RESUMO
Drug affinity responsive target stability (DARTS) is a novel target discovery approach and is particularly adept at screening small molecule (SM) targets without requiring any structural modifications. The DARTS method is capable of revealing drug-target interactions from cells or tissues by tracking changes in the stability of proteins acting as receptors of bioactive SMs. Due to its simple operation and high efficiency, the DARTS method has been applied to uncover the drug-action mechanism. This review summarized analytical principles, protocols, validation approaches, applications, and challenges involved in the DARTS method. Due to the innate advantages of the DARTS method, it is expected to be a powerful tool to accelerate SM target discovery, especially for bioactive natural products with unknown mechanisms.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Descoberta de Drogas/métodos , Bibliotecas de Moléculas Pequenas/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/tendências , Descoberta de Drogas/tendências , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Estabilidade de Medicamentos , Humanos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Ligação Proteica/fisiologia , Bibliotecas de Moléculas Pequenas/metabolismoRESUMO
The annual output of salted duck egg white (SDEW) is estimated to be over 1.5 million tons in China, most of which is discarded due to high salt content. This has led to serious waste and environmental impact. Therefore, we developed an eco-friendly biocoagulation separation technology by combining chitosan and sodium alginate in order to produce a novel iron-binding peptide (DPs-Fe2+) from SDEW. The structure of DPs-Fe2+ was characterized by ultraviolet-visible spectroscopy, fluorescence spectroscopy, and Fourier transform infrared spectroscopy, followed by measuring DPs-Fe2+ response in a simulated digestion/Caco-2 cell model. Results showed that chitosan and sodium alginate complex could remove 91.21% of salt from SDEW, and the protein recovery rate reached 95.50%. Characterization results indicated that DPs bonded with Fe2+ to form a soluble chelate. Moreover, Caco-2 cell monolayer model indicated that the transport rate of Fe2+ was as high as 10.02% at 0.1 mg/ml concentration of digested chelates. The results demonstrate the potential application of DPs as a novel carrier for enhancing iron absorption. This research contributes to the development of an effective industrial desalination method and highlights an opportunity for recycling an otherwise discarded processing byproduct. PRACTICAL APPLICATION: Salted duck egg whites (SDEW) are the primary byproduct of salted egg yolk production, most of which is discarded due to high salt content. Hence, efficient utilization of the high-value proteins in SDEW is an urgent problem that must be resolved. Herein, we developed an effective industrial desalination method by combining chitosan and sodium alginate, which achieved excellent SDEW desalination and protein recovery. Furthermore, we produced a novel iron-binding peptide (DPs-Fe2+), which enhanced the transportation and absorption of Fe2+ in Caco-2 cell model, suggesting its potential as an iron supplement.
Assuntos
Patos , Clara de Ovo , Resíduos Industriais , Ferro , Peptídeos , Animais , Células CACO-2 , Sistemas de Liberação de Medicamentos/tendências , Clara de Ovo/química , Humanos , Resíduos Industriais/prevenção & controle , Ferro/química , Peptídeos/químicaRESUMO
Ferroptosis is a new mode of cell death different from cell necrosis, autophagy, apoptosis, and pyroptosis, which depends on the accumulation of reactive oxygen species (ROS) caused by iron-mediated lipid peroxidation, exhibits cellular, molecular, and gene-level characteristics distinct from other cell deaths. Since ferroptosis discovery, it has become a new target for antitumor therapy actively explored by researchers. In this review, we provide an overview of the known mechanisms that regulate the sensitivity of cancer cells to ferroptosis and the research progress of ferroptosis-related drugs (western medicine, traditional Chinese medicine, and nanomedicine), as well as the relationship between ferroptosis and cancer treatment, tumor drug resistance, and antitumor immunotherapy.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Sistemas de Liberação de Medicamentos/tendências , Resistencia a Medicamentos Antineoplásicos/fisiologia , Ferroptose/fisiologia , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Neoplasias/metabolismo , Piroptose/efeitos dos fármacos , Piroptose/fisiologia , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismoRESUMO
Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient's life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Receptor 4 Toll-Like/metabolismo , Injúria Renal Aguda/imunologia , Animais , Sistemas de Liberação de Medicamentos/tendências , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Glucocorticoides/administração & dosagem , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/imunologiaRESUMO
Alzheimer's disease (AD) is the most common neurodegenerative disease, and its incidence is increasing worldwide with increased lifespan. Currently, there is no effective treatment to cure or prevent the progression of AD, which indicates the need to develop novel therapeutic targets and agents. Sirtuins, especially SIRT3, a mitochondrial deacetylase, are NAD-dependent histone deacetylases involved in aging and longevity. Accumulating evidence indicates that SIRT3 dysfunction is strongly associated with pathologies of AD, hence, therapeutic modulation of SIRT3 activity may be a novel application to ameliorate the pathologies of AD. Natural products commonly used in traditional medicine have wide utility and appear to have therapeutic benefits for the treatment of neurodegenerative diseases such as AD. The present review summarizes the currently available natural SIRT3 activators and their potentially neuroprotective molecular mechanisms of action that make them a promising agent in the treatment and management of neurodegenerative diseases such as AD.
Assuntos
Doença de Alzheimer/enzimologia , Suplementos Nutricionais , Sistemas de Liberação de Medicamentos/métodos , Inibidores Enzimáticos/administração & dosagem , Neuroproteção/fisiologia , Sirtuína 3/metabolismo , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Doença de Alzheimer/dietoterapia , Doença de Alzheimer/tratamento farmacológico , Animais , Compostos de Bifenilo/administração & dosagem , Sistemas de Liberação de Medicamentos/tendências , Glucosídeos/administração & dosagem , Humanos , Hidrazinas/administração & dosagem , Indazóis/administração & dosagem , Lignanas/administração & dosagem , Neuroproteção/efeitos dos fármacos , Fenóis/administração & dosagem , Sirtuína 3/antagonistas & inibidoresRESUMO
Phytocompounds isolated from plants are well appraised for their broad pharmacological propensities in several pathologies. One key benefit of phytoconstituents is their relatively low toxicity and adverse effects. Nonetheless, poor solubility, permeation, and poor specificity at the target site tend to hinder its therapeutic efficacy. Hence, novel technologies for drug delivery systems are being developed via the use of various nanoformulation strategies to overcome these challenges and give uniform medication focusing at the dynamic site in desired concentration and improved therapeutic efficacy. Such approaches comprise of novel drug delivery systems (NDDS). The utilisation of herbal formulations for NDDS is more beneficial and advantageous as opposed to others. The utilisation of ethosome, liposome, emulsion, phytosomes, microsphere, and strong lipid nanoparticles of herbal formulation has improved the remedial impacts of plant extricates. With the utilisation of all these, directed delivery of the formulation is accomplished, because of which the formulation exhibits impact on the site, and its' bioavailability is, likewise, expanded. With these novel medication conveyance frameworks, the actives and concentrates, which are utilised as part of natural formulations, exhibit a sustained release, enhancement in stability, improved therapeutic efficacy, and protection from toxicity. The primary motivation behind creating alternative drug delivery technologies is to expand the effectiveness of drug conveyance and safety in the process and give more comfort to the patient. In this review, the importance of various phytocompounds in the delivery of drugs is highlighted as well as their importance in reducing the risk or diseases.
Assuntos
Sistemas de Liberação de Medicamentos/tendências , Fitoterapia , Extratos Vegetais/administração & dosagem , Humanos , Lipossomos/administração & dosagem , Nanopartículas/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
OBJECTIVES/HYPOTHESIS: Novel laryngotracheal wound coverage devices are limited by complex anatomy, smooth surfaces, and dynamic pressure changes and airflow during breathing. We hypothesize that a bioinspired mucoadhesive patch mimicking how geckos climb smooth surfaces will permit sutureless wound coverage and also allow drug delivery. STUDY DESIGN: ex-vivo. METHODS: Polycaprolactone (PCL) fibers were electrospun onto a substrate and polyethylene glycol (PEG) - acrylate flocks in varying densities were deposited to create a composite patch. Sample topography was assessed with laser profilometry, material stiffness with biaxial mechanical testing, and mucoadhesive testing determined cohesive material failure on porcine tracheal tissue. Degradation rate was measured over 21 days in vitro along with dexamethasone drug release profiles. Material handleability was evaluated via suture retention and in cadaveric larynges. RESULTS: Increased flocking density was inversely related to cohesive failure in mucoadhesive testing, with a flocking density of PCL-PEG-2XFLK increasing failure strength to 6880 ± 1810 Pa compared to 3028 ± 791 in PCL-PEG-4XFLK density and 1182 ± 262 in PCL-PEG-6XFLK density. The PCL-PEG-2XFLK specimens had a higher failure strength than PCL alone (1404 ± 545 Pa) or PCL-PEG (2732 ± 840). Flocking progressively reduced composite stiffness from 1347 ± 15 to 763 ± 21 N/m. Degradation increased from 12% at 7 days to 16% after 10 days and 20% after 21 days. Cumulative dexamethasone release at 0.4 mg/cm2 concentration was maintained over 21 days. Optimized PCL-PEG-2XFLK density flocked patches were easy to maneuver endoscopically in laryngeal evaluation. CONCLUSIONS: This novel, sutureless, patch is a mucoadhesive platform suitable to laryngeal and tracheal anatomy with drug delivery capability. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1958-1966, 2021.
Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Técnicas de Fechamento de Ferimentos/instrumentação , Cicatrização/efeitos dos fármacos , Animais , Materiais Biocompatíveis , Cadáver , Dexametasona/uso terapêutico , Sistemas de Liberação de Medicamentos/tendências , Avaliação Pré-Clínica de Medicamentos , Glucocorticoides/uso terapêutico , Humanos , Laringe/anatomia & histologia , Laringe/patologia , Preparações Farmacêuticas/administração & dosagem , Poliésteres/química , Polietilenoglicóis/química , Procedimentos Cirúrgicos sem Sutura/métodos , Suínos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Traqueia/anatomia & histologia , Traqueia/patologia , Cicatrização/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Triple-negative breast cancer (TNBC) has a poorer prognosis than other subtypes due to its strong invasion and higher risk of distant metastasis. Traditional Chinese medicine (TCM) and natural medicine have the unique advantages of multitargets and small side-effects and may be used as long-term complementary and alternative therapies. AIM OF THE REVIEW: The present article summarizes the classical signaling pathways and potential targets by the action of TCM and natural medicine (including extracts, active constituents and formulas) on TNBC and provides evidence for its clinical efficacy. METHODS: The literature information was acquired from the scientific databases PubMed, Web of Science and CNKI from January 2010 to June 2020, and it was designed to elucidate the internal mechanism and role of TCM and natural medicine in the treatment of TNBC. The search key words included "Triple negative breast cancer" or "triple negative breast carcinoma", "TNBC" and "traditional Chinese medicine" or "Chinese herbal medicine", "medicinal plant", "natural plant", and "herb". RESULTS: We described the antitumor activity of TCM and natural medicine in TNBC based on different signaling pathways. Plant medicine and herbal formulas regulated the related gene and protein expression via pathways such as PI3K/AKT/mTOR, MAPK and Wnt/ß-catenin, which inhibit the growth, proliferation, migration, invasion and metastasis of TNBC cells. CONCLUSION: The inhibitory effect of TCM and natural medicine on tumors was reflected in multiple levels and multiple pathways, providing reasonable evidence for new drug development. To make TCM and natural medicine widely and flexibly used in clinical practice, the efficacy, safety and mechanism of action need more in-depth experimental research.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Medicina Tradicional Chinesa/métodos , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/metabolismo , Produtos Biológicos/metabolismo , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/tendências , Feminino , Humanos , Medicina Tradicional Chinesa/tendências , Transdução de Sinais/fisiologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Inflammation is ubiquitous in the body, and uncontrolled inflammation often contributes to various diseases. Celastrol, a compound isolated from a Chinese medicinal herb, holds great potential in treating multiple inflammation-associated diseases. However, its further clinical use is limited by its poor solubility, bioavailability, and high organ toxicity. With the advancement of nanotechnology, the nano-delivery of celastrol can effectively improve its oral bioavailability, maximize its efficacy and minimize its side effects. Here, we summarize the roles of celastrol in the treatment of various inflammation-associated diseases, with a special emphasis on its role in modulating immune cell signaling or non-immune cell signaling within the inflammatory microenvironment, and we highlight the latest advances in nano-delivery strategies for celastrol to treat diseases associated with inflammation.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Mediadores da Inflamação/antagonistas & inibidores , Nanopartículas/administração & dosagem , Triterpenos/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos/tendências , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Triterpenos Pentacíclicos , Tripterygium , Triterpenos/química , Triterpenos/metabolismoRESUMO
In the past mitochondria were considered as the "powerhouse" of cell, since they generate more than 90% of ATP in aerobic conditions through the oxidative phosphorylation. However, based on the current knowledge, mitochondria play several other cellular functions, including participation in calcium homeostasis, generation of free radicals and oxidative species, triggering/regulation of apoptosis, among others. Additionally, previous discoveries recognized mitochondria as highly dynamic structures, which undergo morphological alterations resulting in long or short fragments inside the living cells. This highly regulated process was referred as mitochondrial dynamics and involves mitochondrial fusion and fission. Thus, the number of mitochondria and the morphology of mitochondrial networks depend on the mitochondrial dynamics, biogenesis, and mitophagy. In each cell, there is a delicate balance between fusion and fission to allow the maintenance of appropriate mitochondrial functions. It has been proposed that the fusion and fission dynamics process controls cell cycle, metabolism, and survival, being implicated in a wide range of physiological and pathological conditions. Mitochondrial fusion is mediated by dynamin-like proteins, including mitofusin 1 (MFN1), mitofusin 2 (MFN2), and optic atrophy 1 protein (OPA1). Conversely, mitochondrial fission results in a large number of small fragments, which is mediated mainly by dynamin-related protein 1 (DRP1). Interestingly, there is growing evidence proposing that tumor cells modify the mitochondrial dynamics rheostat in order to gain proliferative and survival advantages. Increased mitochondrial fission has been reported in several types of human cancer cells (melanoma, ovarian, breast, lung, thyroid, glioblastoma, and others) and some studies have reported a possible direct correlation between increased mitochondrial fusion and chemoresistance of tumor cells. Here, the current knowledge about alterations of mitochondrial dynamics in cancer will be reviewed and its potential as a target for adjuvant cancer chemotherapy will be discussed.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Mitocôndrias/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/metabolismo , Sistemas de Liberação de Medicamentos/tendências , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Dinâmica Mitocondrial/fisiologia , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Therapies of cancer are as diverse as multifaceted the cancer is. Anticancer drugs include, but not limited to synthetic, semisynthetic and natural drugs and monoclonal antibodies. A recent decline in new drug development has led to the rebirth of herbal therapeutics in the form of dietary supplements and botanical preparations. Medicinal plants comprise of complex phytochemicals due to vast biosynthetic capacity. A wide array of phytochemicals has been pharmacologically evaluated for their chemo-preventive and chemotherapeutic potential for several decades. These phytochemicals target cancer at diverse sites such as apoptotic pathways, genetic and epigenetic mutations, damage to deoxyribonucleic acid, production of reactive oxygen species, autophagy, invasion and metastasis of cancer cells, and modulation of cell signaling through Janus-activated kinase/Signal transducer and activator of transcription, Notch, mitogen-activated protein kinase/Extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/Protein kinase B/mammalian target of rapamycin, Nuclear factor kappa B, Wingless-related integration site and Transforming growth factor ß pathways. This review focuses on the therapeutic targets of anticancer and chemo-preventive phytochemicals and their mode of action.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Animais , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Produtos Biológicos/isolamento & purificação , Sistemas de Liberação de Medicamentos/tendências , Humanos , Neoplasias/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Transdução de Sinais/fisiologiaRESUMO
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks.
Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Imunossupressores/uso terapêutico , Nanopartículas/uso terapêutico , Administração Cutânea , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , HumanosRESUMO
Vitamins are a diverse group of "life nourishing" molecules that are essential for proper childhood development, and for maintaining health throughout adulthood into old age. Vitamin supplementation is an important strategy for reducing the severe and chronic effects of malnutrition in subsets of the population of the developing world. Additionally, the precise role of many vitamins in certain conditions, including cancer and cardiovascular disease, remains an area of active research, although guidelines for vitamin supplementation in otherwise adequately nourished populations remain controversial. This review describes vitamin delivery methods and techniques, focusing on the most recent advances and novel approaches. Specific attention has been given to physical methods and novel formulations for delivery with an emphasis on reporting pros and cons of each technique and highlighting future directions. Of particular interest is the potential for transdermal delivery of certain vitamins, which is an approach that may provide advantages in some populations (e.g. for vitamin D), but that still requires considerable additional research and clinical validation.
Assuntos
Suplementos Nutricionais , Sistemas de Liberação de Medicamentos/tendências , Vitaminas/administração & dosagem , Animais , Humanos , Desnutrição/epidemiologia , Desnutrição/prevenção & controleRESUMO
NSAIDs may prevent Alzheimer's disease (AD) but have failed as a treatment, possibly because only 1-2% of an oral NSAID dose reaches the brain. This minuscule dose is enough to have a preventative effect on Alzheimer's disease but not to treat it. We propose a new route of administration for drugs to treat AD: transspinal delivery by transdermal patch over the back-of-neck/cervical spine. The drug would diffuse from the patch through the intervertebral spaces, penetrate the dura, enter the CSF, and reach the brain. For example, diclofenac from a transdermal patch over the back of neck should readily penetrate the dura mater to reach the CSF and brain; since the analgesic ziconotide, and antisense molecules for treating spinal muscular atrophy in children and Huntington's disease, are delivered intrathecally and readily enter the brain. In addition to NSAIDs, an anticancer drug, paclitaxel, has considerable potential as an AD treatment. Paclitaxel is administered IV. But the blood-brain penetration of paclitaxel is poor and paclitaxel has systemic side effects such as anemia, leukopenia, peripheral neuropathy, etc. A high dose of paclitaxel might be administered to the brain by transdermal patch over the back of the neck/cervical spine while avoiding the systemic side effects. A transdermal patch over the cervical spine could revolutionize the drug therapy of AD, and probably other neurodegenerative/neuropsychiatric diseases as well.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Sistemas de Liberação de Medicamentos/tendências , Adesivo Transdérmico , Administração Cutânea , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dorso , Diclofenaco/administração & dosagem , Vias de Administração de Medicamentos , Humanos , Pescoço , Neoplasias/tratamento farmacológicoRESUMO
The technique of delivering various nutrients, supplements, immunostimulants, vaccines, and drugs via the in ovo route is gaining wide attention among researchers worldwide for boosting production performance, immunity and safeguarding the health of poultry. It involves direct administration of the nutrients and biologics into poultry eggs during the incubation period and before the chicks hatch out. In ovo delivery of nutrients has been found to be more effective than post-hatch administration in poultry production. The supplementation of feed additives, nutrients, hormones, probiotics, prebiotics, or their combination via in ovo techniques has shown diverse advantages for poultry products, such as improved growth performance and feed conversion efficiency, optimum development of the gastrointestinal tract, enhancing carcass yield, decreased embryo mortality, and enhanced immunity of poultry. In ovo delivery of vaccination has yielded a better response against various poultry pathogens than vaccination after hatch. So, this review has aimed to provide an insight on in ovo technology and its potential applications in poultry production to deliver different nutrients, supplements, beneficial microbes, vaccines, and drugs directly into the developing embryo to achieve an improvement in post-hatch growth, immunity, and health of poultry. © 2019 Society of Chemical Industry.
Assuntos
Suplementos Nutricionais/análise , Sistemas de Liberação de Medicamentos/veterinária , Preparações Farmacêuticas/administração & dosagem , Doenças das Aves Domésticas/prevenção & controle , Vacinas/administração & dosagem , Animais , Galinhas , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Doenças das Aves Domésticas/imunologiaRESUMO
Traditional Chinese Medicine (TCM) has been used in China for thousands of years for the prevention and treatment of various diseases. The materials that exert a therapeutic effect are called the active ingredients. The bioactive glycosides are important active ingredients from TCM that can make significant contributions to treating diseases. Because of the possibilities of various clinical applications, the properties and administration of these bioactive glycosides deserve further investigation. Their promising treatment effects, however, are hindered by their poor solubility, poor stability and rapid elimination. Therefore, it is necessary that we improve the therapeutic efficacy of bioactive glycosides by overcoming these problems. Meanwhile, some practical design strategies and novel drug delivery vehicles based on drug delivery systems provide favorable support in clinical practice for these active ingredients. This review summarizes diverse pharmacological activities of bioactive glycosides and focuses on recent advances in delivery system for these active constitutes; in particular, some glycol glycosides can effectively cure intractable diseases through targeted drug delivery. This review elucidates some design strategies for drug delivery system that are mainly based on two methods (avoiding physical barriers by changing dosage forms and enhancing the ability to bind to receptors or proteins after administration) and indicate the current challenges during the combination of delivery vehicles and these glycosides in hopes of promoting the process of receiving ideal therapeutic efficacy of them in future studies.
Assuntos
Sistemas de Liberação de Medicamentos/tendências , Medicamentos de Ervas Chinesas/química , Glicosídeos , Formas de Dosagem , Desenho de Fármacos , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Glicosídeos/farmacocinética , Glicosídeos/farmacologia , Humanos , Medicina Tradicional ChinesaRESUMO
Despite remarkable advances in medical science, infection-associated diseases remain among the leading causes of death worldwide. There is a great deal of interest and concern at the rate at which new pathogens are emerging and causing significant human health problems. Expanding our understanding of how cells regulate signaling networks to defend against invaders and retain cell homeostasis will reveal promising strategies against infection. It has taken scientists decades to appreciate that eukaryotic aminoacyl-tRNA synthetases (ARSs) play a role as global cell signaling mediators to regulate cell homeostasis, beyond their intrinsic function as protein synthesis enzymes. Recent discoveries revealed that ubiquitously expressed standby cytoplasmic ARSs sense and respond to danger signals and regulate immunity against infections, indicating their potential as therapeutic targets for infectious diseases. In this review, we discuss ARS-mediated anti-infectious signaling and the emerging role of ARSs in antimicrobial immunity. In contrast to their ability to defend against infection, host ARSs are inevitably co-opted by viruses for survival and propagation. We therefore provide a brief overview of the communication between viruses and the ARS system. Finally, we discuss encouraging new approaches to develop ARSs as therapeutics for infectious diseases.
Assuntos
Aminoacil-tRNA Sintetases/metabolismo , Antibacterianos/metabolismo , Antivirais/metabolismo , Doenças Transmissíveis/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Aminoacil-tRNA Sintetases/antagonistas & inibidores , Animais , Antibacterianos/administração & dosagem , Antivirais/administração & dosagem , Doenças Transmissíveis/tratamento farmacológico , Sistemas de Liberação de Medicamentos/tendências , Humanos , Testes de Sensibilidade Microbiana/métodos , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
Lumazine synthase (LS) is a family of enzyme involved in the penultimate step in the biosynthesis of riboflavin. Its enzymatic mechanism has been well defined, and many LS structures have been solved using X-ray crystallography or cryoelectron microscopy. LS is composed of homooligomers, which vary in size and subunit number, including pentamers, decamers, and icosahedral sixty-mers, depending on its species of origin. Research on LS has expanded beyond the initial focus on its enzymatic function to properties related to its oligomeric structure and exceptional conformational stability. These attributes of LS systems have now been repurposed for use in various biomedical fields. This review primarily focuses on the applications of LS as a flexible vaccine presentation system. Presentation of antigens on the surface of LS results in a high local concentration of antigens displayed in an ordered array. Such repetitive structures enable the cross-linking of B-cell receptors and result in strong immune responses through an avidity effect. Potential issues with the use of this system and corresponding solutions are also discussed with the objective of improved utilization of the LS system in vaccine development.
Assuntos
Sistemas de Liberação de Medicamentos/tendências , Complexos Multienzimáticos/administração & dosagem , Complexos Multienzimáticos/imunologia , Riboflavina Sintase/administração & dosagem , Riboflavina Sintase/imunologia , Animais , Sistemas de Liberação de Medicamentos/métodos , Humanos , Imunogenicidade da Vacina/imunologia , Complexos Multienzimáticos/química , Estrutura Secundária de Proteína , Riboflavina Sintase/químicaRESUMO
Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of ß-amyloid (Aß) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances. Approximately, 60%-80% of all cases of dementia in the world are patients with AD. In view of the continuous rise of this disease especially in the aged population, there is a dire need to come up with a novel compound and/or mixture that could work against this devastating disease. In this regard, the best is to rely on natural compounds rather than synthetic ones, because natural compounds are easily available, cost-effective, and comparatively less toxic. To serve this purpose, lately, scientific community has started exploring the possibility of using different polyphenols either solitary or in combination that can serve as therapeutics against AD. In the current article, we have summarized the role of various polyphenols, namely quercetin, resveratrol, curcumin, gallocatechins, cinnamic acid, caffeine, and caffeic acid as an inhibitor of cholinesterase for the treatment of AD. We have also tried to uncover the mechanistic insight on the action of these polyphenols against AD pathogenicity.