The prevalence and function of CD4+CXCR5+Foxp3+ follicular regulatory T cells in diffuse large B cell lymphoma

Publication date: August 2018
Source:International Immunopharmacology, Volume 61
Author(s): Zhanshan Cha, Haihui Gu, Yan Zang, Zi Wang, Jinqi Li, Weihua Huang, Aihua Qin, Lishuang Zhu, Xiaohua Tu, Ning Cheng, Haihan Song, Baohua Qian
CD4⁺CXCR5⁺Foxp3⁺ follicular regulatory T (Tfr) cells possess critical roles in suppressing the germinal center reaction, B cell activation, and follicular helper T cell (Tfh) cytokine secretion. Since diffuse large B cell lymphoma (DLBCL) can arise from B cells undergoing germinal center reaction and/or differentiation, we hypothesized that Tfr cells might be involved in DLBCL. In the present study, we recruited thirty-five DLBCL patients and twenty-five healthy controls. Data showed that DLBCL patients presented an enrichment of circulating CD4⁺CXCR5⁺Foxp3⁺ Tfr cells compared to controls. In the primary tumor isolated from enlarged lymph nodes, Tfr cells made up of roughly 3% to 16% of infiltrating T cells. Higher levels of tumor-infiltrating Tfr cells were observed in patients with less advanced DLBCL stages, and in patients that stayed in remission 24 months after the initial R-CHOP treatment. High BCL6 and high FOXP3 expression was observed in Tfr cells ex vivo. After anti-CD3/CD28 and IL-2 stimulation, the Tfr cells more closely resembled Treg cells and presented high IL10 and TGFB1 expression. CD4⁺CD25⁺CXCR5⁺ Tfr cells and CD4⁺CD25⁺CXCR5⁻ non-Tfr Treg cells could suppress CD4⁺CD25⁻ Tconv cell and CD8⁺ T cell proliferation with similar capacity. However, Tfr cells were less capable of suppressing IFNG expression than Treg cells, and although both cell types supported CD19⁺ tumor cell proliferation, Tfr cells were less supportive than the non-Tfr Treg cells. Overall, this study suggested that Tfr cells were involved in intratumoral immunity, were likely beneficial to DLBCL patients, and were functionally distinctive from non-Tfr Treg cells. The distribution pattern and the prognostic value of Tfr cells in DLBCL should be examined in further studies.



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Impaired planning in patients with obsessive-compulsive disorder and unaffected first-degree relatives: Evidence for a cognitive endophenotype

Publication date: Available online 1 June 2018
Source:Journal of Anxiety Disorders
Author(s): Katharina Bey, Christian Kaufmann, Leonhard Lennertz, Anja Riesel, Julia Klawohn, Stephan Heinzel, Rosa Grützmann, Norbert Kathmann, Michael Wagner
Patients with obsessive-compulsive disorder (OCD) show deficient planning capacity in the Tower of London (TOL) problem solving task. Preliminary evidence for similar deficits in unaffected first-degree relatives suggests that impaired planning may constitute an endophenotype of OCD. However, results on this issue are inconsistent, possibly owing to small sample sizes and variability in problem structure across TOL tasks. Here, we adopted a computerized version of the TOL task featuring a 2 × 2 factorial design (high/low search depth × full/partial tower goal state) and examined a well-characterized sample of n = 72 OCD patients, n = 76 unaffected first-degree relatives and n = 102 healthy comparison subjects. Both OCD patients and relatives exhibited significantly less accurate problem solving than controls. Search depth, goal hierarchy, or the number of minimum moves did not moderate these group differences. Medication, OCD symptoms, and depressive comorbidity did not affect TOL performance in patients, suggesting a state-independent effect. In conclusion, we confirmed that OCD patients as well as unaffected first-degree relatives show deficient TOL performance across a range of task conditions, strongly supporting the role of impaired planning as an endophenotype of OCD, and contributing to the growing evidence for fronto-striatal dysfunctions in OCD.



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Cuba Si. Cancer No.

Publication date: Available online 1 June 2018
Source:Seminars in Oncology
Author(s): Antonio Tito Fojo
The current double issue of Seminars in Oncology brings 11 contributions from the Center for Genetic Engineering and Biotechnology, the Center of Molecular Immunology, and the Center of Medical and Surgical Research in Cuba. Having left Cuba in 1960, my interest in these submissions admittedly could go beyond the merely scientific. But others, I guarantee, will find EVERY article remarkably interesting and informative. In an era where the overwhelming majority of therapies in development as well as clinical trials being conducted are following well-traveled paths that bring us limited new information, the investigators from Cuba present us with rational, novel approaches to drug development. This is truly out of the box thinking, crafted in a country where resource limitations have clearly incentivized novel approaches. Their basic science is solid and their clinical validation is either mature or a work very much in progress. Cancer, one realizes reading these contributions, is a scourge across the world. Enjoy the refreshing and exciting approach of these investigators!!!



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Editorial Board

Publication date: July 2018
Source:Clinical Immunology, Volume 192





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Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements

Publication date: Available online 1 June 2018
Source:Journal of Genetics and Genomics
Author(s): Hongmei Ke, Zhi Feng, Min Liu, Tianhui Sun, Jianli Dai, Mengqi Ma, Lu-Ping Liu, Jian-Quan Ni, José Carlos Pastor-Pareja
Collagens are large secreted trimeric proteins making up most of the animal extracellular matrix. Secretion of collagen has been a focus of interest for cell biologists in recent years because collagen trimers are too large and rigid to fit into the COPII vesicles mediating transport from the endoplasmic reticulum (ER) to the Golgi. Collagen-specific mechanisms to create enlarged ER-to-Golgi transport carriers have been postulated, including cargo loading by conserved ER exit site (ERES) protein Tango1. Here, we report an RNAi screening for genes involved in collagen secretion in Drosophila. In this screening, we examined distribution of GFP-tagged Collagen IV in live animals and found 88 gene hits for which the knockdown produced intracellular accumulation of Collagen IV in the fat body, the main source of matrix proteins in the larva. Among these hits, only two affected collagen secretion specifically: PH4αEFB and Plod, encoding enzymes known to mediate posttranslational modification of collagen in the ER. Every other intracellular accumulation hit affected general secretion, consistent with the notion that secretion of collagen does not use a specific mode of vesicular transport, but the general secretory pathway. Included in our hits are many known players in the eukaryotic secretory machinery, like COPII and COPI components, SNAREs and Rab-GTPase regulators. Our further analysis of the involvement of Rab-GTPases in secretion shows that Rab1, Rab2 and RabX3, are all required at ERES, each of them differentially affecting ERES morphology. Abolishing activity of all three by Rep knockdown, in contrast, led to uncoupling of ERES and Golgi. We additionally present a characterization of a screening hit we named trabuco (tbc), encoding an ERES-localized TBC domain-containing Rab-GAP. Finally, we discuss the success of our screening in identifying secretory pathway genes in comparison to two previous secretion screenings in Drosophila S2 cells.



https://ift.tt/2HbBYMf

Alcohol consequences, not quantity, predict major depression onset among first-year female college students

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Samantha R. Rosenthal, Melissa A. Clark, Brandon D.L. Marshall, Stephen L. Buka, Kate B. Carey, Robyn L. Shepardson, Michael P. Carey
Alcohol use and its consequences have often been associated with depression, particularly among female college students. Interpretation of this association has been challenging due to potential reverse causation. The current study sought to clarify the temporality of these relationships. We examined: (1) the association between alcohol consumption and onset depression among female college students, and (2) the association between drinking consequences and onset depression among drinkers only. We used a prospective longitudinal design. Participants were first-year female college students who completed a baseline survey at study entry, and monthly assessments of alcohol consumption, drinking consequences, and depression symptoms. Cox proportional hazards regression with time-varying covariates were constructed among the full sample (N = 412) and the drinkers only sample (N = 335). Adjusted hazard ratios accounted for known risk factors for depression such as race/ethnicity, academic challenge, not getting along with one's roommate, sexual victimization prior to college, marijuana use, and socioeconomic status. For each additional average drink per week, adjusting for all covariates, there was no (95% CI: -4%, +4%) increased risk of onset depression. For each additional alcohol consequence, adjusting for all covariates, there was a 19% (95% CI: 5%, 34%) increased risk of onset depression. This significant relationship remained after adjusting for quantity of alcohol consumption. Quantity of alcohol consumed did not predict incident depression. However, experiencing alcohol consequences, regardless of consumption, did increase the risk of incident depression. College substance use and mental health interventions should aim to reduce not only alcohol consumption, but also alcohol-related consequences.



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Spanish adaptation of the Gambling Motives Questionnaire (GMQ): Validation in adult pathological gamblers and relationship with anxious-depressive symptomatology and perceived stress

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Paula Jauregui, Ana Estevez, Jaione Onaindia
Gambling has been found to be related to different motives, such as enhancement, social, and behavioral and emotional coping. The most used instrument in this field is the Gambling Motives Questionnaire (GMQ; Stewart & Zack, 2008), which has not been validated in clinical samples. This study aimed to validate a Spanish version of the GMQ in a sample of adult pathological gamblers and to analyze its relationship with pathological gambling, anxiety, depression, and perceived stress. A sample of 164 gamblers was recruited from centers for the treatment of pathological gambling. The three-factor structure (enhancement, social, and coping motives) of the GMQ was validated through exploratory and confirmatory factorial analyses, and its convergent validity was proven. Gambling motives correlated with pathological gambling, anxiety, depression, and perceived stress. Enhancement motives predicted pathological gambling, while controlling for the effect of anxiety, depression, and perceived stress. These results are relevant for clinical evaluation and intervention with adult pathological gamblers.



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Exploring the role of positive metacognitions in explaining the association between the fear of missing out and social media addiction

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Silvia Casale, Laura Rugai, Giulia Fioravanti
The present study aimed to investigate: a) the contribution of the fear of missing out (FoMO) in explaining social media problematic use taking also into account the fear of being negatively evaluated and the perception of low self-presentational skills; b) the mediating role of positive metacognitions about social media use in the relationship between FoMO and social media problematic use. A sample of 579 undergraduates was recruited (54.6% F; mean age = 22.39 ± 2.82). Among females, the assessed structural model produced good fit to the data [χ² = 101.11, df = 52, p < .001; RMSEA = 0.05 (90% C.I. =0.04–0.07), CFI = 0.98, SRMR = 0.05]. FoMO and self-presentational skills were both directly and indirectly associated with social media problematic use through the mediation of positive metacognitions. Fear of negative evaluation was not associated with social media problematic use. Among males, FoMO had both a direct and an indirect effect on social media problematic use mediated by positive metacognitions. The fear of negative evaluation and self-presentational skills were only indirectly associated with social media problematic use through positive metacognitions. The assessed structural model produced good fit to the data [χ² = 98.02, df = 55, p < .001; RMSEA = 0.05 (90% C.I. =0.04–0.07), CFI = 0.98, SRMR = 0.07]. The present study confirmed the role of FoMO with respect to social media problematic use and highlighted for the first time the mediating role of positive metacognitions in this relationship.



https://ift.tt/2LbxirZ

Photo-excitable hybrid nanocomposites for image-guided photo/TRAIL synergistic cancer therapy

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Gan Lin, Yang Zhang, Congqing Zhu, Chengchao Chu, Yesi Shi, Xin Pang, En Ren, Yayun Wu, Peng Mi, Haiping Xia, Xiaoyuan Chen, Gang Liu
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in cancer cells without toxicity to normal cells. However, the efficiency is greatly limited by its short half-life and wild resistance in various cancer cells. In this study, we reported a micellar hybrid nanoparticle to carry TRAIL ligand (denoted as IPN@TRAIL) for a novel photo-excited TRAIL therapy. These IPN@TRAIL offered increased TRAIL stability, prolonged half-life and enhanced tumor accumulation, monitored by dual mode imaging. Furthermore, IPN@TRAIL nanocomposites enhanced wrapped TRAIL therapeutic efficiency greatly towards resistant cancer cells by TRAIL nanovectorization. More importantly, when upon external laser, these nanocomposites not only triggered tumor photothermal therapy (PTT), but also upregulated the expression of death receptors (DR4 and DR5), resulting in a greater apoptosis mediated by co-delivered TRAIL ligand. Such photo/TRAIL synergistic effect showed its great killing effects in a controllable manner on TRAIL-resistant A549 tumor model bearing mice. Finally, these nanocomposites exhibited rapid clearance without obvious systemic toxicity. All these features rendered our nanocomposites a promising theranostic platform in cancer therapy.



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Blood-brain barrier shuttle peptides enhance AAV transduction in the brain after systemic administration

Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Xintao Zhang, Ting He, Zheng Chai, R. Jude Samulski, Chengwen Li
The adeno-associated virus (AAV) vector has been used in preclinical and clinical trials of gene therapy for central nervous system (CNS) diseases. One of the biggest challenges of effectively delivering AAV to the brain is to surmount the blood-brain barrier (BBB). Herein, we identified several potential BBB shuttle peptides that significantly enhanced AAV8 transduction in the brain after a systemic administration, the best of which was the THR peptide. The enhancement of AAV8 brain transduction by THR is dose-dependent, and neurons are the primary THR targets. Mechanism studies revealed that THR directly bound to the AAV8 virion, increasing its ability to cross the endothelial cell barrier. Further experiments showed that binding of THR to the AAV virion did not interfere with AAV8 infection biology, and that THR competitively blocked transferrin from binding to AAV8. Taken together, our results demonstrate, for the first time, that BBB shuttle peptides are able to directly interact with AAV and increase the ability of the AAV vectors to cross the BBB for transduction enhancement in the brain. These results will shed important light on the potential applications of BBB shuttle peptides for enhancing brain transduction with systemic administration of AAV vectors.

Graphical abstract

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Editorial Board

Publication date: August 2018
Source:Biomaterials, Volume 175





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Scholar : International Journal of Molecular Medicine - Volume:42 Number:2

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TABLE OF CONTENTS August-2018 Volume 42 Issue 2

Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review) Igor Bryukhovetskiy, Arina Ponomarenko, Irina Lyakhova, Sergey Zaitsev, Yulia Zayats, Maria Korneyko, Marina Eliseikina, Polina Mischenko, Valerie Shevchenko, Hari Shanker Sharma, Aruna Sharma, Yuri Khotimchenko View Abstract ❯
CTLA‑4 interferes with the HBV‑specific T cell immune response (Review) Hui Cao, Ruiwen Zhang, Wei Zhang View Abstract ❯
Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review) Masaru Katoh View Abstract ❯
Comparative whole genome transcriptome analysis and fenugreek leaf extract modulation on cadmium‑induced toxicity in liver cells Caroline Odewumi, Lekan M. Latinwo, Roy Leonard Lyles, Veera L.D. Badisa, Cobb‑Abdullah Ahkinyala, Marijo Kent‑First View Abstract ❯
Physcion 8‑O‑β‑glucopyranoside extracted from Polygonum cuspidatum exhibits anti‑proliferative and anti‑inflammatory effects on MH7A rheumatoid arthritis‑derived fibroblast‑like synoviocytes through the TGF‑β/MAPK pathway Qin Geng, Qiaofeng Wei, Shujun Wang, Huili Qi, Qin Zhu, Xia Liu, Xiaojun Shi, Shuyun Wen View Abstract ❯
Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation Yu Liu, Pei‑Hao Wen, Xin‑Xue Zhang, Yang Dai, Qiang He View Abstract ❯
Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2‑mediated STAT3/PI3K/Akt signaling pathway Mei Shen, Xue‑Zhi Zhou, Lei Ye, Qing Yuan, Ce Shi, Pei‑Wen Zhu, Nan Jiang, Ming‑Yang Ma, Qi‑Chen Yang, Yi Shao View Abstract ❯
MicroRNA‑195 inhibits cell proliferation, migration and invasion by targeting defective in cullin neddylation 1 domain containing 1 in cervical cancer Jinyan Zhong, Hui Yuan, Xiangqian Xu, Shoufang Kong View Abstract ❯
Identification and antioxidant activity of synthetic peptides from phycobiliproteins of Pyropia yezoensis Eun‑Young Kim, Youn Hee Choi, Taek‑Jeong Nam View Abstract ❯
High glucose suppresses the viability and proliferation of HTR‑8/SVneo cells through regulation of the miR‑137/PRKAA1/IL‑6 axis Hai‑Yan Peng, Ming‑Qing Li, Hua‑Ping Li View Abstract ❯
Anti‑cancer effects of fisetin on mammary carcinoma cells via regulation of the PI3K/Akt/mTOR pathway: In vitro and in vivo studies Xu Sun, Xueman Ma, Qiwei Li, Yong Yang, Xiaolong Xu, Jiaqi Sun, Mingwei Yu, Kexin Cao, Lin Yang, Guowang Yang, Ganlin Zhang, Xiaomin Wang View Abstract ❯
Expression of annexin II and stromal tenascin C promotes epithelial to mesenchymal transition and correlates with distant metastasis in pancreatic cancer Naoko Yoneura, Shigetsugu Takano, Hideyuki Yoshitomi, Yasuyuki Nakata, Reiri Shimazaki, Shingo Kagawa, Katsunori Furukawa, Tsukasa Takayashiki, Satoshi Kuboki, Masaru Miyazaki, Masayuki Ohtsuka View Abstract ❯
Icariin promotes wound healing by enhancing the migration and proliferation of keratinocytes via the AKT and ERK signaling pathway Bobin Mi, Jing Liu, Guohui Liu, Wu Zhou, Yi Liu, Liangcong Hu, Liming Xiong, Shunan Ye, Yongchao Wu View Abstract ❯
miR‑133b regulates proliferation and apoptosis in high‑glucose‑induced human retinal endothelial cells by targeting ras homolog family member A Jun Yao, Jihong Wang, Yong Yao, Kelei Wang, Qianqian Zhou, Ying Tang View Abstract ❯
Role of Smad3 signaling in the epithelial‑mesenchymal transition of the lens epithelium following injury Fanlan Meng, Jun Li, Xiao Yang, Xiaoyong Yuan, Xin Tang View Abstract ❯
Upregulation of allograft inflammatory factor‑1 expression and secretion by macrophages stimulated with aldosterone promotes renal fibroblasts to a profibrotic phenotype Yushu Li, Xingzhi Wang, Lei Zhang, Xueying Yuan, Jianbing Hao, Jie Ni, Lirong Hao View Abstract ❯
Overexpression of C‑sis inhibits H2O2‑induced Buffalo rat liver cell apoptosis in vitro and alleviates liver injury in a rat model of fulminant hepatic failure Hao Ding, Zhili Wen View Abstract ❯
Correlation between the expression of IL‑18 and deep venous thrombosis Guangdi Li, Rudan Zhou, Xueling Zhao, Riguang Liu, Chuan Ye View Abstract ❯
Role of TGF‑β1 expressed in bone marrow‑derived mesenchymal stem cells in promoting bone formation in a rabbit femoral defect model Bing‑Yin Sun, Bao‑Xiang Zhao, Jie‑Ying Zhu, Zheng‑Ping Sun, Yong‑An Shi, Feng Huang View Abstract ❯
GSK3β‑mediated Ser156 phosphorylation modulates a BH3‑like domain in BCL2L12 during TMZ‑induced apoptosis and autophagy in glioma cells Cheng‑Wei Chu, Ming‑Chang Yang, Chia‑Hua Chou, Wen‑Sheng Huang, Bo‑Xiu Hsiao, Yeng‑Tseng Wang, Shean‑Jaw Chiou, Joon‑Khim Loh, Yi‑Ren Hong View Abstract ❯
Cannabinoid WIN-55,212-2 mesylate inhibits tumor necrosis factor-α-induced expression of nitric oxide synthase in dorsal root ganglion neurons Rong Tan, Lijun Cao View Abstract ❯
Knockdown of TNF‑α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL‑10 expression Zhen Yang, Xue‑Rong Zhang, Qiong Zhao, Sheng‑Lan Wang, Liu‑Lin Xiong, Piao Zhang, Bing Yuan, Zi‑Bing Zhang, Shu‑Yuan Fan, Ting‑Hua Wang, Yun‑Hui Zhang View Abstract ❯
Role of TXNDC5 in tumorigenesis of colorectal cancer cells: In vivo and in vitro evidence Fengbo Tan, Hong Zhu, Xiao He, Nanhui Yu, Xingwen Zhang, Haifan Xu, Haiping Pei View Abstract ❯
Enhanced proliferation and differentiation of HO-1 gene-modified bone marrow-derived mesenchymal stem cells in the acute injured kidney Nanmei Liu, Huiling Wang, Guofeng Han, Jin Cheng, Weifeng Hu, Jinyuan Zhang View Abstract ❯
Regulation of interferon signaling and HCV‑RNA replication by extracellular matrix Takuya Kuwashiro, Shinji Iwane, Xia Jinghe, Sachiko Matsuhashi, Yuichiro Eguchi, Keizo Anzai, Kazuma Fujimoto, Toshihiko Mizuta, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Iwata Ozaki View Abstract ❯
Overexpression of PRDM13 inhibits glioma cells via Rho and GTP enzyme activation protein Linna Zhang, Huimei Cao, Tao He, Jijuan Yang, Hong Tao, Yin Wang, Qikuan Hu View Abstract ❯
MicroRNA‑20b‑5p promotes ventricular remodeling by targeting the TGF‑β/Smad signaling pathway in a rat model of ischemia‑reperfusion injury Zhao‑Guang Liang, Hong Yao, Rong‑Sheng Xie, Chun‑Lin Gong, Ye Tian View Abstract ❯
Engulfment of platelets delays endothelial cell aging via girdin and its phosphorylation Yong Lan, Yongjun Li, Dajun Li, Peng Li, Jiyang Wang, Yongpeng Diao, Guodong Ye, Yangfang Li View Abstract ❯
miR‑494 inhibits cancer‑initiating cell phenotypes and reverses resistance to lapatinib by downregulating FGFR2 in HER2‑positive gastric cancer Yanxia Yu, Xuejuan Yu, Hong Liu, Qingxun Song, Yongmei Yang View Abstract ❯
MicroRNA‑381/Hes1 is a potential therapeutic target for spinal cord injury Wendong Ruan, Guangzhi Ning, Shiqing Feng, Shijie Gao, Yan Hao View Abstract ❯
Cucurbitacin B inhibits tumor angiogenesis by triggering the mitochondrial signaling pathway in endothelial cells Xian-Mei Piao, Feng Gao, Jiu-Xin Zhu, Li-Juan Wang, Xin Zhao, Xin Li, Miao-Miao Sheng, Yan Zhang View Abstract ❯
MicroRNA-137 dysregulation predisposes to osteoporotic fracture by impeding ALP activity and expression via suppression of leucine-rich repeat-containing G-protein-coupled receptor 4 expression Xiangjun Liu, Xiaohui Xu View Abstract ❯
Inhibition of MEK/ERK/STAT3 signaling in oleuropein treatment inhibits myocardial ischemia/reperfusion Hong‑Xu Jin, Yun‑Hu Zhang, Ruo‑Nan Guo, Su‑Nuan Zhao View Abstract ❯
Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication Wenyu Cheng, Huaijie Jia, Xiaoxia Wang, Xiaobing He, Qiwang Jin, Jingxin Cao, Zhizhong Jing View Abstract ❯
CTRP9 ameliorates cellular senescence via PGC‑1α/AMPK signaling in mesenchymal stem cells Qun Li, Zhangzhang Zhu, Chengde Wang, Lin Cai, Jianglong Lu, Yongchun Wang, Jiadong Xu, Zhipeng Su, Weiming Zheng, Xianbin Chen View Abstract ❯
DNAJC3 mutation in Thai familial type 2 diabetes mellitus Sirikul Kulanuwat, Watip Tangjittipokin, Prapaporn Jungtrakoon, Chutima Chanprasert, Jatuporn Sujjitjoon, Ninareeman Binnima, Pa‑Thai Yenchitsomanus, Nattachet Plengvidhya View Abstract ❯
Upregulated 14‑3‑3β aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids Lishuai Feng, Chaoran Dou, Jianbo Wang, Chunyu Jiang, Xu Ma, Jingjing Liu View Abstract ❯
Silencing of miR‑155 suppresses inflammatory responses in psoriasis through inflammasome NLRP3 regulation Quan Luo, Jingxin Zeng, Wei Li, Ling Lin, Xin Zhou, Xin Tian, Weiyu Liu, Lidan Zhang, Xibao Zhang View Abstract ❯
BMP‑6 protects retinal pigment epithelial cells from oxidative stress‑induced injury by inhibiting the MAPK signaling pathways Li Chen, Ming Liu, Yan Luan, Yingfei Liu, Zhichao Zhang, Bo Ma, Xuan Liu, Yong Liu View Abstract ❯
Luteolin induces myelodysplastic syndrome‑derived cell apoptosis via the p53‑dependent mitochondrial signaling pathway mediated by reactive oxygen species Weimin Dong, Yan Lin, Yang Cao, Yue Liu, Xiaobao Xie, Weiying Gu View Abstract ❯
Accumulation of CD69+ tissue‑resident memory T cells in the nasal polyps of patients with chronic rhinosinusitis Pascal Ickrath, Norbert Kleinsasser, Xin Ding, Christian Ginzkey, Niklas Beyersdorf, Rudolf Hagen, Thomas Kerkau, Stephan Hackenberg View Abstract ❯
Connexin 43 reduces susceptibility to sympathetic atrial fibrillation Beibei Luo, Yifei Yan, Zhiyu Zeng, Zhengnan Zhang, Haide Liu, Hao Liu, Jinyi Li, Weiqiang Huang, Jiangtao Wu, Yan He View Abstract ❯
Downregulation of microRNA‑34a inhibits oxidized low‑density lipoprotein‑induced apoptosis and oxidative stress in human umbilical vein endothelial cells Xiaoming Zhong, Peng Li, Juan Li, Ruili He, Guanchang Cheng, Yanming Li View Abstract ❯
E3 ubiquitin ligase Hakai regulates cell growth and invasion, and increases the chemosensitivity to cisplatin in non‑small‑cell lung cancer cells Zi Liu, Yuqing Wu, Zijian Tao, Liang Ma View Abstract ❯
LncRNA uc.48+ is involved in the diabetic immune and inflammatory responses mediated by P2X7 receptor in RAW264.7 macrophages Hong Wu, Fang Wen, Mei Jiang, Qiang Liu, Yijun Nie View Abstract ❯
Apelin protects against sepsis‑induced cardiomyopathy by inhibiting the TLR4 and NLRP3 signaling pathways Qiancheng Luo, Guorong Liu, Guo Chen, Dongfeng Guo, Lei Xu, Min Hang, Mingming Jin View Abstract ❯
Collagen peptides from soft‑shelled turtle induce calpain‑1 expression and regulate inflammatory cytokine expression in HaCaT human skin keratinocytes Tetsushi Yamamoto, Saori Nakanishi, Kuniko Mitamura, Atsushi Taga View Abstract ❯
Efficient delivery of HBV NLS siRNAs into HepG2.2.15 cells for HBV inhibition through novel recombinant preS1‑tP proteins Yanli Zeng, Zixi Li, Jia Shang, Yi Kang View Abstract ❯
Protective effects of dehydrocostuslactone on rat hippocampal slice injury induced by oxygen‑glucose deprivation/reoxygenation Qipeng Zhao, Ailing Chen, Xiaobo Wang, Zhuanzhuan Zhang, Yunsheng Zhao, Yu Huang, Shuanglai Ren, Yafei Zhu View Abstract ❯
[Corrigendum] Protective effect of angiotensin‑(1‑7) against hyperglycaemia‑induced injury in H9c2 cardiomyoblast cells via the PI3K̸Akt signaling pathway Yi-Ying Yang, Xiu-Ting Sun, Zheng-Xun Li, Wei-Yan Chen, Xiang Wang, Mei-Ling Liang, Hui Shi, Zhi-Sheng Yang, Wu-Tao Zeng View Abstract ❯

20-22 September, 2018, Metropolitan Hotel, Athens, Greece 23nd World Congress on Advances in Oncology & 22th International Symposium on Molecular Medicine 18-19 September 2018, Pre-Congress Workshop: 'MicroRNA Analysis'

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The molecular allergology of subtropical grass pollen

Publication date: Available online 31 May 2018
Source:Molecular Immunology
Author(s): Thina Kailaivasan, Janet M. Davies
Grass pollens are amongst the most important aeroallergen sources world-wide triggering allergic rhinoconjunctivitis and asthma in sensitised patients. Much of what we know about the allergen components of grasses is informed by research on pollen of temperate (Pooideae) species that are abundant in the temperate climate zones. However, climate changes are altering the biogeographical distribution as well as timing and allergenicity of grass pollens. This provides an impetus for better understanding of the contribution of subtropical subfamilies of grasses to pollen allergy globally. Pollen of Chloridoideae (e.g. Cynodon dactylon; Bermuda grass) and Panicoideae (e.g. Paspalum notatum; Bahia grass or Sorghum halepense; Johnson grass) subfamilies are clinically important in subtropical zones of Australia, Asia, India, Africa, and America. These grasses differ ecologically and phylogenetically from temperate grasses and, importantly their allergen composition is qualitatively different. For example, subtropical grass pollens appear to lack the major group 5 grass pollen allergen family. In this review we summarize current knowledge of the epidemiology and immunology of subtropical Chloridoideae and Pancoideae pollen allergens, describe the biochemical characteristics of known isoforms and variants as well as properties and structures of subtropical pollen allergen components. Whilst only one subtropical allergen component; Cyn d 1 of Bermuda grass pollen, is available commercially for diagnostic use, in a natural purified form, a number of allergens of Panicoideae grass pollen; Zea m 1, Zea m 3 and Zea m 13 of maize, Pas n 1 and Pas n 13 of Bahia, as well as Sor h 1, Sor h 2, Sor h 13 and Sor h 23 of Johnson grass, have been discovered. Research effort is directed towards making available subtropical grass pollen allergen components as innovative treatment and diagnostic options that more specifically address the needs of patients from warmer regions of the globe.



https://ift.tt/2kGooaL

Spectral Contrast Effects Produced by Competing Speech Contexts.

Author: Feng, Lei; Oxenham, Andrew J.

DOI: 10.1037/xhp0000546

Publication Date: POST AUTHOR CORRECTIONS, 31 May 2018

https://ift.tt/2J8HCAh

Interplay between estrogen-related receptors and steroidogenesis-controlling molecules in adrenals. In vivo and in vitro study

Publication date: Available online 31 May 2018
Source:Acta Histochemica
Author(s): A. Pacwa, E. Gorowska-Wojtowicz, A. Ptak, P. Pawlicki, A. Milon, M. Sekula, K. Lesniak, B. Bilinska, A. Hejmej, M. Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found. Diverse and complex ERRs regulation of multilevel-acting steroidogenic proteins (perilipin; PLIN, cytochrome P450 side-chain cleavage; P450scc, translocator protein; TSPO, steroidogenic acute regulatory protein; StAR, hormone sensitive lipase; HSL and HMG-CoA reductase; HMGCR) was revealed. Blockage of ERRα decreased P450scc, StAR and TSPO expressions. Activation of ERRβ/γ increased P450scc, StAR and HMGCR while decreased HSL expressions. PLIN expression increased either after XCT 790 or DY131 treatment. Additionally, treatment with both XCT 790 or DY131 decreased activity of Ras/Raf, Erk and Akt indicating their involvement in control of morphology and steroidogenic function of cortex cells. ERRs are important in maintaining morpho-function of cortex cells through action in specific, opposite, or common manner on steroidogenic molecules.



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Stereotactic radiation therapy in the strategy of treatment of metastatic renal cell carcinoma: A study of the Getug group

Publication date: July 2018
Source:European Journal of Cancer, Volume 98
Author(s): Emmanuel Meyer, David Pasquier, Guillemette Bernadou, Gilles Calais, Pierre Maroun, Alberto Bossi, Christine Theodore, Laurence Albiges, Dinu Stefan, Renaud D.E. Crevoisier, Christophe Hennequin, Jean-Léon Lagrange, Jean-Michel Grellard, Bénédicte Clarisse, Idlir Licaj, Jean-Louis Habrand, Christian Carrie, Florence Joly
BackgroundRenal cell carcinoma (RCC) is usually considered radioresistant, but stereotactic radiation therapy (SRT) may increase local disease control. This study aimed to assess the benefit of SRT in the management of metastatic RCC patients.MethodsData of all RCC patients who received SRT between 2008 and 2015 with curative intent were retrospectively collected in six French referral centres. Local control (LC), progression-free survival (PFS), local recurrence-free survival (LRFS), time to systemic therapy (TTS) and overall survival (OS) were assessed.ResultsOne hundred and eighty-eight patients treated with SRT for 252 RCC metastases (brain [n = 120]; spine [n = 75]; and others [n = 57]) were recensed. SRT was performed for oligoprogressive disease (101 patients), oligometastatic disease (80 patients) or residual tumour after a partial response to systemic treatment (7 patients). The median biologically effective dose was 78 Gy. For the whole population, local control rates at 6, 12 and 24 months were 87.5%, 82.9% and 77.6%, respectively; median PFS, LRFS, TTS and OS were 8.5, 23.2, 13.2 and 29.2 months, respectively. Among patients treated for oligoprogressive/oligometastatic disease, the median PFS, TTS, and OS were 8.6/7.6, 10.5/14.2 and 23.2/33.9 months, respectively. Among the 7 patients treated with SRT after partial response to systemic treatment, no relapse occurred for 3 of them after a median follow-up of 22 months. Acute and late severe toxicities were noted in 5 (2.6%) patients.ConclusionsSRT is effective and safe for oligometastatic and oligoprogressive RCC patients and may delay introduction or change of systemic therapy.



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Biology, taxonomy, and IPM strategies of Bactrocera tau Walker and complex species (Diptera; Tephritidae) in Asia: a comprehensive review

Abstract

Bactrocera flies are the serious pests of fruit, vegetables, and nuts over the world. Bactrocera tau Walker is an economically important pest of agricultural crops. In Asia, approximately 30–40% losses of agricultural products are caused by B. tau infestation every year. In Asia, the B. tau contains a complex of sibling species that called the tau complex. However, the basic studies of B. tau and complex species are very important for integrated management. A comprehensive review of the B. tau and complex species has not been provided elsewhere. So, considering the importance of B. tau and complex species, this study provides the published information on ecology, nomenclature, identification tools, geographical distribution, potential invasion, and IPM tactics of B. tau and complex species, which would be more informative for publication facilitating related to integrated pest management (IPM) strategies of B. tau and complex species. In IPM of B. tau and complex species, the phytochemical and biological controls have not been applied successfully in Asia; there is an urgent need to study and applications of these two mentioned control techniques against the B. tau and complex species in Asia.

https://ift.tt/2Le7Im5

Monitoring system for investigating the effect of temperature change on optical properties

Abstract

Knowledge about the changes in optical properties is needed for planning safer and more accurate laser treatments. A monitoring system was developed to study how the optical properties of a lipid emulsion are affected by temperature changes. A double-integrating-sphere system is modified with a controlled heating apparatus to measure the temperature-dependent diffuse reflectance and total transmittance values. The absorption and reduced scattering coefficients were estimated from the reflectance and transmittance values using an inverse adding-doubling method. The total transmittance showed positive correlation with temperature while the diffuse reflectance was found to be negatively correlated. Although the absorption coefficient did not demonstrate a statistically significant change with temperature, the reduced scattering coefficient was negatively correlated. By using the obtained optical properties, Monte Carlo simulations were performed to observe the difference in light propagation within a tissue. The results indicate that temperature-dependent changes in optical properties should be taken into consideration for a safer laser treatment.

https://ift.tt/2JjooLT

Synthesis, Structure-Activity Relationship and Molecular Docking Studies of 3-O-Flavonol Glycosides as Cholinesterase Inhibitors

Publication date: Available online 1 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Ehsan Ullah Mughal, Asif Javid, Amina Sadiq, Shahzad Murtaza, Muhammad Naveed Zafar, Bilal Ahmad Khan, Sajjad Hussain Sumra, Muhammad Nawaz Tahir, Kanwal, Khalid Mohammed Khan
The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3-O-flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3-O-flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, ¹H-, ¹³C-NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds (21-30) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another.

Graphical abstract

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Synthesis and biological evaluation of novel N-substituted nipecotic acid derivatives with an alkyne spacer as GABA uptake inhibitors

Publication date: Available online 1 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Krisztián Tóth, Georg Höfner, Klaus T. Wanner
In this study, we present the synthesis and structure-activity relationships (SAR) of novel N–substituted nipecotic acid derivatives closely related to SNAP-5114 (2) in the pursuit of finding new and potent mGAT4 selective inhibitors. By the use of iminium ion chemistry, a series of new N-substituted nipecotic acid derivatives containing a variety of heterocycles, and an alkyne spacer were synthesized. Biological evaluation of the prepared compounds showed, how the inhibitory potency and subtype selectivity for the murine GABA transporters (mGATs) were influenced by the performed modifications.

Graphical abstract

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Levels of retinal IAPP are altered in Alzheimer's disease patients and correlate with vascular changes and hippocampal IAPP levels

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Nina Schultz, Elin Byman, Malin Wennström
Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same. Total IAPP levels and pericyte numbers in retina mirrored corresponding variables in the hippocampus. Moreover, levels of total unmodified IAPP correlated negatively with the vessel length both in retina and hippocampus across the group and positively with pericyte numbers in retina in AD patients. Our studies indicate that changes in brain IAPP are reflected by corresponding levels in the retina. Our results also suggest modification of IAPP as an important event implicated in vascular changes associated with AD.



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A simple and clinically relevant combination of neuroimaging and functional indexes for the identification of those at highest risk of Alzheimer's disease

Publication date: September 2018
Source:Neurobiology of Aging, Volume 69
Author(s): Hossein Tabatabaei-Jafari, Erin Walsh, Marnie E. Shaw, Nicolas Cherbuin
The current challenge in clinical practice is to identify those with mild cognitive impairment (MCI), who are at greater risk of Alzheimer's disease (AD) conversion in the near future. The aim of this study was to assess a clinically practical new hippocampal index—hippocampal volume normalized by cerebellar volume (hippocampus to cerebellum volume ratio) used alone or in combination with scores on the Mini–Mental State Examination, as a predictor of conversion from MCI to AD. The predictive value of the HCCR was also contrasted to that of the hippocampal volume to intracranial volume ratio. The findings revealed that the performance of the combination of measures was significantly better than that of each measure used individually. The combination of Mini–Mental State Examination and hippocampal volume, normalized by the cerebellum or by intracranial volume, accurately discriminated individuals with MCI who progress to AD within 5 years from other MCI types (stable, reverters) and those with intact cognition (area under receiver operating curve of 0.88 and 0.89, respectively). Normalization by cerebellar volume was as accurate as normalization by intracranial volume with the advantage of being more practical, particularly for serial assessments.



https://ift.tt/2J7cPYZ

Reciprocal relationships between daily sleep and mood: A systematic review of naturalistic prospective studies

An intimate relationship exists between sleep and affective states. Disturbances in sleep are common across a spectrum of psychopathologies, and are recognised as precipitating or prodromal factors for mood disorders. Conversely, affective states can impact sleep quality and ability to fall asleep. However, one of the main limitations of this literature is that studies have typically assessed sleep and mood at one time point and studies are often laboratory-based, where measurement of both sleep and mood has dubious ecological validity.

https://ift.tt/2J7yfoz

Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex

Publication date: Available online 1 June 2018
Source:Journal of Autoimmunity
Author(s): Lisa Rizzetto, Francesca Fava, Kieran M. Tuohy, Carlo Selmi
Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in preventing or ameliorating AID. Finally, we suggest that, given consistent observations of microbiota dysbiosis associated with AID and the ability of SCFA and BA to regulate intestinal permeability and inflammation, further mechanistic studies, examining how dietary microbiota modulation can protect against AID, hold considerable potential to tackle increased incidence of AID at the population level.



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