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1.
Nat Commun ; 15(1): 4114, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750057

RESUMO

Cellular sensitivity to ferroptosis is primarily regulated by mechanisms mediating lipid hydroperoxide detoxification. We show that inositol-requiring enzyme 1 (IRE1α), an endoplasmic reticulum (ER) resident protein critical for the unfolded protein response (UPR), also determines cellular sensitivity to ferroptosis. Cancer and normal cells depleted of IRE1α gain resistance to ferroptosis, while enhanced IRE1α expression promotes sensitivity to ferroptosis. Mechanistically, IRE1α's endoribonuclease activity cleaves and down-regulates the mRNA of key glutathione biosynthesis regulators glutamate-cysteine ligase catalytic subunit (GCLC) and solute carrier family 7 member 11 (SLC7A11). This activity of IRE1α is independent of its role in regulating the UPR and is evolutionarily conserved. Genetic deficiency and pharmacological inhibition of IRE1α have similar effects in inhibiting ferroptosis and reducing renal ischemia-reperfusion injury in mice. Our findings reveal a previously unidentified role of IRE1α to regulate ferroptosis and suggests inhibition of IRE1α as a promising therapeutic strategy to mitigate ferroptosis-associated pathological conditions.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Endorribonucleases , Ferroptose , Glutationa , Proteínas Serina-Treonina Quinases , Ferroptose/genética , Endorribonucleases/metabolismo , Endorribonucleases/genética , Animais , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos , Glutationa/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Glutamato-Cisteína Ligase/metabolismo , Glutamato-Cisteína Ligase/genética , Resposta a Proteínas não Dobradas , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/genética , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Masculino , Camundongos Knockout
2.
Opt Express ; 32(1): 52-61, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175062

RESUMO

This paper presents a lean subcarrier modulation-based phase-coded coherent lidar system with a non-quadrature receiver and sampling ratio lower than the Nyquist sampling ratio. Specifically, by utilizing the drawbacks of low Doppler tolerance in encoding signals, phase information can be obtained after pulse compression, and the mirror frequency introduced by real sampling can be negligible. Validation experiments based on inverse synthetic aperture lidar are performed, with the corresponding imaging results having a resolution superior to 4 cm, demonstrating our system's efficiency in phase acquisition that is free from frequency aliasing.

3.
Inflammation ; 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244176

RESUMO

The skin is a complex and dynamic organ where homeostasis is maintained through the intricate interplay between the immune system and metabolism, particularly cholesterol metabolism. Various factors such as cytokines, inflammatory mediators, cholesterol metabolites, and metabolic enzymes play crucial roles in facilitating these interactions. Dysregulation of this delicate balance contributes to the pathogenic pathways of inflammatory skin conditions, notably psoriasis. In this article, we provide an overview of omics biomarkers associated with psoriasis in relation to cholesterol metabolism. We explore multi-omics approaches that reveal the communication between immunometabolism and psoriatic inflammation. Additionally, we summarize the use of multi-omics strategies to uncover the complexities of multifactorial and heterogeneous inflammatory diseases. Finally, we highlight potential future perspectives related to targeted drug therapies and research areas that can advance precise medicine. This review aims to serve as a valuable resource for those investigating the role of cholesterol metabolism in psoriasis.

4.
Pediatr Dermatol ; 41(2): 351-353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37853991

RESUMO

Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis that affects skin, hair, teeth, eyes and central nervous system. We present the case of a female patient with mild IP caused by a hypomorphic pathogenic variant of the inhibitor of the kappa light polypeptide gene enhancer in B cells, kinase gamma (IKBKG) gene. This is the first report of a female IP patient with the hypomorphic variant, NM_001099856.6: c.1423dup, which is causative of anhidrotic ectodermal dysplasia with immune deficiency in males.


Assuntos
Displasia Ectodérmica , Síndromes de Imunodeficiência , Incontinência Pigmentar , Feminino , Humanos , Displasia Ectodérmica/genética , Quinase I-kappa B/genética , Síndromes de Imunodeficiência/genética , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Mutação , Pele/patologia
5.
Front Endocrinol (Lausanne) ; 14: 1212490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075056

RESUMO

Purpose: To evaluate the feasibility, safety, and oncologic outcomes associated with endoscopic thyroidectomy via the areolar approach (ETAA), compared with conventional open thyroidectomy (COT) for the treatment of stage T1 papillary thyroid carcinoma (PTC). Methods: Between January 2021 and June 2022, a total of 1204 patients diagnosed with PTC underwent screening, out of which 138 patients were selected for inclusion in the study population after propensity score matching (92 patients in the ETAA group and 46 patients in the COT group). The study included the collection and analysis of clinicopathologic characteristics, intraoperative outcomes, postoperative outcomes, complications, and follow-up data using R software. Results: The operative time for the ETAA group was longer than that for the COT group (160.42 ± 32.21 min vs. 121.93 ± 29.78 min, p < 0.0001). However, there were no significant differences between the two groups in terms of intraoperative blood loss, the extent of surgical resection, the number of dissected lymph nodes, the number of metastatic lymph nodes, and the rate of parathyroid autotransplantation. Postoperative drainage and C-reactive protein levels were higher in the ETAA group than in the COT group, but there were no significant differences in 24-hour visual analogue scale scores, white blood cell counts, drainage duration, or postoperative hospital stay. Complication rates were similar between the two groups, and no permanent recurrent laryngeal nerve palsy or hypoparathyroidism was observed. Patients who underwent ETAA reported greater cosmetic satisfaction and quality of life than those who underwent COT. During the follow-up phase, only one patient in the COT group developed lateral cervical lymph node involvement requiring reoperation. Conclusion: ETAA is a safe and feasible surgical method for patients with stage T1 PTC, providing results similar to COT in terms of oncologic completeness, while avoiding neck scars, with excellent cosmetic effects. Clinical trial registration: Chinese Clinical Trial Registry center, identifier ChiCTR2300077109.


Assuntos
Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Estudos de Viabilidade , Mamilos/patologia , Qualidade de Vida , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Endoscopia , Resultado do Tratamento
6.
Opt Express ; 31(23): 39088-39101, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017997

RESUMO

Lensless cameras, consisting of only a sensor and a mask, are small and flexible enough to be used in many applications with stringent scale constraints. These mask-based imagers encode scenes in caustic patterns. Most existing reconstruction algorithms rely on multiple iterations based on physical model for deconvolution followed by deep learning for perception, among which the main limitation of reconstruction quality is the mismatch between the ideal and the real model. To solve the problem, we in this work learned a class of multi Wiener deconvolution networks (MWDNs), deconvoluting in multi-scale feature spaces with Wiener filters to reduce the information loss and improving the accuracy of the given model by correcting the inputs. A comparison between the proposed and the state-of-the-art algorithms shows that ours achieves much better images and performs well in real-world environments. In addition, our method takes greater advantage of the computational time due to the abandonment of iterations.

7.
Eur J Med Res ; 28(1): 526, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974233

RESUMO

BACKGROUND: Recent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT. METHODS: We conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings. RESULTS: Seventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324-7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations. CONCLUSION: Our findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.


Assuntos
Artrite Reumatoide , Tireoidite Autoimune , Humanos , Tireoidite Autoimune/genética , Tireoidite Autoimune/complicações , Índice de Massa Corporal , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único/genética
8.
Surg Laparosc Endosc Percutan Tech ; 33(6): 587-591, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37852216

RESUMO

OBJECTIVE: The aim of this study was to evaluate the influence of transoral endoscopic thyroidectomy vestibular approach (TOETVA) on voice changes and swallowing function disorders. MATERIALS AND METHODS: We retrospectively reviewed 215 patients who underwent thyroid surgery with TOETVA (105 cases, endoscopic group) and open approach (110 cases, open group). Major outcomes, the changes in voice and swallowing function in the 2 groups of patients before and after surgery were analyzed by using both subjective and objective evaluation indexes. Subjective evaluation indexes included the Voice Handicap Index, voice GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) classification, and swallowing impairment score; the objective indicators included the fundamental frequency (F0), fundamental frequency perturbation (jitter), amplitude perturbation (shimmer), and maximum phonation time. RESULTS: In terms of subjective evaluation indexes, there were no significant differences (all P> 0.05) between the groups regarding Voice Handicap Index (1 and 3 mo after surgery) and GRBAS (1 and 3 mo after surgery). The incidence rates of swallowing disorder in the endoscopic group were higher than that in the open group according to the outcomes of swallowing impairment score at 1 and 3 months after surgery (both P< 0.05). In addition, no significant changes in terms of jitter, shimmer, and maximum phonation time in both groups of patients at 1 and 3 months after surgery compared with their preoperative values (all P> 0.05). CONCLUSIONS: Voice and swallowing disorders may occur in some patients, either TOETVA or open thyroid surgery, which in most cases will recover within 3 months after surgery. The time to swallowing function recovery is relatively prolonged in patients following TOETVA, which may be probably associated with neck adhesion and fixation after the operation.


Assuntos
Transtornos de Deglutição , Tireoidectomia , Humanos , Tireoidectomia/efeitos adversos , Transtornos de Deglutição/cirurgia , Deglutição , Estudos Retrospectivos , Glândula Tireoide
9.
Surg Laparosc Endosc Percutan Tech ; 33(5): 547-555, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37523575

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) versus conventional open thyroidectomy (COT) for some thyroid diseases. MATERIALS AND METHODS: Databases PubMed, Embase, and Web of Science were searched. Full-text English papers that described TOETVA and COT for people with thyroid diseases were included. Randomized, nonrandomized, controlled, and uncontrolled trials were all included. Extracted data included population characteristics and intraoperative and postoperative complications. RESULTS: A total of 2 randomized controlled trials and 10 retrospective studies, including 3048 patients, were included in the meta-analysis. Meta-analysis results suggested that the intraoperative conditions and postoperative complication rates did not differ significantly between the two groups. However, in the TOETVA group, there is a slightly longer operative time [weighted mean difference (WMD): 73.64; 95% CI: 49.34 to 97.94; P < 0.0001], drainage (WMD: 91.0; 95% CI: 35.52 to 146.48; P = 0.001), and hospital stay (WMD: 0.28; 95% CI: 0.18 to 0.38; P < 0.0001). CONCLUSION: For most of the benign thyroid nodules and selected patients with papillary thyroid cancer, TOETVA seems to be as feasible and safe as COT.

10.
Front Immunol ; 14: 1164124, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37287971

RESUMO

Background: Vitiligo is an acquired, autoimmune, depigmented skin disease with unclear pathogenesis. Mitochondrial dysfunction contributes significantly to vitiligo, and mitophagy is vital for removing damaged mitochondria. Herein, using bioinformatic analysis, we sought to determine the possible role of mitophagy-associated genes in vitiligo and immune infiltration. Methods: Microarrays GSE53146 and GSE75819 were used to identify differentially expressed genes (DEGs) in vitiligo. By crossing vitiligo DEGs with mitophagy-related genes, the mitophagy-related DEGs were identified. Functional enrichment and protein-protein intersection (PPI) analyses were conducted. Then, the hub genes were identified using two machine algorithms, and receiver operating characteristic (ROC) curves were generated. Next, the immune infiltration and its connection with hub genes in vitiligo were investigated. Finally, the Regnetwork database and NetworkAnalyst were used to predict the upstream transcriptional factors (TFs), microRNAs (miRNAs), and the protein-compound network. Results: A total of 24 mitophagy-related genes were screened. Then, five mitophagy hub genes (GABARAPL2, SP1, USP8, RELA, and TBC1D17) were identified using two machine learning algorithms, and these genes showed high diagnostic specificity for vitiligo. The PPI network showed that hub genes interacted with each other. The mRNA expression levels of five hub genes were validated in vitiligo lesions by qRT-PCR and were compatible with the bioinformatic results. Compared with controls, the abundance of activated CD4+ T cells, CD8+ T cells, immature dendritic cells and B cells, myeloid-derived suppressor cells (MDSCs), gamma delta T cells, mast cells, regulatory T cells (Tregs), and T helper 2 (Th2) cells was higher. However, the abundance of CD56 bright natural killer (NK) cells, monocytes, and NK cells was lower. Correlation analysis revealed a link between hub genes and immune infiltration. Meanwhile, we predicted the upstream TFs and miRNAs and the target compounds of hub genes. Conclusion: Five hub mitophagy-related genes were identified and correlated with immune infiltration in vitiligo. These findings suggested that mitophagy may promote the development of vitiligo by activating immune infiltration. Our study might enhance our comprehension of the pathogenic mechanism of vitiligo and offer a treatment option for vitiligo.


Assuntos
Vitiligo , Humanos , Vitiligo/genética , Linfócitos T CD8-Positivos , Mitofagia/genética , Algoritmos , Biologia Computacional , Proteínas Ativadoras de GTPase
11.
Surg Laparosc Endosc Percutan Tech ; 33(4): 365-369, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37311030

RESUMO

OBJECTIVE: Our study aims to compare the effects of different levels of access on postoperative neck bulge and swallowing disorder and provide a better level for endoscopic thyroidectomy. MATERIALS AND METHODS: The patients were selected retrospectively between March 2021 to September 2021 by the Department of Thyroid Surgery, Third Affiliated Hospital of Zunyi Medical University. They were divided into two groups according to the level of the free flap during surgery: group A (the superficial cervical fascial level) and group B (the superficial deep cervical fascial level). Age, sex, body mass index, diameter of the primary lesion, postoperative neck bulge, and swallowing disorders and other complications were compared between the two groups. RESULTS: A total of 40 patients who underwent endoscopic unilateral lobectomy plus central region lymph node dissection were enrolled in our study. Twenty in group A and 20 in group B. The age, gender, body mass index, diameter, and the proportion of benign and malignant primary lesions were not significantly different between the two groups ( P >0.05), and there was also no difference in thyroid function between the two groups ( P >0.05). No significant differences were observed in terms of bleeding and operation time during the operation ( P >0.05). There were also no statistical differences in terms of recurrent laryngeal nerve injury or hypoparathyroidism ( P >0.05). However, patients in group B were superior to those in group A in the occurrence of neck bulge and swallowing disorders ( P <0.05). These symptoms were most evident one month after surgery. Six months after the operation, only 4 patients in group B still complained of neck "swelling" and uncomfortable straining which did not resolve until 1 year after the operation. No statistical significance between long-term results and complication rates could be observed in either group. CONCLUSION: In endoscopic thyroidectomy, the superficial cervical fascial level may be a better option for reducing postoperative neck bulge and swallowing disorders, which needs further validation by conducting a large sample study.


Assuntos
Transtornos de Deglutição , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Esvaziamento Cervical/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
12.
Asian J Surg ; 46(12): 5421-5428, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37344318

RESUMO

BACKGROUND: Preserving parathyroid glands in situ is crucial to avoid surgical hypoparathyroidism, but it is also one of the greatest challenges during thyroid surgery. Magnified endoscopic imaging has been proposed as a way to improve parathyroid preservation. METHODS: 2,603 consecutive patients who underwent thyroid surgery at the First People's Hospital of Zunyi from January 2018 to July 2022 were screened. 1,355 patients were eligible, including 965 endoscopic and 390 open cases. Parathyroid hormone (PTH) loss levels and severe parathyroid injury rates were compared between endoscopic and open cases. Meanwhile, factors that contribute to parathyroid injuries were assessed, including surgical extent, tumor size, carbon nanoparticle guidance, and surgical proficiency. RESULTS: PTH loss levels were similar between endoscopic and open cases (P = 0.440). The incidence of severe parathyroid injuries was also comparable (7.8% for endoscopic vs. 6.9% for open, P = 0.592). The endoscopic group had higher rates of autologous parathyroid transplantation (39.5% vs. 24.4%, P = 0.000), while accidental parathyroidectomy rates were similar (11.4% vs. 10.8%, P = 0.739). Among patients who received the same extent of thyroid surgeries, no significant difference was found in PTH loss levels and severe parathyroid injury rates, except for a higher risk of severe parathyroid injuries in endoscopic bilateral thyroidectomy (18.52% vs. 11.52%, P = 0.033). CONCLUSIONS: Despite the magnified endoscopic imaging facilitating the identification of parathyroid tissues, endoscopic approaches are not superior to open ones for the in-situ preservation of parathyroid glands. For a bilateral thyroidectomy, open approaches are safer for parathyroid preservation.


Assuntos
Glândulas Paratireoides , Neoplasias da Glândula Tireoide , Humanos , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/cirurgia , Mamilos , Neoplasias da Glândula Tireoide/cirurgia , Hormônio Paratireóideo , Tireoidectomia/métodos
13.
Front Immunol ; 14: 1124786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37234169

RESUMO

Psoriasis is a chronic autoinflammatory skin disease associated with multiple comorbidities, with a prevalence ranging from 2 to 3% in the general population. Decades of preclinical and clinical studies have revealed that alterations in cholesterol and lipid metabolism are strongly associated with psoriasis. Cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-17), which are important in the pathogenesis of psoriasis, have been shown to affect cholesterol and lipid metabolism. Cholesterol metabolites and metabolic enzymes, on the other hand, influence not only the biofunction of keratinocytes (a primary type of cell in the epidermis) in psoriasis, but also the immune response and inflammation. However, the relationship between cholesterol metabolism and psoriasis has not been thoroughly reviewed. This review mainly focuses on cholesterol metabolism disturbances in psoriasis and their crosstalk with psoriatic inflammation.


Assuntos
Citocinas , Psoríase , Humanos , Citocinas/metabolismo , Inflamação , Metabolismo dos Lipídeos , Colesterol
14.
Int J Mol Sci ; 24(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37175722

RESUMO

Psoriasis and atopic dermatitis (AD) are multifactorial and heterogeneous inflammatory skin diseases, while years of research have yielded no cure, and the costs associated with caring for people suffering from psoriasis and AD are a huge burden on society. Integrating several omics datasets will enable coordinate-based simultaneous analysis of hundreds of genes, RNAs, chromatins, proteins, and metabolites in particular cells, revealing networks of links between various molecular levels. In this review, we discuss the latest developments in the fields of genomes, transcriptomics, proteomics, and metabolomics and discuss how they were used to identify biomarkers and understand the main pathogenic mechanisms underlying these diseases. Finally, we outline strategies for achieving multi-omics integration and how integrative omics and systems biology can advance our knowledge of, and ability to treat, psoriasis and AD.


Assuntos
Dermatite Atópica , Psoríase , Humanos , Dermatite Atópica/genética , Dermatite Atópica/terapia , Multiômica , Projetos de Pesquisa , Proteômica , Metabolômica , Psoríase/genética , Psoríase/terapia
15.
J Math Anal Appl ; 526(2): 127283, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37035507

RESUMO

Since November 2021, there have been cases of COVID-19's Omicron strain spreading in competition with Delta strains in many parts of the world. To explore how these two strains developed in this competitive spread, a new compartmentalized model was established. First, we analyzed the fundamental properties of the model, obtained the expression of the basic reproduction number, proved the local and global asymptotic stability of the disease-free equilibrium. Then by means of the cubic spline interpolation method, we obtained the data of new Omicron and Delta cases in the United States of new cases starting from December 8, 2021, to February 12, 2022. Using the weighted nonlinear least squares estimation method, we fitted six time series (cumulative confirmed cases, cumulative deaths, new cases, new deaths, new Omicron cases, and new Delta cases), got estimates of the unknown parameters, and obtained an approximation of the basic reproduction number in the United States during this time period as R 0 ≈ 1.5165 . Finally, each control strategy was evaluated by cost-effectiveness analysis to obtain the optimal control strategy under different perspectives. The results not only show the competitive transmission characteristics of the new strain and existing strain, but also provide scientific suggestions for effectively controlling the spread of these strains.

16.
Discov Med ; 35(175): 144-156, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37105924

RESUMO

BACKGROUND: Furin is a calcium-dependent serine protease found in almost all mammals. It plays an important role in embryogenesis, tissue homeostasis, tumors pathogenesis, viral infectious diseases, and neurodegenerative diseases. However, whether furin directly regulates melanin synthesis and transport has rarely been evaluated yet. The present study aimed to investigate furin potential function and mechanisms in melanogenesis. METHODS: Short hairpin RNAs targeting furin gene (sh-furin RNAs) were used to inhibit furin gene expression in human melanoma cell line MNT-1 cells. Then, intracellular melanin content was measured using a sodium hydroxide method. Extracellular melanin content was measured determining cell culture medium absorbance at 450 nm. Levodopa (L-DOPA) oxidation rate was measured to assess the tyrosinase activity. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) were performed to measure melanogenesis-related genes and Notch pathway-related genes expression levels. Human primary melanocytes (MCs) were extracted from foreskin tissues and were stimulated with a furin inhibitor. Then, the extracellular and intracellular melanin content, tyrosinase activity and molecules related to melanogenesis and the Notch pathway expression were measured in MCs with or without a furin inhibitor. Additionally, morpholino technology was used to inhibit furin in zebrafish. Zebrafish pigmentary phenotypes in the control group and furin inhibition group were observed with a stereo microscope. Then, MCs number in the tail and head of the zebrafish were counted using Image J software (version 1.53t, National Institute of Health, Bethesda, MD, USA). Meanwhile, melanin content, tyrosinase activity, and molecules related to melanogenesis and the Notch pathway expression levels were measured. Subsequently, valproic acid (VPA), a Notch pathway agonist, was used in MNT-1 melanoma cells treated with or without sh-furin lentiviral vectors for rescue experiments. RESULTS: Furin inhibition enhanced intracellular and extracellular melanin content, and cellular tyrosinase activity in MNT-1 cells and MCs. Additionally, furin inhibition increased melanin synthesis-associated and transport-associated proteins expression levels while inhibiting Notch pathway-relevant proteins. After using VPA to activate the Notch pathway in MNT-1 cells transfected with a sh-furin RNA, the biological effects resulting from furin knockdown were reversed. In addition, the results of in vivo experiments using morpholino to knock down furin gene in zebrafish further confirmed that furin knockdown regulated melanogenesis and impaired the Notch pathway. CONCLUSIONS: This study clarified that furin affected the synthesis and transport of melanin via Notch pathway. Notch pathway may be a potential therapeutic target for pigmented skin diseases.


Assuntos
Melaninas , Melanoma Experimental , Animais , Humanos , Peixe-Zebra/metabolismo , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Furina/genética , Furina/metabolismo , Pró-Proteína Convertases/metabolismo , Morfolinos , Melanoma Experimental/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Mamíferos/metabolismo
17.
Asian J Surg ; 46(7): 2884-2885, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36732181
18.
Exp Dermatol ; 32(6): 752-765, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36809573

RESUMO

Dowling-Degos disease (DDD) is an autosomal dominant hereditary skin disease characterized by acquired reticular hyperpigmentation in flexural sites, and one of its causative genes is KRT5 gene. But the effect of KRT5, expressed only in keratinocytes, on melanocytes is unclear. Other pathogenic genes of DDD include POFUT1, POGLUT1 and PSENEN genes, which is involved in posttranslational modification of Notch receptor. In this study, we aim to determine the ablation of keratinocyte KRT5 affect melanogenesis in melanocyte through Notch signalling pathway. Here we found that KRT5 downregulation decreased the expression of the Notch ligand in keratinocytes and Notch1 intracellular domain in melanocytes, by establishing two cell models of ablation of KRT5 in keratinocytes based on CRISPR/Cas9 site-directed mutation and lentivirus-mediated shRNA. Treatment of melanocytes with Notch inhibitors had same effects with ablation of KRT5 on increase of TYR and decrease of Fascin1. Activation of Notch signalling reverses the effect of ablation of KRT5 on melanogenesis. Immunohistochemistry of DDD lesions with KRT5 gene mutation confirmed changes in the expression of relevant molecules in Notch signalling. Our research elucidates molecular mechanism of KRT5-Notch signalling pathway in the regulation of melanocytes by keratinocytes, and preliminary reveal the mechanism of DDD pigment abnormality caused by KRT5 mutation. These findings identify potential therapeutic targets of the Notch signalling pathway for the treatment of skin pigment disorders.


Assuntos
Hiperpigmentação , Melaninas , Humanos , Melaninas/metabolismo , Mutação , Queratinócitos/metabolismo , Hiperpigmentação/genética , Melanócitos/metabolismo , Proteínas de Membrana/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Queratina-5/genética , Glucosiltransferases/genética , Glucosiltransferases/metabolismo
20.
J Ultrasound Med ; 42(3): 613-621, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36056908

RESUMO

OBJECTIVES: Subacute thyroiditis (SAT) is a self-limiting, inflammatory thyroid disease possibly caused by viral infection. In recent years, the incidence of SAT is increasing, especially during the pandemic of the COVID-19. This study aimed to evaluate the efficacy, safety, and recovery time of capsular thyroid injection therapy under ultrasound guidance for SAT. METHODS: A total of 73 patients with SAT were divided into two groups. Patients in group A (n = 48) received an ultrasound-guided capsular injection consisting of dexamethasone (DEX) and lidocaine in the thyroid lesion area, while patients in group B (n = 25) received oral prednisolone (PSL). The two groups were compared for pain relief and treatment duration, the recovery time of thyroid function, recurrence rates, hypothyroidism incidence, and drug-related side effects. RESULTS: The follow-up time was 1 year. In group A, the duration of pain relief, treatment, and recovery time of thyroid function were significantly shorter than that in group B (P < .05), and no statistically significant differences in recurrence rate or incidence of hypothyroidism were observed (P > .05). Weight gain was significantly higher in group A at the end of treatment (P < .001). CONCLUSIONS: Compared with oral PSL treatment, ultrasound-guided local injection of DEX and lidocaine into the capsular thyroid is a safe and effective procedure that can significantly reduce the treatment time of SAT.


Assuntos
COVID-19 , Hipotireoidismo , Tireoidite Subaguda , Humanos , Tireoidite Subaguda/diagnóstico por imagem , Tireoidite Subaguda/tratamento farmacológico , Tireoidite Subaguda/patologia , Lidocaína , COVID-19/complicações , Tratamento Farmacológico da COVID-19 , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/etiologia , Ultrassonografia de Intervenção , Dor/tratamento farmacológico , Dexametasona/uso terapêutico
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