nogo-A siRNA (Nogo-A-siRNA), the Nogo-66 functional domain antagonist peptide of Nogo-A (Nep1-40) or a recombinant rat Amino-Nogo-A protein (∆20) into the vitreous cavity to knock down Nogo-A, inhibit Nogo-66 or activate the Amino-Nogo, resparately. Retinal ganglion cell (RGC) density, axon regeneration and the pattern of NPN of visual electrophysiology (flash visual evoked potentials [F-VEP]) at different times post-injury were investigated. RESULTS: Our study revealed a lower RGC survival rate; shorter axonal outgrowth; longer N1, P1 and N2 waves latencies; and lower N1-P1 and P1-N2 amplitudes in the Δ20 group, and Δ20 treatment significantly attenuated integrin αv expression and phosphorylated focal adhesion kinase (p-FAK) levels. In the Nep1-40 and Nogo-A siRNA groups, there were higher RGC survival rates, longer axonal outgrowth, shorter N1 and P1 wave latencies, and higher N1-P1 and P1-N2amplitudes. Nogo-A siRNA treatment significantly increased integrin αv expression and p-FAK levels. Nepl-40 treatment did not alter integrin αv expression. In addition, there was no significant change in integrin α5 in any group. CONCLUSION: These results suggest that the integrin signaling pathway is regulated by Amino-Nogo, which inhibits optic nerve regeneration and functional recovery, and that the integrin subunit involved might be integrin αv but not integrin α5.


Assuntos
Integrina alfaV/metabolismo , Proteínas da Mielina/antagonistas & inibidores , Proteínas da Mielina/química , Regeneração Nervosa , Nervo Óptico/fisiopatologia , Transdução de Sinais , Animais , Potenciais Evocados Visuais , Técnicas de Silenciamento de Genes , Proteínas da Mielina/metabolismo , Proteínas Nogo , Nervo Óptico/citologia , Traumatismos do Nervo Óptico/metabolismo , Traumatismos do Nervo Óptico/fisiopatologia , Fragmentos de Peptídeos/metabolismo , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/metabolismo
8.
Cell Physiol Biochem ; 33(4): 1215-24, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24752241

RESUMO

BACKGROUND/AIMS: The trabecular meshwork (TM) tissue is constantly exposed to dynamic stress caused by intraocular pressure (IOP). The effects of such biomechanical stress on the TM have not been analyzed. This study developed an animal model of fluctuating IOP and evaluated the effects of these fluctuations on TM tissue. METHODS: To create fluctuation in the IOP, one eye of adult SD rats was exposed to cyclic stress with IOP fluctuation ranging from 5 mmHg to 45 mmHg at a 1/60 Hz frequency for 30 minutes every day for several weeks. The other eye was not treated and served as the control. Hematoxylin-eosin staining was used to evaluate changes in the ganglion cells and the morphology, thickness and density of the TM; immunohistochemistry was used to detect α-smooth muscle actin (α-SMA), laminin (LA) and fibronectin (FN) expression in the TM. RESULTS: After several weeks of daily IOP fluctuation, the TM thickness remained unchanged, whereas the density dramatically increased. α-SMA, LA and FN were expressed in rat TM tissue, and the percentages of areas with positive expression significantly increased. The IOP was similar in the treated and control eyes and only tended to increase on day 22 of the experiment. Throughout the 28-day experiment, no ganglion cells were lost. CONCLUSIONS: Large fluctuations in IOP promoted the synthesis of α-SMA, LA and FN in the TM and increased the density of the TM, suggesting that fluctuations in IOP can induce pathological changes in the TM.


Assuntos
Matriz Extracelular/metabolismo , Pressão Intraocular/fisiologia , Malha Trabecular/metabolismo , Actinas/metabolismo , Animais , Fibronectinas/metabolismo , Imuno-Histoquímica , Laminina/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/patologia , Estresse Fisiológico , Malha Trabecular/patologia
9.
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.

10.
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
11.
Neurochem Res ; 38(7): 1365-74, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23579387

RESUMO

Nogo-A is a myelin-derived inhibitor playing a pivotal role in the prevention of axonal regeneration. A functional domain of Nogo-A, Amino-Nogo, exerts an inhibitory effect on axonal regeneration, although the mechanism is unclear. The present study investigated the role of the Amino-Nogo-integrin signaling pathway in primary retinal ganglion cells (RGCs) with respect to axonal outgrowth, which is required for axonal regeneration. Immunohistochemistry showed that integrin αv, integrin α5 and FAK were widely expressed in the visual system. Thy-1 and GAP-43 immunofluorescence showed that axonal outgrowth of RGCs was promoted by Nogo-A siRNA and a peptide antagonist of the Nogo-66 functional domain of Nogo-A (Nep1-40), and inhibited by a recombinant rat Nogo-A-Fc chimeric protein (Δ20). Western blotting revealed increased integrin αv and p-FAK expression in Nogo-A siRNA group, decreased integrin αv expression in Δ20 group and decreased p-FAK expression in Nep1-40 group. Integrin α5 expression was not changed in any group. RhoA G-LISA showed that RhoA activation was inhibited by Nogo-A siRNA and Δ20, but increased by Nep1-40 treatment. These results suggest that Amino-Nogo inhibits RGC axonal outgrowth primarily through the integrin αv signaling pathway.


Assuntos
Axônios , Proteínas da Mielina/metabolismo , Células Ganglionares da Retina/citologia , Transdução de Sinais , Animais , Sequência de Bases , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Técnicas de Silenciamento de Genes , Integrina alfa5/metabolismo , Proteínas da Mielina/genética , Proteínas Nogo , Nervo Óptico/enzimologia , Fosforilação , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Células Ganglionares da Retina/metabolismo , Córtex Visual/enzimologia , Proteína rhoA de Ligação ao GTP/metabolismo
12.
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
13.
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.

14.
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
15.
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
16.
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.

17.
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
18.
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
19.
Zhonghua Yan Ke Za Zhi ; 47(1): 54-8, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21418929

RESUMO

OBJECTIVE: To study the expression of Nogo-A and Nogo receptor (NgR) in the development of neonatal rats retinal and visual cortex and their effects on the development of central nervous system (CNS). METHODS: Immunohistochemical staining method was used to detect the expression of Nogo-A and NgR in neonatal rats retinal and visual cortex at 1, 3, 7, 14, 28, 56 days after birth. One-way Anova was used to analyze the results of Western blot analysis of Nogo-A and NgR in neonatal rats visual cortex. RESULTS: Nogo-A and NgR was found to express in neonatal rats retinal and visual cortex at the developing stage. In 1, 3, 7, 14, 28, 56 days, the IDV ratio of Nogo-A was 0.852 ± 0.026, 0.917 ± 0.024, 0.810 ± 0.028, 0.417 ± 0.053, 0.258 ± 0.029, 0.298 ± 0.054 respectively and the IDV ratio of NgR was 0.070 ± 0.014, 0.185 ± 0.035, 0.678 ± 0.046, 0.705 ± 0.021, 1.210 ± 0.057, 1.140 ± 0.0420 respectively by Western blot analysis. The expression of Nogo-A was decreased (F = 376.56, P = 0.000) and the expression of NgR was increased (F = 888.26, P = 0.000) during postnatal development. CONCLUSION: Nogo-A and NgR is closely related to the CNS growth and development.


Assuntos
Proteínas da Mielina/metabolismo , Receptores de Superfície Celular/metabolismo , Retina/metabolismo , Córtex Visual/metabolismo , Animais , Animais Recém-Nascidos , Proteínas Ligadas por GPI/metabolismo , Proteínas Nogo , Receptor Nogo 1 , Ratos , Ratos Sprague-Dawley
20.
Zhongguo Zhong Yao Za Zhi ; 36(2): 136-41, 2011 Jan.
Artigo em Zh | MEDLINE | ID: mdl-21506409

RESUMO

OBJECTIVE: To study on the differences between chromatopharmacokinetics (pharmacokinetics with fingerprint chromatography) and chromatopharmacodynamics (pharmacodynamics with fingerprint chromatography) of Chinese materia medica formulae to answer the question whether the pharmacokinetic parameters of multiple composites can be utilized to guide the medication of multiple composites. METHOD: On the base of established four chromatopharmacology (pharmacology with chromatographic fingerprint), the pharmacokinetics, and pharmacodynamics were analyzed comparably on their mathematical model and parameter definition. RESULT: On the basis of quantitative pharmacology, the function expressions and total statistical parameters, such as total zero moment, total first moment, total second moment of the pharmacokinetics, and pharmacodynamics were analyzed to the common expressions and elucidated results for single and multiple components in Chinese materia medica formulae. Total quantitative pharmacokinetic, i.e., chromatopharmacokinetic parameter were decided by each component pharmacokinetic parameters, whereas the total quantitative pharmacodynamic, i.e., chromatopharmacodynamic parameter were decided by both of pharmacokinetic and pharmacodynamic parameters of each components. The pharmacokinetic parameters were corresponded to pharmacodynamic parameters with an existing stable effective coefficient when the constitutive ratio of each composite was a constant. CONCLUSION: The effects of Chinese materia medica were all controlled by pharmacokinetic and pharmacodynamic coefficient. It is a special case that the pharmacokinetic parameter could independently guide the clinical medication for single component whereas the chromatopharmacokinetic parameters are not applied to the multiple drug combination system, and not be used to solve problems of chromatopharmacokinetic of Chinese materia medica formulae.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Materia Medica/química , Cromatografia
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