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1.
Front Nephrol ; 4: 1349859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638111

RESUMO

Renal cell carcinoma (RCC), particularly the clear cell subtype (ccRCC), poses a significant global health concern due to its increasing prevalence and resistance to conventional therapies. Early detection of ccRCC remains challenging, resulting in poor patient survival rates. In this study, we employed a bioinformatic approach to identify potential prognostic biomarkers for kidney renal clear cell carcinoma (KIRC). By analyzing RNA sequencing data from the TCGA-KIRC project, differentially expressed genes (DEGs) associated with ccRCC were identified. Pathway analysis utilizing the Qiagen Ingenuity Pathway Analysis (IPA) tool elucidated key pathways and genes involved in ccRCC dysregulation. Prognostic value assessment was conducted through survival analysis, including Cox univariate proportional hazards (PH) modeling and Kaplan-Meier plotting. This analysis unveiled several promising biomarkers, such as MMP9, PIK3R6, IFNG, and PGF, exhibiting significant associations with overall survival and relapse-free survival in ccRCC patients. Cox multivariate PH analysis, considering gene expression and age at diagnosis, further confirmed the prognostic potential of MMP9, IFNG, and PGF genes. These findings enhance our understanding of ccRCC and provide valuable insights into potential prognostic biomarkers that can aid healthcare professionals in risk stratification and treatment decision-making. The study also establishes a foundation for future research, validation, and clinical translation of the identified prognostic biomarkers, paving the way for personalized approaches in the management of KIRC.

2.
Lett Appl Microbiol ; 76(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37673682

RESUMO

The population and modernization of society have increased dramatically from past few decades. In order to meet societal expectations, there has been a massive industrialization and resource exploitation. Anthropogenic practices like disposal of hazardous waste, large carbon footprint release variety of xenobiotic substances into the environment, which endanger the health of the natural ecosystem. Therefore, discovering proper long-term treatment approaches is a global concern. Various physical and chemical approaches are employed to remove contaminants. However, these technologies possess limitations like high cost and low efficacy. Consequently, bioremediation is regarded as one of the most promising remedies to these problems. It creates the option of either totally removing pollutants or transforming them into nonhazardous compounds with the use of natural biological agents. Several microorganisms are being utilized for bioremediation among which yeasts possess benefits such as high biodegradability, ease of cultivation etc. The yeast of Candida genus has the capability to effectively eliminate heavy metal ions, as well as to degrade and emulsify hydrocarbons which makes it a promising candidate for this purpose. The review highlights many potential uses of Candida in various remediation strategies and discusses future directions for research in this field.


Assuntos
Poluentes Ambientais , Íons Pesados , Candida , Biodegradação Ambiental , Ecossistema , Saccharomyces cerevisiae
3.
Mar Pollut Bull ; 191: 114954, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37121188

RESUMO

Facemasks have become a global medical necessity and are a key preventive measure against COVID-19. Typically, facemasks (FMs) are fabricated from non-renewable polymers, particularly polypropylene (PP) and polyethylene (PE), which release secondary microplastic (MPs) due to the chemical, physical, and biological processes. In light of the widespread usage and improper disposal of single-use facemasks, there is concern about their environmental impact since they contribute to plastic pollution during and after pandemics. The repercussions of this have led to millions of tons of plastic waste being dumped into the environment. Due to lack of awareness and improper disposal, the occurrence of micro/nanoplastics released from facemasks in wastewater treatment plants and landfills poses a concern. Infiltration of wastewater treatment processes by micro/nanoplastics at various levels can be problematic because of their chemical nature and broad but small size. Thus, operational and process stability issues can arise during wastewater treatment processes. In addition, landfilling and illegal waste disposal are being used to dispose of potentially infectious COVID-19 waste, leading to an environmental threat to animal and human health and exacerbating plastic pollution. This paper reviews the fate of facemasks in the environment and the repercussions of improper waste management of facemasks in wastewater treatment plants, landfills, and ultimately the environment.


Assuntos
COVID-19 , Poluentes Químicos da Água , Animais , Humanos , Microplásticos , Plásticos , Máscaras , Poluentes Químicos da Água/análise , Monitoramento Ambiental
4.
Sci Rep ; 13(1): 4516, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934129

RESUMO

Heterogeneity in the Diabetic Kidney Disease (DKD) diagnosis makes its rational therapeutics challenging. Although albuminuria characterizes DKD, reports also indicate its prevalence among non-proteinuric. Recent understanding of disease progression has thus inclined the focus on proximal tubular cell damage besides the glomeruli. A non-invasive approach exploiting exosomal miRNA derived from human kidney proximal tubular cell line was, hence, targeted. Upon miRNA profiling, three miRNAs, namely, hsa-miR-155-5p, hsa-miR-28-3p, and hsa-miR-425-5p were found to be significantly upregulated, while hsa-miR-663a was downregulated under diabetic conditions. Among these, hsa-miR-663a downregulation was more pronounced in non-proteinuric than proteinuric DKD subjects and was thus selected for the bioinformatics study. Ingenuity Pathway Analysis (IPA) narrowed on to IL-8 signaling and inflammatory response as the most enriched 'canonical pathway' and 'disease pathway' respectively, during DKD. Further, the putative gene network generated from these enriched pathways revealed experimentally induced diabetes, renal tubular injury, and decreased levels of albumin as part of mapping under 'disease and function'. Genes target predictions and annotations by IPA reiterated miR-663a's role in the pathogenesis of DKD following tubular injury. Overall, the observations might offer an indirect reflection of the underlying mechanism between patients who develop proteinuria and non-proteinuria.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , Humanos , Linhagem Celular , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
5.
Arch Microbiol ; 205(4): 149, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36995448

RESUMO

Biosurfactants are surface-active molecules that are synthesized by many microorganisms like fungi, bacteria, and yeast. These molecules are amphiphilic in nature, possessing emulsifying ability, detergency, foaming, and surface-activity like characteristics. Yeast species belongs to the genus Candida has gained globally enormous interest because of the diverse properties of biosurfactants produced by theme. In contrast to synthetic surfactants, biosurfactants are claimed to be biodegradable and non-toxic which labels them as a potent industrial compound. Biosurfactants produced by this genus are reported to possess certain biological activities, such as anticancer and antiviral activities. They also have potential industrial applications in bioremediation, oil recovery, agricultural, pharmaceutical, biomedical, food, and cosmetic industries. Various species of Candida have been recognized as biosurfactant producers, including Candida petrophilum, Candida bogoriensis, Candida antarctica, Candida lipolytica, Candida albicans, Candida batistae, Candida albicans, Candida sphaerica, etc. These species produce various forms of biosurfactants, such as glycolipids, lipopeptides, fatty acids, and polymeric biosurfactants, which are distinct according to their molecular weights. Herein, we provide a detailed overview of various types of biosurfactants produced by Candida sp., process optimization for better production, and the latest updates on the applications of these biosurfactants.


Assuntos
Candida , Tensoativos , Tensoativos/farmacologia , Tensoativos/química , Bactérias , Leveduras , Candida albicans
6.
ACS Appl Bio Mater ; 6(2): 494-506, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36700824

RESUMO

In pursuit of efficient antimicrobial agents, biomaterials such as hydrogels have drawn a considerable amount of attention due to their numerous advantages such as a high degree of hydration, biocompatibility, stability, and direct application at an infectious site. Particularly, biomaterials such as hydrogels based on Fmoc-protected peptides and amino acids have proven to be immensely advantageous. Such biomaterials can undergo gelation by simple pH modulation and can be used for various biological applications. Keeping this in mind, in this work, we reported the synthesis of Fmoc-phenylalanine (Fmoc-F)-based hydrogels using trisodium citrate as a pH modulator and compared them with the previously reported pH modulator glucono-δ-lactone. The gels were compared using various characterization techniques such as rheometry, field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), small angle X-ray scattering (SAXS), FT-IR, thioflavin T (ThT) binding assay, and zeta potential studies. These studies highlighted the role of pH modulators in affecting various parameters such as the ability to alter the zeta potential of the nanofibrils, improve their bactericidal action, reduce the amyloidic characters, shift the lattice packing from amorphous to crystalline, and introduce fluorescence and thermoreversibility. Interestingly, this is the first report where the Fmoc-F-based hydrogel has been shown to be effective against Gram-negative bacteria along with Gram-positive bacteria as well. Additionally, the mechanism of antimicrobial action was investigated using docking and antioxidant studies.


Assuntos
Antibacterianos , Hidrogéis , Hidrogéis/farmacologia , Hidrogéis/química , Antibacterianos/farmacologia , Antibacterianos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Espalhamento a Baixo Ângulo , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Difração de Raios X , Materiais Biocompatíveis
7.
J Basic Microbiol ; 62(11): 1307-1318, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36257786

RESUMO

The development of novel types of biogenic surface-active compounds is of greater interest for combating many diseases and infections. In this respect research and development of biosurfactant has gained immense importance. Substantially, biosurfactant is defined as a class of active amphiphilic chemical compounds that comprise hydrophobic and hydrophilic moieties on their surfaces. It is generally known that many kinds of microorganisms can be used to produce these surfactants or surface-active compounds. Hosting interesting features such as biodegradability, emulsifying/de-emulsifying capacity, low toxicity, and antimicrobial activities; these amphiphilic compounds in recent years have flourished as an ideal replacement for the chemically synthesized surfactant, and also have various commercial attractions. Both bacteria and fungi are the producers of these amphiphilic molecules; however, the pathogenicity of certain bacterial strains has caused a shift in interest toward fungi. Therefore, various fungi species have been reported for the production of biosurfactants amongst which Candida species have been the most studied strains. Biosurfactants uphold desired properties like antibacterial, antifungal, antiviral, antiadhesion, and anticancer activity which proves them an ideal candidate for the application in various fields like pharmaceutical, gene therapy, medical insertion safety, immunotherapy to fight against many chronic diseases, and so forth. Hence, this review article discusses the pharmaceutical prospects of biosurfactants produced from different fungal species, providing new directions toward the discovery and development of molecules with novel structures and diverse functions for advanced application in the medical field.


Assuntos
Bactérias , Tensoativos , Tensoativos/farmacologia , Tensoativos/química , Interações Hidrofóbicas e Hidrofílicas , Preparações Farmacêuticas
8.
Chembiochem ; 23(22): e202200499, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36177524

RESUMO

Wound dressings are required to provide a moist environment for wounds, protect against invading infections, expedite tissue regeneration, and improve wound healing efficiency. Developing biomaterials with all aforesaid properties is still a big challenge. However, peptide-based hydrogels have the potential to overcome these challenges as they are biocompatible, biodegradable as well as have the ability to mimic the extracellular matrix and provide an appropriate moist environment which is important for wound healing. With this in mind, we report the preparation and comparison of three hexapeptide-based hydrogels, LIVAGD, with the aim to understand the importance of the N-terminal protecting group as well as the C-terminal amino acid substitution on its various biological efficacies. Fmoc and acetyl groups were used for N-terminal peptide protection, while aspartic acid was substituted with lysine at the C-terminus. The resulting peptide-based hydrogels were compared. Fmoc peptide-based hydrogels exhibited efficient anti-inflammatory action along with improved biocompatibility while lysine provided enhanced antibacterial effect to the hydrogel. Additionally, in vivo efficacy was examined using a mouse model, and Fmoc hydrogels demonstrated an improved wound healing ability with ∼40 % faster healing rate in comparison to the reported acetylated peptide hydrogels.


Assuntos
Hidrogéis , Lisina , Hidrogéis/farmacologia , Hidrogéis/química , Cicatrização , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
9.
Med Mycol ; 60(9)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36029277

RESUMO

We describe presenting clinical and imaging manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-associated Rhino-oculo-cerebral mucormycosis (ROCM) in a hospital setting during the second wave of SARS-CoV-2 pandemic in India. Data on the presenting manifestations were collected from 1 March to 31 May 2021. Associations between clinical and imaging findings were explored, specifically: (1) the presence or absence of orbital pain and infiltration of a superior orbital fissure on imaging; (2) the presence of unilateral facial nerve palsy and pterygopalatine fossa infiltration and geniculate ganglion signal on contrast magnetic resonance imaging, and (3) vision loss and optic nerve findings on imaging. Orbital pain was reported by 6/36 subjects. A fixed, frozen eye with proptosis and congestion was documented in 26 (72%), complete vision loss in 23 (64%), and a unilateral lower motor neuron facial nerve palsy in 18 (50%). No association was found between the presence of orbital pain and superior orbital fissure infiltration on imaging. The ipsilateral geniculate ganglion was found to enhance more profoundly in 7/11 subjects with facial palsy and available magnetic resonance (MR) imaging, and the ipsilateral pterygopalatine fossa was found infiltrated in 14. Among 23 subjects with complete loss of vision, 9 (39%) demonstrated long-segment bright signal in the posterior optic nerve on diffusion MR images. We conclude that orbital pain might be absent in SARS-CoV-2-associated ROCM. Facial nerve palsy is more common than previously appreciated and ischemic lesions of the posterior portion of the optic nerve underlie complete vision loss.


Unique clinical and radiological manifestations identified in the outbreak of Rhino-oculo-cerebral mucormycosis (ROCM) during the second epidemic wave of coronavirus disease 2019 (COVID-19) infection included the common occurrence of facial paralysis, frequent absence of ocular pain, and long segments of optic nerve damage.


Assuntos
COVID-19 , Mucormicose , Animais , COVID-19/complicações , COVID-19/veterinária , Humanos , Mucormicose/diagnóstico por imagem , Mucormicose/veterinária , Dor/veterinária , Paralisia/veterinária , SARS-CoV-2
10.
Toxicol In Vitro ; 83: 105418, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35724836

RESUMO

Nano-based products have shown their daunting presence in several sectors. Among them, Zinc Oxide (ZnO) nanoparticles wangled the reputation of providing "next-generation solutions" and are being utilized in plethora of products. Their widespread application has led to increased exposure of these particles, raising concerns regarding toxicological repercussions to the human health and environment. The diversity, complexity, and heterogeneity in the available literature, along with correlation of befitting attributes, makes it challenging to develop one systematic framework to predict this toxicity. The present study aims at developing predictive modelling framework to tap the prospective features responsible for causing cytotoxicity in-vitro on exposure to ZnO nanoparticles. Rigorous approach was used to mine the information from complete body of evidence published to date. The attributes, features and experimental conditions were systematically extracted to unmask the effect of varied features. 1240 data points from 76 publications were obtained, containing 14 qualitative and quantitative attributes, including physiochemical properties of nanoparticles, cell culture and experimental parameters to perform meta-analysis. For the first time, the efforts were made to investigate the degree of significance of attributes accountable for causing cytotoxicity on exposure to ZnO nanoparticles. We show that in-vitro cytotoxicity is closely related with dose concentration of nanoparticles, followed by exposure time, disease state of the cell line and size of these nanoparticles among other attributes.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Linhagem Celular , Sobrevivência Celular , Humanos , Nanopartículas Metálicas/toxicidade , Nanopartículas/química , Nanopartículas/toxicidade , Estudos Prospectivos , Óxido de Zinco/toxicidade
11.
Int J Biol Macromol ; 166: 665-676, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33137384

RESUMO

An RNase produced by Bacillus safensis RB-5 was purified up to 22.32-fold by successive techniques of salting out, DEAE-anion exchange and gel permeation (Sephadex G-100) chromatography techniques with a yield of 2.27%. The purified RNase possessed a single band in SDS-PAGE (Mr ~ 60 kDa). The purified RNase showed optimal activity at temperature of 37 °C and pH 7.5 in the presence of substrate (Yeast RNA) and Mg2+ ions. The RNase activity was strongly inhibited by Hg2+ and mildly by Fe2+, Ba2+ and Zn2+ ions. Its half-life was found to be 8 h at 37 °C. The RNase kinetics study showed Km and Vmax value of 0.3 mM and 9.2 µmol/mg/min, respectively. The purified RNase also showed cytotoxic and antiproliferative activities towards a few transformed cell lines. The purified RNase (IC50 0.035 U/mL) effectively inhibited RD and Hep-2C cells proliferation & migration, while sparing HEK 293 cells. The purified RNase was cytotoxic as well as effective degrader of the RNA of transformed RD cells at low concentration. Moreover, the purified RNase of B. safensis RB-5 was found to possess a little hemolytic activity towards human RBCs.


Assuntos
Bacillus/enzimologia , Proteínas de Bactérias/química , Ribonucleases/química , Células A549 , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/toxicidade , Células CACO-2 , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Estabilidade Enzimática , Eritrócitos/efeitos dos fármacos , Células HEK293 , Hemólise , Células Hep G2 , Humanos , Células MCF-7 , Ribonucleases/metabolismo , Ribonucleases/toxicidade
12.
Front Med (Lausanne) ; 7: 424, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850914

RESUMO

Acute kidney injury (AKI) is a significant global health concern. The primary causes of AKI include ischemia, sepsis and nephrotoxicity. The unraveled interface between nervous system and immune response with specific focus on pain pathways is generating a huge interest in reference to AKI. The nervous system though static executes functions by nerve fibers throughout the body. Neuronal peptides released by nerves effect the immune response to mediate the hemodynamic system critical to the functioning of kidney. Pain is the outcome of cellular cross talk between nervous and immune systems. The widespread release of neuropeptides, neurotransmitters and immune cells contribute to bidirectional neuroimmune cross talks for pain manifestation. Recently, we have reported pain pathway genes that may pave the way to better understand such processes during AKI. An auxiliary understanding of the functions and communications in these systems will lead to novel approaches in pain management and treatment through the pathological state, specifically during acute kidney injury.

13.
Nephrology (Carlton) ; 25(12): 881-887, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32323449

RESUMO

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney associated diseases with non-albuminuria further complicates a timely diagnosis and thus demands an early biomarker. Urinary exosomes, the nanovesicular entities are released by every epithelial cells of the nephron. Their protein or molecular cargo varies in the diseased state which may provide the pathophysiology of the kidney associated diseases. This drives them to be exploited as non-invasive biomarker. This review thus integrates the recent findings on the significance of the urinary exosomes as diagnostic biomarker in kidney-associated diseases, primarily in diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/urina , Exossomos/metabolismo , Biomarcadores/urina , Humanos
14.
Heliyon ; 5(10): e02605, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31687491

RESUMO

Carbon nanotubes (CNTs) hold tremendous potential due to their unique and modifiable properties. Their robust biological applications necessitate minimizing their cytotoxicity and increasing the solubilization. In the present manuscript, we have functionalized multiwalled carbon nanotubes (MWCNTs) using defect functionalization methodology to covalently bind carboxy and amino groups on their walls. This functionalization was reassured through fourier-transform infrared spectroscopy (FTIR), energy dispersive x-ray analysis (EDX), elemental and field emission scanning electron microscopy (FE-SEM) analysis. The observations demonstrated that addition of carboxy as well as amino groups on MWCNTs, besides enabling MWCNTs solubilization also significantly ameliorated the cytotoxicity and the oxidative stress in comparison to pristine MWCNTs. It is envisaged that changes in agglomeration of the functionalized MWCNTs and the acquired surface charge is the reason for the reduction of cytotoxicity. Zebra fish embryo model test system employed for in vivo analysis of the MWCNTs showed no significant toxicity on account of any nanoparticle tested pointing towards intrinsic mechanisms in place for deterring the damage in complex organisms. Overall, the observations besides pointing towards functionalized MWCNTs effectiveness towards weakening the toxicity of pristine MWCNTs also caution for extrapolating in vitro data to in vivo observations. The observations further lend credibility for exploiting the zebra fish as a model system for analyzing the effects of MWCNTs functionalization.

15.
Sci Rep ; 9(1): 11872, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417109

RESUMO

Acute Kidney injury (AKI) is one of the leading health concerns resulting in accumulation of nitrogenous as well as non-nitrogenous wastes in body and characterised by a rapid deterioration in kidney functions. Besides the major toll from the primary insult in the kidney, consequential extra-renal secondary insults endowed with the pathways of inflammatory milieu often complicates the disease outcome. Some of the known symptoms of AKI leading to clinical reporting are fatigue, loss of appetite, headache, nausea, vomiting, and pain in the flanks, wherein proinflammatory cytokines have been strongly implicated in pathogenesis of AKI and neuro-inflammation. Taking in account these clues, we have tried to decode the neuro-inflammation and pain perception phenomenon during the progression of AKI using the pathway integration and biological network strategies. The pathways and networks were generated using bioinformatics software viz. PANTHER, Genomatix and PathVisio to establish the relationship between immune and neuro related pathway in AKI. These observations envisage a neurol-renal axis that is predicted to involve calcium channels in neuro-inflammatory pathway of AKI. These observations, thus, pave a way for a new paradigm in understanding the interplay of neuro-immunological signalling in AKI.


Assuntos
Injúria Renal Aguda/complicações , Biomarcadores , Biologia Computacional , Dor/etiologia , Dor/metabolismo , Transdução de Sinais , Injúria Renal Aguda/etiologia , Animais , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Camundongos , Modelos Biológicos , Anotação de Sequência Molecular , Transcriptoma
16.
Environ Toxicol ; 34(4): 375-387, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30548797

RESUMO

Metal and metal oxide nanoparticles are being used in different industries now-a-days leading to their unavoidable exposure to humans and animals. In the present study, toxicological testing was done using nanoparticles of copper oxide, cerium oxide and their mixture (1:1 ratio) on zebra fish embryos and THP-1 cell line. Zebrafish embryos were exposed to 0.01 µg/ml to 50 µg/ml concentrations of dispersed nanoparticles using a 96 well plate and their effects were studied at different hours post fertilization (hpf) i.e. 0 hpf, 24 hpf, 48 hpf, 72 hpf and 96 hpf respectively. Results showed that copper oxide nanoparticles has drastic effects on the morphology and physiology of zebra fish whereas cerium oxide nanoparticles and mixture of these nanoparticles did not show much of the effects. Comparable results were obtained from in vitro study using human monocyte cell line (THP-1). It is concluded that these nanoparticles may cause toxicological effects to humans and environment.


Assuntos
Cério/toxicidade , Cobre/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Nanopartículas/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra , Animais , Apoptose/efeitos dos fármacos , Técnicas de Cultura de Células , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cério/química , Cobre/química , Dano ao DNA , Relação Dose-Resposta a Droga , Embrião não Mamífero/patologia , Humanos , Nanopartículas/química , Propriedades de Superfície , Poluentes Químicos da Água/química , Peixe-Zebra/embriologia
17.
Mutat Res Rev Mutat Res ; 777: 19-28, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30115428

RESUMO

DNA sequence is a powerful tool that can be used for an individual's identification and investigation of various abnormalities in the genome. However, recent studies have identified other heritable changes by epigenetic mechanisms that cause changes in gene expression without altering the DNA sequence itself. In particular, DNA methylation mediates long-lasting changes in gene promoters, which makes it an appealing epigenetic mechanism to study variation in methylation status that characterizes the extent of drug abuse. We summarize recent findings on methylation alterations in a number of genes caused by various drugs including cocaine, opioids, cannabinoids, amphetamine, phenobarbital, and alcohol in various human and animal model studies. Additionally, a minimal discussion of the basic concepts of methylation is provided. The determination of possible DNA methylation alterations can assist in finding the cause and circumstances of death or ailment, and gene markers can be potentially used as biomarkers in the future.


Assuntos
Alcoolismo/genética , Metilação de DNA , Transtornos Relacionados ao Uso de Substâncias/genética , Animais , Biomarcadores , Transtornos Relacionados ao Uso de Cocaína/genética , Ilhas de CpG , Epigênese Genética , Humanos , Transtornos Relacionados ao Uso de Opioides/genética , Regiões Promotoras Genéticas
18.
Front Plant Sci ; 9: 975, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30042775

RESUMO

Thiamine deficiency is common in populations consuming polished rice as a major source of carbohydrates. Thiamine is required to synthesize thiamine pyrophosphate (TPP), an essential cofactor of enzymes of central metabolism. Its biosynthesis pathway has been partially elucidated and the effect of overexpression of a few genes such as thi1 and thiC, on thiamine accumulation in rice has been reported. Based on current knowledge, this review focuses on the potential of gene editing in metabolic engineering of thiamine biosynthesis pathway to improve thiamine in rice grains. Candidate genes, suitable for modification of the structural part to evolve more efficient versions of enzymes in the pathway, are discussed. For example, adjacent cysteine residues may be introduced in the catalytic domain of thi4 to improve the turn over activity of thiamine thiazole synthase 2. Motif specific editing to modify promoter regulatory regions of genes is discussed to modulate gene expression. Editing cis acting regulatory elements in promoter region can shift the expression of transporters and thiamine binding proteins to endosperm. This can enhance dietary availability of thiamine from rice grains. Differential transcriptomics on rice varieties with contrasting grain thiamine and functional genomic studies will identify more strategic targets for editing in future. Developing functionally enhanced foods by biofortification is a sustainable approach to make diets wholesome.

19.
J Drug Target ; 26(2): 135-149, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28670930

RESUMO

Present work describes a novel composition for encapsulating TRPsiRNA (TRPV1-targeting siRNA) within lipid-matrix (4:1::glyceryl behnate:stearic acid) of SLNs, using suitably modified cold high-pressure homogenisation technique. Optimisation of the method and composition conducted using calf-thymus DNA (ctDNA), to avoid cost of TRPsiRNA molecules, resulted in small size (d50 = 50-100 nm) and high entrapment (77.22-98.5%). Complete masking of extreme negative charge of both ctDNA (-34.50 mV) and TRPsiRNA (-23.98 mV) upon encapsulation in SLNs without employing cationic components is reported herein for the first time. Diffusion-controlled release (90.17% at 72 h) from a rigid matrix shifted to porous matrix (at 24 h) due to solubilisation of stearic acid at 37 °C. Efficient in vitro (HEK293 T cells) and in vivo transfection and expression established the proof-of-concept. PEG600 as supporting-surfactant and vitrifying agent promoted small size, effective transfection and rupture of endosomal membrane to affect endosomal escape. Physiological efficacy in terms of significant increase (p < .0001) in paw-withdrawal-latency, following topical and intradermal application of TRPsiRNA-loaded SLNs, in rats, exposed to thermal hyperalgesia (145 and 182%, respectively) and capsaicin-induced pain (155 and 182%, respectively) indicate effective silencing of skin TRPV1. Significant decrease in intensity and duration (one-fifth) of capsaicin-induced nocifensive behaviour was also observed. Naked TRPsiRNA, however, did not show any effect.


Assuntos
Inativação Gênica , Dor/prevenção & controle , RNA Interferente Pequeno , Canais de Cátion TRPV/administração & dosagem , Administração Tópica , Animais , Capsaicina/toxicidade , Feminino , Dor/induzido quimicamente , Ratos , Ratos Wistar
20.
Clin Exp Ophthalmol ; 46(1): 54-61, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28600806

RESUMO

IMPORTANCE: This study evaluates two rapid electrophysiological glaucoma diagnostic tests that may add a functional perspective to glaucoma diagnosis. BACKGROUND: This study aimed to determine the ability of two office-based electrophysiological diagnostic tests, steady-state pattern electroretinogram and short-duration transient visual evoked potentials, to discern between glaucomatous and healthy eyes. DESIGN: This is a cross-sectional study in a hospital setting. PARTICIPANTS: Forty-one patients with glaucoma and 41 healthy volunteers participated in the study. METHODS: Steady-state pattern electroretinogram and short-duration transient visual evoked potential testing was conducted in glaucomatous and healthy eyes. A 64-bar-size stimulus with both a low-contrast and high-contrast setting was used to compare steady-state pattern electroretinogram parameters in both groups. A low-contrast and high-contrast checkerboard stimulus was used to measure short-duration transient visual evoked potential parameters in both groups. MAIN OUTCOME MEASURES: Steady-state pattern electroretinogram parameters compared were MagnitudeD, MagnitudeD/Magnitude ratio, and the signal-to-noise ratio. Short-duration transient visual evoked potential parameters compared were amplitude and latency. RESULTS: MagnitudeD was significantly lower in glaucoma patients when using a low-contrast (P = 0.001) and high-contrast (P < 0.001) 64-bar-size steady-state pattern electroretinogram stimulus. MagnitudeD/Magnitude ratio and SNR were significantly lower in the glaucoma group when using a high-contrast 64-bar-size stimulus (P < 0.001 and P = 0.010, respectively). Short-duration transient visual evoked potential amplitude and latency were not significantly different between the two groups. CONCLUSIONS AND RELEVANCE: Steady-state pattern electroretinogram was effectively able to discern between glaucomatous and healthy eyes. Steady-state pattern electroretinogram may thus have a role as a clinically useful electrophysiological diagnostic tool.


Assuntos
Eletrorretinografia/métodos , Potenciais Evocados Visuais/fisiologia , Glaucoma de Ângulo Aberto/diagnóstico , Pressão Intraocular/fisiologia , Idoso , Estudos Transversais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Campos Visuais/fisiologia
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