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1.
Hum Genomics ; 18(1): 34, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566255

RESUMO

BACKGROUND: Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. RESULTS: In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics. Through a transcriptome-wide association study and colocalization analysis, we identified 52, 75, and 144 MPB associations for T2, T3, and T4, respectively. To assess the causality of MPB genes, we performed a conditional and joint analysis, which revealed 10, 11, and 54 putative causality genes for T2, T3, and T4, respectively. Finally, we conducted drug repositioning and identified potential drug candidates that are connected to MPB-associated genes. CONCLUSIONS: Overall, through an integrative analysis of gene expression and genotype data, we have identified robust MPB susceptibility genes that may help uncover the underlying molecular mechanisms and the novel drug candidates that may alleviate MPB.


Assuntos
Alopecia , Transcriptoma , Humanos , Masculino , Transcriptoma/genética , Alopecia/genética , Alopecia/metabolismo , Genótipo , Prognóstico , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença
2.
Small ; 20(29): e2311652, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38361217

RESUMO

Modern strides in energy storage underscore the significance of all-solid-state batteries (ASSBs) predicated on solid electrolytes and lithium (Li) metal anodes in response to the demand for safer batteries. Nonetheless, ASSBs are often beleaguered by non-uniform Li deposition during cycling, leading to compromised cell performance from internal short circuits and hindered charge transfer. In this study, the concept of "bottom deposition" is introduced to stabilize metal deposition based on the lithiophilic current collector and a protective layer composed of a polymeric binder and carbon black. The bottom deposition, wherein Li plating ensues between the protective layer and the current collector, circumvents internal short circuits and facilitates uniform volumetric changes of Li. The prepared functional binder for the protective layer presents outstanding mechanical robustness and adhesive properties, which can withstand the volume expansion caused by metal growth. Furthermore, its excellent ion transfer properties promote uniform Li bottom deposition even under a current density of 6 mA·cm-2. Also, scanning electron microscopy analysis reveals a consistent plating/stripping morphology of Li after cycling. Consequently, the proposed system exhibits enhanced electrochemical performance when assessed within the ASSB framework, operating under a configuration marked by a high Li utilization rate reliant on an ultrathin Li.

3.
Korean J Physiol Pharmacol ; 28(4): 303-312, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38926838

RESUMO

Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1ß, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-ß) were reduced by Vinp treatment. Reduction of TGF-ß protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.

4.
J Toxicol Environ Health A ; 86(20): 758-773, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37527000

RESUMO

Potentilla rugulosa Nakai (P. rugulosa) is a perennial herb in the Rosaceae family and found in the Korean mountains. Previously, our findings demonstrated that P. rugulosa contains numerous polyphenols and flavonoids exhibiting important antioxidant and anti-obesity bioactivities. Bisphenol A (BPA) is a xenoestrogen that was shown to produce pulmonary inflammation in humans. However, the mechanisms underlying BPA-induced inflammation remain to be determined. The aim of this study was to examine whether ethanolic extract of P. rugulosa exerted an inhibitory effect on BPA-induced inflammation utilizing an adenocarcinoma human alveolar basal epithelial cell line A549. The P. rugulosa extract inhibited BPA-mediated cytotoxicity by reducing levels of reactive oxygen species (ROS). Further, P. rugulosa extract suppressed the upregulation of various pro-inflammatory mediators induced by activation of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, inhibition of the NF-κB and MAPK signaling pathways by P. rugulosa extract was found to occur via decrease in the transcriptional activity of NF-κB. Further, blockade of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) was noted. Thus, our findings suggest that the ethanolic extract of P. rugulosa may act as a natural anti-inflammatory therapeutic agent.


Assuntos
NF-kappa B , Potentilla , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Potentilla/metabolismo , Células A549 , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , República da Coreia , Lipopolissacarídeos/farmacologia
5.
BMC Public Health ; 23(1): 760, 2023 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-37098559

RESUMO

BACKGROUND: The public experienced loss of resources, including their health and property during the COVID-19 pandemic. The Conservation of Resources (COR) theory is a useful tool to explain the effect of resource loss on mental health. This paper examines the effect of resource loss on depression and peritraumatic distress considering the situational and social context of the COVID-19 pandemic applying COR theory. METHODS: An online survey was conducted for Gyeonggi residents when the second wave of COVID-19 in South Korea declined (5 October to 13 October 2020); 2,548 subjects were included in the hierarchical linear regression analysis. RESULTS: COVID-19 infection-related experiences, resource losses (e.g., financial burden, deterioration of health, and decline of self-esteem), and fear of stigma were related to elevated levels of peritraumatic distress and depression. Risk perception was associated with peritraumatic distress. Reduced income or job loss were related to depression. Social support was a protective factor for mental health. CONCLUSIONS: This study suggests that we need to focus on COVID-19 infection-related experiences and loss of daily resources in order to understand mental health deterioration during the COVID-19 pandemic. Moreover, it is important to monitor the mental health of medically and socially vulnerable groups and those who have lost resources due to the pandemic and to provide them with social support services.


Assuntos
COVID-19 , Pandemias , Humanos , Depressão/epidemiologia , COVID-19/epidemiologia , Meio Social , Apoio Social
6.
Int J Mol Sci ; 24(14)2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37511476

RESUMO

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.


Assuntos
Psoríase , Transcriptoma , Humanos , Estudo de Associação Genômica Ampla , Perfilação da Expressão Gênica , Especificidade de Órgãos , Psoríase/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único
7.
Reprod Biomed Online ; 39(2): 187-195, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31182356

RESUMO

RESEARCH QUESTION: Are single nucleotide polymorphisms of microRNAs (miRNAs) and risk of idiopathic recurrent pregnancy loss (RPL) associated? DESIGN: A total 375 patients with idiopathic RPL (age, mean ± standard deviation [SD] 33.02 ± 4.24 years; body mass index [BMI], mean ± SD, 21.57 ± 3.70 kg/m2) and 276 control participants (age, mean ± SD, 33.01 ± 5.27 years; BMI, mean ± SD, 21.58 ± 3.20) were recruited. Pregnancy loss was diagnosed using human chorionic gonadotrophin concentrations, ultrasonography and/or physical examination prior to 20 weeks of gestation. The genotype of the participants was determined by polymerase chain reaction restriction fragment length polymorphism analysis. Statistical analysis was performed to investigate the differences in frequencies between the control and RPL genotypes RESULTS: The miR-150G>A heterozygous genotype was significantly associated with increased risk of RPL (adjusted odds ratio 2.502, 95% confidence interval 1.555-4.025; P = 0.0002). The miR-1179A>T heterozygous genotype was significantly associated with decreased risk of RPL (adjusted odds ratio 0.633, 95% confidence interval 0.454-0.884; P = 0.007). Some allele combinations that included miR-150A or miRNA-1179T resulted in an increase or decrease in risk of RPL, respectively. CONCLUSIONS: The miR-150G>A and miR-1179A>T polymorphisms were more frequently associated with RPL compared with controls.


Assuntos
Aborto Habitual/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Gravidez , Resultado da Gravidez , Risco
8.
J Assist Reprod Genet ; 35(9): 1623-1630, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30006788

RESUMO

PURPOSE: The aim of this study is to analyze women's opinions and their decision making processes regarding elective oocyte cryopreservation (OC). METHODS: One hundred twenty-four women who had elective OC counseling at the CHA Seoul Fertility Center were asked to complete a survey after their first visit. Data collection regarding age, marital status, monthly income, occupation, religion, reproductive history, questions about the participant's view on their own fecundity, and future parenthood were included. The modified Reproductive Concerns After Cancer scale and the Decisional Conflict Scale were used for analysis. RESULTS: The participants' mean age was 37.1 ± 4.8 years old. Eighty-six percent of the participants had regular periods. Ninety-two percent thought it was important to have their own biological offspring, and 86% were willing to pursue OC. Forty-nine percent appeared to have high DCS scores regarding making a decision of OC. Sixty-eight percent pursued OC, and the mean number of oocytes cryopreserved per patient was 10.5 ± 8.3. Multivariate analysis revealed that age was the only factor associated with high DCS scores (P = 0.002). Feeling less fertile than other women of same age and low DCS scores were the factors associated with pursuing OC (P = 0.02 and 0.004, respectively) after adjusting for possible confounding factors, including age. CONCLUSIONS: Older women had more difficulties in making decisions about OC. Adjusting for age, women who thought that they were less fertile than other women of same age and those with lower decisional conflict were more likely to pursue OC. Further studies should focus on the validation of older women's decisional conflicts regarding OC.


Assuntos
Criopreservação/métodos , Tomada de Decisões , Preservação da Fertilidade/métodos , Oócitos/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Aconselhamento , Feminino , Fertilidade/fisiologia , Humanos , Inquéritos e Questionários
9.
Reprod Biomed Online ; 32(2): 190-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26673101

RESUMO

Vascular endothelial growth factor (VEGF) is involved in embryonic development, decidual vascularization and placenta angiogenesis. This study was performed to determine whether there is an association between genetic polymorphisms in the VEGF gene and the development of recurrent implantation failure (RIF) in Korean women. A total of 119 women diagnosed with RIF and 236 control subjects were genotyped for VEGF polymorphic sites including rs833061 (-460T>C), rs25648 (-7C>T) and rs3025020 (-583C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays and real-time PCR. The VEGF rs833061 C allele and rs25648 T allele were significantly associated with increased RIF risk (odds ratio [OR] = 1.813 [1.161-2.831], P = 0.009, OR = 2.213 [1.254-3.903], P = 0.005). The rs833061/rs25648 TC/CT, TC/CT+TT, and rs833061/rs3025020 TC+CC/TT genotypes were more frequent in the RIF group compared with the control group (OR = 2.130 [1.092-4.156], P = 0.025, OR = 2.130 [1.092-4.156], OR = 4.261 [1.163-15.620], P = 0.028, respectively). The results of this study suggests that VEGF polymorphisms are associated with RIF development. Therefore, we postulate that VEGF polymorphisms might be useful markers to predict RIF development. Further studies are warranted to elucidate the role of VEGF variants and RIF development.


Assuntos
Implantação do Embrião , Variação Genética , Infertilidade Feminina/terapia , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Cariotipagem , Razão de Chances , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , República da Coreia , Risco , Falha de Tratamento , Resultado do Tratamento
10.
J Glob Health ; 14: 05025, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39238359

RESUMO

Background: There is limited evidence on the effectiveness of the existing rehabilitation interventions for old adults with long coronavirus disease (COVID), which is of particular concern among old adults. Methods: We systematically searched studies published in PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases from their inception to 15 November 2023. Randomised controlled trials (RCTs) compared rehabilitation interventions with other controls in old adults (mean/median age of 60 or older) with long COVID were included. We performed a meta-analysis to compare the effects of the rehabilitation interventions with the common control group. Mean difference (MD) or standardised mean difference (SMD) with its 95% confidence intervals (CI) were used as summary statistics. Moreover, subgroup analyses based on the intervention programmes, the severity of acute infection, and the age of participants were carried out. Results: A total of 11 RCTs involving 832 participants (64.37 ± 7.94 years, 52.2% were men) were included in the analysis. Compared with the control groups, rehabilitation interventions significantly improved 6-minute walking test (6 MWT; MD = 15.77 metres (m), 95% CI = 5.40, 26.13, P < 0.01), 30-second sit-to-stand test (MD = 4.11 number of stands (n), 95% CI = 2.46, 5.76, P < 0.001), all aspects of quality of life, independence in activities of daily living (SMD = 0.31, 95% CI = 0.14, 0.48, P < 0.001), and relieved fatigue (SMD = -0.66, 95% CI = -1.13, -0.19, P < 0.01), depression (SMD = -0.89, 95% CI = -1.76, -0.02, P < 0.05) and anxiety (SMD = -0.81, 95% CI = -1.58, -0.05, P < 0.05). However, the improvement of hand grip strength and pulmonary function was not statistically significant (P > 0.05). Subgroup analyses showed that improvements in 6 MWT, fatigue, anxiety, and depression were more pronounced in old patients who received exercise training, while those who received respiratory rehabilitation had more pronounced improvements in pulmonary function and quality of life. Conclusions: Old adults with long COVID who underwent rehabilitation interventions experienced significant improvement in functional capacity, fatigue, quality of life, independence in activities of daily living, and mental health outcomes compared with usual/standard care. These findings suggest that screening, management, and rehabilitation interventions for long COVID in older adults should be strengthened to improve their complete health status and functional status, thereby reducing the long-term disease burden caused by long COVID and fostering healthy aging during the post-pandemic era.


Assuntos
Síndrome de COVID-19 Pós-Aguda , Idoso , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda/diagnóstico , Síndrome de COVID-19 Pós-Aguda/psicologia , Síndrome de COVID-19 Pós-Aguda/reabilitação
11.
Cells ; 13(8)2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38667290

RESUMO

Excessive secretion of pro-inflammatory cytokines leads to the disruption of intestinal barrier in inflammatory bowel disease (IBD). The inflammatory cytokine tumor necrosis factor alpha (TNFα) induces the assembly of the NLRP3 inflammasome, resulting in the augmented secretion of inflammatory cytokines implicated in the pathogenesis of inflammatory bowel disease (IBD). TNFα has also been known to induce the formation of immunoproteasome (IP), which incorporates immunosubunits LMP2, LMP7, and MECL-1. Inhibition of IP activity using the IP subunit LMP2-specific inhibitor YU102, a peptide epoxyketone, decreased the protein levels of NLRP3 and increased the K48-linked polyubiquitination levels of NLRP3 in TNFα-stimulated intestinal epithelial cells. We observed that inhibition of IP activity caused an increase in the protein level of the ubiquitin E3 ligase, tripartite motif-containing protein 31 (TRIM31). TRIM31 facilitated K48-linked polyubiquitination and proteasomal degradation of NLRP3 with an enhanced interaction between NLRP3 and TRIM31 in intestinal epithelial cells. In addition, IP inhibition using YU102 ameliorated the symptoms of colitis in the model mice inflicted with dextran sodium sulfate (DSS). Administration of YU102 in the DSS-treated colitis model mice caused suppression of the NLRP3 protein levels and accompanied inflammatory cytokine release in the intestinal epithelium. Taken together, we demonstrated that inhibiting IP under inflammatory conditions induces E3 ligase TRIM31-mediated NLRP3 degradation, leading to attenuation of the NLRP3 inflammatory response that triggers disruption of intestinal barrier.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Complexo de Endopeptidases do Proteassoma , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Ubiquitina-Proteína Ligases/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Inflamassomos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Camundongos , Humanos , Ubiquitinação/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/patologia , Colite/metabolismo , Colite/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças
12.
Int J Biol Macromol ; 270(Pt 2): 132409, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768918

RESUMO

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.


Assuntos
Materiais Biocompatíveis , Quitosana , Regeneração , Adesivos Teciduais , Adesivos Teciduais/química , Adesivos Teciduais/farmacologia , Animais , Regeneração/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Quitosana/química , Quitosana/farmacologia , Teste de Materiais , Menisco/efeitos dos fármacos , Dextranos/química , Sobrevivência Celular/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Coelhos , Lesões do Menisco Tibial/cirurgia , Humanos , Injeções
13.
Commun Biol ; 7(1): 462, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627534

RESUMO

Plant viruses evolves diverse strategies to overcome the limitations of their genomic capacity and express multiple proteins, despite the constraints imposed by the host translation system. Broad bean wilt virus 2 (BBWV2) is a widespread viral pathogen, causing severe damage to economically important crops. It is hypothesized that BBWV2 RNA2 possesses two alternative in-frame translation initiation codons, resulting in the production of two largely overlapping proteins, VP53 and VP37. In this study, we aim to investigate the expression and function of VP53, an N-terminally 128-amino-acid-extended form of the viral movement protein VP37, during BBWV2 infection. By engineering various recombinant and mutant constructs of BBWV2 RNA2, here we demonstrate that VP53 is indeed expressed during BBWV2 infection. We also provide evidence of the translation of the two overlapping proteins through ribosomal leaky scanning. Furthermore, our study highlights the indispensability of VP53 for successful systemic infection of BBWV2, as its removal results in the loss of virus infectivity. These insights into the translation mechanism and functional role of VP53 during BBWV2 infection significantly contribute to our understanding of the infection mechanisms employed by fabaviruses.


Assuntos
Fabavirus , Vírus de Plantas , Fabavirus/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vírus de Plantas/genética
14.
Sci Rep ; 14(1): 10105, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698020

RESUMO

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.


Assuntos
Adenoma , Neoplasias Colorretais , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Adenoma/genética , Adenoma/imunologia , Adenoma/patologia , República da Coreia , Biologia Computacional/métodos , Masculino , Feminino , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/genética , Estimativa de Kaplan-Meier , Perfilação da Expressão Gênica
15.
NPJ Precis Oncol ; 8(1): 131, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877301

RESUMO

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.

16.
Research (Wash D C) ; 7: 0365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654733

RESUMO

Neutrophils are primed for neutrophil extracellular trap (NET) formation during diabetes, and excessive NET formation from primed neutrophils compromises wound healing in patients with diabetes. Here, we demonstrate that trained immunity mediates diabetes-induced NET priming in neutrophils. Under diabetic conditions, neutrophils exhibit robust metabolic reprogramming comprising enhanced glycolysis via the pentose phosphate pathway and fatty acid oxidation, which result in the accumulation of acetyl-coenzyme A. Adenosine 5'-triphosphate-citrate lyase-mediated accumulation of acetyl-coenzyme A and histone acetyltransferases further induce the acetylation of lysine residues on histone 3 (AcH3K9, AcH3K14, and AcH3K27) and histone 4 (AcH4K8). The pharmacological inhibition of adenosine 5'-triphosphate-citrate lyase and histone acetyltransferases completely inhibited high-glucose-induced NET priming. The trained immunity of neutrophils was further confirmed in neutrophils isolated from patients with diabetes. Our findings suggest that trained immunity mediates functional changes in neutrophils in diabetic environments, and targeting neutrophil-trained immunity may be a potential therapeutic target for controlling inflammatory complications of diabetes.

17.
Nutrition ; 128: 112565, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39326237

RESUMO

OBJECTIVES: This study investigated the therapeutic potential of Lactobacillus plantarum NCHBL-004 (NCHBL-004) in the treatment of obesity and associated metabolic disorders. METHODS: Mice were fed either a normal diet (ND) or a high-fat diet (HFD) with oral administration of NCHBL-004. After euthanasia, blood, liver and adipose tissue were collected. Furthermore, the microbiome and short-chain fatty acids (SCFAs) were analyzed from feces. RESULTS: Oral administration of live NCHBL-004 to mice fed a HFD resulted in notable reductions in weight gain, improvements in glucose metabolism, and maintenance of balanced lipid levels. A comparative analysis with other Lactobacillus strains highlighted the superior efficacy of NCHBL-004. Moreover, heat-killed NCHBL-004 demonstrated beneficial effects similar to those of live NCHBL-004. Additionally, administration of live NCHBL-004 induced glucagon-like peptide 1 (GLP-1) production and increased the levels of short-chain fatty acids (SCFAs), including acetate and propionate, in feces, positively influencing liver lipid metabolism and mitigating inflammation. Consistent with this, analysis of the gut microbiome following NCHBL-004 administration showed increases in SCFA-producing microbes with increased proportions of Lactobacillus spp. and a significant increase in the proportion of microbes capable of promoting GLP-1 secretion. CONCLUSIONS: These findings underscore the potential of both live and inactivated NCHBL-004 as potential therapeutic approaches to managing obesity and metabolic disorders, suggesting avenues for further investigation and clinical applications.

18.
Knee Surg Relat Res ; 35(1): 25, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012738

RESUMO

BACKGROUND: Our study aimed to identify age-related changes in knee proprioception to provide reference values for weight-bearing (WB) and non-weight-bearing (NWB) conditions and to identify factors (age, WB condition, dominance, and sex) that can affect knee proprioception. METHODS: A total of 84 healthy adult men and women were recruited. Active knee joint position sense (JPS) was measured using a digital inclinometer for knee proprioception. The participants performed the required movements actively, with verbal feedback from the examiner, slowly moving to the target angles (30° and 50°) and maintaining them for 5 s before returning to the starting position. Afterward, without assistance from the examiner, the participants actively moved back to the same angle, and the examiner confirmed the angles. This procedure was repeated twice for each target angle, and the average values were used as the data. The participants were barefoot, wearing shorts, and closed their eyes while the measurements were obtained. The measurements were first obtained on the dominant side under the NWB conditions. When a change in posture was needed during the measurement, the participants sat in a resting position for 2 min. RESULTS: Except for age, all other factors (WB condition, dominance, sex) were not statistically significant. Age showed a significant difference in knee JPS, except for the non-dominant side at 30° and the dominant side at 50° in the NWB condition. CONCLUSION: This study indicates that the WB condition, dominant side, and sex need not be considered when measuring and assessing knee JPS. Age shows a negative correlation with knee joint position sense, and the reference values presented in this study can be used as objective target values during the rehabilitation process.

19.
Healthcare (Basel) ; 11(12)2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37372895

RESUMO

(1) Introduction: This study aimed to investigate the effects of curved-path stride gait training on the gait ability of patients with stroke. (2) Materials and Methods: Thirty patients with stroke were randomly assigned to curved-path stride gait training (n = 15) and general gait training groups (n = 15). Both groups underwent training for 30 min five times a week for 8 weeks. The gait ability of each was assessed using the Dynamic Gait Index (DGI), Timed-Up-and-Go (TUG) test, 10-meter walk test, and Figure-of-8 walk test (F8WT). (3) Results: The curved-path gait training group showed significant differences in the DGI, TUG test, 10-m walk test, and F8WT pre- versus post- intervention (p < 0.05). The general gait training group showed no significant difference in F8WT pre- versus post-intervention (p > 0.05). Additionally, there was a statistically significant intergroup difference in gait ability (p < 0.05). (4) Conclusions: Curved-path gait training resulted in greater improvement in gait ability than general gait training. Therefore, curved-path gait training can be a meaningful intervention for improving the gait ability of patients with stroke.

20.
Comput Biol Med ; 167: 107685, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37976829

RESUMO

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by airflow limitation and chronic inflammation of the lungs that is a leading cause of death worldwide. Since the complete pathological mechanisms at the single-cell level are not fully understood yet, an integrative approach to characterizing the single-cell-resolution landscape of COPD is required. To identify the cell types and mechanisms associated with the development of COPD, we conducted a meta-analysis using three single-cell RNA-sequencing datasets of COPD. Among the 154,011 cells from 16 COPD patients and 18 healthy subjects, 17 distinct cell types were observed. Of the 17 cell types, monocytes, mast cells, and alveolar type 2 cells (AT2 cells) were found to be etiologically implicated in COPD based on genetic and transcriptomic features. The most transcriptomically diversified states of the three etiological cell types showed significant enrichment in immune/inflammatory responses (monocytes and mast cells) and/or mitochondrial dysfunction (monocytes and AT2 cells). We then identified three chemical candidates that may potentially induce COPD by modulating gene expression patterns in the three etiological cell types. Overall, our study suggests the single-cell level mechanisms underlying the pathogenesis of COPD and may provide information on toxic compounds that could be potential risk factors for COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Transcriptoma , Humanos , Transcriptoma/genética , Doença Pulmonar Obstrutiva Crônica/genética , Pulmão , Fatores de Risco , RNA
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