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1.
Viruses ; 16(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38400040

RESUMO

We aimed to assess the temporal trends of incident syphilis and its associated risk factors among men with HIV (Human Immunodeficiency Virus) in Korea during the COVID-19 pandemic. We conducted a retrospective cohort study of men with HIV attending an HIV clinic in Korea between 2005 and 2022. Of 767 men with HIV, 499 were included and contributed 3220 person-years (PY) of the observation period. Eighty-two patients were diagnosed with incident syphilis, with an overall incidence of 2.55/100 PY (95% confidence interval [CI] 20.56-31.53). The incidence of syphilis per 100 PY gradually decreased from 2.43 (0.79-7.42) in 2005-2007 to 1.85 (1.08-3.17) in 2014-2016; however, it increased to 3.0 (1.99-4.53) in 2017-2019, and further to 3.33 (2.26-4.89) in 2020-2022. A multivariate analysis identified young age (≤30 years versus >50, adjusted HR 6.27, 95% CI 2.38-16.56, p < 0.001), treponemal test positive at baseline (2.33, 1.48-3.67, p < 0.001), men who have sex with men (2.36, 1.34-4.16, p = 0.003), and history of incarceration (2.62, 1.21-5.67, p = 0.015) as risk factors for incident syphilis. Recently, syphilis incidence in men with HIV has increased in Korea, especially in young patients and at-risk groups, highlighting the need for enhanced regular screening and targeted behavioral interventions among these populations.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Sífilis , Masculino , Humanos , Adulto , Sífilis/complicações , Sífilis/epidemiologia , Sífilis/diagnóstico , Homossexualidade Masculina , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , HIV , Estudos Retrospectivos , Incidência , Pandemias , Fatores de Risco , República da Coreia/epidemiologia
3.
Cell ; 186(16): 3476-3498.e35, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37541199

RESUMO

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Proteogenômica , Feminino , Humanos , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética
4.
Food Funct ; 14(15): 6957-6968, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37435675

RESUMO

Ulcerative colitis (UC) is a chronic disease of the colon characterized by mucosal damage and relapsing gastrointestinal inflammation. Hydrangea serrata (Thunb.) Ser. and its bioactive compound, hydrangenol, are reported to have anti-inflammatory effects, but few studies have investigated the effects of hydrangenol in colitis. In the present study, we evaluated for the first time the anti-colitic effects and molecular mechanisms of hydrangenol in a dextran sodium sulfate (DSS)-induced mouse colitis model. To investigate the anti-colitic effects of hydrangenol, DSS-induced colitis mice, HT-29 colonic epithelial cells treated with supernatant from LPS-inflamed THP-1 macrophages, and LPS-induced RAW264.7 macrophages were used. In addition, to clarify the molecular mechanisms of this study, quantitative real time-PCR, western blot analysis, TUNEL assay, and annexin V-FITC/PI double staining analysis were conducted. Oral administration of hydrangenol (15 or 30 mg kg-1) significantly alleviated DSS-induced colitis by preventing DAI scores, shortening colon length, and colonic structural damage. F4/80+ macrophage numbers in mesenteric lymph nodes and macrophage infiltration in colonic tissues were significantly suppressed following hydrangenol treatment in DSS-exposed mice. Hydrangenol significantly attenuated DSS-induced destruction of the colonic epithelial cell layer through regulation of pro-caspase-3, occludin, and claudin-1 protein expression. Moreover, hydrangenol ameliorated abnormal tight junction protein expression and apoptosis in HT-29 colonic epithelial cells treated with supernatant from LPS-inflamed THP-1 macrophages. Hydrangenol suppressed the expression of pro-inflammatory mediators, such as iNOS, COX-2, TNF-α, IL-6, and IL-1ß through NF-κB, AP-1, and STAT1/3 inactivation in DSS-induced colon tissue and LPS-induced RAW264.7 macrophages. Taken together, our findings suggest that hydrangenol recovers the tight junction proteins and down-regulates the expression of the pro-inflammatory mediators by interfering with the macrophage infiltration in DSS-induced colitis. Our study provides compelling evidence that hydrangenol may be a candidate for inflammatory bowel disease therapy.


Assuntos
Colite Ulcerativa , Colite , Hydrangea , Animais , Camundongos , Sulfato de Dextrana/efeitos adversos , Lipopolissacarídeos/farmacologia , Transdução de Sinais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Colite Ulcerativa/induzido quimicamente , Colo/metabolismo , Macrófagos , NF-kappa B/genética , NF-kappa B/metabolismo , Mediadores da Inflamação/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
5.
Br J Cancer ; 128(8): 1491-1502, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36759727

RESUMO

BACKGROUND: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of CMA in tumour progression under hypoxia. METHODS: The effect of ManA on CMA activation was assessed in mouse xenograft models and cells. The gene expressions of HIF-1α, HSP90AA1, and transcription factor EB (TFEB) were analysed using The Cancer Genome Atlas (TCGA) datasets to assess the clinical relevance of CMA. RESULTS: ManA activates photoswitchable CMA reporter activity and inhibits Hsp90 chaperone function by disrupting the Hsp90/F1F0-ATP synthase complex. Hsp90 inhibition enhances the interaction between CMA substrates and LAMP-2A and TFEB nuclear localisation, suggesting CMA activation by ManA. ManA-activated CMA retards tumour growth and displays cooperative anti-tumour activity with anti-PD-1 antibody. TCGA datasets show that a combined expression of HSP90AA1High/HIF1AHigh or TFEBLow/HIF1AHigh is strongly correlated with poor prognosis in patients with lung cancer. CONCLUSIONS: ManA-induced CMA activation by modulating Hsp90 under hypoxia induces HIF-1α degradation and reduces tumour growth. Thus, inducing CMA activity by targeting Hsp90 may be a promising therapeutic strategy against hypoxic tumours.


Assuntos
Autofagia Mediada por Chaperonas , Neoplasias Pulmonares , Camundongos , Animais , Humanos , Hipóxia , Proteínas de Choque Térmico HSP90/metabolismo , Chaperonas Moleculares , Autofagia/genética
6.
PLoS Pathog ; 19(1): e1011078, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36696451

RESUMO

Distinct viral gene expression characterizes Epstein-Barr virus (EBV) infection in EBV-producing marmoset B-cell (B95-8) and EBV-associated gastric carcinoma (SNU719) cell lines. CCCTC-binding factor (CTCF) is a structural chromatin factor that coordinates chromatin interactions in the EBV genome. Chromatin immunoprecipitation followed by sequencing against CTCF revealed 16 CTCF binding sites in the B95-8 and SNU719 EBV genomes. The biological function of one CTCF binding site (S13 locus) located on the BamHI A right transcript (BART) miRNA promoter was elucidated experimentally. Microscale thermophoresis assay showed that CTCF binds more readily to the stable form than the mutant form of the S13 locus. EBV BART miRNA clusters encode 22 miRNAs, whose roles are implicated in EBV-related cancer pathogenesis. The B95-8 EBV genome lacks a 11.8-kb EcoRI C fragment, whereas the SNU719 EBV genome is full-length. ChIP-PCR assay revealed that CTCF, RNA polymerase II, H3K4me3 histone, and H3K9me3 histone were more enriched at S13 and S16 (167-kb) loci in B95-8 than in the SNU719 EBV genome. 4C-Seq and 3C-PCR assays using B95-8 and SNU719 cells showed that the S13 locus was associated with overall EBV genomic loci including 3-kb and 167-kb region in both EBV genomes. We generated mutations in the S13 locus in bacmids with or without the 11.8-kb BART transcript unit (BART(+/-)). The S13 mutation upregulated BART miRNA expression, weakened EBV latency, and reduced EBV infectivity in the presence of EcoRI C fragment. Another 3C-PCR assay using four types of BART(+/-)·S13(wild-type(Wt)/mutant(Mt)) HEK293-EBV cells revealed that the S13 mutation decreased DNA associations between the 167-kb region and 3-kb in the EBV genome. Based on these results, CTCF bound to the S13 locus along with the 11.8-kb EcoRI C fragment is suggested to form an EBV 3-dimensional DNA loop for coordinated EBV BART miRNA expression and infectivity.


Assuntos
Infecções por Vírus Epstein-Barr , Infecção Latente , MicroRNAs , Humanos , Infecções por Vírus Epstein-Barr/genética , Fator de Ligação a CCCTC/genética , Herpesvirus Humano 4/genética , Histonas/genética , Células HEK293 , MicroRNAs/genética , Cromatina , Sítios de Ligação
7.
J Infect Chemother ; 29(6): 571-575, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36716862

RESUMO

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Neoplasias , Masculino , Humanos , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/tratamento farmacológico , Incidência , Estudos Retrospectivos , Neoplasias/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco
8.
Gut Liver ; 17(3): 430-440, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35975641

RESUMO

Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn's disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 µg/mL at week 6 and 4.0 µg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.


Assuntos
Medicamentos Biossimilares , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Infliximab/uso terapêutico , Doença de Crohn/tratamento farmacológico , Medicamentos Biossimilares/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Resultado do Tratamento , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico
9.
Biomater Res ; 26(1): 41, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064494

RESUMO

BACKGROUND: Although several studies on the Mg-Zn-Ca system have focused on alloy compositions that are restricted to solid solutions, the influence of the solid solution component of Ca on Mg-Zn alloys is unknown. Therefore, to broaden its utility in orthopedic applications, studies on the influence of the addition of Ca on the microstructural, mechanical, and corrosion properties of Mg-Zn alloys should be conducted. In this study, an in-depth investigation of the effect of Ca on the mechanical and bio-corrosion characteristics of the Mg-Zn alloy was performed for the optimization of a clinically approved Mg alloy system comprising Ca and Zn. METHODS: The Mg alloy was fabricated by gravitational melting of high purity Mg, Ca, and Zn metal grains under an Ar gas environment. The surface and cross-section were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to analyze their crystallographic structures. Electrochemical and immersion tests in Hank's balanced salt solution were used to analyze their corrosion resistance. Tensile testing was performed with universal testing equipment to investigate the impact of Ca addition. The examination of cytotoxicity for biometric determination was in line with the ISO10993 standard. RESULTS: In this study, the 0.1% Ca alloy had significantly retarded grain growth due to the formation of the tiny and well-dispersed Ca2Mg6Zn3 phase. In addition, the yield strength and elongation of the 0.1% Ca alloy were more than 50% greater than the 2% Zn alloy. The limited cell viability of the 0.3% Ca alloy could be attributed to its high corrosion rate, whereas the 0.1% Ca alloy demonstrated cell viability of greater than 80% during the entire experimental period. CONCLUSION: The effect of the addition of Ca on the microstructure, mechanical, and corrosion characteristics of Mg-Zn alloys was analyzed in this work. The findings imply that the Mg-Zn alloy system could be optimized by adding a small amount of Ca, improving mechanical properties while maintaining corrosion rate, thus opening the door to a wide range of applications in orthopedic surgery.

10.
Nutrients ; 14(18)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36145056

RESUMO

Excessive lipid accumulation in white adipose tissue (WAT) is the major cause of obesity. Herein, we investigated the anti-obesity effect and molecular mechanism of a botanical mixture of 30% EtOH extract from the leaves of Inula japonica and Potentilla chinensis (EEIP) in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed obese mice. In vitro, EEIP prevented lipid accumulation by downregulating the expression of lipogenesis-related transcription factors such as CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1 via AMP-activated protein kinase (AMPK) activation and G0/G1 cell cycle arrest by regulating the Akt-mTOR pathways without inducing cytotoxicity. In vivo, EEIP significantly reduced body weight gain and body fat mass in the group administered concurrently with HFD (pre-) or administered during the maintenance of HFD (post-) including subcutaneous, gonadal, renal, and mesenteric fats, and improved blood lipid profiles and metabolic hormones. EEIP pre-administration also alleviated WAT hypertrophy and liver lipid accumulation by reducing C/EBPα, PPARγ, and SREBP-1 expression via AMPK activation. In the brown adipose tissue, EEIP pre-administration upregulated the expression of thermogenic factors. Furthermore, EEIP improved the HFD-induced altered gut microbiota in mice. Taken together, our data indicated that EEIP improves HFD-induced obesity through adipogenesis inhibition in the WAT and liver and is a promising dietary natural material for improving obesity.


Assuntos
Inula , Potentilla , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos , Adipogenia , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Dieta Hiperlipídica , Hormônios/metabolismo , Inula/metabolismo , Camundongos , Camundongos Obesos , Obesidade/metabolismo , PPAR gama/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Metabolomics ; 18(7): 48, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35781849

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.


Assuntos
Artrite Reumatoide , Osteoartrite , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Metabolômica/métodos , Osteoartrite/metabolismo , Líquido Sinovial/metabolismo
12.
Sci Rep ; 12(1): 9974, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35705675

RESUMO

Cancers are the leading cause of death among people living with HIV/AIDS (PLWHA); however, nationwide studies on cancer incidence are limited. We aimed to determine the trends in the incidence rates of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) among Korean PLWHA. Data from the National Health Insurance Sharing Service from 2004 to 2017 were collected. Age- and sex-adjusted standardized incidence ratios (SIRs) for various cancer types relative to the general population were calculated. Of the 11,737 PLWHA followed-up for 65,052 person-years (PYs), 445 (ADCs, 130 and NADCs, 298) developed cancer. The incidence rate of ADCs decreased, whereas that of NADCs remained unchanged. PLWHA were at an increased risk of ADCs (SIR: 12.6, 95% CI: 10.6-15.0), including Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, and some NADCs, including anal cancer, lung cancer, liver cancer, and oropharyngeal cancer. Of the 396 patients who received antiretroviral therapy (ART), 215 with optimal adherence had lower incidence rates for ADCs and NADCs than those with non-optimal adherence. The 5-year survival rate of PLWHA with NADCs was 57.8%. Close surveillance and routine screening of cancers and improvement in ART adherence are required to improve the clinical outcomes of PLWHA.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Neoplasias Hepáticas , Neoplasias , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Incidência , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fatores de Risco
13.
J Infect Chemother ; 28(8): 1143-1147, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35450785

RESUMO

INTRODUCTION: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated. METHODS: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies. RESULTS: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/µL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/µL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99). CONCLUSIONS: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years.


Assuntos
Infecções por HIV , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Anticorpos Antibacterianos , Feminino , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Neoplasias Gástricas/complicações , Neoplasias Gástricas/epidemiologia , Centros de Atenção Terciária
14.
J Antimicrob Chemother ; 77(5): 1353-1364, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35224630

RESUMO

OBJECTIVES: To explore extracorporeal membrane oxygenation (ECMO)-related alterations of the pharmacokinetics (PK) of piperacillin/tazobactam and determine an optimal dosage regimen for critically ill adult patients. METHODS: Population PK models for piperacillin/tazobactam were developed using a non-linear mixed effect modelling approach. The percentage of time within 24 h for which the free concentration exceeded the MIC at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. RESULTS: A total of 226 plasma samples from 38 patients were used to develop a population PK model. Piperacillin/tazobactam PK was best described by two-compartment models, in which estimated glomerular filtration rate (eGFR), calculated using CKD-EPI equation based on cystatin C level, was a significant covariate for total clearance of each piperacillin and tazobactam. ECMO use decreased the central volume of distribution of both piperacillin and tazobactam in critically ill patients. Patients with Escherichia coli or Klebsiella pneumoniae infection, but not those with Pseudomonas aeruginosa infection, exhibited a PK/pharmacodynamic target attainment >90% when the target is 50%fT>MIC, as a result of applying the currently recommended dosage regimen. Prolonged or continuous infusion of 16 g/day was required when the treatment goal was 100%fT>MIC or 100%fT>4×MIC, and patients had an eGFR of 130-170 mL/min/1.73 m2. CONCLUSIONS: ECMO use decreases piperacillin/tazobactam exposure. Prolonged or continuous infusion can achieve the treatment target in critically ill patients, particularly when MIC is above 8 mg/L or when patients have an eGFR of 130-170 mL/min/1.73 m2.


Assuntos
Estado Terminal , Oxigenação por Membrana Extracorpórea , Adulto , Antibacterianos/farmacologia , Estado Terminal/terapia , Humanos , Testes de Sensibilidade Microbiana , Ácido Penicilânico/farmacocinética , Piperacilina/farmacocinética , Combinação Piperacilina e Tazobactam/farmacocinética , República da Coreia , Tazobactam/farmacocinética
15.
Cancers (Basel) ; 13(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34503060

RESUMO

Epstein-Barr-virus-associated gastric carcinoma (EBVaGC), first reported in 1992, currently accounts for 10% of all gastric carcinoma worldwide. EBVaGC has unique DNA hypermethylation phenotypes that allow for higher proportions of DNA methylation than any other gastric cancer. CpG islands in the gene promoter region are one of the major regions in which DNA methylation controls gene transcription. Despite cisplatin-based chemotherapy being one of the standard treatment regimens for advanced gastric cancer, including EBVaGC, cisplatin alone or in combination with 5-fluorouracil has been limited by its less potent anticancer activity and the occurrence of cisplatin resistance. Accordingly, the current study evaluated the anticancer activities of a combination of cisplatin and 5-Azacytidine (5-AZA) against EBVaGC. Our findings showed that cisplatin upregulated the DNMT3A gene, whereas shRNA-targeted removal of DNMT3A mRNA contributed to cisplatin-mediated EBV lytic reactivation. Moreover, the removal of DNMT3A mRNA upregulated the ATM gene through DNA demethylation on the ATM promoter. Furthermore, CRISPR/Cas9-targeted removal of the ATM gene resulted in significantly reduced cell susceptibility and EBV lytic reactivation by a combination of cisplatin and DNMT3A inhibitor 5-AZA. Finally, 5-AZA exhibited a synergistic effect with cisplatin in anti-EBV and anti-EBVaGC activities by increasing drug susceptibility and EBV lytic reactivation. The aforementioned results suggest that cisplatin combined with DNA methylation inhibitors could be a novel therapeutic approach for EBVaGC.

16.
Metabolites ; 11(8)2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34436461

RESUMO

The aim of the current study was to examine the antidiabetic effect of noodle containing fermented lettuce extract (FLE) on diabetic mice as a pre-clinical study. The γ-aminobutyric acid (GABA) content, antioxidant capacity, and total polyphenol content of the FLE noodles were analyzed and compared with those of standard noodles. In addition, oral glucose and sucrose tolerance, and fasting blood glucose tests were performed using a high-fat diet/streptozotocin-mediated diabetic mouse model. Serum metabolite profiling of mice feed standard or FLE noodles was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOF-MS) to understand the mechanism changes induced by the FLE noodles. The GABA content, total polyphenols, and antioxidant activity were high in FLE noodles compared with those in the standard noodles. In vivo experiments also showed that mice fed FLE noodles had lower blood glucose levels and insulin resistance than those fed standard noodles. Moreover, glycolysis, purine metabolism, and amino acid metabolism were altered by FLE as determined by GC-TOF-MS-based metabolomics. These results demonstrate that FLE noodles possess significant antidiabetic activity, suggesting the applicability of fermented lettuce extract as a potential food additive for diabetic food products.

17.
Medicine (Baltimore) ; 100(29): e26684, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398039

RESUMO

RATIONALE: Chronic ulcerative colitis is an autoimmune disease in which epithelial injury continuously occurs in the colonic mucosa. While mesalazine (5-aminosalicylic acid) is used to treat ulcerative colitis, it can also cause liver failure, headaches, and abdominal pain; therefore, an alternative treatment is required. The purpose of this study was to evaluate the effectiveness of 80 stellate ganglion blocks in reducing pain and other symptoms in a patient with chronic ulcerative colitis. PATIENT CONCERNS: A 54-year-old female patient with a history of ulcerative colitis was concerned with worsening symptoms, such as abdominal discomfort and bloody-mucous stools, over the past 3 years. DIAGNOSES: Oozing mucosal bleeding and a small amount of exudate were observed on colonoscopy; a diagnosis of ulcerative colitis was made upon histologic examination. INTERVENTIONS AND OUTCOMES: A total of 80 stellate ganglion blocks were administered, after which the patient's symptom and pain level was decreased from 6 to 4 points on the numeric rating scale (11-point, 0 = no pain, 10 = worst pain imaginable). Improved clinical signs were observed on colonoscopy at a follow-up assessment. LESSONS: The stellate ganglion block may be effective for the reduction of pain and other symptoms in patients with chronic ulcerative colitis.


Assuntos
Bloqueio Nervoso Autônomo , Colite Ulcerativa , Dor Intratável/prevenção & controle , Gânglio Estrelado , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor
18.
Plants (Basel) ; 10(8)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34451713

RESUMO

Skin aging induced by ultraviolet (UV) irradiation increases expression of matrix metalloproteinase-1 (MMP-1) and destroys collagen fibers, as a result accelerating wrinkle formation. Natural products have been received scientific attention as utilized agents against photoaging. The aim of this study was to investigate the protective effect of Adenocaulon himalaicum Edgew. extract (AHE) against ultraviolet B (UVB)-induced skin damage, and to explain the underlying mechanisms in human dermal fibroblasts and epidermal keratinocytes. AHE effectively protects skin photoaging by preventing collagen degradation through MMP-1 inhibition via the MAPK/AP-1 signaling pathway. AHE significantly increased the expression of skin hydration factors, such as filaggrin, involucrin, loricrin, and caspase-14. To find how AHE possesses a direct impact on cellular activities, we identified neochlorogenic acid as a bioactive component of AHE for the first time. Neochlorogenic acid showed the anti-photoaging effect through ameliorating UVB-induced collagen degradation, reinforcing the skin barrier. Like the AHE-regulating mechanism, neochlorogenic acid modulates the MAPK/AP-1 signaling pathway and skin hydration factors. Taken together, these results suggest that AHE and neochlorogenic acid are well-qualified candidate for enhancing the conditions of photoaged skin.

19.
Sci Rep ; 11(1): 10174, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986349

RESUMO

Conflicting results have been reported regarding the effectiveness of light treatment (LT) in patients with Alzheimer's disease (AD). We investigated the effectiveness of blue-enriched white LT on sleep, cognition, mood and behavior in patients with mild and moderate AD. The treatment group (n = 14) sat about 60 cm away from a small (136 × 73 × 16 mm) LED light box for 1 h each morning for 2 weeks. The control group (n = 11) wore dark, blue-attenuating sunglasses during the 1 h exposures. The morning light started 9-10 h after each individual's dim light melatonin onset (DLMO). Assessments were done at baseline (T0), immediate post-treatment (T1), and 4 weeks after the end of the 2 weeks of LT (T2). Sleep was measured by actigraphy. Blue-enriched LT had a significantly better effect on the Pittsburgh Sleep Quality Index at T2 compared to blue-attenuated LT, and a trend of better effectiveness on total sleep time at T2. There was a significant increase in Mini-Mental State Examination score at T2 after blue-enriched LT than that at T0. Our findings suggest that morning blue-enriched LT has a benefit in improving sleep and cognitive function in AD patients.


Assuntos
Doença de Alzheimer/terapia , Cognição/efeitos da radiação , Luz , Fototerapia/métodos , Sono/efeitos da radiação , Actigrafia , Afeto/efeitos da radiação , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Comportamento/efeitos da radiação , Ritmo Circadiano/efeitos da radiação , Feminino , Humanos , Masculino , Melatonina/metabolismo , Saliva/metabolismo , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/terapia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
20.
PLoS One ; 16(4): e0249361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793637

RESUMO

BACKGROUND: Data on illicit drug use by Korean people infected with HIV are lacking. Here, we examined the prevalence and patterns of illicit drug use among people infected with HIV in Korea. MATERIAL AND METHODS: In this cross-sectional study, we included all patients infected with HIV who visited a tertiary care hospital in Korea from January 1990 to May 2020. Sociodemographic data of patients, including drug use, were collected at the first visit and during follow-up. RESULTS: Among 1,267 patients, 5.13% reported the use of an illicit drug in their lifetime, and 2.61% were users of injection drugs. The most commonly used drugs were cannabis/marijuana and methamphetamine, followed by nitrite inhalants, cocaine, dextromethorphan, carisoprodol, and 3,4-methylenedioxymethamphetamine. The illicit drug users tended to be younger than non-users, homosexuals/bisexuals, and infected with hepatitis C virus (HCV); they had a higher CD4+ cell count than non-users. Among 65 users of illicit drugs, only 24.6% revealed their drug use at the first visit interview, and 24.6% reported using two or more drugs in their lifetime. Individuals who used injection drugs were more likely to be arrested for drug-related charges than the users of non-injection drugs. Moreover, they tended to be heavy users of illicit drugs, to report using two or more drugs in their lifetime, and to be HCV seropositive. In contrast, the users of non-injection drugs were more likely to be experimental users and to start using drugs overseas for the first time, but less likely to report their drug use at the first interview. CONCLUSIONS: The prevalence of illicit drug use in people with HIV infection in Korea may have been underestimated. Further research based on more accurate measurements are warranted.


Assuntos
Infecções por HIV/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Contagem de Linfócito CD4 , Cocaína/administração & dosagem , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Humanos , Masculino , Fumar Maconha , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Centros de Atenção Terciária
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