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1.
Curr Genomics ; 20(7): 469-482, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32655286

RESUMO

BACKGROUND: Low Birth Weight (LBW) (birth weight <2.5 Kg) newborns are associated with a high risk of infection, morbidity and mortality during their perinatal period. Compromised innate immune responses and inefficient hematopoietic differentiation in term LBW newborns led us to evaluate the gene expression status of hematopoiesis. MATERIALS AND METHODS: In this study, we compared our microarray datasets of LBW-Normal Birth Weight (NBW) newborns with two reference datasets to identify hematopoietic stem cells genes, and their differential expression in the LBW newborns, by hierarchical clustering algorithm using gplots and RcolorBrewer package in R. RESULTS: Comparative analysis revealed 108 differentially expressed hematopoiesis genes (DEHGs), of which 79 genes were up-regulated, and 29 genes were down-regulated in LBW newborns compared to their NBW counterparts. Moreover, protein-protein interactions, functional annotation and pathway analysis demonstrated that the up-regulated genes were mainly involved in cell proliferation and differentiation, MAPK signaling and Rho GTPases signaling, and the down-regulated genes were engaged in cell proliferation and regulation, immune system regulation, hematopoietic cell lineage and JAK-STAT pathway. The binding of down-regulated genes (LYZ and GBP1) with growth factor GM-CSF using docking and MD simulation techniques, indicated that GM-CSF has the potential to alleviate the repressed hematopoiesis in the term LBW newborns. CONCLUSION: Our study revealed that DEHGs belonged to erythroid and myeloid-specific lineages and may serve as potential targets for improving hematopoiesis in term LBW newborns to help build up their weak immune defense against life-threatening infections.

2.
J Mater Sci Mater Med ; 26(2): 118, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25672596

RESUMO

The current study describes the in-depth characterization of agar-gelatin based co-hydrogels, emulgels and bigels to have an insight about the differences in the properties of the formulations. Hydrogels have been extensively studied as vehicle for controlled drug release, whereas, the concept of emulgels and bigels is relatively new. The formulations were characterized by scanning electron microscopy, FTIR spectroscopy, XRD and mechanical properties. The biocompatibility and the ability of the formulations to be used as drug delivery vehicle were also studied. The scanning electron micrographs suggested the presence of internal phases within the agar-gelatin composite matrices of co-hydrogel, emulgel and bigel. FTIR and XRD studies suggested higher crystallinity of emulgels and bigels. Electrical impedance and mechanical stability of the emulgel and the bigel was higher than the hydrogel. The prepared formulations were found to be biocompatible and suitable for drug delivery applications.


Assuntos
Ágar/química , Preparações de Ação Retardada/síntese química , Gelatina/química , Hidrogéis/química , Metronidazol/química , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Força Compressiva , Difusão , Módulo de Elasticidade , Dureza , Teste de Materiais , Metronidazol/administração & dosagem , Transição de Fase
3.
J Arthroplasty ; 30(4): 592-4, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25443361

RESUMO

The risk of revision following unicompartmental arthroplasty (UKA) is greater compared with primary total knee arthroplasty (TKA). Some surgeons report that UKA revision is straightforward with outcomes comparable to TKA. We reviewed all Oxford medial UKAs and TKAs performed at our institution over a five year period. Patient reported outcomes were compared between revised UKAs, successful UKAs and primary TKAs. Out of 546 Oxford medial UKAs, twenty-nine (5.3%) were revised at a mean of 25months. The commonest indications for revision were aseptic loosening and progression of osteoarthritis. Ten patients (34%) required augments, stemmed implants or bone grafts. Outcomes following revision were poorer than those following successful UKA and primary TKA, and were a consequence of poor pre-operative function rather than the complexity of surgery.


Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Reoperação/métodos , Idoso , Artrite/fisiopatologia , Transplante Ósseo , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/cirurgia , Sistema de Registros , Resultado do Tratamento , Reino Unido
4.
AAPS PharmSciTech ; 16(2): 293-305, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25277240

RESUMO

The current study explains the development of sorbitan monostearate and sesame oil-based organogels for topical drug delivery. The organogels were prepared by dissolving sorbitan monostearate in sesame oil (70°C). Metronidazole was used as a model antimicrobial. The formulations were characterized using phase contrast microscopy, infrared spectroscopy, viscosity, mechanical test, and differential scanning calorimetry. Phase contrast microscopy showed the presence of needle-shaped crystals in the organogel matrix. The length of the crystals increased with the increase in the sorbitan monostearate concentration. XRD studies confirmed the amorphous nature of the organogels. Viscosity study demonstrated shear thinning behavior of the organogels. The viscosity and the mechanical properties of the organogels increased linearly with the increase in the sorbitan monostearate concentration. Stress relaxation study confirmed the viscoelastic nature of the organogels. The organogels were biocompatible. Metronidazole-loaded organogels were examined for their controlled release applications. The release of the drug followed zero-order release kinetics. The drug-loaded organogels showed almost similar antimicrobial activity against Escherichia coli when compared to the commercially available Metrogyl® gel. In gist, it can be proposed that the developed organogels had sufficient properties to be used for controlled delivery of drugs.


Assuntos
Anti-Infecciosos/química , Géis/química , Hexoses/química , Metronidazol/química , Óleo de Gergelim/química , Administração Tópica , Anti-Infecciosos/farmacologia , Materiais Biocompatíveis/química , Química Farmacêutica/métodos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Géis/farmacologia , Hexoses/farmacologia , Metronidazol/farmacologia , Viscosidade
5.
AAPS PharmSciTech ; 16(6): 1254-62, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25771735

RESUMO

The present study discusses about the preparation and characterization (thermal, mechanical, and electrical) of the genipin-crosslinked gelatin emulgels. Emulgels have gained importance in recent years due to their improved stability than emulsions and ability to control the drug release. Mustard oil was used as the representative oil. A decrease in the enthalpy and entropy of the formulations was observed with the increase in the oil fraction. The mechanical studies suggested formation of softer emulgels as the oil fraction was increased. As the proportion of the oil fraction was increased in the emulgels, there was a corresponding increase in the impedance. The drug release properties from the emulgels were also studied. Ciprofloxacin was used as the model antimicrobial drug. The drug release was higher from the emulgels whose electrical conductivity was higher.


Assuntos
Emulsões/química , Gelatina/química , Géis/química , Iridoides/química , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/química , Química Farmacêutica/métodos , Ciprofloxacina/administração & dosagem , Ciprofloxacina/química , Liberação Controlada de Fármacos , Eletricidade , Emulsões/administração & dosagem , Gelatina/administração & dosagem , Géis/administração & dosagem , Iridoides/administração & dosagem
6.
J Mater Sci Mater Med ; 25(3): 703-21, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24327110

RESUMO

Gels have been considered as a popular mode of delivering medicament for the treatment of sexually transmitted diseases (STDs) (e.g. human immunodeficiency virus, bacterial vaginosis, epididymitis, human papillomavirus infection and condylomata acuminata etc.). The present study discusses the development of novel olive oil based emulsion hydrogels (EHs) using sorbitan monopalmitate as the structuring agent. The developed EHs may be tried as drug delivery vehicle for the treatment of STDs. The formation of EHs was confirmed by fluorescence and confocal microscopy. FTIR studies suggested intermolecular hydrogen bonding amongst the components of the EHs. X-ray diffraction study suggested the amorphous nature of the EHs. The developed EHs have shown non-Newtonian flow behavior. The EHs were found to be biocompatible. The formulations were able to effectively deliver two model antimicrobial drugs (e.g. ciprofloxacin and metronidazole), commonly used in the treatment of the STDs.


Assuntos
Antibacterianos/administração & dosagem , Bacillus subtilis/fisiologia , Preparações de Ação Retardada/síntese química , Hexoses/química , Hidrogéis/química , Óleos de Plantas/química , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Difusão , Emulsões , Temperatura Alta , Teste de Materiais , Azeite de Oliva
7.
Mol Biotechnol ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652428

RESUMO

Melanin is the major pigment responsible for the coloring of mammalian skin, hair, and eyes to defend against ultraviolet radiation. However, excessive melanin production has resulted in numerous types of hyperpigmentation disorders. Tyrosinase-related protein 1 (TYRP1) is a transmembrane glycoprotein enzyme found in many organisms, including humans, that plays an important role in melanogenesis. Thus, controlling the enzyme activity of TYRP1 with tyrosinase inhibitors is a vital step in the treatment of hyperpigmentation problems in humans. In the present investigation, virtual screening, pharmacokinetics, drug docking, and molecular dynamics (MD) simulation were used to find the most potent drug as an inhibitor of TYRP1 to effectively treat hyperpigmentation disorder. The 3D structure of TYRP1 was retrieved from the Protein Data Bank (PDB) database (PDB ID: 5M8M) and validated by the Ramachandran plot. Pharmacokinetics and drug-likeness showed that mycosporine 2 glycine (M2G) and shinorine (SHI) were the best compounds over other ligands in the same (P-1) structural pose. However, MD simulations of the M2G showed the highest CDOCKER interaction energy (-45.182 kcal/mol) and binding affinity (-65.0529 kcal/mol) as compared to SHI and reference drugs. The molecular binding modes RMSD and RMSF plots have exhibited more relevance to the M2G ligand in comparison to other drug ligands. The bioactivity and ligand efficiency profiles revealed that M2G is the most effective compound as a TYRP1 inhibitor. Thus, M2G could be used as a most effective drug for developing valuable sunscreen products to cure hyperpigmentation-related diseases.

8.
Viruses ; 15(6)2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37376534

RESUMO

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the virus kept developing and mutating into different variants over time, which also gained increased transmissibility and spread in populations at a higher pace, culminating in successive waves of COVID-19 cases. The scientific community has developed vaccines and antiviral agents against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Realizing that growing SARS-CoV-2 variations significantly impact the efficacy of antiviral therapies and vaccines, we summarize the appearance and attributes of SARS-CoV-2 variants for future perspectives in drug design, providing up-to-date insights for developing therapeutic agents targeting the variants. The Omicron variant is among the most mutated form; its strong transmissibility and immune resistance capacity have prompted international worry. Most mutation sites currently being studied are in the BCOV_S1_CTD of the S protein. Despite this, several hurdles remain, such as developing vaccination and pharmacological treatment efficacies for emerging mutants of SARS-CoV-2 strains. In this review, we present an updated viewpoint on the current issues faced by the emergence of various SARS-CoV-2 variants. Furthermore, we discuss the clinical studies conducted to assist the development and dissemination of vaccines, small molecule therapeutics, and therapeutic antibodies having broad-spectrum action against SARS-CoV-2 strains.


Assuntos
COVID-19 , Vacinas , Humanos , SARS-CoV-2/genética , RNA Viral , COVID-19/prevenção & controle
9.
Waste Manag ; 154: 175-186, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36244206

RESUMO

This study presents a novel recycling scheme for spent Li-ion batteries that involves the leaching of lithium in hot water followed by the dissolution of all transition metals in HCl solution and their separation using the ionic liquid Cyphos IL104. The parametric studies revealed that >84 % Li was dissolved while the cathode material was leached at 90 °C for 2 h. Approximately 98 % Li from the non-acidic solution was directly precipitated as Li2CO3 at a Li+:CO32- ratio of 1:1.5. The transition metals from the Li-depleted cathode mass were efficiently (>98 %) dissolved in 3.0 mol·L-1 HCl at 90 °C for a 3 h leaching process. Manganese from the chloride leach liquor was selectively precipitated by adding KMnO4 at a 1.25-fold higher quantity than the stoichiometric ratio, pH value 2.0, and temperature 80 °C. The remaining co-existing metals (Ni and Co) were separated from the chloride solution by contacting it with a phosphonium-based ionic liquid at an equilibrium pH value of 5.4 and an organic-to-aqueous phase ratio of 2/3. The loaded ionic liquid was quantitatively stripped in 2.0 mol·L-1 H2SO4 solution, which yielded high-purity CoSO4·xH2O crystals after evaporation of the stripped liquor. Subsequently, ∼99 % nickel was recovered as nickel carbonate [NiCO3·2Ni(OH)2] from the Co-depleted raffinate by the precipitation performed at Ni2+:CO32- ratio of 1:2.5, pH value of 10.8, and temperature of 50 °C. Finally, a process flow with mass and energy balances yielding a high recovery rate of all metals in the exhausted cathode powder of spent LiBs was proposed.

10.
3 Biotech ; 12(10): 261, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36082361

RESUMO

Pectin lyase (PNL) is an important enzyme of the pectinases group which degrades pectin polymer to 4,5-unsaturated oligogalacturonides by a unique ß-elimination mechanism and is used in several industries. The existence of multigene families of pectin lyases has been investigated by mining microbial genomes. In the present study, 52 pectin lyase genes were predicted from sequenced six species of Fusarium, namely F. fujikuroi, F. graminearum, F. proliferatum, F. oxysporum, F. verticillioides and F. virguliforme. These sequences were in silico characterized for several physico-chemical, structural and functional attributes. The translated PNL proteins showed variability with 344-1142 amino acid residues, 35.44-127.41 kDa molecular weight, and pI ranging from 4.63 to 9.28. The aliphatic index ranged from 75.33 to 84.75. Multiple sequence alignment analysis showed several conserved amino acid residues and five distinct groups marked as I, II, III, IV, and V were observed in the phylogenetic tree. The Three-dimensional Structure of five of these PNLs, each representing a distinct group of phylogenetic trees was predicted using I-TASSER Server and validated. The pectin lyase proteins of Fusarium species revealed close similarity with pectin lyase of Aspergillus niger PelA(1IDJ) and PelB(1QCX). Diversity in the structural motifs was observed among Fusarium species with 2 ß-sheets, 1 ß-hairpin, 7-12 ß bulges, 18-25 strands, 6 -11 helices, 1 helix-helix interaction, 32-49 ß turns, 2-6 γ turns and 2- 3 disulfide bonds. The unique Pec_lyase domain was uniformly observed among all PNL proteins confirming its identity. The genome-wide mining of Fusarium species was attempted to provide the diversity of PNL genes, which could be explored for diverse applications after performing cloning and expression studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03333-w.

11.
Waste Manag ; 121: 175-185, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33360816

RESUMO

This study has attempted to ascertain the linkages between circular bio-economy (CirBioeco) and recycling of electronic (e-)waste by applying microbial activities instead of the smelter and chemical technologies. To build the research hypothesis, the advances on biotechnology-driven recycling processes for metals extraction from e-waste has been analyzed briefly. Thereafter, based on the potential of microbial techniques and research hypothesis, the structural model has been tested for a significance level of 99%, which is supported by the corresponding standardization co-efficient values. A prediction model applied to determine the recycling impact on CirBioeco indicates to re-circulate 51,833 tons of copper and 58 tons of gold by 2030 for the production of virgin metals/raw-materials, while recycling rate of the accumulated e-waste remains to be 20%. This restoration volume of copper and gold through the microbial activities corresponds to mitigate 174 million kg CO2 emissions and 24 million m3 water consumption if compared with the primary production activities. The study potentially opens a new window for environmentally-friendly biotechnological recycling of e-waste under the umbrella concept of CirBioeco.


Assuntos
Resíduo Eletrônico , Cobre , Resíduo Eletrônico/análise , Eletrônica , Ouro , Reciclagem
12.
Mini Rev Med Chem ; 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767940

RESUMO

The article has been withdrawn at the request of the authors and editor of the journal Mini-Reviews in Medicinal Chemistry due to incoherent content. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorialpolicies-main.php Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

13.
Plant Physiol Biochem ; 151: 689-704, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32353675

RESUMO

The maintenance of ROS homeostasis, membrane biogenesis and recycling of molecules are common stress responses involving specific and complex regulatory network. Ubiquitination is an important and common mechanism which facilitates environmental adaptation in eukaryotes. In the present study we have cloned the AlRabring7, an E3-Ub-ligase, previously identified as AlRab7 interacting partner. The role of AlRabring7 for ubiquitinating AlRab7 and facilitating stress tolerance is analysed. The AlRabring7, with an open-reading frame of 702 bp encodes a protein of 233 amino acids, with RING-HC domain of 40 amino acids. In silico analysis shows that AlRabring7 is a C3HC4-type RING E3 Ub ligase. The protein - protein docking show interaction dynamics between AlRab7-AlRabring7-Ubiquitin proteins. The AlRab7 and AlRabring7 transcript showed up-regulation in response to different salts i.e: NaCl, KCl, CaCl2, NaCl + KCl, NaCl + CaCl2, imposing ionic as well as hyperosmotic stress, and also with oxidative stress by H2O2 treatment. Interestingly, the AlRabring7 showed early transcript expression with maximum expression in shoots on combinatorial stresses. The AlRab7 showed delayed and maximum expression with NaCl + CaCl2 stress treatment. The AlRab7 complements yeast ypt7Δ mutants and restored the fragmented vacuole. The in vitro ubiquitination assay revealed that AlRabring7 function as E3 ubiquitin ligase and mediates AlRab7 ubiquitination. Overexpression of AlRab7 and AlRabring7 independently and when co-transformed enhanced the growth of yeast cells during stress conditions. Further, the bimolecular fluorescence complementation assay shows the in planta interaction of the two proteins. Our results suggest that AlRab7 and AlRabring7 confers enhanced stress tolerance in yeast.


Assuntos
Estresse Oxidativo , Saccharomyces cerevisiae , Ubiquitina-Proteína Ligases , Ubiquitinação , Peróxido de Hidrogênio , Estresse Oxidativo/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/genética
14.
Int J Cancer ; 125(5): 1004-15, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19415747

RESUMO

Invasive human breast carcinomas frequently coexpress increased hepatocyte growth factor (HGF) and its receptor Met, suggesting that establishment of an autocrine HGF loop is important in malignant disease. This study examines the expression patterns of HGF and Met activation during tumorigenesis and metastasis using a MCF10A-based model of Ha-Ras-induced human breast cancer progression. Deregulation of cadherin-based cell-cell adhesions, decreased expression of cytokeratins 8/18 and increased activity of matrix metalloproteinases such as MMP-2 occurs in premalignant and malignant (metastatic) cell lines compared to the parental nonmalignant cell line. Compared to the benign parent cell line, premalignant and malignant cell lines exhibit increased secretion of full length HGF alpha-chain and elevated Met tyrosine phosphorylation in complete medium. Interestingly, the premalignant and malignant cells also secrete a approximately 55 kDa HGF fragment. Epitope mapping of the approximately 55 kDa HGF fragment supports the presence of the N-terminal domain of the HGF alpha-chain with a truncation in the C-terminal domain. The approximately 55 kDa HGF fragment shows mobility in SDS-PAGE faster than HGF alpha-chain, but slightly slower than NK4, a previously established full antagonist of HGF. The separated approximately 55 kDa HGF fragment binds to animmobilized Met-IgG fusion protein, and inhibits both HGF/Met-IgG binding and HGF-induced Met-tyrosine phosphorylation. These results are the first demonstration of an antagonistic approximately 55 kDa HGF fragment secreted during breast carcinoma progression, which may have a negative regulatory effect on HGF signaling in premalignant breast epithelial cells.


Assuntos
Neoplasias da Mama/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Fragmentos de Peptídeos/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Western Blotting , Neoplasias da Mama/patologia , Transformação Celular Neoplásica , Meios de Cultivo Condicionados/farmacologia , Progressão da Doença , Genes ras , Fator de Crescimento de Hepatócito/antagonistas & inibidores , Humanos , Mesoderma/citologia , Mesoderma/metabolismo , Invasividade Neoplásica , Fosforilação , Tirosina/metabolismo
15.
J Spinal Cord Med ; 32(5): 583-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20025156

RESUMO

BACKGROUND/OBJECTIVE: Glioblastoma multiforme (GBM) is the most common glial cell tumor of the adult brain. However, primary GBM of the spinal cord is a rare condition. METHODS: Case report. RESULTS: A young man presented with acute onset quadriparesis after a whiplash injury. A magnetic resonance scan showed the typical appearance of a high-grade intramedullary tumor with fusiform expansion of the entire cervical cord. Subtotal decompression and biopsy was done by posterior laminectomy, followed by external beam radiotherapy. Signs and symptoms improved after the completion of radiotherapy but did not resolve completely. Death caused by respiratory failure occurred 3 months later. CONCLUSIONS: This presentation of GBM of the cervical cord is rare; an intramedullary tumor should be considered when minor cervical trauma results in disproportionate neurologic deficit. To the best of our knowledge, this is the first reported case of spinal GBM with extensive pan-cervical involvement.


Assuntos
Glioblastoma/complicações , Quadriplegia/etiologia , Quadriplegia/terapia , Neoplasias da Coluna Vertebral/complicações , Descompressão Cirúrgica , Glioblastoma/cirurgia , Humanos , Laminectomia , Imageamento por Ressonância Magnética , Masculino , Radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento , Adulto Jovem
16.
Cancer Res ; 67(2): 626-33, 2007 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-17234772

RESUMO

Synuclein-gamma (SNCG) plays oncogenic roles in breast carcinogenesis. Although the expression of SNCG is abnormally high in advanced and metastatic breast carcinomas, SNCG is not expressed in normal or benign breast tissues. SNCG is an intrinsically disordered protein known to interact with BubR1, a mitotic checkpoint kinase. The SNCG-BubR1 interaction inhibits mitotic checkpoint control upon spindle damage caused by anticancer drugs, such as nocodazole and taxol. Antimicrotubule drugs that cause mitotic arrest and subsequent apoptosis of cancer cells are frequently used to treat breast cancer patients with advanced or metastatic diseases. However, patient response rates to this class of chemotherapeutic agents vary significantly. In this study, we have designed a novel peptide (ANK) and shown its interaction with SNCG using fluorometry, surface plasmon resonance, and isothermal titration calorimetry. Binding of the ANK peptide did not induce folding of SNCG, suggesting that SNCG can function biologically in its intrinsically disordered state. Microinjection of the ANK peptide in breast cancer cell line overexpressing SNCG (MCF7-SNCG) exhibited a similar cell killing response by nocodazole as in the SNCG-negative MCF7 cells. Overexpression of enhanced green fluorescent protein-tagged ANK reduces SNCG-mediated resistance to paclitaxel treatment by approximately 3.5-fold. Our coimmunoprecipitation and colocalization results confirmed the intracellular association of the ANK peptide with SNCG. This is likely due to the disruption of the interaction of SNCG with BubR1 interaction. Our findings shed light on the molecular mechanism of the ANK peptide in releasing SNCG-mediated drug resistance.


Assuntos
Anquirinas/química , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Nocodazol/farmacologia , Fragmentos de Peptídeos/farmacologia , gama-Sinucleína/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Anquirinas/genética , Anquirinas/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Sequência Conservada , Resistencia a Medicamentos Antineoplásicos , Humanos , Cinética , Microtúbulos/efeitos dos fármacos , Mitose/efeitos dos fármacos , Dados de Sequência Molecular , Proteínas de Neoplasias/metabolismo , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Dobramento de Proteína , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases , gama-Sinucleína/metabolismo
17.
Curr Drug Metab ; 20(6): 416-429, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30227814

RESUMO

BACKGROUND: Nanotechnology is gaining significant attention worldwide for cancer treatment. Nanobiotechnology encourages the combination of diagnostics with therapeutics, which is a vital component of a customized way to deal with the malignancy. Nanoparticles are being used as Nanomedicine which participates in diagnosis and treatment of various diseases including cancer. The unique characteristic of Nanomedicine i.e. their high surface to volume ratio enables them to tie, absorb, and convey small biomolecule like DNA, RNA, drugs, proteins, and other molecules to targeted site and thus enhances the efficacy of therapeutic agents. OBJECTIVE: The objective of the present article is to provide an insight of several aspect of nanotechnology in cancer therapeutics such as various nanomaterials as drug vehicle, drug release strategies and role of nanotechnology in cancer therapy. METHODS: We performed an extensive search on bibliographic database for research article on nanotechnology and cancer therapeutics and further compiled the necessary information from various articles into the present article. RESULTS: Cancer nanotechnology confers a unique technology against cancer through early diagnosis, prevention, personalized therapy by utilizing nanoparticles and quantum dots.Nano-biotechnology plays an important role in the discovery of cancer biomarkers. Quantum dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires etc. have been developed as a carrier of biomolecules that can detect cancer biomarkers. Nanoparticle assisted cancer detection and monitoring involves biomolecules like proteins, antibody fragments, DNA fragments, and RNA fragments as the base of cancer biomarkers. CONCLUSION: This review highlights various approaches of cancer nanotechnology in the advancement of cancer therapy.


Assuntos
Nanomedicina/métodos , Nanotecnologia/métodos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Dendrímeros , Diagnóstico por Imagem , Terapia Genética , Humanos , Micelas , Nanoconchas , Nanotubos , Fototerapia , Pontos Quânticos
18.
Cancer Res ; 66(22): 10741-9, 2006 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17108110

RESUMO

Multiple endocrine neoplasia 2B (MEN 2B) is an inherited syndrome of early onset endocrine tumors and developmental anomalies. The disease is caused primarily by a methionine to threonine substitution of residue 918 in the kinase domain of the RET receptor (2B-RET); however, the molecular mechanisms that lead to the disease phenotype are unclear. In this study, we show that the M918T mutation causes a 10-fold increase in ATP binding affinity and leads to a more stable receptor-ATP complex, relative to the wild-type receptor. Further, the M918T mutation alters local protein conformation, correlating with a partial loss of RET kinase autoinhibition. Finally, we show that 2B-RET can dimerize and become autophosphorylated in the absence of ligand stimulation. Our data suggest that multiple distinct but complementary molecular mechanisms underlie the MEN 2B phenotype and provide potential targets for effective therapeutics for this disease.


Assuntos
Neoplasia Endócrina Múltipla Tipo 2b/genética , Neoplasia Endócrina Múltipla Tipo 2b/metabolismo , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Trifosfato de Adenosina/metabolismo , Sequência de Aminoácidos , Dimerização , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Neoplasia Endócrina Múltipla Tipo 2b/enzimologia , Oncogenes , Fosforilação , Conformação Proteica , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ret/química , Homologia de Sequência de Aminoácidos , Relação Estrutura-Atividade
19.
Front Plant Sci ; 8: 819, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28611792

RESUMO

The WRKY transcription factors (TFs), play crucial role in plant defense response against various abiotic and biotic stresses. The role of WRKY3 and WRKY4 genes in plant defense response against necrotrophic pathogens is well-reported. However, their functional annotation in tomato is largely unknown. In the present work, we have characterized the structural and functional attributes of the two identified tomato WRKY transcription factors, WRKY3 (SlWRKY3), and WRKY4 (SlWRKY4) using computational approaches. Arabidopsis WRKY3 (AtWRKY3: NP_178433) and WRKY4 (AtWRKY4: NP_172849) protein sequences were retrieved from TAIR database and protein BLAST was done for finding their sequential homologs in tomato. Sequence alignment, phylogenetic classification, and motif composition analysis revealed the remarkable sequential variation between, these two WRKYs. The tomato WRKY3 and WRKY4 clusters with Solanum pennellii showing the monophyletic origin and evolution from their wild homolog. The functional domain region responsible for sequence specific DNA-binding occupied in both proteins were modeled [using AtWRKY4 (PDB ID:1WJ2) and AtWRKY1 (PDBID:2AYD) as template protein structures] through homology modeling using Discovery Studio 3.0. The generated models were further evaluated for their accuracy and reliability based on qualitative and quantitative parameters. The modeled proteins were found to satisfy all the crucial energy parameters and showed acceptable Ramachandran statistics when compared to the experimentally resolved NMR solution structures and/or X-Ray diffracted crystal structures (templates). The superimposition of the functional WRKY domains from SlWRKY3 and SlWRKY4 revealed remarkable structural similarity. The sequence specific DNA binding for two WRKYs was explored through DNA-protein interaction using Hex Docking server. The interaction studies found that SlWRKY4 binds with the W-box DNA through WRKYGQK with Tyr408, Arg409, and Lys419 with the initial flanking sequences also get involved in binding. In contrast, the SlWRKY3 made interaction with RKYGQK along with the residues from zinc finger motifs. Protein-protein interactions studies were done using STRING version 10.0 to explore all the possible protein partners involved in associative functional interaction networks. The Gene ontology enrichment analysis revealed the functional dimension and characterized the identified WRKYs based on their functional annotation.

20.
J Mech Behav Biomed Mater ; 75: 538-548, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28850924

RESUMO

The study reports the synthesis and characterization of gelatin-tamarind gum (TG) based filled hydrogels for drug delivery applications. In this study, three different types of carbon nanotubes (CNTs) were incorporated within the dispersed TG phase of the filled hydrogels. The prepared hydrogels were thoroughly characterised using bright field microscope, FESEM, FTIR spectroscopy, differential scanning calorimeter, and mechanical tester. The swelling and the drug (salicylic acid) release properties of the filled hydrogels were also evaluated. The micrographs revealed the formation of biphasic systems. The internal phase appeared as agglomerates, and the CNTs were confined within the dispersed TG phase. FTIR and XRD studies revealed that CNTs promoted associative interactions among the components of the hydrogel, which promoted the formation of large crystallite size. The mechanical study indicated better resistance to the breakdown of the architecture of the CNT-containing filled hydrogels. Drug release studies, both passive and iontophoretic, suggested that the non-Fickian diffusion of the drug was prevalent during its release from hydrogel matrices. The prepared hydrogels were cytocompatible with human keratinocytes. The results suggested the probable use of such hydrogels in wound healing, tissue engineering and drug delivery applications.


Assuntos
Portadores de Fármacos/química , Liberação Controlada de Fármacos , Gelatina/química , Hidrogéis/química , Queratinócitos/efeitos dos fármacos , Tamarindus/química , Humanos , Nanotubos de Carbono/química
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