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1.
J Dermatolog Treat ; 35(1): 2334791, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38565205

RESUMO

Generalized pustular psoriasis (GPP) in pregnancy can lead to severe complications for both mother and fetus. The treatment of this disease is challenging, especially in recalcitrant and severe cases. Until present, there are no evidence-based guidelines for the treatment of GPP in pregnancy. Spesolimab, a human monoclonal antibody against the IL-36 receptor, has recently attracted attention as a new therapy for GPP flare. This biologic provides rapid and sustained control of symptoms of GPP flare, although its use in pregnant women has not been reported to date. Here, we report a pregnant woman with refractory GPP who did not respond well to systemic steroids. Administration of spesolimab resulted in complete control of the disease and the birth of a healthy baby. Our case demonstrates that IL-36RN inhibitors are a potentially effective and safe treatment option for GPP in pregnancy.


Assuntos
Fármacos Dermatológicos , Psoríase , Humanos , Feminino , Gravidez , Fármacos Dermatológicos/uso terapêutico , Psoríase/diagnóstico , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Doença Aguda , Doença Crônica
2.
Ann Lab Med ; 44(4): 343-353, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38433572

RESUMO

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.


Assuntos
Hipotireoidismo Congênito , Humanos , China , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , AMP Cíclico , Oxidases Duais/genética , Mutação , Fenótipo , Receptores da Tireotropina/genética , Tireotropina
5.
Nat Commun ; 14(1): 8082, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057310

RESUMO

The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation.


Assuntos
NF-kappa B , Células Epiteliais da Tireoide , Animais , Camundongos , Células Mieloides , Fator de Necrose Tumoral alfa , Peixe-Zebra
6.
Ann Dermatol ; 35(Suppl 2): S338-S339, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38061735
7.
J Dermatolog Treat ; 34(1): 2279899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010938

RESUMO

Immunoglobulin gamma (IgG) type 4-related disease (IgG4-RD) is a chronic immunologic systemic disorder that could affect multiple organs, which may cause irreversible organ damage or even death. Skin involvement is rare and associated especially with systemic disease. The dermatologist must be equipped to recognize IgG4-RD to prevent delayed identification and treatment. This case reports a very rare case of IgG4-related skin disease (IgG4-RSD) presenting with a generalized angiolymphoid hyperplasia with eosinophilia (ALHE)-like lesions in a middle-aged male patient with no other organ involvement. He was treated with oral glucocorticoid and cyclophosphamide, which resulted in complete remission. No relapse and disease progression were seen with a follow-up for 8 years.


Assuntos
Hiperplasia Angiolinfoide com Eosinofilia , Doença Relacionada a Imunoglobulina G4 , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Angiolinfoide com Eosinofilia/patologia , Hiperplasia Angiolinfoide com Eosinofilia/terapia , Ciclofosfamida/uso terapêutico , Seguimentos , Glucocorticoides/uso terapêutico , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações
8.
Front Med (Lausanne) ; 10: 1226473, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37780558

RESUMO

Objectives: To systematically evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients. Methods: Risk prediction models for postoperative delirium in older adult hip fracture patients were collected from the Cochrane Library, PubMed, Web of Science, and Ovid via the internet, covering studies from the establishment of the databases to March 15, 2023. Two researchers independently screened the literature, extracted data, and used Stata 13.0 for meta-analysis of predictive factors and the Prediction Model Risk of Bias Assessment Tool (PROBAST) to evaluate the risk prediction models for postoperative delirium in older adult hip fracture patients, evaluated the predictive performance. Results: This analysis included eight studies. Six studies used internal validation to assess the predictive models, while one combined both internal and external validation. The Area Under Curve (AUC) for the models ranged from 0.67 to 0.79. The most common predictors were preoperative dementia or dementia history (OR = 3.123, 95% CI 2.108-4.626, p < 0.001), American Society of Anesthesiologists (ASA) classification (OR = 2.343, 95% CI 1.146-4.789, p < 0.05), and age (OR = 1.615, 95% CI 1.387-1.880, p < 0.001). This meta-analysis shows that these were independent risk factors for postoperative delirium in older adult patients with hip fracture. Conclusion: Research on the risk prediction models for postoperative delirium in older adult hip fracture patients is still in the developmental stage. The predictive performance of some of the established models achieve expectation and the applicable risk of all models is low, but there are also problems such as high risk of bias and lack of external validation. Medical professionals should select existing models and validate and optimize them with large samples from multiple centers according to their actual situation. It is more recommended to carry out a large sample of prospective studies to build prediction models. Systematic review registration: The protocol for this systematic review was published in the International Prospective Register of Systematic Reviews (PROSPERO) under the registered number CRD42022365258.

9.
BMC Nephrol ; 24(1): 298, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37821807

RESUMO

BACKGROUND: Low levels of Free Triiodothyronine (FT3) are associated with poor survival in chronic kidney disease, and the aim of this study was to further assess the relationship between changes in FT3 levels and renal damage in patients with type 2 diabetes based on glomerular and tubular markers. METHODS: We retrospectively studied 452 type 2 diabetic patients, measured glomerular damage markers (UACR, eGFR) and tubular damage markers (NAG/Cr,ß2-MG), analyzed the relationship between FT3 and renal damage by logistic regression models, and plotted restrictive cubic splines. RESULTS: 41.6% of subjects had diabetic kidney disease (DKD), and the prevalence of DKD decreased progressively with increasing FT3 levels in the third quartile. Spearman correlation analysis showed that FT3 was negatively associated with UACR, NAG/Cr and ß2-MG, while eGFR was positively associated with FT3. Multifactorial analysis, after adjusting for relevant confounders, revealed that compared with the lowest quartile of FT3, the highest quartile reduced the risk of developing urinary albumin (OR = 0.499,95% CI:0.289-0.856), moderate to severe impairment of glomerular filtration rate (OR = 0.106,95% CI:0.032-0.354), renal tubular marker ß2 -MG positive (OR = 0.516,95% CI:0.299 to 0.883) and the risk of DKD occurrence (OR = 0.450,95% CI:0.260 to 0.774). In the sample model, FT3 levels below 4.39 pmol/L were associated with an increased risk of glomerular tubule injury and DKD occurrence. CONCLUSIONS: FT3 is closely associated with glomerular tubular injury and is a protective factor. As FT3 levels (< 4.39 pmol/L) decrease, the risk of developing DKD becomes higher, and FT3 can be used as an independent predictor of developing DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Tri-Iodotironina , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Biomarcadores , Taxa de Filtração Glomerular
10.
Horm Res Paediatr ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37703865

RESUMO

INTRODUCTION: Congenital hypothyroidism (CH), the most common neonatal endocrine disorder world-wide, can be caused by variants in the thyroid peroxidase (TPO) gene. This study aimed to identify TPO variants in Chinese patients with CH, analyze their impact on TPO function, and establish relationships between TPO genotypes and clinical characteristics. METHODS: A total of 328 patients with CH were screened for TPO variants by performing whole exome sequencing. The function of the detected TPO variants was investigated via transfection assays in vitro. The pathogenic effect of five novel variants was further assessed in silico. RESULTS: Among 328 patients with CH, 19 TPO variants, including six novel ones, were identified in 43 patients. Eighteen patients (5.5%) carried biallelic TPO variants. In vitro experiments showed that TPO activity was impaired to varying degrees in 17 variants. Furthermore, we determined that a residual TPO enzyme activity threshold of 15% may serve as a criterion for differentiating CH severity. CONCLUSIONS: According to our study, the prevalence of TPO variants among Chinese patients with CH was 13.1 %. Five novel variants led to impaired TPO function by altering its structure or by affecting its expression or cellular localization, which should result in impaired thyroid hormone synthesis.

11.
Front Endocrinol (Lausanne) ; 14: 1204678, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600710

RESUMO

Introduction: In recent years, the potential toxicities of different pharmaceuticals toward the thyroid system have received increasing attention. In this study, we aim to evaluate the toxic effects of pazopanib and axitinib, two anti-tumor drugs with widespread clinical use, on thyroid function in the zebrafish model. Methods: We measured levels of thyroid-related hormones using the commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Whole-mount in situ hybridization (WISH) analysis was employed to detect target gene expression changes. Morphology of the thyroid were evaluated by using transgenic Tg (tg: EGFP) fish line under a confocal microscope. The relative mRNA expression of key genes was verified through quantitative real-time polymerase chain reaction (RT‒qPCR). The size and number of the follicles was quantified whereby Hematoxylin-Eosin (H & E) staining under a light microscope. Results: The results revealed that fertilized zebrafish embryos were incubated in pazopanib or axitinib for 96 hours, development and survival were significantly affected, which was accompanied by significant disturbances in thyroid endocrine system (e.g., increased thyroid-stimulating hormone (TSH) content and decreased triiodothyronine (T3) and thyroxine (T4) content, as well as transcription changes of genes associated with the hypothalamus-pituitary-thyroid (HPT) axis. Moreover, based on whole-mount in situ hybridization staining of tg and histopathological examination of zebrafish embryos treated with pazopanib and axitinib, we observed a significantly abnormal development of thyroid follicles in the Tg (tg: EGFP) zebrafish transgenic line. Conclusion: Collectively, these findings indicate that pazopanib and axitinib may have toxic effects on thyroid development and function, at least partially, by influencing the regulation of the HPT axis. Thus, we believe that the potential thyroid toxicities of pazopanib and axitinib in their clinical applications should receive greater attention.


Assuntos
Antineoplásicos , Peixe-Zebra , Animais , Axitinibe , Glândula Tireoide , Larva , Animais Geneticamente Modificados
12.
JAMA Dermatol ; 159(10): 1059-1067, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37585188

RESUMO

Importance: There are limited prognostic statistics and data available on survival outcomes for patients with mycosis fungoides (MF) in Asia. Objective: To determine the prognostic factors and survival outcomes of patients with MF among a cohort in China. Design, Setting, and Participants: This was a retrospective cohort study of patients with MF who received treatment at a tertiary referral center for skin lymphoma (Peking University First Hospital, Beijing, China) from August 1, 2009, to August 31, 2021. Data were analyzed from September 1, 2021, to December 31, 2022. Main Outcomes and Measures: Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS); for prognostic factors, hazard ratios (HRs), and adjusted HRs (aHRs; adjusted for sex, age, and overall TNMB [tumor, node, metastasis, blood] stage) determined using the Cox proportional hazards model. Results: The study cohort comprised 461 patients with MF (median [range] age at diagnosis, 46 [5-87] years; 275 [59.7%] men and 186 [40.3%] women; 461 [100%] Chinese). The overall 5-year rate was 82.2% for OS, 83.5% for DSS, and 79.6% for PFS. Stage-specific 5-year OS rates were 95.7% for stage IA, 93.2% for IB, 95.7% for IIA, 70.1% for IIB, 55.3% for III, and 23.6% for IV. Compared with a UK cohort, our Chinese cohort had a younger median age at diagnosis (46 years vs 54 years) and a more favorable 5-year OS (82.2% vs 75.0%); however, after adjusting for age, the discrepancy in the 5-year OS rate was diminished (77.3% vs 76.4%). Cox models revealed that unfavorable predictors of OS, PFS, and DSS, respectively, were: age older than 60 years (aHR [95% CI], 2.25 [1.28-3.96]; 2.09 [1.16-3.76]; 2.27 [1.39-3.72]); advanced TNMB stage; advanced overall stage; large-cell transformation (aHR [95% CI], 2.16 [1.17-3.99]; 2.29 [1.21-4.33]; 2.21 [1.26-3.86]); and elevated lactate dehydrogenase levels (aHR [95% CI], 3.92 [1.64-9.36]; 4.77 [1.86-12.22]; 5.05 [2.23-11.42]). Biological sex and plaque lesion type were not associated with prognosis among this study cohort. Conclusion and Relevance: The findings of this retrospective cohort study of patients with MF in China suggest that Asian patients are diagnosed at a younger age and have a higher 5-year OS compared with patients of other races in studies in other countries (predominantly White). Prognostic factors were similar to those of previous studies, except for patient sex and plaque lesion type.


Assuntos
Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Masculino , Humanos , Feminino , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Prognóstico , Síndrome de Sézary/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Progressão da Doença , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/patologia , China/epidemiologia
13.
J Cosmet Dermatol ; 22(11): 3168-3175, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37589235

RESUMO

BACKGROUND: The current standard recommendation is to initiate the cosmetic therapies after discontinuing taking oral isotretinoin for at least 6 months. However, this recommendation has been questioned in several recent publications, and it is difficult to operate in clinical practice as early initiation of effective treatment is desirable for patients with acne sequelae. OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of chemical peeling and light/laser or radiofrequency treatments combined with oral isotretinoin for patients with acne vulgaris and acne scars. METHOD: A retrospective study of 511 patients on/or recently administered with isotretinoin treated with glycolic acid, intense pulsed light, nonablative fractional laser, fractional radiofrequency, and ablative carbon dioxide laser. A total of 1352 interventions were performed. The medical follow-up lasted for at least 1 year. The efficacy and safety of different procedures were evaluated. RESULTS: A total of 511 patients, who were treated with isotretinoin orally or stopped for <6 months, received 477 sessions of glycolic acid chemical peeling treatment, 588 sessions of intense pulsed light treatment, 61 sessions of nonablative fractional laser treatment, 101 sessions of fractional radiofrequency treatment, and 125 sessions of ablative fractional carbon dioxide laser treatment. No hypertrophic scars and keloids were found, and the incidence of serious adverse reactions such as scarring, erythema, blisters, and postinflammatory hyperpigmentation did not increase. CONCLUSIONS: It is safe to perform skin procedures in patients with acne and acne scars during or after discontinuation of isotretinoin for <6 months. Invasive treatments such as ablative fractional carbon dioxide laser treatment can be performed, as appropriate, by an experienced physician. The guideline of avoiding chemical and physical procedures in such patients taking oral isotretinoin should to revised.

14.
An. bras. dermatol ; 98(4): 498-505, July-Aug. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1447234

RESUMO

Abstract Background: A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. Objective: To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. Methods: CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. Results: The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAFV600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this datasets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. Study limitations: A small sample of patients were included and there was no follow-up. Conclusions: BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.

15.
Bioengineering (Basel) ; 10(6)2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37370564

RESUMO

Over 70,000 people die of bacterial infections worldwide annually. Antibiotics have been liberally used to treat these diseases and, consequently, antibiotic resistance and drug ineffectiveness has been generated. In this environment, new anti-bacterial compounds are being urgently sought. Around 500 Artemisia species have been identified worldwide. Most species of this genus are aromatic and have multiple functions. Research into the Artemisia plants has expanded rapidly in recent years. Herein, we aim to update and summarize recent information about the phytochemistry, pharmacology and toxicology of the Artemisia plants. A literature search of articles published between 2003 to 2022 in PubMed, Google Scholar, Web of Science databases, and KNApSAcK metabolomics databases revealed that 20 Artemisia species and 75 compounds have been documented to possess anti-bacterial functions and multiple modes of action. We focus and discuss the progress in understanding the chemistry (structure and plant species source), anti-bacterial activities, and possible mechanisms of these phytochemicals. Mechanistic studies show that terpenoids, flavonoids, coumarins and others (miscellaneous group) were able to destroy cell walls and membranes in bacteria and interfere with DNA, proteins, enzymes and so on in bacteria. An overview of new anti-bacterial strategies using plant compounds and extracts is also provided.

16.
An Bras Dermatol ; 98(4): 498-505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37156689

RESUMO

BACKGROUND: A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. OBJECTIVE: To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. METHODS: CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. RESULTS: The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAF V600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this data sets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. STUDY LIMITATIONS: A small sample of patients were included and there was no follow-up. CONCLUSIONS: BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.


Assuntos
Nevo Pigmentado , Nevo , Neoplasias Cutâneas , Humanos , Criança , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Antígeno Ki-67/genética , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Mutação/genética
17.
J Med Genet ; 60(9): 874-884, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36898841

RESUMO

BACKGROUND: In several countries, thyroid dyshormonogenesis is more common than thyroid dysgenesis in patients with congenital hypothyroidism (CH). However, known pathogenic genes are limited to those directly involved in hormone biosynthesis. The aetiology and pathogenesis of thyroid dyshormonogenesis remain unknown in many patients. METHODS: To identify additional candidate pathogenetic genes, we performed next-generation sequencing in 538 patients with CH and then confirmed the functions of the identified genes in vitro using HEK293T and Nthy-ori 3.1 cells, and in vivo using zebrafish and mouse model organisms. RESULTS: We identified one pathogenic MAML2 variant and two pathogenic MAMLD1 variants that downregulated canonical Notch signalling in three patients with CH. Zebrafish and mice treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester, a γ-secretase inhibitor exhibited clinical manifestations of hypothyroidism and thyroid dyshormonogenesis. Through organoid culture of primary mouse thyroid cells and transcriptome sequencing, we demonstrated that Notch signalling within thyroid cells directly affects thyroid hormone biosynthesis rather than follicular formation. Additionally, these three variants blocked the expression of genes associated with thyroid hormone biosynthesis, which was restored by HES1 expression. The MAML2 variant exerted a dominant-negative effect on both the canonical pathway and thyroid hormone biosynthesis. MAMLD1 also regulated hormone biosynthesis through the expression of HES3, the target gene of the non-canonical pathway. CONCLUSIONS: This study identified three mastermind-like family gene variants in CH and revealed that both canonical and non-canonical Notch signalling affected thyroid hormone biosynthesis.


Assuntos
Hipotireoidismo Congênito , Animais , Humanos , Camundongos , Hipotireoidismo Congênito/genética , Proteínas de Ligação a DNA/genética , Células HEK293 , Mutação , Proteínas Nucleares/genética , Hormônios Tireóideos/genética , Transativadores/genética , Fatores de Transcrição/genética , Peixe-Zebra
18.
Mol Med Rep ; 27(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36825576

RESUMO

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the wound­healing assays portrayed in Fig. 2A on p. 6692, in the 0 h row, the 'NG + LI' and 'HG + HI' panels contained overlapping data, such that they appeared to have been derived from the same original source. After having examined their original data, the authors have realized that this figure was inadvertently assembled incorrectly. The corrected version of Fig. 2. showing the correct data for the 'HG + HI' panel, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper, and all the authors agree with the publication of this Corrigendum. Furthermore, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 6690­6696, 2017; DOI: 10.3892/mmr.2017.7420].

19.
JCI Insight ; 8(4)2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36649072

RESUMO

BACKGROUNDImmune checkpoint blockade is an emerging treatment for T cell non-Hodgkin's lymphoma (T-NHL), but some patients with T-NHL have experienced hyperprogression with undetermined mechanisms upon anti-PD-1 therapy.METHODSSingle-cell RNA-Seq, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma who experienced hyperprogression upon anti-PD-1 treatment.RESULTSThe patient was enrolled in a clinical trial of anti-PD-1 therapy and experienced disease hyperprogression. Single-cell RNA-Seq revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4+ malignant T cells, which showed functional PD-1 expression and an exhausted status. Further analyses identified somatic amplification of PRKCQ in the malignant T cells. PRKCQ encodes PKCθ; PKCθ is a key player in the T cell activation/NF-κB pathway. PRKCQ amplification led to high expressions of PKCθ and p-PKCθ (T538) on the malignant T cells, resulting in an oncogenic activation of the T cell receptor (TCR) signaling pathway. PD-1 blockade in this patient released this signaling, derepressed the proliferation of malignant T cells, and resulted in disease hyperprogression.CONCLUSIONOur study provides real-world clinical evidence that PD-1 acts as a tumor suppressor for malignant T cells with oncogenic TCR activation.TRIAL REGISTRATIONClinicalTrials.gov (NCT03809767).FUNDINGThe National Natural Science Foundation of China (81922058), the National Science Fund for Distinguished Young Scholars (T2125002), the National Science and Technology Major Project (2019YFC1315702), the National Youth Top-Notch Talent Support Program (283812), and the Peking University Clinical Medicine plus X Youth Project (PKU2019LCXQ012) supported this work.


Assuntos
Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Adolescente , Humanos , Proteína Quinase C-theta , Receptores de Antígenos de Linfócitos T , Transdução de Sinais
20.
Microb Pathog ; 175: 105970, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36621696

RESUMO

Recent studies have demonstrated that dysbiosis of the gut microbiota is associated with psoriasis, but these studies showed some conflicting results. Our study examined differences in microbiome composition associated in people with psoriasis and those without. Comparing individuals with their healthy partners was a second strategy. We explored the fecal microbiota among 32 nontreated plaque psoriasis patients, 15 healthy controls and 17 healthy couples by metagenomic gene sequencing. The relative levels of intestinal microbiota of the psoriasis cohort differed from those in healthy controls and these patients' partners. However, there was no microbial diversity among these three cohorts. On the level of the phylum, Firmicutes and Bacteroidetes' relative abundances were reversed. Escherichia coli was significantly enriched in the psoriasis group compared with the healthy people and the healthy spouses. Gene functional analysis indicated that Ribosome (ko03010) was upregulated, Flagellar assembly (ko02040) and Bacterial chemotaxis (ko02030) were downregulated in the psoriasis cohort compared with the healthy individuals and the healthy spouses. The microbiota in severe psoriasis patients differed from those with milder conditions. These findings strongly support the association between intestinal flora and psoriasis. It is necessary to perform more meaningful experiments to identify whether the differences of gut microbiota are the cause or consequences of psoriasis in future.


Assuntos
Microbioma Gastrointestinal , Microbiota , Psoríase , Humanos , Microbioma Gastrointestinal/genética , Microbiota/genética , Bactérias/genética , Bacteroidetes , Fezes/microbiologia , Disbiose/microbiologia , RNA Ribossômico 16S/genética
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