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1.
Sci Total Environ ; 930: 172732, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38663609

RESUMEN

East Asian continental outflows with PM2.5, O3, and other species may determine the baseline conditions and affect the air quality in downwind areas via long-range transport (LRT). To gain insight into the impact and spatiotemporal characteristics of airborne pollutants in East Asian continental outflows, a versatile multicopter drone sounding platform was used to simultaneously observe PM2.5, O3, CO2, and meteorological variables (temperature, specific humidity, pressure, and wind vector) above the northern tip of Taiwan, Cape Fuiguei, which often encounters continental outflows during winter monsoon periods. By coordinating hourly high-spatial-resolution profiles provided by drone soundings, WRF/CMAQ model air quality predictions, HYSPLIT-simulated backward trajectories, and MERRA-2 reanalysis data, we analyzed two prominent phenomena of airborne pollutants in continental outflows to better understand their physical/chemical characteristics. First, we found that pollutants were well mixed within a sounding height of 500 m when continental outflows passed through and completely enveloped Cape Fuiguei. Eddies induced by significant fluctuations in wind speeds coupled with minimal temperature inversion and LRT facilitated vertical mixing, possibly resulting in high homogeneity of pollutants within the outflow layer. Second, the drone soundings indicated exceptionally high O3 concentrations (70-100 ppbv) but relatively low concentrations of PM2.5 (10-20 µg/m3), CO2 (420-425 ppmv), and VOCs in some air masses. The low levels of PM2.5, CO2, and VOCs ruled out photochemistry as the cause of the formation of high-level O3. Further coordination of spatiotemporal data with air mass trajectories and O3 cross sections provided by MERRA-2 suggested that the high O3 concentrations could be attributed to stratospheric intrusion and advection via continental outflows. High-level O3 concentrations persisted in the lower troposphere, even reaching the surface, suggesting that stratospheric intrusion O3 may be involved in the rising trend in O3 concentrations in parts of East Asia in recent years in addition to surface photochemical factors.

2.
Vet Med Sci ; 9(6): 2430-2437, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37842865

RESUMEN

OBJECTIVE: Surgical correction of stenotic nares, one component of brachycephalic obstructive airway syndrome (BOAS), is not referenced as often in cats as it is in dogs. Similar to dogs, stenotic nares emerge as a significant contributor in the development of BOAS in cats. In this study, we propose that stenotic nares in brachycephalic cats arise from an elongated dorsal lateral nasal cartilage. The aim of this paper is to illustrate a novel surgical technique to alleviate stenosis-associated clinical signs by performing full-thickness bilateral wedge resection of the excessive cartilage. ANIMALS: Seven cats that underwent rhinoplasty with full-thickness bilateral wedge resection along the dorsal lateral nasal cartilage between 2019 and 2022 at Pan-Asia Veterinary Clinic in Taipei, Taiwan. METHODS: Clinical data of all cats included in the study were retrospectively reviewed. Surgical procedures were recorded. A full-thickness bilateral wedge resection was made along the dorsal lateral nasal cartilage adjacent to the non-hairy area. The full-thickness wedge resection was then apposed and closed, resulting in the abduction of the wing of the nostrils. Postoperative outcomes were evaluated according to follow-up sessions by the authors, and an owner survey was conducted at least 6 months post-surgery. RESULTS: All cats included in this study had a favourable outcome with no complications reported following surgery. The degree of nostril stenosis was improved, and relapse of clinical signs was not reported. Overall, the quality of life of cats that underwent rhinoplasty was significantly improved. CLINICAL RELEVANCE: The results support that the innovative procedure described in this study is highly promising and holds great potential in restoring quality of life and halting disease progression of cats with BOAS.


Asunto(s)
Obstrucción de las Vías Aéreas , Enfermedades de los Gatos , Craneosinostosis , Enfermedades de los Perros , Gatos/cirugía , Animales , Perros , Cartílagos Nasales , Estudios Retrospectivos , Constricción Patológica/cirugía , Constricción Patológica/veterinaria , Calidad de Vida , Enfermedades de los Perros/cirugía , Obstrucción de las Vías Aéreas/cirugía , Obstrucción de las Vías Aéreas/veterinaria , Craneosinostosis/cirugía , Craneosinostosis/veterinaria , Enfermedades de los Gatos/cirugía
3.
Drug Dev Res ; 84(8): 1699-1708, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37688413

RESUMEN

Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection. Over the past 60 years, DENV has spread throughout tropical regions and currently affects more than 50% of the world's population; however, there are as of yet no effective anti-DENV drugs for clinical treatment. A number of research teams have investigated derivatives of glycolipids as possible agents for the inhibition of DENV. Our objective in this research was to study the antiviral effects of trehalose 6-caprate (TMC), trehalose 6-monolaurate (TML), and trehalose 6-monooleate (TMO), based on reports that the corresponding glycosyl, trehalose, reduces the transmission of Zika virus (ZIKV). We also sought to elucidate the molecular mechanisms underlying inhibition using the RNA isolation and reverse transcription-quantitative polymerase chain reaction, western blot analysis, median tissue culture infectious dose (TCID50 ) assay, and immunofluorescence assay and immunochemistry staining, in vitro. This is the first study to demonstrate the TML-induced inhibition of DENV serotype 2 (DENV-2) in a dose-dependent manner. The inhibitory effects of TML in the pretreated, cotreated, and full-treated groups were confirmed using time of addition assays. We determined that TML restricted viral binding, entry, replication, and release. We also confirmed the efficacy of TML against three clinical isolates of DENV serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). The findings obtained in this study identify TML as a promising candidate for the development of drugs to treat DENV infection.


Asunto(s)
Virus del Dengue , Dengue , Infección por el Virus Zika , Virus Zika , Humanos , Virus del Dengue/genética , Dengue/tratamiento farmacológico , Dengue/epidemiología , Virus Zika/genética , Infección por el Virus Zika/epidemiología , Trehalosa/farmacología , Trehalosa/uso terapéutico
4.
EPMA J ; 14(3): 457-475, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37605647

RESUMEN

Purpose: Breast cancer is a complex disease with heterogeneous outcomes that may benefit from the implementation of Predictive, Preventive, and Personalized Medicine (PPPM/3PM) strategies. In this study, we aimed to explore the potential of PPPM approaches by investigating the 10-year trends in quality of life (QOL) and the cost-effectiveness of different types of surgeries for patients with breast cancer. Methods: This prospective cohort study recruited 144 patients undergoing breast conserving surgery (BCS), 199 undergoing modified radical mastectomy (MRM), and 44 undergoing total mastectomy with transverse rectus abdominis myocutaneous flap (TRAMF) from three medical centers in Taiwan between June 2007 and June 2010. Results: All patients exhibited a significant decrease in most QOL dimension scores from before surgery to 6 months postoperatively (p < 0.05); however, from postoperative year 1 to 2, improvement in most QOL dimension scores was significantly better in the TRAMF group than in the BCS and MRM groups (p < 0.05). At 2, 5, and 10 years after surgery, the patients' QOL remained stable. In the Markov decision tree model, the TRAMF group had higher total direct medical costs than the MRM and BCS groups (US$ 32,426, US$ 29,487, and US$ 28,561, respectively) and higher average QALYs gained (7.771, 6.773, and 7.385, respectively), with an incremental cost-utility ratio (ICUR) of US$ 2,944.39 and US$ 10,013.86 per QALY gained. Conclusions: TRAMF appeared cost effective compared with BCS and MRM, and it has been proved with considerable QOL improvements in the framework of PPPM. Future studies should continue to explore the potential of PPPM approaches in breast cancer care. By incorporating predictive models, personalized treatment plans, and preventive strategies into routine clinical practice, we can further optimize patient outcomes and reduce healthcare costs associated with breast cancer treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00326-4.

5.
In Vivo ; 37(5): 2018-2027, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37652509

RESUMEN

BACKGROUND/AIM: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. MATERIALS AND METHODS: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. RESULTS: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). CONCLUSION: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Autoinmunes , Linfocitos B Reguladores , Humanos , Antirreumáticos/uso terapéutico , Antirreumáticos/metabolismo , Anticuerpos Antiproteína Citrulinada/metabolismo , Anticuerpos Antiproteína Citrulinada/uso terapéutico , Linfocitos T Reguladores , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/metabolismo
6.
APMIS ; 131(9): 498-509, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37439387

RESUMEN

Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28-ESR. Overall, 16 cell subsets presented significant differences between the non-response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28-ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Subgrupos de Linfocitos T , Resultado del Tratamiento , Linfocitos T Colaboradores-Inductores , Antirreumáticos/uso terapéutico
7.
Sci Total Environ ; 893: 164709, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37301392

RESUMEN

The immense impacts of coal-fired power plant plumes on the atmospheric environment have caused great concern linked to climate and health issues. However, studies on the field observations of aerial plumes are relatively limited, mainly due to the lack of suitable plume observation tools and techniques. In this study, we use a multicopter unmanned aerial vehicle (UAV) sounding technique to study the influences of the aerial plumes of the world's fourth-largest coal-fired power plant on the atmospheric physical/chemical conditions and air quality. A set of species, including 106 volatile organic compounds (VOCs), CO, CO2, CH4, PM2.5, and O3, and meteorological variables of temperature (T), specific humidity (SH), and wind data, are collected by the UAV sounding technique. The results reveal that the large-scale plumes of the coal-fired power plant cause local temperature inversion and humidity changes, and even affect the dispersion of pollutants below. The chemical compositions of coal-fired power plant plumes are significantly different from those of another ubiquitous vehicular source. High fractions of ethane, ethene, and benzene and low fractions of n-butane and isopentane found in plumes could serve as the key features to help distinguish the influences of coal-fired power plant plumes from other pollution sources in a particular area. By taking the ratios of pollutants (e.g., PM2.5, CO, CH4, and VOCs) to CO2 in plumes and the CO2 emission amounts of the power plant into calculation, we enable the easy quantification of the specific pollutant emissions released from power plant plumes to the atmosphere. In summary, observation by using drone soundings dissecting the aerial plumes provides a new methodology that allows aerial plumes to be readily detected and characterized. Furthermore, the influences of the plumes on the atmospheric physical/chemical conditions and air quality can be assessed rather straightforwardly, which was not easily achievable in the past.

8.
Int J Oncol ; 62(5)2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37083075

RESUMEN

Bladder cancer (BC) cells exhibit a high basal level of autophagy activity, which contributes to the development of a protective mechanism for cellular survival against current treatments. Hsa­microRNA­34a (miR­34a) presents anti­tumor function in several types of cancer. However, the functional mechanism of miR­34a in regulating tumor aggressiveness and protective autophagy of BC remains largely unknown. First, transfected BC cells with miR­34a mimic exhibited LC3­II and p62 accumulation through immunofluorescence staining. It was demonstrated that syntaxin 17 (STX17), which is required for autophagosome­lysosome fusion, was downregulated upon miR­34a mimic treatment. Mechanistically, miR­34a reduced the expression of STX17 proteins that directly bind on STX17 3'­untranslated regions and thus suppressed STX17 mRNA translation to eventually inhibit protective autophagy in BC. Cell viability and colony formation assays revealed that overexpression of miR­34a in BC cells enhances the chemosensitivity of cisplatin, doxorubicin, epirubicin and mitomycin C. Furthermore, miR­34a inhibited cell proliferation and triggered G0/G1 cell cycle arrest by inhibiting cyclin D1 and cyclin E2 protein expression. Moreover, miR­34a suppressed cell motility through the downregulation of epithelial­mesenchymal transition. In summary, miR­34a inhibits cell proliferation, motility and autophagy activity in BC, which can benefit BC treatment.


Asunto(s)
MicroARNs , Neoplasias de la Vejiga Urinaria , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Proliferación Celular/genética , Ciclo Celular/genética , Autofagia/genética , Línea Celular Tumoral , Apoptosis/genética
9.
Int J Biol Sci ; 19(3): 760-771, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36778124

RESUMEN

Background: Metastatic prostate cancer (PCa) predicts a poor prognosis and lower likelihood of survival. Osteoblasts (OBs) are known to be responsible for the synthesis and mineralization of bone, although it is unclear as to whether PCa in the prostate gland cooperates with OBs in bone to promote PCa malignant transformation. We aimed to elucidate how primary PCa cells cooperate with distal OBs and contribute to the vicious cycle that leads to metastatic PCa. Methods: N-cadherin, E-cadherin, and Twist protein expression were measured by Western blot. Twist translocation into the nucleus was detected by the immunofluorescence (IF) assay. Enzyme-linked immunosorbent assay (ELISA) detected protein levels in human serum samples. Levels of candidate protein expression were examined by the human cytokine array. Prostate tumor growth and metastasis were analyzed by orthotopic and metastatic prostate cancer models, respectively. Immunohistochemistry (IHC) staining was used to observe ADAM metallopeptidase domain 9 (ADAM9) and WNT1 inducible signaling pathway protein 1 (WISP-1) expression in tissue. Results: Our in vitro and in vivo analyses have now discovered that primary PCa expressing ADAM9 protein enables the transformation of OBs into PCa-associated osteoblasts (PCa-OBs), inducing WISP-1 secretion from PCa-OBs in the bone microenvironment. The upregulation of WISP-1 in bone provided feedback to primary PCa and promoted PCa cell aggressiveness via epithelial-mesenchymal transition (EMT) activity. Elevated levels of WISP-1 expression were detected in the serum of patients with PCa. ADAM9 levels were overexpressed in tumor tissue from PCa patients; ADAM9 blockade interrupted OB-induced release of WISP-1 and also suppressed primary tumor growth and distal metastasis in orthotopic PCa mouse models. Conclusion: Our study suggests that the ADAM9/WISP-1 axis assists with metastatic PCa progression. Thus, targeting the ADAM9/WISP-1 axis may help to prevent the malignant phenotypes of PCa cells.


Asunto(s)
Proteínas ADAM , Neoplasias de la Próstata , Animales , Humanos , Masculino , Ratones , Proteínas ADAM/metabolismo , Línea Celular Tumoral , Transformación Celular Neoplásica/metabolismo , Modelos Animales de Enfermedad , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Osteoblastos/metabolismo , Neoplasias de la Próstata/metabolismo , Microambiente Tumoral , Regulación hacia Arriba
10.
Chemosphere ; 297: 134165, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35245587

RESUMEN

East Asian continental outflows containing with pollutants may deteriorate air quality in the downwind region via long-range transport (LRT). In particular, cold fronts with high wind speeds generally promote the LRT of air pollutants to further downwind areas, including Taiwan. To gain an insightful understanding of the characteristics and vertical homogeneity of trace gases in East Asian continental outflows, as well as their relation with atmospheric meteorological conditions, whole air samples were collected above a cape at the northern tip of the island of Taiwan during frontal passages. Aerial samples were collected at multiple altitudes from the surface to a maximum height of 700 m with a multicopter sounding platform carrying a robotic whole air sampling device. Simultaneously, aerial meteorological variables of temperature and wind vector from near the surface to a maximum height of 1000 m were also measured during the whole air sampling periods. An array of 106 volatile organic compounds (VOCs) as well as CO, CO2, and CH4 were analyzed to characterize the air composition and vertical homogeneity of trace gases. The results revealed rather homogeneous vertical distributions of most VOCs, CO, CO2, and CH4 in the frontal passages, indicating well-mixed conditions of trace gases in the East Asian continental outflows. The strong wind shear and minimal temperature inversion associated with the frontal passage likely induced turbulence and increased vertical mixing. Furthermore, higher levels of species characteristic of the East Asian continent were observed from the surface up to hundreds of meters above the cape, revealing a strong inflow of polluted air masses from the East Asian continent brought by cold frontal passages.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Compuestos Orgánicos Volátiles , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Dióxido de Carbono , Monitoreo del Ambiente/métodos , Gases , Compuestos Orgánicos Volátiles/análisis
11.
Antiviral Res ; 195: 105188, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34648875

RESUMEN

Zika virus (ZIKV) has been the cause of some epidemics since 2007. The correlations of microcephaly and Guillain-Barré syndrome with ZIKV have been noticed. Unfortunately, researchers have yet to develop an effective vaccine or drug approved for ZIKV infection. Anidulafungin is a member of echinocandins that is used to treat candida infections. This study assessed the antiviral capability of anidulafungin against ZIKV. Anidulafungin was shown to significantly decrease viral RNA levels, protein expression levels, viral yields, and the rate of infection. In time of addition assays, anidulafungin exhibited inhibitory activities in the early stages of ZIKV infection. In binding and entry assays, administering anidulafungin did not lead to a corresponding decrease in quantity of viral RNA, but a significant decrease in ZIKV infectivity was observed in virucidal assays. This indicated that anidulafungin interferes directly with virions. T-1105 is a viral polymerase inhibitor, which functions in the late stage of ZIKV infection. When anidulafungin was administered in combination with T-1105, an obvious synergistic effect was observed, resulting in a combination index (CI) value of 0.85 ± 0.13. Finally, we evaluated the effects of echinocandins in terms of half-maximal inhibitory concentration (IC50), calculation of cytotoxicity concentration 50% (CC50), selectivity index (SI), and Patchdock score. Among the tests, anidulafungin bears the lowest IC50 and highest Patchdock score. Although anidulafungin is classified as a pregnancy category C agent; however, combination therapy of anidulafungin with a viral RNA replication inhibitor could expand treatment options for ZIKV infection.


Asunto(s)
Anidulafungina/farmacología , Antivirales/síntesis química , Pirazinas/farmacología , ARN Viral/efectos de los fármacos , Virus Zika/efectos de los fármacos , Animales , Antivirales/farmacología , Chlorocebus aethiops , Sinergismo Farmacológico , Humanos , Concentración 50 Inhibidora , Células Vero , Virión/efectos de los fármacos , Acoplamiento Viral/efectos de los fármacos , Infección por el Virus Zika/tratamiento farmacológico , Infección por el Virus Zika/virología
12.
Sci Rep ; 11(1): 13965, 2021 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-34234195

RESUMEN

Active fluid droplets surrounded by oil can spontaneously develop circulatory flows. However, the dynamics of the surrounding oil and their influence on the active fluid remain poorly understood. To investigate interactions between the active fluid and the passive oil across their interface, kinesin-driven microtubule-based active fluid droplets were immersed in oil and compressed into a cylinder-like shape. The droplet geometry supported intradroplet circulatory flows, but the circulation was suppressed when the thickness of the oil layer surrounding the droplet decreased. Experiments with tracers and network structure analyses and continuum models based on the dynamics of self-elongating rods demonstrated that the flow transition resulted from flow coupling across the interface between active fluid and oil, with a millimeter-scale coupling length. In addition, two novel millifluidic devices were developed that could trigger and suppress intradroplet circulatory flows in real time: one by changing the thickness of the surrounding oil layer and the other by locally deforming the droplet. This work highlights the role of interfacial dynamics in the active fluid droplet system and shows that circulatory flows within droplets can be affected by millimeter-scale flow coupling across the interface between the active fluid and the oil.

13.
Pharmaceuticals (Basel) ; 14(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33917182

RESUMEN

Dengue fever is an arbovirus disease caused by infection with the dengue virus (DENV). Half of the world's population lives under the threat of dengue fever, however, researchers have yet to develop any drugs that are clinically applicable to this infection. Micafungin is a member of the echinocandins family of anti-fungal drugs, capable of blocking the synthesis of ß-1,3-D-glucan in the walls of fungal cells. Previous studies have demonstrated the effectiveness of Micafungin against infections of enterovirus 71 (EV71) and chikungunya virus (CHIKV). This is the first study demonstrating the effectiveness of micafungin in inhibiting the cytopathic effects of dengue virus serotype 2 (DENV-2) in a dose-dependent manner. Time-of-addition assays verified the inhibitory effects of micafungin in pre-treated, co-treated, and full-treatment groups. Binding and entry assays also demonstrated the effectiveness of micafungin in the early stage of DENV-2 infection. The virucidal efficacy of micafungin appears to lie in its ability to destroy the virion. Molecular docking assays revealed the binding of micafungin to the envelope protein of DENV-2, thereby revealing the mechanism by which micafungin affects the early stage of DENV infection and the stability of DENV. Two other micafungin analogs, caspofungin and anidulafungin, were also shown to have the antiviral effects on DENV-2. Finally, immunofluorescence assay (IFA) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) confirmed the broad anti-DENV ability of micafungin against dengue virus serotypes 1, 3, and 4 (DENV-1, DENV-3, and DENV-4). Taken together, these results demonstrate the potential of micafungin and its analogs as candidates for the development of broad-spectrum treatments for DENV infection.

14.
Biosens Bioelectron ; 183: 113213, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33857754

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the cells through the binding of its spike protein (S-protein) to the cell surface-expressing angiotensin-converting enzyme 2 (ACE2). Thus, inhibition of S-protein-ACE2 binding may impede SARS-CoV-2 cell entry and attenuate the progression of Coronavirus disease 2019 (COVID-19). In this study, an electrochemical impedance spectroscopy-based biosensing platform consisting of a recombinant ACE2-coated palladium nano-thin-film electrode as the core sensing element was fabricated for the screening of potential inhibitors against S-protein-ACE2 binding. The platform could detect interference of small analytes against S-protein-ACE2 binding at low analyte concentration and small volume (0.1 µg/mL and ~1 µL, estimated total analyte consumption < 4 pg) within 21 min. Thus, a few potential inhibitors of S-protein-ACE2 binding were identified. This includes (2S,3aS,6aS)-1-((S)-N-((S)-1-Carboxy-3-phenylpropyl)alanyl)tetrahydrocyclopenta[b] pyrrole-2-carboxylic acid (ramiprilat) and (2S,3aS,7aS)-1-[(2S)-2-[[(2S)-1-Carboxybutyl]amino]propanoyl]-2,3,3a,4,5,6,7,7a-octahydroindole-2-carboxylic acid (perindoprilat) that reduced the binding affinity of S-protein to ACE2 by 72% and 67%; and SARS-CoV-2 in vitro infectivity to the ACE2-expressing human oral cavity squamous carcinoma cells (OEC-M1) by 36.4 and 20.1%, respectively, compared to the PBS control. These findings demonstrated the usefulness of the developed biosensing platform for the rapid screening of modulators for S-protein-ACE2 binding.


Asunto(s)
Técnicas Biosensibles , COVID-19 , Espectroscopía Dieléctrica , Humanos , Unión Proteica , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus
15.
Chemosphere ; 254: 126867, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32957282

RESUMEN

The unique maneuverability, ease of deployment, simplicity in logistics, and relatively low costs of multicopters render them effective vehicles for low atmospheric research. While many efforts have contributed to the fundamental success of atmospheric applications of multicopters in the past, several challenges remain, including limited measurable variables, possible response-delay in real-time observations, insufficient measurement accuracy, endurance of harsh conditions and tolerance towards interferences. To address these challenges and further fortify the applicability in diversified research disciplines, this study developed an optimized multicopter UAV sounding technique (MUST). The MUST serves as an integrated platform by combining self-developed algorithms, optimized working environments for sensors/monitors, and retrofitted sampling devices to probe a comprehensive set of atmospheric variables. These variables of interest include meteorological parameters (temperature, relative humidity, pressure, wind direction and speed), the chemical composition (speciated VOCs, CO, CO2, CH4, CO2 isotopologues, O3, PM2.5, and black carbon), and the radiation flux, as well as visible and thermal images. The aim of this study is to achieve the following objectives: 1. to easily probe a comprehensive set of near-surface atmospheric variables; 2. to improve data quality by correcting for sensors' delay in real-time observations and minimizing environmental interferences; and 3. to enhance the versatility and applicability of aerial measurements by incorporating necessary hardware and software. Field launching cases from the surface to a maximum height of 1000 m were conducted to validate the robustness of the integrated MUST platform with sufficient speed, accuracy and resolution for the target variables.


Asunto(s)
Atmósfera/química , Monitoreo del Ambiente/métodos , Conceptos Meteorológicos , Meteorología , Viento
16.
Langmuir ; 34(19): 5416-5421, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29676918

RESUMEN

Demonstrated herein is an unprecedented porous template-assisted reaction at the solid-liquid interface involving bond formation, which is typically collision-driven and occurs in the solution and gas phases. The template is a TMA (trimesic acid) monolayer with two-dimensional pores that host fullerenes, which otherwise exhibit an insignificant affinity to an undecorated graphite substrate. The confinement of C84 units in the TMA pores formulates a proximity that is ideal for bond formation. The oligomerization of C84 is triggered by an electric pulse via a scanning tunneling microscope tip. The spacing between C84 moieties becomes 1.4 nm, which is larger than the edge-to-edge diameter of 1.1-1.2 nm of C84 due to the formation of intermolecular single bonds. In addition, the characteristic mass-to-charge ratios of dimers and trimers are observed by mass spectrometry. The experimental findings shed light on the active role of spatially tailored templates in facilitating the chemical activity of guest molecules.

17.
J Biomed Inform ; 56: 1-7, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25998519

RESUMEN

PURPOSE: Adjuvant chemotherapy (ACT) is used after surgery to prevent recurrence or metastases. However, ACT for non-small cell lung cancer (NSCLC) is still controversial. This study aimed to develop prediction models to distinguish who is suitable for ACT (ACT-benefit) and who should avoid ACT (ACT-futile) in NSCLC. METHODS: We identified the ACT correlated gene signatures and performed several types of ANN algorithms to construct the optimal ANN architecture for ACT benefit classification. Reliability was assessed by cross-data set validation. RESULTS: We obtained 2 probes (2 genes) with T-stage clinical data combination can get good prediction result. These genes included 208893_s_at (DUSP6) and 204891_s_at (LCK). The 10-fold cross validation classification accuracy was 65.71%. The best result of ANN models is MLP14-8-2 with logistic activation function. CONCLUSIONS: Using gene signature profiles to predict ACT benefit in NSCLC is feasible. The key to this analysis was identifying the pertinent genes and classification. This study maybe helps reduce the ineffective medical practices to avoid the waste of medical resources.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Quimioterapia Adyuvante/métodos , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/tratamiento farmacológico , Redes Neurales de la Computación , Anciano , Algoritmos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Biología Computacional , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Pronóstico , Modelos de Riesgos Proporcionales , Reproducibilidad de los Resultados , Resultado del Tratamiento
18.
Comput Biol Med ; 48: 1-7, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24631783

RESUMEN

Numerous cancer studies have combined gene expression experiments and clinical survival data to predict the prognosis of patients of specific gene types. However, most results of these studies were data dependent and were not suitable for other data sets. This study performed cross-laboratory validations for the cancer patient data from 4 hospitals. We investigated the feasibility of survival risk predictions using high-throughput gene expression data and clinical data. We analyzed multiple data sets for prognostic applications in lung cancer diagnosis. After building tens of thousands of various ANN architectures using the training data, five survival-time correlated genes were identified from 4 microarray gene expression data sets by examining the correlation between gene signatures and patient survival time. The experimental results showed that gene expression data can be used for valid predictions of cancer patient survival classification with an overall accuracy of 83.0% based on survival time trusted data. The results show the prediction model yielded excellent predictions given that patients in the high-risk group obtained a lower median overall survival compared with low-risk patients (log-rank test P-value<0.00001). This study provides a foundation for further clinical studies and research into other types of cancer. We hope these findings will improve the prognostic methods of cancer patients.


Asunto(s)
Perfilación de la Expresión Génica/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Modelos Estadísticos , Redes Neurales de la Computación , Biología Computacional/métodos , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Riesgo
19.
Stud Health Technol Inform ; 180: 1230-2, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22874410

RESUMEN

The aim of this study was to validate a specially designed electronic medical records (EMRs) questionnaire for use in Taiwan. Published reviews of national trends and EMRs characteristics from seven countries in the Americas, Oceania, Europe, and Asia were used to design the Google-based document. This questionnaire is intended for use by medical institutions, government health units, manufacturers, academic institutions, and the public, and may be administered by information officers, non-IT staff (physicians, nurses, policymakers, vendors), and even people. A modified Delphi method was employed to determine the most appropriate content for the questionnaire. In conclusion, this research demonstrated trend analysis of several national EMRs, and also identified the meaningful use of EMR and establishing governmental EMR office are the important directions for Taiwan EMRs.


Asunto(s)
Registros Electrónicos de Salud/estadística & datos numéricos , Registros Electrónicos de Salud/tendencias , Predicción , Registros de Salud Personal , Encuestas y Cuestionarios , Revisión de Utilización de Recursos , Taiwán
20.
Dev Comp Immunol ; 38(1): 78-87, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22564858

RESUMEN

The members of the inhibitor of apoptosis protein (IAP) family are involved in the regulation of diverse cellular processes, including apoptosis, signal transduction and mitosis. Here, we report the cloning and characterization of three IAP genes from Pacific white shrimp Litopenaeus vannamei: LvIAP1, LvIAP2 and LvSurvivin. LvIAP1, the orthologue of Penaeus monodon IAP (PmIAP), consists of three BIR domains and one RING domain; LvIAP2 consists of two BIR domains and LvSurvivin has only one BIR domain. Expression profiling by absolute quantitative real-time RT-PCR revealed that of the three IAP genes, LvIAP1 had the highest expression levels in almost all examined tissues and LvSurvivin had the lowest expression levels. Furthermore, among the examined tissues, the lymphoid organs most strongly expressed all three genes. When LvIAP1 expression was silenced by injection of its corresponding dsRNA, the shrimp died within 48h after injection, whereas injection of the other two dsRNAs did not cause shrimp death. In LvIAP1-silenced shrimp, the number of circulating haemocytes decreased dramatically because of extensive apoptosis. This suggested that LvIAP1 is central to the regulation of shrimp haemocyte apoptosis.


Asunto(s)
Proteínas de Artrópodos/fisiología , Proteínas Inhibidoras de la Apoptosis/fisiología , Penaeidae/fisiología , Animales , Apoptosis , Proteínas de Artrópodos/química , Proteínas de Artrópodos/genética , Clonación Molecular , Proteínas Inhibidoras de la Apoptosis/química , Proteínas Inhibidoras de la Apoptosis/genética , Estructura Terciaria de Proteína , ARN Bicatenario/metabolismo , Análisis de Secuencia de ADN
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