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1.
J Ginseng Res ; 48(2): 211-219, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465216

RESUMO

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0-2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C-O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

2.
Oncogene ; 43(9): 636-649, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38184713

RESUMO

Continuous administration of oxaliplatin, the most widely used first-line chemotherapy drug for colorectal cancer (CRC), eventually leads to drug resistance. Increasing the sensitivity of CRC cells to oxaliplatin is a key strategy to overcome this issue. Impairment of mitochondrial function is a pivotal mechanism determining the sensitivity of CRC to oxaliplatin. We discovered an inverse correlation between Translocase of Outer Mitochondrial Membrane 20 (TOMM20) and oxaliplatin sensitivity as well as an inverse relationship between TOMM20 and HECT, UBA, and WWE domain containing E3 ligase 1 (HUWE1) expression in CRC. For the first time, we demonstrated that HUWE1 ubiquitinates TOMM20 directly and also regulates TOMM20 degradation via the PARKIN-mediated pathway. Furthermore, we showed that overexpression of HUWE1 in CRC cells has a negative effect on mitochondrial function, including the generation of ATP and maintenance of mitochondrial membrane potential, leading to increased production of ROS and apoptosis. This effect was amplified when cells were treated simultaneously with oxaliplatin. Our study conclusively shows that TOMM20 is a novel target of HUWE1. Our findings indicate that HUWE1 plays a critical role in regulating oxaliplatin sensitivity by degrading TOMM20 and inducing mitochondrial damage in CRC.


Assuntos
Proteínas de Membrana Transportadoras , Ubiquitina-Proteína Ligases , Humanos , Oxaliplatina/farmacologia , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas de Transporte , Receptores de Superfície Celular/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
3.
Clin Rheumatol ; 43(3): 921-927, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38267768

RESUMO

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.


Assuntos
Artrite Reumatoide , Iniquidades em Saúde , Feminino , Humanos , Masculino , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/etnologia , Etnicidade/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Projetos de Pesquisa , Estados Unidos , Efeitos Psicossociais da Doença , Negro ou Afro-Americano/estatística & dados numéricos , Asiático/estatística & dados numéricos , Brancos/estatística & dados numéricos
4.
J Ethnopharmacol ; 321: 117574, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38097025

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. AIM OF THE STUDY: Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). MATERIALS AND METHODS: Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of -20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography-mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. RESULTS: Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. CONCLUSIONS: Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products.


Assuntos
Connaraceae , Humanos , Etanol/química , Extratos Vegetais/uso terapêutico , Linhagem Celular , Queratinócitos , Anti-Inflamatórios/uso terapêutico , Raios Ultravioleta/efeitos adversos , Inflamação/tratamento farmacológico , Luciferases
6.
Cell Rep ; 42(10): 113220, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37804509

RESUMO

A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supply GL261 syngeneic glioblastoma (GBM) mice with a short-term high-glucose drink (HGD) and find an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota through HGD supplementation is critical for enhancing the anti-tumor immune response. Single-cell RNA sequencing shows that gut microbiota modulation by HGD supplementation increases the T cell-mediated anti-tumor immune response in GBM mice. We find that the cytotoxic CD4+ T cell population in GBM is increased due to synergy with anti-programmed cell death protein 1 (anti-PD-1) immune checkpoint inhibitors, but this effect depends upon HGD supplementation. Thus, we determine that HGD supplementation enhances anti-tumor immune responses in GBM mice through gut microbiota modulation and suggest that the role of HGD supplementation in GBM should be re-examined.


Assuntos
Neoplasias Encefálicas , Microbioma Gastrointestinal , Glioblastoma , Camundongos , Animais , Glioblastoma/metabolismo , Neoplasias Encefálicas/metabolismo , Glucose , Imunidade , Suplementos Nutricionais , Açúcares
7.
ACS Appl Mater Interfaces ; 15(40): 47799-47809, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37769061

RESUMO

Top-gate self-aligned structured oxide thin-film transistors (TFTs) are suitable for the backplanes of high-end displays because of their low parasitic capacitances. The gate insulator (GI) deposition process should be carefully designed to manufacture a highly stable, high-mobility oxide TFT, particularly for a top-gate structure. In this study, a nanometer-thick Al2O3 layer via plasma-enhanced atomic layer deposition (PE-ALD) is deposited on the top-gate bottom-contact structured oxide TFT as the interface tailoring layer, which can also act as the hydrogen barrier to modulate carrier generation from hydrogen incorporation into the active layer of the TFT during the following process such as postannealing. Al-doped InSnZnO (Al/ITZO) with an Al/In/Sn/Zn atomic ratio composition of 1.7:24.3:40:34 was used for high mobility oxide semiconductors, and an Al2O3/Si3N4 bilayer was used for the GI. The degradation issue due to the excellent barrier characteristics of Al2O3 and Si3N4 can be minimized. An oxide TFT fabricated without the interface tailoring layer exhibits conductor-like characteristics owing to the excessive carrier generation by hydrogen incorporation. However, TFTs with additional interface layers exhibit reasonable characteristics and distinct trends in electrical characteristics depending on the thicknesses of the interface layers. The optimized devices exhibit an average turn-on voltage (Von) of -0.31 V with 33.63 cm2/(V s) of high mobility and 0.09 V/dec of subthreshold swing value. The interfaces between the active layer and hydrogen barriers were investigated using a high-resolution transmission electron microscope, contact angle measurement, and secondary ion mass spectroscopy to reveal the origin of the trends in properties between the devices. The top-gate device with a hydrogen barrier using the four-cycle deposition exhibits optimum electrical characteristics of both high mobility and good stability with only a 0.04 V shift of Von under positive-bias temperature stress (PBTS). We realize a high-end, self-aligned TFT with high mobility [34.7 cm2/(V s)] and negligible Von shift of -0.06 V under PBTS by applying a subnanometer hydrogen barrier.

8.
Biosens Bioelectron ; 241: 115700, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37757509

RESUMO

The simultaneous infection with a tripledemic-simultaneous infection with influenza A pH1N1 virus (Flu), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and respiratory syncytial virus (RSV)-necessitates the development of accurate and fast multiplex diagnostic tests. The coronavirus disease 2019 (COVID-19) pandemic has emphasized the importance of virus detection. Field-effect transistor (FET)-based immuno-biosensors have a short detection time and do not require labeling or polymerase chain reaction. This study demonstrates the rapid, sensitive detection of influenza A pH1N1, SARS-CoV-2, and RSV using a multiplex immunosensor based on a dual-gate oxide semiconductor thin-film transistor (TFT), a type of FET. The dual-gate oxide TFT was modified by adjusting both top and bottom gate insulators to improve capacitive coupling to approximately 120-fold amplification, exhibiting a high pH sensitivity of about 10 V/pH. The dual-gate oxide TFT-based immunosensor detected the target proteins (hemagglutinin (HA) protein of Flu, spike 1 (S1) protein of SARS-CoV-2, and fusion protein of RSV) of each virus, with a limit of detection of approximately 1 fg/mL. Cultured viruses in phosphate-buffered saline or artificial saliva and clinical nasopharynx samples were detected in 1-µL sample volumes within 60 s. This promising diagnosis could be potentially as point-of-care tests to facilitate a prompt response to future pandemics with high sensitivity and multiplexed detection without pretreatment.

9.
Mitochondrial DNA B Resour ; 8(7): 783-786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37521905

RESUMO

The complete chloroplast genome sequence of Crepidomanes latealatum (Bosch) Copel. was determined in the present study. The genome is 145,943 base pairs (bp) in length and comprised two inverted repeats (32,990 bp) between a large single copy (92,170 bp) and a small single copy (20,783 bp). It contains 88 coding genes, 8 rRNA genes, 34 tRNA genes, and 1 pseudogene of trnL-UAA, and the GC content is 37.6%. Molecular phylogenetic analysis based on the plastid genome sequences of related taxa strongly supported the monophyly of the family Hymenophyllaceae, and the genus Vandenboschia was a sister group of Crepidomanes. In addition, compared to C. minutum, two large deletions of 453 bp and 878 bp were found in the IGS regions of petA-psbI and rrn16-trnV-GAC of C. latealatum cp genome, respectively.

10.
Front Psychol ; 14: 1192842, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484076

RESUMO

The indoor environment has been recognized as a crucial factor that can influence health and wellbeing of occupants. This is particularly true in hospital settings, where various environmental attributes can significantly affect patients' recovery and staff members' productivity. The present study aimed to investigate how occupants in hospitals perceived indoor environment, focusing specifically on COVID-19 hospitals across Republic of Korea. The study recruited two groups of participants: patients (n = 100) who had been hospitalized in COVID-19 hospitals and staff members (n = 103) who worked in COVID-19 hospitals. The data collected from the participants were analyzed using multiple regression models to determine which environmental attributes significantly affected their perception of the indoor environment. The study revealed that satisfaction with indoor acoustic environment and odor were significant predictors for how patients perceived the indoor environment as helpful for their recovery from COVID-19. On the other hand, odor was also the significant factor affecting staff members' perceived helpfulness for work. The results suggested that different environmental attributes can have a significant impact on the perception of the indoor environment, depending on the characteristics of occupancy. The study's findings provided insights into the certain environmental factors that COVID-19 hospitals can prioritize. These insights can help policymakers and hospital administrators to develop strategies to create hospital environments that meet the needs of both groups. The study also suggested that further research is needed to investigate additional factors affecting occupants' perception of the indoor environment in hospital settings.

11.
Dermatol Ther (Heidelb) ; 13(11): 2589-2603, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37525000

RESUMO

INTRODUCTION: Deucravacitinib, an oral tyrosine kinase 2 (TYK2) inhibitor, is approved in the United States to treat adults with moderate-to-severe plaque psoriasis (PsO). This study compared the long-term efficacy of deucravacitinib and adalimumab using results from long-term extension (LTE) trials. METHODS: Open-label LTE trials were identified for an indirect treatment comparison (deucravacitinib: POETYK PSO-LTE [NCT04036435]; adalimumab: REVEAL extension [NCT00195676]). To ensure study design comparability, patients initially randomized to placebo and switched to deucravacitinib or adalimumab after week 16 were compared. The primary outcome was an ≥ 75% reduction in Psoriasis Area and Severity Index score (PASI 75) at week 112 postrandomization. Secondary outcomes were PASI 75 at week 52 and an ≥ 90% reduction in PASI score (PASI 90) at weeks 52 and 112. Missing PASI data were imputed. A matching-adjusted indirect comparison was conducted; individual patient-level data from POETYK PSO-LTE were reweighted to balance baseline characteristics with those from the REVEAL extension. RESULTS: Before reweighting, on average, patients in the POETYK PSO-LTE (N = 329) versus the REVEAL (N = 345) extension were older, had a lower body weight, received more prior systemic treatments, and had higher baseline PASI scores and week 16 placebo PASI 75 and PASI 90 response rates. Following reweighting, adjusted week 112 PASI 75 response rates were significantly higher for deucravacitinib versus adalimumab (67.2% vs. 54.0%; mean difference [95% CI], 13.2 [4.0-22.5] percentage points). Deucravacitinib had a numerically higher adjusted week 112 PASI 90 response rate (41.3% vs. 34.0%; mean difference [95% CI], 7.3 [-2.0 to 16.7] percentage points). The treatments had similar week 52 adjusted PASI 75 and PASI 90 response rates. CONCLUSION: In this interim analysis, adults with moderate to severe PsO had higher long-term response rates at 2 years when treated with deucravacitinib versus adalimumab. Deucravacitinib response rates remained stable whereas adalimumab response rates declined in year 2.


Plaque psoriasis is an inflammatory disease that causes red, itchy, dry patches (called plaques) on the skin. The disease cannot be cured, but the symptoms can be treated. Deucravacitinib and adalimumab are two treatments approved for use in adults with moderate to severe plaque psoriasis; deucravacitinib is an oral medication and adalimumab is injected with a needle under the skin. Each treatment has proven its efficacy compared with placebo (a pill or injection with no active effect) in separate clinical trials, but because no two clinical trials are exactly alike, the results cannot be accurately compared. Matching-adjusted indirect comparison is a method used to compare the results of one clinical trial with those of another when a direct comparison is not possible; characteristics from the patients in one trial are made to match the patient population in the other trial, and the adjusted results are compared. We performed a matching-adjusted indirect comparison of an open-label extension trial of deucravacitinib with an open-label extension trial of adalimumab to study the long-term efficacy of each treatment. At 1 year of treatment, we observed that similar proportions of patients receiving each treatment achieved a 75% or 90% improvement from their baseline Psoriasis Area and Severity Index score, called PASI 75 or PASI 90, respectively. At 2 years of treatment, similar proportions achieved PASI 90, but the proportion of patients receiving deucravacitinib who achieved PASI 75 was greater than that of patients receiving adalimumab.

12.
Front Plant Sci ; 14: 1116040, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476173

RESUMO

Natural hybridization between Asplenium incisum and A. ruprechtii has been observed in Northeast Asia and its allotetraploid species, A. castaneoviride, was reported. However, the hybridization process between the parental species and the origin of the allotetraploid taxon remains obscure. Additionally, the systematic affinities of the recently described hybrid A. bimixtum, considered to have originated from the hybridization of A. ruprechtii, A. trichomanes, and A. incisum, is unresolved owing to its similarity to A. castaneoviride. The goals of this study were to (1) investigate the hybridization between A. ruprechtii and A. incisum; (2) verify the origin of A. castaneoviride occurring in Korea, whether it independently arose from 2x sterile hybrids; and (3) elucidate the reliability of identifying A. bimixtum. Three genotypes, A. incisum, A. ruprechtii, and their hybrid, were identified based on the nuclear gene pgiC sequence and finally divided them into six types by ploidy levels: diploid A. incisum, A. ruprechtii, and four hybrid types (diploid A. × castaneoviride, triploid A. × castaneoviride, allotetraploid A. castaneoviride, and A. bimixtum). In the analyses of plastid DNA, all hybrids had an A. ruprechtii-type rbcL gene. In addition, the four plastomes of A. ruprechtii and the hybrids had high pairwise sequence identities greater than 98.48%. They increased up to 99.88% when a large deletion of A. x castaneoriviride (2x) collected from Buramsan populations was ignored. Notably, this large deletion was also found in triploid A. × castaneoviride and allotetraploid A. castaneoviride in the same populations. Sequence data of the nuclear and plastid genes showed that hybridization is unidirectional, and A. ruprechtii is the maternal parent. The large deletion of rpoC2-rps2 commonly found in the different ploidy hybrids of the Buramsan population suggests that the allotetraploid A. castaneoviride can be created independently from sterile hybrids. We assume that both polyploidization driving allopolyploidy and minority cytotype exclusion took place independently in the population, since A castaenoviride co-occurs with A. ruprechtii in small populations. Furthermore, it was also observed that an enlarged noncoding region in fern organelle (ENRIFO) of the plastome was found in the genus Asplenium.

13.
PLoS One ; 18(6): e0286481, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37294739

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has had a major influence on working patterns worldwide, given the various lockdown periods and the shift to remote working. As people's noise perception is known to be closely linked with their work performance and job satisfaction, investigating the noise perception in indoor spaces, especially in situations where people work from home, is crucial; however, studies on this aspect are limited. Thus, here, this study aimed to investigate the relationship between indoor noise perception and remote work during the pandemic. The study assessed how people who worked from home perceived indoor noise, and how it related with their work performance and job satisfaction. A social survey was conducted with respondents who worked from home during the pandemic in South Korea. A total of 1,093 valid responses were used for data analysis. Structural equation modeling was used as a multivariate data analysis method to simultaneously estimate multiple and interrelated relationships. The results showed that indoor noise disturbance significantly affected annoyance and work performance. Annoyance with indoor noise affected job satisfaction. Job satisfaction was found to have a significant impact on work performance, particularly on two dimensions of the work performance that are crucial for achieving organizations' goals. Moreover, one dimension of the work performance had a significant impact on annoyance. The study proposed that reducing negative perception of indoor noise and improvement of job satisfaction can lead to the maximization of one's work performance when working from home.


Assuntos
COVID-19 , Pandemias , Humanos , Teletrabalho , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Percepção , Satisfação no Emprego
14.
Nutrients ; 15(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37299400

RESUMO

Hydrangea serrata is a plant grown in Korea and Japan with a particular natural compound, hydrangenol. H. serrata has been researched for its anti-fungal properties, and ability to attenuate allergies and promote muscle growth. Its ability to reduce skin dryness is poorly understood. For that reason, we investigated whether H. serrata hot water extracts (Hs-WE) can moisturize keratinocytes. In clinical studies (Approval Code: GIRB-21929-NY and approval Date: 5 October 2021), skin wrinkles and skin moisturizing levels were improved in subjects applying 0.5% Hs-WE compared to the placebo group. We confirmed the components of Hs-WE from the LC/MS-MS analysis. Hs-WE and hydrangenol did not show cytotoxicity in HaCaT cells at all concentrations. Cell growth was also promoted by Hs-WE (5-20 µg/mL) and hydrangenol (15-60 µM) in a wound healing assay. Skin moisturizing factors were upregulated by the presence of Hs-WE or hydrangenol, and the hyaluronidases (HYAL) were inhibited at the mRNA level. Meanwhile, COL1A1 was increased by the presence of Hs-WE or hydrangenol. MAPK, AP-1, and Akt/PI3k signaling proteins, which are associated with cell proliferation and moisturizing factors, were increased by the administration of Hs-WE and hydrangenol. Has-1, 2, and 3 levels were enhanced via JNK when using the inhibitors of MAPK proteins and Hs-WE and hydrangenol, respectively. Taken together, Hs-WE could be used as cosmeceutical materials for improving skin conditions.


Assuntos
Hydrangea , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição AP-1/metabolismo , Regulação para Cima , Água/metabolismo
15.
Rheumatol Ther ; 10(4): 951-967, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37231194

RESUMO

INTRODUCTION: The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. METHODS: Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration < 1 year, and Disease Activity Score-28 (DAS28) C-reactive protein (CRP) ≥ 3.2 at baseline; non-SPEAR otherwise. Outcomes included: American College of Rheumatology (ACR) 20/50/70 at week 24; mean change from baseline to week 24 for DAS28 (CRP), Simple Disease Activity Index (SDAI), ACR core components; DAS28 (CRP) and SDAI remission. Adjusted regression analyses among abatacept-treated patients compared SPEAR and non-SPEAR patients, and in full trial population estimating how the efficacy of abatacept versus comparators [adalimumab + methotrexate, methotrexate] was modified by SPEAR status. RESULTS: The study included 1400 SPEAR and 673 non-SPEAR patients; most were female (79.35%), white (77.38%), and with a mean age 49.26 (SD 12.86) years old. Around half with non-SPEAR were RF + and three-quarters ACPA +. Stronger improvements from baseline to week 24 were observed in almost all outcomes for abatacept-treated SPEAR versus non-SPEAR patients or versus SPEAR patients treated with comparators. Larger improvements were observed for SPEAR patients among the abatacept-treated population, and more strongly improved efficacy among SPEAR patients for abatacept than comparators. CONCLUSIONS: This analysis, including large patient numbers of early-RA abatacept trials, confirmed beneficial treatment effects of abatacept in patients with SPEAR versus non-SPEAR.

16.
Plants (Basel) ; 12(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36903948

RESUMO

The skin is the largest organ of the human body, and it is also the one most exposed to external environmental contaminants. The skin is the body's first defense against harmful environmental stimuli, including ultraviolet B (UVB) rays and hazardous chemicals. Therefore, proper care of the skin is required to prevent skin-related diseases and age-related symptoms. In this study, we analyzed anti-aging and anti-oxidative effects of Breynia vitis-idaea ethanol extract (Bv-EE) in human keratinocytes and dermal fibroblasts. The Bv-EE had free radical scavenging activity and decreased the mRNA expression of MMPs and COX-2 in H2O2- or UVB-treated HaCaT cells. The Bv-EE also inhibited AP-1 transcriptional activity and phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and mitogen-activated protein kinase 14 (p38), which are major AP-1 activators upon H2O2 or UVB exposure. Furthermore, the promoter activity and mRNA expression of collagen type I (Col1A1) increased in HDF cells treated with Bv-EE, and Bv-EE recovered the collagen mRNA expression decreased by H2O2 or UVB exposure. These results suggest that Bv-EE has anti-oxidative effects by inhibiting the AP-1 signaling pathway, and shows anti-aging effects by upregulating collagen synthesis.

17.
Br J Soc Psychol ; 62(3): 1230-1250, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36722693

RESUMO

Three studies investigated how speakers' pitch affects listeners' attribution of mental capacity (e.g., the ability to feel emotions and physical sensations such as pain and pleasure; Gray et al., Science, 315, 2007, 619) to them and further explored downstream effects on social judgements. In Study 1 (N = 234), participants perceived more experience in higher-(vs. lower-)pitched speakers, whereas there was no significant difference in perception of agency to lower pitched or higher pitched speakers. In later studies, we expanded the relationship between male speakers' pitch and attributed experience in diverse contexts and observed that participants attributed more experience to higher pitched male victims, which was related to higher estimation of harm severity, leading to more negative judgement of the harmdoers (Study 2; N = 121) as well as recommendation for stronger treatment for the speakers (Study 3; N = 116). Our findings indicate that mind perception can vary as a function of targets' voice pitch, and in turn may influence people's judgements involving the speakers, as well as behavioural intentions towards them.


Assuntos
Voz , Humanos , Masculino , Percepção Social , Emoções , Julgamento
18.
Molecules ; 28(4)2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36838938

RESUMO

Muscle atrophy, also known as muscle wasting, is the thinning of muscle mass due to muscle disuse, aging, or diseases such as cancer or neurological problems. Muscle atrophy is closely related to the quality of life and has high morbidity and mortality. However, therapeutic options for muscle atrophy are limited, so studies to develop therapeutic agents for muscle loss are always required. For this study, we investigated how orally administered specific collagen peptides (CP) affect muscle atrophy and elucidated its molecular mechanism using an in vivo model. We treated mice with dexamethasone (DEX) to induce a muscular atrophy phenotype and then administered CP (0.25 and 0.5 g/kg) for four weeks. In a microcomputed tomography analysis, CP (0.5 g/kg) intake significantly increased the volume of calf muscles in mice with DEX-induced muscle atrophy. In addition, the administration of CP (0.25 and 0.5 g/kg) restored the weight of the gluteus maximus and the fiber cross-sectional area (CSA) of the pectoralis major and calf muscles, which were reduced by DEX. CP significantly inhibited the mRNA expression of myostatin and the phosphorylation of Smad2, but it did not affect TGF-ß, BDNF, or FNDC5 gene expression. In addition, AKT/mTOR, a central pathway for muscle protein synthesis and related to myostatin signaling, was enhanced in the groups that were administered CP. Finally, CP decreased serum albumin levels and increased TNF-α gene expression. Collectively, our in vivo results demonstrate that CP can alleviate muscle wasting through a multitude of mechanisms. Therefore, we propose CP as a supplement or treatment to prevent muscle atrophy.


Assuntos
Colágeno , Atrofia Muscular , Miostatina , Animais , Camundongos , Dexametasona/efeitos adversos , Fibronectinas/metabolismo , Músculo Esquelético/metabolismo , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Microtomografia por Raio-X , Colágeno/farmacologia
19.
Genes Genomics ; 45(3): 261-270, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36609747

RESUMO

Mitochondria are organelles that serve as a central hub for physiological processes in eukaryotes, including production of ATP, regulation of calcium dependent signaling, generation of ROS, and regulation of apoptosis. Cancer cells undergo metabolic reprogramming in an effort to support their increasing requirements for cell survival, growth, and proliferation, and mitochondria have primary roles in these processes. Because of their central function in survival of cancer cells and drug resistance, mitochondria are an important target in cancer therapy and many drugs targeting mitochondria that target the TCA cycle, apoptosis, metabolic pathway, and generation of ROS have been developed. Continued use of mitochondrial-targeting drugs can lead to resistance due to development of new somatic mutations. Use of drugs is limited due to these mutations, which have been detected in mitochondrial proteins. In this review, we will focus on genetic mutations in mitochondrial target proteins and their function in induction of drug-resistance.


Assuntos
Mitocôndrias , Neoplasias , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/metabolismo , Resistencia a Medicamentos Antineoplásicos , Apoptose , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo
20.
Ann Pediatr Endocrinol Metab ; 28(2): 107-115, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35798299

RESUMO

PURPOSE: Hypothalamic damage may increase the risk of adulthood obesity and cardiovascular disease in patients with craniopharyngioma. We evaluated the effects of hypothalamic involvement (HI) and growth hormone (GH) discontinuation on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma. METHODS: Thirty-three patients (17 males, 16 females) underwent retesting for adult GH deficiency (GHD) between 2005 and 2020 at Seoul National University Children's Hospital. Postoperative HI was graded by Puget's criteria and data regarding GH replacement were collected. At retesting, body mass index (BMI), fasting blood glucose, insulin, high-density lipoprotein cholesterol (HDL-C), triglycerides, and blood pressure were assessed. RESULTS: The mean age of commencement and discontinuation of GH replacement for childhood GHD was 10.0±3.6 and 15.3±3.1 years, respectively. The mean age at retesting for adult GHD was 17.7±2.5 years. When patients were categorized by post-GH discontinuation duration, those with durations >6 months (n=27) showed lower HDL-C levels than those with <6 months (P=0.037). Patients with extensive HI (n=16) had higher BMI z-scores than did those with no HI or mild HI (P=0.020). Both the extent of HI and longer post-GH discontinuation duration were significantly predictive for decreased HDL-C levels (P<0.05, for both). CONCLUSION: The extent of HI and GH discontinuation duration during the transition period can increase cardiovascular risks in patients with childhood-onset craniopharyngioma.

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