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1.
Artigo em Inglês | MEDLINE | ID: mdl-38571344

RESUMO

BACKGROUND: Acute Kidney Injury (AKI) is defined as a sudden loss of kidney function, which is often caused by drugs, toxins, and infections. The large spectrum of AKI implies diverse pathophysiological mechanisms. In many cases, AKI can be lethal, and kidney replacement therapy is frequently needed. However, current treatments are not satisfying. Developing novel therapies for AKI is essential. Adult stem cells possess regenerative ability and play an important role in medical research and disease treatment. METHODS: In this study, we isolated and characterized a distinct human urine-derived stem cell, which expressed both proximal tubular cell and mesenchymal stem cell genes as well as certain unique genes. RESULTS: It was found that these cells exhibited robust protective effects on tubular cells and anti- inflammatory effects on macrophages in vitro. In an ischemia-reperfusion-induced acute kidney injury NOD-SCID mouse model, transplantation of USCs significantly protected the kidney morphology and functions in vivo. CONCLUSION: In summary, our results highlighted the effectiveness of USCs in protecting from PTC injury and impeding macrophage polarization, as well as the secretion of pro-inflammatory interleukins, suggesting the potential of USCs as a novel cell therapy in AKI.

2.
Nat Commun ; 15(1): 2623, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521817

RESUMO

In-plane anisotropic van der Waals materials have emerged as a natural platform for anisotropic polaritons. Extreme anisotropic polaritons with in-situ broadband tunability are of great significance for on-chip photonics, yet their application remains challenging. In this work, we experimentally characterize through Fourier transform infrared spectroscopy measurements a van der Waals plasmonic material, 2M-WS2, capable of supporting intrinsic room-temperature in-plane anisotropic plasmons in the far and mid-infrared regimes. In contrast to the recently revealed natural hyperbolic plasmons in other anisotropic materials, 2M-WS2 supports canalized plasmons with flat isofrequency contours in the frequency range of ~ 3000-5000 cm-1. Furthermore, the anisotropic plasmons and the corresponding isofrequency contours can be reversibly tuned via in-situ ion-intercalation. The tunable anisotropic and canalization plasmons may open up further application perspectives in the field of uniaxial plasmonics, such as serving as active components in directional sensing, radiation manipulation, and polarization-dependent optical modulators.

3.
J Clin Invest ; 134(4)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175710

RESUMO

Blood vessels are continually exposed to circulating lipids, and elevation of ApoB-containing lipoproteins causes atherosclerosis. Lipoprotein metabolism is highly regulated by lipolysis, largely at the level of the capillary endothelium lining metabolically active tissues. How large blood vessels, the site of atherosclerotic vascular disease, regulate the flux of fatty acids (FAs) into triglyceride-rich (TG-rich) lipid droplets (LDs) is not known. In this study, we showed that deletion of the enzyme adipose TG lipase (ATGL) in the endothelium led to neutral lipid accumulation in vessels and impaired endothelial-dependent vascular tone and nitric oxide synthesis to promote endothelial dysfunction. Mechanistically, the loss of ATGL led to endoplasmic reticulum stress-induced inflammation in the endothelium. Consistent with this mechanism, deletion of endothelial ATGL markedly increased lesion size in a model of atherosclerosis. Together, these data demonstrate that the dynamics of FA flux through LD affects endothelial cell homeostasis and consequently large vessel function during normal physiology and in a chronic disease state.


Assuntos
Aterosclerose , Lipase , Camundongos , Animais , Triglicerídeos/metabolismo , Lipase/genética , Lipase/metabolismo , Lipólise , Metabolismo dos Lipídeos , Endotélio Vascular/metabolismo , Aterosclerose/genética , Aterosclerose/metabolismo
4.
IEEE J Biomed Health Inform ; 28(3): 1374-1385, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37824310

RESUMO

Transcutaneous vagus nerve stimulation (tVNS) shows a potential regulatory role for motor planning. Still, existing research mainly focuses on behavioral studies, and the neural modulation mechanism needs to be clarified. Therefore, we designed a multi-condition (active or sham, pre or under, difficult or easy, left-hand or right-hand) motor planning experiment to explore the effect of online tVNS (i.e., tVNS and tasks synchronized). Twenty-eight subjects were recruited and randomly assigned to active and sham groups. Both groups performed the same tasks in the experiment and separately collected task-state EEG and 5-min eye-open resting-state EEG. The results showed that the changes in event-related potential (ERP) and movement-related cortical potential (MRCP) amplitudes were more significant for the left-hand difficult task (LD) under active-tVNS. According to the power spectrum results, active-tVNS significantly modulated the activities of the contralateral motor cortex at beta and gamma bands in the resting state. The functional connectivity based on partial directed coherence (PDC) showed significant changes in the parietal lobe after active-tVNS. These findings suggest that tVNS is a promising way to improve motor planning ability.


Assuntos
Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Estimulação do Nervo Vago/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Potenciais Evocados , Nervo Vago/fisiologia , Eletroencefalografia
5.
Am J Trop Med Hyg ; 109(6): 1393-1396, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37931316

RESUMO

We report 26 cases of eye injuries resulting from cobra venom sprayed by Naja atra. This accounts for 14.5% of patients (26/173) treated for cobra injuries who presented to the emergency department of a snakebite treatment center in Guangzhou, South China. Pain, blurred vision, lacrimation, photophobia, and foreign body sensation were the most common symptoms, found in 24 patients. Ophthalmic examination revealed eyelid swelling and conjunctival congestion. Eye slit lamp examination showed obvious punctate corneal epithelial defects in four patients. Five patients received an intravenous infusion of antivenom. All patients' eyes were rinsed completely with normal saline after their arrival at the hospital. Prophylactic topical antibiotics were given to all patients. All eyes were cured without long-term sequelae.


Assuntos
Endoftalmite , Mordeduras de Serpentes , Animais , Humanos , Elapidae , Venenos Elapídicos , Venenos de Serpentes , Endoftalmite/etiologia , Antivenenos/uso terapêutico , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/tratamento farmacológico
6.
Nat Commun ; 14(1): 5314, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658093

RESUMO

The evolution of excitons from 2D to 3D is of great importance in photo-physics, yet the layer-dependent exciton polarizability hasn't been investigated in 2D semiconductors. Here, we determine the exciton polarizabilities for 3- to 11-layer black phosphorus-a direct bandgap semiconductor regardless of the thickness-through frequency-resolved photocurrent measurements on dual-gate devices and unveil the carrier screening effect in relatively thicker samples. By taking advantage of the broadband photocurrent spectra, we are also able to reveal the exciton response for higher-index subbands under the gate electrical field. Surprisingly, dark excitons are brightened with intensity even stronger than the allowed transitions above certain electrical field. Our study not only sheds light on the exciton evolution with sample thickness, but also paves a way for optoelectronic applications of few-layer BP in modulators, tunable photodetectors, emitters and lasers.

7.
J Biosci ; 482023.
Artigo em Inglês | MEDLINE | ID: mdl-37539552

RESUMO

N6-methyladenosine modification and lncRNAs are closely related to the prognosis and immunotherapy response of breast cancer patients. LncRNAs related to m6 A-associated genes were predicted based on coexpression analysis of the TCGA database. We established a novel 7-m6 A-associated lncRNA signature for predicting patient prognosis and validated it. The model was significantly correlated with survival time and survival status and was an independent predictor of overall survival (OS). Except for the M1 disease group, the model had good predictive value for OS in different subgroups. We constructed a prognostic model based on 7 m6 A-associated lncRNAs in breast cancer. This model could serve as an independent prognostic factor with tremendous predictive ability for breast cancer patients.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Bases de Dados Factuais
8.
J Thromb Haemost ; 21(12): 3597-3607, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37604334

RESUMO

BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive platelet aggregation disorder caused by mutations in ITGA2B or ITGB3. OBJECTIVES: We aimed to assess the phenotype and investigate the genetic etiology of a GT pedigree. METHODS: A patient with bleeding manifestations and mild mental retardation was enrolled. Complete blood count, coagulation, and platelet aggregation tests were performed. Causal mutations were identified via whole exome and genome sequencing and subsequently confirmed through polymerase chain reaction and Sanger sequencing. The transcription of ITGB3 was characterized using RNA sequencing and reverse transcription polymerase chain reaction. The αⅡb and ß3 biosynthesis was investigated via whole blood flow cytometry and in vitro studies. RESULTS: GT was diagnosed in a patient with defective platelet aggregation. Novel compound heterozygous ITGB3 variants were identified, with a maternal nonsense mutation (c.2222G>A, p.Trp741∗) and a paternal SINE-VNTR-Alu (SVA) retrotransposon insertion. The 5' truncated SVA element was inserted in a sense orientation in intron 11 of ITGB3, resulting in aberrant splicing of ITGB3 and significantly reducing ß3 protein content. Meanwhile, both the expression and transportation of ß3 were damaged by the ITGB3 c.2222G>A. Almost no αⅡb and ß3 expressions were detected on the patient's platelets surface. CONCLUSION: Novel compound heterozygous ITGB3 mutations were identified in the GT pedigree, resulting in defects of αⅡbß3 biosynthesis. This is the first report of SVA retrotransposon insertion in the genetic pathogenesis of GT. Our study highlights the importance of combining multiple high-throughput sequencing technologies for the molecular diagnosis of genetic disorders.


Assuntos
Trombastenia , Humanos , Trombastenia/diagnóstico , Trombastenia/genética , Retroelementos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Fenótipo , Plaquetas/metabolismo , Integrina beta3/genética , Integrina beta3/metabolismo
9.
Light Sci Appl ; 12(1): 193, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37553359

RESUMO

Naturally existing in-plane hyperbolic polaritons and the associated optical topological transitions, which avoid the nano-structuring to achieve hyperbolicity, can outperform their counterparts in artificial metasurfaces. Such plasmon polaritons are rare, but experimentally revealed recently in WTe2 van der Waals thin films. Different from phonon polaritons, hyperbolic plasmon polaritons originate from the interplay of free carrier Drude response and interband transitions, which promise good intrinsic tunability. However, tunable in-plane hyperbolic plasmon polariton and its optical topological transition of the isofrequency contours to the elliptic topology in a natural material have not been realized. Here we demonstrate the tuning of the optical topological transition through Mo doping and temperature. The optical topological transition energy is tuned over a wide range, with frequencies ranging from 429 cm-1 (23.3 microns) for pure WTe2 to 270 cm-1 (37.0 microns) at the 50% Mo-doping level at 10 K. Moreover, the temperature-induced blueshift of the optical topological transition energy is also revealed, enabling active and reversible tuning. Surprisingly, the localized surface plasmon resonance in skew ribbons shows unusual polarization dependence, accurately manifesting its topology, which renders a reliable means to track the topology with far-field techniques. Our results open an avenue for reconfigurable photonic devices capable of plasmon polariton steering, such as canaling, focusing, and routing, and pave the way for low-symmetry plasmonic nanophotonics based on anisotropic natural materials.

10.
Nano Lett ; 23(15): 6907-6913, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37494570

RESUMO

Stacking bilayer structures is an efficient way to tune the topology of polaritons in in-plane anisotropic films, e.g., by leveraging the twist angle (TA). However, the effect of another geometric parameter, the film thickness ratio (TR), on manipulating the plasmon topology in bilayers is elusive. Here, we fabricate bilayer structures of WTe2 films, which naturally host in-plane hyperbolic plasmons in the terahertz range. Plasmon topology is successfully modified by changing the TR and TA synergistically, manifested by the extinction spectra of unpatterned films and the polarization dependence of the plasmon intensity measured in skew ribbon arrays. Such TR- and TA-tunable topological transitions can be well explained based on the effective sheet optical conductivity by adding up those of the two films. Our study demonstrates TR as another degree of freedom for the manipulation of plasmonic topology in nanophotonics, exhibiting promising applications in biosensing, heat transfer, and the enhancement of spontaneous emission.

11.
J Nucl Med ; 64(9): 1487-1494, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321825

RESUMO

Calcific aortic valve disease (CAVD) is a prevailing disease with increasing occurrence and no known medical therapy. Dcbld2-/- mice have a high prevalence of bicuspid aortic valve (BAV), spontaneous aortic valve calcification, and aortic stenosis (AS). 18F-NaF PET/CT can detect the aortic valve calcification process in humans. However, its feasibility in preclinical models of CAVD remains to be determined. Here, we sought to validate 18F-NaF PET/CT for tracking murine aortic valve calcification and leveraged it to examine the development of calcification with aging and its interdependence with BAV and AS in Dcbld2-/- mice. Methods: Dcbld2-/- mice at 3-4 mo, 10-16 mo, and 18-24 mo underwent echocardiography, 18F-NaF PET/CT (n = 34, or autoradiography (n = 45)), and tissue analysis. A subset of mice underwent both PET/CT and autoradiography (n = 12). The aortic valve signal was quantified as SUVmax on PET/CT and as percentage injected dose per square centimeter on autoradiography. The valve tissue sections were analyzed by microscopy to identify tricuspid and bicuspid aortic valves. Results: The aortic valve 18F-NaF signal on PET/CT was significantly higher at 18-24 mo (P < 0.0001) and 10-16 mo (P < 0.05) than at 3-4 mo. Additionally, at 18-24 mo BAV had a higher 18F-NaF signal than tricuspid aortic valves (P < 0.05). These findings were confirmed by autoradiography, with BAV having significantly higher 18F-NaF uptake in each age group. A significant correlation between PET and autoradiography data (Pearson r = 0.79, P < 0.01) established the accuracy of PET quantification. The rate of calcification with aging was significantly faster for BAV (P < 0.05). Transaortic valve flow velocity was significantly higher in animals with BAV at all ages. Finally, there was a significant correlation between transaortic valve flow velocity and aortic valve calcification by both PET/CT (r = 0.55, P < 0.001) and autoradiography (r = 0.45, P < 0.01). Conclusion: 18F-NaF PET/CT links valvular calcification to BAV and aging in Dcbld2-/- mice and suggests that AS may promote calcification. In addition to addressing the pathobiology of valvular calcification, 18F-NaF PET/CT may be a valuable tool for evaluation of emerging therapeutic interventions in CAVD.


Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Humanos , Camundongos , Animais , Valva Aórtica/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Modelos Animais de Doenças , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia
12.
Materials (Basel) ; 16(7)2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37048930

RESUMO

Cement-treated sand reinforced with geogrids (CTSGs) has higher bending resistance and toughness than cement-treated sands (CTSs). To explore the reinforcement mechanism of geogrids with different stiffness and layers on CTSGs, three-point bending tests and numerical tests based on DEM are carried out on CTS specimens and CTSG specimens considering different reinforcement conditions. The results show that the geogrids and cement-treated sands have good cooperative working performance. Compared with CTSs, CTSG specimens show better ductility, flexural strength and toughness. The increase in geogrid stiffness and geogrid layers promote the reinforcement effect. On the meso-level, different geogrid stiffness and layers affect the crack propagation speed and distributions of cracks due to the anchorage action of geogrids, resulting in different reinforcement effects. In addition, the layers and stiffness of geogrids affect the evolution of the internal force chains of CTSG specimens. Both the increase in geogrid layers and decrease in geogrid stiffness reduce the average internal force of geogrids and weaken the anisotropy of the normal contact force of the specimens. The simulation results interpret the reinforcement mechanism of a CTSG specimen from crack development and internal force evolution, which can support a mesoscopic supplement to laboratory tests.

13.
iScience ; 26(4): 106467, 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37020957

RESUMO

Understanding development of the cerebral vasculature is essential for the central nervous system (CNS) research and therapeutic developments. Here, we developed a simple, convenient, and fast method-the flattened cortex whole mount (FCWM) technique-for imaging of pial cerebral vessels. FCWM involves dissection of the whole cerebral cortex followed by flattening, sectioning and application of CLARITY technology. Compared to conventional methods, FCWM offers several advantages including (1) high-resolution visualization of the whole cortex pial surface vessel structures and distributions; (2) precise localization of a particular blood vessel, allowing observations of a desired blood vessel during normal development or in disease settings; (3) compatibility with confocal imaging. Application of FCWM for examination of cerebral vasculature during postnatal development or in stroke settings allowed us to demonstrate that cerebral blood vessels manifest type-specific maturation and remodeling which are linked to the rate of endothelial proliferation.

14.
J Cosmet Dermatol ; 22(6): 1852-1862, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36762408

RESUMO

BACKGROUND: In recent years, platelet-rich plasma (PRP) has been used in plastic surgery, dermatology, and other treatment procedures worldwide. Since the number of scientific writings has been significantly increasing, it is challenging to generate a manual compilation and systematic review of PRP's therapeutic applications in dermatology and plastic surgeries. This study aimed to make a bibliometric analysis of the literature in the field and evaluate research hotspots and frontiers in this field in the past 20 years. METHODS: Using the Academic Search Premier and ScienceDirect defined search terms, we searched the Web of Science Core Collection (WoSCC) and Scopus databases. All data were analyzed using CiteSpace 5.8.R3 and VOSviewer, including countries, institutions, authors, keywords, cited authors, cited journals, cited references, discovered research hotspots, and frontiers. RESULTS: A total of 1931 studies were retrieved. The number of publications on PRP application in dermatology and plastic surgeries showed a yearly increase. The United States was the most significant contributor to this field, while Italy's contribution was noteworthy. The journal with the highest number of relevant articles in dermatology and plastic surgery included the Journal of Cosmetic Dermatology. However, the Wound Repair and Regeneration and International Journal of Molecular Sciences were the leading journals that should be paid attention to in the future. Author Anitua E from the Tor Vergata University of Rome published the most publications in this field. In the keyword co-occurrence analysis, all keywords were divided into six clusters, and the most common one in recent years was "PRP for facial beauty." Facial rejuvenation, scar, and alopecia were the main hotspots and research trends in this field. CONCLUSIONS: Based on the current global trends, the use of PRP in cosmetics and skin care is receiving increasing attention from researchers and clinicians. Recently, an increasing number of articles on PRP's application in skin tissue repair have been published in the United States and Italy. The number of studies on hair loss, facial rejuvenation, and scar management is increasing, suggesting that these subjects may become research hotspots for PRP in dermatology and cosmetic surgeries in recent years.


Assuntos
Procedimentos de Cirurgia Plástica , Plasma Rico em Plaquetas , Cirurgia Plástica , Humanos , Cicatriz , Alopecia , Bibliometria
15.
Langmuir ; 39(5): 1775-1785, 2023 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-36701766

RESUMO

Corrosion is an irreversible phenomenon in nature that has been a major source of metal degradation. We herein provide a unique approach for embedding nanoparticles into epoxy resins via hydrogen bonding adsorption of in situ hydrophilic silica. Based on this adsorption action, a super-anticorrosive epoxy-based Teflon (MEP-PTFE) coating for usage on metals such as aluminum alloys was developed utilizing one-step dip coating, with promising engineering and public applications. It should be noted that the binding strength between the resultant MEP-PTFE coating and the substrate was 13.5 N. This coating had an impedance modulus of over 8 × 109 Ω·cm2 at 0.01 Hz and an impressive corrosion inhibition efficiency of 99.999%. The anticorrosion barrier from the diffusion control to the charge transfer control was revealed for the future good design of resin matrix coatings with excellent corrosion resistance.

16.
J Refract Surg ; 39(1): 48-55, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36630430

RESUMO

PURPOSE: To investigate refractive prediction accuracy with the OA-2000 (Tomey), Anterion (Heidelberg Engineering), and IOLMaster 500 (Carl Zeiss Meditec AG) in patients with cataract. METHODS: Patients with cataract referred for phacoemulsification were enrolled and scanned with the OA-2000, Anterion, and IOLMaster 500 in random order. The success rate of axial length (AL) measurements per device was calculated and a chi-square test was used to identify the differences in acquisition rate between the three devices. The Bland-Altman method was used to appraise the agreement of biometric parameters between the three devices. Four different formulas (Barrett Universal II [BUII], Haigis, Holladay 1, and SRK/T) were included in the study. The parameters of refractive prediction accuracy comprised predictive error (PE), absolute PE (AE), and percentages of eyes with a PE within ±0.50, ±0.75, and ±1.00 diopters (D). RESULTS: The acquisition rates of AL measurements with the OA-2000 and Anterion were 97.35% and 94.70%, respectively (chi-square = 3.82, P > .05). A significantly lower acquisition rate of 84.82% was obtained with the IOLMaster 500 compared with the other two devices (P < .05). Bland-Altman analysis identified good agreement between the three biometers with narrow 95% limits of agreement for flat and steep keratometry (K1 and K2), anterior chamber depth (ACD), and AL. For PE, only the differences between the Anterion and IOLMaster 500 with the Barrett UII and Haigis formulas were statistically significant (P < .05). The three devices revealed no statistically significant differences in MAE, MedAE, and the proportion of eyes with a PE within ±0.50, ±0.75, and ±1.00 D (P > .05). CONCLUSIONS: The OA-2000 and Anterion showed a similarly higher acquisition rate of AL measurements than the IOLMaster 500 in patients with cataract. Good agreement for K1, K2, ACD, and AL was found between the three biometers. Regarding refractive prediction accuracy, the Anterion did not significantly outperform both the OA-2000 and IOLMaster 500. [J Refract Surg. 2023;39(1):48-55.].


Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Dispositivos Ópticos , Facoemulsificação , Humanos , Refração Ocular , Catarata/diagnóstico , Facoemulsificação/métodos , Biometria/métodos , Óptica e Fotônica , Comprimento Axial do Olho , Estudos Retrospectivos
17.
J Clin Invest ; 133(6)2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36602862

RESUMO

Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit in Grn-/- mice, the exact mechanism for neurodegeneration in FTLD-GRN remains unclear. By performing comparative single-cell transcriptomics in the thalamus and frontal cortex of Grn-/- mice and patients with FTLD-GRN, we have uncovered a highly conserved astroglial pathology characterized by upregulation of gap junction protein GJA1, water channel AQP4, and lipid-binding protein APOE, and downregulation of glutamate transporter SLC1A2 that promoted profound synaptic degeneration across the two species. This astroglial toxicity could be recapitulated in mouse astrocyte-neuron cocultures and by transplanting induced pluripotent stem cell-derived astrocytes to cortical organoids, where progranulin-deficient astrocytes promoted synaptic degeneration, neuronal stress, and TDP-43 proteinopathy. Together, these results reveal a previously unappreciated astroglial pathology as a potential key mechanism in neurodegeneration in FTLD-GRN.


Assuntos
Demência Frontotemporal , Degeneração Lobar Frontotemporal , Humanos , Animais , Camundongos , Progranulinas/genética , Demência Frontotemporal/genética , Astrócitos/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Mutação , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia
18.
Circ Res ; 132(4): 432-448, 2023 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-36691905

RESUMO

BACKGROUND: Matrix metalloproteinase (MMP)-12 is highly expressed in abdominal aortic aneurysms and its elastolytic function has been implicated in the pathogenesis. This concept is challenged, however, by conflicting data. Here, we sought to revisit the role of MMP-12 in abdominal aortic aneurysm. METHODS: Apoe-/- and Mmp12-/-/Apoe-/- mice were infused with Ang II (angiotensin). Expression of neutrophil extracellular traps (NETs) markers and complement component 3 (C3) levels were evaluated by immunostaining in aortas of surviving animals. Plasma complement components were analyzed by immunoassay. The effects of a complement inhibitor, IgG-FH1-5 (factor H-immunoglobulin G), and macrophage-specific MMP-12 deficiency on adverse aortic remodeling and death from rupture in Ang II-infused mice were determined. RESULTS: Unexpectedly, death from aortic rupture was significantly higher in Mmp12-/-/Apoe-/- mice. This associated with more neutrophils, citrullinated histone H3 and neutrophil elastase, markers of NETs, and C3 levels in Mmp12-/- aortas. These findings were recapitulated in additional models of abdominal aortic aneurysm. MMP-12 deficiency also led to more pronounced elastic laminae degradation and reduced collagen integrity. Higher plasma C5a in Mmp12-/- mice pointed to complement overactivation. Treatment with IgG-FH1-5 decreased aortic wall NETosis and reduced adverse aortic remodeling and death from rupture in Ang II-infused Mmp12-/- mice. Finally, macrophage-specific MMP-12 deficiency recapitulated the effects of global MMP-12 deficiency on complement deposition and NETosis, as well as adverse aortic remodeling and death from rupture in Ang II-infused mice. CONCLUSIONS: An MMP-12 deficiency/complement activation/NETosis pathway compromises aortic integrity, which predisposes to adverse vascular remodeling and abdominal aortic aneurysm rupture. Considering these new findings, the role of macrophage MMP-12 in vascular homeostasis demands re-evaluation of MMP-12 function in diverse settings.


Assuntos
Aneurisma da Aorta Abdominal , Metaloproteinase 12 da Matriz , Camundongos , Animais , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Aneurisma da Aorta Abdominal/metabolismo , Apolipoproteínas E , Elastase Pancreática/metabolismo , Homeostase , Macrófagos/metabolismo , Angiotensina II/toxicidade , Angiotensina II/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Knockout
19.
PeerJ ; 10: e14257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312756

RESUMO

Herein, a versatile fluorescent bioanalysis platform for sensitive and specific screening of target miRNA (miR-129-2-3p) was innovatively designed by applying target-induced rolling circle amplification (RCA) for efficient signal amplification. Specifically, miR-129-2-3p was used as a ligation template to facilitate its ligation with padlock probes, followed by an RCA reaction in the presence of phi29 DNA polymerase. The dsDNA fragments and products were stained by SYBR Green I and then detected by fluorescence spectrophotometry. As a result, miR-129-2-3p concentrations as low as 50 nM could be detected. Furthermore, the expression of miR-129-2-3p in breast cancer patients was about twice that in healthy people. Therefore, the results indicated that the RCA-based biosensor system could be a valuable platform for miRNA detection in clinical diagnosis and biomedical study.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , MicroRNAs , Humanos , Técnicas Biossensoriais/métodos , Neoplasias da Mama/genética , Corantes , DNA/genética , DNA Polimerase Dirigida por DNA/genética , MicroRNAs/genética
20.
J Glaucoma ; 31(7): 602-608, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35763682

RESUMO

PURPOSE: The aim was to evaluate the repeatability and agreement of two swept-source optical coherence tomographers for anterior segment parameters in healthy subjects. PATIENTS AND METHODS: Automated mark of scleral spur and angle recess for the CASIA2 and manual mark of scleral spur and angle recess for the Anterion were performed, and then the measurement values of the related parameters were automatically generated. Subjects with pupil diameter (PD) differing by <15% between the 2 devices were included. PD, lens vault (LV), anterior chamber depth (ACD), angle to angle distance (ATA), anterior chamber width (ACW), anterior chamber angle (ACA), angle opening distance (AOD), and trabecular iris space area (TISA) were measured in the horizontal images with both CASIA2 and Anterion. Intraclass correlation coefficient (ICC) was used to evaluate intradevice repeatability. Bland-Altman plots were performed to assess the agreement between the 2 devices. RESULTS: Thirty-five right eyes of 35 subjects were included with a mean age of 25.60±3.00 years. The CASIA2 showed moderate to good intradevice repeatability (ICCs ranged from 0.786 to 0.989) whereas the Anterion showed good intradevice repeatability (ICCs ranged from 0.921 to 0.998) for anterior segment parameters. Compared with the CASIA2, the Anterion offered larger values of ACA500/750, AOD500/750, and TISA500/750 but smaller values of PD, LV, ACD, ATA, and ACW. Good agreement for PD, ACD, ATA, and ACW was detected with 95% limits of agreement of -1.02 to 1.02 mm, -0.11 to 0.14 mm, -0.17 to 0.19 mm, -0.13 to 0.28 mm, respectively. Poor agreement for LV, ACA500/750, AOD500/750, and TISA500/750 was achieved with the 2 devices. CONCLUSIONS: Anterion outperformed CASIA2 on intradevice repeatability. While agreement was noted for some parameters using manual Anterion and automated CASIA2 approaches, poor agreement of LV and angle parameters indicates that measurements from these optical coherence tomography devices should not be considered interchangeable.


Assuntos
Segmento Anterior do Olho , Pressão Intraocular , Adulto , Câmara Anterior/diagnóstico por imagem , Segmento Anterior do Olho/diagnóstico por imagem , Humanos , Iris/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto Jovem
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