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1.
Photodiagnosis Photodyn Ther ; 46: 104041, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460656

RESUMO

Photodynamic therapy (PDT) is a non-invasive, effective treatment for superficial skin conditions, offering superior cosmetic outcomes compared with traditional therapies. Bowen's disease (BD) of the nipple-areola complex (NAC) is rare and thus, lacks a standardized treatment approach. This report details the case of a 48-year-old woman who was successfully treated for BD of the NAC using PDT. Over a follow-up period of 30 months, there was no evidence of disease recurrence, underscoring the potential of PDT as a viable treatment option for this rare manifestation of BD.

2.
Org Lett ; 26(13): 2546-2551, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38522077

RESUMO

A copper-catalyzed highly para-selective electrophilic aromatic alkylation of monosubstituted simple arenes has been accomplished. This method provides a practical platform for the transformation from simple commercial arenes to well-defined di- and multisubstituted aromatics with high added value. Control experiments and DFT calculations reveal that the achievement of the excellent site-selectivity is ascribed to the controlled deprotonation of the Wheland intermediates. Remarkably, the type of alkylating regent has been shown to have a significant impact on site-selectivity.

3.
Nat Biotechnol ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418648

RESUMO

Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation. Intracerebral transplantation of these organoids reliably generated a diverse repertoire of cortical neurons and anatomical subclasses of human astrocytes. Spatial transcriptome profiling identified layer-specific expression patterns among distinct subclasses of astrocytes within organoid transplants. Using an in vivo acute neuroinflammation model, we identified a subpopulation of astrocytes that rapidly activates pro-inflammatory pathways upon cytokine stimulation. Additionally, we demonstrated that CD38 signaling has a crucial role in mediating metabolic and mitochondrial stress in reactive astrocytes. This model provides a robust platform for investigating human astrocyte function.

4.
Chemosphere ; 352: 141404, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38342148

RESUMO

Antibiotic residues and their chlorinated disinfection by-products (Cl-DBPs) have adverse effects on organisms in aquaculture water. Taking enrofloxacin (ENR) as target antibiotic, this study investigated the degradation and transformation of ENR Cl-DBPs in constructed wetlands (CWs). Results showed that, ENR and its Cl-DBPs affected the biodegradation of CWs at the preliminary stage, but did not affect the adsorption by plant roots, substrates, and biofilms. The piperazine group of ENR had great electronegativity, and was prone to electrophilic reactions. The carboxyl on quinolone group of ENR had strong nucleophilicity, and was prone to nucleophilic reactions. C atoms with significant negative charges on the aromatic structure of quinolone group were prone to halogenation. During the chlorination of ENR, one pathway was the reaction of quinolone group, in which nucleophilic substitution reaction by chlorine occurred at C26 atom on carboxyl group, then halogenation occurred under the action of Cl+ at C17 site on the aromatic ring; the other pathway was the reaction of piperazine group, in which N7 atom was firstly attacked by HOCl, resulting in piperazine ring cleavage, then followed by deacylation, dealkylation, and halogenation. During the biodegradation of ENR Cl-DBPs, the reactivity of piperazine structure was strong, especially at N6, N7, C13, and C14 sites, while the ring structure of quinolone group was quite stable, and only occurred decyclopropyl at N5 site. Overall, the biodegradation of ENR Cl-DBPs in CWs went through processes including piperazine ring cleavage, tertiary amine splitting, dealkylation, and aldehyde oxidation under the action of coenzymes, in which metabolites such as ketones, aldehydes, carboxylic acids, amides, primary amines, secondary amines, tertiary amines and acetaldehyde esters were produced. Most ENR Cl-DBPs had greater bioaccumulation potential and stronger toxicity than their parent compound, fortunately, CWs effectively reduced the environmental risk of ENR Cl-DBPs through the cooperation of adsorption and biodegradation.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Enrofloxacina , Desinfecção/métodos , Halogenação , Áreas Alagadas , Antibacterianos/química , Aminas , Purificação da Água/métodos , Piperazinas , Poluentes Químicos da Água/análise , Cloro/química , Desinfetantes/química
5.
Nat Commun ; 15(1): 1122, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321056

RESUMO

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAVMUSE-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.


Assuntos
Alprostadil , Cicloparafinas , Camundongos , Humanos , Animais , Alprostadil/metabolismo , Transgenes , Cicloparafinas/metabolismo , Odorantes , Receptores Acoplados a Proteínas G/metabolismo , Dependovirus/genética , Vetores Genéticos
6.
Photodiagnosis Photodyn Ther ; 45: 103982, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38244653

RESUMO

Seborrheic keratosis(SK) is a very common skin tumor which is mostly frequently observed in the trunck, head, neck. SK in the auricle is rare and this condition should be excluded the possibility of malignancy by pathologic diagnosis. We report a case of 66-year-old man who presented with a brownish, papillomatous, verrucous mass in the auricle for the past seven years, which began to growing faster during the previous year. Dermoscopy and histopathological examination were performed and the patient was diagnosed with SK. He was treated with the carbon dioxide(CO2) laser and aminolevulinate photodynamic therapy (ALA-PDT). The CO2 laser was used for the removal of the thick hypertrophic lesions and to enhance the transdermal absorption efficiency of ALA. A 20% ALA cream(118 mg/cm2) was applied to his lesion and sealed for 3 h without light, followed by irradiation with 630-nm LED light (96 J/cm2, 80 mw/cm2). We use fluorescent diagnosis with aminolevulinic acid to define the tumor margins at the first session of ALA-PDT. After 4 sessions of ALA-PDT, the lesion was completely removed and did not recur. Therefore, we consider that ALA-PDT combined with CO2 laser is a safe and effective choice for the treatment of seborrheic keratosis in the auricle.


Assuntos
Ceratose Seborreica , Lasers de Gás , Fotoquimioterapia , Masculino , Humanos , Idoso , Fotoquimioterapia/métodos , Dióxido de Carbono , Fármacos Fotossensibilizantes/uso terapêutico , Ceratose Seborreica/tratamento farmacológico , Ceratose Seborreica/cirurgia , Lasers de Gás/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico
7.
Analyst ; 149(4): 1221-1228, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38221877

RESUMO

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.


Assuntos
Neoplasias , Pontos Quânticos , Humanos , Óxido Nítrico , Carbono , Fluorescência , Levofloxacino , Neoplasias/patologia , Espécies Reativas de Oxigênio , Guanidinas/uso terapêutico , Pontos Quânticos/toxicidade
8.
ACS Nano ; 18(2): 1690-1701, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38165832

RESUMO

The combination of immune checkpoint blockade (ICB) and chemotherapy has shown significant potential in the clinical treatment of various cancers. However, circulating regeneration of PD-L1 within tumor cells greatly limits the efficiency of chemo-immunotherapy and consequent patient response rates. Herein, we report the synthesis of a nanoparticle-based PD-L1 inhibitor (FRS) with a rational design for effective endogenous PD-L1 suppression. The nanoinhibitor is achieved through self-assembly of fluoroalkylated competitive peptides that target PD-L1 palmitoylation. The FRS nanoparticles provide efficient protection and delivery of functional peptides to the cytoplasm of tumors, showing greater inhibition of PD-L1 than nonfluorinated peptidic inhibitors. Moreover, we demonstrate that FRS synergizes with chemotherapeutic doxorubicin (DOX) to boost the antitumor activities via simultaneous reduction of PD-L1 abundance and induction of immunogenic cell death in murine colon tumor models. The nano strategy of PD-L1 regulation present in this study is expected to advance the development of ICB inhibitors and overcome the limitations of conventional ICB-assisted chemo-immunotherapy.


Assuntos
Antígeno B7-H1 , Imunoterapia , Humanos , Animais , Camundongos , Ligantes , Apoptose , Peptídeos/farmacologia , Linhagem Celular Tumoral
9.
Eur J Med Res ; 29(1): 65, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245791

RESUMO

Asthma represents a significant global challenge that affects individuals across all age groups and imposes substantial social and economic burden. Due to heterogeneity of the disease, not all patients obtain benefit with current treatments. The objective of this study was to explore the impact of MD2 on the progression of asthma using L6H21, a novel MD2 inhibitor, to identify potential targets and drug candidates for asthma treatment. To establish an asthma-related murine model and evaluate the effects of L6H21, ovalbumin (OVA) was used to sensitize and challenge mice. Pathological changes were examined with various staining techniques, such as H&E staining, glycogen staining, and Masson staining. Inflammatory cell infiltration and excessive cytokine secretion were evaluated by analyzing BALF cell count, RT-PCR, and ELISA. The TLR4/MD2 complex formation, as well as the activation of the MAPK and NF-кB pathways, was examined using western blot and co-IP. Treatment with L6H21 demonstrated alleviation of increased airway resistance, lung tissue injury, inflammatory cell infiltration and excessive cytokine secretion triggered by OVA. In addition, it also ameliorated mucus production and collagen deposition. In the L6H21 treatment group, inhibition of MAPK and NF-кB activation was observed, along with the disruption of TLR4/MD2 complex formation, in contrast to the model group. Thus, L6H21 effectively reduced the formation of the MD2 and TLR4 complex induced by OVA in a dose-dependent manner. This reduction resulted in the attenuation of MAPKs/NF-κB activation, enhanced suppression of inflammatory factor secretion, reduced excessive recruitment of inflammatory cells, and ultimately mitigated airway damage. MD2 emerges as a crucial target for asthma treatment, and L6H21, as an MD2 inhibitor, shows promise as a potential drug candidate for the treatment of asthma.


Assuntos
Asma , Chalcona , Chalconas , Humanos , Camundongos , Animais , Chalcona/uso terapêutico , Ovalbumina/uso terapêutico , NF-kappa B/genética , NF-kappa B/metabolismo , Chalconas/farmacologia , Chalconas/uso terapêutico , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/uso terapêutico , Asma/induzido quimicamente , Asma/tratamento farmacológico , Asma/patologia , Pulmão/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
10.
Environ Pollut ; 344: 123310, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38190872

RESUMO

Disinfection by-products (DBPs) formed from chlorination of antibiotics have greater toxicity than their parent compounds. Herein, this study investigated the biotransformation process of sulfadiazine Cl-DBPs in constructed wetlands (CWs). Results showed that, S atom on sulfonyl group, and N atoms on primary and secondary amine groups were the most reactive sites of sulfadiazine molecule. S1-N4 and S1-C8 of sulfadiazine are the most vulnerable bonds to cleave, followed by C14-N4 and C11-N5 bonds. In the chlorination process, sulfadiazine went through C-N bond cleavage, N-reductive alkylation, halogenation, and desulfonation to produce two aromatic Cl-DBPs. In the biodegradation process in CWs, sulfadiazine Cl-DBPs went through processes mainly including dechlorination, S-N bond cleavage, aniline-NH2 oxidation, desulfonation, phenol-OH oxidation, benzene ring cleavage, C-N bond cleavage, and ß-oxidation of fatty acids under the action of a variety of oxidoreductases and hydrolases, during which a total of ten biodegradation products was identified. Moreover, sulfadiazine affected the biodegradation rather than the adsorption process in CWs. The two aromatic sulfadiazine Cl-DBPs had much higher bioaccumulation potentials than their parent sulfadiazine, but for the ten biodegradation products of sulfadiazine Cl-DBPs in CWs, 70% and almost 100% of them had lower bioaccumulation potentials than sulfadiazine and their parent sulfadiazine Cl-DBPs, respectively. The CWs were effective in reducing the environmental risk of sulfadiazine Cl-DBPs.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção/métodos , Halogenação , Sulfadiazina , Áreas Alagadas , Biodegradação Ambiental , Purificação da Água/métodos , Poluentes Químicos da Água/análise , Desinfetantes/química , Cloro/química
11.
Biomimetics (Basel) ; 8(5)2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37754162

RESUMO

In this paper, a new hybrid Manta Ray Foraging Optimization (MRFO) with Cuckoo Search (CS) algorithm (AMRFOCS) is proposed. Firstly, quantum bit Bloch spherical coordinate coding is used for the initialization of the population, which improves the diversity of the expansion of the traversal ability of the search space. Secondly, the dynamic disturbance factor is introduced to balance the exploratory and exploitative search ability of the algorithm. Finally, the unique nesting strategy of the cuckoo and Levy flight is introduced to enhance the search ability. AMRFOCS is tested on CEC2017 and CEC2020 benchmark functions, which is also compared and tested by using different dimensions and other state-of-the-art metaheuristic algorithms. Experimental results reveal that the AMRFOCS algorithm has a superior convergence rate and optimization precision. At the same time, the nonparametric Wilcoxon signed-rank test and Friedman test show that the AMRFOCS has good stability and superiority. In addition, the proposed AMRFOCS is applied to the three-dimensional WSN coverage problem. Compared with the other four 3D deployment methods optimized by metaheuristic algorithms, the AMRFOCS effectively reduces the redundancy of sensor nodes, possesses a faster convergence speed and higher coverage and then provides a more effective and practical deployment scheme.

12.
Clin Transl Med ; 13(8): e1382, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37620295

RESUMO

BACKGROUND: Precise regulation of partial critical proteins in cancer cells, such as anti-apoptotic proteins, is one of the crucial strategies for treating cancer and discovering related molecular mechanisms. Still, it is also challenging in actual research and practice. The widely used CRISPR/Cas9-based gene editing technology and proteolysis-targeting chimeras (PROTACs) have played an essential role in regulating gene expression and protein function in cells. However, the accuracy and controllability of their targeting remain necessary. METHODS: Construction of UMUC-3-EGFP stable transgenic cell lines using the Sleeping Beauty system, Flow cytometry, quantitative real-time PCR, western blot, fluorescence microplate reader and fluorescence inverted microscope analysis of EGFP intensity. Characterization of Survivin inhibition was done by using Annexin V-FITC/PI apoptosis, calcein/PI/DAPI cell viability/cytotoxicity assay, cloning formation assay and scratch assay. The cell-derived xenograft (CDX) model was constructed to assess the in vivo effects of reducing Survivin expression. RESULTS: Herein, we established a synergistic control platform that coordinated photoactivatable split-Cas9 targeted gene editing and light-induced protein degradation, on which the Survivin gene in the nucleus was controllably edited by blue light irradiation (named paCas9-Survivin) and simultaneously the Survivin protein in the cytoplasm was degraded precisely by a nanobody-mediated target (named paProtacL-Survivin). Meanwhile, in vitro experiments demonstrated that reducing Survivin expression could effectively promote apoptosis and decrease the proliferation and migration of bladder cancerous cells. Furthermore, the CDX model was constructed using UMUC-3 cell lines, results from animal studies indicated that both the paCas9-Survivin system and paProtacL-Survivin significantly inhibited tumour growth, with higher inhibition rates when combined. CONCLUSIONS: In short, the coordinated regulatory strategies and combinable technology platforms offer clear advantages in controllability and targeting, as well as an excellent reference value and universal applicability in controlling the fate of cancer cells through multi-level regulation of key intracellular factors.


Assuntos
Sistemas CRISPR-Cas , Neoplasias , Humanos , Animais , Survivina/genética , Sistemas CRISPR-Cas/genética , Edição de Genes , Proteólise , Apoptose/genética , Modelos Animais de Doenças , Neoplasias/genética , Neoplasias/terapia
13.
J Agric Food Chem ; 71(22): 8317-8331, 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37249228

RESUMO

Consumption of fruits and vegetables has been associated with a reduced risk of multiple diseases, such as metabolic disorders. Flavonols are the most ubiquitous flavonoids in fruits and vegetables. However, dietary flavonols exhibit a general low oral bioavailability for their extensive biotransformation mediated by phase II enzymes in enterocytes and liver as well as by microbiota in the gut lumen. In this context, flavonols have brought attention to a paradox between low bioavailability and health-promoting effects. Flavonols are often transformed prior to absorption, which could change their biological activity. Compared to their parent compounds, the corresponding metabolites of flavonols in vivo might exhibit similar or higher intrinsic bioactivities, or perhaps a decreased efficacious effectiveness. Indeed, a growing body of evidence from biological function studies of metabolites supports the positive and significant contribution of in vivo metabolic processes, particularly conversion mediated by gut microbiota, to the health-promoting benefits of flavonols. As such, further understanding of the metabolic fate of flavonols and biological activities of their metabolites as well as the possible impact of microbiota-mediated conversion on the bioactivity is of great significance to guide a rational diet with flavonol-rich fruits and vegetables and/or flavonol-containing functional foods.


Assuntos
Flavonóis , Microbioma Gastrointestinal , Flavonoides/metabolismo , Dieta , Verduras/metabolismo , Biotransformação
14.
Biol Psychiatry ; 93(7): 616-621, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36739209

RESUMO

Human brain organoids are 3-dimensional cell aggregates that are generated from pluripotent stem cells and recapitulate features of the early developing human brain. Brain organoids mainly consist of cells from the neural lineage, such as neural progenitor cells, neurons, and astrocytes. However, current brain organoid systems lack functional vasculature as well as other non-neuronal cells that are indispensable for oxygen and nutrient supply to the organoids, causing cell stress and formation of a necrotic center. Attempts to utilize intracerebral transplantation approaches have demonstrated successful vascularization of brain organoids and robust neurodifferentiation. In this review, we summarize recent progress and discuss ethical considerations in the field of brain organoid transplantation.


Assuntos
Células-Tronco Pluripotentes Induzidas , Células-Tronco Neurais , Células-Tronco Pluripotentes , Humanos , Encéfalo , Organoides , Células-Tronco Pluripotentes/fisiologia , Neurônios
15.
Chemosphere ; 321: 138135, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36796524

RESUMO

Linear alkylbenzene sulfonates (LAS) are the most commonly-used anionic surfactants in cleaning agents and detergents. Taking sodium dodecyl benzene sulfonate (SDBS) as the target LAS, this study investigated the degradation and transformation of LAS in integrated constructed wetland-microbial fuel cell (CW-MFC) systems. Results showed that, SDBS was able to improve the power output and reduce the internal resistance of CW-MFCs by reducing transmembrane transfer resistance of organics and electrons because of the amphiphilicity and solubilization, however, SDBS with relatively high concentration had a great potential to inhibit electricity generation and organics biodegradation of CW-MFCs because of the toxic effects on microorganisms. C atoms on alkyl group and O atoms on sulfonic acid group of SDBS had greater electronegativity and were prone to oxidation reaction. The biodegradation of SDBS in CW-MFCs was a process of alkyl chain degradation, desulfonation and benzene ring cleavage in sequence via ω, ß and/or α-oxidations and radical attacks under the action of coenzymes and oxygen, in which 19 intermediates were produced, including four anaerobic degradation products (toluene, phenol, cyclohexanone and acetic acid). Especially, for the first time cyclohexanone was detected during the biodegradation of LAS. The bioaccumulation potential of SDBS was greatly reduced through the degradation by CW-MFCs, and thus the environmental risk of SDBS was effectively reduced.


Assuntos
Fontes de Energia Bioelétrica , Benzeno , Cicloexanonas , Alcanossulfonatos , Áreas Alagadas
16.
Bio Protoc ; 13(3): e4600, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36816991

RESUMO

Secreted reporters have been demonstrated to be simple and useful tools for analyzing transcriptional regulation in mammalian cells. The distinctive feature of these assays is the ability to detect reporter gene expression in the culture supernatant without affecting the cell physiology or leading to cell lysis, which allows repeated experimentation and sampling of the culture medium using the same cell cultures. Secreted embryonic alkaline phosphatase (SEAP) is one of the most widely used reporter, which can be easily detected using colorimetry following incubation with a substrate, such as p-nitrophenol phosphate. In this report, we present detailed procedures for detection and quantification of the SEAP reporter. We believe that this step-by-step protocol can be easily used by researchers to monitor and measure molecular genetic events in a variety of mammalian cells due to its simplicity and ease of handling. Graphical abstract Schematic overview of the workflow described in this protocol.

17.
Br J Ophthalmol ; 107(10): 1458-1466, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35840290

RESUMO

OBJECTIVE: This study aimed to investigate the prevalence of glaucoma with associated factors in the rural populations of 10 provinces in China. DESIGN: A population-based cross-sectional study. METHODS: All participants aged 6 years or older from 10 provinces completed visual acuity testing, slit-lamp examination, ophthalmoscopy and non-contact tonometry. Glaucoma suspects underwent fundus photography, Goldmann applanation tonometry, visual field testing and gonioscopy. Glaucoma was determined according to the International Society of Geographical and Epidemiological Ophthalmology classification scheme. Associations of demographics and medical factors with glaucoma were assessed using multiple logistic regression models. RESULTS: From June 2017 to October 2018, 48 398 of 52 041 participants were included in the final analyses. The age-standardised prevalence of glaucoma was 1.7% (95% CI 1.55% to 1.78%) among the participants older than 6 years, which was 2.1% (95% CI 1.93% to 2.23%) in participants aged over 40 years. The constituent ratios of glaucoma were: 44.4% primary angle-closure glaucoma (PACG), 34.7% primary open-angle glaucoma, 2.6% congenital glaucoma and 18.3% other types of glaucoma. Increasing age, smoking, cerebral stroke, type 2 diabetes, higher education (college or more) and higher personal income were significant risk factors for PACG. The unilateral and bilateral blindness rates in the entire study population were 4.692% and 1.068%, respectively. A family history of glaucoma was a significant risk factor for the prevalence of glaucoma and blindness in at least one eye. CONCLUSIONS: Rural populations have a high prevalence of glaucoma, which should be included in chronic disease management programmes in China for long-term care.


Assuntos
Diabetes Mellitus Tipo 2 , Glaucoma de Ângulo Fechado , Glaucoma de Ângulo Aberto , Humanos , Adulto , Pessoa de Meia-Idade , Pressão Intraocular , Estudos Transversais , Glaucoma de Ângulo Aberto/diagnóstico , População Rural , Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Fechado/epidemiologia , Distribuição por Idade , Cegueira/epidemiologia , Gonioscopia , Prevalência , China/epidemiologia
18.
Adv Sci (Weinh) ; 10(4): e2202858, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36507552

RESUMO

Pluripotent stem cells (PSCs) hold great promise for cell-based therapies, disease modeling, and drug discovery. Classic somatic cell reprogramming to generate induced pluripotent stem cells (iPSCs) is often achieved based on overexpression of transcription factors (TFs). However, this process is limited by side effect of overexpressed TFs and unpredicted targeting of TFs. Pinpoint control over endogenous TFs expression can provide the ability to reprogram cell fate and tissue function. Here, a light-inducible cell reprogramming (LIRE) system is developed based on a photoreceptor protein cryptochrome system and clustered regularly interspaced short palindromic repeats/nuclease-deficient CRISPR-associated protein 9 for induced PSCs reprogramming. This system enables remote, non-invasive optogenetical regulation of endogenous Sox2 and Oct4 loci to reprogram mouse embryonic fibroblasts into iPSCs (iPSCLIRE ) under light-emitting diode-based illumination. iPSCLIRE cells can be efficiently differentiated into different cells by upregulating a corresponding TF. iPSCLIRE cells are used for blastocyst injection and optogenetic chimeric mice are successfully generated, which enables non-invasive control of user-defined endogenous genes in vivo, providing a valuable tool for facile and traceless controlled gene expression studies and genetic screens in mice. This LIRE system offers a remote, traceless, and non-invasive approach for cellular reprogramming and modeling of complex human diseases in basic biological research and regenerative medicine applications.


Assuntos
Reprogramação Celular , Células-Tronco Pluripotentes Induzidas , Animais , Humanos , Camundongos , Reprogramação Celular/genética , Optogenética , Fibroblastos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Diferenciação Celular
19.
Nat Commun ; 13(1): 6357, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289204

RESUMO

Surgical resection is the main treatment option for most solid tumors, yet cancer recurrence after surgical resection remains a significant challenge in cancer therapy. Recent advances in cancer immunotherapy are enabling radical cures for many tumor patients, but these technologies remain challenging to apply because of side effects related to uncontrollable immune system activation. Here, we develop far-red light-controlled immunomodulatory engineered cells (FLICs) that we load into a hydrogel scaffold, enabling the precise optogenetic control of cytokines release (IFN-ß, TNF-α, and IL-12) upon illumination. Experiments with a B16F10 melanoma resection mouse model show that FLICs-loaded hydrogel implants placed at the surgical wound site achieve sustainable release of immunomodulatory cytokines, leading to prevention of tumor recurrence and increased animal survival. Moreover, the FLICs-loaded hydrogel implants elicit long-term immunological memory that prevents against tumor recurrence. Our findings illustrate that this optogenetic perioperative immunotherapy with FLICs-loaded hydrogel implants offers a safe treatment option for solid tumors based on activating host innate and adaptive immune systems to inhibit tumor recurrence after surgery. Beyond extending the optogenetics toolbox for immunotherapy, we envision that our optogenetic-controlled living cell factory platform could be deployed for other biomedical contexts requiring precision induction of bio-therapeutic dosage.


Assuntos
Recidiva Local de Neoplasia , Optogenética , Camundongos , Animais , Fator de Necrose Tumoral alfa , Imunoterapia , Fatores Imunológicos , Hidrogéis , Citocinas , Interleucina-12/genética
20.
Front Neurol ; 13: 1014596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313488

RESUMO

Purpose: To compare the safety and efficacy of PipelineTM and TubridgeTM Flow Diverter devices (FDs) in the treatment of intracranial wide-necked aneurysms. Methods: We retrospectively analyzed the clinical data of 92 patients with intracranial wide-necked aneurysms who were treated with those two flow-diverter devices (FDs) at four participating centers between July 2012 and December 2020. Results: This study included 92 patients who underwent endovascular therapy using either Pipeline™ (n = 39) or TubridgeTM (n = 53) for treating intracranial wide-necked aneurysms. The periprocedural complication developed in 2.56% (1/39) patients of Pipeline group and 3.77% (2/53) patients of the TubridgeTM group. During perioperative period, one patient in Pipeline™ group showed subarachnoid hemorrhage (2.56%, 1/39) and two ischemic complications in the Tubridge™ group (3.77%, 2/53). Follow-up assessments were conducted on 31 patients (79.49%) in the Pipeline™ group (the mean follow-up period was 9.7 ± 3.3 months). The rate of complete aneurysm occlusion at the final angiographic follow-up was 77.42%. Patients with a modified Rankin scale (mRS) score of 0.44 ± 0.31. Follow-up assessments were conducted on 42 patients (79.25%) in the TubridgeTM group (the mean follow-up period was 9.1 ± 4.4 months). The rate of complete aneurysm occlusion at the final angiographic follow-up was 85.71%. Patients with mRS score of 0.52 ± 0.28. Three patients showed parent artery stenosis, and one showed parent artery occlusion. Conclusion: Both the PipelineTM and TubridgeTM are safe and effective for the treatment of intracranial wide-necked aneurysms, with no significant difference in the rate of complete aneurysm occlusion and perioperative complications between the two FDs.

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