The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled ...trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly.
ClnicalTrials.gov NCT01596205.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects ...the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and compa- rability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily iden- tify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines includ- ing CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing. KCI Citation Count: 0
Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In ...this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy.
BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors.
BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing heterodimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation.
BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.
The therapeutic antibody drug market has experienced explosive growth as mAbs become the main therapeutic modality for a variety of diseases. Characterization of glycosylation that directly affects ...the efficacy and safety of therapeutic monoclonal antibodies (mAbs) is critical for therapeutics development, bioprocess system optimization, lot release, and comparability evaluation. The LC/MS approach has been widely used to structurally characterize mAbs, and recently attempts have been made to obtain comprehensive information on the primary structure and post-translational modifications (PTMs) of mAbs through intact protein analysis. In this study, we performed state-of-the-art LC/MS based intact protein analysis to readily identify and characterize glycoforms of various mAbs. Different glycoforms of mAbs produced in different expression cell lines including CHO, SP2/0 and HEK cells were monitored and compared. In addition, the comparability of protein molecular weight, glycoform pattern, and relative abundances of glycoforms between the commercialized trastuzumab biosimilar and the original product was determined in detail using the given platform. Intact mAb analysis allowed us to gain insight into the overall mAb structure, including the complexity and diversity of glycosylation. Furthermore, our analytical platform with high reproducibility is expected to be widely used for biopharmaceutical characterization required at all stages of drug development and manufacturing.
In this study, a new ejector-porous tube diluter was developed to accurately in situ measure particulate matter at the source, e.g., emissions at coal-fired power plants, and its dilution ratio and ...particle loss were compared to those of a commercial model. Whereas commercial models supply air to the porous tube diluter (PRD) using a high-pressure compressor, our device replaces the latter with a ring blower, thereby decreasing the power consumption for the same airflow rate. As a demonstration, particle size volume distributions of fly ash at a coal-fired power plant stack were determined for different dilution ratios. PRD flow rates of 10 and 20 L min^(-1) for the commercial diluter produced ~2-μm particle volume concentrations of 382 and 572 μm^3 cm^(-3), respectively, from an initial (undiluted) volume concentration of 756 μm^3 cm^(-3). However, PRD flow rates of 10 and 30 L min^(-1) for the developed device produced ~2-μm particle volume concentrations of 506 and 500 μm^3 cm^(-3), respectively, from an initial volume concentration of 532 μm^3 cm^(-3). These particle loss rates were confirmed through field testing.
Twenty-one angular dihydropyranocoumarins and a linear furanocoumarin, including four previously undescribed compounds (1–4), were isolated from the flowers of Peucedanum japonicum (Umbelliferae). ...The structures of 1–4, along with their absolute stereochemistry, were determined to be (3′S,4′S)-3′-O-propanoyl-4′-O-(3‴-methyl-2‴-butenoyl)khellactone (1), (3′S,4′S)-3′-O-propanoyl-4′-O-(2‴-methyl-2‴Z-butenoyl)khellactone (2), (3′S,4′S)-3′-O-propanoyl-4′-O-(2‴-methylbutanoyl)khellactone (3), and (3′S,4′S)-3′-O-(2″-methylpropanoyl)-4′-O-(3‴-methyl-2‴-butenoyl)khellactone (4) using one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectroscopy, and electronic circular dichroism spectroscopy. In addition, the absolute configuration of the three angular dihydropyranocoumarins (5–7) was determined for the first time in this study. Among the previously reported compounds isolated in this study, 8 and 9 were isolated for the first time from the genus Peucedanum, whereas 10 and 11 were previously unreported and had not been isolated from P. japonicum to date. Furthermore, all isolated compounds were evaluated for their aldo–keto reductase 1C1 inhibitory activities on A549 human non-small-cell lung cancer cells. Compounds 10 and 12 exhibited substantial AKR1C1 inhibitory activities with IC50 values of 35.8 ± 0.9 and 44.2 ± 1.5 μM, respectively.
Four previously undescribed angular dihydropyranocoumarins (1–4), along with eighteen known compounds were identified from the flowers of Peucedanum japonicum. Bioactivity assay revealed that two isolates (10 and 12) showed aldo-keto reductase1C1 inhibitory activity. Display omitted
•Four previously undescribed angular dihydropyranocoumarins were isolated from Peucedanum japonicum.•The absolute configurations of three angular dihydropyranocoumarins were determined.•Four known angular dihydropyranocoumarins were isolated from P. japonicum for the first time.•Compounds 10 and 12 inhibited aldo-keto reductase 1C1 activity for anti-cancer effects.
We report the draft genome sequence of Bacillus thuringiensis serovar aizawai AS23, an insecticidal strain targeting lepidopteran pests, which was isolated from the rhizosphere of Korean melon ...(Cucumis melo L.). The genome of strain AS23 comprising 6,846,584 bp with a G + C content of 34.83% was assembled to 11 contigs obtained using hybrid assembly. Additionally, we mined the genome for pesticidal genes, identifying several insecticidal genes, including Cry1Aa3, Cry1Ca9, Cry1Da2, Cry1Ia44, Cry2Ab41, Cry9Ea9, Spp1Aa1, and Vip3Aa86. KCI Citation Count: 0
Accumulating evidence demonstrates that the activity regulation of ELK3, a member of the E26 transformation-specific oncogene family, is critical to regulating cell proliferation, migration, and ...survival in human cancers. However, the molecular mechanisms of how ELK3 induces chemoresistance in prostate cancer (PCa) have not been elucidated. In this study, we found that SPOP and ELK3 are an interacting partner. The interaction between SPOP and ELK3 resulted in increased ELK3 ubiquitination and destruction, assisted by checkpoint kinase-mediated ELK3 phosphorylation. Notably, the modulation of SPOP-mediated ELK3 protein stability affected the c-Fos-induced cell proliferation and invasion of PCa cells. The clinical involvement of the SPOP-ELK3 axis in PCa development was confirmed by an immunohistochemical assay on 123 PCa tissues, with an inverse correlation between increased ELK3 and decreased SPOP being present in ~80% of the specimens. This observation was supported by immunohistochemistry analysis using a SPOP-mutant PCa specimen. Finally, docetaxel treatment induced cell death by activating checkpoint kinase- and SPOP-mediated ELK3 degradation, while SPOP-depleted or SPOP-mutated PCa cells showed cell death resistance. Notably, this observation was correlated with the protein levels of ELK3. Taken together, our study reveals the precise mechanism of SPOP-mediated degradation of ELK3 and provides evidence that SPOP mutations contribute to docetaxel resistance in PCa.
► Silver nanoparticles (AgNPs) were synthesized in a sodium alginate solution. ► Alginate–AgNPs composite sponge was prepared from the nanocolloid solution. ► The alginate–AgNPs composite sponge had ...a highly enhanced antimicrobial activity. ► The amount of proinflammatory cytokines was reduced with the composite sponge.
Silver-based biomaterials have been developed in a variety of bactericidal applications, especially for wound dressings. In this study, silver nanoparticles (AgNPs) were synthesized in a sodium alginate solution and then the composite sponge containing AgNPs was prepared from the nanocolloid solution. The alginate-stabilized AgNPs had the mean negative zeta potential of −52.5mV, suggesting that the surface charge prevents the nanoparticles from aggregating through electrostatic repulsion. The alginate–AgNPs composite sponge had a highly enhanced antimicrobial activity compared to the alginate sponge. In spite of excellent cytocompatibility of the alginate sponge, the viability of the cell treated with the alginate–AgNPs composite sponge extract decreased to 86% of the control. The amount of proinflammatory cytokines released from macrophages treated with the alginate–AgNPs composite sponge was reduced. For the preparation of AgNPs-embedded composites, alginate can be a potential candidate stabilizing AgNPs and providing synergistic antimicrobial and antiinflammatory activities with AgNPs.
BackgroundCancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) contribute to an impaired functionality of natural killer (NK) cells that have emerged as a promising therapeutic ...modality. The interaction between CAFs and NK cells within the TME exerts major inhibitory effects on immune responses, indicating CAF-targeted therapies as potential targets for effective NK-mediated cancer killing.MethodsTo overcome CAF-induced NK dysfunction, we selected an antifibrotic drug, nintedanib, for synergistic therapeutic combination. To evaluate synergistic therapeutic efficacy, we established an in vitro 3D Capan2/patient-derived CAF spheroid model or in vivo mixed Capan2/CAF tumor xenograft model. The molecular mechanism of NK-mediated synergistic therapeutic combination with nintedanib was revealed through in vitro experiments. In vivo therapeutic combination efficacy was subsequently evaluated. Additionally, the expression score of target proteins was measured in patient-derived tumor sections by the immunohistochemical method.ResultsNintedanib blocked the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway and diminished the activation and growth of CAFs, markedly reducing CAF-secreted IL-6. Moreover, coadministration of nintedanib improved the mesothelin (MSLN) targeting chimeric antigen receptor-NK-mediated tumor killing abilities in CAF/tumor spheroids or a xenograft model. The synergistic combination resulted in intense NK infiltration in vivo. Nintedanib alone exerted no effects, whereas blockade of IL-6 trans-signaling ameliorated the function of NK cells. The combination of the expression of MSLN and the PDGFRβ+-CAF population area, a potential prognostic/therapeutic marker, was associated with inferior clinical outcomes.ConclusionOur strategy against PDGFRβ+-CAF-containing pancreatic cancer allows improvements in the therapy of pancreatic ductal adenocarcinoma.
PDF
