1,144 results on '"H, Kanaoka"'
Search Results
202. Plasma exosome-encapsulated microRNA-21 and microRNA-92a are promising biomarkers for the prediction of peritoneal recurrence in patients with gastric cancer.
- Author
-
Soeda, Naruyoshi, Iinuma, Hisae, Suzuki, Yusuke, Tsukahara, Daisuke, Midorikawa, Hironori, Igarashi, Yuichi, Kumata, Yoshimasa, Horikawa, Masahiro, Kiyokawa, Takashi, Fukagawa, Takeo, and Fukushima, Ryoji
- Subjects
STOMACH cancer ,PROSTAGLANDIN receptors ,APOPTOSIS ,CA 19-9 test ,CANCER patients ,DNA microarrays - Abstract
In patients with gastric cancer (GC), peritoneal recurrence is a common risk and associated with poor prognosis. A novel biomarker for the prediction of high-risk peritoneal recurrence in patients with GC is desirable. The present study investigated the effectiveness of exosome-encapsulated microRNAs (ex-miRNAs) as minimally invasive biomarkers in patients with GC that received curative surgery. Recurrence-specific ex-miRNAs were selected following comparison of miRNA microarray data from patients with TNM stage II GC with peritoneal recurrence (n=3) and without peritoneal recurrence following curative surgery (n=3), and three healthy volunteers. In this analysis, exosome-encapsulated miRNA-21 (ex-miR-21) and exosomal miR-92a (ex-miR-92a) exhibited the greatest alterations in expression patterns. Using plasma exosome samples collected from another 129 patients with stage II and III GC, the present study investigated the potential value of ex-miR-21 and ex-miR-92a as biomarkers. Ex-miRNA levels were measured using TaqMan miRNA assays. Ex-miR-21 levels were significantly higher and ex-miR-92a levels were significantly lower in samples from patients with GC compared with healthy controls. The overall survival (OS) and peritoneal recurrence-free survival (PRFS) were poorer in stage II and III patients with high ex-miR-21 levels than in patients with low miR-21 levels. OS and PRFS of stage II and III patients with low ex-miR92a levels were significantly worse than those with high ex-miR92a levels. Cox multivariate analyses indicated that ex-miR-21 and ex-miR-92a were independent prognostic factors for OS and PRFS in stage II and III GC. A negative correlation was detected between expression levels of miR-21 and programmed cell death protein 4 mRNA, and miR-92a and prostaglandin E receptor 4 mRNA. Therefore, ex-miR-21 and ex-miR-92a may function as effective and minimally invasive biomarkers for the prediction of peritoneal recurrence and the prognosis of patients with stage II/III GC. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
203. Assessment by miRNA microarray of an autologous cancer antigen‐pulsed adoptive immune ensemble cell therapy (AC‐ACT) approach; demonstrated induction of anti‐oncogenic and anti‐PD‐L1 miRNAs.
- Author
-
Chinami, Masanobu, Iwabuchi, Kaoru, Muto, Yoshiteru, Uchida, Yasuhiko, Arita, Ryu, Shuraim, Rana A., and Adra, Chaker N.
- Subjects
CELLULAR therapy ,MICRORNA ,RECTAL cancer ,CANCER treatment - Abstract
A 60‐year‐old woman with stage IV rectal cancer received adoptive cell therapy with autologous cancer antigen (AC‐ACT) causing induction of anti‐oncogenic and anti‐PD‐L1 miRNAs as assessed by miRNA microarray. More than 1 year after AC‐ACT, metastases have been arrested, and the patient reports good quality of life. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
204. Identification of glycyrrhizin metabolites in humans and of a potential biomarker of liquorice-induced pseudoaldosteronism: a multi-centre cross-sectional study.
- Author
-
Takahashi, Kanon, Yoshino, Tetsuhiro, Maki, Yasuhito, Ishiuchi, Kan'ichiro, Namiki, Takao, Ogawa-Ochiai, Keiko, Minamizawa, Kiyoshi, Makino, Toshiaki, Nakamura, Tomonori, Mimura, Masaru, and Watanabe, Kenji
- Subjects
METABOLITES ,CROSS-sectional method ,ASIAN medicine ,UNIVERSITY hospitals ,MASS spectrometers ,HERBAL medicine ,CELL aggregation ,BLOOD pressure - Abstract
Liquorice [main ingredient, glycyrrhizin (GL)] is widely used as a food sweetener and herbal medicine. Occasionally, liquorice consumption causes pseudoaldosteronism as a side effect which causes oedema, hypokalaemia, and hypertension due to hyperactivity of mineral corticoid receptor. We aimed to detect GL metabolites in human blood and urine samples and to determine the pathological relationship between GL metabolites and pseudoaldosteronism. For this multi-centre, retrospective, cross-sectional study, we recruited patients who had visited Center for Kampo Medicine in Keio University Hospital, Department of Japanese Oriental (Kampo) Medicine in Chiba University Hospital, Clinic of Japanese Oriental (Kampo) Medicine in Kanazawa University Hospital, and Department of Oriental Medicine in Kameda Medical Center from November 2011 to July 2018. We collected laboratory data including concentration of serum potassium, plasma activity of renin and aldosterone, and residual blood and/or urine samples of participants who had experienced symptoms/signs of pseudoaldosteronism in the form of increase in blood pressure and occurrence or aggregation of oedema while taking liquorice-containing herbal preparations, and measured GL metabolites using a highly selective liquid chromatography tandem mass spectrometer system. We registered 97 participants (mean age 60 ± 15 years; male:female 14:83). 18β-glycyrrhetinic acid (GA) was detected in 67 serum samples (median 122 nM, range 5 nM–1.8 µM) and 18β-glycyrrhetyl-3-O-sulfate (compound 3) in 68 samples (median 239 nM, range 2 nM–4.2 µM). 3-Monoglucuronyl 18β-glycyrrhetinic acid, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate-30-glucuronide, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate, and GL itself were not or rarely detected. We could not find any correlation between blood pressure or peripheral oedema and serum concentration of GL metabolites. Sulfotransferase 2A1 catalysed the metabolic reaction of GA to compound 3, a major GL metabolite in human blood. High serum concentration of compound 3 was related to lower renin, aldosterone, and potassium levels, suggesting a pathological relationship between compound 3 and liquorice-induced pseudoaldosteronism. This is the first study to identify the association between a novel metabolite, compound 3, and the incidence of pseudoaldosteronism, highlighting it as a promising biomarker. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
205. Gut microbiota: what is its place in pharmacology?
- Author
-
Tarasiuk, Aleksandra and Fichna, Jakub
- Subjects
GUT microbiome ,DRUG toxicity ,FOOD habits ,GASTROINTESTINAL system ,HUMAN physiology ,INTESTINES ,PHARMACOLOGY - Abstract
Introduction: In each section of the human gastrointestinal (GI) tract we may find bacteria that are adapted to local conditions and fulfill an important role in the proper functioning of the body. The gut microorganisms are crucial in human physiology in areas as diverse as the brain and the immune system functions. Therefore, there is a close relationship between the intestinal microbiota, its metabolic activity, and health of the host. Areas covered: In this review, we explore the host–microbiome interactions and characterize the role they may play in drug metabolism and toxicity. The study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect databases. Expert opinion: Increasing unhealthy eating habits, stress, antibiotic therapy, unfavorable environmental factors, and genetic predisposition contribute to imbalances in the composition and function of the GI tract microbes and the initiation and progression of disease processes. Restoration of the balanced gut microbiota composition is possible by oral administration of probiotics. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
206. From Cyanobacteria to Human, MAPEG-Type Glutathione-S-Transferases Operate in Cell Tolerance to Heat, Cold, and Lipid Peroxidation.
- Author
-
Kammerscheit, Xavier, Chauvat, Franck, and Cassier-Chauvat, Corinne
- Subjects
PHYSIOLOGICAL effects of cold temperatures ,LIPIDS ,HEAT ,PEROXIDATION ,AUTOTROPHIC bacteria ,BIOMASS production ,PHYSIOLOGICAL effects of heat - Abstract
The MAPEG2 sub-family of glutathione-S-transferase proteins (GST) has been poorly investigated in vivo , even in prokaryotes such as cyanobacteria the organisms that are regarded as having developed glutathione-dependent enzymes to protect themselves against the reactive oxygen species (ROS) often produced by their powerful photosynthesis. We report the first in vivo analysis of a cyanobacterial MAPEG2-like protein (Sll1147) in the model cyanobacterium Synechocystis PCC 6803. While Sll1147 is dispensable to cell growth in standard photo-autotrophic conditions, it plays an important role in the resistance to heat and cold, and to n- tert butyl hydroperoxide (n- t BOOH) that induces lipid peroxidation. These findings suggest that Sll1147 could be involved in membrane fluidity, which is critical for photosynthesis. Attesting its sensitivity to these stresses, the Δ sll1147 mutant lacking Sll1147 challenged by heat, cold, or n- t BOOH undergoes transient accumulation of peroxidized lipids and then of reduced and oxidized glutathione. These results are welcome because little is known concerning the signaling and/or protection mechanisms used by cyanobacteria to cope with heat and cold, two inevitable environmental stresses that limit their growth, and thus their production of biomass for our food chain and of biotechnologically interesting chemicals. Also interestingly, the decreased resistance to heat, cold and n- t BOOH of the Δ sll1147 mutant could be rescued back to normal (wild-type) levels upon the expression of synthetic MAPEG2-encoding human genes adapted to the cyanobacterial codon usage. These synthetic hmGST2 and hmGST3 genes were also able to increase the Escherichia coli tolerance to heat and n- t BOOH. Collectively, these finding indicate that the activity of the MAPEG2 proteins have been conserved, at least in part, during evolution from (cyano)bacteria to human. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
207. The Chinese Association for the Study of Pain (CASP): Consensus on the Assessment and Management of Chronic Nonspecific Low Back Pain.
- Author
-
Ma, Ke, Zhuang, Zhi-Gang, Wang, Lin, Liu, Xian-Guo, Lu, Li-Juan, Yang, Xiao-Qiu, Lu, Yan, Fu, Zhi-Jian, Song, Tao, Huang, Dong, Liu, Hui, Huang, You-Qing, Peng, Bao-Gan, and Liu, Yan-Qing
- Published
- 2019
- Full Text
- View/download PDF
208. First in vivo Evidence That Glutathione-S-Transferase Operates in Photo-Oxidative Stress in Cyanobacteria.
- Author
-
Kammerscheit, Xavier, Chauvat, Franck, and Cassier-Chauvat, Corinne
- Subjects
PHOTOOXIDATIVE stress ,GLUTATHIONE transferase ,CYANOBACTERIA ,METHYLENE blue ,OXIDATIVE stress ,CELL growth ,REACTIVE oxygen species - Abstract
Although glutathione (GSH) and GSH-dependent enzymes, such as glutathione transferases (GSTs), are thought to have been developed by cyanobacteria to cope with the reactive oxygen species (ROS) that they massively produced by their active photosynthesis, there had been no in vivo analysis of the role of GSTs in cyanobacteria so far. Consequently, we have analyzed two of the six GSTs of the model cyanobacterium Synechocystis PCC 6803, namely Sll1545 (to extend its in vitro study) and Slr0236 (because it is the best homolog to Sll1545). We report that Sll1545 is essential to cell growth in standard photo-autotrophic conditions, whereas Slr0236 is dispensable. Furthermore, both Sll1545 and Slr0236 operate in the protection against stresses triggered by high light, H
2 O2 , menadione and methylene blue. The absence of Slr0236 and the depletion of Sll1545 decrease the tolerance to methylene blue in a cumulative way. Similarly, the combined absence of Slr0236 and depletion of Sll1545 decrease the resistance to high light. Attesting their sensitivity to high-light or methylene blue, these Δ slr0236-sll1545 cells transiently accumulate ROS, and then reduced and oxidized glutathione in that order. In contrast, the absence of Slr0236 and the depletion of Sll1545 increase the tolerance to menadione in a cumulative way. This increased menadione resistance is due, at least in part, to the higher level of catalase and/or peroxidase activity of these mutants. Similarly, the increased H2 O2 resistance of the Δ slr0236-sll1545 cells is due, at least in part, to its higher level of peroxidase activity. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
209. A questionnaire-based study for weight loss by using herbal drugs in Dammam (Eastern Region), Kingdom of Saudi Arabia.
- Author
-
Ahmad, Wasim, Ahmad, Ayaz, Ali, Mohammad, Amin, Yousif, Sheikh, Sukainah, Usmani, Anjum, Otaibi, Rawan, Rashidi, Sarah, Salih, Noura, and Mostafa, Omnia
- Subjects
DATE palm ,WEIGHT loss ,MORBID obesity ,DRUG side effects ,FLAXSEED ,DRUG efficacy ,GREEN tea - Abstract
Background: Obesity is a common health problem and it is increasing around the world. Herbal drugs are the most commonly used alternative treatment for weight reduction. The aim of this study was to identify the most commonly used plants for the treatment of obesity or to reduce the weight of patients with obesity and to determine the usage rate of herbal drugs in Dammam, Kingdom of Saudi Arabia. Materials and Methods: This cross-sectional study was performed on people who were overweight and obese in Dammam (Eastern Region), Kingdom of Saudi Arabia, by using pretested questionnaire. Participants were randomly selected for this questionnaire study. P value was calculated by using chi-square test. Results: A total of 500 participants were selected, of which 355 participants completed the questionnaire-based study and the remaining 145 were excluded from the study. The majority (n = 190, 53.52%, P > 0.05) used herbal drugs to reduce weight. The most commonly used herbal drugs included green tea (53.52%, P > 0.05), ginger (31.54%, P < 0.01), and flax seed (17.46%, P < 0.01). However, nearly 35% of participants stated that they had unwanted effects; therefore, majority of the participants stated they would use herbal drugs in future to reduce weight. Conclusion: This investigation showed that the treatment to reduce weight of those who were overweight or obese by herbal drugs and the usage rate of herbal drugs/fruits/vegetables were high in Dammam. Further investigations are required to prove the efficacy of herbal drugs and their side effects for the treatment of obesity. A community awareness program is essential to explain the positive and adverse effects of herbal drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
210. Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice.
- Author
-
Toko Maehara, Tatsuro Nakamura, Shingo Maeda, Kosuke Aritake, Masataka Nakamura, and Takahisa Murata
- Published
- 2019
- Full Text
- View/download PDF
211. Comparison of the Effect of Fimasartan versus Valsartan on Blood Pressure Variability in Acute Ischemic Stroke: A Double-Blind Randomized Trial.
- Author
-
Shin, Dong Hoon, Song, Soohwa, and Lee, Yeong Bae
- Subjects
ALTEPLASE ,BLOOD pressure ,STROKE ,HYPERTENSION - Abstract
Higher blood pressure variability (BPV) is associated with poor functional outcome and mortality in acute stroke. This randomized controlled trial was conducted to compare the effect on BPV between fimasartan and valsartan (Boryung Pharmaceutical Co., Ltd., Seoul, Republic of Korea) in patients with acute ischemic stroke. Eighty patients were randomly assigned to receive either valsartan or fimasartan after 7 days of acute ischemic stroke onset, for duration of 8 weeks. Of them, 62 patients completed the study [valsartan (n=31), fimasartan (n=31)]. We measured BP for 24 hours using ambulatory BP monitoring device before and after 8 weeks of starting BP medication. We calculated several indexes such as standard deviation (SD), weighted 24-hour BP with SD (wSD), coefficient of variation (CV), and average real variability (ARV) to assess BPV and to compare indexes of BPV between 2 drugs. SD values of systolic BP in daytime, nighttime, and 24 h period (15.55±4.02 versus 20.55±8.77, P=0.006; 11.98±5.52 versus 16.47±6.94, P=0.007; 17.22±5.30 versus 21.45±8.51, P=0.024), wSD of systolic BP (8.27±3.01 versus 10.77±4.18, P=0.010), and ARV of systolic BP (15.85±6.17 versus 19.68±7.83, P=0.040) of patients receiving fimasartan after 8 weeks were significantly lower than patients receiving valsartan. In paired t-test, SD values of daytime, nighttime, and 24 h period of systolic BP of patients receiving fimasartan were significantly decreased after 8 weeks (15.55±4.02 versus 18.70±7.04, P=0.038; 11.98±5.52 versus 17.19±7.35, P=0.006; 17.22±5.30 versus 20.59±5.91, P=0.015). Our study showed that fimasartan had greater effect on reducing BPV after acute ischemic stroke than valsartan. Trials registry number is KCT0003254. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
212. Hematopoietic prostaglandin D synthase-derived prostaglandin D2 ameliorates adjuvant-induced joint inflammation in mice.
- Author
-
Yoshiki Tsubosaka, Toko Maehara, Daiki Imai, Tatsuro Nakamura, Koji Kobayashi, Nanae Nagata, Wataru Fujii, and Takahisa Murata
- Published
- 2019
- Full Text
- View/download PDF
213. Risk factors associated with pseudoaldosteronism in patients with chronic hepatitis: A retrospective cohort study.
- Author
-
Komatsu, Akihiro, Yoshino, Tetsuhiro, Suzuki, Takeshi, Nakamura, Tomonori, Kanai, Takanori, and Watanabe, Kenji
- Subjects
HYPOKALEMIA ,MULTIDRUG resistance ,BILIRUBIN ,HEPATITIS C virus ,BIOLOGICAL tags - Abstract
Glycyrrhizin is used to treat chronic hepatitis, but it also plays an important role in pseudoaldosteronism. Multidrug resistance‐associated protein 2 is important for glycyrrhizin excretion. Dysfunction of this transporter increases the serum levels of direct bilirubin, glycyrrhizin and its metabolites. Hence, elevated direct‐bilirubin levels could predict the risk of pseudoaldosteronism. This study aimed to evaluate the relationship between elevated direct‐bilirubin levels and hypokalaemia, which is the most sensitive marker of pseudoaldosteronism. This retrospective cohort study was conducted in a Japanese university hospital. The occurrence of hypokalaemia is defined as a serum potassium level of ≤3.5 mEq/L after the administration of a glycyrrhizin‐containing medication, and a further decline of ≥0.5 mEq/L or an increase of ≥0.5 mEq/L after discontinuing the glycyrrhizin‐containing medication was examined in patients with chronic hepatitis between January 2009 and December 2015. This analysis involved 1392 patients, including 596 women. Hepatitis C virus infections were the most common cause of chronic hepatitis in this study. Seventy‐nine patients received glycyrrhizin (exposed group; mean age: 60.5 ± 14.2) and 1313 did not receive glycyrrhizin (control group; mean age: 58.3 ± 15.8 years). Synergistic effects of glycyrrhizin‐containing medications and elevated direct‐bilirubin levels were associated with hypokalaemia. Elevated direct‐bilirubin levels and hypoalbuminaemia were associated with hypokalaemia in the exposed group. Older age, female sex, high daily glycyrrhizin dosage, longer duration of glycyrrhizin intake, and potassium‐lowering medications were not associated with hypokalaemia after the model adjustment. Elevated direct‐bilirubin levels and hypoalbuminaemia may predict pseudoaldosteronism caused by glycyrrhizin. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
214. Influence of baseline anemia on long-term clinical outcomes in patients with venous thromboembolism: from the COMMAND VTE registry.
- Author
-
Yamashita, Yugo, Morimoto, Takeshi, Amano, Hidewo, Takase, Toru, Hiramori, Seiichi, Kim, Kitae, Oi, Maki, Akao, Masaharu, Kobayashi, Yohei, Toyofuku, Mamoru, Izumi, Toshiaki, Tada, Tomohisa, Chen, Po-Min, Murata, Koichiro, Tsuyuki, Yoshiaki, Saga, Syunsuke, Sasa, Tomoki, Sakamoto, Jiro, Kinoshita, Minako, and Togi, Kiyonori
- Abstract
The influence of anemia on the long-term clinical outcomes has not been fully evaluated in patients with venous thromboembolism (VTE). We evaluated the influence of anemia among 3012 patients in the COMMAND VTE Registry with a median follow-up period of 1219 days. The outcomes measures were ISTH major bleeding, recurrent VTE and all-cause death. There were 1012 patients (34%) with moderate/severe anemia (Hb ≤ 10.9 g/dl), 615 patients (20%) with mild anemia (Hb 11.0–12.9 g/dl for men, and 11.0–11.9 g/dl for women), and 1385 patients (46%) without anemia. The cumulative 5-year incidence of major bleeding was significantly higher in patients with anemia (moderate/severe anemia: 17.6%, mild anemia: 12.1%, and no anemia: 8.7%, P < 0.001). After adjusting the confounders, the excess risk of mild and moderate/severe anemia, respectively, relative to no anemia for major bleeding remained significant (mild: adjusted HR 1.41: [95% CI 1.00–1.98], P = 0.048; moderate/severe: adjusted HR 1.91: [95% CI 1.42–2.58], P < 0.001, respectively). The excess risk of moderate/severe anemia relative to no anemia was also significant for mortality (adjusted HR 2.89: 95% CI 2.45–3.42, P < 0.001), but the risk was neutral for recurrent VTE (adjusted HR 1.05: 95% CI 0.76–1.45, P = 0.77). In conclusions, VTE patients with mild and moderate/severe anemia had higher risk for major bleeding events without significant excess risk for recurrent VTE events, and the risk for major bleeding events increased according to the severity of anemia. We should pay more attention to the optimal intensity and duration of anticoagulation in VTE patients with anemia. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
215. Blood Flow Assessment of Arteriovenous Malformations Using Intraoperative Indocyanine Green Videoangiography.
- Author
-
Kato, Naoki, Prinz, Vincent, Dengler, Julius, and Vajkoczy, Peter
- Subjects
INDOLE compounds ,ANGIOGRAPHY ,BLOOD circulation ,CEREBRAL circulation ,CEREBRAL edema ,DIAGNOSTIC imaging ,INTRAOPERATIVE monitoring ,MAGNETIC resonance imaging ,COMPUTERS in medicine ,ARTERIOVENOUS malformation ,DESCRIPTIVE statistics ,THERAPEUTICS - Abstract
Intraoperative indocyanine green (ICG) videoangiography is widely used in patients undergoing neurosurgery. FLOW800 is a recently developed analytical tool for ICG videoangiography to assess semi-quantitative flow dynamics; however, its efficacy is unknown. In this study, we evaluated its functionality in the assessment of flow dynamics of arteriovenous malformation (AVM) through ICG videoangiography under clinical settings. ICG videoangiography was performed in the exposed AVM in eight patients undergoing surgery. FLOW800 analysis was applied directly, and gray-scale and color-coded maps of the surgical field were obtained. After surgery, a region of interest was placed on the individual vessels to obtain time-intensity curves. Parameters of flow dynamics, including the maximum intensity, transit time, and cerebral blood flow index, were calculated using the curves. The color-coded maps provided high-resolution images; however, reconstruction of colored images was restricted by the depth, approach angle, and brain swelling. Semi-quantitative parameters were similar among the feeders, niduses, and drainers. However, a higher cerebral blood flow index was observed in the feeders of large AVM (>3 cm) than in those of small AVM (P < 0.05). Similarly, the cerebral blood flow index values were positively correlated with the nidus volume (P < 0.01). FLOW800 enabled visualization of the AVM structure and safer resection, except in case of deep-seated AVM. Moreover, semi-quantitative values in the individual vessels through using ICG intensity diagram showed different patterns according to size of the AVM. ICG videoangiography showed good performance in evaluating flow dynamics of the AVM in patients undergoing surgery. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
216. Characterization of Organic Solvent-Tolerant Lipolytic Enzyme from Marinobacter lipolyticus Isolated from the Antarctic Ocean.
- Author
-
Park, Se Hyeon, Kim, Soo-jin, Park, Seongsoon, and Kim, Hyung Kwoun
- Abstract
The Antarctic marine environment provides a good source of novel lipolytic enzymes that possess beneficial properties, i.e., resistance to extreme physical and chemical conditions. We found a lipolytic Escherichia coli colony that was transformed using genomic DNA from Marinobacter lipolyticus 27-A9 isolated from the Antarctic Ross Sea. DNA sequence analysis revealed an open reading frame of lipolytic enzyme gene. The gene translates a protein (LipA9) of 404 amino acids with molecular mass of 45,247 Da. Recombinant LipA9 was expressed in E. coli BL21 (DE3) cells and purified by anion exchange and gel filtration chromatography. The k
cat /Km of LipA9 was 175 s−1 μM−1 , and the optimum temperature and pH were 70 °C and pH 8.0, respectively. LipA9 had quite high organic solvent stability; it was stable toward several common organic solvents up to 50% concentration. Substrate specificity studies showed that LipA9 preferred a short acyl chain length of p-nitrophenyl ester and triglyceride. Sequence analysis showed that LipA9 contained catalytic Ser72 and Lys75 in S-x-x-K motif, like family VIII esterases. Homology modeling and site-directed mutagenesis studies revealed that Tyr141 and Tyr188 residues were located near the conserved motif and played an important role in catalytic activity. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
217. Pharmacokinetic Study of Compound K in Japanese Subjects After Ingestion of Panax ginseng Fermented by Lactobacillus paracasei A221 Reveals Significant Increase of Absorption into Blood.
- Author
-
Fukami, Hiroyuki, Ueda, Taro, and Matsuoka, Nobuya
- Published
- 2019
- Full Text
- View/download PDF
218. Extracellular Vesicles: Mechanisms in Human Health and Disease.
- Author
-
Malloci, Marine, Perdomo, Liliana, Veerasamy, Maëva, Andriantsitohaina, Ramaroson, Simard, Gilles, and Martínez, M. Carmen
- Published
- 2019
- Full Text
- View/download PDF
219. A combined computational strategy of sequence and structural analysis predicts the existence of a functional eicosanoid pathway in Drosophila melanogaster.
- Author
-
Scarpati, Michael, Qi, Yan, Govind, Shubha, and Singh, Shaneen
- Subjects
STRUCTURAL analysis (Engineering) ,EICOSANOIDS ,DROSOPHILA melanogaster ,LIPOXYGENASES ,BIOINFORMATICS - Abstract
This study reports on a putative eicosanoid biosynthesis pathway in Drosophila melanogaster and challenges the currently held view that mechanistic routes to synthesize eicosanoid or eicosanoid-like biolipids do not exist in insects, since to date, putative fly homologs of most mammalian enzymes have not been identified. Here we use systematic and comprehensive bioinformatics approaches to identify most of the mammalian eicosanoid synthesis enzymes. Sensitive sequence analysis techniques identified candidate Drosophila enzymes that share low global sequence identities with their human counterparts. Twenty Drosophila candidates were selected based upon (a) sequence identity with human enzymes of the cyclooxygenase and lipoxygenase branches, (b) similar domain architecture and structural conservation of the catalytic domain, and (c) presence of potentially equivalent functional residues. Evaluation of full-length structural models for these 20 top-scoring Drosophila candidates revealed a surprising degree of conservation in their overall folds and potential analogs for functional residues in all 20 enzymes. Although we were unable to identify any suitable candidate for lipoxygenase enzymes, we report structural homology models of three fly cyclooxygenases. Our findings predict that the D. melanogaster genome likely codes for one or more pathways for eicosanoid or eicosanoid-like biolipid synthesis. Our study suggests that classical and/or novel eicosanoids mediators must regulate biological functions in insects–predictions that can be tested with the power of Drosophila genetics. Such experimental analysis of eicosanoid biology in a simple model organism will have high relevance to human development and health. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
220. Glycerol Mediated Synthesis, Biological Evaluation, and Molecular Docking Study of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines as Potent Antitubercular Agents.
- Author
-
Jamale, Dattatraya K., Undare, Santosh S., Valekar, Navanath J., Sarkate, Aniket P., Kolekar, Govind B., and Anbhule, Prashant V.
- Subjects
GLYCERIN ,MOLECULAR docking ,ANTITUBERCULAR agents ,SPECTROSCOPIC imaging ,MYCOBACTERIUM tuberculosis - Abstract
A series of 4‐(1H‐pyrazol‐4‐yl)‐polyhydroquinolines were synthesized through one‐pot four‐component Hantzsch condensation of 1,3‐diphenyl‐1H‐pyrazole‐4‐carbaldehydes, ammonium acetate, dimedone, and alkyl acetoacetate in glycerol as a green reaction medium. The structures of the compounds are verified by spectroscopic methods and screened for their antimicrobial activity against Mycobacterium tuberculosis H37RV strain. Almost all the synthesized derivatives reveal excellent antitubercular activity based on minimum inhibitory concentration. Especially the compounds 5h and 5k exhibit outstanding antitubercular activity with minimum inhibitory concentration 1.6 μg/mL. In addition, molecular docking study of synthesized scaffolds against enoyl‐acyl carrier protein reductase from M. tuberculosis was performed to propose the binding modes. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
221. Fine Particle Filtration Technology Using Fiber as Dust Collection Medium.
- Author
-
Chikao Kanaoka
- Subjects
FILTERS & filtration ,DUST collectors (Machinery) ,THERMAL analysis ,PARTICLE emissions ,EMPIRICAL research - Abstract
Researches relating dust collector using fiber as particle collection body i.e., air filter, cartridge filter and nonwoven bag filter, were reviewed. Their filtration process was classified into 3 stages, i.e., Stage 1.inner filtration I, Stage 2.inner filtration II and Stage 3.surface filtration. Collection mechanisms of fresh circular fiber have been well understood and so-called classic filtration theory is applicable except single nano-particle, where discussion about the possibility of thermal rebound is necessary. In Stage 1, effects of shape of both fiber and particle, and filter structure, non-uniformity are the important issues. In Stages 2 and 3, filtration process becomes very complicated because of many affecting parameters. Main target in Stage 2 is to develop effective scheme to describe the phenomena and to find filter structure having a large holding capacity. Most important issue in Stage 3 is to develop the effective cleaning technique to minimize the dust emission based on rational but not empirical scheme. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
222. Effects of ginsenoside CK pretreatment on oxidative stress and inflammation in rats with cerebral ischemia/reperfusion injury.
- Author
-
Jiang, Shuang, Zhang, Haina, Qian, Min, Su, Xin, Sun, Xiaoqi, Wu, Tianqi, and Song, Wu
- Subjects
ISCHEMIA ,REPERFUSION injury ,OXIDATIVE stress ,NIMODIPINE ,INFLAMMATION - Abstract
The prevention and treatment of cerebral ischemia/reperfusion injury has become a key link in the treatment of ischemic cerebrovascular diseases. In this study, Wistar rats were randomly divided into Sham, low-dose ginsenoside (L-CK), high-dose ginsenoside (H-CK) and nimodipine groups, and the rats in the L-CK, H-CK, and nimodipine groups were intragastrically given the corresponding agents successively once a day for 15 days before surgery. At 1 h after the last administration, a rat cerebral ischemia/reperfusion model was established by suture-occluded method and the effects of ginsenoside CK on the neurological scores, brain tissue water content, brain infarct volume, oxidative stress and inflammation were investigated. The results showed that, compared with those in the model group, the neurological behaviour scores in the L- and H-CK groups, the brain tissue water content in the H-CK group, and the brain infarct volume ratios in the L- and H-CK groups were significantly reduced. Compared with those in the model group, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities increased, whereas the malondialdehyde (MDA) content decreased significantly in the brain tissue of the rats in the L- and H-CK groups. Compared with that in the model group, the content of TNF-α in the H-CK group, the content of IL-1β and the expression of HMGB1 protein in the L- and H-CK groups were significantly reduced. These results suggest that ginsenoside CK can protect against cerebral ischemia reperfusion injury in rats, which may be related to its anti-oxidative, anti-inflammatory and HMGB1-expression inhibitory activity. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
223. Ginsenoside F1 Promotes Cytotoxic Activity of NK Cells via Insulin-Like Growth Factor-1-Dependent Mechanism.
- Author
-
Kwon, Hyung-Joon, Lee, Heejae, Choi, Go-Eun, Kwon, Soon Jae, Song, Ah Young, Kim, So Jeong, Choi, Woo Seon, Hwang, Sang-Hyun, Kim, Sun Chang, and Kim, Hun Sik
- Abstract
Ginsenosides are the principal active components of ginseng and are considered attractive candidates for combination cancer therapy because they can kill tumors and have favorable safety profiles. However, the overall benefit of ginsenosides remains unclear, particularly in cancer immunosurveillance, considering the controversial results showing repression or promotion of immune responses. Here we identify a potentiating role of ginsenoside F1 (G-F1) in cancer surveillance by natural killer (NK) cells. Among 15 different ginsenosides, G-F1 most potently enhanced NK cell cytotoxicity in response to diverse activating receptors and cancer cells. G-F1 also improved cancer surveillance in mouse models of lymphoma clearance and metastatic melanoma that rely on NK cell activity. G-F1-treated NK cells exhibited elevated cytotoxic potential such as upregulation of cytotoxic mediators and of activation signals upon stimulation. NK cell potentiation by G-F1 was antagonized by insulin-like growth factor (IGF)-1 blockade and recapitulated by IGF-1 treatment, suggesting the involvement of IGF-1. Thus, our results suggest that G-F1 enhances NK cell function and may have chemotherapeutic potential in NK cell-based immunotherapy. We anticipate our results to be a starting point for further comprehensive studies of ginsenosides in the immune cells mediating cancer surveillance and the development of putative therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
224. Clinical and Genetic Factors to Inform Reducing Colorectal Cancer Disparitites in African Americans.
- Author
-
Carethers, John M.
- Abstract
Colorectal cancer (CRC) is the third most prevalent and second deadliest cancer in the U.S. with 140,250 cases and 50,630 deaths for 2018. Prevention of CRC through screening is effective. Among categorized races in the U.S., African Americans (AAs) show the highest incidence and death rates per 100,000 when compared to Non-Hispanic Whites (NHWs), American Indian/Alaskan Natives, Hispanics, and Asian/Pacific Islanders, with an overall AA:NHW ratio of 1.13 for incidence and 1.32 for mortality (2010-2014, seer.cancer.gov). The disparity for CRC incidence and worsened mortality among AAs is likely multifactorial and includes environmental (e.g., diet and intestinal microbiome composition, prevalence of obesity, use of aspirin, alcohol, and tobacco use), societal (e.g., socioeconomic status, insurance and access to care, and screening uptake and behaviors), and genetic (e.g., somatic driver mutations, race-specific variants in genes, and inflammation and immunological factors). Some of these parameters have been investigated, and interventions that address specific parameters have proven to be effective in lowering the disparity. For instance, there is strong evidence raising screening utilization rates among AAs to that of NHWs reduces CRC incidence to that of NHWs. Reducing the age to commence CRC screening in AA patients may further address incidence disparity, due to the earlier age onset of CRC. Identified genetic and epigenetic changes such as reduced MLH1 hypermethylation frequency, presence of inflammation-associated microsatellite alterations, and unique driver gene mutations (FLCN and EPHA6) among AA CRCs will afford more precise approaches toward CRC care, including the use of 5-fluorouracil and anti-PD-1. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
225. Mutant voltage-gated Na+ channels can exert a dominant negative effect through coupled gating.
- Author
-
Clatot, Jérôme, Yang Zheng, Girardeau, Aurore, Haiyan Liu, Laurita, Kenneth R., Marionneau, Céline, and Deschênes, Isabelle
- Abstract
Mutations in voltagegated Naα channels have been linked to several channelopathies leading to a wide variety of diseases including cardiac arrhythmias, epilepsy, and myotonia. We have previously demonstrated that voltage- gated Na± channel (Nav)1.5 trafficking-deficient mutant channels could lead to a dominant negative effect by impairing trafficking of the wild-type (WT) channel. We also reported that voltage-gated Na± channels associate as dimers with coupled gating properties. Here, we hypothesized that the dominant negative effect of mutant Na± channels could also occur through coupled gating. This was tested using cell surface biotinylation and single channel recordings to measure the gating probability and coupled gating of the dimers. As previously reported, coexpression of Nav1.5-L325R with WT channels led to a dominant negative effect, as reflected by a 75% reduction in current density. Surprisingly, cell surface biotinylation showed that Nav1.5- L325R mutant is capable of trafficking, with 40% of Nav1.5-L325R reaching the cell surface when expressed alone. Importantly, even though a dominant negative effect on the Na± current is observed when WT and Nav1.5-L325R are expressed together, the total Nav channel cell surface expression was not significantly altered compared with WT channels alone. Thus, the trafficking deficiency could not explain the 75% decrease in inward Na± current. Interestingly, single channel recordings showed that Nav1.5-L325R exerted a dominant negative effect on the WT channel at the gating level. Both coupled gating and gating probability of WT:L325R dimers were drastically impaired. We conclude that dominant negative suppression exerted by Nav1.5 mutants can also be caused by impairing the WT gating probability, a mechanism resulting from the dimerization and coupled gating of voltage-gated Na± channel α-subunits. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
226. Effectiveness of mobile application for menstrual management of working women in Japan: randomized controlled trial and medical economic evaluation.
- Author
-
Song, Mihyon and Kanaoka, Hidenobu
- Published
- 2018
- Full Text
- View/download PDF
227. VOLTAGE-SENSING PHOSPHATASES: BIOPHYSICS, PHYSIOLOGY, AND MOLECULAR ENGINEERING.
- Author
-
Yasushi Okamura, Akira Kawanabe, and Takafumi Kawai
- Subjects
PHOSPHATASES ,PHOSPHOINOSITIDES ,BIOPHYSICS ,CELL membranes ,CELLULAR signal transduction - Abstract
Voltage-sensing phosphatase (VSP) contains a voltage sensor domain (VSD) similar to that in voltage-gated ion channels, and a phosphoinositide phosphatase region similar to phosphatase and tensin homolog deleted on chromosome 10 (PTEN). The VSP gene is conserved from unicellular organisms to higher vertebrates. Membrane depolarization induces electrical driven conformational rearrangement in the VSD, which is translated into catalytic enzyme activity. Biophysical and structural characterization has revealed details of the mechanisms underlying the molecular functions of VSP. Coupling between the VSD and the enzyme is tight, such that enzyme activity is tuned in a graded fashion to the membrane voltage. Upon VSP activation, multiple species of phosphoinositides are simultaneously altered, and the profile of enzyme activity depends on the history of the membrane potential. VSPs have been the obvious candidate link between membrane potential and phosphoinositide regulation. However, patterns of voltage change regulating VSP in native cells remain largely unknown. This review addresses the current understanding of the biophysical biochemical properties of VSP and provides new insight into the proposed functions of VSP. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
228. Voltage-gated sodium currents in cerebellar Purkinje neurons: functional and molecular diversity.
- Author
-
Ransdell, Joseph L. and Nerbonne, Jeanne M.
- Subjects
PURKINJE cells ,VOLTAGE-gated ion channels ,NEURONS ,GABA ,CEREBELLAR nuclei ,CEREBELLUM ,CEREBELLAR cortex ,CELLULAR control mechanisms - Abstract
Purkinje neurons, the sole output of the cerebellar cortex, deliver GABA-mediated inhibition to the deep cerebellar nuclei. To subserve this critical function, Purkinje neurons fire repetitively, and at high frequencies, features that have been linked to the unique properties of the voltage-gated sodium (Nav) channels expressed. In addition to the rapidly activating and inactivating, or transient, component of the Nav current (I
NaT ) present in many types of central and peripheral neurons, Purkinje neurons, also expresses persistent (INaP ) and resurgent (INaR ) Nav currents. Considerable progress has been made in detailing the biophysical properties and identifying the molecular determinants of these discrete Nav current components, as well as defining their roles in the regulation of Purkinje neuron excitability. Here, we review this important work and highlight the remaining questions about the molecular mechanisms controlling the expression and the functioning of Nav currents in Purkinje neurons. We also discuss the impact of the dynamic regulation of Nav currents on the functioning of individual Purkinje neurons and cerebellar circuits. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
229. Overview upon miR-21 in lung cancer: focus on NSCLC.
- Author
-
Bica-Pop, Cecilia, Cojocneanu-Petric, Roxana, Magdo, Lorand, Raduly, Lajos, Gulei, Diana, and Berindan-Neagoe, Ioana
- Subjects
LUNG cancer ,NON-small-cell lung carcinoma ,MICRORNA ,ONCOGENES ,GENE expression ,GENETIC regulation ,CANCER cell proliferation ,CANCER cell growth - Abstract
Considering the high mortality rate encountered in lung cancer, there is a strong need to explore new biomarkers for early diagnosis and also improved therapeutic targets to overcome this issue. The implementation of microRNAs as important regulators in cancer and other pathologies expanded the possibilities of lung cancer management and not only. MiR-21 represents an intensively studied microRNA in many types of cancer, including non-small cell lung cancer (NSCLC). Its role as an oncogene is underlined in multiple studies reporting the upregulated expression of this sequence in patients diagnosed with this malignancy; moreover, several studies associated this increased expression of miR-21 with a worse outcome within NSCLC patients. The same pattern is supported by the data existent in the Cancer Genome Atlas (TCGA). The carcinogenic advantage generated by miR-21 in NSCLC resides in the target genes involved in multiple pathways such as cell growth and proliferation, angiogenesis, invasion and metastasis, but also chemo- and radioresistance. Therapeutic modulation of miR-21 by use of antisense sequences entrapped in different delivery systems has shown promising results in impairment of NSCLC. Hereby, we review the mechanisms of action of miR-21 in cancer and the associated changes upon tumor cells together a focused perspective on NSCLC signaling, prognosis and therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
230. Pass-Band Characteristics of an L-Shaped Waveguide in a Diamond Structure Photonic Crystal.
- Author
-
Chen, Shibin, Ma, Jingcun, Yao, Yunshi, Liu, Xin, and Lin, Ping
- Subjects
PHOTONIC crystals ,PHOTONIC band gap structures ,WAVEGUIDES ,TITANIUM dioxide ,LINE defects (Crystallography) - Abstract
The conduction characteristics of a L-shaped waveguide in a diamond structure photonic crystal is investigated in this paper. The waveguides were fabricated with titanium dioxide ceramic via 3-D printing and sintering. The effects of the position and size of line defects on the transmission characteristics are first simulated using a finite-difference time-domain method. The simulated results show that, when the length of the rectangular defect equals the lattice constant, multiple extended modes are generated. When the centers of the single unit cell of the diamond structure and the line defect waveguide coincide, higher transmission efficiency in the line defect can be achieved. In addition, the corner of the L-shaped waveguide was optimized to reduce reflection loss at the turning point using the arc transition of the large diameter. Our experimental results indicate that L-shaped waveguides with an optimized photonic band gap structure and high-K materials can produce a pass-band between 13.8 GHz and 14.4 GHz and increase transmission efficiency. The computed results agree with the experimental results. Our results may help the integration of microwave devices in the future and possibly enable new applications of photonic crystals. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
231. Compound Ammonium Glycyrrhizin Protects Hepatocytes from Injury Induced by Lipopolysaccharide/Florfenicol through a Mitochondrial Pathway.
- Author
-
Wenyang Li, Ying Li, Xiangyuan Jiang, Xiaohui Li, and Zugong Yu
- Subjects
LIPOPOLYSACCHARIDES ,LIVER cells ,AMMONIUM sulfate ,APOPTOSIS ,FLOW cytometry - Abstract
Florfenicol (FFC), a widely used drug for chicken diseases, can aggravate lipopolysaccharide (LPS) damage to the liver. For this condition, natural or synthetic products displaying strong antioxidant capacity are expected to prevent LPS/FFC from inducing liver injury, so in our study, the compound ammonium glycyrrhizin (CAG) is used as the protective drug to decrease the injury to liver. The research aims to illustrate the underlying mechanism of combining LPS with FFC-induced liver injury and the protective role of CAG by using primary chicken hepatocytes as an in vitro model. The results show that LPS/FFC induced cell apoptosis and CAG protected hepatocytes from injury. The permeability of the cell membrane is elevated by LPS/FFC, leading to the efflux of enzymes (ALT, AST). Flow cytometry analysis indicates that LPS/FFC treatment increased the apoptosis rate significantly. Furthermore, with the up-regulation of apoptosis genes bax, cytochrome c and the down-regulation of bcl-2, caspase-3 and caspase-9 are activated at the gene level. LPS/FFC-induced mitochondrial damage is accompanied by a significant decrease in mitochondrial membrane potential (MMP) and severe mitochondrial damage. However, CAG improves the situation for the purpose of protecting the liver. In conclusion, it is speculated that LPS/FFC induces severe liver injury through apoptosis and the CAG protects hepatocytes from injury via the mitochondria-mediated apoptosis pathway. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
232. Exosome-encapsulated microRNA-23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage.
- Author
-
Kumata, Yoshimasa, Iinuma, Hisae, Suzuki, Yusuke, Tsukahara, Daisuke, Midorikawa, Hironori, Igarashi, Yuichi, Soeda, Naruyoshi, Kiyokawa, Takashi, Horikawa, Masahiro, and Fukushima, Ryoji
- Published
- 2018
- Full Text
- View/download PDF
233. Decreased levels of serum exosomal miR‐638 predict poor prognosis in hepatocellular carcinoma.
- Author
-
Shi, Min, Jiang, Ye, Yang, Lu, Yan, Shushan, Wang, Yu‐Gang, and Lu, Xiao‐Jie
- Published
- 2018
- Full Text
- View/download PDF
234. Exosome‑encapsulated microRNA‑223‑3p as a minimally invasive biomarker for the early detection of invasive breast cancer.
- Author
-
Yoshikawa, Mio, Iinuma, Hisae, Umemoto, Yasuko, Yanagisawa, Takako, Matsumoto, Akiko, and Jinno, Hiromitsu
- Subjects
BREAST cancer ,CARCINOMA in situ ,EXOSOMES ,EARLY detection of cancer ,TUMOR markers - Abstract
Patients diagnosed preoperatively with ductal carcinoma in situ (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome‑encapsulated microRNA‑223‑3p (miR‑223‑3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR‑223‑3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR‑223‑3p levels of IDC patients demonstrated the highest fold‑change compared with those in the DCIS patients and healthy controls. The potential of miR‑223‑3p for cell proliferation and cell invasion were examined in vitro using MCF7 cells transfected with the miR‑223‑3p gene. MCF7 cells transfected with the miR‑223‑3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR‑223‑3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR‑223‑3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR‑223‑3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR‑223‑3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR‑223‑3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome‑encapsulated miR‑223‑3p level was significantly associated with the malignancy of breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
235. Exosomes: Definition, Role in Tumor Development and Clinical Implications.
- Author
-
Carretero-González, Alberto, Otero, Irene, Carril-Ajuria, Lucía, de Velasco, Guillermo, and Manso, Luis
- Abstract
Exosomes are microvesicles released by cells in both physiological and pathological situations. They are surrounded by a lipid bilayer with proteins derived from the origin cell, and contain a variety of molecules, such as nucleic acids. They represent an emerging mechanism of intercellular communication, and they play an important role in the pathogenesis of cancer, stimulating proliferation and aggressiveness of cancer cells, inducing a microenvironment favorable to tumor development and controlling immune responses. Because of the growing understanding of the potential implications of extracellular vesicles in the development of malignancies, research on exosomes, and its role as a diagnostic and therapeutic tool, constitutes nowadays a very exciting and promising field. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
236. Compound K Inhibits the Lipopolysaccharide-Induced Inflammatory Responses in Raw 264.7 Cell Line and Zebrafish.
- Author
-
Ryu, Su-Jung, Choi, Jia, Lee, Jong-Seok, Choi, Hyeon-Son, Yoon, Kye-Yoon, Hwang, Ji-Hyun, Kim, Kui Jin, and Lee, Boo-Yong
- Subjects
LIPOPOLYSACCHARIDES ,LOGPERCH ,NITRIC oxide - Abstract
Compound K, a major metabolite of ginsenosides Rb1, which is produced by human intestinal bacteria after oral administration, is one of the main pharmacologic compounds found in ginseng. In our previous study, we demonstrated that compound K inhibited the production of nitric oxide (NO) and prostaglandin E2 in lipopolysaccharide (LPS)-treated RAW264.7 cells. However, the mechanisms by which compound K may be effective against inflammation remain unknown. In the present study, compound K significantly inhibited LPS-induced NO production by suppression of inducible NO synthase (iNOS) in LPS-treated RAW264.7 cells. Compound K also inhibited LPS-induced cyclooxygenase-2 (COX-2) expression at both the mRNA and protein levels. It effectively suppressed both the release and mRNA expression levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-6. The anti-inflammatory effects of compound K appeared to occur via inhibition of LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) and inhibition of NF-κB translocation from the cytosol to the nucleus by suppressing phosphorylation of inhibitory kappa B-α (IκB-α). Furthermore, we showed that compound K inhibited LPS-induced NO generation in an experimental zebrafish model. Considering these results, compound K could potentially be developed as a natural anti-inflammatory agent. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
237. Extracellular Vesicles: A New Perspective in Tumor Therapy.
- Author
-
Sun, Yan-Zi, Ruan, Jun-Shan, Jiang, Zong-Sheng, Wang, Ling, and Wang, Shao-Ming
- Subjects
TUMOR prevention ,IMMUNOTHERAPY ,METASTASIS ,ONCOLOGY ,TUMORS ,PARTICULATE matter - Abstract
In recent years, the study of extracellular vesicles has been booming across various industries. Extracellular vesicles are considered one of the most important physiological endogenous carriers for the specific delivery of molecular information (nucleonic acid, cytokines, enzymes, etc.) between cells. It has been discovered that they perform a critical role in promoting tumor cell growth, proliferation, tumor cell invasion, and metastatic ability and regulating the tumor microenvironment to promote tumor cell communication and metastasis. In this review, we will discuss (1) the mechanism of extracellular vesicles generation, (2) their role in tumorigenesis and cancer progression (cell growth and proliferation, tumor microenvironment, epithelial-mesenchymal transition (EMT), invasion, and metastasis), (3) the role of extracellular vesicles in immune therapy, (4) extracellular vesicles targeting in tumor therapy, and (5) the role of extracellular vesicles as biomarkers. It is our hope that better knowledge and understanding of the extracellular vesicles will offer a wider range of effective therapeutic targets for experimental tumor research. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
238. Exosomes as diagnostic biomarkers in cancer.
- Author
-
Kim, Jung-Hee, Kim, Eunjoo, and Lee, Mi Young
- Abstract
Purpose of review: Exosomes are extracellular vesicles of 30-150 nm diameter, secreted from nearly all mammalian cells through fusion of multivesicular bodies with the plasma membrane. Owing to the differences in the properties of exosomes and microvesicles released through outward budding of the plasma membrane, exosomes have recently received increasing interest. This review discusses the current status of exosome research for diagnostic biomarkers in cancers. The scope of information that can be acquired from exosomal contents potentially include tumour progression, detection of metastasis, and possible chemotherapeutic resistance, which can facilitate clinical decisions in precision medicine.Recent findings: Exosomes protect molecular components including miRNAs and proteins from enzymatic degradation during circulation and serve as stable cargo for them. miRNAs transferred by exosomes have emerged as novel regulators of cellular function in various types of cancers. In addition, exosomes contain numerous plasma membrane and cytosolic proteins and exosome- specific proteins. However, many of the experiments are limited in their methods for the isolation and purification of exosomes. Nevertheless, the physiological and pathological significance of the role of exosomes in miRNA- or protein-based cell-to-cell or tissue-to-tissue communication has been highlighted. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
239. Usefulness of Plasma Exosomal MicroRNA-451a as a Noninvasive Biomarker for Early Prediction of Recurrence and Prognosis of Non-Small Cell Lung Cancer.
- Author
-
Kanaoka, Rie, Iinuma, Hisae, Dejima, Hitoshi, Sakai, Takashi, Uehara, Hirofumi, Matsutani, Noriyuki, and Kawamura, Masafumi
- Subjects
LUNG cancer prognosis ,BIOMARKERS ,CANCER relapse ,MULTIVARIATE analysis ,RNA ,SURVIVAL ,PROPORTIONAL hazards models ,MICROARRAY technology ,EXOSOMES - Abstract
The aim of this study was to clarify the usefulness of plasma exosomal microRNA-451a (miR-451a) as a novel biomarker for the early prediction of recurrence and prognosis in non-small cell lung cancer (NSCLC) patients after curative resection.Objectives: Before surgery, plasma samples were collected and exosomal microRNA (miRNA) levels were evaluated. We first profiled specific exosomal miRNAs related to recurrence in 6 NSCLC patients with stage IA cancer by miRNA microarray. We then validated the usefulness of selected miRNAs as biomarkers using the other 285 NSCLC patients.Methods: Plasma exosomal miR-451a showed the highest upregulation in the NSCLC patients with recurrence in the miRNA microarray analysis. A significant positive correlation was demonstrated between exosomal miR-451a levels and NSCLC tissue miR-451a levels. Exosomal miR-451a showed a significant association with lymph node metastasis, vascular invasion, and stage. In stage I, II, or III patients, the overall survival (OS) and disease-free survival (DFS) rates among the high-exosomal-miR-451a patients were significantly worse than those among the low-exosomal-miR-451a patients. In Cox multivariate analysis, exosomal miR-451a showed significance for OS and DFS.Results: Plasma exosomal miR-451a might serve as a reliable biomarker for the prediction of recurrence and prognosis in NSCLC patients with stage I, II, or III cancer. [ABSTRACT FROM AUTHOR]Conclusion: - Published
- 2018
- Full Text
- View/download PDF
240. Glutathionylation: a regulatory role of glutathione in physiological processes.
- Author
-
Dominko, Kristina and Đikić, Domagoj
- Published
- 2018
- Full Text
- View/download PDF
241. Altered Circadian Timing System-Mediated Non-Dipping Pattern of Blood Pressure and Associated Cardiovascular Disorders in Metabolic and Kidney Diseases.
- Author
-
Rahman, Asadur, Hasan, Arif Ul, Nishiyama, Akira, and Kobori, Hiroyuki
- Subjects
BLOOD pressure ,CARDIOVASCULAR diseases risk factors ,METABOLIC disorders ,KIDNEY diseases ,CIRCADIAN rhythms ,SUPRACHIASMATIC nucleus ,NEUROENDOCRINE system - Abstract
The morning surge in blood pressure (BP) coincides with increased cardiovascular (CV) events. This strongly suggests that an altered circadian rhythm of BP plays a crucial role in the development of CV disease (CVD). A disrupted circadian rhythm of BP, such as the non-dipping type of hypertension (i.e., absence of nocturnal BP decline), is frequently observed in metabolic disorders and chronic kidney disease (CKD). The circadian timing system, controlled by the central clock in the suprachiasmatic nucleus of the hypothalamus and/or by peripheral clocks in the heart, vasculature, and kidneys, modulates the 24 h oscillation of BP. However, little information is available regarding the molecular and cellular mechanisms of an altered circadian timing system-mediated disrupted dipping pattern of BP in metabolic disorders and CKD that can lead to the development of CV events. A more thorough understanding of this pathogenesis could provide novel therapeutic strategies for the management of CVD. This short review will address our and others’ recent findings on the molecular mechanisms that may affect the dipping pattern of BP in metabolic dysfunction and kidney disease and its association with CV disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
242. Deep Venous Thrombosis Of The Lower Extremity
- Author
-
Schick MA and Pacifico L
- Abstract
Deep Vein Thrombosis (DVT) is a major cause of morbidity and mortality, and sequelae range from venous stasis to pulmonary embolism (PE). DVT occurs when a thrombus (thrombus) forms in one of the deep veins of the body., (Copyright © 2022, StatPearls Publishing LLC.)
- Published
- 2022
243. Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots (Gancao) after dosing LianhuaQingwen capsule.
- Author
-
Lan XF, Olaleye OE, Lu JL, Yang W, Du FF, Yang JL, Cheng C, Shi YH, Wang FQ, Zeng XS, Tian NN, Liao PW, Yu X, Xu F, Li YF, Wang HT, Zhang NX, Jia WW, and Li C
- Subjects
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 antagonists & inhibitors, 11-beta-Hydroxysteroid Dehydrogenase Type 2 metabolism, Administration, Oral, Animals, Antiviral Agents administration & dosage, Antiviral Agents adverse effects, Biological Availability, Biotransformation, Capsules, Drugs, Chinese Herbal administration & dosage, Drugs, Chinese Herbal adverse effects, Female, Glycyrrhiza adverse effects, HEK293 Cells, Humans, Liddle Syndrome chemically induced, Liddle Syndrome enzymology, Male, Patient Safety, Phytochemicals administration & dosage, Phytochemicals adverse effects, Rats, Sprague-Dawley, Risk Assessment, Rats, Antiviral Agents pharmacokinetics, Drugs, Chinese Herbal pharmacokinetics, Phytochemicals pharmacokinetics, COVID-19 Drug Treatment
- Abstract
LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11β-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11β-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 μmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2
D ; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D . Circulating 8 and M2D , having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11β-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D . This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)- Published
- 2021
- Full Text
- View/download PDF
244. [Extracellular vesicles-associated biomarkers: Opportunities and challenges in cardiovascular diseases and cancer].
- Author
-
Bonifay A, Ghayad S, Lacroix R, and Dignat-George F
- Subjects
- Biomarkers, Humans, Cardiovascular Diseases diagnosis, Extracellular Vesicles, Neoplasms diagnosis, Neoplasms therapy
- Abstract
Cardiovascular diseases and cancer are the leading causes of mortality and morbidity in the world. The search for pertinent biomarkers for risk stratification and treatment monitoring is a challenge. Rapid advances in the identification of the molecular and functional content of extracellular vesicles (EV) and ongoing progress in developing highly sensitive methodologies, identify EV as promising biomarkers easily accessible in liquid biopsies. Thanks to robust and sensitive methodologies, the measurability of biological targets on EV allows to define vesicular biomarkers pertinent for disease management. Adaptation of the pre-analytical and analytical steps to each EV-associated biomarker, technological improvement and standardization efforts driven by scientific societies are essential prerequisites to accelerate the transfer of these EV-associated biomarkers to the clinics and to support the development of personalized medicine., (© 2021 médecine/sciences – Inserm.)
- Published
- 2021
- Full Text
- View/download PDF
245. Characterization and selective incorporation of small non-coding RNAs in non-small cell lung cancer extracellular vesicles.
- Author
-
Li, Chuang, Qin, Fang, Hu, Fen, Xu, Hui, Sun, Guihong, Han, Guang, Wang, Tao, and Guo, Mingxiong
- Subjects
RNA ,LIPIDS ,MICRORNA - Abstract
Background: Extracellular vesicles (EVs) play important roles in intercellular communication through the delivery of their cargoes, which include proteins, lipids, and RNAs. Increasingly, multiple studies have reported the association between EV small non-coding RNAs and cancer, due to their regulatory functions in gene expression. Hence, analysis of the features of small non-coding RNA expression and their incorporation into EVs is important for cancer research. Results: We performed deep sequencing to investigate the expression of small RNAs in plasma EVs from lung adenocarcinoma (ADC) patients, lung squamous cell carcinoma (SQCC) patients, and healthy controls. Then, eighteen differently expressed miRNAs in plasma EVs was validated by QRT-PCR. The small RNA expression profiles of plasma EVs were different among lung ADC, SQCC patients, and healthy controls. And many small RNAs, including 5' YRNA hY4-derived fragments, miR-451a, miR-122-5p, miR-20a-5p, miR-20b-5p, miR-30b-5p, and miR-665, were significantly upregulated in non-small cell lung cancer (NSCLC) EVs. And the cell viability assays indicated that hY4-derived fragments inhibited the proliferation of lung cancer cell A549. By comparing the cellular and EV expression levels of six miRNAs in NSCLC cells, we found that miR-451a and miR-122-5p were significantly downregulated in NSCLC cell lysates, while significantly upregulated in NSCLC EVs. Conclusions: The differently expressed EV small RNAs may serve as potential circulating biomarkers for the diagnosis of NSCLC. Particularly, YRNA hY4-derived fragments can serve as a novel class of biomarkers, which function as tumor suppressors in NSCLC. Additionally, miR-451a and miR-122-5p may be sorted into NSCLC EVs in a selective manner. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
246. Modulating secreted components of tumor microenvironment: A masterstroke in tumor therapeutics.
- Author
-
Patel, Himadri, Nilendu, Pritish, Jahagirdar, Devashree, Pal, Jayanta K., and Sharma, Nilesh Kumar
- Abstract
The microenvironment in which cancer resides plays an important role in regulating cancer survival, progression, malignancy and drug resistance. Tumor microenvironment (TME) consists of heterogeneous number and types of cellular and non-cellular components that vary in relation to tumor phenotype and genotype. In recent, non-cellular secreted components of microenvironmental heterogeneity have been suggested to contain various growth factors, cytokines, RNA, DNA, metabolites, structural matrix and matricellular proteins. These non-cellular components have been indicated to orchestrate numerous ways to support cancer survival and progression by providing metabolites, energy, growth signals, evading immune surveillance, drug resistance environment, metastatic and angiogenesis cues. Thus, switching action from pro-cancer to anti-cancer activities of these secreted components of TME has been considered as a new avenue in cancer therapeutics and drug resistance. In this report, we summarize the recent pre-clinical and clinical evidences to emphasize the importance of non-cellular components of TME in achieving precision therapeutics and biomarker study. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
247. Exosome-mediated delivery of MALAT1 induces cell proliferation in breast cancer.
- Author
-
Zhang, Ping, Zhou, Hongxing, Lu, Kefeng, Lu, Yunou, Wang, Yan, and Feng, Tongbao
- Subjects
EXOSOMES ,BREAST cancer treatment ,CANCER cell proliferation ,CELL communication ,CANCER invasiveness ,NON-coding RNA - Abstract
Background: Breast cancer is the most common cancer in women worldwide. Cancer-secreted exosomes have recently been recognized as important mediators of intercellular communication. The aim of this study was to determine the role of exosomal long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in breast cancer progression. Materials and methods: Breast cancer specimens were obtained with informed consent from patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect MALAT1 expression, and cellular proliferation was measured using cell counting kit-8 (CCK-8) assay. Results: MALAT1 was highly expressed in breast cancer tissues and associated with disease progression. Breast cancer exosomes promoted cell proliferation and exosome-mediated MALAT1 to induce cell proliferation. Conclusion: These findings indicated that exosomal MALAT1 could regulate cancer progression and represent a novel strategy for overcoming breast cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
248. The small vesicular culprits: the investigation of extracellular vesicles as new targets for cancer treatment.
- Author
-
Urabe, Fumihiko, Kosaka, Nobuyoshi, Yoshioka, Yusuke, Egawa, Shin, and Ochiya, Takahiro
- Subjects
MICRORNA ,NON-coding RNA ,MESSENGER RNA ,BIOLOGICAL fluid dynamics ,FLUID dynamics - Abstract
Extracellular vesicles (EVs) are membranous vesicles released from almost all type of cells including cancer cells. EVs transfer their components, such as microRNAs (miRNAs), messenger RNAs, lipids and proteins, from one cell to another, affecting the target cells. Emerging evidence suggests that reciprocal interactions between cancer cells and the cells in their microenvironment via EVs drive disease progression and therapy resistance. Therefore, understanding the roles of EVs in cancer biology will provide us with new opportunities to treat patients. EVs are also useful for monitoring disease processes. EVs have been found in many kinds of biological fluids such as blood, urine, saliva and semen. Because of their accessibility, EVs offer ease of collection with minimal discomfort to patients and are preferred for serial collection. In addition, they reflect and carry dynamic changes in disease, allowing us to access crucial molecular information about the disease status. Therefore, EVs hold great possibility as clinically useful biomarkers to provide multiple non-invasive snapshots of primary and metastatic tumors. In this review, we summarize current knowledge of miRNAs in EVs in cancer biology and as biomarkers. Furthermore, we discuss the potential of miRNAs in EVs for clinical application. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
249. The Photocatalytic Application of Semiconductor Stibnite Nanostructure Synthesized via a Simple Microwave-Assisted Approach in Propylene Glycol for Degradation of Dye Pollutants and its Optical Property.
- Author
-
Saksornchai, Eksuree, Kavinchan, Jutarat, Thongtem, Somchai, and Thongtem, Titipun
- Subjects
STIBNITE ,PHOTOCATALYSIS ,PROPYLENE glycols ,NANOSTRUCTURES ,DYES & dyeing - Abstract
Stibnite (SbS) semiconducting material was successfully synthesized by a rapid and facile microwave route using antimony chloride (SbCl) and sodiumthiosulfate (NaSO) dissolved in propylene glycol (PG) containing different hydroxyethyl cellulose (HEC) masses. The phase identification, morphology, and elemental composition of products were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), field- emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) spectroscopy, and Fourier transform infrared spectroscopy (FTIR). The results revealed the orthorhombic phase of SbS single crystal-forming sheaf-like nanostructure, and a possible formation mechanism was proposed and discussed. Its direct band gap calculated from UV-visible absorption is 1.60 eV. In this research, the photocatalytic activities of SbS nanostructure were investigated through the degradation of methyl orange (MO) and methylene blue (MB) under visible light irradiation. The as-obtained 0.30 g HEC-added solution (0.3 HEC-SbS) photocatalyst exhibited better photocatalytic activity than the other products, which degraded 91% of MO within 300 min and 90% of MB within 240 min under the Xe-lamp irradiation. The first-order plot was fitted with this experiment which the rate constant ( k) of 0.3 HEC-SbS for MO and MB degradation are 0.0085 and 0.0098 min, respectively. Therefore, the new experience with a novel and simple synthetic procedure of SbS photocatalyst that exhibits the characteristics of a highly effective photocatalyst under visible light irradiation was discovered. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
250. Distribution and function of voltage-gated sodium channels in the nervous system.
- Author
-
Wang, Jun, Ou, Shao-Wu, and Wang, Yun-Jie
- Published
- 2017
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.