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A thixotropic colloidal gel constituting an aqueous dispersion of synthetic clay Laponite with varying concentrations of salt has been studied for its rheological and tribological performance as a lubricant. We observed that the incorporation of NaCl induces notable enhancements in the colloidal gel's relaxation time, elastic modulus, and yield stress. Although an increase in NaCl concentration decreases the material's relaxation time dependence on waiting time (tw), overall, the strength of its thixotropic character has been observed to increase with an increase in salt concentration. The analysis of friction and wear indicated that the utilization of a thixotropic colloidal gel of Laponite with a higher concentration of NaCl resulted in progressively greater reductions in both the coefficient of friction and specific wear rates under various load-speed conditions. Severe abrasive wear on disc surface under dry test, gradually mitigated upon the introduction of these lubricants. Two simultaneous lubricating mechanisms, first, the smooth sliding of the friction pair, facilitated by the alignment of Laponite particles in the direction of shear forces, and second, the stable structure of Laponite, coupled with the addition of NaCl, enabling continuous replenishment of the wear track with lubricant, are attributed to lubrication effectiveness.
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Soft amorphous materials are viscoelastic solids ubiquitously found around us, from clays and cementitious pastes to emulsions and physical gels encountered in food or biomedical engineering. Under an external deformation, these materials undergo a noteworthy transition from a solid to a liquid state that reshapes the material microstructure. This yielding transition was the main theme of a workshop held from January 9 to 13, 2023 at the Lorentz Center in Leiden. The manuscript presented here offers a critical perspective on the subject, synthesizing insights from the various brainstorming sessions and informal discussions that unfolded during this week of vibrant exchange of ideas. The result of these exchanges takes the form of a series of open questions that represent outstanding experimental, numerical, and theoretical challenges to be tackled in the near future.
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BACKGROUND: One of the most prevalent respiratory disorders in modern society is chronic obstructive pulmonary disease (COPD). Frequent comorbidities in patients with COPD are abnormal nutritional status and body composition variations. Malnutrition-sarcopenia syndrome, which occurs when the 2 conditions - malnutrition and sarcopenia - coexist, raises the risk of death more than either condition alone. The current study sought to determine the prevalence of malnutrition, sarcopenia, and malnutrition-sarcopenia syndrome in patients with COPD as well as the association between these diseases and the severity of COPD. METHODS: The study was an analytical cross-sectional study conducted on hospitalized patients with COPD. The sample size of the study was calculated to be 160. A self-structured questionnaire was used to collect the data, containing sociodemographic characteristics, clinical profiles, anthropometric assessment, and bioimpedance indices. Sarcopenia was diagnosed with low muscle strength and muscle mass by the EWGSOP2 recommendations. Muscle mass is measured by BIA and muscle strength (Handgrip) was measured by a Hand Dynamometer. Assessment of the risk of malnutrition was performed using the Mini Nutritional Assessment-Short Form questionnaire and was confirmed by GLIM criteria. The COPD assessment test (CAT) tool determined the severity of the condition. For the data analysis, comparisons were made using Student's t test and Mann-Whitney test in bivariate analysis. Multivariate logistic regression analyses were performed considering the outcomes of patients with COPD by CAT scores, prolonged length of stay, and hospital readmission 6 months after discharge. RESULTS: The mean age of the participants was 48 ± 5 years. Approximately 61.9% were found to be sarcopenic. Approximately 45.6% of participants had malnutrition. Malnutrition sarcopenia syndrome was diagnosed in 32.5% of patients. The study analysis revealed that patients with COPD with malnutrition-sarcopenia syndrome had more than twice the odds of prolonged hospital stay, re-admission within 6 months, and higher CAT scores. CONCLUSION: The study revealed a high prevalence of sarcopenia, malnutrition, and malnutrition sarcopenia syndrome in patients with COPD. These conditions were found to be statistically significant with prolonged length of stay, re-admission within 6 months, and CAT scores. The findings highlight the importance of addressing these conditions as part of the management of the patients.
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Desnutrição , Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Adulto , Pessoa de Meia-Idade , Sarcopenia/diagnóstico , Estudos Transversais , Força da Mão/fisiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Desnutrição/epidemiologia , Desnutrição/diagnóstico , Estado NutricionalRESUMO
BACKGROUND: India is experiencing a rising burden of chronic disease multimorbidity due to an aging population and epidemiological transition. Older adults residing in urban slums are especially vulnerable due to challenges in managing multimorbidity amid deprived living conditions. This study aimed to assess the prevalence of multimorbidity, associated health literacy, and quality of life impact in this population. METHODS: A community-based cross-sectional study was conducted among 800 adults aged ≥ 65 years in an urban slum in Gujarat, India. Data on sociodemographics, physical and mental health conditions, health literacy (HLS-SF-47), quality of life (Short Form-12 scale), and social determinants of health were collected. Multimorbidity is ≥ 2 physical or mental health conditions in one person. RESULTS: The prevalence of multimorbidity was 62.5% (500/800). Multimorbidity was significantly associated with lower physical component summary (PCS) and mental component summary (MCS) scores on the SF-12 (p < 0.001). After adjusting for sociodemographic variables, the odds ratio of 0.81 indicates that for every 1 unit increase in the health literacy score, the odds of having multimorbidity decrease by 19%. Older age within the older adult cohort (per year increase) was associated with greater odds of multimorbidity (AOR 1.05, 95% CI 1.02-1.09). Physical inactivity (AOR 1.68, 95% CI 1.027-2.77) and lack of social support (AOR 1.57, 95% CI 1.01-2.45) also increased the likelihood of multimorbidity. CONCLUSION: There is a substantial burden of multimorbidity among urban slum dwellers aged ≥ 65 years in India, strongly linked to modifiable risk factors like poor health literacy and social determinants of health. Targeted interventions are essential to alleviate this disproportionate burden among urban slum older adults.
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Letramento em Saúde , Multimorbidade , Áreas de Pobreza , Qualidade de Vida , População Urbana , Humanos , Índia/epidemiologia , Estudos Transversais , Masculino , Feminino , Idoso , Letramento em Saúde/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Idoso de 80 Anos ou mais , Prevalência , Determinantes Sociais da SaúdeRESUMO
The circadian clock protein basic helix-loop-helix aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a transcription factor that impacts kidney function, including blood pressure (BP) control. Previously, we have shown that male, but not female, kidney-specific cadherin Cre-positive BMAL1 knockout (KS-BMAL1 KO) mice exhibit lower BP compared with littermate controls. The goal of this study was to determine the BP phenotype and immune response in male KS-BMAL1 KO mice in response to a low-K+ high-salt (LKHS) diet. BP, renal inflammatory markers, and immune cells were measured in male mice following an LKHS diet. Male KS-BMAL1 KO mice had lower BP following the LKHS diet compared with control mice, yet their circadian rhythm in pressure remained unchanged. Additionally, KS-BMAL1 KO mice exhibited lower levels of renal proinflammatory cytokines and immune cells following the LKHS diet compared with control mice. KS-BMAL1 KO mice were protected from the salt-sensitive hypertension observed in control mice and displayed an attenuated immune response following the LKHS diet. These data suggest that BMAL1 plays a role in driving the BP increase and proinflammatory environment that occurs in response to an LKHS diet.NEW & NOTEWORTHY We show here, for the first time, that kidney-specific BMAL1 knockout mice are protected from blood pressure (BP) increases and immune responses to a salt-sensitive diet. Other kidney-specific BMAL1 knockout models exhibit lower BP phenotypes under basal conditions. A salt-sensitive diet exacerbates this genotype-specific BP response, leading to fewer proinflammatory cytokines and immune cells in knockout mice. These data demonstrate the importance of distal segment BMAL1 in BP and immune responses to a salt-sensitive environment.
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Fatores de Transcrição ARNTL , Hipertensão , Animais , Masculino , Camundongos , Fatores de Transcrição ARNTL/metabolismo , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Citocinas , Dieta , Hipertensão/genética , Hipertensão/prevenção & controle , Rim/metabolismo , Camundongos Knockout , Cloreto de Sódio na DietaRESUMO
A system undergoing sol-gel transition passes through a unique point, known as the critical gel state, where it forms the weakest space spanning percolated network. We investigate the nonlinear viscoelastic behavior of a colloidal dispersion at the critical gel state using large amplitude oscillatory shear rheology. The colloidal gel at the critical point is subjected to oscillatory shear flow with increasing strain amplitude at different frequencies. We observe that the first harmonic of the elastic and viscous moduli exhibits a monotonic decrease as the material undergoes a linear to nonlinear transition. We analyze the stress waveform across this transition and obtain the nonlinear moduli and viscosity as a function of frequency and strain amplitude. The analysis of the nonlinear moduli and viscosities suggests intracycle strain stiffening and intracycle shear thinning in the colloidal dispersion. Based on the insights obtained from the nonlinear analysis, we propose a potential scenario of the microstructural changes occurring in the nonlinear region. We also develop an integral model using the time-strain separable Kaye-Bernstein-Kearsley-Zapas constitutive equation with a power-law relaxation modulus and damping function obtained from experiments. The proposed model with a slight adjustment of the damping function inferred using a spectral method, compares well with experimental data at all frequencies.
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BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.
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Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Idoso , Sudeste Asiático , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Estudos Transversais , Diagnóstico Tardio , Ásia Oriental , Feminino , Humanos , Fatores Imunológicos , Incidência , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Mesalamina , FenótipoRESUMO
Amyloidosis is a well-known but poorly understood phenomenon caused by the aggregation of proteins, often leading to pathological conditions. For example, the aggregation of insulin poses significant challenges during the preparation of pharmaceutical insulin formulations commonly used to treat diabetic patients. Therefore, it is essential to develop inhibitors of insulin aggregation for potential biomedical applications and for important mechanistic insights into amyloidogenic pathways. Here, we have identified a small molecule M1, which causes a dose-dependent reduction in insulin fibril formation. Biophysical analyses and docking results suggest that M1 likely binds to partially unfolded insulin intermediates. Further, M1-treated insulin had lower cytotoxicity and remained functionally active in regulating cell proliferation in cultured Drosophila wing epithelium. Thus, M1 is of great interest as a novel agent for inhibiting insulin aggregation during biopharmaceutical manufacturing.
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Amiloide/metabolismo , Amiloidose/prevenção & controle , Insulina/metabolismo , Fármacos Neuroprotetores/farmacologia , Amiloide/ultraestrutura , Animais , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Drosophila , Eletroforese em Gel de Poliacrilamida , Células HEK293 , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de TransmissãoRESUMO
In this work, we study the effect of the deformation field on the physical aging behavior of an aqueous Carbopol dispersion. It is composed of soft swollen particles of gel that get deformed and acquire a polygonal shape, with flat interfaces rendering the dispersion a soft solid-like consistency as filled volume fraction approaches unity. It has been proposed that owing to release of stored elastic energy in the deformed particles, Carbopol dispersion undergoes microstructural evolution that is reminiscent of physical aging in soft glassy materials. We observe that application of moderate magnitude of oscillatory strain to Carbopol dispersion slows down its relaxation dynamics, thereby showing characteristics of overaging. On the other hand, the sufficiently high magnitude of strain makes the relaxation dynamics faster, causing rejuvenation. We also solve the soft glassy rheology model, which, when subjected to the same flow field, corroborates with experimental observations on the Carbopol dispersion. This behavior, therefore, suggests that in a system of jammed soft particles of Carbopol, the particles occupying shallow energy wells upon application of moderate strain field adjust themselves in such a manner that they predominantly occupy the deeper energy wells leading to observe the overaging dynamics.
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Prostate cancer is a clinically heterogeneous disease and accurately risk-stratifying patients is a key clinical challenge. We hypothesized that the concurrent identification of the DNA copy number alterations 10q23.3 (PTEN) deletion and 16p13.3 (PDPK1) gain, related to the PI3K/AKT survival pathway, would improve prognostication. We assessed PTEN deletion status using fluorescence in situ hybridization (FISH) and evaluated its clinical significance in combination with the 16p13.3 gain in a set of 332 primary radical prostatectomy cases on a tissue microarray with clinical follow-up. The PTEN deletion was detected in 34% (97/287) of the evaluable tumors and was significantly associated with high Gleason grade group (P < 0.0001) and advanced pathological tumor stage (pT-stage, P < 0.001). The PTEN deletion emerged as a significant predictor of biochemical recurrence independent of the standard clinicopathologic parameters (hazard ratio: 3.00, 95% confidence interval: 1.81-4.98; P < 0.0001) and further stratified patients with low and intermediate risk of biochemical recurrence [Gleason grade group 1-2 (≤3 + 4), Gleason grade group 2 (3 + 4), pT2, prostate-specific antigen ≤ 10, low and intermediate CAPRA-S score; log-rank P ≤ 0.007]. A PTEN deletion also increased the risk of distant metastasis (log-rank, P = 0.001), further supporting its role in prostate cancer progression. Combining both 16p13.3 gain and PTEN deletion improved biochemical recurrence risk stratification and provided prognostic information beyond the established CAPRA-S score (co-alteration: hazard ratio: 4.70, 95% confidence interval: 2.12-10.42; P < 0.0001). Our study demonstrates the potential clinical utility of PTEN genomic deletion in low-intermediate risk patients and highlights the enhanced prognostication achieved when assessed in combination with another genomic biomarker related to the PI3K/AKT pathway, thereby supporting their promising usefulness in clinical management of prostate cancer.
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Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Biomarcadores Tumorais/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Adulto , Idoso , Variações do Número de Cópias de DNA , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Prostatectomia , Neoplasias da Próstata/mortalidadeRESUMO
Bijels (bicontinuous interfacially jammed emulsion gels) have the potential to be useful in many different applications due to their internal connectivity and the possibility of efficient mass transport through the channels. Recently, new methods of making the bijel have been proposed, which simplify the fabrication process, making commercial application more realistic. Here, we study the flow properties of bijels prepared by mixing alone using oscillatory rheology combined with confocal microscopy and also squeezing flow experiments. We found that the bijel undergoes a two-step yielding process where the first step corresponds to the fluidizing of the interface, allowing the motion of the structure, and the second step corresponds to the breaking of the structure. In the squeeze flow experiments, the yield stress of the bijel is observed to show a power law dependence on squeezing speed. However, when stress in excess of yield stress is plotted against shear rate, all the different squeeze flow data show a superposition.
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Yielding transition in isotropic soft materials under the superposition of orthogonal deformation fields is known to follow von Mises' criterion. However, in anisotropic soft materials, von Mises' criterion fails owing to the preferred directions associated with the system. In this work we study a model anisotropic yield stress system: electrorheological (ER) fluids which show structural formation in the direction of an electric field. We subject the ER fluids to the superposition of orthogonal stress fields which leads to different yield stress values. We obtain a yielding state diagram by plotting the normalized rotational shear stress against the normalized radial shear stress corresponding to a yield point for a given electric field. Remarkably, the state diagram validates the Hill yielding criterion, which is a general yielding criterion for materials with anisotropy along three orthogonal directions, originally developed for metallic systems. Validation of Hill's criterion suggests the universality of its application in anisotropic systems including conventional anisotropic soft materials having yield stress.
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In the present study, the adhesive and viscoelastic properties of polydimethylsiloxane (PDMS) based nanocomposite pressure sensitive adhesives (PSAs) with embedded electrospun polyacrylonitrile (PAN) and polyvinyl alcohol (PVA) nanofibers as fillers were investigated. PDMS nanocomposite adhesive films using PAN and PVA nanofibers were synthesized by dispersing fillers in the matrix by a solvent mixing process. The adhesion strength and reusability of the prepared nanocomposite PSA films were measured using peel tests as the fraction of nanofibers in the polymer matrix is increased. The variations of the adhesive properties of the PSAs as function of the type and loading of filler were related to their rheological properties in terms of shear and elastic moduli. Although 3-fold enhancement of the adhesion strength was achieved with 0.5 wt% loading for both types (PAN and PVA) of nanocomposites as compared to elastic PDMS, the composite adhesive with PAN nanofibers can provide a superior balance of rheological properties, resulting in improved reusability over other PSAs. The differences in the adhesion and viscoelastic properties of the composite PSAs are attributed to the polymer chemistry, processability, and architecture of the electrospun nanofibers in the soft PDMS matrix.
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Synthetic hectorite clay Laponite RD/XLG is composed of disk-shaped nanoparticles that acquire dissimilar charges when suspended in an aqueous medium. Owing to their property to spontaneously self-assemble, Laponite is used as a rheology modifier in a variety of commercial water-based products. In particular, an aqueous dispersion of Laponite undergoes a liquid-to-solid transition at about 1 vol % concentration. The evolution of the physical properties as the dispersion transforms to the solid state is reminiscent of physical aging in molecular as well as colloidal glasses. The corresponding soft glassy dynamics of an aqueous Laponite dispersion, including the rheological behavior, has been extensively studied in the literature. In this feature article, we take an overview of recent advances in understanding soft glassy dynamics and various efforts taken to understand the peculiar rheological behavior. Furthermore, the continuously developing microstructure that is responsible for the eventual formation of a soft solid state that supports its own weight against gravity has also been a topic of intense debate and discussion. In particularly, extensive experimental and theoretical studies lead to two types of microstructures for this system: an attractive gel-like or a repulsive glass-like structure. We carefully examine and critically analyze the literature and propose a state (phase) diagram that suggests an aqueous Laponite dispersion to be present in an attractive gel state.
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Fabrication of large area, multiscale microtextured surfaces engineered for antiadhesion properties remains a challenge. Compared to an elastic surface, viscoelastic solids show much higher surface stickiness, tack, and adhesion owing to the increased contact area and energy dissipation. Here, we show a simple, low cost, large-area and high throughput method with roll-to-roll compatibility to fabricate multiscale, rough microstructures resistant to adhesion in a viscoelastic layer by controlled tearing of viscous film. Even a high adhesive strength viscoelastic solid layer, such as partially cured PDMS, is made nonsticky simply by its controlled tearing. The torn surface shows a fracture induced, self-organized leaflike micropattern resistant to sticking. The topography and adhesion strength of these structures are readily tuned by changing the tearing speed and the film thickness. The microtexture displays a springlike recovery, low adhesive strength, and easy release properties even under the high applied loads.
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We investigate surface and sub-surface nanomechanical properties of nanocomposites based on a crosslinked polydimethylsiloxane (PDMS) elastomer and electrospun polyacrylonitrile (PAN) nanofibers. Fabrication of PDMS substrates with anisotropy with respect to surface elasticity and their characterization in terms of local nanomechanical properties are important for many areas of adhesion applications. PDMS nanocomposite substrates with variations in surface elasticity over large areas are prepared by controllably embedding electrospun PAN nanofibers (â¼600 nm) in a PDMS matrix using the solution casting technique. Variations of local surface stiffness properties of prepared composites are measured using force spectroscopy and force mapping modes of atomic force microscopy and compared with their macroscopic (bulk) mechanical properties. Since the surface of the prepared nanocomposite is elastically non-homogeneous, our studies are mainly focused on the investigation of the hysteresis (plasticity index) between loading and unloading curves which is a measure of energy dissipation in AFM indentation experiments. The distribution of the local plasticity index in the PAN/PDMS composites is related to the specific organization of electrospun nanofibers at the surface and sub-surface layers of the PDMS matrix. We observed that embedding 0.1-1% PAN nanofibers induces anti-plasticization effects for lower (0.1%) and higher (1%) concentrations of PAN nanofibers which represent the formation of interpenetrating networks and mat-like blended structures of PAN nanofibers within the PDMS matrix.
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While there are targeted treatments for triple positive breast cancers, lack of specific biomarkers for triple-negative breast cancers (TNBC) has hindered the development of therapies for this subset of cancers. In this study, we evaluated the anticancer properties of cardiac glycoside Digitoxin (Dtx) and its synthetic analog MonoD on breast cancer cell lines MCF-7 (estrogen receptor-positive breast cancer) and MDA-MB-468 (triple-negative breast cancer). Both cardiac glycosides, at concentrations within the therapeutic range, increased the fraction of cells in the G0/G1 phase of the cell cycle, decreased viability, and inhibited the migration of MCF-7 and MDA-MB-468 cells. Both cardiac glycosides increased production of superoxide and induced apoptosis in both cell types. Reduced protein levels of nuclear factor kappa B and IkappaB kinase-beta were found in cardiac glycoside-treated cells, indicating that the cellular effects of these compounds are mediated via nuclear factor kappa B pathway. This study demonstrates the cytotoxic potential of digitoxin, and more importantly its synthetic analog MonoD, in the treatment of triple-positive breast cancer and more importantly the aggressive triple-negative breast cancer. Collectively, this study provides a basis for the reevaluation of cardiac glycosides in the treatment of breast cancer and more importantly reveals their potential in the treatment of triple-negative breast cancers.
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Digitoxina/administração & dosagem , Receptores de Estrogênio/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Carcinogênese/genética , Glicosídeos Cardíacos/genética , Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Digitoxina/análogos & derivados , Feminino , Humanos , Células MCF-7 , Camundongos , NF-kappa B/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Investigating microstructure of suspensions with particles having anisotropic shape that share complex interactions is a challenging task leading to competing claims. This work investigates phase behavior of one such system: aqueous Laponite suspension, which is highly contested in the literature, using rheological and microscopic tools. Remarkably, we observe that over a broad range of Laponite (1.4 to 4 wt %) and salt concentrations (0 to 7 mM), the system overwhelmingly demonstrates all the rheological characteristics of the sol-gel transition leading to a percolated network. Analysis of the rheological response leads to fractal dimension that primarily depends on the Laponite concentration. We also obtain the activation energy for gelation, which is observed to decrease with increase in Laponite as well as salt concentration. Significantly, the cryo-TEM images of the postgel state clearly show the presence of a percolated network formed by interparticle bonds. The present work therefore conclusively establishes the system to be in an attractive gel state resolving a long-standing debate in the literature.
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Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with a life expectancy of less than 5 years post diagnosis for most patients. Poor molecular characterization of IPF has led to insufficient understanding of the pathogenesis of the disease, resulting in lack of effective therapies. In this study, we have integrated a label-free LC-MS based approach with systems biology to identify signaling pathways and regulatory nodes within protein interaction networks that govern phenotypic changes that may lead to IPF. Ingenuity Pathway Analysis of proteins modulated in response to bleomycin treatment identified PI3K/Akt and Wnt signaling as the most significant profibrotic pathways. Similar analysis of proteins modulated in response to vascular endothelial growth factor (VEGF) inhibitor (CBO-P11) treatment identified natural killer cell signaling and PTEN signaling as the most significant antifibrotic pathways. Mechanistic/mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) were identified to be key mediators of pro- and antifibrotic response, where bleomycin (BLM) treatment resulted in increased expression and VEGF inhibitor treatment attenuated expression of mTOR and ERK. Using a BLM mouse model of pulmonary fibrosis and VEGF inhibitor CBO-P11 as a therapeutic measure, we identified a comprehensive set of signaling pathways and proteins that contribute to the pathogenesis of pulmonary fibrosis that can be targeted for therapy against this fatal disease.