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1.
Chem Rec ; 22(7): e202200030, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35475530

RESUMO

The emerging concept of the hydrogen economy is facing challenges associated with hydrogen storage and transport. The utilization of ammonia as an energy (hydrogen) carrier for the on-site generation of hydrogen via ammonia decomposition has gained attraction among the scientific community. Ruthenium-based catalysts are highly active but their high cost and less abundance are limitations for scale-up application. Therefore, combining ruthenium with cheaper transition metals such as nickel, cobalt, iron, molybdenum, etc., to generate metal-metal (bimetallic) surfaces suitable for ammonia decomposition has been investigated in recent years. Herein, the recent trends in developing bimetallic catalyst systems, the role of metal type, support materials, promoter, synthesis techniques, and the investigations of the reaction kinetics and mechanism for ammonia decomposition have been reviewed.

2.
J Contemp Dent Pract ; 20(1): 83-88, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31058618

RESUMO

AIM: To evaluate solubility of soft denture liner material and acrylic denture base resin when stored in 8% and 50% concentration of alcohol and tea(with milk and green tea) at an interval of 4,7,11 and 15 days. MATERIALS AND METHODS: An in vitro study wasdone on 75 standardized samples in disk form (15 mm × 2 mm), each for soft-liner and acrylic denture base resin. Samples were divided into 5 groups (15 per group/per material) and stored in distilled water (A), 8% alcohol (B), 50% alcohol (C), tea with milk (D) and green tea (E). Solubility was determined at each time interval by dividing difference of weight (taken after drying the sample in a desiccator) from day 1 divided by surface area of the specimen. For each day (i.e., 4, 7, 11 and 15),one-way analysis of variance (ANOVA) test was used to determine if the distribution of mean solubility was similar in five groups followed by post-hoc Tukey's test for pair-wise comparisons. RESULTS: Mean solubility of soft-liner was the highest tea with milk (D) followed by green tea (E), then 50% and 8 % alcohol (C and B) and was least in group A at each time of measurement. Mean solubility of an acrylic resin was highest for 8% alcohol (B) and all other groups it was similar. CONCLUSION: This study shows increased solubility for soft-liners when immersed in tea with milk, green tea, and alcohol at 8% and 50% concentration. The solubility of acrylic resin also increases at 8% alcohol concentration. CLINICAL SIGNIFICANCE: Drinks/beverages used in our study are commonly consumed, the results of this study caution for restricting the frequency of intake. However, this needs to be confirmed by in-vivo studies designed to prove the association of denture life with the consumption pattern of these drinks/ beverages.


Assuntos
Polimetil Metacrilato , Chá , Teste de Materiais , Solubilidade , Propriedades de Superfície
3.
Pak J Pharm Sci ; 30(2): 449-457, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28649069

RESUMO

Antibacterial effect is one of the major therapeutic activities of plant-derived Curcumin. This work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of Curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. Toxicological effects of Curcumin towards human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were also investigated. Curcumin exhibited weak activity against gram-negative bacteria, except Escherichia coli and Shigella flexneri were susceptible and was most active against gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis. The antibacterial activity was impaired in the presence of bovine serum albumin (BSA), human plasma and whole blood. Curcumin was not toxic to PBMCs and RBCs at 200µg/mL. Furthermore, Curcumin showed synergistic activity in combination with antibiotics: Ciprofloxacin, Gentamicin, Vancomycin and Amikacin against Staphylococcus aureus. This study demonstrated that the interaction of Curcumin with plasma proteins diminishes its in vitro antibacterial activity. Curcumin derivatives with reduced affinity for plasma protein may improve the bioavailability and antibacterial activities.


Assuntos
Antibacterianos/farmacologia , Fenômenos Fisiológicos Sanguíneos , Curcumina/farmacologia , Albumina Sérica/efeitos adversos , Antibacterianos/efeitos adversos , Curcumina/efeitos adversos , Sinergismo Farmacológico , Eritrócitos/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Testes de Sensibilidade Microbiana
4.
Mol Cell Proteomics ; 12(7): 1881-99, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23547263

RESUMO

Although it has been established that all toxicoferan squamates share a common venomous ancestor, it has remained unclear whether the maxillary and mandibular venom glands are evolving on separate gene expression trajectories or if they remain under shared genetic control. We show that identical transcripts are simultaneously expressed not only in the mandibular and maxillary glands, but also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin), cobra venom factor, cystatin, epididymal secretory protein, kunitz, L-amino acid oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also discovered a novel low-molecular weight disulfide bridged peptide class in pythonid snake glands. In the iguanian lizards, the most highly expressed are potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin), with crotamine (beta-defensin) also the most diverse. However, a number of proteins characterized from anguimorph lizards and caenophidian snakes with hemotoxic or neurotoxic activities were recruited in the common toxicoferan ancestor and remain expressed, albeit in low levels, even in the iguanian lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as the dominant transcripts. Even in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom thus appears to play little role in feeding behavior of most iguanian lizards or the powerful constricting snakes, and the low levels of expression argue against a defensive role. However, clearly the incipient or secondarily atrophied venom systems of these taxa may be a source of novel compounds useful in drug design and discovery.


Assuntos
Lagartos/genética , Serpentes/genética , Peçonhas/genética , Sequência de Aminoácidos , Animais , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Transcriptoma , Peçonhas/química
5.
J Cell Sci ; 125(Pt 11): 2732-9, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22393235

RESUMO

The osteogenic and oncogenic transcription factor RUNX2 downregulates the RNA polymerase I (RNA Pol I)-mediated transcription of rRNAs and changes histone modifications associated with the rDNA repeat. However, the mechanisms by which RUNX2 suppresses rRNA transcription are not well understood. RUNX2 cofactors such as histone deacetylases (HDACs) play a key role in chromatin remodeling and regulation of gene transcription. Here, we show that RUNX2 recruits HDAC1 to the rDNA repeats in osseous cells. This recruitment alters the histone modifications associated with active rRNA-encoding genes and causes deacetylation of the protein upstream binding factor (UBF, also known as UBTF). Downregulation of RUNX2 expression reduces the localization of HDAC1 to the nucleolar periphery and also decreases the association between HDAC1 and UBF. Functionally, depletion of HDAC1 relieves the RUNX2-mediated repression of rRNA-encoding genes and concomitantly increases cell proliferation and global protein synthesis in osseous cells. Our findings collectively identify a RUNX2-HDAC1-dependent mechanism for the regulation of rRNA-encoding genes and suggest that there is plasticity to RUNX2-mediated epigenetic control, which is mediated through selective mitotic exclusion of co-regulatory factors.


Assuntos
Proteínas Correpressoras/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação da Expressão Gênica , Histona Desacetilase 1/metabolismo , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , RNA Ribossômico/genética , Acetilação , Linhagem Celular , Nucléolo Celular/metabolismo , Proliferação de Células , Cromatina/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/química , DNA Ribossômico/metabolismo , Técnicas de Silenciamento de Genes , Loci Gênicos/genética , Histonas/metabolismo , Humanos , Interfase , Ligação Proteica , Biossíntese de Proteínas , Transporte Proteico , RNA Ribossômico/metabolismo , RNA Interferente Pequeno/metabolismo , Transcrição Gênica
6.
J Mol Evol ; 76(4): 192-204, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23456102

RESUMO

In this study, we report for the first time a detailed evaluation of the phylogenetic history and molecular evolution of the major coleoid toxins: CAP, carboxypeptidase, chitinase, metalloprotease GON-domain, hyaluronidase, pacifastin, PLA2, SE-cephalotoxin and serine proteases, with the carboxypeptidase and GON-domain documented for the first time in the coleoid venom arsenal. We show that although a majority of sites in these coleoid venom-encoding genes have evolved under the regime of negative selection, a very small proportion of sites are influenced by the transient selection pressures. Moreover, nearly 70 % of these episodically adapted sites are confined to the molecular surface, highlighting the importance of variation of the toxin surface chemistry. Coleoid venoms were revealed to be as complex as other venoms that have traditionally been the recipient of the bulk of research efforts. The presence of multiple peptide/protein types in coleoids similar to those present in other animal venoms identifies a convergent strategy, revealing new information as to what characteristics make a peptide/protein type amenable for recruitment into chemical arsenals. Coleoid venoms have significant potential not only for understanding fundamental aspects of venom evolution but also as an untapped source of novel toxins for use in drug design and discovery.


Assuntos
Estruturas Animais/química , Decapodiformes/química , Evolução Molecular , Octopodiformes/química , Filogenia , Proteínas/genética , Peçonhas/química , Sequência de Aminoácidos , Estruturas Animais/anatomia & histologia , Animais , Sequência Conservada , Decapodiformes/genética , Venenos de Peixe/química , Venenos de Peixe/genética , Biblioteca Gênica , Dados de Sequência Molecular , Venenos de Moluscos/química , Venenos de Moluscos/genética , Mutação , Octopodiformes/genética , Estrutura Terciária de Proteína , Proteínas/química , Seleção Genética , Peçonhas/genética
7.
BMC Biotechnol ; 13: 107, 2013 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-24304876

RESUMO

BACKGROUND: HIV genome is packaged and organized in a conical capsid, which is made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary structural component and due to its critical roles in both late and early stages of the HIV replication cycle, CA has attracted increased interest as a drug discovery target in recent years. Drug discovery studies require large amounts of highly pure and biologically active protein. It is therefore desirable to establish a simple and reproducible process for efficient production of HIV-1 CA. RESULT: In this work, 6-His-tagged wild type CA from HIV-1 (NL4.3) was expressed in rare tRNA-supplemented NiCo21(DE3) Escherichia coli, and its production was studied in shake flask culture condition of expression. Influences of various key cultivation parameters were examined to identify optimal conditions for HIV-1 CA production. It was found that a culture temperature of 22°C and induction with 0.05 mM IPTG at the early stage of growth were ideal, leading to a maximum biomass yield when grown in Super broth supplemented with 1% glucose. With optimized culture conditions, a final biomass concentration of ~27.7 g L⁻¹ (based on optical density) was obtained in 12 hours post-induction, leading to a yield of about ~170 mg L⁻¹ HIV-1 CA. A two-step purification strategy (chitin beads + IMAC) was employed, which efficiently removed metal affinity resin-binding bacterial proteins that contaminate recombinant His-tagged protein preparation, and resulted in highly pure HIV-1 CA. The purified protein was capable of polymerization when tested in an in vitro polymerization assay. CONCLUSIONS: By using this optimized expression and purification procedure, milligram amounts of highly pure and polymerization-competent recombinant HIV-1 CA can be produced at the lab-scale and thus used for further biochemical studies.


Assuntos
Proteínas do Capsídeo/biossíntese , Escherichia coli/genética , Proteína do Núcleo p24 do HIV/biossíntese , HIV-1/genética , Proteínas do Capsídeo/genética , Meios de Cultura , Escherichia coli/metabolismo , Células HEK293 , Proteína do Núcleo p24 do HIV/genética , HIV-1/fisiologia , Humanos , Plasmídeos/genética , Polimerização , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Replicação Viral
8.
J Virol ; 86(1): 406-19, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22013042

RESUMO

Nef is secreted from infected cells in exosomes and is found in abundance in the sera of HIV-infected individuals. Secreted exosomal Nef (exNef) induces apoptosis in uninfected CD4⁺ T cells and may be a key component of HIV pathogenesis. The exosomal pathway has been implicated in HIV-1 virus release, suggesting a possible link between these two viral processes. However, the underlying mechanisms and cellular components of exNef secretion have not been elucidated. We have previously described a Nef motif, the secretion modification region (SMR; amino acids 66 to 70), that is required for exNef secretion. In silico modeling data suggest that this motif can form a putative binding pocket. We hypothesized that the Nef SMR binds a cellular protein involved in protein trafficking and that inhibition of this interaction would abrogate exNef secretion. By using tandem mass spectrometry and coimmunoprecipitation with a novel SMR-based peptide (SMRwt) that blocks exNef secretion and HIV-1 virus release, we identified mortalin as an SMR-specific cellular protein. A second set of coimmunoprecipitation experiments with full-length Nef confirmed that mortalin interacts with Nef via Nef's SMR motif and that this interaction is disrupted by the SMRwt peptide. Overexpression and microRNA knockdown of mortalin revealed a positive correlation between exNef secretion levels and mortalin protein expression. Using antibody inhibition we demonstrated that the Nef/mortalin interaction is necessary for exNef secretion. Taken together, this work constitutes a significant step in understanding the underlying mechanism of exNef secretion, identifies a novel host-pathogen interaction, and introduces an HIV-derived peptide with antiviral properties.


Assuntos
Espaço Extracelular/metabolismo , Infecções por HIV/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Peptídeos/metabolismo , Produtos do Gene nef do Vírus da Imunodeficiência Humana/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Linhagem Celular , Exossomos/genética , Exossomos/metabolismo , Infecções por HIV/genética , Infecções por HIV/virologia , HIV-1/genética , HIV-1/metabolismo , Proteínas de Choque Térmico HSP70/genética , Humanos , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/genética , Ligação Proteica , Transporte Proteico , Produtos do Gene nef do Vírus da Imunodeficiência Humana/química , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética
9.
Proc Natl Acad Sci U S A ; 107(9): 4165-9, 2010 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-20160071

RESUMO

Epigenetic control of ribosomal RNA (rRNA) gene transcription by cell type-specific regulators, such as the osteogenic transcription factor Runx2, conveys cellular memory of growth and differentiation to progeny cells during mitosis. Here, we examined whether coregulatory proteins contribute to epigenetic functions that are mitotically transmitted by Runx2 in osteoblastic cells. We show that the transcriptional corepressor Transducin Like Enhancer-1 (TLE1) associates with rRNA genes during mitosis and interphase through interaction with Runx2. Mechanistically, depletion of TLE1 relieves Runx2-mediated repression of rRNA genes transcription and selectively increases histone modifications linked to active transcription. Biologically, loss of TLE-dependent rRNA gene repression coincides with increased global protein synthesis and enhanced cell proliferation. Our findings reinforce the epigenetic marking target genes by phenotypic transcription factors in mitosis and demonstrate a requirement for retention of coregulatory factors to sustain physiological control of gene expression during proliferation of lineage committed cells.


Assuntos
Epigênese Genética , RNA Ribossômico/genética , Proteínas Repressoras/fisiologia , Transcrição Gênica , Linhagem Celular Tumoral , Proteínas Correpressoras , Humanos , Imunoprecipitação , Microscopia de Fluorescência , Região Organizadora do Nucléolo
10.
Mol Cancer ; 11: 27, 2012 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-22537242

RESUMO

BACKGROUND: The Runt-related transcription factor Runx2 is essential for bone development but is also implicated in progression of several cancers of breast, prostate and bone, where it activates cancer-related genes and promotes invasive properties. The transforming growth factor ß (TGF-ß) family member bone morphogenetic protein-3B (BMP-3B/GDF10) is regarded as a tumor growth inhibitor and a gene silenced in lung cancers; however the regulatory mechanisms leading to its silencing have not been identified. RESULTS: Here we show that Runx2 is highly expressed in lung cancer cells and downregulates BMP-3B. This inverse relationship between Runx2 and BMP-3B expression is further supported by increased expression of BMP-3B in mesenchymal cells from Runx2 deficient mice. The ectopic expression of Runx2, but not DNA binding mutant Runx2, in normal lung fibroblast cells and lung cancer cells resulted in suppression of BMP-3B levels. The chromatin immunoprecipitation studies identified that the mechanism of Runx2-mediated suppression of BMP-3B is due to the recruitment of Runx2 and histone H3K9-specific methyltransferase Suv39h1 to BMP-3B proximal promoter and a concomitant increase in histone methylation (H3K9) status. The knockdown of Runx2 in H1299 cells resulted in decreased histone H3K9 methylation on BMP-3B promoter and increased BMP-3B expression levels. Furthermore, co-immunoprecipitation studies showed a direct interaction of Runx2 and Suv39h1 proteins. Phenotypically, Runx2 overexpression in H1299 cells increased wound healing response to TGFß treatment. CONCLUSIONS: Our studies identified BMP-3B as a new Runx2 target gene and revealed a novel function of Runx2 in silencing of BMP-3B in lung cancers. Our results suggest that Runx2 is a potential therapeutic target to block tumor suppressor gene silencing in lung cancer cells.


Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Inativação Gênica , Fator 10 de Diferenciação de Crescimento/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Animais , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/biossíntese , Fator 10 de Diferenciação de Crescimento/deficiência , Neoplasias Pulmonares/patologia , Mesoderma/citologia , Mesoderma/metabolismo , Metiltransferases , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , Proteínas Repressoras , Crânio/citologia
11.
Am J Ophthalmol Case Rep ; 27: 101608, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35692436

RESUMO

Purpose: DiGeorge (22q11.2 deletion) syndrome is the most common human deletion syndrome with wide range of ocular manifestations. Herein we describe a case with novel retinal observations in this conditions. Observations: Retinal vascular dysplasia, peripapillary, intraretinal and vitreous hemorrhage were observed in a premature child with DiGeorge syndrome. Vitreous hemorrhage was treated with intravitreal injection of anti-angiogenicagents and pars plana vitrectomy surgery. Fundus fluorescein angiography did not confirm leakage of dye from dysplastic retinal vessels. Conclusions and Importance: Patients with DiGeorge syndrome may develop retinal vascular dysplasia, peripapillary, intraretinal and vitreous hemorrhage.

12.
Sci Total Environ ; 838(Pt 2): 155845, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35561902

RESUMO

Recent drought events in the Mekong River Basin (MRB) have resulted in devastating environmental and economic losses, and climate change and human-induced alterations have exacerbated drought conditions. Using hydrologic models and multiple climate change scenarios, this study quantified the future climate change impacts on conventional and flash drought conditions in the MRB. The Soil and Water Assessment Tool (SWAT) and Variable Infiltration Capacity (VIC) models were applied to estimate long-term drought indices for conventional and flash drought conditions over historical and future periods (1966-2099), using two emission scenarios (RCP 4.5 and RCP8.5), and four climate models from the Coupled Model Intercomparison Project Phase 5 (CMIP5). For the conventional drought assessment, monthly scale drought indices were estimated, and pentad-scale (5 days) drought indices were computed for the flash drought evaluations. There were overall increases in droughts from the SWAT model for the conventional drought conditions and overall decreases from the VIC model. For the flash drought conditions, the SWAT-driven drought indices showed overall increases in drought occurrences (up to 165%). On the contrary, the VIC-driven drought indices presented decreases in drought occurrences (up to -44%). The conventional and flash drought evaluations differ between these models as they partition the water budget, specifically soil moisture differently. We conclude that the proposed framework, which includes hydrologic models, various emission scenarios, and projections, allows us to assess the various perspectives on drought conditions. Basin countries have differential impacts, so targeted future adaptation strategy is required.


Assuntos
Mudança Climática , Rios , Secas , Humanos , Solo , Água
13.
JCI Insight ; 7(8)2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35271506

RESUMO

The persistence of virally infected cells as reservoirs despite effective antiretroviral therapy is a major barrier to an HIV/SIV cure. These reservoirs are predominately contained within cells present in the B cell follicles (BCFs) of secondary lymphoid tissues, a site that is characteristically difficult for most cytolytic antiviral effector cells to penetrate. Here, we identified a population of NK cells in macaque lymph nodes that expressed BCF-homing receptor CXCR5 and accumulated within BCFs during chronic SHIV infection. These CXCR5+ follicular NK cells exhibited an activated phenotype coupled with heightened effector functions and a unique transcriptome characterized by elevated expression of cytolytic mediators (e.g., perforin and granzymes, LAMP-1). CXCR5+ NK cells exhibited high expression of FcγRIIa and FcγRIIIa, suggesting a potential for elevated antibody-dependent effector functionality. Consistently, accumulation of CXCR5+ NK cells showed a strong inverse association with plasma viral load and the frequency of germinal center follicular Th cells that comprise a significant fraction of the viral reservoir. Moreover, CXCR5+ NK cells showed increased expression of transcripts associated with IL-12 and IL-15 signaling compared with the CXCR5- subset. Indeed, in vitro treatment with IL-12 and IL-15 enhanced the proliferation of CXCR5+ granzyme B+ NK cells. Our findings suggest that follicular homing NK cells might be important in immune control of chronic SHIV infection, and this may have important implications for HIV cure strategies.


Assuntos
Infecções por HIV , Interleucina-15 , Humanos , Interleucina-12/metabolismo , Interleucina-15/metabolismo , Células Matadoras Naturais , Linfonodos , Receptores CXCR5/metabolismo
14.
Proc Natl Acad Sci U S A ; 105(18): 6632-7, 2008 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-18445650

RESUMO

Ribosomal RNA (rRNA) genes are down-regulated during osteogenesis, myogenesis, and adipogenesis, necessitating a mechanistic understanding of interrelationships between growth control and phenotype commitment. Here, we show that cell fate-determining factors [MyoD, myogenin (Mgn), Runx2, C/EBPbeta] occupy rDNA loci and suppress rRNA expression during lineage progression, concomitant with decreased rRNA expression and reciprocal loss of occupancy by c-Myc, a proliferation-specific activator of rRNA transcription. We find interaction of phenotypic factors with the polymerase I activator upstream binding factor UBF-1 at interphase nucleoli, and this interaction is epigenetically retained on mitotic chromosomes at nucleolar organizing regions. Ectopic expression and RNA interference establish that MyoD, Mgn, Runx2, and C/EBPbeta each functionally suppress rRNA genes and global protein synthesis. We conclude that epigenetic control of ribosomal biogenesis by lineage-specific differentiation factors is a general developmental mechanism for coordinate control of cell growth and phenotype.


Assuntos
Epigênese Genética , Fatores de Transcrição/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Linhagem da Célula , Proliferação de Células , DNA Ribossômico/genética , Regulação para Baixo/genética , Mesoderma/citologia , Camundongos , Proteína MyoD/metabolismo , Miogenina/metabolismo , Região Organizadora do Nucléolo , Fenótipo , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , Ligação Proteica , Biossíntese de Proteínas , Transporte Proteico , RNA Ribossômico/genética , Sequências Repetitivas de Ácido Nucleico , Transcrição Gênica
16.
Cureus ; 13(7): e16395, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34408948

RESUMO

14q22q23 microdeletion syndrome, also called Frias syndrome, is an extremely rare partial deletion of the long arm of chromosome 14 characterized by the anomalies of the pituitary gland, eyes, and hand/foot. Intellectual disability and facial dysmorphism are other common manifestations. Haploinsufficiency of the genes bone morphogenetic protein 4 (BMP4) and orthodenticle homeobox 2 (OTX2) accounts for most of the phenotypic abnormalities seen in these patients. There are only a few cases reported with Frias syndrome in the literature, and there are multiple variations present, which are not well recognized due to different set of genes involved. This case report presents the case of a young child with a deletion in 14q22.2q23.1 region containing both BMP4 and OTX2 genes as well as sineoculis homeobox homolog 1 (SIX1) and sineoculis homeobox homolog 6 (SIX6) genes. The case report illustrates the wide phenotypic findings associated with these genes along with additional unique findings that previously have not been commonly reported.

17.
Front Cell Dev Biol ; 9: 568660, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33869165

RESUMO

The mammary gland is a unique apocrine gland made up of a branching network of ducts that end in alveoli. It is an ideal system to study the molecular mechanisms associated with cell proliferation, differentiation, and oncogenesis. MFG-E8, also known as Lactadherin, is a vital glycoprotein related to the milk fat globule membrane and initially identified to get secreted in bovine milk. Our previous report suggests that a high level of MFG-E8 is indicative of high milk yield in dairy animals. Here, we showed that MFG-E8 controls the cell growth and morphology of epithelial cells through a network of regulatory transcription factors. To understand the comprehensive action, we downregulated its expression in MECs by MFG-E8 specific shRNA. We generated a knockdown proteome profile of differentially expressed proteins through a quantitative iTRAQ experiment on a high-resolution mass spectrometer (Q-TOF). The downregulation of MFG-E8 resulted in reduced phagocytosis and cell migration ability, whereas it also leads to more lifespan to knockdown vis-a-vis healthy cells, which is confirmed through BrdU, MTT, and Caspase 3/7. The bioinformatics analysis revealed that MFG-E8 knockdown perturbs a large number of intracellular signaling, eventually leading to cessation in cell growth. Based on the directed network analysis, we found that MFG-E8 is activated by CX3CL1, TP63, and CSF2 and leads to the activation of SOCS3 and CCL2 for the regulation of cell proliferation. We further proved that the depletion of MFG-E8 resulted in activated cytoskeletal remodeling by MFG-E8 knockdown, which results in the activation of three independent pathways ZP4/JAK-STAT5, DOCK1/STAT3, and PIP3/AKT/mTOR. Overall, this study suggests that MFG-E8 expression in mammary epithelial cells is an indication of intracellular deterioration in cell health. To date, to the best of our knowledge, this is the first study that explores the downstream targets of MFG-E8 involved in the regulation of mammary epithelial cell health.

18.
Toxins (Basel) ; 13(2)2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540884

RESUMO

Snakes of the genera Pseudocerastes and Eristicophis (Viperidae: Viperinae) are known as the desert vipers due to their association with the arid environments of the Middle East. These species have received limited research attention and little is known about their venom or ecology. In this study, a comprehensive analysis of desert viper venoms was conducted by visualising the venom proteomes via gel electrophoresis and assessing the crude venoms for their cytotoxic, haemotoxic, and neurotoxic properties. Plasmas sourced from human, toad, and chicken were used as models to assess possible prey-linked venom activity. The venoms demonstrated substantial divergence in composition and bioactivity across all experiments. Pseudocerastes urarachnoides venom activated human coagulation factors X and prothrombin and demonstrated potent procoagulant activity in human, toad, and chicken plasmas, in stark contrast to the potent neurotoxic venom of P. fieldi. The venom of E. macmahonii also induced coagulation, though this did not appear to be via the activation of factor X or prothrombin. The coagulant properties of P. fieldi and P. persicus venoms varied among plasmas, demonstrating strong anticoagulant activity in the amphibian and human plasmas but no significant effect in that of bird. This is conjectured to reflect prey-specific toxin activity, though further ecological studies are required to confirm any dietary associations. This study reinforces the notion that phylogenetic relatedness of snakes cannot readily predict venom protein composition or function. The significant venom variation between these species raises serious concerns regarding antivenom paraspecificity. Future assessment of antivenom is crucial.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Junção Neuromuscular/efeitos dos fármacos , Comportamento Predatório , Proteínas de Répteis/toxicidade , Mordeduras de Serpentes/metabolismo , Peçonhas/toxicidade , Viperidae/metabolismo , Animais , Anuros , Linhagem Celular Tumoral , Galinhas , Humanos , Masculino , Junção Neuromuscular/fisiopatologia , Proteoma , Proteômica , Proteínas de Répteis/metabolismo , Mordeduras de Serpentes/sangue , Mordeduras de Serpentes/fisiopatologia , Especificidade da Espécie , Peçonhas/metabolismo
19.
AJR Am J Roentgenol ; 194(3): 721-7, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20173151

RESUMO

OBJECTIVE: The objective of our study was to assess patellofemoral measurements on MRI and to correlate the measurements with different grades of cartilage defect. MATERIALS AND METHODS: Axial and sagittal MR images of 100 patients with various pathologic knee conditions were analyzed. The patients were divided into two age groups: < 40 years and > or = 40 years. Patellar measurements of facet asymmetry, the patella-to-patellar tendon ratio, and the amount of patellotrochlear cartilage overlap were obtained in each subject. Similarly, trochlear measurements of the ventral trochlear prominence, trochlear depth, facet asymmetry, sulcus angle, and lateral inclination were obtained. Axial and sagittal MR images were reviewed to grade the severity of focal cartilage defects in the patellofemoral region on the basis of the depth of the lesion. Measurements in knees without a chondral defect were compared with knees with mild and severe chondral defects. RESULTS: There was a statistically significant difference in the trochlear measurements of the ventral prominence (p = 0.012), trochlear depth (p = 0.001), sulcus angle (p = 0.208), and lateral inclination (p = 0.154) between normal knees and knees with severe cartilage defects in patients younger than 40 years. No significant difference was seen in the patellar measurements between normal knees and knees with severe cartilage defects. CONCLUSION: There is an association between abnormal trochlear morphology and severe patellofemoral cartilage defects in patients younger than 40 years.


Assuntos
Cartilagem Articular/patologia , Fêmur/patologia , Imageamento por Ressonância Magnética/métodos , Patela/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Dor Patelofemoral/patologia , Estudos Retrospectivos
20.
JOP ; 11(1): 41-4, 2010 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-20065551

RESUMO

CONTEXT: Intrahepatic pancreatic pseudocyst extension is a rare but complex clinical entity requiring multimodality approach for management. There is no consensus regarding the optimal strategy for the treatment of intrahepatic pancreatic pseudocyst and the literature is limited to a few case reports. Most of the published cases were managed by surgical or percutaneous drainage. CASE REPORT: We hereby report a case of intrahepatic pancreatic pseudocyst extension which failed to resolve by percutaneous drainage. Endoscopic transpapillary drainage was utilized which led to complete resolution of the intrahepatic pancreatic pseudocyst. CONCLUSION: The excellent results obtained in our patient suggest that it should be considered as primary treatment and may obviate the need for more aggressive and potentially morbid procedures.


Assuntos
Endoscopia/métodos , Fígado/cirurgia , Pseudocisto Pancreático/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Drenagem , Humanos , Masculino , Pessoa de Meia-Idade , Pseudocisto Pancreático/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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