Silk hydrogel has recently received great attention for its excellent biocompatibility. The property of silk hydrogel is, however, not only hardly controlled but very limited due to non-variability ...of silk fibroin (SF) molecule. In this study, alkaline hydrolysis was utilized to manipulate the silk hydrogel properties. By regulating the hydrolysis time (10–180 min), a broad molecular weight range of SF was obtained (263.1–82.7 kDa) Gel point increased with a decrease of SF molecular weight. The change of molecular weight of SF also greatly affected the physical properties (i.e., swelling ratio, shear modulus, transparency) as well as cell adhesion of SF hydrogels. As a result of structural analysis, the molecular weight of SF played a crucial role in the construction of microscopic structure of SF hydrogel. These findings indicate that SF hydrogels of variable physical properties can be fabricated based on molecular weight control for diverse purposes in biomedical engineering.
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•Molecular weight of SF critically affected the physical properties of SF hydrogel.•Microscopic structure and secondary structure of SF hydrogel affected the optical property of SF hydrogel.•SF hydrogel with different molecular weight could be utilized for diverse purpose in biomedical engineering.
Although the BCL-2 family constitutes a crucial checkpoint in apoptosis, the intricate interplay between these family members remains elusive. Here, we demonstrate that BIM and PUMA, similar to ...truncated BID (tBID), directly activate BAX-BAK to release cytochrome c. Conversely, anti-apoptotic BCL-2-BCL-X(L)-MCL-1 sequesters these 'activator' BH3-only molecules into stable complexes, thus preventing the activation of BAX-BAK. Extensive mutagenesis of BAX-BAK indicates that their activity is not kept in check by BCL-2-BCL-X(L)-MCL-1. Anti-apoptotic BCL-2 members are differentially inactivated by the remaining 'inactivator' BH3-only molecules including BAD, NOXA, BMF, BIK/BLK and HRK/DP5. BAD displaces tBID, BIM or PUMA from BCL-2-BCL-X(L) to activate BAX-BAK, whereas NOXA specifically antagonizes MCL-1. Coexpression of BAD and NOXA killed wild-type but not Bax, Bak doubly deficient cells or Puma deficient cells with Bim knockdown, indicating that activator BH3-only molecules function downstream of inactivator BH3-only molecules to activate BAX-BAK. Our data establish a hierarchical regulation of mitochondrion-dependent apoptosis by various BCL-2 subfamilies.
Summary
Background
Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammation‐associated diseases. Clusterin levels in childhood asthma have ...not been evaluated.
Objectives
(1) To evaluate sputum clusterin levels in children with asthma compared to a control group. (2) To assess the relationships between sputum clusterin levels and airway inflammation, pulmonary function, and bronchial hyperresponsiveness.
Methods
This study included 170 children aged 5–18 years with stable asthma (n = 91), asthma exacerbation (n = 29), or no asthma (healthy controls; n = 50). Induced sputum, pulmonary function, and methacholine challenge tests were performed. Stable asthma was classified into two groups according to the severity. Clusterin levels in sputum were measured using an enzyme‐linked immunosorbent assay.
Results
Children with stable asthma had a higher clusterin level than healthy controls 4540 (3872–5651) pg/mL vs. 3857 (1054–4369) pg/mL, P < 0.001. The clusterin level was also more elevated in eosinophil‐dominant sputum than in non‐eosinophilic sputum in stable asthma 5094 (4243–6257) pg/mL vs. 4110 (1871–4839) pg/mL, P = 0.0017. Clusterin levels were associated with asthma severity. Paradoxically, clusterin levels were lower during asthma exacerbation than in stable asthma 1838 (350–4790 pg/mL vs. 4540 (3872–5651) pg/mL, P < 0.001. Clusterin levels were strongly correlated with the methacholine concentration that caused a 20% decrease in the forced expiratory volume in 1 s (r = −0.617, P < 0.001); there was no significant correlation between clusterin levels and other pulmonary function parameters.
Conclusions and Clinical Relevance
Clusterin levels were altered in children with stable asthma and asthma exacerbation because of its antioxidant and anti‐inflammatory effects. Clusterin may be a marker that reflects airway inflammation and severity of symptoms, and it can be used in the assessment and management of childhood asthma.
Summary
Oxidative stress is involved in the pathophysiology of rheumatoid arthritis (RA). We investigated the therapeutic potential of rebamipide, a gastroprotective agent with a property of reactive ...oxygen species scavenger, on the development of inflammatory polyarthritis and the pathophysiological mechanisms by which rebamipide might confer anti‐arthritic effects in SKG mice, an animal model of RA. Intraperitoneal (i.p.) injection of rebamipide attenuated the severity of clinical and histological arthritis. Rebampide treatment reduced the number of T helper type 1 (Th1), Th2, Th17, inducible T cell co‐stimulator (ICOS)+ follicular helper T (Tfh) transitional type (T2) and mature B cells in the spleen, but increased the number of regulatory T (Treg), CD19+ CD1dhigh CD5high, CD19+ CD25high forkhead box protein 3 (FoxP3)+ regulatory B (Breg) cells, memory B cells, and transitional type 1 (T1) B cells. In addition, flow cytometric analysis revealed significantly decreased populations of FAS+GL‐7+ germinal centre B cells and B220− CD138+ plasma cells in the spleens of rebamipide‐treated SKG mice compared to controls. Rebamipide decreased germinal centre B cells and reciprocally induced Breg cells in a dose‐dependent manner in vitro. Rebamipide‐induced Breg cells had more suppressive capacity in relation to T cell proliferation and also inhibited Th17 differentiation from murine CD4+ T cells. Together, these data show that i.p. administration of rebamipide suppresses arthritis severity by inducing Breg and Treg cells and suppressing Tfh and Th17 cells in a murine model of RA.
Summary
Sarcopenia means the progressive loss of skeletal muscle mass and strength with aging. In this study, we found that insulin resistance, chronic kidney disease stage 3, and osteoporosis at the ...femur neck were closely associated with sarcopenia in elderly men. These conditions modified to slow down the progression of sarcopenia.
Introduction
Sarcopenia is known to have multiple contributing factors; however, its modifiable risk factors have not yet been determined. The aim of this study was to identify the most influential and modifiable risk factors for sarcopenia in elderly.
Methods
This was a population-based, cross-sectional study using data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV), 2008–2009. This study included 940 men and 1,324 women aged 65 years and older who completed a body composition analysis using dual-energy X-ray absorptiometry. Sarcopenia was defined as an appendicular skeletal muscle mass divided by height
2
of less than 1 standard deviation below the sex-specific mean for a younger reference group.
Results
Using univariate analysis, age, body mass index (BMI), homeostasis model assessment for insulin resistance (HOMA-IR), limitations in daily activities, regular exercise, high-risk drinking, family income, osteoporosis, daily energy, and protein intake were associated with sarcopenia in men; age, BMI, limitations in daily activities, regular exercise, occupation, osteoporosis at the total hip, and daily energy intake were associated with sarcopenia in women. In the multivariate logistic regression analysis, HOMA-IR ≥2.5 (odds ratio OR for sarcopenia, 2.27; 95 % confidence interval CI, 1.21–4.25), chronic kidney disease stage 3 (OR, 3.13; 95 % CI, 1.14–8.61), and osteoporosis at the femur neck (OR, 6.83; 95 % CI, 1.08–43.41) were identified as risk factors for sarcopenia in men.
Conclusions
Insulin resistance, chronic kidney disease, and osteoporosis at the femur neck should be modified to prevent the acceleration of skeletal muscle loss in elderly men.
Lysophosphatidic acid (LPA), produced extracellularly by autotaxin (ATX), has diverse biological activities implicated in tumor initiation and progression, including increasing cell survival, ...angiogenesis, invasion and metastasis. ATX, LPA and the matrix metalloproteinase (MMP)-9 have all been implicated in hepatocellular carcinoma (HCC) invasion and metastasis. We, thus sought to determine whether ATX with subsequent LPA production and action, including induction of MMP-9 could provide a unifying mechanism. ATX transcripts and LPA receptor type 1 (LPA1) protein are elevated in HCC compared with normal tissues. Silencing or pharmacological inhibition of LPA1 significantly attenuated LPA-induced MMP-9 expression and HCC cell invasion. Further, reducing MMP-9 activity or expression significantly inhibits LPA-induced HCC cell invasion, demonstrating that MMP-9 is downstream of LPA1. Inhibition of phosphoinositide-3 kinase (PI3K) signaling or dominant-negative mutants of protein kinase Cδ and p38 mitogen-activated protein kinase (MAPK) abrogated LPA-induced MMP-9 expression and subsequent invasion. We thus demonstrate a mechanistic cascade of ATX-producing LPA with LPA activating LPA1 and inducing MMP-9 through coordinate activation of the PI3K and the p38 MPAK signaling cascades, providing novel biomarkers and potential therapeutic targets for HCC.
Many interesting materials phenomena such as the emergence of high-Tc superconductivity in the cuprates and colossal magnetoresistance in the manganites arise out of a doping-driven competition ...between energetically similar ground states. Doped multiferroics present a tantalizing evolution of this generic concept of phase competition. Here, we present the observation of an electronic conductor-insulator transition by control of band-filling in the model antiferromagnetic ferroelectric BiFeO3 through Ca doping. Application of electric field enables us to control and manipulate this electronic transition to the extent that a p-n junction can be created, erased and inverted in this material. A 'dome-like' feature in the doping dependence of the ferroelectric transition is observed around a Ca concentration of approximately 1/8, where a new pseudo-tetragonal phase appears and the electric modulation of conduction is optimized. Possible mechanisms for the observed effects are discussed on the basis of the interplay of ionic and electronic conduction. This observation opens the door to merging magnetoelectrics and magnetoelectronics at room temperature by combining electronic conduction with electric and magnetic degrees of freedom already present in the multiferroic BiFeO3.
•First stilbene glucoside-specific β-glucosidase from lactic acid bacterium.•Stilbene glucoside-specific enzyme showed various stilbene glucosides.•The enzyme showed the highest activity to methoxy ...stilbene, isorhaponticin.•The enzyme converted polydatin into resveratrol as 100% yield.•The enzyme was effectively used in production of bioactive compounds.
This study aimed to develop viable enzymes for bioconversion of resveratrol-glucoside into resveratrol. Out of 13 bacterial strains tested, Lactobacillus kimchi JB301 could completely convert polydatin into resveratrol. The purified enzyme had an optimum temperature of 30–40°C and optimum pH of pH 5.0 against polydatin. This enzyme showed high substrate specificities towards different substrates in the following order: isorhaponticin>>polydatin>>mulberroside A>oxyresveratrol-3-O-glucoside. Additionally, it rarely hydrolyzed astringin and desoxyrhaponticin. Based on these catalytic specificities, we suggest this enzyme be named stilbene glucoside-specific β-glucosidase. Furthermore, polydatin extracts from Polygonum cuspidatum were successfully converted to resveratrol with a high yield (of over 99%). Stilbene glucoside-specific β-glucosidase is the first enzyme isolated from lactic acid bacteria capable of bio-converting various stilbene glucosides into stilbene.
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