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This present study investigated the effect of cold atmospheric plasma (CAP) pre-treatment on the quality of ready-to-eat drunken red shrimp (Solenocera crassicornis) during chilled storage. The shrimp were pre-treated with the CAP at 40 kV and 36 kH for 100 s in a plasma generating equipment before the drunken treatment and compared with an untreated control sample. The results showed that the CAP pre-treatment significantly inhibited the total viable count (TVC) values, total volatile basic nitrogen (TVB-N) content, and polyphenol oxidase (PPO) activity of the drunken shrimp compared to the control treatment. Furthermore, the CAP pre-treatment also significantly maintained the myofibrillar protein (MP) content, texture properties, and a more stable histological structure of muscle fibers compared to the control. High-throughput sequencing results confirmed that the CAP pre-treatment significantly reduced the diversity and abundance of several bacteria in the shrimp. Gas chromatography-ion mobility spectrometry (GC-IMS) analysis detected that the CAP pre-treatment effectively maintained the stability of volatile organic compounds (VOCs). These findings provide valuable theoretical support for the processing and storage of drunken shrimp.
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OBJECTIVES: This study aimed to analyse the effect of using phosphate buffer solution (PBS) on the solubility, pH changes, surface structure, and elemental composition of a new bioceramic Cerafill sealer compared with Endosequence sealer and AH26 resin-based sealer. METHODS: A fresh mixture of each sealer moistened with either deionised water or PBS was subjected to a setting time test. Set discs (n = 10) were submerged in either deionised water or PBS to evaluate pH changes and solubility at 1, 7, 14, 21, and 28 days. Surface characterisation of the sealers was done before and after solubility tests using scanning electron microscopy (SEM), energy-dispersive X-ray (EDX), and Fourier transform infrared (FTIR) spectroscopy analyses. RESULTS: An analysis of variance revealed a significant delay in setting of BC-Endosequence (P < .001) with no significant difference when each sealer was moistened with deionised water or PBS (P > .05). Both bioceramic sealers exhibited highly alkaline pH (range, 9.47-10.72). When the sealer was submerged in deionised water, Endosequence exhibited significantly greater solubility, whilst Cerafill and AH26 gained weight. When the sealers were submerged in PBS, both bioceramic sealers gained more weight, with significantly greater values for Endosequence (P < .001). Hydroxyapatite formation was revealed by SEM/EDX and FTIR. CONCLUSIONS: PBS promoted the formation of hydroxyapatite crystals that protect the bioceramic sealers from dissolving.
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Compuestos de Calcio , Cavidad Pulpar , Humanos , Solubilidad , Compuestos de Calcio/química , Ensayo de Materiales , Agua , HidroxiapatitasRESUMEN
Objective: Knee osteoarthritis (KOA) is a highly prevalent musculoskeletal disorder characterized by degeneration of cartilage and abnormal remodeling of subchondral bone (SCB). Teriparatide (PTH (1-34)) is an effective anabolic drug for osteoporosis (OP) and regulates osteoprotegerin (OPG)/receptor activator of nuclear factor ligand (RANKL)/RANK signaling, which also has a therapeutic effect on KOA by ameliorating cartilage degradation and inhibiting aberrant remodeling of SCB. However, the mechanisms of PTH (1-34) in treating KOA are still uncertain and remain to be explored. Therefore, we compared the effect of PTH (1-34) on the post-traumatic KOA mouse model to explore the potential therapeutic effect and mechanisms. Methods: In vivo study, eight-week-old male mice including wild-type (WT) (n â= â54) and OPG-/- (n â= â54) were investigated and compared. Post-traumatic KOA model was created by destabilization of medial meniscus (DMM). WT mice were randomly assigned into three groups: the sham group (WT-sham; n â= â18), the DMM group (WT-DMM; n â= â18), and the PTH (1-34)-treated group (WT-DMM â+ âPTH (1-34); n â= â18). Similarly, the OPG-/- mice were randomly allocated into three groups as well. The designed mice were executed at the 4th, 8th, and 12th weeks to evaluate KOA progression. To further explore the chondro-protective of PTH (1-34), the ATDC5 chondrocytes were stimulated with different concentrations of PTH (1-34) in vitro. Results: Compared with the WT-sham mice, significant wear of cartilage in terms of reduced cartilage thickness and glycosaminoglycan (GAG) loss was detected in the WT-DMM mice. PTH (1-34) exhibited cartilage-protective by alleviating wear, retaining the thickness and GAG contents. Moreover, the deterioration of the SCB was alleviated and the expression of PTH1R/OPG/RANKL/RANK were found to increase after PTH (1-34) treatment. Among the OPG-/- mice, the cartilage of the DMM mice displayed typical KOA change with higher OARSI score and thinner cartilage. The damage of the cartilage was alleviated but the abnormal remodeling of SCB didn't show any response to the PTH (1-34) treatment. Compared with the WT-DMM mice, the OPG-/--DMM mice caught more aggressive KOA with thinner cartilage, sever cartilage damage, and more abnormal remodeling of SCB. Moreover, both the damaged cartilage from the WT-DMM mice and the OPG-/--DMM mice were alleviated but only the deterioration of SCB in WT-DMM mice was alleviated after the administration of PTH (1-34). In vitro study, PTH (1-34) could promote the viability of chondrocytes, enhance the synthesis of extracellular matrix (ECM) (AGC, COLII, and SOX9) at the mRNA and protein level, but inhibit the secretion of inflammatory cytokines (TNF-α and IL-6). Conclusion: Both wear of the cartilage was alleviated and aberrant remodeling of the SCB was inhibited in the WT mice, but only the cartilage-protective effect was observed in the OPG-/- mice. PTH (1-34) exhibited chondro-protective effect by decelerating cartilage degeneration in vivo as well as by promoting the proliferation and enhancing ECM synthesis of chondrocytes in vitro. The current investigation implied that the rescue of the disturbed SCB is dependent on the regulation of OPG while the chondro-protective effect is independent of modulation of OPG, which provides proof for the treatment of KOA. The translational potential of this article: Systemic administration of PTH (1-34) could exert a therapeutic effect on both cartilage and SCB in different mechanisms to alleviate KOA progression, which might be a novel therapy for KOA.
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In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
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BACKGROUND: Conventional treatment for toxoplasmosis have severe side effects and the inability to completely eradicate the disease. Therefore, the acquisition of new anti-Toxoplasma drugs has always been of interest among researchers. In the present study, we prepare a new indole-triazole derivatives and evaluated their potential anti-parasitic activity against tachyzoites of Toxoplasma RH strain. MATERIALS AND METHODS: In this study, after synthesis of the two new compounds of indole-triazole, the effect of their different concentrations (2-1024 µg/ml) were determined on Toxoplasma tachyzoites using flow cytometry. Furthermore, tachyzoites were exposed to different concentrations of compounds (4, 16, 64, 265, 1024 µg/ml) for 1.5 h and their infectivity were evaluated in BALB/c mice. RESULTS: The flow cytometry results indicated the benzyl derivative of indole-triazole in various concentrations had a lethal effect on tachyzoites between 11.93% and 89.66%, while the naphthalene derivative had a lethality of 26.63%-66.82%. The infectivity analysis showed that the survival time of mice at concentrations of 1024 µg/ml and 512 µg/ml of benzyl derivatives was significantly increased (P = 0.008 and P = 0.016, respectively), compared to that in the negative control group. Furthermore, survival time of mice was statistically significant at the concentration of 1024 µg/ml for naphthyl derivative (P = 0.012). CONCLUSION: Findings of the current study suggested indole triazole compounds, based on their structure and enzymes targeting, have a considerable effect on tachyzoites of T. gondii RH strain and can be considered as a new anti-Toxoplasma agent.
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Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG2K) is utilized to achieve core-matched PEGylating modification via the πâπ stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG2K shell. Compared to PCL-PEG2K with similar molecular weight, PPa-PEG2K significantly increases the stability, prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly. As a result, PPa/PPa-PEG2K NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model. Together, such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.
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The electrochemical behavior of commercially pure titanium (CP Ti) and Ti-6Al-4V (Grade 5) alloy in phosphate buffered saline solution (PBS, pH = 7.4) at 37 °C (i.e., in simulated physiological solution in the human body) was examined using open circuit potential measurements, linear and potentiodynamic polarization and electrochemical impedance spectroscopy methods. After the impedance measurements and after potentiodynamic polarization measurements, the surface of the samples was investigated by scanning electron microscopy, while the elemental composition of oxide film on the surface of each sample was determined by EDS analysis. The electrochemical and corrosion behavior of CP Ti and Ti-6Al-4V alloys is due to forming a two-layer model of surface oxide film, consisting of a thin barrier-type inner layer and a porous outer layer. The inner barrier layer mainly prevents corrosion of CP Ti and Ti-6Al-4V alloy, whose thickness and resistance increase sharply in the first few days of exposure to PBS solution. With longer exposure times to the PBS solution, the structure of the barrier layer subsequently settles, and its resistance increases further. Compared to Ti-6Al-4V alloy, CP Ti shows greater corrosion stability.
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BACKGROUND: Despite widespread use of repeated doses of potent bone-targeting agents (BTA) in oncology patients, relatively little is known about their in vivo effects on bone homeostasis, bone quality, and bone architecture. Traditionally bone quality has been assessed using a trans-iliac bone biopsy with a 7 mm "Bordier" core needle. We examined the feasibility of using a 2 mm "Jamshidi™" core needle as a more practical and less invasive technique. METHODS: Patients with metastatic breast cancer on BTAs were divided according to the extent of bone metastases. They were given 2 courses of tetracycline labeling and then underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for the extent of tumor invasion and parameters of bone turnover and bone formation by histomorphometry. RESULTS: Twelve patients were accrued, 1 had no bone metastases, 3 had limited bone metastases (LSM) (<3 lesions) and 7 had extensive bone metastases (ESM) (>3 lesions). Most of the primary tumors were estrogen receptor (ER)/progesterone receptor (PR) positive. The procedure was well tolerated. The sample quality was sufficient to analyze bone trabecular structure and bone turnover by histomorphometry in 11 out of 12 patients. There was a good correlation between imaging data and morphometric analysis of tumor invasion. Patients with no evidence or minimal bone metastases had no evidence of tumor invasion. Most had suppressed bone turnover and no detectable bone formation when treated with BTA. In contrast, 6 out of 7 patients with extensive bone invasion by imaging and evidence of tumor cells in the marrow had intense osteoclastic activity as measured by the number of osteoclasts. Of these 7 patients with ESM, 6 were treated with BTA with 5 showing resistance to BTA as demonstrated by the high number of osteoclasts present. 3 of these 6 patients had active bone formation. Based on osteoblast activity and bone formation, 3 out of 6 patients with ESM responded to BTA compared to all 3 with LSM. Compared to untreated patients, all patients treated with BTA showed a trend towards suppression of bone formation, as measured by tetracycline labelling. There was also a trend towards a significant difference between ESM and LSM treated with BTA, highly suggestive of resistance although limited by the small sample size. DISCUSSION: Our results indicate that trans-iliac bone biopsy using a 2 mm trephine shows excellent correlation between imaging assessment of tumor invasion and tumor burden by morphometric analysis of bone tissues. In addition, our approach provides additional mechanistic information on therapeutic response to BTA supporting the current clinical understanding that the majority of patients with extensive bone involvement eventually fail to suppress bone turnover (Petrut B, et al. 2008). This suggests that antiresorptive therapies become less effective as disease progresses.
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INTRODUCTION: The skin is comprised of various kinds of cells and has three layers, the epidermis, dermis and subcutaneous adipose tissue. Stem cells in each tissue duplicate themselves and differentiate to supply new cells that function in the tissue, and thereby maintain the tissue homeostasis. In contrast, senescent cells accumulate with age and secrete senescence-associated secretory phenotype (SASP) factors that impair surrounding cells and tissues, which lowers the capacity to maintain homeostasis in each tissue. Previously, we found Gremlin 2 (GREM2) as a novel SASP factor in the skin and reported that GREM2 suppressed the differentiation of adipose-derived stromal/stem cells. In the present study, we investigated the effects of GREM2 on stem cells in the epidermis and dermis. METHODS: To examine whether GREM2 expression and the differentiation levels in the epidermis and dermis are correlated, the expressions of GREM2, stem cell markers, an epidermal differentiation marker Keratin 10 (KRT10) and a dermal differentiation marker type 3 procollagen were examined in the skin samples (n = 14) randomly chosen from the elderly where GREM2 expression level is high and the individual differences of its expression are prominent. Next, to test whether GREM2 affects the differentiation of skin stem cells, cells from two established lines (an epidermal and a dermal stem/progenitor cell model) were cultured and induced to differentiate, and recombinant GREM2 protein was added. RESULTS: In the human skin, the expression levels of GREM2 varied among individuals both in the epidermis and dermis. The expression level of GREM2 was not correlated with the number of stem cells, but negatively correlated with those of both an epidermal and a dermal differentiation markers. The expression levels of epidermal differentiation markers were significantly suppressed by the addition of GREM2 in the three-dimensional (3D) epidermis generated with an epidermal stem/progenitor cell model. In addition, by differentiation induction, the expressions of dermal differentiation markers were induced in cells from a dermal stem/progenitor cell model, and the addition of GREM2 significantly suppressed the expressions of the dermal differentiation markers. CONCLUSIONS: GREM2 expression level did not affect the numbers of stem cells in the epidermis and dermis but affects the differentiation and maturation levels of the tissues, and GREM2 suppressed the differentiation of stem/progenitor cells in vitro. These findings suggest that GREM2 may contribute to the age-related reduction in the capacity to maintain skin homeostasis by suppressing the differentiation of epidermal and dermal stem/progenitor cells.
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The bromodomain and extraterminal (BET) family member BRD4 is pivotal in the pathogenesis of cardiac hypertrophy. BRD4 induces hypertrophic gene expression by binding to the acetylated chromatin, facilitating the phosphorylation of RNA polymerases II (Pol II) and leading to transcription elongation. The present study identified a novel post-translational modification of BRD4: poly(ADP-ribosyl)ation (PARylation), that was mediated by poly(ADP-ribose)polymerase-1 (PARP1) in cardiac hypertrophy. BRD4 silencing or BET inhibitors JQ1 and MS417 prevented cardiac hypertrophic responses induced by isoproterenol (ISO), whereas overexpression of BRD4 promoted cardiac hypertrophy, confirming the critical role of BRD4 in pathological cardiac hypertrophy. PARP1 was activated in ISO-induced cardiac hypertrophy and facilitated the development of cardiac hypertrophy. BRD4 was involved in the prohypertrophic effect of PARP1, as implied by the observations that BRD4 inhibition or silencing reversed PARP1-induced hypertrophic responses, and that BRD4 overexpression suppressed the anti-hypertrophic effect of PARP1 inhibitors. Interactions of BRD4 and PARP1 were observed by co-immunoprecipitation and immunofluorescence. PARylation of BRD4 induced by PARP1 was investigated by PARylation assays. In response to hypertrophic stimuli like ISO, PARylation level of BRD4 was elevated, along with enhanced interactions between BRD4 and PARP1. By investigating the PARylation of truncation mutants of BRD4, the C-terminal domain (CTD) was identified as the PARylation modification sites of BRD4. PARylation of BRD4 facilitated its binding to the transcription start sites (TSS) of hypertrophic genes, resulting in enhanced phosphorylation of RNA Pol II and transcription activation of hypertrophic genes. The present findings suggest that strategies targeting inhibition of PARP1-BRD4 might have therapeutic potential for pathological cardiac hypertrophy.
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BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.
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Anticarcinógenos/farmacología , Artemisininas/farmacología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/efectos de los fármacos , Neoplasias Gástricas/prevención & control , Animales , Artesunato/farmacología , Adhesión Bacteriana/efectos de los fármacos , Línea Celular Tumoral , Citocinas/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Allergic rhinitis is the main symptom of pollinosis, relieved by non-specific treatment universally. This study aimed to find the changes of serum metabolites between the seizure and remission periods of pollinosis and provide assistance in the diagnosis and/or therapy. METHODS: Metabonomics based on 1H nuclear magnetic resonance (NMR) was used to study the 37 serum samples of pollinosis patients. RESULTS: We believed that the decreased levels of isoleutine, leutine, valine, 3-hydroxybutyric acid, allo-threonine, alanine, methionine, glutamine, lysine, glycine, l-tyrosine, histidine, phenylalanine, lactate, acetate, O-acetylcholine, creatine and creatinine and the increased level of N-acetylglutamine at the seizure stage were statistically significant. CONCLUSIONS: Pollinosis could change the metabolic profiles of energy, amino acid and lipid in patients, which might be the diagnosis and/or prognosis markers for hay fever patients.
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In this study, a new series of N,N-bis(alkanol)amine aryl ester heterodimers was synthesized and studied. The new compounds were designed based on the structures of our previous arylamine ester derivatives endowed with high P-gp-dependent multidrug resistance reversing activity on a multidrug-resistant leukemia cell line. All new compounds were active in the pirarubicin uptake assay on the doxorubicin-resistant erythroleukemia K562â¯cells (K562/DOX). Compounds bearing a linker made up of 10 methylenes showed unprecedented high reversal activities regardless of the combination of aromatic moieties. Docking results obtained by an in silico study supported the data obtained by the biological tests and a study devoted to establish the chemical stability in phosphate buffer solution (PBS) and human plasma showed that only a few compounds exhibited a significant degradation in the human plasma matrix. Ten selected non-hydrolysable derivatives were able to inhibit the P-gp-mediated rhodamine-123 efflux on K562/DOX cells, and the evaluation of their apparent permeability and ATP consumption on other cell lines suggested that the compounds can behave as unambiguous or not transported substrates. The activity of these the compounds on the transport proteins breast cancer resistance protein (BCRP) and multidrug resistance associated protein 1 (MRP1) was also analyzed. All tested derivatives displayed a moderate potency on the BCRP overexpressing cells; while only four molecules showed to be effective on MRP1 overexpressing cells, highlighting a clear structural requirement for selectivity. In conclusion, we have identified a new very powerful series of compounds which represent interesting leads for the development of new potent and efficacious P-gp-dependent MDR modulators.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Aminas/farmacología , Antineoplásicos/farmacología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Ésteres/farmacología , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/antagonistas & inhibidores , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Aminas/síntesis química , Aminas/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Células CACO-2 , Dimerización , Relación Dosis-Respuesta a Droga , Ésteres/síntesis química , Ésteres/química , Humanos , Células K562 , Modelos Moleculares , Estructura Molecular , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Relación Estructura-Actividad , Células Tumorales CultivadasRESUMEN
Objective: To investigate the effect of varying concentrations of polyethylene glycol(PEG)400 in receiving solution on in vitro transdermal test of drugs. Method: 5-Fluorouracil(5-FU) was selected as a model drug,by preparing different concentrations of PEG400-phosphate buffer solution(PBS) as the receiving solution,the receiving chamber did not add drug,the excised rat skins were treated with various additives for 12 h,then replaced by PBS and added the saturated model drug into the donor compartment to determine the transdermal parameters of the drug.Meanwhile,scanning electron microscopy(SEM) was employed to monitor the effect of PEG400 with different concentration on the stratum corneum of rat skin. Result: The 10%,15% and 40% PEG400-PBS groups had no significant effect on in vitro transdermal absorption parameters of the 5-FU.The steady transdermal rate and cumulative penetration rate of the drug in 20% and 30% PEG400-PBS groups were significantly higher than that in the PBS group(PPConclusion: In the rat skin transdermal test,the concentration of PEG400 in receiving solution should be controlled below 20%.
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INTRODUCTION: It is generally recognized that a wide variety of morphogens and growth factors bind to the glycosaminoglycans (GAG) of proteoglycans (PG) to affect their bioavailability to ligands. Many growth factors involving in osteogenic differentiation require the GAG side chains to facilitate their interaction to the cell surface receptors and the biosynthesis of osteogenic proteins. The objective of this study is to investigate the secretion of GAG from MC3T3-E1 pre-osteoblasts of a murine bone calvaria during the osteogenic differentiation. METHODS: When MC3T3-E1 cells were cultured in the differentiation medium (DM) containing bone morphogenetic protein (BMP)-2, the alkaline phosphatase activity, calcium content and the amount of basic fibroblast growth factor (bFGF)- or BMP-2-bound sulfated GAG were determined. Moreover, the disaccharide analysis of the GAG was performed. RESULTS: When MC3T3-E1 cells were cultured in the differentiation medium (DM) containing bone morphogenetic protein (BMP)-2, the alkaline phosphatase activity and calcium content were significantly enhanced compared with those of the BMP-2-free DM and normal medium with or without BMP-2. Significantly higher amount of GAG secreted was detected for cells cultured in the DM containing BMP-2, in contrast to other culture conditions. The GAG secreted had an affinity for BMP-2 and basic fibroblast growth factor (bFGF). The disaccharide analysis of GAG demonstrated that the percentage of ΔHexA α1,4GlcNSO3 and ΔHexA (2-OSO3) α1,4GlcNSO3 increased, but that of ΔHexA α1,4GlcNSO3(6-OSO3) decreased (ΔHexA: unsaturated uronic acid residue, GlcNSO3: N-sulfated glucosamine, ΔHexA (2-OSO3): unsaturated uronic acid 2-sulfate residue, GlcNSO3(6-OSO3): N-sulfated glucosamine 6-sulfated). CONCLUSION: It was found that the osteogenic differentiation allowed cells to enhance the secretion of GAG with an affinity for BMP-2 and bFGF.
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Momordica charantia (M. charantia) is known for its antioxidant and antidiabetic properties. The aim of this study is to investigate the renoprotective effects of M. charantia in rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. Adult male Sprague-Dawley rats weighing 178.1-220.5 g (n = 36) were divided into six groups (A-F) with each group comprising of six (n = 6) rats. The drugs and extract were administered via oral gavage. The therapeutic dose of triplavar was adjusted using the human therapeutic dose equivalent for the rat model. Animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. Levels of oxidative stress enzymes (superoxide dismutase-SOD, catalase-CAT, and reduced glutathione-GSH) were significantly lowered in all groups not receiving M. charantia. The levels of thiobarbituric acid reactive substances (TBARS) were increased resulting in free radical formation via auto-oxidation. Renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine (SCr) and electrolytes in groups treated with M. charantia. HAART treated (Group B) showed severe albuminuria, a significantly (p < 0.05) raised BUN and SCr and gross electrolyte disturbances. Blood glucose levels were significantly raised in groups not receiving the adjuvant M. charantia (p < 0.05). Histopathology in HAART treated animals showed glomerular capillary abnormalities and cellular infiltrations while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. In conclusion M. charantia extract administration improved blood glucose levels, restored renal histology, reinstate renal function, reduce body weight loss and restores hyperglycemia.
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The demands for applicable tissue-engineered scaffolds that can be used to repair load-bearing segmental bone defects (SBDs) is vital and in increasing demand. In this study, seven different combinations of 3 dimensional (3D) novel nanocomposite porous structured scaffolds were fabricated to rebuild SBDs using an extraordinary blend of cockle shells (CaCo3) nanoparticles (CCN), gelatin, dextran and dextrin to structure an ideal bone scaffold with adequate degradation rate using the Freeze Drying Method (FDM) and labeled as 5211, 5400, 6211, 6300, 7101, 7200 and 8100. The micron sized cockle shells powder obtained (75 µm) was made into nanoparticles using mechano-chemical, top-down method of nanoparticles synthesis with the presence of the surfactant BS-12 (dodecyl dimethyl bataine). The phase purity and crystallographic structures, the chemical functionality and the thermal characterization of the scaffolds' powder were recognized using X-Ray Diffractometer (XRD), Fourier transform infrared (FTIR) spectrophotometer and Differential Scanning Calorimetry (DSC) respectively. Characterizations of the scaffolds were assessed by Scanning Electron Microscopy (SEM), Degradation Manner, Water Absorption Test, Swelling Test, Mechanical Test and Porosity Test. Top-down method produced cockle shell nanoparticles having averagely range 37.8±3-55.2±9 nm in size, which were determined using Transmission Electron Microscope (TEM). A mainly aragonite form of calcium carbonate was identified in both XRD and FTIR for all scaffolds, while the melting (Tm) and transition (Tg) temperatures were identified using DSC with the range of Tm 62.4-75.5 °C and of Tg 230.6-232.5 °C. The newly prepared scaffolds were with the following characteristics: (i) good biocompatibility and biodegradability, (ii) appropriate surface chemistry and (iii) highly porous, with interconnected pore network. Engineering analyses showed that scaffold 5211 possessed 3D interconnected homogenous porous structure with a porosity of about 49%, pore sizes ranging from 8.97 to 337 µm, mechanical strength 20.3 MPa, Young's Modulus 271±63 MPa and enzymatic degradation rate 22.7 within 14 days.
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The aim of this work was to use substrate without buffer solution in a microbial reverse-electrodialysis electrolysis cell (MREC) for hydrogen production under continuous flow condition (10 cell pairs of RED stacks, HRT=5, 7.5, and 15h). Decreasing in the HRT (increasing in the organic matter) made cell current stable and increased. Hydrogen gas was produced at a rate of 0.61m(3)-H2/m(3)-Van/d in H-MREC, with a COD removal efficiency of 81% (1.55g/L/d) and a Coulombic efficiency of 41%. This MREC system without buffer solution could successfully produce hydrogen gas at a consistent rate.
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Fuentes de Energía Bioeléctrica , Electrólisis/instrumentación , Electrólisis/métodos , Hidrógeno/metabolismo , Tampones (Química) , Electricidad , Electrodos , Soluciones , Factores de TiempoRESUMEN
INTRODUCTION: Hepatocellular Carcinoma (HCC) is one of most lethal cancers worldwide. The prognosis is very poor and therapeutic options are limited. The aim of this study was to determine the correlation of the [(18)F]FDG uptake profile of three HCC cell lines with p53 and glucose transporters (GLUTs) 1, 2, 3, 5 and 12 expression and with the glucose level present in the cell culture medium. METHODS: Cell lines used are HepG2 (wp53), HuH7 (overexpress p53) and Hep3B2.1-7 (p53null). An immunocytochemical analysis was performed to evaluate p53 expression. Through uptake studies were analyzed the [(18)F]FDG uptake profiles of all cell lines under study. The expression of GLUTs were quantified by flow cytometry. The [(18)F]FDG uptake studies GLUTs expression analysis were performed on cells that grew in a high and low glucose medium in order to determine the effect of glucose concentration on GLUTs expression and on [(18)F]FDG uptake. RESULTS: Immunocytochemical analysis confirmed the p53 expression profiles of all cell lines. It was found out that for all cell lines, [(18)F]FDG uptake is higher when cells grow in low glucose medium, however, the glucose level doesn't affect mostly the GLUTs expression. The Hep3B2.1-7 (p53null) is always the one that have higher [(18)F]FDG uptake. It was found that not always GLUT1 and GLUT3 are the most expressed by these cell lines. CONCLUSIONS: Our results shown that the p53 expression influences [(18)F]FDG uptake. This suggests that [(18)F]FDG may be used in HCC diagnosis, and may even provide some information about the genetic profile of the tumor.
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A wide variety of signaling transduction pathways contribute to tumorigenesis. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including colorectal cancer. However, the molecular mechanisms by which FOXQ1 promotes tumorigenesis, especially cancer cell invasion and metastasis in colorectal cancer, have not been fully elucidated. In the present study, we demonstrate that FOXQ1 is overexpressed in colorectal tumor tissues and its expression level is closely correlated with the stage and lymph node metastasis of colorectal cancer. In in vitro cultured SW480 colorectal cancer cells, knockdown of FOXQ1 expression by small interfering RNA greatly diminished the aggressive tumor behaviors of SW480 cells, including angiogenesis, invasion, epithelial-mesenchymal transition, and resistance to chemotherapy drug-induced apoptosis. Further mechanistic investigation showed that FOXQ1 silencing prevents the nuclear translocation of ß-catenin, thus reducing the activity of Wnt signaling. Moreover, TGF-ß1 induced the expression of FOXQ1 as well as the migration and invasion of SW480 cells, which was partially prevented following knockdown of FOXQ1. Our results demonstrate that FOXQ1 plays a critical role during the tumorigenesis of colorectal cancer and is a mediator of the crosstalk between Wnt and TGF-ß signaling pathways. Our findings provide further insight into the cancer biology of colorectal cancer and suggest that FOXQ1 is a potential therapeutic target for the development of therapies for colorectal cancer.