RESUMO
Bryophytes have historically been employed as verdant medicine in China, Native America and India. Phenolics, glycosides, fatty acids, other rare aromatic compounds and Terpenoids found in bryophytes may help prevent cancer and other chronic disorders. Liverworts have historically been utilized in traditional medicine and also as immu-nomodulators or immunostimulants. Diterpenoids, Lipophilic mono-, sesqui- and aromatic compounds assisting to the biological activities of liverworts. For their biological functions more than 220 aromatic compounds and 700 terpenoids and other chemicals discovered in liverworts scrutinized for their pharmacological, cytotoxic, immunostimulant and auto-immune efficacies.
Assuntos
Antineoplásicos , Briófitas , Diterpenos , Hepatófitas , Humanos , Hepatófitas/química , Adjuvantes Imunológicos , Briófitas/química , Terpenos/química , Terpenos/farmacologiaRESUMO
Juvenile dermatomyositis (JDM) is associated with many distinguishing features including cutaneous calcinosis, vasculitis, and ulcerated lesions. In this case, we describe an unusual presentation in a 12-year-old girl who had muscle weakness along with linear morphea over the right upper and lower extremities with overlying lichen sclerosus and calcinosis cutis. Of interest, these initial cutaneous manifestations occurred years before onset of myositis.
Assuntos
Calcinose Cutânea , Calcinose , Dermatomiosite , Líquen Escleroso e Atrófico , Esclerodermia Localizada , Feminino , Humanos , Criança , Dermatomiosite/complicações , Dermatomiosite/patologia , Esclerodermia Localizada/complicações , Esclerodermia Localizada/patologia , Líquen Escleroso e Atrófico/complicações , Calcinose/complicações , Calcinose/patologiaRESUMO
Gastric cancer represents a deadly malignancy worldwide, yet current therapeutic regimens remain ineffective. Nanoparticle (NP) -based solutions could allow the design of novel therapeutic methods to eliminate this fatal disease. NPs typically carry out a significant role in multifunctional, multimodal imaging, and drug delivery carriers. In the recent decade, they have emerged as candidate approaches for the design of novel treatment strategies. Tumor nanotherapeutics characteristically possess various distinct advantages compared to conventional anti-cancer medications, which suffer from nonspecific bio-distribution, low solubility, and poor bioavailability. In this review, we will discuss the application of NPs in diagnosis and controlled drug delivery in gastric cancer (GC). We will focus on various NPs-based strategies employed against GC.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Imagem Multimodal/métodos , Nanopartículas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Animais , Disponibilidade Biológica , Humanos , Nanopartículas/química , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologiaRESUMO
Colorectal cancer (CRC) is one of the deadliest diseases worldwide due to a lack of early detection methods and appropriate drug delivery strategies. Conventional imaging techniques cannot accurately distinguish benign from malignant tissue, leading to frequent misdiagnosis or diagnosis at late stages of the disease. Novel screening tools with improved accuracy and diagnostic precision are thus required to reduce the mortality burden of this malignancy. Additionally, current therapeutic strategies, including radio- and chemotherapies carry adverse side effects and are limited by the development of drug resistance. Recent advances in nanotechnology have rendered it an attractive approach for designing novel clinical solutions for CRC. Nanoparticle-based formulations could assist early tumor detection and help to overcome the limitations of conventional therapies including poor aqueous solubility, nonspecific biodistribution and limited bioavailability. In this review, we shed light on various types of nanoparticles used for diagnosis and drug delivery in CRC. In addition, we will explore how these nanoparticles can improve diagnostic accuracy and promote selective drug targeting to tumor sites with increased efficiency and reduced cytotoxicity against healthy colon tissue.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Imagem Multimodal/métodos , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Animais , Neoplasias Colorretais/diagnóstico por imagem , Humanos , Nanopartículas/químicaRESUMO
Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide making it a serious global challenge. CRC progression results from dysregulated cytoplasmic transcription factors, including signal transducer and activator of transcription (STAT) proteins that are involved in JAK-STAT pathway. The STAT proteins contain a conserved SH2 domain that facilitates the initiation of STAT activation via binding to tyrosine motifs followed by STAT dimerization. The STAT proteins include STAT1, STAT2 and STAT3 which all facilitate therapeutic targets for many drugs, since they are associated with pathogenesis in various cancers such as CRC. Genistein is an efficient chemopreventive phytochemical drug against CRC. The current investigation presents a computational study performed to investigate the molecular interaction between STAT1, STAT2 and STAT3 proteins with genistein. The molecular dynamic simulation was conducted for STAT2 protein. The studies from molecular docking revealed that the interaction of STAT proteins and genistein is predicted to be effective with better binding energies. Furthermore, targeting STAT3 could be an efficient therapeutic target and understanding the interaction between STAT3 and genistein can help to contribute to a better inhibition process for CRC progression. Treatment with genistein led to significant suppression of cell proliferation and STAT3 protein expression in both CRC (HCT 116 and HT-29) cell lines. This further provides development of efficient STAT inhibitors with better potency and bioavailability.
Assuntos
Neoplasias Colorretais/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT2/metabolismo , Fator de Transcrição STAT3/metabolismo , Sítios de Ligação , Proliferação de Células , Neoplasias Colorretais/genética , Biologia Computacional , Genisteína/farmacologia , Células HCT116 , Células HT29 , Humanos , Inflamação , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Domínios Proteicos , Processamento de Proteína Pós-Traducional , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT2/genética , Fator de Transcrição STAT3/genética , Transdução de SinaisRESUMO
Hypoxia-inducible factor-1 alpha (HIF-1α) has been recognized as one of the essential regulators that is expressed in greater levels in pancreatic cancer (PC) and is connected with poor prognosis. Resveratrol was identified as a natural compound with many biological functions, with anti-inflammatory, antioxidant, and anticancer effects that inhibit the proliferation and progression of PC cells caused by HIF-1α. The current investigation explored the binding affinity and ligand efficacy of resveratrol against HIF-1α using an in silico approach, and the execution of molecular dynamics simulation (MDS) increased the prediction precision of these outcomes. This is the first study that provides an in silico characterization of the interaction between resveratrol and HIF-1α and its spatial structural arrangements in pancreatic cancer therapy, providing an in-depth analysis of their drug target interactions.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Resveratrol/farmacologia , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Estilbenos/farmacologia , Neoplasias PancreáticasRESUMO
Raf-1 kinase inhibitory protein (RKIP) acts as a tumor cell metastasis suppressor and prognostic indicator for survival in various cancers. Its use is predicted to improve therapy for various malignancies, including colorectal cancer (CRC). RKIP, frequently denoted as phosphatidylethanolamine-binding protein 1, is expressed in all normal mammalian tissues. RKIP functions as an inhibitor of the Raf-1, PI-3K, and MAP kinase (MAPK) pathways. In this study, we found that resveratrol induced the expression of RKIP at protein levels. To elucidate the structural basis of the interaction between resveratrol and RKIP, we performed computational studies that explore the binding affinity and ligand efficacy of resveratrol against RKIP. This study reveals the prognostic significance of RKIP metastasis suppressor activity against CRC and its structural arrangements during drug-target interactions.
Assuntos
Antioxidantes/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Resveratrol/farmacologia , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Humanos , Proteína de Ligação a Fosfatidiletanolamina/química , Conformação Proteica , Células Tumorais CultivadasRESUMO
Protein-protein interactions (PPIs) are important biochemical processes that represent a major challenge in modern biology. Current approaches, which include high-throughput screening and computer aided ligand design, have limitations regarding the identification of hit matter. This current investigation focuses on computational study for protein-protein docking of hypoxia inducible factor-1α (HIF-1α), a tumor inducible factor, and Raf-1 kinase inhibitory protein (RKIP), a tumor metastasis suppressor. These are individually crystallized structures of interacting proteins, which interact to generate a conformational space. HIF activity in pancreatic tumors is determined by hypoxia and HIF-1α subunit availability. RKIP can be used as a prognostic indicator in a number of tumors. The interaction of RKIP with HIF-1α protects against pancreatic cancer (PC) metastasis by inhibiting its hypoxia function. We have explored the binding affinity between both the proteins with the HADDOCK (high ambiguity driven protein-protein docking) server, which determined that 158 structures in 11 clusters represent 79.0% of water-refined models. Of the best 10 clusters, the structures of cluster 2 were found to be better, as they had the lowest Z-score. Further supporting HIF-1α-RKIP interaction, pulldown assay has shown dissociation of RKIP from HIF-1α after CoCl2 treatment in both PC cell lines.
Assuntos
Biologia Computacional/métodos , Subunidade alfa do Fator 1 Induzível por Hipóxia/química , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Simulação de Acoplamento Molecular , Neoplasias Pancreáticas/patologia , Proteína de Ligação a Fosfatidiletanolamina/química , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Domínios e Motivos de Interação entre Proteínas , Cristalografia por Raios X , Humanos , Neoplasias Pancreáticas/metabolismo , Conformação ProteicaRESUMO
Autoimmune diseases occur when the body's natural defense system fails to differentiate its own cells from the foreign cells and mistakenly attacks the healthy cells. Among the autoimmune diseases, the most common serious disease is the type 1 diabetes (T1D). Biomarkers like c-peptide, autoantibodies, and glycated molecules are now widely used for the early diagnosis of diabetes. However, the diverse nature of biomarkers and the available autoantibodies as biomarkers are not enough to differentiate the heterogeneity inherent in T1D. Novel biomarkers have allowed the introduction of bioinformatics for assimilating the new data into clinical tools. Computer-aided drug design contributes to the discovery of novel autoantibodies, and molecular docking promises to enhance it. Moreover, the study of the pathophysiology of diabetes via molecular simulation has been proposed. In this review article, we focus on the characterization of the etiology, epidemiological factors, and mechanisms of hyperglycemia that induce cellular damage due to oxidative stress and proinflammatory responses. We also decribe novel biomarkers used for the detection of ß-cell destruction and diagnosis at early stages. Bioinformatics tools including molecular docking, sequence alignment, and homology modeling are also presented. This report supports researchers in drug design, in disease detection at an early phase, and in therapy development for T1D-associated complications.
Assuntos
Diabetes Mellitus Tipo 1/imunologia , Imunoterapia/tendências , Animais , Autoimunidade , Biomarcadores , Biologia Computacional , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Humanos , Terapia de Alvo MolecularRESUMO
The transcription factor NF-κB plays a central role in angiogenesis in colorectal cancer (CRC). Curcumin is a natural dietary product that inhibits NF-κB. The objective of this study is to evaluate the antiangiogenic effects of curcumin and two potent synthetic analogues (EF31 and UBS109) in CRC. IC50 values for curcumin, EF31, and UBS109 were determined in the HCT116 and HT-29 cell lines. HUVEC tube formation, egg CAM assay, and matrigel plug assays revealed decreased angiogenesis in cell lines treated with curcumin, EF31, or UBS109. Curcumin and its analogues significantly inhibited VEGF-A synthesis and secretion in both cell lines in association with loss of HIF-1α, COX-2, and p-STAT-3 expression. Nuclear NF-κB expression was inhibited by curcumin, EF31, and UBS109. Transfection of p65-NF-κB in HCT116 and HT-29 cells resulted in increased expression of HIF-1α, COX-2, STAT-3, and VEGF-A. Treatment with curcumin, EF31, or UBS109 inhibited these effects in transfected cell lines. In mice carrying HCT116 and HT-29 cell xenografts, EF31 and UBS109 inhibited subcutaneous tumor growth and potentiated the effects of oxaliplatin and 5-FU. Tumors from treated animals revealed inhibition of HIF-1α, COX-2, p-STAT-3, and VEGF expression. Our findings suggest that inhibition of NF-κB leading to decreased transcription and expression of HIF-1α, COX-2, STAT-3, and VEGF is a rational approach for antiangiogenic therapy in CRC. The distinctive properties of EF31 and UBS109 make them promising therapeutic agents for development in CRC as single agents or as part of combination chemotherapy regimens. © 2016 Wiley Periodicals, Inc.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Colo/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Curcumina/análogos & derivados , Neovascularização Patológica/tratamento farmacológico , Piperidonas/uso terapêutico , Piridinas/uso terapêutico , Reto/efeitos dos fármacos , Inibidores da Angiogênese/farmacologia , Animais , Galinhas , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Feminino , Células HCT116 , Células HT29 , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos Nus , NF-kappa B/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Piperidonas/farmacologia , Piridinas/farmacologia , Ratos , Reto/metabolismo , Reto/patologia , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoAssuntos
Linfoma Cutâneo de Células T , Linfoma de Células T , Paniculite , Neoplasias Cutâneas , Humanos , Linfoma Cutâneo de Células T/patologia , Metotrexato/uso terapêutico , Recidiva Local de Neoplasia , Paniculite/diagnóstico , Paniculite/tratamento farmacológico , Paniculite/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Colon and pancreatic cancers have high mortality rates due to early metastasis prior to the onset of symptoms. Screening tests for colorectal cancer are invasive and expensive. No effective screening is available for pancreatic cancer. Identification of biomarkers for early detection in both of these cancers is being extensively researched. MicroRNAs (miRNA) are small non-coding molecule biomarkers that regulate cancers. Measurement of miRNAs in pancreatic fluid or blood could be a preferred non-invasive screening method. The regulation of colon and pancreatic cancers by miRNA is complex. miRNA play a central role in inflammation, invasiveness, and tumor progression in these two cancers, as well as regulation of the NF-κB pathway. miRNA's evolving role in screening is also reviewed.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/terapia , Progressão da Doença , Perfilação da Expressão Gênica , Humanos , Inflamação , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Resultado do TratamentoRESUMO
Pancreatic cancer (PC), a disease with high heterogeneity and a dense stromal microenvironment, presents significant challenges and a bleak prognosis. Recent breakthroughs have illuminated the crucial interplay among RAS, epidermal growth factor receptor (EGFR), and hedgehog pathways in PC progression. Small molecular inhibitors have emerged as a potential solution with their advantages of oral administration and the ability to target intracellular and extracellular sites effectively. However, despite the US FDA approving over 100 small-molecule targeted antitumor drugs, challenges such as low response rates and drug resistance persist. This review delves into the possibility of using small molecules to treat persistent or spreading PC, highlighting the challenges and the urgent need for a diverse selection of inhibitors to develop more effective treatment strategies.
Assuntos
Antineoplásicos , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Resistencia a Medicamentos Antineoplásicos , Terapia de Alvo Molecular , Receptores ErbB/antagonistas & inibidores , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/metabolismo , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêuticoRESUMO
Background: Hirsutism is the presence of excessive terminal hair on androgen-dependent sites of the body. Lasers like Alexandrite, diode, and Nd:Yag lasers have been used for hair reduction with varying efficacy. Trichoscopy of hair is a simple noninvasive method of hair assessment. However, it has not been used in the assessment of diode laser hair reduction. Objectives: This study aimed to assess the efficacy and safety of diode laser hair reduction in skin color with the help of clinical and trichoscopic assessment. Materials and Methods: This prospective observational study included 73 patients of hirsutism recruited in 18-month period. All participants received sessions of 805 nm diode laser at monthly intervals up to six sessions. Clinical and trichoscopic evaluation along with photographs were obtained at each visit. Side effects, if any, were noted in every sitting. Results: All patients were females of Fitzpatrick skin types III-V. All clinical parameters showed statistically significant hair reduction when compared with baseline. Trichoscopic parameters of hair reduction like total hair count, terminal hair count, and terminal/vellus hair ratio showed reduction compared to baseline which was statistically significant (P < 0.05). The most common side effect noted in our study was pain followed by erythema and perifollicular edema. Conclusions: Diode laser is an effective and safe procedure for the reduction of unwanted facial hair, even in darker skin types. We also wish to emphasize that trichoscopy for the assessment of laser hair reduction is a recent, noninvasive, simple, and underutilized tool. No serious adverse events were noted in our study.