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1.
Environ Geochem Health ; 46(8): 270, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954122

RESUMO

Radioactive nuclides cesium (Cs) and strontium (Sr) possess long half-lives, with 135Cs at approximately 2.3 million years and 87Sr at about 49 billion years. Their persistent accumulation can result in long-lasting radioactive contamination of soil ecosystems. This study employed geo-accumulation index (Igeo), pollution load index (PLI), potential ecological risk index (PEPI), health risk assessment model (HRA), and Monte Carlo simulation to evaluate the pollution and health risks of Cs and Sr in the surface soil of different functional areas in a typical mining city in China. Positive matrix factorization (PMF) model was used to elucidate the potential sources of Cs and Sr and the respective contribution rates of natural and anthropogenic sources. The findings indicate that soils in the mining area exhibited significantly higher levels of Cs and Sr pollution compared to smelting factory area, agricultural area, and urban residential area. Strontium did not pose a potential ecological risk in any studied functional area. The non-carcinogenic health risk of Sr to the human body in the study area was relatively low. Because of the lack of parameters for Cs, the potential ecological and human health risks of Cs was not calculated. The primary source of Cs in the soil was identified as the parent material from which the soil developed, while Sr mainly originated from associated contamination caused by mining activities. This research provides data for the control of Cs and Sr pollution in the surface soil of mining city.


Assuntos
Radioisótopos de Césio , Mineração , Poluentes Radioativos do Solo , Medição de Risco , China , Poluentes Radioativos do Solo/análise , Radioisótopos de Césio/análise , Humanos , Radioisótopos de Estrôncio/análise , Césio/análise , Cidades , Solo/química , Método de Monte Carlo , Monitoramento de Radiação
2.
BMC Med ; 21(1): 461, 2023 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996906

RESUMO

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.


Assuntos
Técnicas de Ablação , Fibrilação Atrial , Ablação por Cateter , Embolia Intracraniana , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Estudos Prospectivos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/prevenção & controle , Incidência , Técnicas de Ablação/efeitos adversos , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Recidiva
3.
Cardiovasc Diabetol ; 22(1): 293, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891556

RESUMO

OBJECTIVE: Diabetic kidney disease (DKD) is characterized by the abnormal deposition of oxidized low-density lipoprotein (ox-LDL), which contributes to podocyte damage. Klotho, an aging suppressor that plays a critical role in protecting podocytes in DKD, is mainly expressed in kidney tubular epithelium and secreted in the blood. However, it has not been established whether Klotho can alleviate podocyte injury by inhibiting renal ox-LDL deposition, and the potential molecular mechanisms require further investigation. METHODS: We conducted a comprehensive analysis of serum and kidney biopsy samples obtained from patients diagnosed with DKD. Additionally, to explore the underlying mechanism of Klotho in the deposition of ox-LDL in the kidneys, we employed a mouse model of DKD with the Klotho genotype induced by streptozotocin (STZ). Furthermore, we conducted meticulous in vitro experiments on podocytes to gain further insights into the specific role of Klotho in the deposition of ox-LDL within the kidney. RESULTS: Our groundbreaking study unveiled the remarkable ability of the soluble form of Klotho to effectively inhibit high glucose-induced ox-LDL deposition in podocytes affected by DKD. Subsequent investigations elucidated that Klotho achieved this inhibition by reducing the expression of the insulin/insulin-like growth factor 1 receptor (IGF-1R), consequently leading to a decrease in the expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) and an enhancement of mitochondrial function. Ultimately, this series of events culminated in a significant reduction in the expression of the oxidized low-density lipoprotein receptor (OLR1), thereby resulting in a notable decrease in renal ox-LDL deposition in DKD. CONCLUSION: Our findings suggested that Klotho had the potential to mitigate podocyte injury and reduced high glucose-induced ox-LDL deposition in glomerulus by modulating the IGF-1R/RAC1/OLR1 signaling. These results provided valuable insights that could inform the development of novel strategies for diagnosing and treating DKD.


Assuntos
Nefropatias Diabéticas , Proteínas Klotho , Podócitos , Animais , Humanos , Camundongos , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/prevenção & controle , Glucose/metabolismo , Rim/metabolismo , Lipoproteínas LDL/metabolismo , Podócitos/metabolismo , Podócitos/patologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/farmacologia , Receptores Depuradores Classe E/metabolismo , Proteínas Klotho/metabolismo , Transdução de Sinais
4.
Eur J Nucl Med Mol Imaging ; 51(1): 295-303, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37592084

RESUMO

PURPOSE: There is an emerging role of the use of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in renal cell carcinoma. Herein, we report our experience in use of PSMA PET in recurrent or metastatic renal cell carcinoma (RCC). METHODS: A retrospective analysis of all patients who underwent PSMA PET for suspected recurrent or de-novo metastatic RCC between 2015 and 2020 at three institutions was performed. The primary outcome was change in management (intensification or de-intensification) following PSMA PET scan. Secondary outcomes included histopathological correlation of PSMA avid sites, comparison of sites of disease on PSMA PET to diagnostic CT and time to systemic treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Neoplasias da Próstata , Masculino , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/patologia , Próstata/patologia , Estudos Retrospectivos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Radioisótopos de Gálio
5.
Environ Geochem Health ; 45(7): 5343-5356, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37138141

RESUMO

Fluorine (F) is not an essential element for vegetation and excessive F can be phytotoxic to plant growth, which can cause fluorosis to human beings by ingesting F-contaminated plant. Although there have been some studies focusing on the toxicity of F to plants and the retarding effect of Ca to F-stress plant, atmospheric F contamination to vegetation and the role of the application of foliar Ca are scantly reported. This study investigated several biochemical parameters to evaluate F toxicity under both F-exposure (root and leaf F-exposure) and the remedial effects of foliar Ca. The results showed that F concentration of pakchoi leaves was correlated with exogenous F level positively in both foliar and root F-exposure series, and F concentration of pakchoi roots was only changed under root F-exposure treatments. Ca supplement (0.5 g/L and 1 g/L) significantly decreased plant F concentration. Both F-exposure treatments caused lipid peroxidation in plants and exogenous Ca alleviated the toxicity of F to pakchoi. Meanwhile, chlorophyll-a concentration was decreased by foliar and root F, whereas chlorophyll-b concentration was only affected by foliar F, and chlorophyll-a concentration could be elevated by exogenous Ca but chlorophyll-b could not. It was concluded that both atmospheric and root F can impair pakchoi growth and disturb photosynthesis, and foliar Ca showed an ameliorative effect to F toxicity of pakchoi through alleviating chlorophyll decomposition, increasing protein content and alleviating oxidative damage.


Assuntos
Clorofila , Flúor , Humanos , Flúor/toxicidade , Clorofila/metabolismo , Fotossíntese , Estresse Oxidativo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo
6.
Bull Environ Contam Toxicol ; 111(5): 59, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37903975

RESUMO

Vanadium (V) contamination in soil has received extensive attention due to its high toxicity. The change of mobility and bioavailability of soil V and the effects of V on the soil microbial community were studied under conditions of different V(V) spiking concentrations (0, 100, 250, and 500 mg kg-1) and aging time (1, 7, 14, 30, 45, and 60 d). The results showed that soil V mainly presented as V(IV) of all treatments throughout the aging process. At high levels of V(V) loading (250 and 500 mg kg-1), soil V(V) showed a downward trend, while bioavailable V did not change significantly within 60 d's aging. The analysis of soil bacterial community showed that Proteobacteria was the most abundant phylum in all soils, and the dominant genera Sphingomonas and Lysobacter can well adapt to high concentration V. These microorganisms exhibited great potential for bioremediation of V-contaminated soils.


Assuntos
Microbiota , Poluentes do Solo , Vanádio/toxicidade , Vanádio/análise , Solo/química , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Sequenciamento de Nucleotídeos em Larga Escala , Microbiologia do Solo
7.
J Transl Med ; 20(1): 480, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266725

RESUMO

BACKGROUND: Proteinuria is an unfavorable clinical condition highly associated with a risk of renal and cardiovascular disease in chronic kidney disease (CKD). However, whether all proteinuria forms are linked to renal impairment are still unclear. Cubilin is an endocytic receptor highly expressed in renal proximal tubules mediating uptake of albumin, transferrin and α1-microglobulin. METHODS: Exome sequencing method initially identified candidate genes. With the application of exome sequencing combined with Sanger sequencing, we further focused on CUBN through bioinformatics analysis. The pathogenic effects of the potentially causative variants were verified utilizing complementary analysis of clinical data and systematic characterization of the variants' expression and function with clinical samples and in vitro experiments in HEK293T cell lines along with in vivo experiments in mice. RESULTS: In this study, we identified four novel variants locating after the vitamin B12 (vitB12)-binding domain of Cubilin (encoded by CUBN, NM_001081.3: c.4397G > A (p.C1466Y), c.6796C > T (p.R2266X), c.6821 + 3A > G and c.5153_5154delCT (p.S1718X)) in two families. Moreover, the variants severely affected the expression and function of Cubilin in renal proximal tubules and caused albuminuria, increasing levels in urine transferrin and α1-microglobulin, but without progressive glomerular filtration barrier (GFB) impairment, vitB12 deficiencies or abnormal blood levels of HDL and albumin. Further mechanistic insights showed that the variants after the vitB12-binding domain of CUBN merely disrupted the association with Amnionless (AMN) that exhibited aberrant localization in cell cytoplasm rather than membrane. CONCLUSIONS: Here, our findings suggested that different mutation types after the vitB12-binding domain of CUBN uncouple proteinuria from glomerular filtration barrier, that may be an unexpectedly common benign condition in humans and may not require any proteinuria-lowering treatment or renal biopsy.


Assuntos
Rim , Proteinúria , Animais , Humanos , Camundongos , Albuminas/metabolismo , Células HEK293 , Rim/patologia , Proteinúria/complicações , Proteinúria/genética , Transferrinas/metabolismo , Vitamina B 12/metabolismo
8.
Cell Immunol ; 371: 104453, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808442

RESUMO

A20, encoded by TNFAIP3, is an effective anti-inflammatory molecule that plays a crucial role in inhibiting NF-κB signal transmission and is linked to multiple inflammatory diseases. It has been reported that the haploinsufficiency of A20 (HA20) caused by multiple base mutations in TNFAIP3 shows early-onset spontaneous Behçet-like disease. However, the mechanisms by which A20 mutations involved in inflammatory disease are incompletely defined. Herein, we reported a novel TNFAIP3 (c.1804A > T, p.T602S) variation, which has not been reported before. Summarizing the patient's immunodeficiency phenotype, we aimed to delineate the underlying mechanism for regulation of inflammation and immunity. Candidate genes associated with the Behçet-like phenotypes of the patient were screened and identified by using whole-exome and sanger sequencing. Functional studies were performed in A20(c.1804A > T, p.T602S) patient-derived peripheral blood mononuclear cells (PBMCs) and THP-1 cell lines by lentivirus mediating stable over-expression of A20 and A20(c.1804A > T, p.T602S) to analyze the activity of NF-κB signaling pathway. The clinical manifestations in patients with syndrome are Behçet-like disorder, and sequencing revealed heterozygous mutation in TNFAIP3 (c.1804A > T, p.T602S). Functional tests found that the PBMCs of the patient and his family carrying this heterozygous variant stimulated by LPS, TNF-α, or IL-1ß, increased the levels of inflammatory factors and induced over-activation of the canonical NF-κB signaling pathway. Similar results were also observed in the stable transduction THP-1 (A20, c.1804A>T) cell line stimulated by LPS, TNF-α or IL-1ß. The novel loss-of-function A20 variation (c.1804A > T, p.T602S) causes over-activation of the canonical NF-κB signaling pathway and fail to terminate NF-κB signaling in response to stimulation by inflammatory cytokines. The variation triggers a dominantly-inherited Behçet-like disorder caused by haploinsufficiency of the A20 protein. Identification of the novel A20 mutation attaches great importance to prenatal diagnosis and fetal therapeutic intervention, drastically reducing the risk of newborns suffering from HA20.


Assuntos
Síndrome de Behçet/genética , Haploinsuficiência/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Linhagem Celular Tumoral , Pré-Escolar , Citocinas/metabolismo , Predisposição Genética para Doença/genética , Humanos , Inflamação/patologia , Masculino , Mutação de Sentido Incorreto/genética , NF-kappa B/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Células THP-1 , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo
9.
BMC Infect Dis ; 22(1): 348, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392833

RESUMO

BACKGROUND: Our aim was to evaluate the effect of setting up a full-time infection control nursing service on reducing the prevalence of multidrug-resistant organism (MDRO) in the orthopedic ward. METHODS: From January 2015 to March 2019, routine prevention and control measures were taken for patients infected/colonized with MDRO in this ward, which was set as the pre-intervention period. The intervention period was from April 2019 to June 2021. The study was designed to evaluate whether the establishment of a full-time infection control nursing service could reduce the positive density of MDRO in the hospital by using an interrupted time-series model of a quasi experimental study. RESULTS: There were 11,759 patients during pre-intervention period and 8142 patients during intervention period. The total number of MDRO isolated before intervention was 177, of which 145 were obtained in hospital and 32 were brought in from outside hospital. The total number of MDRO isolated after intervention was 47, of which 29 were obtained in hospital and 18 were brought in from outside hospital. Before intervention, the positive density of MDRO in the orthopedic ward showed an increasing trend (ß1 = 0.02, P = 0.003). After intervention, the positive density of MDRO showed a downward trend (ß3 = - 0.05, P = 0.018). CONCLUSIONS: The establishment of the full-time infection control nursing service in the orthopedic ward can effectively reduce the nosocomial prevalence of MDRO.


Assuntos
Infecção Hospitalar , Serviços de Enfermagem , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Farmacorresistência Bacteriana Múltipla , Hospitais , Humanos , Controle de Infecções
10.
Bioorg Chem ; 121: 105674, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35182887

RESUMO

Fla-CN is a flavonoid derivative with anti-diabetic and anti-obesity effects; however, its biological targets are still unknown. In this study, we developed bifunctional affinity-based probes to identify the direct targets of Fla-CN. When using probe 3, we observed the co-location of probe 3 and mitochondria in both HepG2 and 3T3-L1 cells. The putative target proteomes were obtained using activity-based protein profiling (ABPP) and photo-affinity labelling. Pyruvate carboxylase, mitochondrial malate dehydrogenase, mitochondrial complex I, and F1FO-ATPase were validated as the direct targets of Fla-CN by surface plasmon resonance (SPR) and biochemical assays. It was elucidated that the Tyr651, Gln870 and Lys912 were the key amino acid residues near the binding site of pyruvate carboxylase with Fla-CN. The direct interaction of Fla-CN and the above four targets allowed elucidation of its complicated molecular mechanism, including the activation of adenosine 5-monophosphate (AMP)-activated protein kinase (AMPK), and the inhibition of gluconeogenesis. Further investigation for activation of AMPK in normal and insulin resistance (IR) HepG2 cells, indicated that Fla-CN could target insulin resistance tissues.


Assuntos
Diabetes Mellitus , Resistência à Insulina , Proteínas Quinases Ativadas por AMP/metabolismo , Flavonoides/química , Flavonoides/farmacologia , Humanos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Piruvato Carboxilase
11.
Int J Clin Pharmacol Ther ; 60(1): 57-66, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34672254

RESUMO

OBJECTIVE: This study was conducted to assess the pharmacokinetic and safety profiles between a new oral formulation of terazosin hydrochloride capsule compared with the brand-name drug. MATERIALS AND METHODS: A randomized, open-label, single-dose, 2-period crossover study under fasting or fed conditions was conducted in healthy Chinese subjects. 24 individuals were selected, respectively. Each subject was randomized at the beginning to receive a 2-mg capsule of the test or the reference terazosin during the first period and then received the alternate formulation during the second period following a 1-week washout period. Blood samples were collected at pre-dose and up to 60 hours after administration. Plasma terazosin was quantified by a validated LC-MS/MS method. RESULTS: 48 healthy subjects were enrolled, and 47 completed the study. Cmax, AUC0-t, and AUC0-∞ were similar and the 90% CIs for the geometric mean ratios of these parameters between the two groups were all bounded within the predefined bioequivalence criterion of 80 - 125% under both fasting and fed conditions. Throughout the study period, a total of 30 treatment-emergent adverse events (TEAEs) were reported under fasting condition. 35 TEAEs were observed under fed conditions. No serious adverse event was observed. CONCLUSION: The test and reference formulations of terazosin were bioequivalent and well tolerated under both fasting and fed conditions.


Assuntos
Jejum , Espectrometria de Massas em Tandem , Área Sob a Curva , China , Cromatografia Líquida , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Prazosina/análogos & derivados , Comprimidos , Equivalência Terapêutica
12.
Bull Environ Contam Toxicol ; 107(3): 559-564, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216229

RESUMO

Pot experiments with alfalfa, milkvetch root and swamp morning glory were conducted to elucidate the effect of soil vanadium (V) on plant growth and to evaluate their phytoremediation potential under V(V) exposure. Based on biomass analysis, swamp morning glory showed higher tolerance than alfalfa and milkvetch root in response to different soil V(V) levels. The accumulation of V in plants increased with the increasing soil V and the V concentration in roots was 1.95-4.31 times that in shoots. After planting, soil total V, V(V), bioavailable V and water-soluble V all reduced, and the decreases in bioavailable V and V(V) showed significant. The decreased percentage of V(V) in total V in soils demonstrated that the planting process may stimulate the mechanism of V(V) reduction to V(IV). Therefore, the three tested plants, particularly swamp morning glory can be promising phytostabilizers applied to V phytoremediation practices.


Assuntos
Medicago sativa , Poluentes do Solo , Biodegradação Ambiental , Raízes de Plantas/química , Solo , Poluentes do Solo/análise , Vanádio
13.
J Infect Dis ; 222(2): 189-193, 2020 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-32382737

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Técnicas Imunoenzimáticas/métodos , Pneumonia Viral/diagnóstico , Testes Sorológicos/métodos , Adulto , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Pandemias , Peptídeos/imunologia , Pneumonia Viral/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Sensibilidade e Especificidade , Proteínas Virais/imunologia
14.
Child Care Health Dev ; 46(4): 485-494, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32396218

RESUMO

BACKGROUND: This study explored the relationship between self-perceived stigmatization (affiliate stigma), stress and quality of life among parents of children with autism spectrum disorder (ASD). METHOD: Participants (N = 110) filled-in the Affiliate Stigma Scale, the Caregiver Burden Inventory and the CarerQOL scale. RESULTS: Parents reported low scores on stigma and fair levels of stress and quality of life, indicating that parents do not feel stigmatized by affiliation with a child with ASD nor are they stressed from affiliate stigma. After controlling for demographic factors, both the relationships of affiliate stigma with stress and with quality of life were weak, indicating that stigma may have little to no effect on stress and quality of life. CONCLUSION: Cultural and religious beliefs may play a part in the acceptance of a child's condition, resulting in less impact of stigma on the parents.


Assuntos
Povo Asiático/psicologia , Transtorno do Espectro Autista/psicologia , Pais/psicologia , Qualidade de Vida , Estigma Social , Estresse Psicológico/etiologia , Adulto , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/terapia , Criança , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Autoimagem , Adulto Jovem
15.
Oncology ; 97(5): 270-276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31266008

RESUMO

INTRODUCTION: The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for "screen failure" (RFSF) are well documented; however, their effect on subsequent standard therapy (SST) and outcomes is unclear. METHODS: This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage/prior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. RESULTS: Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%); 90% were metastatic. The most common RFSF were rapid disease progression (PD; 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT; 12%). After screen failure, 129/217 (59%) had SST; 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, p = 0.0006; 71/109 vs. 15/42, p = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%); the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM; 13/72). CONCLUSIONS: RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve/phase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.


Assuntos
Ensaios Clínicos como Assunto , Neoplasias/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico , Neoplasias/patologia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Environ Sci Technol ; 53(13): 7782-7791, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31244059

RESUMO

Methylmercury (MeHg) is a well-known environmental neurotoxicant affecting millions worldwide who consume contaminated fishes and other food commodities. Exposure to MeHg has been shown to associate positively with some chronic diseases including cardiovascular diseases, but the mechanism is poorly characterized. MeHg had been shown to affect prostaglandin (PG) regulations in in vitro studies, but neither in vivo nor human studies investigating the effects of MeHg on PG regulations has been reported. Thus, the current study aimed to investigate the association between MeHg exposure and serum PG concentrations in a cross-sectional study among human adults followed by a validation investigation on the cause-effect relationship using a rat model. First, a total of 121 women were recruited from two cities: Wanshan and Leishan in Guizhou, China. Statistical analysis of the human data showed a positive association between blood total mercury (THg) levels and serum concentrations of PGF2α, 15-deoxy-PGJ2, and PGE2 after adjusting for site effects. In the animal study, adult female Sprague-Dawley rats were dosed with 40 µg MeHg/kg body weight/day for 12 weeks. Serum 15-deoxy-PGJ2 and 2,3 d-6-keto-PGF1α concentrations were found to increase significantly after 6 and 10 weeks of MeHg dosing, respectively, while serum PGF2α concentration increased significantly after 12 weeks of MeHg dosing. Combined results of our human and rat studies have shown that chronic MeHg exposure induced dysregulation of PG metabolism. As PGs are a set of mediators with very diverse functions, its abnormal production may serve as the missing mechanistic link between chronic MeHg exposure and various kinds of associated clinical conditions including neurodegeneration and cardiovascular diseases.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Oryza , Adulto , Animais , China , Estudos Transversais , Monitoramento Ambiental , Feminino , Humanos , Prostaglandinas , Ratos , Ratos Sprague-Dawley
17.
Artigo em Inglês | MEDLINE | ID: mdl-30224531

RESUMO

The capsid of the hepatitis B virus is an attractive antiviral target for developing therapies against chronic hepatitis B infection. Currently available core protein allosteric modulators (CpAMs) mainly affect one of the two major types of protein-protein interactions involved in the process of capsid assembly, namely, the interaction between the core dimers. Compounds targeting the interaction between two core monomers have not been rigorously screened due to the lack of screening models. We report here a cell-based assay in which the formation of core dimers is indicated by split luciferase complementation (SLC). Making use of this model, 2 compounds, Arbidol (umifenovir) and 20-deoxyingenol, were identified from a library containing 672 compounds as core dimerization regulators. Arbidol and 20-deoxyingenol inhibit the hepatitis B virus (HBV) DNA replication in vitro by decreasing and increasing the formation of core dimer and capsid, respectively. Our results provided a proof of concept for the cell model to be used to screen new agents targeting the step of core dimer and capsid formation.


Assuntos
Antivirais/farmacologia , Diterpenos/farmacologia , Regulação Viral da Expressão Gênica , Vírus da Hepatite B/efeitos dos fármacos , Indóis/farmacologia , Multimerização Proteica/efeitos dos fármacos , Proteínas do Core Viral/antagonistas & inibidores , Capsídeo/efeitos dos fármacos , Capsídeo/metabolismo , Capsídeo/ultraestrutura , Linhagem Celular , Replicação do DNA/efeitos dos fármacos , DNA Viral/antagonistas & inibidores , DNA Viral/biossíntese , DNA Viral/genética , Genes Reporter , Células HEK293 , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Ensaios de Triagem em Larga Escala , Humanos , Luciferases/genética , Luciferases/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas do Core Viral/genética , Proteínas do Core Viral/metabolismo
19.
J Asian Nat Prod Res ; 16(5): 440-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24625225

RESUMO

Three new pregnane alkaloids, named terminamines H-J (1-3), together with two known alkaloids (4 and 5), were isolated from the ethanol extract of Pachysandra terminalis. The structures of isolated compounds were elucidated by spectroscopic methods, including (1)H and (13)C NMR, 2D NMR, and HR-ESI-MS. Compounds 1, 4, and 5 revealed significant anti-metastasis activities. In addition, compound 1 inhibited the expression of p-PKCζ in MDA-MB-231 cells, and compound 4 inhibited the expressions of p-PKCζ in MDA-MB-231 and A549 cells.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Pachysandra/química , Pregnanos/isolamento & purificação , Alcaloides/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pregnanos/química , Pregnanos/farmacologia
20.
Clin Kidney J ; 17(3): sfae037, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455522

RESUMO

Background: Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. Methods: We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5ß2γ1, and Integrin α3ß1, across prevalent pediatric glomerular diseases. Results: We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases. Conclusion: In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

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