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1.
Artigo em Inglês | MEDLINE | ID: mdl-38912732

RESUMO

Fibrostenosing Crohn's disease (CD) represents a challenging clinical condition characterized by the development of symptomatic strictures within the gastrointestinal tract. Despite therapeutic advancements in managing inflammation, the progression of fibrostenotic complications remains a significant concern, often necessitating surgical intervention. Recent investigations have unveiled the pivotal role of smooth muscle cell hyperplasia in driving luminal narrowing and clinical symptomatology. Drawing parallels to analogous inflammatory conditions affecting other organs, such as the airways and blood vessels, sheds light on common underlying mechanisms of muscular hyperplasia. This review synthesizes current evidence to elucidate the mechanisms underlying smooth muscle cell proliferation in CD-associated strictures, offering insights into potential therapeutic targets. By highlighting the emerging significance of muscle thickening as a novel therapeutic target, this review aims to inform future research endeavors and clinical strategies with the goal to mitigate the burden of fibrostenotic complications in CD and other conditions.

2.
Biophys J ; 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717144

RESUMO

Macromolecular solubility is an important contributor to the driving forces for phase separation. Formally, the driving forces in a binary mixture comprising a macromolecule dissolved in a solvent can be quantified in terms of the saturation concentration, which is the threshold macromolecular concentration above which the mixture separates into coexisting dense and dilute phases. In addition, the second virial coefficient, which measures the effective strength of solvent-mediated intermolecular interactions provides direct assessments of solvent quality. The sign and magnitude of second virial coefficients will be governed by a combination of solution conditions and the nature of the macromolecule of interest. Here, we show, using a combination of theory, simulation, and in vitro experiments, that titrations of crowders, providing they are true depletants, can be used to extract the intrinsic driving forces for macromolecular phase separation. This refers to saturation concentrations in the absence of crowders and the second virial coefficients that quantify the magnitude of the incompatibility between macromolecules and the solvent. Our results show how the depletion-mediated attractions afforded by crowders can be leveraged to obtain comparative assessments of macromolecule-specific, intrinsic driving forces for phase separation.

3.
Small ; 19(14): e2204637, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36642859

RESUMO

Interest in the development of new generation injectable bone cements having appropriate mechanical properties, biodegradability, and bioactivity has been rekindled with the advent of nanoscience. Injectable bone cements made with calcium sulfate (CS) are of significant interest, owing to its compatibility and optimal self-setting property. Its rapid resorption rate, lack of bioactivity, and poor mechanical strength serve as a deterrent for its wide application. Herein, a significantly improved CS-based injectable bone cement (modified calcium sulfate termed as CSmod ), reinforced with various concentrations (0-15%) of a conductive nanocomposite containing gold nanodots and nanohydroxyapatite decorated reduced graphene oxide (rGO) sheets (AuHp@rGO), and functionalized with vancomycin, is presented. The piezo-responsive cement exhibits favorable injectability and setting times, along with improved mechanical properties. The antimicrobial, osteoinductive, and osteoconductive properties of the CSmod cement are confirmed using appropriate in vitro studies. There is an upregulation of the paracrine signaling mediated crosstalk between mesenchymal stem cells and human umbilical vein endothelial cells seeded on these cements. The ability of CSmod to induce endothelial cell recruitment and augment bone regeneration is evidenced in relevant rat models. The results imply that the multipronged activity exhibited by the novel-CSmod cement would be beneficial for bone repair.


Assuntos
Cimentos Ósseos , Nanocompostos , Ratos , Animais , Humanos , Cimentos Ósseos/farmacologia , Durapatita , Ouro , Sulfato de Cálcio , Células Endoteliais , Regeneração Óssea , Fosfatos de Cálcio , Força Compressiva
4.
Arch Biochem Biophys ; 717: 109124, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35085577

RESUMO

The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2) with an estimated fatality rate of less than 1%. The SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 possess putative functions to manipulate host immune mechanisms. These involve interferons, which appear as a consensus function, immune signaling receptor NLRP3 (NLR family pyrin domain-containing 3) inflammasome, and inflammatory cytokines such as interleukin 1ß (IL-1ß) and are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins were observed across six continents of all complete SARS-CoV-2 proteomes based on the data reported before November 2020. A decreasing order of percentage of unique variations in the accessory proteins was determined as ORF3a > ORF8 > ORF7a > ORF6 > ORF10 > ORF7b across all continents. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. These findings suggest that the wide variations in accessory proteins seem to affect the pathogenicity of SARS-CoV-2.


Assuntos
COVID-19/virologia , SARS-CoV-2/genética , Proteínas Virais/genética , Proteínas Viroporinas/genética , COVID-19/patologia , Variação Genética , Humanos , Filogenia , SARS-CoV-2/patogenicidade
5.
Biotechnol Bioeng ; 119(2): 452-469, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34811720

RESUMO

Chemically defined (CD) media are routinely used in the production of biologics in Chinese hamster ovary (CHO) cell culture and provide enhanced raw material control. Nutrient optimized CD media is an important path to increase cell growth and monoclonal antibody (mAb) productivity in recombinant CHO cell lines. However, nutrient optimization efforts for CD media typically rely on multifactorial and experimental design of experiment approaches or complex mathematical models of cellular metabolism or gene expression systems. Moreover, the majority of these efforts are aimed at amino acids since they constitute essential nutrients in CD media as they directly contribute to biomass and protein production. In this study, we demonstrate the utilization of multivariate data analytics (MVDA) coupled with amino acid stoichiometric balances (SBs) to increased cell growth and mAb productivity in efforts to support CD media development efforts. SBs measure the difference between theoretical demand of amino acids and the empirically measured fluxes to identify various catabolic or anabolic states of the cell. When coupled with MVDA, the statistical models were not only able to highlight key amino acids toward cell growth or productivity, but also provided direction on metabolic favorability of the amino acid. Experimental validation of our approach resulted in a 55% increase in total cell growth and about an 80% increase in total mAb productivity. Increased specific consumption of stoichiometrically balanced amino acids and decreased specific consumption of glucose was also observed in optimized CD media suggesting favorable consumption of desired nutrients and a potential for energy redistribution toward increased cellular growth and mAb productivity.


Assuntos
Aminoácidos , Técnicas de Cultura de Células/métodos , Biologia Computacional/métodos , Meios de Cultura , Análise Multivariada , Aminoácidos/análise , Aminoácidos/química , Aminoácidos/metabolismo , Animais , Anticorpos Monoclonais/metabolismo , Células CHO , Proliferação de Células/fisiologia , Cricetinae , Cricetulus , Meios de Cultura/química , Meios de Cultura/metabolismo , Análise dos Mínimos Quadrados
6.
Environ Res ; 204(Pt D): 112407, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34801543

RESUMO

The current nanotechnological advancements provide an astonishing insight to fabricate nanomaterials for nano-bioremediation purposes. Exciting characteristics possessed by hybrid matrices at the nanoscale knock endless opportunities to nano-remediate environmentally-related pollunanomaterials tants of emerging concern. Nanometals are considered among the oldest generation of the world has ever noticed. These tiny nanometals and nanometal oxides showed enormous potential in almost every extent of industrial and biotechnological domains, including their potential multipurpose approach to deal with water impurities. In this manuscript, we discussed their role in the diversity of water treatment technologies used to remove bacteria, viruses, heavy metals, pesticides, and organic impurities, providing an ample perspective on their recent advances in terms of their characteristics, attachment strategies, performance, and their scale-up challenges. Finally, we tried to explore their futuristic contribution to nano-remediate environmentally-related pollutants of emerging concern aiming to collect treated yet safe water that can be reused for multipurpose.


Assuntos
Nanopartículas Metálicas , Metais Pesados , Purificação da Água , Biodegradação Ambiental , Descontaminação
7.
Environ Res ; 204(Pt B): 112092, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34562480

RESUMO

Various lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have contributed to prolongation of the Coronavirus Disease 2019 (COVID-19) pandemic. Several non-synonymous mutations in SARS-CoV-2 proteins have generated multiple SARS-CoV-2 variants. In our previous report, we have shown that an evenly uneven distribution of unique protein variants of SARS-CoV-2 is geo-location or demography-specific. However, the correlation between the demographic transmutability of the SARS-CoV-2 infection and mutations in various proteins remains unknown due to hidden symmetry/asymmetry in the occurrence of mutations. This study tracked how these mutations are emerging in SARS-CoV-2 proteins in six model countries and globally. In a geo-location, considering the mutations having a frequency of detection of at least 500 in each SARS-CoV-2 protein, we studied the country-wise percentage of invariant residues. Our data revealed that since October 2020, highly frequent mutations in SARS-CoV-2 have been observed mostly in the Open Reading Frame (ORF) 7b and ORF8, worldwide. No such highly frequent mutations in any of the SARS-CoV-2 proteins were found in the UK, India, and Brazil, which does not correlate with the degree of transmissibility of the virus in India and Brazil. However, we have found a signature that SARS-CoV-2 proteins were evolving at a higher rate, and considering global data, mutations are detected in the majority of the available amino acid locations. Fractal analysis of each protein's normalized factor time series showed a periodically aperiodic emergence of dominant variants for SARS-CoV-2 protein mutations across different countries. It was noticed that certain high-frequency variants have emerged in the last couple of months, and thus the emerging SARS-CoV-2 strains are expected to contain prevalent mutations in the ORF3a, membrane, and ORF8 proteins. In contrast to other beta-coronaviruses, SARS-CoV-2 variants have rapidly emerged based on demographically dependent mutations. Characterization of the periodically aperiodic nature of the demographic spread of SARS-CoV-2 variants in various countries can contribute to the identification of the origin of SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Mutação , Incerteza
8.
Pain Pract ; 22(4): 432-439, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34845813

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) continues to gain increasing popularity in the pain management field for the treatment of different painful conditions; however, to-date, the correlation between the SCS effectiveness and biological sex has not been fully established. We aimed to investigate the correlation between the biological sex and SCS outcomes. METHODS: Following Institutional Review Board approval, a retrospective cohort study was performed by collecting data for patients treated with SCS at a tertiary academic center between the years 2002 and 2019. Data was assessed with multivariable linear regression to investigate the association between biological sex and pain scores at baseline, 6-, and 12- months following SCS implantation. Propensity score matching (PSM) was performed based on a set of covariates including age, duration of pain, time since implant, BMI, opioid medications use, smoking, depression and history of alcohol, or substance abuse. RESULTS: Of the patients treated with SCS implants, 418 patients fit the inclusion and exclusion criteria, out of which the majority were females (272, 65%). The pre-matching data reported a significant difference in history of diabetes and depression and was also significant for greater opioid use in male patients at baseline, 6-, and 12-months post-SCS implant. Propensity score matching (PSM) was performed based on the above mentioned covariant. After matching, no statistical difference was found among the variables, in both groups. Furthermore, after matching no significant differences in the pain scores at baseline, 6-, and 12-months post-SCS implant were observed. CONCLUSION: No biological sex-based differences in the analgesic response to SCS therapy was detected at 6- and 12-months post-SCS implant between groups with similar demographics, biomedical, and psychological values.


Assuntos
Dor Crônica , Estimulação da Medula Espinal , Analgésicos Opioides , Dor Crônica/psicologia , Feminino , Humanos , Masculino , Manejo da Dor/efeitos adversos , Estudos Retrospectivos , Medula Espinal , Estimulação da Medula Espinal/efeitos adversos , Resultado do Tratamento
9.
Breast Cancer Res Treat ; 189(2): 333-345, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34241740

RESUMO

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks targeted therapies. Patients with TNBC have a very poor prognosis because the disease often metastasizes. New treatment approaches addressing drivers of metastasis and tumor growth are crucial to improving patient outcomes. Developing targeted gene therapy is thus a high priority for TNBC patients. PEA15 (phosphoprotein enriched in astrocytes, 15 kDa) is known to bind to ERK, preventing ERK from being translocated to the nucleus and hence blocking its activity. The biological function of PEA15 is tightly regulated by its phosphorylation at Ser104 and Ser116. However, the function and impact of phosphorylation status of PEA15 in the regulation of TNBC metastasis and in epithelial-to-mesenchymal transition (EMT) are not well understood. METHODS: We established stable cell lines overexpressing nonphosphorylatable (PEA15-AA) and phospho-mimetic (PEA15-DD) mutants. To dissect specific cellular mechanisms regulated by PEA15 phosphorylation status, we performed RT-PCR immune and metastasis arrays. In vivo mouse models were used to determine the effects of PEA15 phosphorylation on tumor growth and metastasis. RESULTS: We found that the nonphosphorylatable mutant PEA15-AA prevented formation of mammospheres and expression of EMT markers in vitro and decreased tumor growth and lung metastasis in in vivo experiments when compared to control, PEA15-WT and phosphomimetic PEA15-DD. However, phosphomimetic mutant PEA15-DD promoted migration, mesenchymal marker expression, tumorigenesis, and lung metastasis in the mouse model. PEA15-AA-mediated inhibition of breast cancer cell migratory capacity and tumorigenesis was the partial result of decreased expression of interleukin-8 (IL-8). Further, we identified that expression of IL-8 was possibly mediated through one of the ERK downstream molecules, Ets-1. CONCLUSIONS: Our results show that PEA15 phosphorylation status serves as an important regulator for PEA15's dual role as an oncogene or tumor suppressor and support the potential of PEA15-AA as a therapeutic strategy for treatment of TNBC.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Transição Epitelial-Mesenquimal , Neoplasias de Mama Triplo Negativas , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8 , Camundongos , Neoplasias de Mama Triplo Negativas/genética
10.
Soft Matter ; 17(1): 16-23, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33155586

RESUMO

Macromolecular crowding and the presence of surfaces can significantly impact the spatial organization of biopolymers. While the importance of crowding-induced depletion interactions in biology has been recognized, much remains to be understood about the effect of crowding on biopolymers such as DNA plasmids. A fundamental problem highlighted by recent experiments is to characterize the impact of crowding on polymer-polymer and polymer-surface interactions. Motivated by the need for quantitative insight, we studied flexible ring polymers in crowded environments using Langevin dynamics simulations. The simulations demonstrated that crowding can lead to compaction of isolated ring polymers and enhanced interactions between two otherwise repulsive polymers. Using umbrella sampling, we determined the potential of mean force (PMF) between two ring polymers as a function of their separation distance at different volume fractions of crowding particles, φ. An effective attraction emerged at φ≈ 0.4, which is similar to the degree of crowding in cells. Analogous simulations showed that crowding can lead to strong adsorption of a ring polymer to a wall, with an effective attraction to the wall emerging at a smaller volume fraction of crowders (φ≈ 0.2). Our results reveal the magnitude of depletion interactions in a biologically-inspired model and highlight how crowding can be used to tune interactions in both cellular and cell-free systems.


Assuntos
DNA , Polímeros , Adsorção , Biopolímeros , Substâncias Macromoleculares
11.
J Chem Phys ; 155(3): 034904, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34293868

RESUMO

Macromolecular crowding is a feature of cellular and cell-free systems that, through depletion effects, can impact the interactions of semiflexible biopolymers with surfaces. In this work, we use computer simulations to study crowding-induced adsorption of semiflexible polymers on otherwise repulsive surfaces. Crowding particles are modeled explicitly, and we investigate the interplay between the bending stiffness of the polymer and the volume fraction and size of crowding particles. Adsorption to flat surfaces is promoted by stiffer polymers, smaller crowding particles, and larger volume fractions of crowders. We characterize transitions from non-adsorbed to partially and strongly adsorbed states as a function of bending stiffness. The crowding-induced transitions occur at smaller values of the bending stiffness as the volume fraction of crowders increases. Concomitant effects on the size and shape of the polymer are reflected by crowding- and stiffness-dependent changes to the radius of gyration. For various polymer lengths, we identify a critical crowding fraction for adsorption and analyze its scaling behavior in terms of polymer stiffness. We also consider crowding-induced adsorption in spherical confinement and identify a regime in which increasing the bending stiffness induces desorption. The results of our simulations shed light on the interplay of crowding and bending stiffness on the spatial organization of biopolymers in encapsulated cellular and cell-free systems.


Assuntos
Biopolímeros/química , Adsorção , Simulação por Computador , Fenômenos Mecânicos
12.
J Assoc Physicians India ; 69(2): 49-53, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527811

RESUMO

INTRODUCTION: The thyroid hormones perpetuate a fine equilibrium of glucose metabolism. Abnormalities of thyroid function can disrupt this balance leading to glucose metabolism abnormalities and insulin resistance. OBJECTIVES: We studied the correlation between insulin resistance and thyroid status in hyperthyroid, euthyroid, and hypothyroid individuals. METHODS: In this observational comparative analysis conducted at a tertiary care center, the 3 study groups comprised of 35 patients each with newly detected hyperthyroidism, hypothyroidism and euthyroid individuals. Assays were conducted for serum insulin, thyroid profile, blood sugar and routine biochemistry in the fasting state. The homeostasis model assessment for insulin resistance (HOMA-IR) was used to evaluate insulin resistance. RESULTS: The mean HOMA-IR was highest in patients with hypothyroidism (3.22 ± 2.69) followed by the hyperthyroid group (2.25 ± 1.59). It was lowest in the euthyroid group (0.79 ± 0.58) with the intergroup difference being statistically significant (P<0.001). Hypothyroid patients showed a significant a positive correlation between TSH and HOMA-IR (r=0.945, P=<0.001) whereas hyperthyroid patients showed positive correlation between FT3 and insulin resistance (r=0.706, P<0.001). CONCLUSION: Thyroid dysfunction is associated with an increase in insulin resistance and glucose abnormalities validating the resultant higher risk of related cardiovascular and metabolic abnormalities observed in these patients.


Assuntos
Resistência à Insulina , Doenças da Glândula Tireoide , Humanos , Índia/epidemiologia , Centros de Atenção Terciária , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/epidemiologia
13.
Mol Cell Biochem ; 471(1-2): 129-142, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504365

RESUMO

Activation of epithelial-AR signaling is identified as the major cause of hyperproliferation of the cells during benign and malignant prostate conditions. However, the contribution of stromal-AR is also precarious due to its secretory actions that contribute to the progression of benign and malignant tumors. The present study was aimed to understand the influence of stromal-AR mediated actions on epithelial cells during BPH condition. The secretome (conditioned media-CM) was collected from AR agonist (testosterone-propionate-TP) and antagonist (Nilutamide-Nil) treated BPH patient-derived stromal cells and exposed to BPH epithelial cells. Epithelial cells exhibited increased cell proliferation with the treatment of CM derived from TP-treated stromal cells (TP-CM) but did not support the clonogenic growth of BPH epithelial cells. However, CM derived from Nil-treated stromal cells (Nil-CM) depicted delayed and aggressive BPH epithelial cell proliferation with increased clonogenicity of BPH epithelial cells. Further, decreased AR levels with increased cMyc transcripts and pAkt levels also validated the clonogenic transformation under the paracrine influence of inhibition of stromal-AR. Moreover, the CM of stromal-AR activation imparted positive regulation of basal/progenitor pool through LGR4, ß-Catenin, and ΔNP63α expression. Hence, the present study highlighted the restricted disease progression and retains the basal/progenitor state of BPH epithelial cells through the activation of stromal-AR. On the contrary, AR-independent aggressive BPH epithelial cell growth due to paracrine action of loss stromal-AR directs us to reform AR pertaining treatment regimes for better clinical outcomes.


Assuntos
Células Epiteliais/patologia , Imidazolidinas/farmacologia , Hiperplasia Prostática/patologia , Receptores Androgênicos/metabolismo , Células Estromais/metabolismo , Propionato de Testosterona/farmacologia , Antagonistas de Androgênios/farmacologia , Proliferação de Células , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Células Epiteliais/metabolismo , Humanos , Masculino , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/metabolismo , Transdução de Sinais , Células-Tronco/metabolismo , Células Estromais/efeitos dos fármacos
14.
Bioorg Chem ; 104: 104326, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33142431

RESUMO

SARS-CoV-2 (COVID-19) epidemic has created an unprecedented medical and economic crisis all over the world. SARS-CoV-2 is found to have more contagious character as compared to MERS-CoV and is spreading in a very fast manner all around the globe. It has affected over 31 million people all over the world till date. This virus shares around 80% of genome similarity with SARS-CoV. In this perspective, we have explored three major targets namely; SARS-CoV-2 spike (S) protein, RNA dependent RNA polymerase, and 3CL or Mpro Protease for the inhibition of SARS-CoV-2. These targets have attracted attention of the medicinal chemists working on computer-aided drug design in developing new small molecules that might inhibit these targets for combating COVID-19 disease. Moreover, we have compared the similarity of these target proteins with earlier reported coronavirus (SARS-CoV). We have observed that both the coronaviruses share around 80% similarity in their amino acid sequence. The key amino acid interactions which can play a crucial role in designing new small molecule inhibitors against COVID-19 have been reported in this perspective. Authors believe that this study will help the medicinal chemists to understand the key amino acids essential for interactions at the active site of target proteins in SARS-CoV-2, based on their similarity with earlier reported viruses. In this review, we have also described the lead molecules under various clinical trials for their efficacy against COVID-19.


Assuntos
Antivirais/metabolismo , SARS-CoV-2/química , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/química , Proteínas não Estruturais Virais/metabolismo , Proteínas Estruturais Virais/metabolismo , Sequência de Aminoácidos , Animais , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/epidemiologia , COVID-19/virologia , Reposicionamento de Medicamentos , Humanos , Ligação Proteica , SARS-CoV-2/efeitos dos fármacos , Proteínas não Estruturais Virais/química , Proteínas Estruturais Virais/química , Tratamento Farmacológico da COVID-19
15.
Drug Dev Ind Pharm ; 46(6): 878-888, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32338544

RESUMO

Nanoparticles have emerged as an important carrier system to treat wounds as they permit the topical administration of an antimicrobial drug in a sustained and effective manner. On the other hand, if active excipients are added during the formulation, such as chitosan or graphene oxide, the developed Nano formulation could significantly improve its potential for chronic wound healing. Given that, we have conceived the fabrication and evaluation of rosmarinic acid loaded chitosan encapsulated graphene nanoparticles (RA-CH-G-NPOs) formulation to enhance wound healing capacity. The prepared nanoparticles were characterized by particle size, Zeta potential, FT-IR, SEM, TEM and AFM. It was observed the average diameter of RA-CH-G-NPOS is around 417.5 ± 18.3 nm and showed sustained release behavior. Optimized RA-CH-G-NPOs were incorporated into Carbopol gel and evaluated for drug content, pH, in vitro release, texture analysis, and viscosity. The antibacterial activity of optimized formulation was examined as a minimum inhibitory concentration against Staphylococcus aureus. The fabricated RA-CH-G-NPOs were than evaluated for in vitro antimicrobial activity by microdilution assay The combination of RA, Chitosan and Graphene oxide (GO) showed higher antibacterial activity of 0.0038 ± 0.2 mg/mL. Further, these nanoparticles were evaluated in- vivo for wound healing efficacy in Sprague Dawley rats. Histopathological evaluations demonstrated that RA-CH-G-NPOs showed significantly enhanced wound contraction, enhanced cell adhesion, epithelial migration, and high hydroxyproline content leading to faster and more efficient collagen synthesis as compared to plain carbopol, plain RA and controls. Hence the topical administration of fabricated RA-CH-G-NPOs appears to be an interesting and suitable strategy for the treatment of chronic wounds.


Assuntos
Quitosana , Cinamatos/química , Depsídeos/química , Grafite , Animais , Cinamatos/farmacologia , Depsídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização/efeitos dos fármacos , Ácido Rosmarínico
16.
Molecules ; 25(24)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33322198

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the findings propose a possible SARS-CoV-2 transmission flow across these nineteen species.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/genética , COVID-19/metabolismo , COVID-19/transmissão , Gatos , Bovinos , Cães , Humanos , Pan troglodytes , Domínios Proteicos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Especificidade da Espécie , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
17.
AAPS PharmSciTech ; 20(2): 50, 2019 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-30617637

RESUMO

Gene therapy involving p11 cDNA has been thought to be a futuristic approach for the effective management of depression as the existing treatment regimen presents many issues regarding late onset of action, patient withdrawal and their side effects. For the effective transfection of p11 gene intracellularly, two cationic lipids based on phospholipid DOPE conjugated to basic amino acids histidine and arginine were synthesised, used for liposome formulation and evaluated for their ability as gene delivery vectors. They were further converted using IGF-II mAb into immunoliposomes for CNS targeting and mAb conjugation to liposomes were characterised by SDS-PAGE. They were further analysed by in vitro characterisation studies that include erythrocyte aggregation study, electrolyte-induced study, heparin compatibility study and serum stability studies. SHSY5Y cells were used for conducting cytotoxicity of synthesised lipids and live imaging of cell uptake for 25 min. Finally, the brain distribution studies and western blot were carried out in animals to evaluate them for their BBB permeation ability and effects on p11 protein which is believed to be a culprit. These formulated liposomes from synthesised lipids offer a promising approach for the treatment of depression.


Assuntos
Encéfalo/metabolismo , Peptídeos Penetradores de Células/genética , Depressão/genética , Terapia Genética/métodos , Fator de Crescimento Insulin-Like II/genética , Nanopartículas/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/metabolismo , Depressão/metabolismo , Depressão/terapia , Marcação de Genes/métodos , Técnicas de Transferência de Genes , Humanos , Fator de Crescimento Insulin-Like II/administração & dosagem , Fator de Crescimento Insulin-Like II/metabolismo , Lipossomos/química , Masculino , Camundongos , Nanopartículas/administração & dosagem , Ratos , Ratos Sprague-Dawley
19.
Breast Cancer Res Treat ; 151(3): 501-13, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25971596

RESUMO

Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. CD44, a putative breast cancer stem cell (CSC) marker, is overexpressed in trastuzumab-resistant breast cancer cells. While CSC-related genes may play a role in the development of trastuzumab resistance, conflicting results have been published about CSC response to trastuzumab. We hypothesized that CD44 contributes to trastuzumab resistance independently of its role as a CSC marker. We used trastuzumab-sensitive breast cancer cell lines and their trastuzumab-resistant isogenic counterparts to evaluate the role of CD44 in response to trastuzumab. miRNA and mRNA expression were analyzed using microarray chips. A gene set enrichment analysis was created and matched with response to trastuzumab in cells and patient samples. The proportions of CSC in trastuzumab-resistant cells were similar to or lower than in the trastuzumab-sensitive cells. However, CD44 expression levels were significantly higher in both trastuzumab-resistant cell lines and its knockdown led to an increased response to trastuzumab. The invasiveness and anchorage-independent growth of trastuzumab-resistant cells were higher and blocked by downregulation of CD44. Results also showed that CD44-related resistance to trastuzumab is regulated by miRNAs. We identified a CD44-related gene expression profile that correlated with response to trastuzumab in cell lines and breast cancer patients. CD44 mediates trastuzumab resistance in HER2-positive breast cancer cells independently of its role as a CSC marker and that this role of CD44 is partly regulated by miRNA.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Expressão Gênica , Receptores de Hialuronatos/genética , Receptor ErbB-2/metabolismo , Trastuzumab/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , RNA Interferente Pequeno/genética
20.
Cureus ; 16(2): e55043, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38550462

RESUMO

Phantom bladder pain, a rare condition following cystectomy, can pose a challenge to pain management providers. We present the case of a 43-year-old male who developed severe phantom bladder pain post-cystectomy. Despite multiple treatments, his symptoms persisted, significantly affecting his quality of life. Dorsal root ganglion stimulation (DRGS) was attempted after conventional therapies failed. The DRGS trial provided significant relief, leading to permanent implantation and a 90% reduction in pain. This case highlights DRGS as a potential treatment for phantom bladder pain, expanding its applications beyond traditional uses. Further research is needed to elucidate its mechanisms and broader applicability.

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