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1.
ACS Infect Dis ; 10(6): 1890-1895, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38738652

RESUMEN

Currently used visible light catalysts either operate with high-power light sources or require prolonged periods of time for catalytic reactions. This presents a limitation regarding facile application in indoor environments and spaces frequented by the public. Furthermore, this gives rise to elevated power consumption. Here, we enhance photocatalytic performance with blue TiO2 and WO3 complexes covalently coupled through an organic molecule, 3-mercaptopropionic acid, under indoor light. Antibacterial experiments against 108 CFU/mL Escherichia coli (E. coli) suspensions were conducted under indoor light exposure conditions. They showed a sterilization effect of almost 90% within 70 min and nearly 100% after 110 min. The complex generates reactive oxygen species (ROS), such as •OH and O2•-, under natural air conditions. We also showed that h+ and •OH are important for sterilizing E. coli using common scavengers. This research highlights the potential of these complexes to generate ROS, effectively playing a crucial role in antibacterial effects under indoor light.


Asunto(s)
Antibacterianos , Escherichia coli , Luz , Especies Reactivas de Oxígeno , Titanio , Tungsteno , Escherichia coli/efectos de los fármacos , Escherichia coli/efectos de la radiación , Titanio/química , Titanio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Tungsteno/química , Tungsteno/farmacología , Catálisis , Especies Reactivas de Oxígeno/metabolismo , Óxidos/farmacología , Óxidos/química , Pruebas de Sensibilidad Microbiana
2.
Radiother Oncol ; 195: 110231, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38518958

RESUMEN

BACKGROUND: There is lack of evidence on chronic fatigue (CF) following radiotherapy (RT) in survivors of head and neck cancer (HNC). We aimed to compare CF in HNC survivors > 5 years post-RT with a reference population and investigate factors associated with CF and the possible impact of CF on health-related quality of life (HRQoL). MATERIAL AND METHODS: In this cross-sectional study we included HNC survivors treated in 2007-2013. Participants filled in patient-reported outcome measures and attended a one-day examination. CF was measured with the Fatigue Questionnaire and compared with a matched reference population using t-tests and Cohen's effect size. Associations between CF, clinical and RT-related factors were investigated using logistic regression. HRQoL was measured with the EORTC Quality of Life core questionnaire. RESULTS: The median age of the 227 HNC survivors was 65 years and median time to follow-up was 8.5 years post-RT. CF was twice more prevalent in HNC survivors compared to a reference population. In multivariable analyses, female sex (OR 3.39, 95 % CI 1.82-6.31), comorbidity (OR 2.17, 95 % CI 1.20-3.94) and treatment with intensity-modulated RT (OR 2.13, 95 % CI 1.16-3.91) were associated with CF, while RT dose parameters were not. Survivors with CF compared to those without, had significantly worse HRQoL. CONCLUSIONS: CF in HNC survivors is particularly important for female patients, while specific factors associated with RT appear not to play a role. The high CF prevalence in long-term HNC survivors associated with impaired HRQoL is important information beneficial for clinicians and patients to improve patient follow-up.


Asunto(s)
Supervivientes de Cáncer , Fatiga , Neoplasias de Cabeza y Cuello , Calidad de Vida , Humanos , Femenino , Masculino , Neoplasias de Cabeza y Cuello/radioterapia , Estudios Transversales , Anciano , Fatiga/etiología , Persona de Mediana Edad , Enfermedad Crónica , Encuestas y Cuestionarios , Medición de Resultados Informados por el Paciente
3.
Neurology ; 102(7): e209275, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38471067
4.
Nat Commun ; 15(1): 2219, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472255

RESUMEN

Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.


Asunto(s)
Enfermedades Neurodegenerativas , Animales , Humanos , Enfermedades Neurodegenerativas/patología , Microfluídica , Organoides/patología , Dispositivos Laboratorio en un Chip
5.
Radiother Oncol ; 190: 110044, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38061420

RESUMEN

BACKGROUND: Although dysphagia is a common side effect after radiotherapy (RT) of head and neck cancer (HNC), data on long-term dysphagia is scarce. We aimed to 1) compare radiation dose parameters in HNC survivors with and without dysphagia, 2) investigate factors associated with long-term dysphagia and its possible impact on health-related quality of life (HRQoL), and 3) investigate how our data agree with existing NTCP models. METHODS: This cross-sectional study conducted in 2018-2020, included HNC survivors treated in 2007-2013. Participants attended a one-day examination in hospital and filled in patient questionnaires. Dysphagia was measured with the EORTC QLQ-H&N35 swallowing scale. Toxicity was scored with CTCAE v.4. We contoured swallowing organs at risk (SWOAR) on RT plans, calculated dose-volume histograms (DVHs), performed logistic regression analyses and tested our data in established NTCP models. RESULTS: Of the 239 participants, 75 (31%) reported dysphagia. Compared to survivors without dysphagia, this group had reduced HRQoL and the DVHs for infrahyoid SWOAR were significantly shifted to the right. Long-term dysphagia was associated with age (OR 1.07, 95% CI 1.03-1.10), female sex (OR 2.75, 95% CI 1.45-5.21), and mean dose to middle pharyngeal constrictor muscle (MD-MPCM) (OR 1.06, 95% CI 1.03-1.09). NTCP models overall underestimated the risk of long-term dysphagia. CONCLUSIONS: Long-term dysphagia was associated with higher age, being female, and high MD-MPCM. Doses to distally located SWOAR seemed to be risk factors. Existing NTCP models do not sufficiently predict long-term dysphagia. Further efforts are needed to reduce the prevalence and consequences of this late effect.


Asunto(s)
Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Humanos , Femenino , Masculino , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Calidad de Vida , Estudios Transversales , Neoplasias de Cabeza y Cuello/radioterapia , Deglución/efectos de la radiación
6.
Radiol Case Rep ; 18(11): 3917-3921, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37663558

RESUMEN

A ductus arteriosus aneurysm is a rare congenital lesion with a localized saccular or tubular dilation of the ductus arteriosus. This lesion usually appears in all ages. Some case reports suggest the most common age of diagnosis is less than 2 months. We reported a case of an asymptomatic ductus arteriosus aneurysm in neonates. Echocardiography at 2 days of age revealed a tubular dilation of the ductus arteriosus connected to the pulmonary artery. Computed tomography angiogram showed a ductus arteriosus aneurysm with thrombus at the pulmonary end. It resolved spontaneously in the six months of life without serious complications.

7.
RSC Adv ; 13(14): 9732-9748, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-37008403

RESUMEN

In this work, we study the charge transfer improvement by the combination of two semiconductors of SERS. The energy levels of the semiconductor, when combined, become intermediate energy levels that support the charge transfer from the HOMO to the LUMO level, amplifying the Raman signal of the organic molecules. The SERS substrates of Ag/a-Al2O3-Al/ZnO nanorods with high sensitivity are prepared for detecting dye rhodamine 6G (R6G) and metronidazole (MNZ) standard. The highly ordered vertically grown ZnO nanorods (NRs) are first developed on a glass substrate by a wet chemical bath deposition method. Then, ZnO NRs are covered with an amorphous oxidized aluminum thin film by a vacuum thermal evaporation method to produce a platform with a large surface area and high charge transfer performance. Finally, silver nanoparticles (NPs) are decorated onto this platform to form an active SERS substrate. The structure, surface morphology, optical properties, and elements in the sample are investigated by Raman spectroscopy, X-ray diffractometry, field-emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectroscopy (UV-vis), reflectance spectroscopy, and energy dispersion X-ray spectroscopy (EDS). Rhodamine 6G is used as a reagent to evaluate the SERS substrates with an analytical enhancement factor (EF) of ∼1.85 × 1010 at the limit of detection (LOD) of 10-11 M. These SERS substrates are used to detect metronidazole standard at a LOD of 0.01 ppm and an EF of 2.2 × 106. The SERS substrate exhibits high sensitivity and stability for promising wide application in chemical, biomedical, and pharmaceutical detection.

8.
J Am Heart Assoc ; 12(1): e026942, 2023 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-36565192

RESUMEN

Background Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin-4 (Fbln4) in smooth muscle cells (SMKO) leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although Fbln4 is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo-arterial integrity are not fully understood. Methods and Results Gene silencing of FBLN4 was conducted on human aortic ECs to evaluate morphological changes and gene expression profile. Fbln4 double knockout (DKO) mice in ECs and smooth muscle cells were generated and subjected to histological analysis, echocardiography, Western blotting, RNA sequencing, and immunostaining. An evaluation of the thoracic aortic aneurysm phenotype and screening of altered signaling pathways were performed. Knockdown of FBLN4 in human aortic ECs induced mesenchymal cell-like changes with the upregulation of mesenchymal genes, including TAGLN and MYL9. DKO mice showed the exacerbation of thoracic aortic aneurysms when compared with those of SMKO and upregulated Thbs1, a mechanical stress-responsive molecule, throughout the aorta. DKO mice also showed progressive aortic valve thickening with collagen deposition from postnatal day 14, as well as turbulent flow in the ascending aorta. Furthermore, RNA sequencing and immunostaining of the aortic valve revealed the upregulation of genes involved in endothelial-to-mesenchymal transition, inflammatory response, and tissue fibrosis in DKO valves and the presence of activated valve interstitial cells. Conclusions The current study uncovers the pivotal role of endothelial fibulin-4 in the maintenance of valvulo-arterial integrity, which influences thoracic aortic aneurysm progression.


Asunto(s)
Aneurisma de la Aorta Torácica , Células Endoteliales , Ratones , Animales , Humanos , Aorta/patología , Arterias , Aneurisma de la Aorta Torácica/metabolismo , Miocitos del Músculo Liso/metabolismo
9.
Wellcome Open Res ; 8: 473, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-39114816

RESUMEN

Research capacity is increasing in low- and middle-income countries (LMICs), with progressive development in the range and complexity of studies being undertaken, often in collaboration with high-income country partners. Although senior local stakeholders are typically involved in ensuring that research is conducted according to accepted standards for ethical and scientific quality, to date there has been little exploration of the views of younger generations around the ethics of research involving human subjects. We present our protocol to establish a longitudinal mixed-methods student cohort at the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam, that is investigating students' views around the ethics of clinical and public-health oriented research. We use a synergistic approach involving initial deliberative engagement activities ( e.g. science cafes, debates) to inform participants about complex concepts, prior to formal quantitative and qualitative methods (surveys, focus group discussions and in-depth interviews) that are designed to explore the students' views in detail. We focus in particular on dengue research, i.e. research that addresses a locally relevant disease with which the students are likely familiar, and probe their thoughts on such themes as appropriate remuneration for research participants, involvement of vulnerable groups, use of human challenge trials in LMICs etc. A snapshot of the cohort and its activities after one year is also presented; among 429 active students, primarily from the Faculty of Medicine, the proportions of male and female students were similar, the majority were from southern or central Vietnam where dengue is endemic, and available data indicates the cohort to be representative of the expected spectrum of socioeconomic groups. The cohort provides a unique resource to investigate the views of young people on medical ethics, an important but hitherto underrepresented group in such discussions. Feedback indicates a clear interest in contributing thoughts and ideas to the development of clinical research in Vietnam.

10.
Front Vet Sci ; 9: 909401, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36532351

RESUMEN

Introduction: Piglet facial and sow teat lesions are the main reported reasons why pig producers routinely practice teeth resection. This is a painful procedure performed on piglets, where their needle teeth are clipped or ground to resect the pointed tip. The practice raises welfare concerns. In contrast to other procedures, such as tail docking, we know little about the risk factors for these two types of lesions. Methods: We employed two methods to answer these questions: (1) reviewing the literature to identify potential risk factors, and (2) surveying pig production stakeholders worldwide to identify the occurrence of these lesions and the strategies used in practice that enable pig producers to manage or prevent these lesions while avoiding teeth resection. For the literature review, we used Google Scholar to include peer-reviewed publications and gray literature. We distributed the survey using convenience sampling and documented information on the current situation regarding teeth resection, including the methods, frequencies, and reasons for resecting piglets' teeth, the occurrence of piglet facial and sow teat lesions, and measures used to prevent and control these lesions. Results: The literature review identified six major risk factors for both lesions, including the presence or absence of teeth resection, housing system, litter size, piglet management, environmental enrichment, milk production and other piglet management practices. However, most studies focused on the effects of the first two factors with very few studies investigating the other risk factors. There were 75 responses to the survey from 17 countries. The survey showed that half of the respondents practiced teeth resection with many recognizing that facial and teat lesions are the main reasons behind this practice. However, many producers used other interventions rather than teeth resection to prevent these lesions. These interventions focused on improving milk production of the sow, managing large litters, and providing environmental enrichment. Discussion: More research is needed to validate these interventions and more science-based advice is needed to bridge the gap between research and practice to help more producers further understand the cause of piglet facial and sow teat lesions to transition toward the cessation of routine teeth resection.

11.
Artículo en Inglés | MEDLINE | ID: mdl-35287310

RESUMEN

Introduction: Sweet wormwood and tortoise shell decoction, Thanh Hao Miet Giap Thang (THMGT) in Vietnamese, a traditional formula composed of five ingredients, is used in complementary care in Vietnam for patients who underwent conventional cancer treatment. To expand the clinical use and explore novel functions of THMGT, this study was conducted to investigate the effect of THMGT in terms of antiproliferative activity and selective cytotoxicity toward human breast cancer cells MCF-7. Methods: Cytotoxicity of THMGT against human breast cancer cells MCF-7 and primary fibroblasts from a heathy donor were studied using sulforhodamine B (SRB) assay. Flow cytometry analysis, immunofluorescence, and western blotting were also performed to elucidate underlying mechanisms of THMGT action. Results: The SRB assay on treated MCF-7 cells and primary fibroblasts from a heathy donor indicated selective cytotoxicity of THMGT with a selective index of 3.92. Annexin V/PI staining and flow cytometric analysis on stained MCF-7 cells showed that the THMGT-treated cells were arrested at the S phase and subsequently underwent apoptosis. Western blot analysis showed an upregulation of γ-H2AX, increased protein levels of phosphorylated CHK1, TP53, and phosphorylated TP53 in a time-dependent manner, and a downregulated expression of ATR and MDM2. Conclusion: These results suggested DNA damaging effect and ATR-CHK1-mediated cell cycle arrest of THMGT on MCF-7 cells resulting in apoptosis induction.

12.
Nat Prod Res ; 36(8): 1966-1972, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33258382

RESUMEN

Chemical investigation of chloroform extract of Flacourtia rukam Zoll. & Moritzi stems led to the isolation of one new compound namely rukamtenol together with four known compounds, viz., chaulmooric acid, flacourtin, 3,4,5-trimethoxyphenyl ß-D-glucopyranoside, and daucosterol. Their structures and relative stereochemistry have been determined by 1D and 2D NMR analysis, high resolution mass spectroscopy, and compared with those in literatures. Rukamtenol represented the first 2-oxaspiro[4.4]non-8-en-3-one in nature. The relative configuration of rukamtinol was defined using DFT-NMR chemical shift calculations and subsequent DP4 probability method. Rukamtenol, flacourtin, and 3,4,5-trimethoxyphenyl ß-D-glucopyranoside were tested for cytotoxic activity toward three MDA-MB-231, HepG2, and RD cancer cell lines. However, they failed to reveal any activity (IC50 > 100 µM) on these cell lines.


Asunto(s)
Antineoplásicos , Flacourtia , Compuestos de Espiro , Antineoplásicos/química , Estructura Molecular , Vietnam
13.
Microbiol Resour Announc ; 10(44): e0059521, 2021 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-34734766

RESUMEN

Different rice farming systems affect the soil microbial communities. Here, we report the results of 16S rRNA gene amplicon sequencing of soils collected from intensive rice cultivation and rice-shrimp farming systems in Soc Trang, Vietnam. The dominant phyla in these systems were Firmicutes, Actinobacteriota, Chloroflexi, Myxococcota, and Acidobacteriota.

14.
Circ J ; 85(9): 1469-1478, 2021 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-34011823

RESUMEN

BACKGROUND: Dilated cardiomyopathy (DCM) is an important cause of heart failure and cardiac transplantation. This study determined the prevalence of DCM-associated genes and evaluated the genotype-phenotype correlation in Vietnamese patients.Methods and Results:This study analyzed 58 genes from 230 patients. The study cohort consisted of 64.3% men; age at diagnosis 47.9±13.7 years; familial (10.9%) and sporadic DCM (82.2%). The diagnostic yield was 23.5%, 44.0% in familial and 19.6% in sporadic DCM.TTNtruncating variants (TTNtv) were predominant (46.4%), followed byTPM1,DSP,LMNA,MYBPC3,MYH6,MYH7,DES,TNNT2,ACTC1,ACTN2,BAG3,DMD,FKTN,PLN,TBX5,RBM20,TCAP(2-6%). Familial DCM, genotype-positive andTTNtv-positive patients were younger than those with genotype-negative and sporadic DCM. Genotype-positive patients displayed a decreased systolic blood pressure and left ventricular wall thickness compared to genotype-negative patients. Genotype-positive patients, particularly those withTTNtv, had a family history of DCM, higher left atrial volume index and body mass index, and lower right ventricle-fractional area change than genotype-negative patients. Genotype-positive patients reached the combined outcomes more frequently and at a younger age than genotype-negative patients. Major cardiac events occurred more frequently in patients positive with genes other thanTTNtv. CONCLUSIONS: The study findings provided an overview of Vietnamese DCM patients' genetic profile and suggested that management of environmental factors may be beneficial for DCM patients.


Asunto(s)
Cardiomiopatía Dilatada , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Estudios de Cohortes , Estudios de Asociación Genética , Genotipo , Humanos , Vietnam
15.
EBioMedicine ; 58: 102931, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32739874

RESUMEN

Chimeric antigen receptor (CAR) T cells use re-engineered cell surface receptors to specifically bind to and lyse oncogenic cells. Two clinically approved CAR-T-cell therapies have significant clinical efficacy in treating CD19-positive B cell cancers. With widespread interest to deploy this immunotherapy to other cancers, there has been great research activity to design new CAR structures to increase the range of targeted cancers and anti-tumor efficacy. However, several obstacles must be addressed before CAR-T-cell therapies can be more widely deployed. These include limiting the frequency of lethal cytokine storms, enhancing T-cell persistence and signaling, and improving target antigen specificity. We provide a comprehensive review of recent research on CAR design and systematically evaluate design aspects of the four major modules of CAR structure: the ligand-binding, spacer, transmembrane, and cytoplasmic domains, elucidating design strategies and principles to guide future immunotherapeutic discovery.


Asunto(s)
Linfocitos B/inmunología , Neoplasias/terapia , Receptores Quiméricos de Antígenos/metabolismo , Antígenos CD19/metabolismo , Humanos , Inmunoterapia Adoptiva , Neoplasias/inmunología
16.
Arterioscler Thromb Vasc Biol ; 40(8): 1905-1917, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32580633

RESUMEN

OBJECTIVE: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4SMKO), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4SMKO mice and generated double knockout mice (DKO, Fbln4SMKO; Egr1-/-). Aneurysms were prevented in DKO mice (42.8%) and Fbln4SMKO; Egr1+/- mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. CONCLUSIONS: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.


Asunto(s)
Aneurisma de la Aorta Torácica/etiología , Proteína 1 de la Respuesta de Crecimiento Precoz/fisiología , Proteínas de la Matriz Extracelular/fisiología , Receptor PAR-1/fisiología , Anciano , Anciano de 80 o más Años , Animales , Proteínas de la Matriz Extracelular/deficiencia , Femenino , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/fisiología , Ratones , Persona de Mediana Edad , Receptor PAR-1/antagonistas & inhibidores , Estrés Mecánico , Trombina/farmacología
17.
Data Brief ; 31: 105731, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32509936

RESUMEN

Vietnam is one of the top shrimp producing and exporting countries in the world [1]. However, viral and bacterial epidemic diseases cause severe damages to shrimp farming, resulting in millions of US dollars losses annually [2]. Furthermore, inappropriate use of antibiotics in shrimp rearing lead to increased emergence of drug resistant pathogens [3]. Current practices for water quality control, mostly based on chemical and physical parameters; neglected biological criteria necessary for maintaining pond health. Ninh Thuan is a region situated in the South Central Coast of Vietnam. Due to its geographic location, a large part of this region is dedicated to shrimp (Litopenaeus vannamei) post-larvae production and rearing. This article presents a microbiome dataset from two water samples collected in a shrimp rearing pond in Ninh Thuan. We used Oxford Nanopore Technologies (ONT) for metagenomic sequencing of the samples to characterize microbial communities and antibiotic resistance profiles. The metagenome dataset generated will provide an understanding and comparison framework of the microbial diversity and functionality among shrimp ponds with potential application in health management and shrimp rearing industry.

18.
ACS Nano ; 14(6): 6548-6558, 2020 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-32167289

RESUMEN

Progressive Alzheimer's disease is correlated with the oligomerization and fibrillization of the amyloid beta (Aß) protein. We identify the fibrillization stage of the Aß protein through label-free near-field THz conductance measurements in a buffer solution. Frequency-dependent conductance was obtained by measuring the differential transmittance of the time-domain spectroscopy in the THz range with a molar concentration of monomer, oligomer, and fibrillar forms of the Aß protein. Conductance at the lower frequency limit was observed to be high in monomers, reduced in oligomers, and dropped to an insulating state in fibrils and increased proportionally with the Aß protein concentration. The monotonic decrease in the conductance at low frequency was dominated by a simple Drude component in the monomer with concentration and nonlinear conductance behaviors in the oligomer and fibril. By extracting the structural localization parameter, a dimensionless constant, with the modified Drude-Smith model, we defined a dementia quotient (DQ) value (0 < De < 1) as a discrete metric for a various Aß proteins at a low concentration of 0.1 µmol/L; DQ = 1.0 ± 0.002 (fibril by full localization, mainly by Smith component), DQ = 0.64 ± 0.013 (oligomer by intermixed localization), and DQ = 0.0 ± 0.000 (monomer by Drude component). DQ values were discretely preserved independent of the molar concentration or buffer variation. This provides plenty of room for the label-free diagnosis of Alzheimer's disease using the near-field THz conductance measurement.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Enfermedad de Alzheimer/diagnóstico , Humanos
19.
PLoS Negl Trop Dis ; 13(11): e0007142, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31675360

RESUMEN

BACKGROUND: Dengue is the most prevalent arboviral disease of humans. Virus neutralizing antibodies are likely to be critical for clinical immunity after vaccination or natural infection. A number of human monoclonal antibodies (mAbs) have previously been characterized as able to neutralize the infectivity of dengue virus (DENV) for mammalian cells in cell-culture systems. METHODOLOGY/PRINCIPLE FINDINGS: We tested the capacity of 12 human mAbs, each of which had previously been shown to neutralize DENV in cell-culture systems, to abrogate the infectiousness of dengue patient viremic blood for mosquitoes. Seven of the twelve mAbs (1F4, 14c10, 2D22, 1L12, 5J7, 747(4)B7, 753(3)C10), almost all of which target quaternary epitopes, inhibited DENV infection of Ae. aegypti. The mAbs 14c10, 747(4)B7 and 753(3)C10 could all inhibit transmission of DENV in low microgram per mL concentrations. An Fc-disabled variant of 14c10 was as potent as its parent mAb. CONCLUSIONS/SIGNIFICANCE: The results demonstrate that mAbs can neutralize infectious DENV derived from infected human cells, in the matrix of human blood. Coupled with previous evidence of their ability to prevent DENV infection of mammalian cells, such mAbs could be considered attractive antibody classes to elicit with dengue vaccines, or alternatively, for consideration as therapeutic candidates.


Asunto(s)
Aedes/virología , Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Virus del Dengue/inmunología , Dengue/inmunología , Dengue/prevención & control , Viremia/inmunología , Animales , Anticuerpos Monoclonales/sangre , Anticuerpos Antivirales/sangre , Dengue/transmisión , Dengue/virología , Vacunas contra el Dengue , Epítopos/inmunología , Humanos , Viremia/virología
20.
Circ J ; 83(9): 1908-1916, 2019 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-31308319

RESUMEN

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.Methods and Results:Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype. CONCLUSIONS: We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.


Asunto(s)
Miosinas Cardíacas/genética , Cardiomiopatía Hipertrófica/genética , Mutación , Cadenas Pesadas de Miosina/genética , Sarcómeros/genética , Tropomiosina/genética , Troponina T/genética , Adulto , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/epidemiología , Cardiomiopatía Hipertrófica/fisiopatología , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Penetrancia , Fenotipo , Prevalencia , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vietnam/epidemiología
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