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1.
Bioconjug Chem ; 35(7): 996-1006, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38946349

RESUMEN

Biosensors based on immobilized antibodies require molecular strategies that (i) couple the antibodies in a stable fashion while maintaining the conformation and functionality, (ii) give outward orientation of the paratope regions of the antibodies for good accessibility to analyte molecules in the biofluid, and (iii) surround the antibodies by antibiofouling molecules. Here, we demonstrate a method to achieve oriented coupling of antibodies to an antifouling poly(l-lysine)-grafted-poly(ethylene glycol) (PLL-g-PEG) substrate, using glycan remodeling to create antibody-DNA conjugates. The coupling, orientation, and functionality of the antibodies were studied using two analysis methods with single-molecule resolution, namely single-molecule localization microscopy and continuous biosensing by particle motion. The biosensing functionality of the glycan-remodeled antibodies was demonstrated in a sandwich immunosensor for procalcitonin. The results show that glycan-remodeled antibodies enable oriented immobilization and biosensing functionality with low nonspecific binding on antifouling polymer substrates.


Asunto(s)
Anticuerpos Inmovilizados , Técnicas Biosensibles , Polisacáridos , Técnicas Biosensibles/métodos , Polisacáridos/química , Polisacáridos/inmunología , Anticuerpos Inmovilizados/inmunología , Anticuerpos Inmovilizados/química , Polietilenglicoles/química , Incrustaciones Biológicas/prevención & control , Polilisina/química , Anticuerpos/inmunología , Anticuerpos/química , Humanos , Polímeros/química
2.
Analyst ; 149(13): 3530-3536, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38757525

RESUMEN

ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.


Asunto(s)
Adenosina Trifosfato , Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , Compuestos Ferrosos , Oro , Metalocenos , Adenosina Trifosfato/análisis , Aptámeros de Nucleótidos/química , Humanos , Oro/química , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Metalocenos/química , Compuestos Ferrosos/química , Técnicas Biosensibles/métodos , Electrodos , Polímeros/química , Nanocables/química , Límite de Detección , Células HeLa
3.
J Periodontal Res ; 59(3): 565-575, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38240289

RESUMEN

BACKGROUND AND OBJECTIVE: Clinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis. METHODS: We used silk thread ligation to induce periodontitis in HGF-overexpressing transgenic (HGF-Tg) and wild-type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL-6 and TNF-α) and lymphocytes in periodontitis tissues by enzyme-linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways. RESULTS: We found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF-Tg mice than in wild-type mice. In the late stage, HGF-Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL-17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis. CONCLUSION: HGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.


Asunto(s)
Pérdida de Hueso Alveolar , Factor de Crecimiento de Hepatocito , Ratones Endogámicos C57BL , Ratones Transgénicos , Periodontitis , Microtomografía por Rayos X , Animales , Factor de Crecimiento de Hepatocito/metabolismo , Periodontitis/metabolismo , Periodontitis/patología , Ratones , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/patología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Transducción de Señal , Masculino , Ensayo de Inmunoadsorción Enzimática
4.
Environ Res ; 251(Pt 2): 118657, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38521354

RESUMEN

BACKGROUND: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. METHODS: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. RESULTS: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). CONCLUSIONS: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.


Asunto(s)
Ritmo Circadiano , Luz , Melatonina , Humanos , Masculino , Femenino , Adulto Joven , Estudios Transversales , China , Iluminación , Saliva/química , Saliva/efectos de la radiación , Adulto , Pueblos del Este de Asia
5.
J Formos Med Assoc ; 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38246800

RESUMEN

BACKGROUND/PURPOSE: Zirconia has been a popular material in dental implantology with good biocompatibility. But few research focused on its application in implant drills. This study aimed to investigate the physical, thermal, and biological effects on using the zirconia and stainless-steel drills for implant bone site preparation. METHODS: We performed a series of experiments to evaluate the physical wearing properties of zirconia and stainless-steel drills of identical diameter and similar shape. During the implant site preparation thermal test, we subjected both drills onto a resin-embedded bone, utilizing a thermal couple device without irrigation. Moreover, we conducted a cell study by collecting bone cells in vivo while preparing the implant site with both tested drills. The cell activity was evaluated through cell proliferation colorimetric analysis (XTT) and alkaline phosphatase (ALP) activity measurements. RESULTS: The zirconia drill outperforms the stainless-steel drill in terms of requiring less force, maintaining stability over repeated cutting tests, and generating lower temperatures during drilling (stainless-steel drill: 45.48 ± 1.31 °C; zirconia-coated drill: 32.98 ± 1.21 °C, P = 0.000247). Meanwhile, both types of drills show similar results in XTT colorimetric analysis and ALP activity test. CONCLUSION: The thermal effect study is more favorable for using the zirconia drill than the stainless-steel drill for bone preparation. Cytological analysis indicate that the zirconia drill produces a similar impact on bone cells activity as the stainless-steel drill. Therefore, we conclude that the zirconia drills offer a good cutting effect similar to currently available stainless-steel drills in various aspects.

6.
J Oral Rehabil ; 51(3): 526-535, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37904309

RESUMEN

BACKGROUND: Human neuroimaging studies have revealed the association between brain structure and masticatory function. However, the majority of the studies adopted a cross-sectional design, which hardly reveals the change in masticatory function and brain structure between different timepoints, and the dynamical association between changes in masticatory function and changes in brain structure has not been elucidated. OBJECTIVE: With a longitudinal design, we assessed the association between changes in masticatory performance (MP) and regional brain volume. METHODS: Twenty-two elderly participants received assessments of the number of missing teeth and MP (via colour-changeable chewing gum) when they entered the study (i.e. the initial stage, T0 ), approximately 6 months later (T0.5 ), and approximately 1-2 years later (T1 ). Difficulty of food intake was assessed using a questionnaire. The participants received magnetic resonance imaging (MRI) at T0 and T1 . The brain volume of the motor-related area was estimated using FreeSurfer for MRI data. The associations between different stages were analysed using Spearman's rho correlation coefficients. RESULTS: (1) Individually, a smaller volume of right primary motor cortex at T0 was associated with increased MP from T0 to T1 , suggesting the brain's role in changing oral functions; (2) higher MP at T0 was associated with an increased volume of the left superior frontal cortex from T0 to T1 p, suggesting a potential effect on brain plasticity, and (3) increased difficulty to eat was associated with decrease MP but not brain volume of motor-related area. CONCLUSIONS: The preliminary findings revealed a complicated pattern of structural brain features and masticatory function in elderly people, and either the hypothesis that the brain predisposes masticatory function or the hypothesis that mastication reshapes the brain is oversimplified.


Asunto(s)
Encéfalo , Estado de Salud , Humanos , Anciano , Estudios Transversales , Encéfalo/diagnóstico por imagen , Diagnóstico Bucal , Neuroimagen , Masticación
7.
Int J Paediatr Dent ; 34(5): 534-545, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38229230

RESUMEN

BACKGROUND: No studies have evaluated the unique potential of nurse-led silver diamine fluoride (SDF) application for children to bridge the gap in interprofessional collaboration. AIM: To investigate the attitudes, beliefs and perceptions of nurses regarding nurse-led SDF application at the well-child visit and identify possible barriers and make recommendations. DESIGN: Mixed methods design involving a questionnaire and semi-structured individual interviews were conducted. RESULTS: All eligible nurses (n = 110) completed the questionnaire, and 16 were interviewed. Questionnaire responses highlighted that nurses were not confident in providing oral health services (score: <3 of 5) beyond oral hygiene advice (score: ≥3.9 of 5) but believed that they should be providing these services for individuals with difficulty accessing care. Interviews reflected that most nurses viewed oral health care as an important part of paediatric health but were limited by knowledge, time and manpower. Most were willing to expand their job scope to include SDF application with formal education and training, competency assessments and approaches to counter time limitations. CONCLUSION: Where nurses are already providing basic oral healthcare, nurse-led SDF application could be the next step. Findings suggest that systemic changes should include strategies to empower and motivate nurses to apply SDF at the well-child visit.


Asunto(s)
Actitud del Personal de Salud , Fluoruros Tópicos , Compuestos de Amonio Cuaternario , Compuestos de Plata , Humanos , Fluoruros Tópicos/uso terapéutico , Compuestos de Amonio Cuaternario/uso terapéutico , Encuestas y Cuestionarios , Femenino , Niño , Masculino , Adulto , Cariostáticos/uso terapéutico , Atención Dental para Niños/métodos
8.
Anal Chem ; 95(48): 17912-17919, 2023 12 05.
Artículo en Inglés | MEDLINE | ID: mdl-37972240

RESUMEN

The organic photoelectrochemical transistor (OPECT) has been proven to be a promising platform to study the rich light-matter-bio interplay toward advanced biomolecular detection, yet current OPECT is highly restrained to its intrinsic electronic amplification. Herein, this work first combines chemical amplification with electronic amplification in OPECT for dual-amplified bioanalytics with high current gain, which is exemplified by human immunoglobulin G (HIgG)-dependent sandwich immunorecognition and subsequent alkaline phosphatase (ALP)-mediated chemical redox cycling (CRC) on a metal-organic framework (MOF)-derived BiVO4/WO3 gate. The target-dependent redox cycling of ascorbic acid (AA) acting as an effective electron donor could lead to an amplified modulation against the polymer channel, as indicated by the channel current. The as-developed bioanalysis could achieve sensitive HIgG detection with a good analytical performance. This work features the dual chemical and electronic amplification for OPECT bioanalysis and is expected to stimulate further interest in the design of CRC-assisted OPECT bioassays.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Humanos , Técnicas Electroquímicas , Oxidación-Reducción , Polímeros , Límite de Detección
9.
Crit Rev Food Sci Nutr ; 63(28): 9425-9435, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-35585831

RESUMEN

Food packaging is important for today's globalized food system, but food contact materials (FCMs) can also be a source of hazardous chemicals migrating into foodstuffs. Assessing the impacts of FCMs on human health requires a comprehensive identification of the chemicals they contain, the food contact chemicals (FCCs). We systematically compiled the "database on migrating and extractable food contact chemicals" (FCCmigex) using information from 1210 studies. We found that to date 2881 FCCs have been detected, in a total of six FCM groups (Plastics, Paper & Board, Metal, Multi-materials, Glass & Ceramic, and Other FCMs). 65% of these detected FCCs were previously not known to be used in FCMs. Conversely, of the more than 12'000 FCCs known to be used, only 1013 are included in the FCCmigex database. Plastic is the most studied FCM with 1975 FCCs detected. Our findings expand the universe of known FCCs to 14,153 chemicals. This knowledge contributes to developing non-hazardous FCMs that lead to safer food and support a circular economy.


Asunto(s)
Contaminación de Alimentos , Embalaje de Alimentos , Humanos , Contaminación de Alimentos/análisis , Sustancias Peligrosas/análisis , Bases de Datos Factuales , Plásticos
10.
J Adv Nurs ; 79(8): 3025-3034, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36695405

RESUMEN

AIMS: The study aimed to explore farmers' self-care behaviours including oral hygiene, remaining natural teeth, cardiometabolic risks, hepatitis, risk of stroke and their determinant factors. METHODS: This cross-sectional study was conducted between June 2020 and March 2021 in the south-western remote areas of Taiwan. We recruited current farmers who participated in an annual community health screening conducted by a collaborated local hospital. Data were collected through face-to-face interviews using a semi-structured questionnaire. Blood samples were drawn and stored in the central laboratory of the cooperating hospital. The study outcomes included cardiometabolic risks, the remaining natural teeth, and farmers' self-care behaviours including oral hygiene, adopting a healthy diet and substance use. RESULTS: Overall, 183 current farmers (55.2% women, aged 66.9 ± 11.7 years) were enrolled. Abnormal blood pressure, high risk of stroke, metabolic syndrome and hepatitis C virus infection were found among the participants. The average remaining teeth were 12.1, 73.2% of participants had <20 teeth; 90.2% and 71% did not undergo regular dental check-ups and scaling or use dental floss, respectively. The determinant factors associated with the remaining teeth included a high risk of stroke, teeth scaling and dental floss use. Although only 3.8% felt mentally distressed, many farmers were unaware of having potential cardiometabolic diseases and curable viral hepatitis, and only two had received antiviral treatment. CONCLUSION: The farmers in this study had a high prevalence of cardiometabolic risks, a high probability of stroke, inadequate number of remaining teeth and poor oral hygiene behaviours. These findings can provide evidence to develop health promotion programmes for farmers. IMPACT: This study demonstrates the health needs of farmers. We strongly recommend that community nurses empower farmers to engage in self-care behaviours through tailored health promotion programmes. For instance, by discussing cardiometabolic risk prevention from the farmers' perspectives to improve their health literacy.


Asunto(s)
Agricultores , Accidente Cerebrovascular , Humanos , Femenino , Masculino , Estudios Transversales , Autocuidado , Higiene Bucal
11.
Int J Mol Sci ; 24(4)2023 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-36834663

RESUMEN

This study aimed to develop a drug delivery system with hybrid biodegradable antifungal and antibacterial agents incorporated into poly lactic-co-glycolic acid (PLGA) nanofibers, facilitating an extended release of fluconazole, vancomycin, and ceftazidime to treat polymicrobial osteomyelitis. The nanofibers were assessed using scanning electron microscopy, tensile testing, water contact angle analysis, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. The in vitro release of the antimicrobial agents was assessed using an elution method and a high-performance liquid chromatography assay. The in vivo elution pattern of nanofibrous mats was assessed using a rat femoral model. The experimental results demonstrated that the antimicrobial agent-loaded nanofibers released high levels of fluconazole, vancomycin, and ceftazidime for 30 and 56 days in vitro and in vivo, respectively. Histological assays revealed no notable tissue inflammation. Therefore, hybrid biodegradable PLGA nanofibers with a sustainable release of antifungal and antibacterial agents may be employed for the treatment of polymicrobial osteomyelitis.


Asunto(s)
Nanofibras , Osteomielitis , Ratas , Animales , Antibacterianos/química , Vancomicina , Ceftazidima/química , Antifúngicos/uso terapéutico , Nanofibras/química , Preparaciones de Acción Retardada , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Fluconazol , Ácido Poliglicólico/química , Ácido Láctico/química , Osteomielitis/tratamiento farmacológico
12.
BMC Oral Health ; 23(1): 178, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-36973692

RESUMEN

BACKGROUND: Uric acid, a formerly-known antioxidant that has recently been linked to numerous inflammatory diseases as a pro-inflammatory and -oxidative mediator in pathological conditions. It is imperative to reassess the association between periodontitis and uric acid locally and systematically. The aim of this systematic review was to systemically evaluate the association between periodontitis and the uric acid (UA) levels in blood, saliva and gingival crevicular fluid (GCF). METHODS: Relevant clinical studies up to January 28, 2023 were identified and retrieved from electronic databases including PubMed, Scopus, EMBASE and Web of Science, with periodontitis, uric acid, hyperuricemia and gout as the keywords. The weighted (WMD) or standardized mean difference (SMD) was calculated using fixed- or random-effect models. Methodological heterogeneity was assessed. RESULTS: Sixteen eligible observational studies and one RCT were enrolled, which included 1354 patients with periodontitis and 989 controls. Three sample types for UA detection were involved, including blood (n = 8), saliva (n = 9) and GCF (n = 1). Meta-analysis demonstrated an enhanced plasma UA concentration (WMD = 1.00 mg/dL, 95% CI 0.63 to 1.37, P < 0.001) but a decreased salivary UA level (SMD = -0.95, 95% CI -1.23 to -0.68, P < 0.001) in periodontitis versus control. Statistical heterogeneity among the plasma- and saliva-tested studies were moderate (I2 = 58.3%, P = 0.066) and low (I2 = 33.8%, P = 0.196), respectively. CONCLUSIONS: Within the limitations of the enrolled studies, it seems that there is an association between periodontitis and increased blood UA and decreased salivary UA. (Registration no. CRD42020172535 in Prospero).


Asunto(s)
Hiperuricemia , Periodontitis , Humanos , Ácido Úrico , Periodontitis/complicaciones , Hiperuricemia/diagnóstico , Líquido del Surco Gingival , Saliva
13.
Gut ; 71(9): 1843-1855, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34921062

RESUMEN

OBJECTIVE: Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC. DESIGN: Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro-in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo. RESULTS: The delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy. CONCLUSION: The co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animales , Carcinoma Ductal Pancreático/patología , Humanos , Ratones , Nanogeles , Óxido Nítrico , Neoplasias Pancreáticas/patología , Ligando Inductor de Apoptosis Relacionado con TNF/farmacología , Microambiente Tumoral , Neoplasias Pancreáticas
14.
Mol Biol Evol ; 38(11): 4732-4747, 2021 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-34175931

RESUMEN

Prior and extensive plastic rewiring of a transcriptional network, followed by a functional switch of the conserved transcriptional regulator, can shape the evolution of a new network with diverged functions. The presence of three distinct iron regulatory systems in fungi that use orthologous transcriptional regulators suggests that these systems evolved in that manner. Orthologs of the transcriptional activator Sef1 are believed to be central to how iron regulatory systems developed in fungi, involving gene gain, plastic network rewiring, and switches in regulatory function. We show that, in the protoploid yeast Lachancea kluyveri, plastic rewiring of the L. kluyveri Sef1 (Lk-Sef1) network, together with a functional switch, enabled Lk-Sef1 to regulate TCA cycle genes, unlike Candida albicans Sef1 that mainly regulates iron-uptake genes. Moreover, we observed pervasive nonfunctional binding of Sef1 to its target genes. Enhancing Lk-Sef1 activity resuscitated the corresponding transcriptional network, providing immediate adaptive benefits in changing environments. Our study not only sheds light on the evolution of Sef1-centered transcriptional networks but also shows the adaptive potential of nonfunctional transcription factor binding for evolving phenotypic novelty and diversity.


Asunto(s)
Redes Reguladoras de Genes , Plásticos , Candida albicans/genética , Plásticos/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Levaduras/genética
15.
J Virol ; 95(6)2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33408178

RESUMEN

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot, and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a dose that was lethal for 14-day-old suckling mice. Within 14 days postchallenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs), and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future.IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs), and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and the EP and FP mixture were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar to immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.


Asunto(s)
Enterovirus Humano A/inmunología , Enfermedad de Boca, Mano y Pie/prevención & control , Vacunación/métodos , Vacunas Virales/administración & dosificación , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Chlorocebus aethiops , Modelos Animales de Enfermedad , Enfermedad de Boca, Mano y Pie/virología , Ratones , Serogrupo , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Células Vero , Carga Viral , Vacunas Virales/inmunología , Virión/inmunología
16.
Toxicol Appl Pharmacol ; 453: 116212, 2022 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-36057402

RESUMEN

Microplastic particles degraded from plastic litters are recognized as a global environmental pollutant, which can be transferred and enriched via the food chain to impact ecosystems and human health. A balanced gut microbiota contributes to human health through host-gut interactions, environmentally-driven factors such as microplastic exposure would disturb the gut bacteria and affect its functionality. Dietary compounds can remodel the compositions of gut microbes, and interact with bacteria exerting profound effects on host physiology. This study explored the effects of bayberry-derived anthocyanin cyanidin-3-O-glucoside (C3G) and microplastic polystyrene (PS) on the gut microbiome in C57BL/6 mice, especially the alterations in gut bacteria and its metabolites. Using 16S rRNA high-throughput sequencing, variations in gut bacterial composition and enrichment of functional pathways were found upon PS and C3G administration. Meanwhile, the differential metabolites and metabolic pathways were identified by metabolomic analysis. Importantly, colonic and fecal PS levels were found to be strongly correlated with key microbiota-derived metabolites, which are associated with xenobiotic metabolism via regulation of xenobiotics-metabolizing enzymes and transporters. These results may offer new insights regarding the protective effects of C3G against xenobiotic PS exposure and the roles of gut bacterial metabolites.


Asunto(s)
Antocianinas , Microbiota , Microplásticos , Animales , Antocianinas/farmacología , Bacterias/genética , Bacterias/metabolismo , Glucósidos/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Plásticos/metabolismo , Poliestirenos/metabolismo , Poliestirenos/toxicidad , ARN Ribosómico 16S/genética , Xenobióticos/metabolismo
17.
Biomacromolecules ; 23(12): 5330-5339, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36454623

RESUMEN

To alleviate the dilemma of drug administration in Alzheimer's disease (AD) patients, it is of great significance to develop a new drug delivery system. In this study, a subcutaneously implanted microneedle (MN) device with a swellable gelatin methacryloyl (GelMA) needle body and a dissolvable polyvinyl alcohol (PVA) backing layer was designed. The backing layer quickly dissolved once the MN was introduced into the subcutaneous, and the hydrogel needles were implanted in the subcutaneous to enable prolonged drug release. Compared with oral administration, the MN system offers the benefits of a high administration rate, a fast onset of effect, and a longer duration of action. By detecting the concentration of acetylcholine (ACH) and Aß 1-42, it was found that MN administration exhibited a stronger therapeutic effect. The biological safety of the MN system was also assessed, and no obvious signs of hemolysis, cytotoxicity, and inflammatory reaction were observed. Together, these findings suggested that the MN system is a convenient, efficient, and safe method of delivering donepezil hydrochloride (DPH) and may provide AD patients with a novel medicine administration option.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Donepezilo/farmacología , Donepezilo/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Agujas , Sistemas de Liberación de Medicamentos , Alcohol Polivinílico , Administración Cutánea
18.
J Nanobiotechnology ; 20(1): 311, 2022 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-35794602

RESUMEN

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes (molar masses of 479.1-1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). The result showed a substantial improvement over the loading of commercial dyes (3.7-50% loading) while preventing their spontaneous aggregation in aqueous solutions. This packaging strategy includes our newly synthesized organic dyes (> 85% loading) designed for OPVs (242), DSSCs (YI-1, YI-3, YI-8), and OLEDs (ADF-1-3, and DTDPTID) applications. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to near-infrared (NIR) emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.


Asunto(s)
Nanopartículas , Fotoquimioterapia , Colorantes , Polímeros , Agua
19.
J Craniofac Surg ; 33(3): e316-e318, 2022 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-35727658

RESUMEN

ABSTRACT: Clinical T4b oral squamous cell carcinoma is traditionally considered nonoperable. We present a case of right mandibular squamous cell carcinoma (PT4bN0M0, stage IVB). The tumor had extended to the right mandibular condylar head and masticatory space. The patient received right modified radical neck dissection and radical operation with hemimandibulectomy to remove the right mandibular condyle. Then, we reconstructed the resected portion with an anterior lateral thigh free flap and bridging plate, which was bent to form an artificial condyle and fixed using the modified Dautrey procedure. The patient had stable postoperative occlusion and normal hinge movement of the temporomandibular joint. After postoperative concurrent chemotherapy and radiotherapy, the patient is under regular out patient department follow-up with satisfactory jaw function and oral intake.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de la Boca , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Humanos , Cóndilo Mandibular/cirugía , Osteotomía Mandibular , Prótesis Mandibular , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/cirugía
20.
BMC Oral Health ; 22(1): 284, 2022 07 12.
Artículo en Inglés | MEDLINE | ID: mdl-35820884

RESUMEN

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) is rapidly changed medical habits, and dental clinics have been forced to adapt. This study explored the pandemic-induced changes in patient utilization of dental services to assist practitioners in responding efficiently to similar public crises as references in the future. METHODS: We retrospectively analyzed the correlation between patient profiles and dental visits attendance within 2 months before and during the outbreak. RESULTS: A total of 332 patients, 210 women and 122 men (total number of visits: 1068) were enrolled in this study. A significantly lower attendance rate was noted during the COVID-19 period (70.3%) than prior to the pandemic (83.4%). The rate of return visits for patients with a high education level during the COVID-19 period was significantly reduced from 96.5 to 93.1%. In addition, the number of days between two visits significantly increased during the pandemic. CONCLUSIONS: Our results indicate that, during the pandemic period, the attendance rates of return dental appointments decreased, and the rate of missed appointments for patients with a high educational levels was higher than that of patients with a low educational level. CLINICAL RELEVANCE: Preventive management of these patients who are easy to miss dental appointments may enable more effective use of medical resources.


Asunto(s)
COVID-19 , Pandemias , Citas y Horarios , Femenino , Humanos , Masculino , Cooperación del Paciente , Estudios Retrospectivos
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