Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Biochem Med (Zagreb) ; 34(1): 010901, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38361737

RESUMEN

Introduction: Internal quality control (IQC) is a core pillar of laboratory quality control strategies. Internal quality control commercial materials lack the same characteristics as patient samples and IQC contributes to the costs of laboratory testing. Patient data-based quality control (PDB-QC) may be a valuable supplement to IQC; the smaller the biological variation, the stronger the ability to detect errors. Using the potassium concentration in serum as an example study compared error detection effectiveness between PDB-QC and IQC. Materials and methods: Serum potassium concentrations were measured by using an indirect ion-selective electrode method. For the training database, 23,772 patient-generated data and 366 IQC data from April 2022 to September 2022 were used; 15,351 patient-generated data and 246 IQC data from October 2022 to January 2023 were used as the testing database. For both PDB-QC and IQC, average values and standard deviations were calculated, and z-score charts were plotted for comparison purposes. Results: Five systematic and three random errors were detected using IQC. Nine systematic errors but no random errors were detected in PDB-QC. The PDB-QC showed systematic error warnings earlier than the IQC. Conclusions: The daily average value of patient-generated data was superior to IQC in terms of the efficiency and timeliness of detecting systematic errors but inferior to IQC in detecting random errors.


Asunto(s)
Laboratorios , Humanos , Control de Calidad
2.
J Imaging Inform Med ; 37(1): 374-385, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38343259

RESUMEN

Fully supervised medical image segmentation methods use pixel-level labels to achieve good results, but obtaining such large-scale, high-quality labels is cumbersome and time consuming. This study aimed to develop a weakly supervised model that only used image-level labels to achieve automatic segmentation of four types of uterine lesions and three types of normal tissues on magnetic resonance images. The MRI data of the patients were retrospectively collected from the database of our institution, and the T2-weighted sequence images were selected and only image-level annotations were made. The proposed two-stage model can be divided into four sequential parts: the pixel correlation module, the class re-activation map module, the inter-pixel relation network module, and the Deeplab v3 + module. The dice similarity coefficient (DSC), the Hausdorff distance (HD), and the average symmetric surface distance (ASSD) were employed to evaluate the performance of the model. The original dataset consisted of 85,730 images from 316 patients with four different types of lesions (i.e., endometrial cancer, uterine leiomyoma, endometrial polyps, and atypical hyperplasia of endometrium). A total number of 196, 57, and 63 patients were randomly selected for model training, validation, and testing. After being trained from scratch, the proposed model showed a good segmentation performance with an average DSC of 83.5%, HD of 29.3 mm, and ASSD of 8.83 mm, respectively. As far as the weakly supervised methods using only image-level labels are concerned, the performance of the proposed model is equivalent to the state-of-the-art weakly supervised methods.

3.
J Neurosci Res ; 102(1): e25265, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284863

RESUMEN

The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of ß-amyloid (Aß). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.


Asunto(s)
Enfermedad de Alzheimer , Trastornos del Conocimiento , Disfunción Cognitiva , Masculino , Animales , Ratones , Memoria a Corto Plazo , Cognición , Disfunción Cognitiva/diagnóstico , Placa Amiloide
4.
BMC Biol ; 21(1): 171, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568146

RESUMEN

BACKGROUND: Working memory capacity impairment is an early sign of Alzheimer's disease, but the underlying mechanisms remain unclear. Clarifying how working memory capacity is affected will help us better understand the pathological mechanism of Alzheimer's disease. We used the olfactory working memory capacity paradigm to evaluate memory capacity in 3-month-old 5XFAD (an animal model of Alzheimer's disease) mice. Immunofluorescence staining of the prefrontal cortex was performed to detect the number of FOS-positive neurons, calmodulin-dependent protein kinase II-positive neurons, and glutamate decarboxylase-positive neurons in the prelimbic cortex and infralimbic cortex. A chemogenetic method was then used to modulate the inhibition and activation of excitatory neurons in the prelimbic cortex of wild-type and 5XFAD mice and to measure the memory capacity of mice. RESULTS: Working memory capacity was significantly diminished in 5XFAD mice compared to littermate wild-type mice. Neuronal activation of the prelimbic cortex, but not the infralimbic cortex, was attenuated in 5XFAD mice performing the olfactory working memory capacity task. Subsequently, the FOS-positive neurons were co-localized with both calmodulin-dependent protein kinase II-positive neurons and glutamate decarboxylase-positive neurons. The results showed that the activation of excitatory neurons in the prelimbic cortex was correlated with working memory capacity in mice. Our results further demonstrate that the chemogenetic inhibition of prelimbic cortex excitatory neurons resulted in reduced working memory capacity in wild-type mice, while the chemogenetic activation of prelimbic cortex excitatory neurons improved the working memory capacity of 5XFAD mice. CONCLUSION: The diminished activation of prelimbic cortex excitatory neurons in 5XFAD mice during task performance is associated with reduced working memory capacity, and activation modulation of excitatory neurons by chemogenetic methods can improve memory capacity impairment in 5XFAD mice. These findings may provide a new direction for exploring Alzheimer's disease therapeutic approaches.


Asunto(s)
Enfermedad de Alzheimer , Memoria a Corto Plazo , Ratones , Animales , Memoria a Corto Plazo/fisiología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Glutamato Descarboxilasa/metabolismo , Neuronas/metabolismo , Modelos Animales de Enfermedad , Ratones Transgénicos
5.
Lab Med ; 54(3): 282-286, 2023 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-36222001

RESUMEN

OBJECTIVE: We evaluated the intraday changes of thyroid function biomarkers in healthy subjects to help clinicians diagnose thyroid diseases in appropriate timing. METHODS: Blood samples were collected from 31 subjects at 0:00, 4:00, 8:00, 12:00, 16:00 and 20:00 on the sampling day and analyzed for thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4). The intraday concentration changes were analyzed using Friedman's 2-way analysis of variance by ranks. RESULTS: The concentrations of TSH, T3, T4, FT3, and FT4 in males were significantly higher than those in females (P < .01). The obvious peak circadian rhythm of TSH was observed at 0:00 AM with gradual decline thereafter, whereas other biomarkers showed no rhythmic changes. CONCLUSION: Sex differences should be considered in interpreting thyroid function tests. It is important to select the sampling time according to the clinician's diagnostic needs, especially at night when TSH secretion peaks.


Asunto(s)
Glándula Tiroides , Triyodotironina , Humanos , Masculino , Femenino , Voluntarios Sanos , Tiroxina , Tirotropina
6.
Artículo en Inglés | MEDLINE | ID: mdl-36293972

RESUMEN

BACKGROUND: While a number of population preventive measures for COVID-19 exist that help to decrease the spread of the virus in the community, there are still many areas in preventative efforts that need improvement or refinement, particularly as new strains of the virus develop. Some of the key issues currently include incorrect and/or inconsistent use of face masks, low acceptance of early screening or vaccination for COVID-19, vaccine hesitance, and misinformation. This is particularly the case in some vulnerable populations, such as older people with chronic illnesses, ethnic minorities who may not speak the mainstream language well and children. The current protocol introduces a large programme of research through five interrelated studies that all focus on social and behavioural interventions to improve different aspects of community-related preventative indicators. Hence, the specific objectives of the overall programme are to (1) increase early testing for COVID-19 and promote the uptake of COVID-19 vaccines in the community (Study 1); (2) increase COVID-19-related health literacy and vaccine literacy and promote improved preventative measures in minority ethnic groups, chronically ill populations and caregivers (Study 2); (3) strengthen the public's motivation to stay at home and avoid nonessential high-risk activities (Study 3); (4) decrease COVID-19 vaccine hesitancy (Study 4); and (5) enhance the adherence to COVID-19-related hygiene practices and the uptake of early testing in school children (Study 5). METHODS: We will utilise a community-based participatory research (CBPR) approach in the proposed studies. All studies will incorporate an intervention development phase in conjunction with key community stakeholders, a feasibility study and an execution stage. A variety of self-reported and objective-based measures will be used to assess various outcomes, based on the focus of each study, in both the short- and long-term, including, for example, the 8-item self-reported eHealth Literacy Scale (eHEAL) and objective measures such as vaccine uptake. DISCUSSION: Theory-driven interventions will address each study's focus (e.g., social distancing, promotion of vaccine uptake, eHealth education, preventive measures and early detection). Improvements are expected to be seen in the outcomes of vulnerable and high-risk groups. Decreased infection rates are expected due to improved preventative behaviours and increased vaccine uptake. Long-term sustainability of the approach will be achieved through the CBPR model. The publication of this protocol can assist not only in sharing a large-scale and complex community-based design, but will also allow all to learn from this, so that we will have better insight in the future whether sharing of study designs can elicit timely research initiatives.


Asunto(s)
COVID-19 , Vacunas , Niño , Humanos , Anciano , SARS-CoV-2 , COVID-19/epidemiología , COVID-19/prevención & control , Investigación Participativa Basada en la Comunidad , Vacunas contra la COVID-19 , Hong Kong/epidemiología , Prueba de COVID-19 , Enfermedad Crónica
7.
Brain Behav ; 12(8): e2703, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35849713

RESUMEN

BACKGROUND: Working memory capacity (WMC) is the ability to maintain information over a few seconds. Although it has been extensively studied in healthy subjects and neuropsychiatric patients, few tasks have been developed to measure such changes in rodents. Many procedures have been used to measure WM in rodents, including the radial arm maze, the WM version of the Morris swimming task, and various delayed matching and nonmatching-to-sample tasks. It should be noted, however, that the memory components assessed in these procedures do not include memory capacity. METHODS: We developed an olfactory working memory capacity (OWMC) paradigm to assess the WMC of 3-month-old 5×FAD mice, a mouse model of Alzheimer's disease. The task is divided into five phases: context adaptation, digging training, rule learning for nonmatching to a single sample odor (NMSS), rule learning for nonmatching to multiple sample odors (NMMS), and capacity testing. RESULTS: In the NMSS rule-learning phase, there was no difference between wild-type (WT) mice and 5×FAD mice in the performance correct rate, correct option rate, and correct rejection rate. The WT mice and 5×FAD mice showed similar memory capacity in the NMMS rule-learning phase. After capacity test, we found that the WMC was significantly diminished in 5×FAD mice. As the memory load increased, 5×FAD mice also made significantly more errors than WT mice. CONCLUSION: The OWMC task, based on a nonmatch-to-sample rule, is a sensitive and robust behavioral assay that we validated as a reliable method for measuring WMC and exploring different components of memory in mice.


Asunto(s)
Enfermedad de Alzheimer , Memoria a Corto Plazo , Enfermedad de Alzheimer/psicología , Animales , Modelos Animales de Enfermedad , Flavina-Adenina Dinucleótido , Humanos , Aprendizaje por Laberinto , Ratones , Ratones Transgénicos , Olfato
8.
Biomed Environ Sci ; 35(4): 296-311, 2022 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-35473894

RESUMEN

Objective: The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake. Methods: DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD. Results: Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight. Conclusion: The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.


Asunto(s)
Pironas , Animales , Peso Corporal , Tamaño de los Órganos , Ratas , Ratas Sprague-Dawley
9.
Pharmacol Res ; 177: 106050, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34973468

RESUMEN

Sorafenib is a clinically useful multiple kinase inhibitor for the treatment of kidney cancer, liver cancer and acute myelocytic leukemia, while it has shown weak efficacy in suppressing breast cancer. Since sirtuin2 (SIRT2) is an important epigenetic regulator and associated with several cancer types including breast cancer, development and evaluation of new SIRT2 inhibitors to probe their therapeutic potentials is currently desirable. A highly selective SIRT2 inhibitor named I was previously developed by us, which showed activity to inhibit non-small cell lung cancer cell lines in vitro. We herein report expanded screening of I and its structurally similar inactive compound II against other cancer cell lines, and found that I had a wide spectrum of anticancer activity while II had no such effects. The I-sorafenib combination treatment exerted obvious synergistic reduction on cell viability of MCF-7 cells. We observed that the combination treatment could suppress cell proliferation, survival and migration, arrest cell cycle at G0/G1 phase, and induce apoptosis in MCF-7 cells, when compared with the single treatment. In vivo studies revealed that the combination treatment showed stronger tumor growth inhibition (87%), comparing with I-(42.8%) or sorafenib-solely-treated groups (61.1%) in MCF-7 xenograft model. In conclusion, this work clearly revealed a potential synthetic lethality effect for I combined with sorafenib, and will probably offer a new strategy at least for breast cancer treatment.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Niacinamida/farmacología , Niacinamida/uso terapéutico , Compuestos de Fenilurea/farmacología , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Sirtuina 2 , Sorafenib/farmacología , Sorafenib/uso terapéutico , Mutaciones Letales Sintéticas , Ensayos Antitumor por Modelo de Xenoinjerto
10.
World J Clin Cases ; 9(31): 9564-9570, 2021 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-34877291

RESUMEN

BACKGROUND: Primary soft tissue giant cell tumor (GCT-ST) is rare and has relatively low malignant potential. Most reports are pathological and clinical studies, while imaging studies have only been reported in cases of adjacent bone or with atypical cystic degeneration. With regard to the findings on magnetic resonance imaging (MRI) or ultrasonography, superficial masses can be further identified based on facial edema, skin thickening, skin contact, internal hemorrhage or necrosis and lobulation of the mass. Unlike deep-seated masses, MRI features do not always provide an accurate diagnosis for benign and malignant patients with superficial soft-tissue lesions. Thus, the application of diffusion-weighted imaging (DWI) to evaluate superficial soft tissue tumors is necessary. CASE SUMMARY: A 36-year-old woman who had a suspected malignant tumor in the upper limb on ultrasound and computed tomography is reported. The signal intensity of the suspected tumor was heterogeneous on plain MRI; nodular and heterogeneous enhancement was observed in the tumor with irregular shapes and blurred margins on dynamic contrast-enhanced MRI. The lesion on DWI was hyperintense with a higher mean apparent diffusion coefficient (ADC) value. Finally, a GCT-ST was confirmed by pathology. This case suggests that GCT-ST should be distinguished as a benign soft tissue mass from giant cell-rich soft tissue neoplasms or malignant tumors. CONCLUSION: The MRI features of the superficial GCT-ST in the upper limb included heterogeneous signal intensity within the lesion on T2-weighted image (T2WI) and T1-weighted fat-saturation spoiled gradient recalled echo (T1 FSPGR), nodular enhancement with blurred margins, irregular shapes, and a slow-increased enhancement. DWI could be used to differentiate a benign soft tissue mass from a malignant mass by the mean ADC value and provide more radiologic-pathologic information for the diagnosis of GCT-ST. Comprehensive imaging of primary GCT-ST could help complete tumor resection, and in turn likely prolong survival after surgery.

11.
Clin Chim Acta ; 523: 519-524, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34762936

RESUMEN

BACKGROUND: Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), and free T4 (FT4) are used to diagnose thyroid diseases and monitor treatment effects. Reliable biological variation (BV) data is required to ensure accurate clinical decisions. METHODS: Blood samples were collected from 31 healthy subjects at 00:00, 04:00, 08:00, 12:00, 16:00, and 20:00; each sample was analyzed twice for TSH, T3, T4, FT3, and FT4. After outlier exclusion, normality assessment, and variance homogeneity, sex-stratified BV, including within-subject (CVI) and between-subject (CVG), was defined using nested ANOVA. RESULTS: Concentrations of five biomarkers were significantly different between sexes. The CVI and CVG estimates were 34.54% and 34.43% for TSH, 5.89% and 14.18% for T3, 4.48% and 14.96% for T4, 5.37% and 11.23% for FT3, and 3.57% and 8.03% for FT4, respectively. The individual indexes (IIs) of all the biomarkers (except TSH) were ≤ 0.63. Males had lower CVIs and IIs than females. CONCLUSION: CVI estimates of all hormones, except TSH, were lower than those reported on the BV website, showing low IIs and differences between sexes. We provide updated data on the short-term BV of thyroid function biomarkers according to sex and complement BV data of thyroid function biomarkers.


Asunto(s)
Glándula Tiroides , Triyodotironina , Biomarcadores , Femenino , Humanos , Masculino , Valores de Referencia , Tirotropina , Tiroxina
12.
Transl Psychiatry ; 10(1): 431, 2020 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-33319773

RESUMEN

A decline in working memory (WM) capacity is suggested to be one of the earliest symptoms observed in Alzheimer's disease (AD). Although WM capacity is widely studied in healthy subjects and neuropsychiatric patients, few tasks are developed to measure this variation in rodents. The present study describes a novel olfactory working memory capacity (OWMC) task, which assesses the ability of mice to remember multiple odours. The task was divided into five phases: context adaptation, digging training, rule-learning for non-matching to a single-sample odour (NMSS), rule-learning for non-matching to multiple sample odours (NMMS) and capacity testing. During the capacity-testing phase, the WM capacity (number of odours that the mice could remember) remained stable (average capacity ranged from 6.11 to 7.00) across different testing sessions in C57 mice. As the memory load increased, the average errors of each capacity level increased and the percent correct gradually declined to chance level, which suggested a limited OWMC in C57 mice. Then, we assessed the OWMC of 5 × FAD transgenic mice, an animal model of AD. We found that the performance displayed no significant differences between young adult (3-month-old) 5 × FAD mice and wild-type (WT) mice during the NMSS phase and NMMS phase; however, during the capacity test with increasing load, we found that the OWMC of young adult 5 × FAD mice was significantly decreased compared with WT mice, and the average error was significantly increased while the percent correct was significantly reduced, which indicated an impairment of WM capacity at the early stage of AD in the 5 × FAD mice model. Finally, we found that FOS protein levels in the medial prefrontal cortex and entorhinal cortex after the capacity test were significantly lower in 5 × FAD than WT mice. In conclusion, we developed a novel paradigm to assess the capacity of olfactory WM in mice, and we found that OWMC was impaired in the early stage of AD.


Asunto(s)
Enfermedad de Alzheimer , Memoria a Corto Plazo , Animales , Humanos , Aprendizaje , Recuerdo Mental , Ratones , Ratones Transgénicos
13.
Eur J Med Chem ; 192: 112201, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32163813

RESUMEN

Sirtuins (SIRTs) are NAD+-dependent lysine deacylases, regulating many important biological processes such as metabolism and stress responses. SIRT inhibitors may provide potential benefits against SIRT-driven human diseases. Development of efficient assay platforms based on fluorogenic substrates will facilitate the discovery of high-quality SIRT inhibitors. We here report 16 new fluorogenic peptide substrates (P1-P16) designed with structurally diverse tetrapeptides and acyl modifications. Tests of P1-P16 against SIRT isoforms identified several sensitive substrates for SIRT1, SIRT2, SIRT3 and SIRT5, which manifested lower KM values and higher catalytic efficiency, and particularly had less signal interference in inhibitor screening compared with our previously reported internally quenched fluorescent substrates. Co-crystallization of sensitive substrates P13 and P15 with SIRT5 revealed an unexpected binding mode, involving interactions with residues from active site bordering surfaces, different from that observed for other peptides derived from natural protein substrates. By using SIRT5 sensitive substrates, we found that TW-37, a Bcl-2 inhibitor, displayed low micromolar inhibition to SIRT5, which was further validated by isothermal titration calorimetry analyses, offering a new point to develop dual-action SIRT5/Bcl-2 inhibitors against cancers. This work provides assay platform and structural basis for developing new substrates and inhibitors targeting human SIRTs.


Asunto(s)
Descubrimiento de Drogas , Inhibidores Enzimáticos/farmacología , Colorantes Fluorescentes/farmacología , Sirtuinas/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Colorantes Fluorescentes/química , Humanos , Estructura Molecular , Sirtuinas/metabolismo , Relación Estructura-Actividad
16.
PLoS One ; 13(7): e0201049, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30048531

RESUMEN

BACKGROUND AND AIMS: 1~4% of acute hepatitis B (AHB) cases in adults progresses to acute liver failure (ALF).The predictors of ALF and prognosis for patients with ALF are not clear. This study investigated some of predictive and prognostic factors for AHB progression to ALF. METHODS: A retrospective analysis was used to assess the clinical and laboratory features of 293 patients diagnosed with AHB; the patients were divided into the following two groups: ALF (n = 13) and non-ALF (n = 280). RESULTS: In total,13 of the 293 (4.43%) patients developed ALF (10 recovered、3 died). The variables of age, anti-HBc IgM titers≥10 S/CO, HBeAg negativity, and total bilirubin (TB) at admission were significantly higher in ALF patients than in non-ALF patients. Compared to non-ALF patients, ALF patients had significantly lower values for prothrombin time activity (PTA), serum albumin, and HBV DNA. At discharge, ALF patients had lower TB normalization rates and much faster clearance of HBsAg, HBeAg and HBVDNA than non-ALF patients. In multivariate analysis, TB≥5×upper limit of normal (ULN) and HBeAg negative status were independent predictors for ALF development at admission, with 84.6% sensitivity, 85.7% specificity, a likelihood ratio of 5.91 and an area under the receiver operating characteristics curve (AUROC) of 0.850.Those who died had lower levels of peak PTA (<20%) and higher levels of peak hepatic encephalopathy (HE) grade (III-IV) than those who recovered. CONCLUSIONS: Of the patients with ALF, 23.1% died. TB≥5×ULN and HBeAg negative status were the most effective and practicable factors distinguishing ALF from AHB at admission before the onset of encephalopathy. Peak PTA<20% and/or HE grade III-IV were independent predictors of a high probability of death or a need for transplantation.


Asunto(s)
Progresión de la Enfermedad , Hepatitis B/complicaciones , Fallo Hepático/complicaciones , Fallo Hepático/diagnóstico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto Joven
17.
Eur J Med Chem ; 155: 806-823, 2018 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-29957526

RESUMEN

Human sirtuin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase, and is implicated in human diseases including cancer. Selective small-molecule inhibitors for SIRT2 are sought as chemical tools and potential therapeutics. Here we report the X-ray crystal structure guided structure-activity relationship studies of new N-(3-(phenoxymethyl)phenyl)acetamide derivatives with SIRT2, which led to the identification of potent, selective SIRT2 inhibitors. Crystallographic analyses reveal that the new inhibitors act via inducing the formation of an enlarged hydrophobic pocket and particularly mimicking the interactions made by myristoylated-lysine substrates. The most potent inhibitor 24a could dose-dependently elevate the acetylation level of α-tubulin in the non-small cell lung cancer H441 cells, which have a high expression level of SIRT2 as determinated by Western blotting analyses. Further cellular assays reveal that 24a restrains cell growth mainly through inhibiting cellular proliferation rather than inducing apoptosis. Moreover, 24a could suppress the migration and invasion of H441 cells. These results provide an excellent basis for further development of new potent, selective, and cell active SIRT2 inhibitors as chemical tools and potential therapeutics for SIRT2-driven non-small cell lung cancers.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Descubrimiento de Drogas , Inhibidores de Histona Desacetilasas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Sirtuina 2/antagonistas & inhibidores , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Histona Desacetilasas/síntesis química , Inhibidores de Histona Desacetilasas/química , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Modelos Moleculares , Estructura Molecular , Sirtuina 2/metabolismo , Relación Estructura-Actividad , Células Tumorales Cultivadas
18.
Chem Biol Drug Des ; 91(1): 257-268, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28756638

RESUMEN

Human sirtuin 5 (SIRT5) is a protein deacylase regulating metabolic pathways and stress responses and is implicated in metabolism-related diseases. Small-molecule inhibitors for SIRT5 are sought as chemical tools and potential therapeutics. Herein, we proposed a customized virtual screening approach targeting catalytically important and unique residues Tyr102 and Arg105 of SIRT5. Of the 20 tested virtual screening hits, six compounds displayed marked inhibitory activities against SIRT5. For the hit compound 19, a series of newly synthesized (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues were carried out structure-activity relationship analyses, resulting in new more potent inhibitors, among which 37 displayed the most potent inhibition to SIRT5 with an IC50 value of 5.59 ± 0.75 µM. The biochemical studies revealed that 37 likely acts via competitive inhibition with the succinyl-lysine substrate, rather than the NAD+ cofactor, and it manifested substantial selectivity for SIRT5 over SIRT2 and SIRT6. This study will aid further efforts to develop new selective SIRT5 inhibitors as tools and therapeutics.


Asunto(s)
Acrilamidas/química , Sirtuinas/antagonistas & inhibidores , Acrilamidas/metabolismo , Sitios de Unión , Unión Competitiva , Diseño de Fármacos , Humanos , Concentración 50 Inhibidora , Lisina/química , Lisina/metabolismo , Simulación del Acoplamiento Molecular , NAD/química , NAD/metabolismo , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/metabolismo , Estructura Terciaria de Proteína , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/aislamiento & purificación , Sirtuinas/genética , Sirtuinas/metabolismo , Relación Estructura-Actividad , Especificidad por Sustrato
19.
Medicine (Baltimore) ; 96(49): e8928, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29245257

RESUMEN

RATIONALE: Endometrial stromal sarcoma (ESS) is rare, representing only approximately 0.2% of all uterine malignancies. Mixed type endometrial carcinomas (MT-ECs) are rare tumors with both type I and II features, and are difficult to diagnose. Cases of ESS and MT-ECs coexisting in the same patient are extremely rare. This study aimed to describe a case of ESS in combination with MT-ECs in a 47-year-old premenopausal woman. PATIENT CONCERNS: A woman presented to the hospital complaining of occasional abdominal pain and had high tumor markers: cancer antigen (CA) 19-9 (263.6 U/mL) and CA 125 (428.0 U/mL). Transvaginal ultrasound examination revealed a complex mass (12.3 × 9.1 × 6.3 cm) with solid and cystic components on the right rear wall of the uterus. Abdominopelvic computed tomography images showed a pelvic cystic-solid mixed mass. The patient underwent an exploratory midline laparotomy. The mass was hypothesized to be malignant on the uterine posterior wall. Tumor deposits were found on bilateral parametrium. On peritoneal implantation, multiple metastases were seen on the serosal surface of the bowel and greater omentum. A frozen section revealed a spindle cell sarcoma. DIAGNOSES: Pathological reports following surgery revealed concurrent ESS and MT-ECs. INTERVENTIONS: The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, total omentectomy, and macroscopic clearance of the tumor. Adjuvant chemotherapy was given. OUTCOMES: The patient was still alive when this report was written. LESSONS: Considering the rarity of ESS in combination with MT-ECs, this study presented an overview of the literature and discussed a number of histological and clinical issues. Nevertheless, etiology and pathogenesis of these tumors need further investigation.


Asunto(s)
Neoplasias Endometriales/diagnóstico , Sarcoma Estromático Endometrial/diagnóstico , Sarcoma/diagnóstico , Neoplasias Uterinas/diagnóstico , Biomarcadores de Tumor/sangre , Diagnóstico Diferencial , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Ovariectomía , Salpingooforectomía , Sarcoma/patología , Sarcoma/cirugía , Sarcoma Estromático Endometrial/patología , Sarcoma Estromático Endometrial/cirugía , Tomografía Computarizada por Rayos X , Ultrasonografía , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía
20.
J Food Sci ; 82(4): 1006-1011, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28241105

RESUMEN

Rosemary extract has a potent antioxidant activity and is widely used in the food industry. In this study, the lifespan prolonging and antioxidant activity of rosemary extract was evaluated by high-fat-induced oxidative damage in Drosophila melanogaster. The results revealed that the lifespan and climbing ability of fruit flies was enhanced significantly by feeding rosemary extract. Furthermore, feeding with rosemary extract significantly increased the enzyme activity of superoxide dismutase (SOD) and catalase (CAT), and significantly decreased the level of malonaldehyde. The gene expression of SOD, CAT, and nuclear factor erythroid-2 related factor 2 was enhanced and that for methuselah was significantly reduced. The comet assay showed that high-fat diet-induced DNA lesion was significantly reduced in larvae treated with the rosemary extract. Our results suggest that feeding with rosemary extract is effective to the extended lifespan in fruit flies by strengthening of the resistance to high-fat-induced oxidative stress and by stimulating, at least in part, the endogenous antioxidant response.


Asunto(s)
Daño del ADN/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Drosophila melanogaster/efectos de los fármacos , Estrés Oxidativo , Extractos Vegetales/farmacología , Rosmarinus/química , Animales , Antioxidantes/farmacología , Catalasa/genética , Catalasa/metabolismo , Longevidad , Masculino , Factor de Transcripción NF-E2/genética , Factor de Transcripción NF-E2/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...