RESUMO
2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal D-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for D-galactose catabolism. The presence of KDGal enantiomers, L-KDGal and D-KDGal, varies across these pathways. Fungal pathways generate L-KDGal through the reduction and dehydration of D-galacturonate, whereas bacterial pathways produce D-KDGal through the oxidation and dehydration of D-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that L-KDGal, identified in the bacterial catabolism of 3,6-anhydro-L-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and D- and L-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of L-KDGal and D-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. KEY POINTS: ⢠KDGal is a metabolic intermediate in fungal and bacterial pathways ⢠Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal ⢠KDGal can be used to induce pectin catabolism or produce functional materials.
Assuntos
Redes e Vias Metabólicas , Açúcares Ácidos , Açúcares Ácidos/metabolismo , Galactose/metabolismo , Galactose/análogos & derivados , Fungos/metabolismo , Fungos/enzimologia , Bactérias/metabolismo , Bactérias/enzimologia , Escherichia coli/metabolismo , Escherichia coli/genética , EstereoisomerismoRESUMO
Although real-world studies have found that remdesivir is effective in preventing poor prognosis, more information is needed on the optimal timing of remdesivir administration in high-risk coronavirus disease 2019 (COVID-19) patients in the Omicron era. From February 2022 to January 2023, a single-center retrospective study was performed in Korea. We compared the clinical characteristics and treatment outcomes between early (remdesivir treatment within 0-3 days from symptom onset) and late (≥ 4 days from symptom onset) treatment groups of patients who received remdesivir monotherapy. Of 284 patients, 225 were classified into the early treatment group and 59 were classified into the late treatment group. The early treatment group had a lower rate of 28-day progression to severe disease than the late treatment group (1.4% vs 7.4%, Pâ =â .03). Delaying remdesivir treatmentâ ≥â 4 days from symptom onset (adjusted odds ratio [aOR], 6.17; 95% CI, 1.18-32.44; Pâ =â .03) and Charlson comorbidity indexâ ≥â 3 (aOR, 9.62; 95% CI, 1.65-56.10; Pâ =â .01) were independent risk factors for 28-day progression to severe disease. Our results suggest that early administration of remdesivir could be associated with better prognosis in COVID-19 patients with the Omicron variant, and within 3 days from symptom onset seems to be the appropriate timing.
Assuntos
Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/administração & dosagem , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/administração & dosagem , Masculino , Feminino , Estudos Retrospectivos , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Pessoa de Meia-Idade , República da Coreia , Idoso , Resultado do Tratamento , COVID-19 , Hospitalização , Tempo para o Tratamento , Fatores de Tempo , Progressão da DoençaRESUMO
BACKGROUND: The ongoing, observational BICSTaR (BICtegravir Single Tablet Regimen) cohort study is evaluating real-world effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV across 14 countries over 24 months. We present 12-month data from the BICSTaR Asia cohort. METHODS: Data were pooled from retrospective and prospective cohorts of antiretroviral therapy (ART)-naïve (hereafter, TN) and ART-experienced (hereafter, TE) people with HIV (aged ≥21 years) receiving B/F/TAF in routine clinical care in the Republic of Korea, Singapore, and Taiwan. Analyses included effectiveness (primary endpoint: HIV-1 RNA <50 copies/ml, missing = excluded analysis), CD4 count, CD4/CD8 ratio, safety, treatment persistence, and patient-reported outcomes (prospective group). RESULTS: The analysis population included 328 participants (80 retrospective, 248 prospective; 65 TN, 263 TE). Participants were predominantly male (96.9% TN, 93.2% TE) with ≥1 comorbidity (52.3% TN, 57.8% TE); median age (years) was 31 (TN) and 42 (TE). Following 12 months of B/F/TAF, HIV-1 RNA was <50 copies/ml in 98.2% (54/55) of TN and 97.0% (227/234) of TE participants. Median (Q1, Q3) CD4 cell count increased by +187 (119, 291) cells/µl in the TN group (p < 0.001) and remained stable (+8 [-91, 110] cells/µl) in the TE group. B/F/TAF persistence was high in the prospective group, with 1/34 (2.9%) TN and 5/214 (2.3%) TE participants discontinuing treatment within 12 months. Drug-related adverse events occurred in 5.8% (19/328) of participants, leading to treatment discontinuation in 0.6% (2/328). CONCLUSIONS: Real-world evidence from BICSTaR supports the effectiveness, safety and tolerability of B/F/TAF in people with HIV in Asia.
RESUMO
PURPOSE: This study aimed to examine the adequacy of current nurse staffing levels by identifying nursing activities and workload. METHODS: The study used a mixed-method design. A nursing activity survey was conducted using the work sampling method over 2 working days with 119 general ward nurses. A focus group interview was conducted with 12 nurses. Quantitative and qualitative data were analyzed using SPSS 20.0 and content analysis, respectively. RESULTS: The most amount of time was spent on medication (in direct nursing) and electronic medical record documentation (in indirect nursing). The appropriate nurse-to-patient ratio is 1:7.7 for the day shift, 1:9.0 for the evening shift, and 1:11.9 for the night shift. However, the current nurse-to-patient ratio is 1:9.4, 1:11.0, and 1:13.8 for the day, evening, and night shifts, respectively. Therefore, the current nurse staffing level is insufficient for the workload. In the focus group interview, the main reasons cited for being unable to complete tasks within working hours were communication and coordination, and the nursing electronic medical record. The essential nursing activities of basic nursing and emotional support were overlooked owing to a heavy workload. Therefore, an adequate nurse staffing level should be higher than the measured quantitative workload. CONCLUSION: These results suggest the general wards of tertiary hospitals should evaluate the adequacy of their current nurse staffing and allocate sufficient nurses to improve patient safety and nursing care quality.
Assuntos
Grupos Focais , Entrevistas como Assunto , Recursos Humanos de Enfermagem Hospitalar , Admissão e Escalonamento de Pessoal , Centros de Atenção Terciária , Carga de Trabalho , Humanos , Recursos Humanos de Enfermagem Hospitalar/psicologia , Adulto , Inquéritos e Questionários , Feminino , Masculino , Registros Eletrônicos de SaúdeRESUMO
MHV-A59 is a beta-coronavirus that causes demyelinating encephalitis and hepatitis in mice. Recently, the mouse infection model of MHV-A59 has been used as an alternative animal infection model for SARS-CoV and SARS-CoV-2, aiding the development of new antiviral drugs. In this study, the MHV-A59 model was employed to investigate the potential of SARS-CoV-2 UTRs as new targets for antiviral drugs. Optimal targets within the MHV-A59 UTRs were identified using a shRNA and siRNA design tool, focusing on RNA secondary stem-loop (SL) structures in the UTRs. We then examined whether the designed RNAi constructs could inhibit MHV-A59 replication. In the 5'UTR, the stem-loop 1 (SL1) was identified as the most effective target, while in the 3'UTR, the minimal element for the initiation of negative-strand RNA synthesis (MIN) proved to be the most effective. Importantly, siRNAs targeting SL1 and MIN structures significantly reduced total RNA synthesis, negative-strand genomic RNA synthesis, subgenomic (sg) RNA synthesis, viral titer, and the plaque size of MHV-A59 compared to the control. Although not statistically significant, the combination of siSL1 and siMIN had a stronger effect on inhibiting MHV-A59 replication than either siRNA monotherapy. Interestingly, while the SL1 structure is present in both MHV and SARS-CoV-2, the MIN structure is unique to MHV. Thus, the SL1 of SARS-CoV-2 may represent a novel and promising target for RNAi-based antiviral drugs.
RESUMO
BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.
Assuntos
Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Humanos , Estudos Prospectivos , Incidência , Conduta Expectante , Infecção Hospitalar/epidemiologia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/epidemiologia , República da Coreia/epidemiologia , Centros de Atenção Terciária , Seguro SaúdeRESUMO
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/epidemiologiaRESUMO
OBJECTIVE: We aimed to examine the effectiveness of personalized light intervention using a blue-enriched light-emitting-diodes device on rest-activity rhythm (RAR) and light exposure rhythm (LER) in patients with mild and moderate Alzheimer's disease (AD). METHODS: AD patients with poor sleep quality and/or insomnia symptoms were assigned into either an experimental group (EG) or control group (CG) in a single-blind design. Personalized light intervention was given at 9-10 h after individual dim light melatonin onset, lasting for 1 h every day for two weeks in the EG (77.36±5.79 years, n=14) and CG (78.10±7.98 years, n=10). Each patient of CG wore blue-attenuating sunglasses during the intervention. Actigraphy recording at home for 5 days was done at baseline (T0), immediate postintervention (T1), and at four weeks after intervention (T2). The variables of RAR and LER were derived using nonparametric analysis. RESULTS: We found a significant time effect on the intradaily variability (IV) of RAR at T2 with respect to T0 (p=0.039), indicating reduced IV of RAR at four weeks after personalized light intervention regardless of blue-enriched light intervention. There was a time effect on the IV of LER at T1 with respect to T0 (p=0.052), indicating a reduced tendency in the IV of LER immediately after intervention. CONCLUSION: Our personalized light intervention, regardless of blue-enriched light source, could be useful in alleviating fragmentation of RAR and LER in AD patients.
RESUMO
Menopause is a significant phase in a woman's life. Menopausal symptoms can affect overall well-being and quality of life. Conventionally, hormone replacement therapy (HRT) is used to alleviate menopausal symptoms; however, depending on the conditions, HRT may lead to side effects, necessitating the exploration of alternative therapies with fewer side effects. In this study, we investigated the effects of a combination of soybean germ extract (S30) containing 30% (w/w) isoflavone and a probiotic, Lactobacillus gasseri (LGA1), on menopausal conditions in an ovariectomized (OVX) rat model. We evaluated the impact of S30+LGA on body weight, estrogen markers, uterine and bone health, vascular markers, and neurotransmitter levels. The results revealed that treatment with S30+LGA1 significantly improved body weight and uterine and bone health. Moreover, S30+LGA1 demonstrated promising effects on lipid profile, liver function, and vascular markers and positively impacted serotonin and norepinephrine levels, indicating potential mood-enhancing effects. In conclusion, S30+LGA1, possessing anti-menopausal effects in vitro and in vivo, can be recommended as a soy-based diet, which offers various health benefits, especially for menopausal women.
Assuntos
Glycine max , Lactobacillus gasseri , Ratos , Animais , Feminino , Humanos , Qualidade de Vida , Menopausa , Extratos Vegetais/farmacologia , Peso CorporalRESUMO
BACKGROUND: The prevalence of HIV and hepatitis B virus (HBV) co-infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. Important routes of transmission of both these infections include high-risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV-induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV. OBJECTIVES: This article describes the prevalence of co-infection, current clinical practice, and recommendations for the management of people living with HIV-HBV co-infection in Asia. RESULTS AND CONCLUSIONS: Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV-HBV co-infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co-infection rates. Mother-to-child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.
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/genéticaRESUMO
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 C57BLRESUMO
Agarobiose (AB; d-galactose-ß-1,4-AHG), produced by one-step acid hydrolysis of agarose of red seaweed, is considered a promising cosmetic ingredient due to its skin-moisturizing activity. In this study, the use of AB as a cosmetic ingredient was found to be hampered due to its instability at high temperature and alkaline pH. Therefore, to increase the chemical stability of AB, we devised a novel process to synthesize ethyl-agarobioside (ethyl-AB) from the acid-catalyzed alcoholysis of agarose. This process mimics the generation of ethyl α-glucoside and glyceryl α-glucoside by alcoholysis in the presence of ethanol and glycerol during the traditional Japanese sake-brewing process. Ethyl-AB also showed in vitro skin-moisturizing activity similar to that of AB, but showed higher thermal and pH stability than AB. This is the first report of ethyl-AB, a novel compound produced from red seaweed, as a functional cosmetic ingredient with high chemical stability.
Assuntos
Bebidas Alcoólicas , Alga Marinha , Sefarose/química , Fermentação , Alga Marinha/química , GlucosídeosRESUMO
PURPOSE: The number of Korean midwifery licensing examination applicants has steadily decreased due to the low birth rate and lack of training institutions for midwives. This study aimed to evaluate the adequacy of the examination-based licensing system and the possibility of a training-based licensing system. METHODS: A survey questionnaire was developed and dispatched to 230 professionals from December 28, 2022 to January 13, 2023, through an online form using Google Surveys. Descriptive statistics were used to analyze the results. RESULTS: Responses from 217 persons (94.3%) were analyzed after excluding incomplete responses. Out of the 217 participants, 198 (91.2%) agreed with maintaining the current examination-based licensing system; 94 (43.3%) agreed with implementing a training-based licensing system to cover the examination costs due to the decreasing number of applicants; 132 (60.8%) agreed with establishing a midwifery education evaluation center for a training-based licensing system; 163 (75.1%) said that the quality of midwifery might be lowered if midwives were produced only by a training-based licensing system, and 197 (90.8%) said that the training of midwives as birth support personnel should be promoted in Korea. CONCLUSION: Favorable results were reported for the examination-based licensing system; however, if a training-based licensing system is implemented, it will be necessary to establish a midwifery education evaluation center to manage the quality of midwives. As the annual number of candidates for the Korean midwifery licensing examination has been approximately 10 in recent years, it is necessary to consider more actively granting midwifery licenses through a training-based licensing system.
Assuntos
Tocologia , Gravidez , Humanos , Feminino , Coreia (Geográfico) , Licenciamento , Inquéritos e Questionários , República da CoreiaRESUMO
This study analyzed HGA and SFTS in patients with suspected tick-borne infection by focusing on key differences that clinicians can easily recognize. A retrospective analysis was performed on confirmed patients with HGA or SFTS in 21 Korean hospitals from 2013 to 2020. A scoring system was developed by multivariate regression analysis and accuracy assessment of clinically easily discriminable parameters was performed. The multivariate logistic regression analysis revealed that sex (especially male sex) (odds ratio [OR] 11.45, P = 0.012), neutropenia (< 1500) (OR 41.64, P < 0.001), prolonged activated partial thromboplastin time (OR 80.133, P < 0.001), and normal C-reactive protein concentration (≤ 1.0 mg/dL; OR 166.855, P = 0.001) were significantly associated with SFTS but not with HGA. Each factor, such as meaningful variables, was given 1 point, and a receiver-operating characteristic curve with a cutoff value (> 1) in a 5-point scoring system (0-4 points) was analyzed to evaluate the accuracy of differentiation between HGA and SFTS. The system showed 94.5% sensitivity, 92.6% specificity, and an area under the receiver-operating characteristic curve of 0.971 (0.949-0.9). Where HGA and SFTS are endemic, the scoring system based on these four parameters such as sex, neutrophil count, activated partial thromboplastin time, and C-reactive protein concentration will facilitate the differential diagnosis of HGA and SFTS in the emergency room in patients with suspected tick-borne infectious diseases.
Assuntos
Anaplasmose , Neutropenia , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Doenças Transmitidas por Carrapatos , Animais , Humanos , Masculino , Anaplasmose/diagnóstico , Anaplasmose/epidemiologia , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Estudos Retrospectivos , Diagnóstico Diferencial , Proteína C-Reativa/análise , Doenças Transmitidas por Carrapatos/diagnóstico , Neutropenia/diagnósticoRESUMO
Play is regarded as a child's primary occupation and provides valuable information about the child's abilities. Thus, informative assessment tools of play skills are critical for establishing play-related treatment goals in occupational therapy. The objective of this study is to present a practical method for occupational therapists to develop intervention goals using the Yonsei-Social Play Evaluation Tool (Y-SPET) keyforms. Parent responses (n = 310) for preschool children (three to six years old) who did not have a medical diagnosis were examined. The Rasch measurement model was used to create keyforms for the Y-SPET. All children's raw scores were converted into individual Rasch-calibrated logit scores and standard errors were estimated to establish logically attainable treatment goals. Results showed use of the keyforms could logically identify the intervention goals of the children's social play. This suggests that the Y-SPET keyforms are helpful for assessing the level of children's social play and establishing practical treatment goals.
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/genéticaRESUMO
Obesity is a major cause of conditions such as type 2 diabetes and non-alcoholic fatty liver disease, posing a threat to public health worldwide. Here, we analyzed the anti-obesity effects of a standardized ethanol extract of Cassia mimosoides var. nomame Makino (EECM) in vitro and in vivo. Treatment of 3T3-L1 adipocytes with EECM suppressed adipogenesis and lipogenesis via the AMP-activated protein kinase pathway by downregulating the expression levels of CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1, and fatty acid synthase and upregulating the acetyl-CoA carboxylase. EECM inhibited mitotic clonal expansion during early adipocyte differentiation. Oral administration of EECM for 10 weeks significantly alleviated body weight gain and body fat accumulation in high-fat diet (HFD)-fed mice. EECM mitigated adipogenesis and lipid accumulation in white adipose and liver tissues of HFD-induced obese mice. It regulated the levels of adipogenic hormones including insulin, leptin, and adipokine in the blood plasma. In brown adipose tissue, EECM induced the expression of thermogenic factors such as uncoupling protein-1, PPAR-α, PPARγ co-activator-1α, sirtuin 1, and cytochrome c oxidase IV. EECM restored the gut microbiome composition at the phylum level and alleviated dysbiosis. Therefore, EECM may be used as a promising therapeutic agent for the prevention of obesity.
Assuntos
Fármacos Antiobesidade , Cassia , Diabetes Mellitus Tipo 2 , Extratos Vegetais , Animais , Camundongos , Células 3T3-L1 , Adipogenia , Fármacos Antiobesidade/farmacologia , Cassia/química , Diabetes Mellitus Tipo 2/complicações , Dieta Hiperlipídica/efeitos adversos , Lipogênese , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , PPAR gama/metabolismo , Extratos Vegetais/farmacologiaRESUMO
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.