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1.
Environ Res ; 246: 118200, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38220077

RESUMO

Organic polymers hold great potential in photocatalysis considering their low cost, structural tailorability, and well-controlled degree of conjugation for efficient electron transfer. Among the polymers, Schiff base networks (SNWs) with high nitrogen content have been noticed. Herein, a series of SNWs is synthesized based on the melamine units and dialdehydes with different bonding sites. The chemical and structural variation caused by steric hindrance as well as the related photoelectric properties of the SNW samples are investigated, along with the application exploration on photocatalytic degradation and energy production. The results demonstrate that only SNW-o based on o-phthalaldehyde responds to visible light, which extends to over 550 nm. SNW-o shows the highest tetracycline degradation rate of 0.02516 min-1, under 60-min visible light irradiation. Moreover, the H2O2 production of SNW-o is 2.14 times higher than that of g-C3N4. The enhanced photocatalytic activity could be ascribed to the enlarged visible light adsorption and intramolecular electron transfer. This study indicates the possibility to regulate the optical and electrical properties of organic photocatalysts on a molecular level, providing an effective strategy for rational supramolecular engineering to the applications of organic materials in photocatalysis.


Assuntos
Peróxido de Hidrogênio , Bases de Schiff , Luz , Antibacterianos , Polímeros
2.
J Nanobiotechnology ; 22(1): 522, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39215337

RESUMO

Titanium alloys represent the prevailing material employed in orthopedic implants, which are present in millions of patients worldwide. The prolonged presence of these implants in the human body has raised concerns about possible health effects. This study presents a comprehensive analysis of titanium implants and surrounding tissue samples obtained from patients who underwent revision surgery for therapeutic reasons. The surface of the implants exhibited nano-scale corrosion defects, and nanoparticles were deposited in adjacent samples. In addition, muscle in close proximity to the implant showed clear evidence of fibrotic proliferation, with titanium content in the muscle tissue increasing the closer it was to the implant. Transcriptomics analysis revealed SNAI2 upregulation and activation of PI3K/AKT signaling. In vivo rodent and zebrafish models validated that titanium implant or nanoparticles exposure provoked collagen deposition and disorganized muscle structure. Snai2 knockdown significantly reduced implant-associated fibrosis in both rodent and zebrafish models. Cellular experiments demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced fibrotic gene expression at sub-cytotoxic doses, whereas Snai2 knockdown significantly reduced TiO2 NPs-induced fibrotic gene expression. The in vivo and in vitro experiments collectively demonstrated that Snai2 plays a pivotal role in mediating titanium-induced fibrosis. Overall, these findings indicate a significant release of titanium nanoparticles from the implants into the surrounding tissues, resulting in muscular fibrosis, partially through Snai2-dependent signaling.


Assuntos
Fibrose , Fatores de Transcrição da Família Snail , Titânio , Peixe-Zebra , Titânio/química , Animais , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Humanos , Próteses e Implantes , Masculino , Transdução de Sinais/efeitos dos fármacos , Nanopartículas Metálicas/química , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Ratos , Camundongos
3.
Aesthet Surg J ; 44(8): NP574-NP584, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38591553

RESUMO

Non-tuberculous mycobacteria (NTM) infection of the skin and soft tissues is a complication of cosmetic procedures. The incidence of cutaneous NTM infections has increased significantly as aesthetic operations have become more commonplace. With the rise of cosmetic tourism, the geographic expansion of NTM infections is a major concern. Due to the unique pathogenesis of NTM infections, diagnosis and treatment remain significant challenges for clinicians. Clinical management relies on a combination of antibiotic therapy with drug susceptibility testing and appropriate surgical debridement. Some new drugs, photodynamic therapy, and bacteriophage therapy have been developed in recent years, and may improve the aesthetic outcomes. This review summarizes the cosmetic procedures prone to NTM infections in recent years and their clinical features. We propose a 2-stage treatment procedure, including a hospitalization phase and a follow-up phase. We aim to increase the alertness of clinicians to NTM infections for timely detection and treatment.


Assuntos
Antibacterianos , Técnicas Cosméticas , Infecções por Mycobacterium não Tuberculosas , Humanos , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/etiologia , Infecções por Mycobacterium não Tuberculosas/terapia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Técnicas Cosméticas/efeitos adversos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Micobactérias não Tuberculosas/isolamento & purificação
4.
Ecotoxicol Environ Saf ; 264: 115435, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37722303

RESUMO

Introducing co-catalysts to enhance the activation of cuprous-mediated peroxymonosulfate (PMS) and induce the continuous generation of highly reactive oxygen species is promising. The function, effectiveness, and acceleration mechanism of co-catalysts in the cuprous-mediated PMS activation process were fully explored in this work, which focused on rhodamine B as the target contaminants. The results demonstrated that molybdenum (Mo) powder was a superb co-catalyst, and that the reaction of cuprous-mediated PMS system was carried out by surface Mo species as opposed to Mo ions in the solution. The Cu (II)/Cu(I) cycle was primarily encouraged by the Mo0, which also caused abundant ·HO and 1O2 and minimal SO4·- and ·O2- to be produced from PMS. The Mo/Cu2+/PMS system exhibited high removal efficiency towards typical pollutants, especially ciprofloxacin, methyl orange, malachite green, and crystal violet, with removal rates up to 93%, 99%, 97%, and 92%, respectively. Additionally, this system showed excellent adaptability to complex water environments. After four cycles, the Mo powder retained its properties and morphology, and the target pollutants could still maintain an 82% degradation efficiency. This study provides a basis for enhancing cuprous-mediated PMS activation for wastewater treatment.


Assuntos
Poluentes Ambientais , Peróxidos , Pós , Peróxidos/química , Espécies Reativas de Oxigênio/química , Molibdênio , Poluentes Ambientais/química
5.
Inflammopharmacology ; 31(5): 2269-2282, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37429997

RESUMO

Pyroptosis, a form of programmed cell death with a high pro-inflammatory effect, causes cell lysis and leads to the secretion of countless interleukin-1ß (IL-1ß) and IL-18 cytokines, resulting in a subsequent extreme inflammatory response through the caspase-1-dependent pathway or caspase-1-independent pathway. Adult-onset Still's disease (AOSD) is a systemic inflammatory disease with extensive disease manifestations and severe complications such as macrophage activation syndrome, which is characterized by high-grade inflammation and cytokine storms regulated by IL-1ß and IL-18. To date, the pathogenesis of AOSD is unclear, and the available therapy is unsatisfactory. As such, AOSD is still a challenging disease. In addition, the high inflammatory states and the increased expression of multiple pyroptosis markers in AOSD indicate that pyroptosis plays an important role in the pathogenesis of AOSD. Accordingly, this review summarizes the molecular mechanisms of pyroptosis and describes the potential role of pyroptosis in AOSD, the therapeutic practicalities of pyroptosis target drugs in AOSD, and the therapeutic blueprint of other pyroptosis target drugs.


Assuntos
Doença de Still de Início Tardio , Adulto , Humanos , Doença de Still de Início Tardio/tratamento farmacológico , Doença de Still de Início Tardio/etiologia , Doença de Still de Início Tardio/patologia , Interleucina-18 , Piroptose , Citocinas , Biomarcadores , Caspase 1
6.
Pharmacol Res ; 176: 106057, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34995795

RESUMO

Systemic sclerosis (SSc) is a connective tissue disease with the involvement of complex signaling pathways, such as TGF-ß/Smad2/3. SSc can lead to severe multiple organ fibrosis, but no effective therapy is currently available because of its unclear pathogenesis. Exploring new treatments is the focus of recent research on SSc. Recent studies have implied a potential antifibrotic role of esomeprazole (ESO), but with currently unidentified mechanisms. Signaling of AhR, a ligand-dependent transcription factor, has been described as a key controller of fibrosis, tumorigenesis, and immune balance. Recently, it has been reported that ESO may be an exogenous agonist of AhR signaling, while no previous study has revealed the effects of ESO on SSc and its underlying mechanisms. In this study, we demonstrate that ESO suppresses the migration of SSc dermal fibroblasts, downregulates profibrotic markers, including COLIA1, α-SMA CTGF and MMP1, and limits collagen production potentially via the activation of AhR signaling. More importantly, ESO could block Smad2/3 phosphorylation concurrently with the reduction in collagen via AhR signaling. Moreover, our results from the bleomycin (BLM)-induced SSc model in skin and lung shows that ESO ameliorates fibrosis in vivo, which in keeping with our in vitro results. We conclude that ESO is a potential therapeutic drug for SSc fibrosis.


Assuntos
Esomeprazol/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Actinas/genética , Animais , Bleomicina , Células Cultivadas , Cadeia alfa 1 do Colágeno Tipo I/genética , Fator de Crescimento do Tecido Conjuntivo/genética , Citocinas/genética , Esomeprazol/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia
7.
Dermatol Ther ; 35(12): e15942, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36254686

RESUMO

We here report a case of a middle-aged man with an unusual case of bullous lichen sclerosus complicated with generalized morphea. He showed initial recurrent flaccid bullae, followed by ivory-white sclerotic plaques and extensive skin sclerosis, with additional walking disorder caused by knee-joint contracture, and ulcers on the lower extremities and back. The patient had no visceral involvement. After oral hydroxychloroquine and oral corticosteroids failed, the patient was given tofacitinib, which resolved his ulcers after 4 weeks and ameliorated his knee-joint contracture and skin sclerosis within 4 months. Owing to the occurrence of diffuse large B-cell lymphoma, he stopped using tofacitinib, and the ulcer and walking disorder reappeared. This is rare case of bullous lichen sclerosus-generalized morphea overlap syndrome. The patient recovered well after treatment with tofacitinib. His symptoms recurred after discontinuation of tofacitinib.


Assuntos
Contratura , Líquen Escleroso e Atrófico , Esclerodermia Localizada , Escleroderma Sistêmico , Dermatopatias , Pessoa de Meia-Idade , Masculino , Humanos , Esclerodermia Localizada/complicações , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/tratamento farmacológico , Esclerose/complicações , Úlcera , Recidiva Local de Neoplasia
8.
Acta Derm Venereol ; 102: adv00658, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35083492

RESUMO

Nonsense mutations cause the premature termination of protein translation via premature termination codons (PTCs), leading to the synthesis of incomplete functional proteins and causing large numbers of genetic disorders. The emergence of nonsense suppression therapy is considered to be an effective method for the treatment of hereditary diseases, but its application in hereditary skin diseases is relatively limited. This review summarizes the current research status of nonsense suppression therapy for hereditary skin diseases, and discusses the potential opportunities and challenges of applying new technologies related to nonsense suppression therapy to dermatology. Further research is needed into the possible use of nonsense suppression therapy as a strategy for the safer and specific treatment of hereditary skin diseases.


Assuntos
Códon sem Sentido , Dermatopatias , Humanos , Biossíntese de Proteínas , Dermatopatias/tratamento farmacológico , Dermatopatias/genética
9.
J Environ Manage ; 317: 115437, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35661878

RESUMO

Biochar can achieve multiple benefits including solid waste management, polluted water remediation, carbon sequestration, and emission reduction. However, various environmental factors (such as temperature variations and dry-wet alternation) and microbial activity may lead to the fragmentation, dissolution, and oxidation of biochar. These accelerate the dissolution of biochar-derived dissolved organic matter (DOM) and then influence disinfection byproducts formation potential (DBPFP) throughout the water treatment process. In this paper, biochars from six biomass feedstocks with five aging processes were prepared, and the DBPFP of biochar and its derived DOM were first studied systematically. Different aging processes might increase the DBPFP of biochar by increasing DOM content and changing the fraction distribution of DOM derived from biochar. Especially, the DBPFP of biochar increased apparently with the chemical aging process. Coexisting with the environmental concentration of humic acid, even aged biochar showed the potential to reduce DBPFP and integrated toxic risk value of the mixed system. In this study, the DBPFP of biochar-derived DOM during the disinfection process is confirmed, and the results can give information to the selection of biomass feedstocks of biochar and its service life in the water treatment process.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Carvão Vegetal/química , Desinfecção/métodos , Matéria Orgânica Dissolvida , Halogenação , Poluentes Químicos da Água/química
10.
Pharmacol Res ; 160: 105180, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32877693

RESUMO

The aryl hydrocarbon receptor (AhR) is a highly conserved transcription factor that can be activated by small molecules provided by dietary, plant, or microbial metabolites, and environmental pollutants. AhR is expressed in many cell types and engages in crosstalk with other signaling pathways, and therefore provides a molecular pathway that integrates environmental cues and metabolic processes. Fibrosis, which is defined as an aberrant extracellular matrix formation, is a reparative process in the terminal stage of chronic diseases. Both environmental and internal factors have been shown to participate in the pathogenesis of fibrosis; however, the underlying mechanisms still remain elusive. In this review, the potential role of AhR in the process of fibrosis, as well as potential opportunities and challenges in the development of AhR targeting therapeutics, are summarized.


Assuntos
Poluentes Ambientais/toxicidade , Fibrose/induzido quimicamente , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Fibrose/patologia , Humanos
11.
Ecotoxicol Environ Saf ; 189: 109914, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761551

RESUMO

Recently, a large quantity of carbon nanotubes (CNTs) enters the environment due to the increasing production and applications. More and more researches are focused on the fate and possible ecological risks of CNTs. Some literatures summarized the effects of CNTs on the chemical behavior and fate of pollutants. However, little reviewed the effects of CNTs on the biodegradation of pollutants. In general, the effects of CNTs on the biodegradation of pollutants and the related mechanisms were summarized in this review. CNTs have positive or negative effects on the biodegradation of contaminants by affecting the functional microorganisms, enzymes and the bioavailability of pollutants. CNTs may affect the microbial growth, activity, biomass, community composition, diversity and the activity of enzymes. The decrease of the bioavailability of pollutants due to the sorption on CNTs also causes the reduction of the biodegradation of contaminants. In addition, the roles of CNTs are controlled by multiple mechanisms, which are divided into three aspects i.e., properties of CNTs, environment condition, and microorganisms themself. The better understanding of the fate of CNTs and their impacts on the biochemical process in the environment is conducive to determine the release of CNTs into the environment.


Assuntos
Biodegradação Ambiental , Poluentes Ambientais , Nanotubos de Carbono , Biomassa
12.
Chem Soc Rev ; 48(2): 488-516, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30565610

RESUMO

As a newly emerging class of porous materials, covalent organic frameworks (COFs) have attracted much attention due to their intriguing structural merits (e.g., total organic backbone, tunable porosity and predictable structure). However, the insoluble and unprocessable features of bulk COF powder limit their applications. To overcome these limitations, considerable efforts have been devoted to exploring the fabrication of COF thin films with controllable architectures, which open the door for their novel applications. In this critical review, we aim to provide the recent advances in the fabrication of COF thin films not only supported on substrates but also as free-standing nanosheets via both bottom-up and top-down strategies. The bottom-up strategy involves solvothermal synthesis, interfacial polymerization, room temperature vapor-assisted conversion, and synthesis under continuous flow conditions; whereas, the top-down strategy involves solvent-assisted exfoliation, self-exfoliation, mechanical delamination, and chemical exfoliation. In addition, the applications of COF thin films including energy storage, semiconductor devices, membrane-separation, sensors, and drug delivery are summarized. Finally, to accelerate further research, a personal perspective covering their synthetic strategies, mechanisms and applications is presented.

13.
Small ; 14(32): e1800871, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29952105

RESUMO

Graphene has been employed as an excellent support for metal nanomaterials because of its unique structural and physicochemical properties. Silver nanoparticles (AgNPs) with exceptional properties have received considerable attention in various fields; however, particle aggregation limits its application. Therefore, the combination of AgNPs and graphene based nanocomposites (Ag-graphene based nanocomposites) has been widely explored to improve their properties and applications. Excitingly, enhanced antimicrobial, catalytic, and surface enhanced Raman scattering properties are obtained after their combination. In order to have a comprehensive knowledge of these nanocomposites, this Review highlights the chemical and biological synthesis of Ag-graphene nanocomposites. In particular, their applications as antimicrobial agents, catalysts, and sensors in biomedicine, agricultural protection, and environmental remediation and detection are covered. Meanwhile, the factors that influence the synthesis and applications are also briefly discussed. Furthermore, several important issues on the challenges and new directions are also provided for further development of these nanocomposites.


Assuntos
Grafite/química , Nanocompostos/química , Prata/química , Anti-Infecciosos/farmacologia , Incrustação Biológica , Catálise
15.
Int Immunopharmacol ; 133: 112132, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38691918

RESUMO

OBJECTIVE: This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites. METHODS: We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases. RESULTS: Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08-1.27), psoriasis (OR 1.10; 95 % CI 1.04-1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23-1.63), pernicious anemia (OR 1.23; 95 % CI 1.12-1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11-1.26), alopecia areata (OR 1.22; 95 % CI 1.10-1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12-1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated. CONCLUSIONS: We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities.


Assuntos
Doenças Autoimunes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Vitiligo , Vitiligo/genética , Vitiligo/sangue , Humanos , Doenças Autoimunes/sangue , Doenças Autoimunes/genética , Polimorfismo de Nucleotídeo Único
16.
Chemosphere ; 350: 140998, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142881

RESUMO

Aggregation kinetics of plastics are affected by the surface functional groups and exposure orders (electrolyte and protein) with kinds of mechanisms in aquatic environment. This study investigates the aggregation of polystyrene nanoplastics (PSNPs) with varying surface functional groups in the presence of common electrolytes (NaCl, CaCl2, Na2SO4) and bovine serum albumin (BSA). It also examines the impact of different exposure orders, namely BSA + NaCl (adding them together), BSA → NaCl (adding BSA firstly and then NaCl), and NaCl → BSA (adding NaCl firstly and then BSA), on PSNPs aggregation. The presence of BSA decreased the critical coagulation concentration in NaCl (CCCNa+) of the non-modified PS-Bare from 222.17 to 142.81 mM (35.72%), but increased that of the carboxyl-modified PS-COOH from 157.34 to 160.03 mM (1.71%). This might be ascribed to the thicker absorbed layer of BSA onto the PS-Bare surface, known from Ohshima's soft particle theory. Their aggregation in CaCl2 was both increased because of Ca2+ bridging. Different from the monotonous effects of BSA on PS-Bare and PS-COOH, BSA initially facilitated PS-NH2 aggregation via patch-charge attraction, then inhibited it at higher salt levels through steric repulsion. Furthermore, exposure orders had no significant effect on PS-Bare and PS-COOH, but had a NaCl concentration-dependent impact on PS-NH2. At the low NaCl concentrations (10 and 100 mM), no obvious influence could be observed. While, at 300 mM NaCl, the high concentrations of BSA could not totally stabilize the salt-induced aggregates in NaCl → BSA, but could achieve it in the other two orders. These might be attributed to the electrical double layer compression by NaCl, "patch-charge" force and steric hindrance by BSA. These experimental findings shed light on the potential fate and transport of nanoparticles in aquatic environments.


Assuntos
Nanopartículas , Poliestirenos , Microplásticos , Cloreto de Sódio , Cloreto de Cálcio , Eletrólitos , Soroalbumina Bovina
17.
Front Endocrinol (Lausanne) ; 15: 1388047, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39286278

RESUMO

Background: To clarify the controversy between inflammatory or autoimmune skin diseases and thyroid diseases, we performed two-sample Mendelian randomization (MR) analyses. Participants: Genetic data on factors associated with atopic dermatitis (AD, n=40,835), seborrheic dermatitis (SD, n=339,277), acne (n=363,927), rosacea (n=299,421), urticaria (n=374,758), psoriasis (n=373,338), psoriasis vulgaris (n=369,830), systemic lupus erythematosus (SLE, n=14,267), vitiligo (n=353,348), alopecia areata (AA, n=361,822), pemphigus (n=375,929), bullous pemphigoid (BP, n=376,274), systemic sclerosis (SSc, n=376,864), localized scleroderma (LS, n=353,449), hypothyroidism (n=314,995 or n=337,159), and hyperthyroidism (n=281,683 or n=337,159) were derived from genome-wide association summary statistics of European ancestry. Main measures: The inverse variance weighted method was employed to obtain the causal estimates of inflammatory or autoimmune skin diseases on the risk of thyroid diseases, complemented by MR-Egger, weighted median, and MR-pleiotropy residual sum and outlier (MR-PRESSO). Key results: AD, SLE, SD, and psoriasis vulgaris were associated with an increased risk of hypothyroidism, whereas BP was associated with a lower risk of hypothyroidism (all with p < 0.05). The multivariable MR analyses showed that AD (OR = 1.053; 95%CI: 1.015-1.092; p = 0.006), SLE (OR = 1.093; 95%CI: 1.059-1.127; p < 0.001), and SD (OR = 1.006; 95%CI: 1.002-1.010; p = 0.006) independently and predominately contributed to the genetic causal effect on hypothyroidism after adjusting for smoking. The results showed no causal effects of inflammatory or autoimmune skin diseases on hyperthyroidism. Conclusion: The findings showed a causal effect of AD, SLE, SD on hypothyroidism, but further investigations should be conducted to explore the pathogenic mechanisms underlying these relationships.


Assuntos
Doenças Autoimunes , Análise da Randomização Mendeliana , Dermatopatias , Doenças da Glândula Tireoide , Humanos , Doenças Autoimunes/genética , Doenças Autoimunes/epidemiologia , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/epidemiologia , Dermatopatias/genética , Dermatopatias/epidemiologia , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Inflamação/genética , Polimorfismo de Nucleotídeo Único
18.
iScience ; 27(8): 110483, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39156653

RESUMO

Systemic sclerosis (SSc) is an autoimmune disease affecting multiple tissues. The underlying causes and mechanisms of subcutaneous adipose tissue (SAT) loss in SSc remain unclear. Recent studies have highlighted the role of microRNAs in adipogenesis. Our study found that miR-4769-3p was upregulated in SSc patients and its silencing promoted SAT recovery in bleomycin-induced SSc mice, suggesting that miR-4769-3p might affect adipogenesis in SSc. Manipulating miR-4769-3p expression in 3T3-L1 cells revealed that its inhibition enhanced adipogenesis, while its overexpression weakened it. Further investigations showed that miR-4769-3p bound to 3'UTR of ubiquitin-specific protease-18 (USP18), inhibiting its expression, while USP18 interacted with voltage-dependent anion channel-2 (VDAC2), both of which were reduced in SSc. Silencing either USP18 or VDAC2 attenuated adipogenesis. Notably, USP18 inhibited VDAC2 ubiquitination and degradation, whereas miR-4769-3p reversed the VDAC2-induced elevation of adipogenesis, suggesting that miR-4769-3p inhibited adipogenesis by negatively regulating the USP18/VDAC2 pathway, providing a potential therapeutic target for SSc.

19.
Environ Pollut ; 355: 124194, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38782158

RESUMO

Nowadays, silica products are widely used in daily life, especially in skin applications, which inevitably increases the risk of silica exposure in general population. However, inadequate awareness of silica's potential hazards and lack of self-protection are of concern. Systemic sclerosis (SSc) is characterized by progressive tissue fibrosis under environmental and genetic interactions. Silica exposure is considered an important causative factor for SSc, but its pathogenesis remains unclear. Within this study, we showed that lower doses of silica significantly promoted the proliferation, migration, and activation of human skin fibroblasts (HSFs) within 24 h. Silica injected subcutaneously into mice induced and exacerbated skin fibrosis. Notably, silica increased histone deacetylase-4 (HDAC4) expression by inducing its DNA hypomethylation in normal HSFs. The elevated HDAC4 expression was also confirmed in SSc HSFs. Furthermore, HDAC4 was positively correlated with Smad2/3 phosphorylation and COL1, α-SMA, and CTGF expression. The HDAC4 inhibitor LMK235 mitigated silica-induced upregulation of these factors and alleviated skin fibrosis in SSc mice. Taken together, silica induces and exacerbates skin fibrosis in SSc patients by targeting the HDAC4/Smad2/3 pathway. Our findings provide new insights for evaluating the health hazards of silica exposure and identify HDAC4 as a potential interventional target for silica-induced SSc skin fibrosis.


Assuntos
Fibrose , Histona Desacetilases , Escleroderma Sistêmico , Dióxido de Silício , Pele , Proteína Smad2 , Proteína Smad3 , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/induzido quimicamente , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Animais , Camundongos , Humanos , Proteína Smad3/metabolismo , Pele/metabolismo , Proteína Smad2/metabolismo , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacos , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Transdução de Sinais/efeitos dos fármacos
20.
Curr Med Chem ; 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36757030

RESUMO

The fibrosis of tissues and organs occurs via an aberrant tissue remodeling process characterized by an excessive deposition of extracellular matrix, which can lead to organ dysfunction, organ failure, and death. Because the pathogenesis of fibrosis remains unclear and elusive, there is currently no medication to reverse it; hence, this process deserves further study. Activating protein-1 (AP-1)-comprising Jun (c-Jun, JunB, JunD), Fos (c-fos, FosB, Fra1, and Fra2), and activating transcription factor-is a versatile dimeric transcription factor. Numerous studies have demonstrated that AP-1 plays a crucial role in advancing tissue and organ fibrosis via induction of the expression of fibrotic molecules and activating fibroblasts. This review focuses on the role of AP-1 in a range of fibrotic disorders as well as on the antifibrotic effects of AP-1 inhibitors. It also discusses the potential of AP-1 as a new therapeutic target in conditions involving tissue and organ fibrosis.

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