Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 68
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Nat Prod Rep ; 41(2): 208-227, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-37294301

RESUMEN

Covering: 2008 to 2023This review will describe oxidative phenol coupling as applied in the total synthesis of natural products. This review covers catalytic and electrochemical methods with a brief comparison to stoichiometric and enzymatic systems assessing their practicality, atom economy, and other measures. Natural products forged by C-C and C-O oxidative phenol couplings as well as from alkenyl phenol couplings will be addressed. Additionally, exploration into catalytic oxidative coupling of phenols and other related species (carbazoles, indoles, aryl ethers, etc.) will be surveyed. Future directions of this particular area of research will also be assessed.


Asunto(s)
Productos Biológicos , Fenol , Acoplamiento Oxidativo , Fenoles , Estrés Oxidativo
2.
Am J Pathol ; 193(12): 1900-1909, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37673331

RESUMEN

The gut microbiota was initially thought to develop into a stable, adult-like profile during early postnatal life. The formation of the gut microbiota during early life has been shown to contribute to healthy growth and has lifelong implications for host health. Adolescence, the developmental period between childhood and adulthood, is a critical window for healthy growth and maturation. The composition of the gut microbiota in adolescents is distinct from that of children and adults, which supports the premise that the gut microbiota continues to develop during adolescence toward an adult-like profile. Research has begun to shift its focus from understanding the gut microbiome at the extremes of the life span to evaluating the importance of the gut microbiome during adolescence and its role in healthy development. This article provides an overview of adolescent development, host-microbiota interactions, and experimental models used to discern effects of gut microbiota on health and disease. Herein, the role of the gut microbiota is reviewed as it relates to adolescent: i) brain development, cognition, and behavior; ii) metabolism and adiposity; and iii) skeletal growth and bone mass accrual. Future directions are addressed, including omics investigations defining mechanisms through which the gut microbiota influences adolescent development. Furthermore, we discuss advancing noninvasive interventions targeting the adolescent gut microbiota that could be employed to support healthy growth and maturation.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Niño , Adulto , Adolescente , Humanos , Cognición , Longevidad , Obesidad
3.
Am J Pathol ; 193(6): 796-812, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36906264

RESUMEN

Antibiotic administration during early life has been shown to have lasting effects on the gut microbiota, which have been linked to sustained alterations in liver metabolism and adiposity. Recent investigations have discerned that the gut microbiota continues to develop toward an adult-like profile during adolescence. However, the impact of antibiotic exposure during adolescence on metabolism and adiposity is unclear. Herein, a retrospective analysis of Medicaid claims data was performed, which indicated that tetracycline class antibiotics are commonly prescribed for the systemic treatment of adolescent acne. The purpose of this was to discern the impact of a prolonged tetracycline antibiotic exposure during adolescence on the gut microbiota, liver metabolism, and adiposity. Male C57BL/6T specific pathogen-free mice were administered a tetracycline antibiotic during the pubertal/postpubertal adolescent growth phase. Groups were euthanized at different time points to assess immediate and sustained antibiotic treatment effects. Antibiotic exposure during adolescence caused lasting genera-level shifts in the intestinal bacteriome and persistent dysregulation of metabolic pathways in the liver. Dysregulated hepatic metabolism was linked to sustained disruption of the intestinal farnesoid X receptor-fibroblast growth factor 15 axis, a gut-liver endocrine axis that supports metabolic homeostasis. Antibiotic exposure during adolescence increased subcutaneous, visceral, and marrow adiposity, which intriguingly manifested following antibiotic therapy. This preclinical work highlights that prolonged antibiotic courses for the clinical treatment of adolescent acne may have unintended deleterious effects on liver metabolism and adiposity.


Asunto(s)
Adiposidad , Antibacterianos , Masculino , Ratones , Animales , Antibacterianos/efectos adversos , Estudios Retrospectivos , Ratones Endogámicos C57BL , Obesidad/metabolismo , Hígado/metabolismo , Tetraciclinas/metabolismo
4.
J Org Chem ; 89(5): 3419-3429, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38365194

RESUMEN

Herein, we describe a dual photocatalytic system to synthesize phenol-pyridinium salts using visible light. Utilizing both electron donor-acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C-N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (SNAr) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol-pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.

5.
PLoS Comput Biol ; 18(8): e1010397, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35921268

RESUMEN

The National Institutes of Health (NIH) Policy for Data Management and Sharing (DMS Policy) recognizes the NIH's role as a key steward of United States biomedical research and information and seeks to enhance that stewardship through systematic recommendations for the preservation and sharing of research data generated by funded projects. The policy is effective as of January 2023. The recommendations include a requirement for the submission of a Data Management and Sharing Plan (DMSP) with funding applications, and while no strict template was provided, the NIH has released supplemental draft guidance on elements to consider when developing a plan. This article provides 10 key recommendations for creating a DMSP that is both maximally compliant and effective.


Asunto(s)
Investigación Biomédica , Manejo de Datos , National Institutes of Health (U.S.) , Estados Unidos
6.
J Clin Periodontol ; 50(12): 1670-1684, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37667415

RESUMEN

AIM: Antimicrobial-induced shifts in commensal oral microbiota can dysregulate helper T-cell oral immunity to affect osteoclast-osteoblast actions in alveolar bone. Antibiotic prophylaxis is commonly performed with dental implant placement surgery to prevent post-surgical complications. However, antibiotic prophylaxis effects on osteoimmune processes supporting dental implant osseointegration are unknown. The aim of the study was to discern the impact of antibiotic prophylaxis on dental implant placement surgery-induced osteoimmune wound healing and osseointegration. MATERIALS AND METHODS: We performed SHAM or dental implant placement surgery in mice. Groups were administered prophylactic antibiotics (amoxicillin or clindamycin) or vehicle. Gingival bacteriome was assessed via 16S sequencing. Helper T-cell oral immunity was evaluated by flow cytometry. Osteoclasts and osteoblasts were assessed via histomorphometry. Implant osseointegration was evaluated by micro-computed tomography. RESULTS: Dental implant placement surgery up-regulated TH 1, TH 2 and TREG cells in cervical lymph nodes (CLNs), which infers helper T-cell oral immunity contributes to dental implant placement osseous wound healing. Prophylactic antibiotics with dental implant placement surgery caused a bacterial dysbiosis, suppressed TH 1, TH 2 and TREG cells in CLNs, reduced osteoclasts and osteoblasts lining peri-implant alveolar bone, and attenuated the alveolar bone-implant interface. CONCLUSIONS: Antibiotic prophylaxis dysregulates dental implant placement surgery-induced osteoimmune wound healing and attenuates the alveolar bone-implant interface in mice.


Asunto(s)
Implantes Dentales , Animales , Ratones , Profilaxis Antibiótica , Interfase Hueso-Implante , Microtomografía por Rayos X , Implantación Dental Endoósea/métodos , Oseointegración/fisiología , Cicatrización de Heridas/fisiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico
7.
BMC Palliat Care ; 22(1): 85, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37393250

RESUMEN

BACKGROUND: Clinical trial participation for patients with non-curative cancer is unlikely to present personal clinical benefit, which raises the bar for informed consent. Previous work demonstrates that decisions by patients in this setting are made within a 'trusting relationship' with healthcare professionals. The current study aimed to further illuminate the nuances of this relationship from both the patients' and healthcare professionals' perspectives. METHODS: Face-to-face interviews using a grounded theory approach were conducted at a regional Cancer Centre in the United Kingdom. Interviews were performed with 34 participants (patients with non-curative cancer, number (n) = 16; healthcare professionals involved in the consent process, n = 18). Data analysis was performed after each interview using open, selective, and theoretical coding. RESULTS: The 'Trusting relationship' with healthcare professionals underpinned patient motivation to participate, with many patients 'feeling lucky' and articulating an unrealistic hope that a clinical trial could provide a cure. Patients adopted the attitude of 'What the doctor thinks is best' and placed significant trust in healthcare professionals, focusing on mainly positive aspects of the information provided. Healthcare professionals recognised that trial information was not received neutrally by patients, with some expressing concerns that patients would consent to 'please' them. This raises the question: Within the trusting relationship between patients and healthcare professionals, 'Is it possible to provide balanced information?'. The theoretical model identified in this study is central to understanding how the trusting professional-patient relationship influences the decision-making process. CONCLUSION: The significant trust placed on healthcare professionals by patients presented an obstacle to delivering balanced trial information, with patients sometimes participating to please the 'experts'. In this high-stakes scenario, it may be pertinent to consider strategies, such as separation of the clinician-researcher roles and enabling patients to articulate their care priorities and preferences within the informed consent process. Further research is needed to expand on these ethical conundrums and ensure patient choice and autonomy in trial participation are prioritised, particularly when the patient's life is limited.


Asunto(s)
Neoplasias , Confianza , Humanos , Teoría Fundamentada , Personal de Salud , Consentimiento Informado , Relaciones Profesional-Paciente , Ensayos Clínicos como Asunto
8.
Lab Invest ; 102(4): 363-375, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34934182

RESUMEN

The alveolar bone is a unique osseous tissue due to the presence of the teeth and the proximity of commensal oral microbes. Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal gut microbes is unknown. Study purpose was to elucidate whether commensal gut microbes regulate osteoimmune mechanisms and skeletal homeostasis in alveolar bone. Male C57BL/6T germfree (GF) littermate mice were maintained as GF or monoassociated with segmented filamentous bacteria (SFB), a commensal gut bacterium. SFB has been shown to elicit broad immune response effects, including the induction of TH17/IL17A immunity, which impacts the development and homeostasis of host tissues. SFB colonized the gut, but not oral cavity, and increased IL17A levels in the ileum and serum. SFB had catabolic effects on alveolar bone and non-oral skeletal sites, which was attributed to enhanced osteoclastogenesis. The alveolar bone marrow of SFB vs. GF mice had increased dendritic cells, activated helper T-cells, TH1 cells, TH17 cells, and upregulated Tnf. Primary osteoblast cultures from SFB and GF mice were stimulated with vehicle-control, IL17A, or TNF to elucidate osteoblast-derived signaling factors contributing to the pro-osteoclastic phenotype in SFB mice. Treatment of RAW264.7 osteoclastic cells with supernatants from vehicle-stimulated SFB vs. GF osteoblasts recapitulated the osteoclast phenotype found in vivo. Supernatants from TNF-stimulated osteoblasts normalized RAW264.7 osteoclast endpoints across SFB and GF cultures, which was dependent on the induction of CXCL1 and CCL2. This report reveals that commensal gut microbes have the capacity to regulate osteoimmune processes in alveolar bone. Outcomes from this investigation challenge the current paradigm that alveolar bone health and homeostasis is strictly regulated by oral microbes.


Asunto(s)
Huesos , Osteoclastos , Animales , Bacterias , Homeostasis , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos/metabolismo , Células Th17
9.
FASEB J ; 35(11): e22015, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34699641

RESUMEN

Periodontitis-mediated alveolar bone loss is caused by dysbiotic shifts in the commensal oral microbiota that upregulate proinflammatory osteoimmune responses. The study purpose was to determine whether antimicrobial-induced disruption of the commensal microbiota has deleterious effects on alveolar bone. We administered an antibiotic cocktail, minocycline, or vehicle-control to sex-matched C57BL/6T mice from age 6- to 12 weeks. Antibiotic cocktail and minocycline had catabolic effects on alveolar bone in specific-pathogen-free (SPF) mice. We then administered minocycline or vehicle-control to male mice reared under SPF and germ-free conditions, and we subjected minocycline-treated SPF mice to chlorhexidine oral antiseptic rinses. Alveolar bone loss was greater in vehicle-treated SPF versus germ-free mice, demonstrating that the commensal microbiota drives naturally occurring alveolar bone loss. Minocycline- versus vehicle-treated germ-free mice had similar alveolar bone loss outcomes, implying that antimicrobial-driven alveolar bone loss is microbiota dependent. Minocycline induced phylum-level shifts in the oral bacteriome and exacerbated naturally occurring alveolar bone loss in SPF mice. Chlorhexidine further disrupted the oral bacteriome and worsened alveolar bone loss in minocycline-treated SPF mice, validating that antimicrobial-induced oral dysbiosis has deleterious effects on alveolar bone. Minocycline enhanced osteoclast size and interface with alveolar bone in SPF mice. Neutrophils and plasmacytoid dendritic cells were upregulated in cervical lymph nodes of minocycline-treated SPF mice. Paralleling the upregulated proinflammatory innate immune cells, minocycline therapy increased TH 1 and TH 17 cells that have known pro-osteoclastic actions in the alveolar bone. This report reveals that antimicrobial perturbation of the commensal microbiota induces a proinflammatory oral dysbiotic state that exacerbates naturally occurring alveolar bone loss.


Asunto(s)
Pérdida de Hueso Alveolar/microbiología , Antibacterianos/efectos adversos , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Interacciones Microbiota-Huesped , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL
10.
Palliat Med ; 36(7): 1118-1128, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35729767

RESUMEN

BACKGROUND: Cardiac Cachexia is a wasting syndrome that has a significant impact on patient mortality and quality of life world-wide, although it is poorly understood in clinical practice. AIM: Identify the prevalence of cardiac cachexia in patients with advanced New York Heart Association (NYHA) functional class and explore its impact on patients and caregivers. DESIGN: An exploratory cross-sectional study. The sequential approach had two phases, with phase 1 including 200 patients with NYHA III-IV heart failure assessed for characteristics of cardiac cachexia. Phase 2 focussed on semi-structured interviews with eight cachectic patients and five caregivers to ascertain the impact of the syndrome. SETTING/PARTICIPANTS: Two healthcare trusts within the United Kingdom. RESULTS: Cardiac Cachexia was identified in 30 out of 200 participants, giving a prevalence rate of 15%. People with cachexia had a significantly reduced average weight and anthropometric measures (p < 0.05). Furthermore, individuals with cachexia experienced significantly more fatigue, had greater issues with diet and appetite, reduced physical wellbeing and overall reduced quality of life. C-reactive protein was significantly increased, whilst albumin and red blood cell count were significantly decreased in the cachectic group (p < 0.05). From qualitative data, four key themes were identified: (1) 'Changed relationship with food and eating', (2) 'Not me in the mirror', (3) 'Lack of understanding regarding cachexia' and (4) 'Uncertainty regarding the future'. CONCLUSIONS: Cardiac cachexia has a debilitating effect on patients and caregivers. Future work should focus on establishing a specific definition and clinical pathway to enhance patient and caregiver support.


Asunto(s)
Caquexia , Insuficiencia Cardíaca , Caquexia/epidemiología , Caquexia/etiología , Cuidadores , Estudios Transversales , Insuficiencia Cardíaca/complicaciones , Humanos , Prevalencia , Calidad de Vida
11.
BMC Palliat Care ; 19(1): 166, 2020 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-33126874

RESUMEN

BACKGROUND: Clinical cancer research trials may offer little or no direct clinical benefit to participants where a cure is no longer possible. As such, the decision-making and consent process for patient participation is often challenging. AIM: To gain understanding of how patients make decisions regarding clinical trial participation, from the perspective of both the patient and healthcare professionals involved. METHODS: In-depth, face to face interviews using a grounded theory approach. This study was conducted in a regional Cancer Centre in the United Kingdom. Of the 36 interviews, 16 were conducted with patients with cancer that had non-curative intent and 18 with healthcare professionals involved in the consent process. RESULTS: 'Nothing to lose' was identified as the core category that underpinned all other data within the study. This highlighted the desperation articulated by participants, who asserted trial participation was the 'only hope in the room'. The decision regarding participation was taken within a 'trusting relationship' that was important to both patients and professionals. Both were united in their 'fight against cancer'. These two categories are critical in understanding the decision-making/consent process and are supported by other themes presented in the theoretical model. CONCLUSION: This study presents an important insight into the complex and ethically contentious situation of consent in clinical trials that have non-curative intent. It confirms that patients with limited options trust their doctor and frequently hold unrealistic hopes for personal benefit. It highlights a need for further research to develop a more robust and context appropriate consent process.


Asunto(s)
Personal de Salud/psicología , Consentimiento Informado/normas , Pacientes/psicología , Adulto , Toma de Decisiones , Femenino , Teoría Fundamentada , Personal de Salud/estadística & datos numéricos , Humanos , Consentimiento Informado/estadística & datos numéricos , Entrevistas como Asunto/métodos , Masculino , Oncología Médica/instrumentación , Oncología Médica/métodos , Persona de Mediana Edad , Pacientes/estadística & datos numéricos , Investigación Cualitativa , Investigación/normas , Investigación/estadística & datos numéricos , Reino Unido
13.
Eur Heart J Suppl ; 21(Suppl L): L32-L35, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31885511

RESUMEN

Heart failure (HF) professionals are managing an older population with multiple, often interconnected comorbidities. The average age of the HF patient has increased substantially and many have a number of comorbidities. For the older HF patient, diligent planning of care has the potential to reduce hospitalization, improve quality of life and mortality; nevertheless, this vital component is often overlooked. Frailty, cachexia, sarcopenia, and cognitive impairment are all common in the older HF patient and require special care considerations. Many older HF patients live for many years with troublesome symptoms that could be better addressed through the incorporation of a palliative approach to care. Effective care plans can help patients maximize their health potential through both lifestyle and pharmacological interventions. However, current evidence remains scarce on what constitutes an optimal plan, therefore further studies are urgently needed. We review the care that could be implemented for the complex older HF patient with comorbidities.

14.
BMC Palliat Care ; 18(1): 82, 2019 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-31630685

RESUMEN

BACKGROUND: Cachexia is a complex and multifactorial syndrome defined as severe weight loss and muscle wasting which frequently goes unrecognised in clinical practice [1]. It is a debilitating syndrome, resulting in patients experiencing decreased quality of life and an increased risk of premature death; with cancer cachexia alone resulting in 2 million deaths per annum [2]. Most work in this field has focused on cancer cachexia, with cardiac cachexia being relatively understudied - despite its potential prevalence and impact in patients who have advanced heart failure. We report here the protocol for an exploratory study which will: 1. focus on determining the prevalence and clinical implications of cardiac cachexia within advanced heart failure patients; and 2. explore the experience of cachexia from patients' and caregivers' perspectives. METHODS: A mixed methods cross-sectional study. Phase 1: A purposive sample of 362 patients with moderate to severe heart failure from two Trusts within the United Kingdom will be assessed for known characteristics of cachexia (loss of weight, loss of muscle, muscle mass/strength, anorexia, fatigue and selected biomarkers), through basic measurements (i.e. mid-upper arm circumference) and use of three validated questionnaires; focusing on fatigue, quality of life and appetite. Phase 2: Qualitative semi-structured interviews with patients (n = 12) that meet criteria for cachexia, and their caregivers (n = 12), will explore their experience of this syndrome and its impact on daily life. Interviews will be digitally recorded and transcribed verbatim, prior to qualitative thematic and content analysis. Phase 3: Workshops with key stakeholders (patients, caregivers, healthcare professionals and policy makers) will be used to discuss study findings and identify practice implications to be tested in further research. DISCUSSION: Data collected as part of this study will allow the prevalence of cardiac cachexia in a group of patients with moderate to severe heart failure to be determined. It will also provide a unique insight into the implications and personal experience of cardiac cachexia for both patients and carers. It is hoped that robust quantitative data and rich qualitative perspectives will promote crucial clinical discussions on implications for practice, including targeted interventions to improve patients' quality of life where appropriate.


Asunto(s)
Caquexia/psicología , Corazón/fisiopatología , Prevalencia , Caquexia/epidemiología , Protocolos Clínicos , Estudios Transversales , Corazón/crecimiento & desarrollo , Humanos , Entrevistas como Asunto/métodos , Investigación Cualitativa , Calidad de Vida/psicología , Reino Unido/epidemiología
15.
Cells Tissues Organs ; 206(1-2): 106-118, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30677765

RESUMEN

Polyphenols are known for their antimicrobial activity, whilst both polyphenols and the globular protein ß-lactoglobulin (bLG) are suggested to have antioxidant properties and promote cell proliferation. These are potentially useful properties for a tissue-engineered construct, though it is unknown if they are retained when both compounds are used in combination. In this study, a range of different microbes and an osteoblast-like cell line (human fetal osteoblast, hFOB) were used to assess the combined effect of: (1) green tea extract (GTE), rich in the polyphenol epigallocatechin gallate (EGCG), and (2) whey protein isolate (WPI), rich in bLG. It was shown that approximately 20-48% of the EGCG in GTE reacted with WPI. GTE inhibited the growth of Gram-positive bacteria, an effect which was potentiated by the addition of WPI. GTE alone also significantly inhibited the growth of hFOB cells after 1, 4, and 7 days of culture. Alternatively, WPI significantly promoted hFOB cell growth in the absence of GTE and attenuated the effect of GTE at low concentrations (64 µg/mL) after 4 and 7 days. Low concentrations of WPI (50 µg/mL) also promoted the expression of the early osteogenic marker alkaline phosphatase (ALP) by hFOB cells, whereas GTE inhibited ALP activity. Therefore, the antioxidant effects of GTE can be boosted by WPI, but GTE is not suitable to be used as part of a tissue-engineered construct due to its cytotoxic effects which negate any positive effect WPI has on cell proliferation.


Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Osteogénesis/efectos de los fármacos , Polifenoles/farmacología , Té/química , Proteína de Suero de Leche/farmacología , Adulto , Antibacterianos/química , Antioxidantes/química , Bacterias/efectos de los fármacos , Catequina/análogos & derivados , Catequina/química , Catequina/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Masculino , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Polifenoles/química , Proteína de Suero de Leche/química , Adulto Joven
16.
Mar Drugs ; 16(9)2018 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-30231464

RESUMEN

Marine organisms represent a highly diverse reserve of bioactives which could aid in the treatment of a wide range of diseases, including various musculoskeletal conditions. Osteoporosis in particular would benefit from a novel and effective marine-based treatment, due to its large disease burden and the inefficiencies of current treatment options. Osteogenic bioactives have been isolated from many marine organisms, including nacre powder derived from molluscan shells and fucoidan-the sulphated polysaccharide commonly sourced from brown macroalgae. Such extracts and compounds are known to have a range of osteogenic effects, including stimulation of osteoblast activity and mineralisation, as well as suppression of osteoclast resorption. This review describes currently known soluble osteogenic extracts and compounds from marine invertebrates and algae, and assesses their preclinical potential.


Asunto(s)
Organismos Acuáticos/metabolismo , Factores Biológicos/farmacología , Desarrollo Óseo/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Animales , Factores Biológicos/aislamiento & purificación , Factores Biológicos/metabolismo , Calcificación Fisiológica/efectos de los fármacos , Conservación de los Recursos Naturales , Humanos , Moluscos/metabolismo , Nácar/aislamiento & purificación , Nácar/metabolismo , Nácar/farmacología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Polisacáridos/aislamiento & purificación , Polisacáridos/metabolismo , Polisacáridos/farmacología , Algas Marinas/metabolismo , Cicatrización de Heridas/efectos de los fármacos
17.
Bioorg Med Chem Lett ; 24(15): 3459-63, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24974344

RESUMEN

Modulation of the vitamin D receptor (VDR) with a ligand has the potential to be useful for the oral treatment of osteoporosis. One component of our lead generation strategy to identify synthetic ligands for VDR included a fragment based drug design approach. Screening of ligands in a VDR fluorescence polarization assay and a RXR/VDR conformation sensing assay resulted in the identification of multiple fragment hits (lean >0.30). These fragment scaffolds were subsequently evaluated for interaction with the VDR ligand binding domain using hydrogen-deuterium exchange (HDX) mass spectrometry. Significant protection of H/D exchange was observed for some fragments in helixes 3, 7, and 8 of the ligand binding domain, regions which are similar to those seen for the natural hormone VD3. The fragments appear to mimic the A-ring of VD3 thereby providing viable starting points for synthetic expansion.


Asunto(s)
Medición de Intercambio de Deuterio , Compuestos Orgánicos/farmacología , Receptores de Calcitriol/metabolismo , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ligandos , Espectrometría de Masas , Modelos Moleculares , Estructura Molecular , Compuestos Orgánicos/química , Relación Estructura-Actividad
18.
BMC Bioinformatics ; 14: 227, 2013 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-23865838

RESUMEN

BACKGROUND: Identification of transcription factor binding sites (also called 'motif discovery') in DNA sequences is a basic step in understanding genetic regulation. Although many successful programs have been developed, the problem is far from being solved on account of diversity in gene expression/regulation and the low specificity of binding sites. State-of-the-art algorithms have their own constraints (e.g., high time or space complexity for finding long motifs, low precision in identification of weak motifs, or the OOPS constraint: one occurrence of the motif instance per sequence) which limit their scope of application. RESULTS: In this paper, we present a novel and fast algorithm we call TFBSGroup. It is based on community detection from a graph and is used to discover long and weak (l,d) motifs under the ZOMOPS constraint (zero, one or multiple occurrence(s) of the motif instance(s) per sequence), where l is the length of a motif and d is the maximum number of mutations between a motif instance and the motif itself. Firstly, TFBSGroup transforms the (l, d) motif search in sequences to focus on the discovery of dense subgraphs within a graph. It identifies these subgraphs using a fast community detection method for obtaining coarse-grained candidate motifs. Next, it greedily refines these candidate motifs towards the true motif within their own communities. Empirical studies on synthetic (l, d) samples have shown that TFBSGroup is very efficient (e.g., it can find true (18, 6), (24, 8) motifs within 30 seconds). More importantly, the algorithm has succeeded in rapidly identifying motifs in a large data set of prokaryotic promoters generated from the Escherichia coli database RegulonDB. The algorithm has also accurately identified motifs in ChIP-seq data sets for 12 mouse transcription factors involved in ES cell pluripotency and self-renewal. CONCLUSIONS: Our novel heuristic algorithm, TFBSGroup, is able to quickly identify nearly exact matches for long and weak (l, d) motifs in DNA sequences under the ZOMOPS constraint. It is also capable of finding motifs in real applications. The source code for TFBSGroup can be obtained from http://bioinformatics.bioengr.uic.edu/TFBSGroup/.


Asunto(s)
Algoritmos , Regiones Promotoras Genéticas , Análisis de Secuencia de ADN/métodos , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , ADN/química , Escherichia coli K12/genética , Escherichia coli K12/metabolismo , Ratones , Motivos de Nucleótidos
19.
Learn Health Syst ; 7(2): e10339, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37066097

RESUMEN

Introduction: Enterprise data warehouses (EDWs) serve as foundational infrastructure in a modern learning health system, housing clinical and other system-wide data and making it available for research, strategic, and quality improvement purposes. Building on a longstanding partnership between Northwestern University's Galter Health Sciences Library and the Northwestern Medicine Enterprise Data Warehouse (NMEDW), an end-to-end clinical research data management (cRDM) program was created to enhance clinical data workforce capacity and further expand related library-based services for the campus. Methods: The training program covers topics such as clinical database architecture, clinical coding standards, and translation of research questions into queries for proper data extraction. Here we describe this program, including partners and motivations, technical and social components, integration of FAIR principles into clinical data research workflows, and the long-term implications for this work to serve as a blueprint of best practice workflows for clinical research to support library and EDW partnerships at other institutions. Results: This training program has enhanced the partnership between our institution's health sciences library and clinical data warehouse to provide support services for researchers, resulting in more efficient training workflows. Through instruction on best practices for preserving and sharing outputs, researchers are given the tools to improve the reproducibility and reusability of their work, which has positive effects for the researchers as well as for the university. All training resources have been made publicly available so that those who support this critical need at other institutions can build on our efforts. Conclusions: Library-based partnerships to support training and consultation offer an important vehicle for clinical data science capacity building in learning health systems. The cRDM program launched by Galter Library and the NMEDW is an example of this type of partnership and builds on a strong foundation of past collaboration, expanding the scope of clinical data support services and training on campus.

20.
J Biomed Opt ; 28(9): 094802, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36911164

RESUMEN

Significance: The scanning fiber endoscope (SFE), an ultrasmall optical imaging device with a large field-of-view (FOV) for having a clear forward view into the interior of blood vessels, has great potential in the cardiovascular disease diagnosis and surgery assistance, which is one of the key applications for short-wave infrared biomedical imaging. The state-of-the-art SFE system uses a miniaturized refractive spherical lens doublet for beam projection. A metalens is a promising alternative that can be made much thinner and has fewer off-axis aberrations than its refractive counterpart. Aim: We demonstrate a transmissive metalens working at 1310 nm for a forward viewing endoscope to achieve a shorter device length and better resolution at large field angles. Approach: We optimize the metalens of the SFE system using Zemax, fabricate it using e-beam lithography, characterize its optical performances, and compare them with the simulations. Results: The SFE system has a resolution of ∼ 140 µ m at the center of field (imaging distance 15 mm), an FOV of ∼ 70 deg , and a depth-of-focus of ∼ 15 mm , which are comparable with a state-of-the-art refractive lens SFE. The use of the metalens reduces the length of the optical track from 1.2 to 0.86 mm. The resolution of our metalens-based SFE drops by less than a factor of 2 at the edge of the FOV, whereas the refractive lens counterpart has a ∼ 3 times resolution degradation. Conclusions: These results show the promise of integrating a metalens into an endoscope for device minimization and optical performance improvement.


Asunto(s)
Cristalino , Lentes , Endoscopía Gastrointestinal , Cintigrafía , Refracción Ocular
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA