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BACKGROUND: Keloids and hypertrophic scars result from abnormal collagen accumulation and the inhibition of its degradation. Although the pathogenesis remains unclear, excessive accumulation of the extracellular matrix (ECM) is believed to be associated with the TGF-ß/SMAD pathway. Zinc-alpha-2-glycoprotein (ZAG) inhibits TGF-ß-mediated epithelial-to-mesenchymal transdifferentiation and impacts skin barrier functions. In this study, we investigated the potential of a small ZAG-derived peptide against hypertrophic scars and keloids. METHODS: The study examined cell proliferation and mRNA expression of collagen types I and III in human dermal fibroblast (HDF) cell lines and keloid-derived fibroblasts (KF) following ZAG peptide treatment. A rat incisional wound model was used to evaluate the effect of ZAG peptide in scar tissue. RESULTS: Significantly lower mRNA levels of collagen types I and III were observed in ZAG-treated fibroblasts, whereas matrix metalloproteinase (MMP)-1 and MMP-3 mRNA levels were significantly increased in HDFs and KFs. Furthermore, ZAG peptide significantly reduced protein expression of collagen type I and III, TGF-ß1, and p-Smad2/3 complex in KFs. Rat incisional scar models treated with ZAG peptide presented narrower scar areas and reduced immature collagen deposition, along with decreased expression of collagen type I, α-SMA, and p-Smad2/3. CONCLUSION: ZAG peptide effectively suppresses the TGF-ß and p-Smad2/3 pathway and inhibits excessive cell proliferation during scar formation, suggesting its potential therapeutic implications against keloids and hypertrophic scars.
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Colágeno Tipo III , Colágeno Tipo I , Fibroblastos , Queloide , Transducción de Señal , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta , Zn-alfa-2-Glicoproteína , Animales , Queloide/metabolismo , Queloide/tratamiento farmacológico , Queloide/patología , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Humanos , Colágeno Tipo I/metabolismo , Proteína smad3/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo III/genética , Proteína Smad2/metabolismo , Ratas , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal/efectos de los fármacos , Ratas Sprague-Dawley , Regulación hacia Abajo/efectos de los fármacos , Masculino , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Péptidos/farmacología , FemeninoRESUMEN
This study aimed to investigate the influence of abnormal body weight on inflammatory markers and adipokine levels across varied body mass index (BMI) categories. The cohort included 46 participants categorized into normal BMI (group I; n = 19), overweight (group II; n = 14), and obesity (group III; n = 13). Inflammatory markers (hsCRP and IL-6) and adipokines (Adiponectin, Leptin, Nesfatin-1, and Zinc-α2-glycoprotein) were assessed to discern effective indicators of inflammation in individuals with abnormal body weight. Additionally, the full lipid profile was also assessed (total cholesterol, triglycerides, LDL-C, HDL-C). The results indicated significant biochemical changes, particularly in IL-6 and Leptin levels, in participants with a BMI over 25. The levels of ZAG protein were negatively correlated with the HDL-C and LDC-L levels with statistical significance (Pearson: -0.57, p = 0.001, and Pearson: -0.41, p = 0.029, for HDL-C and LDL-C, respectively), suggesting that the level of ZAG is also inversely proportional to the amount of cholesterol. Statistical analyses revealed decreased Zinc-α2-glycoprotein (ZAG) levels and increased Adiponectin, Leptin, and IL-6 levels in individuals with abnormal body weight. Correlation analyses demonstrated a statistically significant upward trend for IL-6 (p = 0.0008) and Leptin (p = 0.00001), with a similar trend observed for hsCRP without statistical significance (p = 0.113). IL-6 levels in the overweight group were 158.71% higher than in the normal-weight group, while the obese group exhibited a 229.55% increase compared to the normal-weight group. No notable changes have been recorded for the levels of Nesfatin-1. Based on our results, we propose IL-6, Leptin, and ZAG as potential biomarkers for monitoring interventions and assessing patient conditions in those with abnormal BMIs. Further research with a larger patient cohort is warranted to validate these correlations in overweight and obese individuals.
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Obesity is a predisposition factor for breast cancer, suggesting a localized, reciprocal interaction between breast cancer cells and the surrounding mammary white adipose tissue. To investigate how breast cancer cells alter the composition and function of adipose tissue, we screened the secretomes of ten human breast cancer cell lines for the ability to modulate the differentiation of adipocyte stem and progenitor cells (ASPC). The screen identified a key adipogenic modulator, Zinc Alpha-2-Glycoprotein (ZAG/AZGP1), secreted by triple-negative breast cancer (TNBC) cells. TNBC-secreted ZAG inhibits adipogenesis and instead induces the expression of fibrotic genes. Accordingly, depletion of ZAG in TNBC cells attenuates fibrosis in white adipose tissue and inhibits tumor growth. Further, high expression of ZAG in TNBC patients, but not other clinical subtypes of breast cancer, is linked to poor prognosis. Our findings suggest a role of TNBC-secreted ZAG in promoting the transdifferentiation of ASPCs into cancer-associated fibroblasts to support tumorigenesis.
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BACKGROUND: Skin aging, characterized by the deterioration of skin density and elasticity, is a common concern among individuals seeking to maintain a youthful appearance. Zinc-α2-glycoprotein (ZAG) is secreted by various body fluids, and is associated with lipolysis and identified as an atopic dermatitis biomarker. This study evaluated the potential of ZAG peptides, which exert multiple benefits such as anti-aging. MATERIALS AND METHODS: We conducted a 4-week clinical trial on patients with noticeable periorbital wrinkles (n = 22) using a ZAG peptide-containing product. The effects of the products on skin density, elasticity, and the depth of periorbital wrinkles were evaluated using Cutometer Dual MPA580, Ultrascan, and Antera 3D CS, respectively. The effect of ZAG peptides on UVB-treated keratinocyte cells was evaluated in vitro to understand the mechanisms underlying its effects against impaired skin barrier function, collagen degradation, and senescence. In addition, the effects of ZAG peptides on cell viability and expression of aging and skin barrier-related genes were assessed using cell counting kit assay and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: The patients demonstrated improved skin density, elasticity, and reduced periorbital wrinkles. Further, more than 85% patients scored the product as satisfactory regarding anti-aging effects. Furthermore, ZAG peptides reduced SA-ß-gal staining, downregulated the senescence-related genes, and upregulated the skin barrier function-related genes in UVB-irradiated keratinocyte cells. CONCLUSIONS: Our clinical and in vitro findings showed that ZAG peptides exert anti-aging effects and improve skin barrier functions, suggesting their promising potential as therapeutic agents to combat skin aging and improve skin health.
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Lipólisis , Zn-alfa-2-Glicoproteína , Humanos , Piel , Envejecimiento , ZincRESUMEN
Objective Zinc-α2-glycoprotein (ZAG) is secreted by various organs, such as liver, kidney and adipose tissue, is involved in lipolysis, and may contribute to the pathogenesis of chronic liver disease (CLD). We therefore assessed whether or not ZAG is a surrogate marker for the hepatorenal function, body composition and all causes of mortality, as well as complications, including ascites, hepatic encephalopathy (HE) and portosystemic shunts (PSS) in CLD. Methods Serum ZAG levels were measured in 180 CLD patients upon hospital admission. The associations of ZAG levels with the liver functional reserve and clinical parameters were investigated using a multiple regression analysis. Kaplan-Meier analyses were performed to evaluate the associations of the ZAG/creatinine ratio (ZAG/Cr) and prognostic factors with mortality. Results High serum ZAG levels were associated with preserving the liver function and renal insufficiency. A multiple regression analysis showed that the estimated glomerular filtration rate (p<0.0001), albumin-bilirubin (ALBI) score (p=0.0018) and subcutaneous fat area (p=0.0023) had a significant independent correlation with serum ZAG levels. Serum ZAG levels were elevated in the absence of HE (p=0.0023) and PSS (p=0.0003). In all patients and those without hepatocellular carcinoma (HCC), the cumulative mortality rate was significantly decreased in patients with a high ZAG/Cr compared with those with a low ZAG/Cr (p=0.0018 and p=0.0002, respectively). The ZAG/Cr, presence of HCC, ALBI score and psoas muscle index were independent predictors of the prognosis in CLD patients. Conclusion Serum ZAG levels are associated with the hepatorenal function and can be used to predict the survival in CLD patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Tejido Adiposo , Zn-alfa-2-Glicoproteína , ZincRESUMEN
Zinc α2-glycoprotein (ZAG) has been implicated in fatty acid metabolism and utilization and is lower in obese and higher in cachexic adults compared to those of normal weight. Previous studies suggest that ZAG binds to the beta3-adrenergic receptor (ß3AR) to influence fatty acid metabolism in adipose tissue by regulating hormone sensitive lipase (HSL). The purpose of this study is to investigate the effects of a six-month weight loss (WL) or aerobic exercise (AEX) intervention on adipose tissue and skeletal muscle ZAG mRNA levels and protein expression, as well as the expression of ß3AR, and HSL. Abdominal adipose tissue (AB) and gluteal adipose tissue (Glut) and vastus lateralis muscle biopsies were performed before and after WL (n = 13) or AEX (n = 13). ZAG, HSL, and ß3AR expressions were determined by RT-PCR, and ZAG and HSL plasma levels by ELISA. Body weight decreased by 9.69% (p < 0.001) in WL and did not change with AEX. Maximal oxygen consumption (VO2max) increased by 7.1% (p < 0.005) after WL and by 16.69% (p < 0.001) after AEX. WL significantly decreased body weight with a reduction of percentage of fat, fat mass, fat-free mass (FFM). AEX decreased percent fat and increased VO2max, but did not change fat mass and FFM. Abdominal ZAG and HSL mRNA levels did not change significantly after WL or AEX. There were no changes in plasma ZAG, HSL and adipose tissue ß3AR mRNA levels after WL and AEX. ZAG, HSL and ß3AR mRNA expressions in adipose tissue are positively associated each other. Adipose tissue abdominal and gluteal HSL are negatively associated with HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), and both ZAG and HSL adipose tissue are negatively associated with fasting glucose and the glucose area under the curve. Further work is needed to elucidate the role of ZAG and HSL in the propensity for weight gain and the ability of exercise to mitigate these responses.
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Ejercicio Físico , Obesidad , Pérdida de Peso , Humanos , Peso Corporal , Ejercicio Físico/fisiología , Ácidos Grasos , Glucosa , Glicoproteínas , Obesidad/genética , Obesidad/terapia , ARN Mensajero/genética , ZincRESUMEN
In view of global environmental change, ecological factors especially temperature, affect development of the poikilotherms like insects. Since ladybirds are at risk of injury under mass-rearing conditions, their ability to regenerate injured limbs is highly crucial for their survival. Therefore, the effect of limb regeneration in relation to temperature forms the basis of the present study. The immature stages of insects, being more vulnerable to the surrounding temperature, were considered to study the effect of the prior thermal experience of larvae on regeneration. We exposed the early larval stages of the ladybird beetle, Cheilomenes sexmaculata, to different temperature conditions pre- and postamputation. Exposure of immature stages to extreme temperatures did not affect the ability to regenerate and regeneration occurred at given temperature conditions. However, the regenerated legs were smaller in size across given temperatures as compared to unamputated legs. Body weights in amputated treatments showed no difference and remained unchanged across temperatures when compared to unamputated treatments. Postamputation developmental duration, equivalent to recovery time postlimb amputation, was found to be affected by larval thermal conditions. Recovery was faster in larval treatments exposed to higher temperatures. Thus, larval thermal conditions though did not affect the ability to regenerate lost limbs directly, it does modulate the time taken to regenerate.
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Escarabajos , Animales , Larva , Regeneración , Temperatura , ExtremidadesRESUMEN
Circumcoronene is a highly symmetric polybenzenoid hydrocarbon that has fascinated organic chemists and materials scientists for decades. However, until recently, it had only been studied theoretically, because its synthesis in solution remained challenging. In a recent report, Wu and co-workers described the first successful solution-phase synthesis and isolation of crystalline circumcoronene derivatives, validating the long-predicted Clar structure. Their synthetic approach enables preparation of new polycyclic benzenoid hydrocarbons with multiple K-regions, which are difficult to obtain, and expands our understanding of the chemistry of these systems.
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Objective: The aim of the study was to compare the cleaning efficacy and plaque control of the straight and angled bristle design manual toothbrushes. Materials and Methods: It was a pilot randomized trial comprising 30 dental students divided into 2 groups (group I flat bristle design toothbrush and group II zig-zag bristle design toothbrush) with 15 in each group. Prebrushing and postbrushing plaque scores were recorded at the baseline and at the end of 4 weeks using Turesky modification of Quigley and Hein plaque index. Results: Plaque and gingival scores were reduced significantly at 1 month in group II with P < 0.05 than compared to group I where P > 0.05. Mean GI and plaque scores of the criss-cross design were reduced significantly after 1 month (P < 0.05). Intergroup comparisons revealed that plaque and gingival scores significantly reduced (P < 0.05) at 1-month interval. Conclusion: Bristle design has significant impact on plaque removal capacity of a toothbrush. Toothbrush with zig-zag bristle design is efficient in removing plaque than the flat design of a toothbrush.
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We study solitons in a zig-zag lattice of magnetic dipoles. The lattice comprises two sublattices of parallel chains with magnetic dipoles at their vertices. Due to orthogonal easy planes of rotation for dipoles belonging to different sublattices, the total dipolar energy of this system is separable into a sum of symmetric and chiral long-ranged interactions between the magnets where the last takes the form of Dzyaloshinskii-Moriya (DM) coupling. For a specific range of values of the offset between sublattices, the dipoles realize an equilibrium magnetic state in the lattice plane, consisting of one chain settled in an antiferromagnetic (AF) parallel configuration and the other in a collinear ferromagnetic fashion. If the offset grows beyond this value, the internal DM field stabilizes two Bloch domain walls at the edges of the AF chain. The dynamics of these solitons is studied by deriving the long-wavelength lagrangian density for the easy axis antiferromagnet. We find that the chiral couplings between sublattices give rise to an effective magnetic field that stabilizes the solitons in the antiferromagnet. When the chains displace respect to each other, an emergent Lorentz force accelerates the domain walls along the lattice.
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The wave propagation has the significant role in the field of coastal engineering and ocean. In the geographical fields, waves are primary source of environmental process owed to energy conveyance on floating structure. This study aims to investigate the system of cold bosonic atoms in zig-zag optics lattices. The solitonic patterns of the considered model successfully surveyed by using two integrated analytical techniques new extended direct algebraic and G ' G 2 expansion method. The exact solutions are presented by rational, trigonometric, hyperbolic and exponential functions. On the basis of solitons, we need to show that which one is more integrated and robust scheme. These solutions will help to understood the dynamics of cold bosonic atoms in zig-zag optical lattices and the several other systems. Three dimensional as well as two dimensional comparison presented for a cold bosonic atoms model solutions which are revealed diagrammatically for appropriate parameters by using Mathematica. This study will help physicists to predict some new hypothesis and theories in the field of mathematical physics.
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To increase the probability of detecting odour plumes, and so increase prey capture success, when winds are stable central place foraging seabirds should fly crosswind to maximize the round-trip distance covered. At present, however, there is no empirical evidence of this theoretical prediction. Here, using an extensive GPS tracking dataset, we investigate, for the first time, the foraging movements of Bulwer's petrels (Bulweria bulwerii) in the persistent North Atlantic trade winds. To test the hypotheses that, in stable winds, petrels use crosswind to maximize both the distance covered and the probability of detecting olfactory cues, we combine state-space models, generalized additive models and Gaussian plume models. Bulwer's petrels had the highest degree of selectivity for crosswinds documented to date, often leading to systematic zig-zag flights. Crosswinds maximized both the distance travelled and the probability of detecting odour plumes integrated across the round-trip (rather than at any given point along the route, which would result in energetically costly return flight). This evidence suggests that petrels plan round-trip flights at departure, integrating expected costs of homeward journeys. Our findings, which are probably true for other seabirds in similar settings, further highlight the critical role of wind in seabird foraging ecology.
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Aves , Conducta Alimentaria , Animales , Señales (Psicología) , Olfato , VientoRESUMEN
Photocatalytic degradation method has been recognized as an effective way to eliminate the contamination of environment. However, developing photocatalysts with excellent photocatalytic properties are still a big challenge. In this paper, Ag doped ZnO coating with a layer of N doped porous carbon (Ag/ZnO@N-carbon) was successfully synthesized by using polyvinyl pyrrolidone (PVP) modified ZIF-8 as precursor via adsorption, hydrothermal treatment, in situ growth and carbonization processes. The physical and chemical properties of all samples were characterized by X-ray powder diffraction (XRD), scanning electron microscope (SEM), electron transmission microscopy (TEM) and so on. The results show that Ag doping does not change the crystallinity of ZnO, but broaden its photo-response property. The coating of N doped carbon can improve the specific surface area of photocatalyst. The photocatalytic activity of all samples was evaluated by degradation of rhodamine B (RhB) solution under UV light irradiation for 25 min. Ag/ZnO@N-carbon exhibits the highest photocatalytic activity for degradation of RhB with a degradation of 98.65%. Furthermore, Ag/ZnO@N-carbon also has high stability. Based on the characterization, possible mechanism for degradation of RhB by Ag/ZnO@N-carbon under UV light irradiation was proposed.
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BACKGROUND AND AIMS: The level of albuminuria is used to evaluate diabetic nephropathy (DN). However, to detect or predict the early stages of DN, better biomarkers are needed. METHODS: This study is a case-control observational study. 80 Egyptians participated in the study: 60 patients with type 2 diabetes mellitus (T2DM) were divided into three groups (20 patients each), and 20 healthy subjects with matched age and gender were used as controls. Demographic and laboratory data were analyzed. An enzyme-linked immunosorbent assay was used to determine the levels of four biomarkers of DN; urinary adiponectin (ADP), urinary transferrin, serum Zinc Alpha 2 Glycoprotein (ZAG), and urinary Retinol Binding Protein (RBP). RESULTS: The levels of DN biomarkers urinary ADP, transferrin, RBP, and serum, ZAG were significantly higher in patients with T2DM than in controls. The ROC curve of the validity of the simultaneous use of all four biomarkers in predicting albuminuria indicates a sensitivity of 90% and a specificity of 90%. The Area Under the Curve (AUC) was 0.948, the 95% confidence interval was 0.998-0.897, and the p-value was 0.001. CONCLUSIONS: In patients with T2DM, urine adiponectin, transferrin, RBP, and serum ZAG concentration may be useful biomarkers in the early diagnosis of DN. A further longitudinal prospective study is required to explore the potential utility of these biomarkers.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Femenino , Humanos , Masculino , Adiponectina , Albuminuria/diagnóstico , Biomarcadores , Estudios de Casos y Controles , Diagnóstico Precoz , Glicoproteínas , Proteínas de Unión al Retinol , Transferrina , ZincRESUMEN
Aluminum hydrolysis chemistry is an important part of modern society because of the dominance of Al(III) as a highly effective antiperspirant active. However, the century-old chemistry centered on aluminum chloride (ACL) is not comprehensive enough to address all of the in vivo events associated with current commercial antiperspirants and their mechanism of action. The present study aims to address the knowledge gap among extensively studied benchmark ACL, its modified version aluminum chlorohydrate (ACH), and a more complex but less explored group of aluminum zirconium chlorohydrate glycine complexes (ZAG salts) toward understanding the mechanism of action under consumer-relevant conditions. ACH, which is the Al source used in the manufacture of ZAG salts, provides a bridge between ACL and ZAG chemistry. High viscosity and gel formation driven by pH and a specific Al(III) salt upon hydrolysis are considered the criteria for building an in vivo occlusive mass to retard or stop the flow of sweat to the skin surface, thus providing an antiperspirant effect. Rheological studies indicated that ACL and aluminum zirconium tetrachlorohydrex glycine (TETRA) were the most efficacious salt actives. Spectroscopic studies, diffraction studies, and elemental analysis suggested that small metal oxide and hydroxide species with coparticipating glycine as well as various polynuclear and oligomeric species are the key to gel formation. At a given pH, the key ingredients (NaCl, urea, bovine serum albumin, and lactic acid) in artificial sweat were found to have little influence on Al(III) salt hydrolysis. The effects of the sweat components were mostly limited to local complex formation and kinetic modification. The in vitro comparative experiments with various Al(III) and ZAG salt systems offer unprecedented insights into the chemistry of different salt types, thus paving the way for engineering more efficacious antiperspirant systems.
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Compuestos de Aluminio/química , Antitranspirantes/química , Glicina/química , Sales (Química)/química , Circonio/química , Hidrogeles/química , Concentración de Iones de Hidrógeno , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Viscosidad , Difracción de Rayos XRESUMEN
CONTEXT: Resistance exercise training has recently been considered as an effective type of training to increase energy metabolism and insulin sensitivity. However, mechanisms of the resistance training-induced improvements in energy metabolism and insulin sensitivity have not been fully understood. Zinc-α2-glycoprotein (ZAG), which is a novel adipokine, has beneficial effects on energy metabolism and insulin sensitivity. OBJECTIVE: We investigated the effect of a single bout of resistance exercise on the ZAG concentration. METHODS: Nine healthy men were enrolled. They performed a single bout of resistance exercise (bench press and leg press) consisting of 10 repetitions of five sets at 70% of maximum strength with 90-s rests in between sets. Blood samples were obtained before and after acute resistance exercise to measure the ZAG concentration. RESULTS: The serum ZAG concentration significantly increased following acute resistance exercise. CONCLUSION: This result suggests that a single bout of resistance exercise may enhance the ZAG concentration.
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Resistencia a la Insulina , Entrenamiento de Fuerza , Zn-alfa-2-Glicoproteína/sangre , Humanos , MasculinoRESUMEN
Objective The efficacy of tolvaptan, an orally active vasopressin V2-receptor antagonist, has recently been reported in patients with massive ascites unresponsive to conventional diuretics. However, the effect of tolvaptan varies among patients. Recently, the prognostic role of the tolvaptan response in cases of decompensated liver cirrhosis (LC) has been attracting increasing attention. Using serum copeptin (vasopressin precursor), zinc-α2-glycoprotein (ZAG), cystatin C (renal biomarker), neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), we explored which factors portend a good response to tolvaptan in LC patients with ascites. Methods We enrolled 113 LC patients and divided them into the tolvaptan treatment group and non-treatment group. Tolvaptan (3.75 or 7.5 mg/day) was administrated to 38 LC patients with ascites, and a follow-up assessment was performed after a 7-day tolvaptan treatment regimen. Results We determined the predictive ability for kidney and/or liver damage of serum copeptin, ZAG, cystatin C, NGAL and L-FABP levels in all patients. After 7-day tolvaptan treatment, 19 patients had lost more than 1.5 kg of body weight (Responders), while 19 showed no marked change in their body weight (Non-responders). Basal blood urea nitrogen (BUN) (p=0.0014), serum copeptin (p=0.0265) and serum ZAG levels (p=0.0142) were significantly higher in the Non-responders than in the Responders. BUN (odds ratio 7.43, p=0.0306), copeptin (odds ratio 9.12, p=0.0136) and ZAG (odds ratio 7.43, p=0.0306) were determined to be predictive factors of drug responsiveness using a multivariate logistic regression analysis. Conclusion Serum BUN, copeptin and ZAG levels predict the patient response to tolvaptan, even when measured prior to treatment.
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Antagonistas de los Receptores de Hormonas Antidiuréticas , Ascitis , Adipoquinas , Antagonistas de los Receptores de Hormonas Antidiuréticas/uso terapéutico , Ascitis/tratamiento farmacológico , Benzazepinas/uso terapéutico , Biomarcadores , Glicopéptidos , Glicoproteínas , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Tolvaptán , ZincRESUMEN
PURPOSE: Accumulating evidence has attracted attention to the androgen receptor (AR) as a biomarker and therapeutic target in breast cancer. We hypothesized that AR activity within the tumor has clinical implications and investigated whether androgen responsive serum factors might serve as a minimally invasive indicator of tumor AR activity. METHODS: Based on a comprehensive gene expression analysis of an AR-positive, triple negative breast cancer patient-derived xenograft (PDX) model, 163 dihydrotestosterone (DHT)-responsive genes were defined as an androgen responsive gene set. Among them, we focused on genes that were DHT-responsive that encode secreted proteins, namely KLK3, AZGP1 and PIP, that encode the secreted factors prostate specific antigen (PSA), zinc-alpha-2-glycoprotein (ZAG) and prolactin induced protein (PIP), respectively. Using AR-positive breast cancer cell lines representing all breast cancer subtypes, expression of candidate factors was assessed in response to agonist DHT and antagonist enzalutamide. Gene set enrichment analysis (GSEA) was performed on publically available gene expression datasets from breast cancer patients to analyze the relationship between genes encoding the secreted factors and other androgen responsive gene sets in each breast cancer subtype. RESULTS: Anti-androgen treatment decreased proliferation in all cell lines tested representing various tumor subtypes. Expression of the secreted factors was regulated by AR activation in the majority of breast cancer cell lines. In GSEA, the candidate genes were positively correlated with an androgen responsive gene set across breast cancer subtypes. CONCLUSION: KLK3, AZGP1 and PIP are AR regulated and reflect tumor AR activity. Further investigations are needed to examine the potential efficacy of these factors as serum biomarkers.
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Adipoquinas/metabolismo , Neoplasias de la Mama/metabolismo , Calicreínas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Antígeno Prostático Específico/metabolismo , Receptores Androgénicos/metabolismo , Adipoquinas/genética , Antagonistas de Receptores Androgénicos/farmacología , Andrógenos/farmacología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Calicreínas/genética , Masculino , Proteínas de Transporte de Membrana/genética , Ratones , Antígeno Prostático Específico/genética , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Meander-line, or zig-zag, MRI surface coils theoretically promise spatially uniform fields with optimal field localization close to the coil. In reality, they suffer poorer than expected field localizations and acquired images are often highly inhomogeneous, plagued by repeating stripe-like signal-loss artifacts. We show that both these detrimental effects arise from coil design based on the same invalid approximation in the underlying theory. Here, the conventional approximation is corrected, yielding a modified coil design that validates the new theory by rectifying the above problems. Specifically, an easily implementable coil correction, which amounts to the addition of a single extra turn of wire, is introduced and shown to increase signal uniformity by an order of magnitude, eliminate image artifacts, and reduce unwanted signal interference from deeper within the sample by tightening the coil field localization to close to the coil, as intended for zig-zag designs. With independent optimization of coil size and imaging depth possible, such corrected meander-lines surface coils may be well suited for large area, near-surface imaging and spectroscopy applications.