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Calcium (Ca2+) homeostasis is a crucial determinant of cellular function and survival. Endoplasmic reticulum (ER) acts as the largest intracellular Ca2+ store that maintains Ca2+ homeostasis through the ER Ca2+ uptake pump, sarco/ER Ca2+ ATPase, ER Ca2+ release channels, inositol 1,4,5-trisphosphate receptor channel, ryanodine receptor, and Ca2+-binding proteins inside of the ER lumen. Alterations in ER homeostasis trigger ER Ca2+ depletion and ER stress, which have been associated with the development of a variety of diseases. In addition, recent studies have highlighted the role of ER Ca2+ imbalance caused by dysfunction of sarco/ER Ca2+ ATPase, ryanodine receptor, and inositol 1,4,5-trisphosphate receptor channel in various kidney diseases. Despite progress in the understanding of the importance of these ER Ca2+ channels, pumps, and binding proteins in the pathogenesis of kidney disease, treatment is still lacking. This mini-review is focused on: i) Ca2+ homeostasis in the ER, ii) ER Ca2+ dyshomeostasis and apoptosis, and iii) altered ER Ca2+ homeostasis in kidney disease, including podocytopathy, diabetic nephropathy, albuminuria, autosomal dominant polycystic kidney disease, and ischemia/reperfusion-induced acute kidney injury.

Melanoma is the most threatening form of metastatic skin cancer that develops from melanocytes and causes a large majority of deaths due to poor therapeutic prognosis. It has significant limitations in treatment because it shows great resistance to chemotherapy, radiotherapy, and other therapeutic methods. A noninvasive and clinically accepted therapeutic modality, photodynamic therapy (PDT), is a promising treatment option, but it is limitedly applied for melanoma skin cancer treatment. This is because most of the photosensitizers are unlikely to be expected to have a remarkable effect on melanoma due to drug efflux by melanin pigmentation and intrinsic antioxidant defense mechanisms. Moreover, melanin is a dominant absorber in the spectral region of 500-600 nm that can cause the decreased photoreaction efficiency of photosensitizers. Herein, to overcome these drawbacks, we have developed a phenylthiourea-conjugated BODIPY photosensitizer (

Purpose: This study was conducted to evaluate the efficacy of a community-based follow-up program on parenting stress, parenting efficacy, and coping among parents with premature infants.Methods: A non-equivalent control group pre-post quasi-experimental design was used. This program consisted of structured home visits and self-help group meetings for 6 months. The experimental group (n=29) received visits by an experienced neonatal intensive care unit (NICU) nurse and the control group (n=27) was visited by a visiting nurse. Data were analyzed using the x2 test, t-test, and analysis of covariance.Results: Parents' coping behavior significantly differed in the experimental group compared to the control group (t=3.14, p=.003). In particular, coping subscale I, for maintaining the family situation (t=2.63, p=.011), and subscale III, for understanding the infant's medical situation (t=4.30, p

The inevitable challenge in conventional chemotherapy is to deliver the anticancer drugs to the dense population of tumors cells while minimizing the drug-associated side effects on the normal cells. Cancer cells' preference for glycolysis for energy production is well recognized. Intuitively, taking advantage of such cancer-associated metabolism would be a promising strategy for anticancer drug delivery with minimal side effects. In this investigation, we have designed a binary prodrug

Summary: Purpose: Mothers who give birth prematurely experience parenting stress after their babies are discharged and find it difficult to emotionally bond with them. Forming an emotional bond with a baby promotes the baby's growth and development, helps the mother cope with parenting stress after discharge, and is important for maintaining family functioning. This study aimed to identify the attachment experiences of mothers with low-birth-weight infants (LBWIs) in a follow-up program using early intervention. Methods: A phenomenological perspective was used for this qualitative research. Data were collected from in-depth interviews with twelve mothers who participated in a follow-up program using early intervention for mothers with LBWIs from September 2017 to December 2017. Colaizzi's method was used to analyze the data. Results: The experience of mothers' attachment was investigated on the basis of three categories: ‘beginning of changes in parenting methods,’ ‘forming an intimate mother–child bond,’ and ‘concerns and expectation about the child's development.’ Conclusion: The results indicate that the follow-up program using an early intervention designed to increase mothers' confidence in their parenting skills can promote mother’ attachment and the quality of life of families with LBWIs. Keywords: affect, early intervention, infant, low birth weight, qualitative research

Emerging evidence has established primary nephrotic syndrome (NS), including focal segmental glomerulosclerosis (FSGS), as a primary podocytopathy. Despite the underlying importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of NS, no treatment currently targets the podocyte ER. In our monogenic podocyte ER stress-induced NS/FSGS mouse model, the podocyte type 2 ryanodine receptor (RyR2)/calcium release channel on the ER was phosphorylated, resulting in ER calcium leak and cytosolic calcium elevation. The altered intracellular calcium homeostasis led to activation of calcium-dependent cytosolic protease calpain 2 and cleavage of its important downstream substrates, including the apoptotic molecule procaspase 12 and podocyte cytoskeletal protein talin 1. Importantly, a chemical compound, K201, can block RyR2-Ser2808 phosphorylation-mediated ER calcium depletion and podocyte injury in ER-stressed podocytes, as well as inhibit albuminuria in our NS model. In addition, we discovered that mesencephalic astrocyte-derived neurotrophic factor (MANF) can revert defective RyR2-induced ER calcium leak, a bioactivity for this ER stress-responsive protein. Thus, podocyte RyR2 remodeling contributes to ER stress-induced podocyte injury. K201 and MANF could be promising therapies for the treatment of podocyte ER stress-induced NS/FSGS.

The N-glycosylation of proteins is one of the most important post-translational modifications relevant to various biological functions. The identification and quantification of N-glycoproteins in liquid chromatography-mass spectrometry (LC-MS) is challenging because of their low analytical sensitivity and selectivity. This is due to their microheterogeneity and the difficulty of synthesizing N-glycopeptides as an internal standard. Parallel reaction monitoring (PRM) is widely used in targeted LC-MS. The key advantage of LC-PRM is that it can identify N-glycopeptides using tandem mass spectrometry (MS/MS) fragmentation, even without an internal standard. We investigated the feasibility of analyzing N-glycoproteins using multiplex immunoprecipitation to improve sensitivity and selectivity. We targeted N-glycoproteins [α-fetoprotein (AFP), vitronectin (VTN), and α-1-antichymotrypsin (AACT)] that are abnormally glycosylated in hepatocellular carcinoma (HCC). Their tryptic N-glycopeptides were selected to determine the percentages of fucosylated N-glycopeptides using Y ions, which include glycopeptide fragments with amino acid sequences. Finally, we confirmed that the area under the receiver operating characteristic curve (AUC = 0.944) for the combination of AFP and VTN increased more so than for a single glycopeptide (AUC = 0.889 for AFP and 0.792 for VTN) with respect to discriminating between HCC and cirrhosis serum. This study shows that an LC-PRM method using multiplex N-glycoproteins immunoprecipitated from serum could be applied to develop and verify cancer biomarkers. Graphical abstract.

In past few years, cancer specific targeted drug formulations have shown some hope of improving the therapeutics with minimized associated side effects of chemotherapy. However, the benefits has proven modest due to lack of systems that can be assessed easily from parent drugs while maintaining the same features of cancer associated prodrug activation. We developed a small molecule-based, carboxylesterase responsive theranostic, EDOX, with tumor-specific enzymatic activation for targeted delivery of the anticancer drug, Doxorubicin (Dox), to hepatocellular carcinoma (HCC) cells. Easy synthetic access, physiological stability, tumor-selective activation, and sustained drug release make EDOX an excellent candidate for use as a next-generation drug delivery system for HCC.

Simple Summary Non-small-cell lung carcinoma (NSCLC) covers for almost 85% of all lung cancers and a major contributor to the overall cancer death rate. Erlotinib is used to treat NSCLC via inhibition of epithelial growth factor receptor (EGFR) kinase activity. Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. We performed DARTS LC-MS/MS with SWATH of DIA analysis and identified a novel binding protein of Erlotinib that may underlie NSCLC resistance. Our study indicated that Erlotinib binds POLA2 in addition to EGFR. This was confirmed by DARTS and CETSA results. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC. Abstract Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas the overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.

Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy, verified by bio-statistical analysis (Pearson correlation coefficient, R=0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.

The advent of next-generation sequencing (NGS) in recent years has led to a rapid discovery of novel or rare genetic variants in human kidney cell genes, which is transforming the risk assessment, diagnosis, and treatment of kidney disease. Mutations may lead to protein misfolding, disruption of protein trafficking, and endoplasmic reticulum (ER) retention. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and unfolded protein response. Mutations in nephrin (NPHS1), podocin (NPHS2), laminin β2 (LAMB2), and α-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV α chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease. Meanwhile, ER resident protein SEC63 may modify disease severity in autosomal dominant polycystic kidney disease. These findings underscore the importance of ER stress in the pathogenesis of monogenic kidney disease. Recently, we have identified mesencephalic astrocyte-derived neurotrophic factor (MANF) and cysteine-rich with EGF-like domains 2 (CRELD2) as urinary ER stress biomarkers in ER stress-mediated kidney diseases.

Insulin signaling is essential for regulating glucose homeostasis. Numerous studies have demonstrated that reactive oxygen species (ROS) affect insulin signaling, and low ROS levels can act as a signal to regulate cellular function. Peroxiredoxins (Prxs) are highly abundant and widely expressed antioxidant enzymes. However, it is unclear whether antioxidant enzymes, such as Prx2, mediate insulin signaling. The aim of our study was to investigate the influence of Prx2 deficiency on insulin signaling. Our western blot results showed that Prx2 deficiency enhanced insulin signaling and increased oxidation of protein tyrosine phosphatase 1B (PTP1B) and phosphatase and tensin homologue (PTEN) in mouse embryonic fibroblasts (MEFs) treated with insulin. In addition, we assessed ROS levels with a Cytosol-HyPer H2O2 sensor. As a result, increased ROS levels and Akt activation were decreased by N-acetyl-cysteine (Nac), which acted as an antioxidant in Prx2-deficient MEFs. Body weight measurements and glucose tolerance test (GTT) revealed significant body weight reduction and increase in glucose clearance in Prx2-/- mice fed a high-fat diet. Interestingly, glucose transporter type 4 (GLUT4) was significantly higher in Prx2-/- mice than in wild-type mice according to western blotting results. Western blotting also revealed that Akt phosphorylation was higher in Prx2-/- MEFs and muscle tissue than in wild-type. Together, our findings indicate that increased ROS due to Prx2 deficiency promotes insulin sensitivity and glucose clearance in skeletal muscles by increasing protein tyrosine phosphatase (PTPs) oxidation. These results provide novel insights into the fundamental mechanisms of insulin signaling induced by Prx2 deficiency and suggest that ROS-based therapeutic strategies can be used to suppress insulin resistance.

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages. The cytoprotective mechanisms of MANF on ER stress are currently under active investigation. In addition, for the first time, we have discovered that MANF can potentially serve as a urinary ER stress biomarker in ER stress-mediated kidney disease. These studies have underscored the diagnostic and therapeutic importance of MANF in ER diseases.

Flag leaves (FL) and second leaves (SL) in rice show differential aging patterns during monocarpic senescence. Coordination of aging programs between FL and SL is important for grain yield and quality. However, the molecular bases for differential aging programs between FL and SL have not been systematically explored in rice. Here, we performed mRNA-sequencing of FL and SL at six time points during grain-filling and identified four molecular bases for differential aging programs between FL and SL: phenylpropanoid biosynthesis, photosynthesis, amino acid (AA) transport, and hormone response. Of them, photosynthesis (carbon assimilation) and AA transport (nitrogen remobilization) predominantly occurred in FL and SL, respectively, during grain-filling. Unlike other molecular bases, AA transport showed consistent differential expression patterns between FL and SL in independent samples. Moreover, long-distance AA transporters showed invariant differential expression patterns between FL and SL after panicle removal, which was consistent to invariant differential nitrogen contents between FL and SL after panicle removal. Therefore, our results suggest that the supplies of carbon and nitrogen to seeds is functionally segregated between FL and SL and that long-distance AA transport is an invariant core program for high nitrogen remobilization in SL.

Luteal regression is a natural and necessary event to regulate the reproductive process in all mammals. Prostaglandin F2α (PGF2α) is the main factor that causes functional and structural regression of the corpus luteum (CL). It is well known that PGF2α-mediated ROS generation is closely involved in luteal regression. Peroxiredoxin 2 (Prx2) as an antioxidant enzyme plays a protective role against oxidative stress-induced cell death. However, the effect of Prx2 on PGF2α-induced luteal regression has not been reported. Here, we investigated the role of Prx2 in functional and structural CL regression induced by PGF2α-mediated ROS using Prx2-deficient (-/-) mice. We found that PGF2α-induced ROS generation was significantly higher in Prx2-/- MEF cells compared with that in wild-type (WT) cells, which induced apoptosis by activating JNK-mediated apoptotic signaling pathway. Also, PGF2α treatment in the CL derived from Prx2-/- mice promoted the reduction of steroidogenic enzyme expression and the activation of JNK and caspase3. Compared to WT mice, serum progesterone levels and luteal expression of steroidogenic enzymes decreased more rapidly whereas JNK and caspase3 activations were significantly increased in Prx2-/- mice injected with PGF2α. However, the impaired steroidogenesis and PGF2α-induced JNK-dependent apoptosis were rescued by the addition of the antioxidant N-acetyl-L-cysteine (NAC). This is the first study to demonstrate that Prx2 deficiency ultimately accelerated the PGF2α-induced luteal regression through activation of the ROS-dependent JNK pathway. These findings suggest that Prx2 plays a crucial role in preventing accelerated luteal regression via inhibition of the ROS/JNK pathway.

Decreased swallowing function is a common and main cause of malnutrition and aspiration pneumonia in patients with Parkinson's disease. The aims of this systematic review were to summarize and qualitatively analyze the studies that have been published on behavioral therapies for improving swallowing functions in patients with Parkinson's disease. Studies published from January 2000 to December 2015 were identified via electronic database searches using Ovid-MEDLINE, Ovid-EMBASE, the Cochrane Library, and 8 Korean databases. Two reviewers independently evaluated the studies using inclusion criteria. Nine studies were included, of which 6 evaluated rehabilitation technique studies and 3 evaluated compensatory strategies. The 9 studies were evaluated qualitatively using a methodology checklist of the Scottish Intercollegiate Guideline Network, according to which all of the studies had acceptable quality. The available data on the effects of rehabilitation techniques and compensatory strategies remain insufficient. Further randomized controlled studies should be done to investigate the effect of behavioral therapy on improving swallowing functions in patients with Parkinson's disease.

XBP1 (X-box-binding protein 1) is activated in cancer and has a pivotal role in tumorigenesis and progression of human cancer. In particular, the XBP1 transcriptional regulatory network is well known to drive cancer development, but little is known about whether the stability of XBP1 is regulated and, if so, what controls the stability of XBP1. In the present study we show that PIN1 prolyl isomerase interacts with the active form of XBP1 (XBP1s) in a phosphorylation-dependent manner and promotes XBP1s-induced cell proliferation and transformation through the regulation of XBP1 stability. By contrast, depletion of Pin1 in cancer cells reduced XBP1s expression, which subsequently inhibits cell proliferation and transformation. Interestingly, XBP1s activates multiple oncogenic pathways including NF-κB (nuclear factor κB), AP1 (activator protein 1) and Myc, and down-regulates PIN1 transcription via a negative-feedback mechanism through p53 induction. Ultimately, reciprocal regulation of Pin1 and XBP1s is associated with the activation of oncogenic pathways, and the relationship of PIN1 and XBP1 may be an attractive target for novel therapy in cancers.

Fucosylation of N-glycoproteins has been implicated in various diseases, such as hepatocellular carcinoma (HCC). However, few studies have performed site-specific analysis of fucosylation in liver-secreted proteins. In this study, we characterized the fucosylation patterns of liver-secreted proteins in HCC plasma using a workflow to identify site-specific N-glycoproteins, where characteristic B- and/or Y-ion series with and without fucose in collision-induced dissociation were used in tandem mass spectrometry. In total, 71 fucosylated N-glycopeptides from 13 major liver-secreted proteins in human plasma were globally identified by LC-MS/MS. Additionally, 37 fucosylated N-glycopeptides were newly identified from nine liver-secreted proteins, including alpha-1-antichymotrypsin, alpha-1-antitrypsin, alpha-2-HS-glycoprotein, ceruloplasmin, alpha-1-acid glycoprotein 1/2, alpha-2-macroglobulin, serotransferrin, and beta-2-glycoprotein 1. Of the fucosylated N-glycopeptides, bi- and tri-antennary glycoforms were the most common ones identified in liver-secreted proteins from HCC plasma. Therefore, we suggest that this analytical method is effective for characterizing fucosylation in liver-secreted proteins. Graphical abstract A global map of fucosylated and non-fucosylated glycopeptides from 13 liver-secreted glycoproteins in hepatocellular carcinoma plasma.

Isoliquritigenin (ISL) is an abundant dietary flavonoid with a chalcone structure, which is an important constituent in Glycyrrhizae Radix (GR). ISL exhibits anti-oxidant activity, and this activity has been shown to play a beneficial role in various health conditions. However, it is unclear whether the anti-oxidant activity of ISL affects insulin signaling pathway and lipid accumulation of adipocytes. We sought to investigate the effects and molecular mechanisms of ISL on insulin-stimulated adipogenesis in 3T3-L1 cells. We investigated whether ISL attenuates insulin-induced Reactive Oxygen Species (ROS) generation, and whether ISL inhibits the lipid accumulation and the expression of adipogenic-genes during the differentiation of 3T3-L1 cells. ISL blocked the ROS generation, suppressed the lipid accumulation and the expression of adipocyte-specific proteins, which are increased in response to insulin stimulation during adipocyte differentiation of 3T3-L1 cells. We also investigated whether the anti-oxidant capacity of ISL is involved in regulating the molecular events of insulin-signaling cascade in 3T3-L1 adipocytes. ISL restores PTP1B activity by inhibiting PTP1B oxidation and IR/PI3K/AKT phosphorylation during the early stages of insulin-induced adipogenesis. Our findings show that the anti-oxidant capacity of ISL attenuated insulin IR/PI3K/AKT signaling through inhibition of PTP1B oxidation, and ultimately attenuated insulin-induced adipocyte differentiation of 3T3-L1 cells.

Aims Leydig cells are characterized by their ability to produce testosterone. When the Leydig cells are unable to produce enough testosterone, spermatogenesis fails completely. Considering this, it is of great interest to investigate whether the expressions of steroidogenic enzymes are affected by testicular heat stress. This study aimed to demonstrate that heat induced ER-stress significantly influences steroidogenic enzyme expression and testosterone production in the Leydig cells. Main methods C57BL/6 mice were subjected to repetitive testicular heat-treatment at 42 °C for 15 min per day, and heat-treated mLTC-1 cells following hCG treatment for 1 h. The protein and RNA expressions were measured by Western blot, RT-PCR. The testosterone and progesterone levels were detected by EIA. The histological and pathological characteristics using hematoxylin and eosin (H&E) and antibody stains. Key findings The 3β-HSD expression was decreased by heat-stress and hCG treatment. While the GRP78/BiP and CHOP levels were increased by ER-stress inducers, those of the steroidogenic enzyme and progesterone were decreased. In contrast, an ER-stress inhibitor rescued the testosterone levels, even under heat-stress conditions. Moreover, the Leydig cells were randomly scattered, and severely damaged upon repetitive testicular heat-treatment. Additionally, immunohistochemical analyses revealed that cleaved caspase-3 was elevated in the testicular Leydig cells, and rescued by TUDCA. Thus, repetitive testicular heat-treatment in mice promotes excessive ER-stress, thereby leading to apoptosis of the Leydig cells and thus, decreased testosterone production. Significance Our findings help to provide an ER-stress mediate mechanistic explanation to the impairment of spermatogenesis upon elevation of the testicular temperature.

The effects of liquid ammonia (L/A) treatment on the mechanical properties and hand of 100 % hemp woven fabrics were investigated by the KES-FB (Kawabata Evaluation System for Fabric). Tensile energy and tensile resilience were increased by the L/A treatment. Bending and shearing values such as bending rigidity, bending moment, shear stiffness, shear hysteresis of the L/A treated fabrics were lower than those of the untreated ones. Compressional linearity and compressional energy were decreased while the compressional resilience was increased by the L/A treatment. From the hand evaluation, the primary hand values as well as total hand value of the hemp fabric were markedly increased by the L/A treatment, especially when yarn number was fine. Therefore, L/A treatment was found to be an effective method of improving the flexibility and softness of hemp woven fabrics.

Many therapeutic enzymes for lysosomal storage diseases require a high content of mannose-6-phosphate (M6P) glycan, which is important for cellular uptake and lysosomal targeting. We constructed glyco-engineered yeast harboring a high content of mannosylphosphorylated glycans, which can be converted to M6P glycans by uncapping of the outer mannose residue. In this study, the cell wall of this yeast was employed as a natural M6P glycan source for conjugation to therapeutic enzymes. The extracted cell wall mannoproteins were digested by pronase to generate short glycopeptides, which were further elaborated by uncapping and α(1,2)-mannosidase digestion steps. The resulting glycopeptides containing M6P glycans (M6PgPs) showed proper cellular uptake and lysosome targeting. The purified M6PgPs were successfully conjugated to a recombinant acid α-glucosidase (rGAA), used for the treatment of Pompe disease, by two-step reactions using two hetero-bifunctional crosslinkers. First, rGAA and M6PgPs were modified with crosslinkers containing azide and dibenzocyclooctyne, respectively. In the second reaction using copper-free click chemistry, the azide-functionalized rGAA was conjugated with dibenzocyclooctyne-functionalized M6PgPs without the loss of enzyme activity. The M6PgP-conjugated rGAA had a 16-fold higher content of M6P glycan than rGAA, which resulted in greatly increased cellular uptake and efficient digestion of glycogen accumulated in Pompe disease patient fibroblasts.

PURPOSE Alpha-fetoprotein (AFP) is a widely used serological marker that is associated with hepatocellular carcinoma (HCC). Although the level of AFP is increased in HCC, its sensitivity for diagnosis is poor because AFP levels are also increased in liver diseases. Changes in glycoform, especially fucosylation, have been reported to be associated with the development of HCC. EXPERIMENTAL DESIGN The authors introduce the monitoring of fucosylated glycopeptides by liquid chromatography (LC)-mass spectrometry (MS) combined with immunoprecipitation, where glycan-cleaved fragments with an amino acid sequence are used as transitions. Furthermore, neuraminidase for desialylation is useful to improve the MS detection limit (limit of detection [LOD]

Reactive oxygen species (ROS) produced in biological reactions have been shown to contribute to ovarian aging. Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that protects cells by scavenging ROS; however, its effect on age-related, oxidative stress-associated ovarian failure has not been reported. Here, we investigated its role in age-related ovarian dysfunction and 4-vinylcyclohexene diepoxide (VCD)-induced premature ovarian failure using Prx2-deficient mice. Compared to those in wildtype (WT) mice, serum levels of anti-Mullerian hormone, 17β-estradiol, and progesterone and numbers of follicles and corpora lutea were significantly lower in 18-month-old Prx2-/- mice. Moreover, levels of Bax, cytochrome c, cleaved caspase-3, and phosphorylated JNK proteins were higher and numbers of apoptotic (terminal deoxynucleotidyl transferase dUTP nick end labeling-positive) cells were considerably greater in 18-month-old Prx2-/- ovaries than WT ovaries. Furthermore, the effects of the ovarian toxicant VCD in significantly enhancing ROS levels and apoptosis through activation of JNK-mediated apoptotic signaling were more pronounced in Prx2-/- than WT mouse embryonic fibroblasts. Expression of the steroidogenic proteins StAR, CYP11A1, and 3β-HSD and serum levels of 17β-estradiol and progesterone were also reduced to a greater extent in Prx2-/- mice than WT mice after VCD injection. This reduced steroidogenesis was rescued by addition of the Prx mimic ebselen or JNK inhibitor SP600125. This constitutes the first report that Prx2 deficiency leads to acceleration of age-related or VCD-induced ovarian failure by activation of the ROS-induced JNK pathway. These findings suggest that Prx2 plays an important role in preventing accelerated ovarian failure by inhibiting ROS-induced JNK activation.

Previous studies have reported that exposure to lead and cadmium can damage the inner ear receptor, which perceives high-frequency sounds. However, few studies have used the pure-tone average (PTA), including high-frequency ranges, for the estimation of hearing loss caused by lead and cadmium exposure. We estimated hearing loss using the PTA test, in low-frequency, speech frequency, and high-frequency ranges and compared the differences in the results using 3 PTA calculation methods. We analyzed the data of 2,387 participants, between the ages of 19 and 85 years, that were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) of 2010–2012. A dose-response relationship between hearing loss and heavy metal exposure was observed in the high-frequency method after adjustment for confounding factors. When using the high-frequency PTA, it was found that doubling of the levels of lead and cadmium in the blood was associated with a 1.88- (95% CI 1.11–3.17) and 1.89-fold (95% CI 1.02–3.50) increase in the OR for hearing loss. In the case of the low-frequency and speech frequency PTA, however, there were no significant relationships between hearing loss and the concentrations of lead and cadmium in the blood. The outcomes of the present study suggest that the estimation of hearing loss caused by environmental exposure to lead and cadmium is affected by the frequencies used in the PTA calculation.

Elevated levels of reactive oxygen species (ROS) are a hallmark of obesity. Peroxiredoxin 5 (Prx5), which is a cysteine-dependent peroxidase enzyme, has an intensive ROS scavenging activity because it is located in the cytosol and mitochondria. Therefore, we focused on the role of Prx5 in regulating mitochondrial ROS and adipogenesis. We demonstrated that Prx5 expression was upregulated during adipogenesis and Prx5 overexpression suppressed adipogenesis by regulating cytosolic and mitochondrial ROS generation. Silencing Prx5 promoted preadipocytes to differentiate into adipocytes accumulating lipids by activating adipogenic protein expression. Prx5-deletion mice fed on a high-fat diet (HFD) exhibited significant increase in body weight, enormous fat pads, and adipocyte hypertrophy in comparison to wild type mice. Prx5 deletion also remarkably induced adipogenesis-related gene expression in white adipose tissue. These phenotypic changes in Prx5-deletion mice were accompanied with lipid metabolic disorders, such as excessive lipid accumulation in the liver, severe hepatic steatosis, and high levels of triglyceride in the serum. These results demonstrated that Prx5 deletion increased the susceptibility to HFD-induced obesity and several of its associated metabolic disorders. In conclusion, we suggest that Prx5 inhibits adipogenesis by modulating ROS generation and adipogenic gene expression, implying that Prx5 may serve as a potential strategy to prevent and treat obesity.

Although statin is one of the most widely used drugs worldwide, the association between statin use and hepatocellular carcinoma (HCC) risk remains controversial. This study aims to investigate the association between statin use and risk of HCC in a large scale population-based prospective cohort. We selected participants aged >40 years in 2002 whose health examination data were available from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. We collected statin exposure data and medical information of the population in the database over 5 years (2002–2006), and followed up eligible participants for HCC development over the next 7 years (2007–2013). We used Cox proportional hazard regression models to calculate the hazard ratios of statin use and HCC risk, after adjusting for sex, age, incoming status, disability, body mass index, smoking status, alcohol consumption, physical activity, comorbidity, underlying liver disease, and medication use. Overall, 443,239 participants were included in the analysis, including 3,147 cases of HCC during the observation period. The adjusted hazard ratio for HCC in statin users was 0.66 (95% confidence interval [CI], 0.56–0.77), indicating a 34% risk reduction in a dose-response manner (P for trend < 0.001). Sensitivity analysis showed a reduced risk of HCC in statin users in all subgroups, in terms of age and sex, as well as a stronger risk reduction in patients with underlying liver disease. In conclusion, statin use is associated with a reduced risk of HCC in a dose-response manner.

ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations, a prototypical tubular ER stress disease. In addition, in pediatric patients undergoing cardiac surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly associate with severe AKI after surgery. In conclusion, our study has identified CRELD2 as a potentially novel urinary ER stress biomarker with potential utility in early diagnosis, risk stratification, treatment response monitoring, and directing of ER-targeted therapies in selected patient subgroups in the emerging era of precision nephrology.

Department of Reproductive Medicine, University of California, San Diego, 9500 Gilman Drives, La Jolla, California 92093, USAReceived July 17, 2014/Revised August 11, 2014/Accepted August 11, 2014This study analyzed whether human chorionic gonadotropin (hCG) induces ER stress via the IRE/XBP1 pathway in mouse Leydig tumor (mLTC-1) cells. In a previous study, we demonstrated that the unfolding protein response (UPR) plays an important role in the expression of steroidogenic enzymes by modulating the ATF6 pathway, as well as ER stress-mediated apoptosis in hCG-stimu-lated Leydig cells. Although UPR signaling has been reported to regulate the IRE1/XBP1 pathway, it is not known whether hCG-induced ER stress in Leydig cells can activate the pathway. To inves-tigate the activation of the IRE1/XBP1 pathway in mLTC-1 cells after hCG treatment, we performed a Western blot analysis to detect the phospho-IRE1 protein and an RT-PCR analysis to validate splic-ing of XBP1 mRNA. We used ER stress-activated indicator (ERAI) constructs for monitoring the activ-ity of IRE1 and then analyzed by fluorescence microscopy and flow cytometry. The expression levels of the phospho-IRE1 protein markedly increased in response to the hCG treatment. In the mLTC-1 cells transfected with an F-XBP1-venus/F-XBP1△DBD-venus construct, the hCG treatment led to the appearance of green fluorescent cells and detectable fluorescence in the nucleus and cytosol, respectively. In addition, splicing of XBP1 mRNA significantly increased after the hCG treatment. Taken together, these results indicate that hCG-induced ER stress leads to activation of the IRE1/XBP pathway in Leydig cells. Keywords

Aims We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. Main methods The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Key findings Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. Significance These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span.

The purpose of this study was to investigate the effects of prenatal Qi exercise on mother–infant interaction and the behavioral state of the infant. A prospective, quasi-experimental design was used in 70 healthy pregnant women of more than 18 weeks of gestation. Pregnant women in the intervention group received 90 minutes of prenatal Qi exercise twice a week for 12 weeks. Prenatal Qi exercise group’s Nursing Child Assessment of Feeding Scale scores was higher in mother’s sensitivity to cues, responses to distress, socioemotional growth fostering, and cognitive fostering and for children in responsiveness. There was no significant difference in Anderson Behavioral State Scoring System scores between groups. The results suggested that prenatal Qi exercise is a valuable approach to positively influence mother–infant interaction postdelivery.

The corpus luteum (CL) is a transient endocrine organ. Development, maintenance, and regression of CL are effectively controlled by dynamic changes in gene expression. However, it is unknown what types of gene are affected during the CL life span of the estrous cycle in bovine. Here, we determined whether unfolded protein response (UPR) signaling via eIF2α/ATF4/GADD34, p90ATF6/p50ATF6, and IRE1/XBP1, which is a cellular stress response associated with the endoplasmic reticulum (ER), is involved in the bovine CL life span. Our results indicated that expression of Grp78/Bip, the master UPR regulator, was increased during the maintenance stage and rapidly decreased at the regression stage. Additionally, UPR signaling pathways genes were found to be involved in luteal phase progression during the estrous cycle. Our findings suggested that Grp78/Bip, ATF6, and XBP1 act as ER chaperones for initiating CL development and maintaining the CL. In addition, we investigated whether ER stress-mediated apoptosis is occurred through three UPR signaling pathways in CL regression stage. Interestingly, pIRE1 and CHOP were found to be involved in both the adaptive response and ER stress-mediated apoptosis. During the CL regression stage, increased expression of pJNK and CHOP, two components of ER stress-mediated apoptotic cascades, occurred before increased level of cleaved caspase 3 were observed. The present investigation was performed to identify a functional link between UPR signaling and CL life span during the bovine estrous cycle. Taken together, results from this study demonstrated that UPR protein/gene expression levels were different at various stages of the bovine CL life span. Variations in the expression of these protein/genes may play important roles in luteal stage progression during the estrous cycle.

Department of Herbal Pharmaceutical Science, Joongbu University, Geumsan 312-702, Korea.ABSTRACTS : The purpose of this study was to examined the antioxidant activities by water and 70% ethanol extractfrom durian (Durio zibethinus.) seed, sarcocarp and peel. Durian extract were studied for reducing sugar content, polyphe-nol content, superoxide dismutase (SOD) like activity, electron donating ability, nitrite scavenging ability, flavonoid content,hydroxy radical scavenging activity. Reducing sugar content were increased peel > sarcocarp > seed. Total polyphenol, fla-vonoid content, DPPH radical scavenging ability and SOD like activity were increased seed > peel > sarcocarp. Totalpolyphenol content was relatively high as 21.90 ± 0.50 mg/g in the ethanol extract of the seed. DPPH radical scavenging abil-ity was relatively high as 62.08 ± 2.63% in the water extract of the seed. Nitrite scavenging ability was no significant differ-ence. Hydroxy radical scavenging activity was increased seed > peel > sarcocarp, was relatively high as 58.27 ± 1.13% inthe water extract of the seed.Key Words : Durian, Durio zibethinus, Antioxidative Activity, Seed, Sarcocarp, Peel

Over-activation of microglia cells in the brain contributes to neurodegenerative processes promoted by the production of various neurotoxic factors including pro-inflammatory cytokines and nitric oxide. Recently, accumulating evidence has suggested that mitochondrial dynamics are an important constituent of cellular quality control and function. However, the role of mitochondrial dynamics in microglial activation is still largely unknown. In this study, we determined whether mitochondrial dynamics are associated with the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated immortalization of murine microglial cells (BV-2) by a v-raf/v-myc carrying retrovirus (J2). Excessive mitochondrial fission was observed in lentivirus-transfected BV-2 cells stably expressing DsRed2-mito following LPS stimulation. Furthermore, mitochondrial localization of dynamin-related protein 1 (Drp1) (a key regulator of mitochondrial fission) was increased and accompanied by de-phosphorylation of Ser637 in Drp1. Interestingly, inhibition of LPS-induced mitochondrial fission and reactive oxygen species (ROS) generation by Mdivi-1 and Drp1 knock-down attenuated the production of pro-inflammatory mediators via reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. Our results demonstrated for the first time that mitochondrial fission regulates mitochondrial ROS production in activated microglial cells and influences the expression of pro-inflammatory mediators through the activation of NF-κB and MAPK. We therefore suggest that mitochondrial dynamics may be essential for understanding pro-inflammatory mediator expression in activated microglial cells. This could represent a new therapeutic approach for preventing neurodegenerative diseases.

Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in leptin signaling result in obesity and diabetes. The ATP-sensitive potassium (K ATP ) channels couple glucose metabolism to insulin secretion in pancreatic β-cells. In this study, we provide evidence that leptin modulates pancreatic β-cell functions by promoting K ATP channel translocation to the plasma membrane via AMP-activated protein kinase (AMPK) signaling. K ATP channels were localized mostly to intracellular compartments of pancreatic β-cells in the fed state and translocated to the plasma membrane in the fasted state. This process was defective in leptin-deficient ob /ob mice, but restored by leptin treatment. We discovered that the molecular mechanism of leptin-induced AMPK activation involves canonical transient receptor potential 4 and calcium/calmodulin-dependent protein kinase kinase β. AMPK activation was dependent on both leptin and glucose concentrations, so at optimal concentrations of leptin, AMPK was activated sufficiently to induce K ATP channel trafficking and hyperpolarization of pancreatic β-cells in a physiological range of fasting glucose levels. There was a close correlation between phospho-AMPK levels and β-cell membrane potentials, suggesting that AMPK-dependent K ATP channel trafficking is a key mechanism for regulating β-cell membrane potentials. Our results present a signaling pathway whereby leptin regulates glucose homeostasis by modulating β-cell excitability.

Sargassum serratifolium was found to contain high concentrations of meroterpenoids, having strong antioxidant, anti-inflammatory, and neuroprotective activities. This study aims to investigate the anti-inflammatory mechanisms of an ethanolic extract of S. serratifolium (ESS) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells and to identify the anti-inflammatory components in ESS. The level of proinflammatory cytokines was measured by enzyme-linked immunosorbent assay. The expression of inflammation-related proteins and mRNA was evaluated by Western blot and reverse transcription-polymerase chain reaction analysis, respectively. Anti-inflammatory activities of isolated components from ESS were analyzed in LPS-stimulated BV2 cells. ESS inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 and the expression of inducible NO synthase and cyclooxygenase-2. ESS also decreased the release of proinflammatory cytokines in a dose-dependent manner. LPS-induced nuclear factor-kappa B (κB)...

Purpose The purpose was to examine gender differences between parental problem drinking (PPD) and early adolescents' Internet addiction (IA). Design and Methods This was a cross-sectional, correlational design with 519 (266 boys and 253 girls) early adolescents. Results PPD had a significant direct effect on IA in boys but not in girls. Significant indirect effects of PPD on IA were evidenced via anxiety-depression and aggression for boys and via family function and aggression for girls. Practice Implications Findings suggest that tailored interventions for the prevention of IA should consider gender.

Backgrounds: Juxtacortical spots on fluid-attenuated inversion recovery (FLAIR) images can be frequently detected in patients with migraine. However, the origins of the cerebral lesions (including juxtacortical spots on FLAIR images) found in the previous studies are not known. We sought to investigate the association between juxtacortical spots on FLAIR images and right-to-left shunt (RLS) in migraine patients. Methods: Juxtacortical spots on FLAIR images were arbitrarily defined as small areas of hyperintensities in the juxtacortex and cortico-subcortical junction. The presence of RLS was examined by a transcranial Dopper (TCD) with the agitated saline test. The degree of RLS was categorized into four grades according to the number of microemboli: no shunt, 10 MB single spots pattern, and >10 MB shower/curtain pattern. We compared the results for migraine patients (n = 49) with those for healthy controls (n = 49). Results: Juxtacortical spots on FLAIR images occurred in 38/98 subjects; of them, 27/49 (55.1%) had migraines and 11/49 (22.2%) were healthy controls (P = 0.002). The independent factors associated with juxtacortical spots on FLAIR images were female, migraine patients, and RLS by multivariate analysis. In migraine patients, RLS was independently associated with juxtacortical spots on FLAIR images. Conclusion: Our results suggest that juxtacortical spots on FLAIR images were frequently found in migraine patients and might be associated with the presence of RLS in those patients. Further studies are needed to assess whether juxtacortical spots have clinical implications in patients with migraine.

For demands of optical systems in a off-axis three-mirror camera on the optical-mechanical structure,an appropriate optical-mechanical structure was designed by taking Carbon Fiber Composite(CFC) as the key components of the camera.The weight of CFC in designed camera makes up 32% that of the total system.Furthermore,this optical-mechanical structure is asymmetric,the system spacing in the primary,secondary mirror is 850 mm,and the mirror positioning accuracy demands its interval,eccentric and tilt to be 0.005 mm,0.005 mm,and 5″,respectively.The Finite Element method was used to analyze and optimize the design,results show that the optical-mechanical structure has better stiffness,lighter weight,and can meet the requirements of optical system for intervals,eccentrics and tilts.A mechanics environmental test and a thermal vacuum test were performed,and results demonstrate that the optical-mechanical structure in the camera has excellent stability in mechanics,thermal and other environmental conditions,its first order harmonic frequencies are above 120 Hz,and the modulation transfer function is more than 0.2.These results prove that the proposed structure can provide reasonable spatial location and stability for the reflective mirrors in off-axis three-mirror cameras.

Background: Meridian Massage is a traditional practice that manually stimulates the body's meridian system – the same network of vital energy channels used in acupuncture. The present study was to assess the effect of Meridian Massage on physical growth and infants' health as perceived by mothers. Methods: A study was conducted in a community health center in Korea. A total of 169 healthy infant–mother dyads were assigned to the Meridian Massage group (n= 89) or the gentle touch massage group (n= 80), based on the mother's preference. All massages were conducted by the mothers for 15 min per session, one time daily over a course of 6 weeks. In each group, the infant's weights, heights, and the number of days with illness as perceived by mothers and related clinic visits were measured. Results: Significant differences were observed in weight and height after 6 weeks between the Meridian group and the gentle touch massage group (P < 0.001). Infants in the Meridian Massage group showed a significantly different number of days with perceived clinic visits compared to those in the control group (P < 0.001). Conclusions: Meridian Massage may facilitate physical growth and improve infants' health outcome as perceived by mothers. A randomized controlled trial is required to further explore the effects of Meridian Massage in early infancy.

Background: Although photodynamic therapy (PDT) using intralesional injection (ILI) can theoretically enhance the efficacy of the PDT, the effect of ILI-PDT on warts has not been reported in the literature so far. Methods: Eight patients with multiple viral warts were enrolled in the study. PDT was performed after the incubation for 1 h, followed by the ILI of aminolevulinic acid (ALA) into the warts. The treatment was repeated at 2–3 week intervals. Results: Fifty percent of patients showed good to cure response. Complete remission was observed in two patients. There was no apparent correlation between the initial severity of warts and the likelihood of response. No one reported severe adverse reaction. Conclusions: The present study suggests that intralesional administration of ALA might be a safe and effective treatment option of thick treatment-resistant warts and can be performed with a shorter incubation period.

BACKGROUND: Movement of the cerebrospinal fluid (CSF) is one of the most important factors in determining the intrathecal spread of isobaric spinal anesthetics. Preanesthetic administration of either crystalloid or colloid immediately before spinal anesthesia (preload) may result in different CSF pulsatile movement because of their different physical properties. We examined whether preload of crystalloid versus colloid may have different effects on the intrathecal spread of isobaric spinal anesthetics as a result of their different CSF dynamics regarding its pulsatile movement. METHODS: In a clinical study of isobaric spinal anesthesia, patients were allocated into 1 of 2 groups according to preload with either crystalloid (n = 30) or colloid (n = 30) before spinal anesthesia with 0.5% isobaric tetracaine. The pulsatile movements of CSF at the L2-3 intervertebral space and midportion of the aqueduct of Sylvius were also examined by magnetic resonance images in healthy volunteers (n = 23) at 0, 30, and 60 minutes after administering either crystalloid or colloid. RESULTS: In the clinical study, the time to reach the peak sensory block level was delayed significantly in the crystalloid preload group (27.2 ± 17.8 minutes; P < 0.01) compared with the colloid preload group (13.9 ± 7.0 minutes). The median sensory block levels of the crystalloid preload group at 15 minutes (T10, P < 0.05) and 20 minutes (T9.5, P < 0.05) were significantly lower than those (T8, T7, respectively) of the colloid preload group. In the magnetic resonance imaging study, cranially directed CSF pulsatile movement decreased significantly at the L2-3 intervertebral intrathecal space at 30 minutes after crystalloid administration, but not after colloid administration. The CSF production rate significantly increased at 30 minutes (637 μL/min, P < 0.05) after crystalloid preload compared with the baseline measurement (448 μL/min), and then slightly decreased (609 μL/min) at 60 minutes. In the colloid preload group, the CSF production rate was not statistically significant compared with the baseline measurement (464, 512, and 542 μL/min at baseline, 30, and 60 minutes, respectively). CONCLUSIONS: Compared with a colloid preload, which may be comparable to the no-preload condition, crystalloid preload prolonged the time to reach the peak sensory block level in isobaric spinal anesthesia, which might have been caused by a significant decrease in CSF pulsatile movement. This attenuated CSF pulsatile movement in the crystalloid preload group might have resulted from significant increases of CSF production.

Background Chronic graft-versus-host disease (cGVHD) is a major complication in long-term survivors of hematopoietic stem cell transplantation (HSCT). Cutaneous manifestations are frequently the presenting features; therefore, the dermatologist needs to be aware of the wide spectrum of cutaneous cGVHD. Methods We retrospectively evaluated patients’ characteristics, clinical, and histological features of cutaneous cGVHD and analyzed factors influencing the severity of cutaneous cGVHD in 100 Korean HSCT recipients between January 1, 1995, and December 31, 2007. Results Clinical manifestations of cutaneous cGVHD mainly presented as lichenoid (60.0%), sclerodermoid (12.0%), or erythematous maculopapular (22.0%) patterns. Other less common findings included xerosis, dyspigmentation, acquired ichthyosis, eczema, exfoliative dermatitis, alopecia, erythema multiforme-like or keratosis pilaris-like eruption. Among 100 patients, 46 patients were investigated for nail involvement, and 29 (63.0%) of them were accompanied with nail abnormalities. Histologically, characteristic lichenoid lesions were observed in 53%, sclerodermoid in 9%, and acute/chronic overlap syndrome in 28% of patients. We also discovered that HSCT from female donors to male recipients increased the severity of cutaneous cGVHD. Conclusions We report a large study about cutaneous cGVHD in Asian patients. Cutaneous cGVHD presented with a wide spectrum of clinical and histological manifestations.

Objective To investigate the effects of Qi exercise on maternal outcomes during pregnancy. Design A prospective, two-group, quasi-experimental, pretest/post test design was used. Setting A convenience sample was recruited from one women's wellness center and one women's health clinic in Seoul, Korea. Participants Participants were healthy pregnant women at more than 18 weeks gestation. A total of 70 women were included in the final analysis. Methods Qi exercise was carried out for 90 minutes, twice a week for 12 weeks. Study outcomes were measured by the Intrapersonal Communication Questionnaire (Talking to Your Baby), Zung's Self-rating Depression Scale (ZSDS), the State Trait Anxiety Inventory (STAI), and the Pregnancy Mild Discomfort Index. Analysis of covariance was used to compare outcomes between groups, after adjusting for baseline scores. Results The Qi exercise group had higher post test maternal/fetal interaction and lower maternal depressive symptoms and physical discomfort scores than the control group. There was no difference in anxiety. Conclusion The findings suggest that the holistic approach of Qi exercise may positively influence maternal/fetal interaction and mother's health. Whether these beneficial effects can be sustained throughout pregnancy requites additional research.

Concerning about the negative impact of chemical pesticides on human health and the environment has been leading to dramatic increase of research in natural product-based pesticides. An antagonistic bacterium Streptomyces sp. S-1110 was isolated from apple farm soil. The culture filtrate of the strain showed growth inhibition effects to apple pathogenic fungi, Botryosphaeria dothidea, Colletotrichum gloeosporioides and Rhizoctonia solani . The unidentified antibiotic substances from the strain kept antagonistic activity either after heat treatment at 121 ℃ for 1 h or pH treatment at range of pH 3 - pH 12 for 24 h. The substances also prevented apple fruit from spoiling by inoculated two pathogenic molds, B. dothidea and C. gloeosporioides . These results suggested that the isolated strain would be useful as a biocontrol agent to control apple spoiling occurred from mold.Key Words: Antagonistic bacteria, Biocontrol agent, Botryosphaeria dothidea, Colletotrichum gloeosporioides, Rhizoctonia solani