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1.
Huan Jing Ke Xue ; 45(6): 3142-3152, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897738

RESUMO

Groundwater contaminants pose a great threat to water safety and human health. Therefore, in this study, the traditional hazard assessment method was improved and a comprehensive system covering hazard assessment, screening, and characterization by combining the toxicological priority index (Tox Pi) framework; absorption, distribution, metabolism, and excretory (ADME) analysis; and bipartite network analysis was constructed. Then, the system was applied to hazard assessment and toxic pollutants screening from the 234 hydrophobic organic contaminants (HOCs) identified in the groundwater of Beijing. First, the top 20 pollutants with hazard potential were screened out using the Tox Pi method. Subsequently, 17 high-priority HOCs were further identified based on the ADME property analysis. Then, the molecular targets of these 17 high-priority HOCs were characterized through systematic bipartite network analysis. Finally, ten HOCs with high hazard were screened through correlation and weighted average analysis, and it was revealed that their toxic effects were mainly concentrated in the endocrine-disrupting effect, carcinogenic effect, and genetic toxicity. This study provides technical support for the prevention of regional groundwater contaminants.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Água Subterrânea/análise , Monitoramento Ambiental/métodos , Pequim , Substâncias Perigosas/análise , Compostos Orgânicos/análise , Medição de Risco
2.
Anal Sci ; 40(6): 1203-1207, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38443591

RESUMO

We present an optimization of Reverse NOE-pumping (RNP) in order to observe the 1H signals of ligands bound to proteins. Although various ligand-based NMR screening methods have been proposed, the most frequently used method has been Saturation-Transfer Difference (STD), owing to the relatively easy setup of experiments. Yet the critical point of STD is the selective irradiation of protein without irradiating ligand, and thus the STD technique is unable to observe 1H ligand signals, which resonate across the entire 1H spectral width. In the present study, the RNP experiment has been improved to develop an effective NMR-based screening technique. The optimized RNP spectra reveal less subtraction artifacts and phase distortion than the original RNP spectra, indicating its applicability to any type of ligand molecules.

3.
Curr Gene Ther ; 24(3): 193-207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38310456

RESUMO

With the discovery of CRISPR-Cas9, drug development and precision medicine have undergone a major change. This review article looks at the new ways that CRISPR-based therapies are being used and how they are changing the way medicine is done. CRISPR technology's ability to precisely and flexibly edit genes has opened up new ways to find, validate, and develop drug targets. Also, it has made way for personalized gene therapies, precise gene editing, and advanced screening techniques, all of which hold great promise for treating a wide range of diseases. In this article, we look at the latest research and clinical trials that show how CRISPR could be used to treat genetic diseases, cancer, infectious diseases, and other hard-to-treat conditions. However, ethical issues and problems with regulations are also discussed in relation to CRISPR-based therapies, which shows how important it is to use them safely and responsibly. As CRISPR continues to change how drugs are made and used, this review shines a light on the amazing things that have been done and what the future might hold in this rapidly changing field.


Assuntos
Sistemas CRISPR-Cas , Desenvolvimento de Medicamentos , Medicina de Precisão , Humanos , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Edição de Genes/métodos , Terapia Genética/métodos , Neoplasias/terapia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Medicina de Precisão/métodos
4.
ACS Appl Mater Interfaces ; 15(38): 44621-44630, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37721709

RESUMO

Membrane-active molecules are of great importance to drug delivery and antimicrobials applications. While the ability to prototype new membrane-active molecules has improved greatly with the advent of automated chemistries and rapid biomolecule expression techniques, testing methods are still limited by throughput, cost, and modularity. Existing methods suffer from feasibility constraints of working with pathogenic living cells and by intrinsic limitations of model systems. Herein, we demonstrate an abiotic sensor that uses semiconducting single-walled carbon nanotubes (SWCNTs) as near-infrared fluorescent transducers to report membrane interactions. This sensor is composed of SWCNTs aqueously suspended in lipid, creating a cylindrical, bilayer corona; these SWCNT probes are very sensitive to solvent access (changes in permittivity) and thus report morphological changes to the lipid corona by modulation of fluorescent signals, where binding and disruption are reported as brightening and attenuation, respectively. This mechanism is first demonstrated with chemical and physical membrane-disruptive agents, including ethanol and sodium dodecyl sulfate, and application of electrical pulses. Known cell-penetrating and antimicrobial peptides are then used to demonstrate how the dynamic response of these sensors can be deconvoluted to evaluate different parallel mechanisms of interaction. Last, SWCNTs functionalized in several different bacterial lipopolysaccharides (Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli) are used to evaluate a panel of known membrane-disrupting antimicrobials to demonstrate that drug selectivity can be assessed by suspension of SWCNTs with different membrane materials.

5.
Front Oncol ; 13: 993540, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36895474

RESUMO

Breast cancer is the leading cause of cancer in women with a huge medical, social and economic impact. Mammography (MMG) has been the gold standard method until now because it is relatively inexpensive and widely available. However, MMG suffers from certain limitations, such as exposure to X-rays and difficulty of interpretation in dense breasts. Among other imaging methods, MRI has clearly the highest sensitivity and specificity, and breast MRI is the gold standard for the investigation and management of suspicious lesions revealed by MMG. Despite this performance, MRI, which does not rely on X-rays, is not used for screening except for a well-defined category of women at risk, because of its high cost and limited availability. In addition, the standard approach to breast MRI relies on Dynamic Contrast Enhanced (DCE) MRI with the injection of Gadolinium based contrast agents (GBCA), which have their own contraindications and can lead to deposit of gadolinium in tissues, including the brain, when examinations are repeated. On the other hand, diffusion MRI of breast, which provides information on tissue microstructure and tumor perfusion without the use of contrast agents, has been shown to offer higher specificity than DCE MRI with similar sensitivity, superior to MMG. Diffusion MRI thus appears to be a promising alternative approach to breast cancer screening, with the primary goal of eliminating with a very high probability the existence of a life-threatening lesion. To achieve this goal, it is first necessary to standardize the protocols for acquisition and analysis of diffusion MRI data, which have been found to vary largely in the literature. Second, the accessibility and cost-effectiveness of MRI examinations must be significantly improved, which may become possible with the development of dedicated low-field MRI units for breast cancer screening. In this article, we will first review the principles and current status of diffusion MRI, comparing its clinical performance with MMG and DCE MRI. We will then look at how breast diffusion MRI could be implemented and standardized to optimize accuracy of results. Finally, we will discuss how a dedicated, low-cost prototype of breast MRI system could be implemented and introduced to the healthcare market.

6.
Eur J Ophthalmol ; 32(5): 2532-2546, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35313744

RESUMO

PURPOSE: To quantify the false positive rates for keratoconus (KC) and potential ectatic corneal conditions in highly astigmatism eyes when using published parameters/indices obtained from the Pentacam and Galilei units. SETTING: Oftalmosalud Instituto de Ojos, Lima, Peru. DESIGN: Prospective cohort study. METHODS: 67 consecutive eyes with corneal astigmatism > 1.5 D, with a minimum follow ups of 36 months after an uneventful LASIK procedure were included. Indices for KC and other potential ectatic corneal conditions (subclinical KC, forme fruste KC, suspect KC) were obtained using the Pentacam and Galilei Scheimpflug cameras. MAIN OUTCOME MEASURES: The false positive rates for KC and potential ectatic corneal conditions were measured. Cut off values provided by previous studies and company-based parameters were used to assess the rate of false positivity. RESULTS: The range of false positive rates for a KC diagnosis depending on the lowest and highest cutoff values were: index of height decentration (61% - 1%), index of surface variance (76% - 0%), Posterior elevation (55% - 0%), maximum Ambrosio Relational thickness (100% - 13%), Belin Ambrosio enhanced ectasia display total deviation value (100% - 4%), Average pachymetric progression index (69% - 3%), Pachymetry at the thinnest point (58% - 1%), CSI Center Surround Index (100%), Differential sector index (51%). CONCLUSION: The false positive rates for KC and ectatic corneal conditions vary dramatically depending on the cut-off values used. Some indexes used for diagnosis of potential ectatic corneal conditions are inaccurate in normal, highly astigmatic eyes.


Assuntos
Astigmatismo , Ceratocone , Córnea , Paquimetria Corneana , Topografia da Córnea/métodos , Dilatação Patológica/diagnóstico , Humanos , Ceratocone/diagnóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Tecnologia
7.
Am J Otolaryngol ; 43(2): 103302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34894446

RESUMO

PURPOSE: We aim to investigate the true benefits of free individual HNC screening in a high-risk urban population as well as the associated risks. MATERIALS AND METHODS: This is a retrospective descriptive study. Free HNC screening was performed from 2014 to 2019. Participants were issued a questionnaire at the time of screening. After exemption by the Institutional Review Board, completed screening questionnaires were entered into a database and descriptive statistics were generated. The primary outcome measure for this study was the detection rate for HNC. We hypothesized that screening would be low yield based on previous studies (Gogarty et al., 2016). RESULTS: This was a volunteer sample with a total of 410 participants, and the highest yield screening year was 2019 (n = 187). For all years, the cancer detection rate was 0%. In 2019, 134 (77.9%) of participants did not recognize the early symptoms of HNC, and 120 (73.2%) reported the screening program increased their awareness of the disease. 13 (7.6%) reported HPV vaccination while 126 (71.2%) were unaware that HPV has been linked with head and neck cancer. CONCLUSIONS: HNC screening is an excellent opportunity for education regarding HNC risk factors. However, it is not a cost-effective use of physician time, does not increase detection rates even in high-risk segments of the general population, and is not completely without risk in the context of COVID-19. Perhaps the focus of HNC screening should shift from individualized screening to education and health promotion.


Assuntos
COVID-19 , Neoplasias de Cabeça e Pescoço , COVID-19/epidemiologia , COVID-19/prevenção & controle , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Programas de Rastreamento , Estudos Retrospectivos , SARS-CoV-2
8.
Viruses ; 13(3)2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807824

RESUMO

The Human Immunodeficiency Virus type 1 (HIV-1) virion contains a conical shell, termed capsid, encasing the viral RNA genome. After cellular entry of the virion, the capsid is released and ensures the protection and delivery of the HIV-1 genome to the host nucleus for integration. The capsid relies on many virus-host factor interactions which are regulated spatiotemporally throughout the course of infection. In this paper, we will review the current understanding of the highly dynamic HIV-1 capsid-host interplay during the early stages of viral replication, namely intracellular capsid trafficking after viral fusion, nuclear import, uncoating, and integration of the viral genome into host chromatin. Conventional anti-retroviral therapies primarily target HIV-1 enzymes. Insights of capsid structure have resulted in a first-in-class, long-acting capsid-targeting inhibitor, GS-6207 (Lenacapavir). This inhibitor binds at the interface between capsid protein subunits, a site known to bind host factors, interferes with capsid nuclear import, HIV particle assembly, and ordered assembly. Our review will highlight capsid structure, the host factors that interact with capsid, and high-throughput screening techniques, specifically genomic and proteomic approaches, that have been and can be used to identify host factors that interact with capsid. Better structural and mechanistic insights into the capsid-host factor interactions will significantly inform the understanding of HIV-1 pathogenesis and the development of capsid-centric antiretroviral therapeutics.


Assuntos
Proteínas do Capsídeo/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Vírion/imunologia , Humanos , Desenvelopamento do Vírus
9.
Syst Rev ; 10(1): 108, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33849664

RESUMO

BACKGROUND: Globally, cancer is generally recognized as a developmental threat yet most countries in Africa lack capacity to diagnose cancer especially gynecological cancers resulting in late detection and poor outcomes. However, most studies on gynecological cancers in Africa tend to focus on cervical cancer compared to the other gynecological cancers. Therefore, this scoping review will aim to describe the existing literature on the epidemiological burden of ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in Africa to identify priority research gaps for further research to inform health policy decisions. METHODS: The framework promulgated by Arksey and O'Malley and improved by Levac et al. will be used as a guide for this scoping review. A comprehensive search for relevant published studies in PubMed, CINAHL, SCOPUS, Google Scholar, and ScienceDirect with no date limitation to the last search date. The database search strategy will include keywords, Boolean operators, and medical subject heading terms. We will additionally consult the WHO/IARC website, IHME/Global Burden of Disease Study. A snowball approach will also be used to search the reference list of all included studies to obtain relevant papers for possible inclusion in this review. We will include articles that involve African countries, focused on ovarian, endometrial, vaginal, and vulva cancers, their risk factors, and potential screening methods/techniques in any language. We will exclude studies on cervical cancer and other cancers as well as review articles. The abstracts and full-text selection will be conducted by two independent reviewers using this review's eligibility criteria as a guide. All the review selection tools, and the data extraction form will be pilot tested for accuracy and consistency. The data will be organized into thematic areas, summarized and the results communicated narratively. DISCUSSION: It is anticipated that this review will reveal important literature gaps to guide future research to inform health policy decisions about ovarian, endometrial, and rare gynecological neoplasms in Africa. This review's findings will be disseminated via peer review journals, conferences, and other social media such Twitter and LinkedIn.


Assuntos
Neoplasias Vulvares , África/epidemiologia , Feminino , Humanos , Pesquisa , Literatura de Revisão como Assunto , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologia
10.
Risk Manag Healthc Policy ; 13: 1499-1512, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982508

RESUMO

INTRODUCTION: Colorectal cancer (CRC) is a significant health problem with an increasing incidence worldwide. Screening is one of the ways, in which cases and deaths of CRC can be prevented. The objective of this systematic review was to evaluate the cost-effectiveness of the different CRC screening techniques and to specify the efficient technique from a cost-effectiveness perspective. METHODS: The economic studies of CRC screening in general populations (average risk), aged 50 years and above were reviewed. Two reviewers independently reviewed the titles, abstracts, and full-texts of the studies in five databases: Cochrane, Embase, Scopus, Web of Science and PubMed. The disagreements between reviewers were resolved through the authors' consensus. The main outcome measures in this systematic review were the incremental cost-effectiveness ratio (ICER) of screening versus no-screening and then in comparison with other screening techniques. The ICER is defined by the difference in cost between two possible interventions, divided by the difference in their effect. RESULTS: Eight studies were identified and retained for the final analysis. In this study, when screening techniques were compared to no-screening, all CRC screening techniques showed to be cost-effective. The lowest ICER calculated was $PPP -16265/quality-adjusted life-year (QALY) (the negative ICERs were between purchasing power parity in US dollar ($PPP) -16265/QALY to $PPP -1988/QALY, whereas the positive ICERs were between $PPP 1257/QALY to $PPP 55987/QALY). For studies comparing various screening techniques, there was great heterogeneity in terms of the structures of the analyses, leading to diverse conclusions about their incremental cost-effectiveness. CONCLUSION: All CRC screening techniques were cost-effective, compared with the no-screening methods. The cost-effectiveness of the various screening techniques mainly was dependent on the context-specific parameters and highly affected by the framework of the cost-effectiveness analysis. In order to make the studies comparable, it is important to adopt a reference-based methodology for economic evaluation studies.

11.
Euphytica ; 216(6): 88, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32587414

RESUMO

Cowpea (Vigna unguiculata (L. Walp) is an important grain legume for human and livestock nutrition, especially in sub-Saharan Africa. Aphid, Aphis craccivora Koch (Homoptera: Aphididae), is one of the most widespread and destructive insect pests of cowpea and host-plant resistance is an effective approach to minimize the pest damage at seedling stage. This study was aimed at identifying resistant sources to A. craccivora within the cowpea mini core collection, a set of accessions from the largest world cowpea germplasm collection maintained at the International Institute of Tropical Agriculture (IITA). A total of 375 lines including 373 from IITA mini core collection, one resistant (TVu-801) and one susceptible (TVx-3236) checks were evaluated through artificial infestation in screening cages during the seedling stage. In cages, genotypes were planted in single rows containing four plants. They were arranged in an augmented design in which the two checks were sown in individual cages. Scoring for aphid population and damage levels were carried out on individual plants at 7, 14, and 21 days after planting. Advanced bioassays and biochemical analyses were conducted to investigate the mechanism of resistance to A. craccivora. Overall, three genotypes TVu-6464, TVu-1583, and TVu-15445 showed good levels of resistance comparable to the resistant check TVu-801. The HPLC analyses proved that both low sucrose levels in the plant, as well as high levels of kaempferol and quercetin, aglycones of phenolic compounds, were related with high resistance to aphids. The above genotypes with promising levels of resistance to A. craccivora will be used in cowpea breeding programs to develop improved resistant lines against this pest.

12.
Biochem Soc Trans ; 48(1): 271-280, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31985743

RESUMO

Fragment-based drug discovery (FBDD) has become a mainstream technology for the identification of chemical hit matter in drug discovery programs. To date, the food and drug administration has approved four drugs, and over forty compounds are in clinical studies that can trace their origins to a fragment-based screen. The challenges associated with implementing an FBDD approach are many and diverse, ranging from the library design to developing methods for identifying weak affinity compounds. In this article, we give an overview of current progress in fragment library design, fragment to lead optimisation and on the advancement in techniques used for screening. Finally, we will comment on the future opportunities and challenges in this field.


Assuntos
Desenho de Fármacos , Descoberta de Drogas/métodos , Descoberta de Drogas/tendências , Bibliotecas de Moléculas Pequenas/química , Cristalografia por Raios X , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Ensaios de Triagem em Larga Escala/tendências , Humanos , Espectroscopia de Ressonância Magnética , Ligação Proteica
13.
Anal Chim Acta ; 1072: 61-74, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31146866

RESUMO

In the recent years, the number of commercial products containing engineered nanomaterials (ENMs) has increased exponentially. Consequently, the toxicological profile of ENMs on the ecosystems as well as on human health has to be carefully evaluated. Nanotoxicology, an interdisciplinary research area devoted to assessing the hazards associated with ENMs, is expanding rapidly. Many physicochemical techniques and biochemical methodologies have been proposed and are currently used to characterize nanomaterials from a toxicological point of view. Electroanalytical and bioelectrochemical methods can be useful in expanding the repertoire of accessible nanotoxicity-assessment technologies and to accelerate the testing and screening of the toxicological effects of ENMs. These methods can be used for elucidating the toxicological behavior of ENMs at single cell, cell population and whole-organism levels, for in vitro and in vivo measurements, respectively. The aim of this review is to provide an overview on the bioelectrochemical approaches that have been proposed for ENMs toxicity assessment. Furthermore, an overview on cutting-edge electroanalytical devices with a potential impact to this peculiar application is provided.


Assuntos
Técnicas Eletroquímicas , Nanoestruturas , Nanotecnologia , Animais , Humanos , Nanoestruturas/efeitos adversos , Nanoestruturas/análise , Nanoestruturas/toxicidade
14.
Methods Mol Biol ; 1966: 175-192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31041747

RESUMO

Nuclear receptors act as ligand-activated transcription factors translating ligand signals into changes in gene expression. The 48 members of the superfamily of nuclear receptors identified so far are involved amongst others in maintenance of metabolic balance, inflammation, and cancer. Thus, they hold enormous potential for drug discovery and some nuclear receptors are experiencing considerable academic and industrial interest. Nuclear receptor modulator discovery requires reliable, robust, and economic test systems that allow for high throughput. In this chapter, we discuss the principle, strengths, and advantages of hybrid reporter gene assays for nuclear receptor focused drug discovery and describe how they can be developed, established, and validated.


Assuntos
Bioensaio/métodos , Descoberta de Drogas/métodos , Genes Reporter , Receptores Citoplasmáticos e Nucleares/metabolismo , Linhagem Celular Transformada , Escherichia coli , Humanos , Ligantes
15.
Artigo em Inglês | MEDLINE | ID: mdl-30555254

RESUMO

Breast cancer is the most common cancer among women around the world. Despite enormous medical progress, breast cancer has still remained the second leading cause of death worldwide; thus, its early diagnosis has a significant impact on reducing mortality. However, it is often difficult to diagnose breast abnormalities. Different tools such as mammography, ultrasound, and thermography have been developed to screen breast cancer. In this way, the computer helps radiologists identify chest abnormalities more efficiently using image processing and artificial intelligence (AI) tools. This article examined various methods of AI using image processing to diagnose breast cancer. It was a review study through library and Internet searches. By searching the databases such as Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Springer, IEEE, ScienceDirect, and Gray Literature (including Google Scholar, articles published in conferences, government technical reports, and other materials not controlled by scientific publishers) and searching for breast cancer keywords, AI and medical image processing techniques were extracted. The results were provided in tables to demonstrate different techniques and their results over recent years. In this study, 18,651 articles were extracted from 2007 to 2017. Among them, those that used similar techniques and reported similar results were excluded and 40 articles were finally examined. Since each of the articles used image processing, a list of features related to the image used in each article was also provided. The results showed that support vector machines had the highest accuracy percentage for different types of images (ultrasound =95.85%, mammography =93.069%, thermography =100%). Computerized diagnosis of breast cancer has greatly contributed to the development of medicine, is constantly being used by radiologists, and is clear in ethical and medical fields with regard to its effects. Computer-assisted methods increase diagnosis accuracy by reducing false positives.

16.
Front Genet ; 9: 206, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29963073

RESUMO

Breast cancer is one of the most common invasive tumors causing high mortality among women. It is characterized by high heterogeneity regarding its biological and clinical characteristics. Several high-throughput assays have been used to collect genome-wide information for many patients in large collaborative studies. This knowledge has improved our understanding of its biology and led to new methods of diagnosing and treating the disease. In particular, system biology has become a valid approach to obtain better insights into breast cancer biological mechanisms. A crucial component of current research lies in identifying novel biomarkers that can be predictive for breast cancer patient prognosis on the basis of the molecular signature of the tumor sample. However, the high dimension and low sample size of data greatly increase the difficulty of cancer survival analysis demanding for the development of ad-hoc statistical methods. In this work, we propose novel screening-network methods that predict patient survival outcome by screening key survival-related genes and we assess the capability of the proposed approaches using METABRIC dataset. In particular, we first identify a subset of genes by using variable screening techniques on gene expression data. Then, we perform Cox regression analysis by incorporating network information associated with the selected subset of genes. The novelty of this work consists in the improved prediction of survival responses due to the different types of screenings (i.e., a biomedical-driven, data-driven and a combination of the two) before building the network-penalized model. Indeed, the combination of the two screening approaches allows us to use the available biological knowledge on breast cancer and complement it with additional information emerging from the data used for the analysis. Moreover, we also illustrate how to extend the proposed approaches to integrate an additional omic layer, such as copy number aberrations, and we show that such strategies can further improve our prediction capabilities. In conclusion, our approaches allow to discriminate patients in high-and low-risk groups using few potential biomarkers and therefore, can help clinicians to provide more precise prognoses and to facilitate the subsequent clinical management of patients at risk of disease.

17.
Biomed Pharmacother ; 87: 8-19, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28040600

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. Since CRC is largely asymptomatic until alarm features develop to advanced stages, the implementation of the screening programme is very much essential to reduce cancer incidence and mortality rates. CRC occurs predominantly from accumulation of genetic and epigenetic changes in colon epithelial cells, which later gets transformed into adenocarcinomas. SCOPE OF REVIEW: The current challenges of screening paradigm and diagnostic ranges are from semi-invasive methods like colonoscopy to non-invasive stool-based test, have resulted in over-diagnosis and over-treatment of CRC. Hence, new screening initiatives and deep studies are required for early diagnosis of CRC. In this regard, we not only summarise current predictive and prognostic biomarkers with their potential for diagnostic and therapeutic applications, but also describe current limitations, future perspectives and challenges associated with the progression of CRC. MAJOR CONCLUSIONS: Currently many potential biomarkers have already been successfully translated into clinical practice eg. Fecal haemoglobin, Carcinoembryonic antigen (CEA) and CA19.9, although these are not highly promising diagnostic target for personalized medicine. So there is a critical need for reliable, minimally invasive, highly sensitive and specific genetic markers of an individualised and optimised patient treatment at the earliest disease stage possible. GENERAL SIGNIFICANCE: Identification of a new biomarker, or a set of biomarkers to the development of a valid, and clinical sensible assay that can be served as an alternative tool for early diagnosis of CRC and open up promising new targets in therapeutic intervention strategies.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Animais , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Colonoscopia/tendências , Neoplasias Colorretais/genética , Epigênese Genética/fisiologia , Humanos , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
18.
Drug Deliv Transl Res ; 6(4): 426-39, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26419676

RESUMO

Nail disorders are beyond cosmetic concern; besides discomfort in the performance of daily chores, they disturb patients psychologically and affect their quality of life. Fungal nail infection (onychomycosis) is the most prevalent nail-related disorder affecting a major population worldwide. Overcoming the impenetrable nail barrier is the toughest challenge for the development of efficacious topical ungual formulation. Sophisticated techniques such as iontophoresis and photodynamic therapy have been proven to improve transungual permeation. This article provides an updated and concise discussion regarding the conventional approach and upcoming novel approaches focused to alter the nail barrier. A comprehensive description regarding preformulation screening techniques for the identification of potential ungual enhancers is also described in this review while highlighting the current pitfalls for the development of ungual delivery.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Unhas/metabolismo , Administração Tópica , Humanos
19.
Arch Toxicol ; 90(8): 1785-802, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26341667

RESUMO

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.


Assuntos
Biologia Computacional/métodos , Desenho de Fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Preparações Farmacêuticas , Toxicologia/métodos , Avaliação Pré-Clínica de Medicamentos , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade
20.
Expert Opin Drug Deliv ; 12(10): 1661-75, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26067386

RESUMO

INTRODUCTION: Pressurised metered dose inhalers (pMDIs) are subject to rigorous physical and chemical stability tests during formulation. Due to the time and cost associated with product development studies, there is a need for online techniques to fast screen new formulations in terms of physical and chemical (physico-chemical) stability. The problem with achieving this is that pMDIs are by their definition, pressurised, making the direct observation of physico-chemical properties in situ difficult. AREAS COVERED: This review highlights the characterisation tools that can enhance the product development process for pMDIs. Techniques investigated include: laser diffraction, Raman spectroscopy, isothermal ampoule calorimetry, titration calorimetry and gas perfusion calorimetry. The operational principles behind each technique are discussed and complemented with examples from the literature. EXPERT OPINION: Laser diffraction is well placed to analyse real-time physical stability as a function of particle size; however, its use is restricted to suspension pMDIs. Raman spectroscopy can be potentially used to attain both suspension and solution pMDI spectra in real time; however, the majority of experiments are ex-valve chemical composition mapping. Calorimetry is an effective technique in capturing both chemical and physical degradations of APIs in real time but requires redevelopment to withstand pressure for the purposes of pMDI screening.


Assuntos
Estabilidade de Medicamentos , Inaladores Dosimetrados , Preparações Farmacêuticas/química , Animais , Varredura Diferencial de Calorimetria , Química Farmacêutica , Humanos , Tamanho da Partícula , Análise Espectral Raman , Suspensões
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