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https://www.readbyqxmd.com/read/28803568/history-of-child-maltreatment-and-telomere-length-in-immune-cell-subsets-associations-with-stress-and-attachment-related-hormones
#1
Christina Boeck, Sabrina Krause, Alexander Karabatsiakis, Katharina Schury, Harald Gündel, Christiane Waller, Iris-Tatjana Kolassa
Experiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels...
August 14, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28796194/a-murine-model-of-persistent-inflammation-immune-suppression-and-catabolism-syndrome
#2
Amanda M Pugh, Nicholas J Auteri, Holly S Goetzman, Charles C Caldwell, Vanessa Nomellini
Critically ill patients that survive sepsis can develop a Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS), which often leads to extended recovery periods and multiple complications. Here, we utilized a cecal ligation and puncture (CLP) method in mice with the goal of creating a model that concurrently displays all the characteristics of PICS. We observed that, after eight days, mice that survive the CLP develop persistent inflammation with significant myelopoiesis in the bone marrow and spleen...
August 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28793242/frequency-specific-alteration-of-functional-connectivity-density-in-antipsychotic-naive-adolescents-with-early-onset-schizophrenia
#3
Xiao Wang, Yan Zhang, Zhiliang Long, Junjie Zheng, Youxue Zhang, Shaoqiang Han, Yifeng Wang, Xujun Duan, Mi Yang, Jingping Zhao, Huafu Chen
Early-onset schizophrenia (EOS) is a severe mental illness associated with dysconnectivity that widespread in the brain. However, the functional dysconnectivity in EOS are still mixed. Recently, studies have identified that functional connectivity (FC) arises from a band-limited slow rhythmic mechanism and suggested that the dysconnectivity at specific frequency bands may provide more robust biomarkers for schizophrenia. The frequency-specific changes of FC pattern in EOS remain unclear. To address this issue, resting-state functional magnetic resonance imaging data scans from 39 EOS patients (drug-naive) and 31 healthy controls (HCs) were used to assess the FC density (FCD) across slow-4 (0...
July 19, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#4
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28792003/vaccine-modified-nf-kb-and-gr-signaling-in-cervicovaginal-epithelium-correlates-with-protection
#5
L Shang, A J Smith, C S Reilly, L Duan, K E Perkey, S Wietgrefe, M Zupancic, P J Southern, R P Johnson, J V Carlis, A T Haase
Cervicovaginal epithelium plays a critical role in determining the outcome of virus transmission in the female reproductive tract (FRT) by initiating or suppressing transmission-facilitating mucosal immune responses in naïve and SIVmac239Δnef-vaccinated animals, respectively. In this study, we examined the very early responses of cervical epithelium within 24 h after vaginal exposure to SIV in naive and SIVmac239Δnef-vaccinated rhesus macaques. Using both ex vivo and in vivo experimental systems, we found that vaginal exposure to SIV rapidly induces a broad spectrum of pro-inflammatory responses in the epithelium associated with a reciprocal regulation of NF-kB and glucocorticoid receptor (GR) signaling pathways...
August 9, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28791972/hcv-co-infection-is-associated-with-metabolic-abnormalities-among-haart-naive-hiv-infected-persons
#6
M A Kuti, J O Akinyemi, B O Ogunbosi, K M Kuti, O A Adesina, O A Awolude, O S Michael, I F Adewole
OBJECTIVES: To determine the metabolic abnormalities among Hepatitis C Virus (HCV) co infected HAART naïve HIV infected persons within the adult ARV clinic of the University College Hospital/University of Ibadan, Ibadan, Nigeria Methods: This was a retrospective study involving the review of clinical records of newly recruited HIV-infected persons in the adult antiretroviral (ARV) clinic over a 12 month period (January - December 2006). Baseline results for fasting plasma glucose (FPG) and fasting lipid profile were retrieved...
July 2017: Nigerian Journal of Clinical Practice
https://www.readbyqxmd.com/read/28783663/memory-phenotype-cd4-t-cells-spontaneously-generated-under-steady-state-conditions-exert-innate-th1-like-effector-function
#7
Takeshi Kawabe, Dragana Jankovic, Shuko Kawabe, Yuefeng Huang, Ping-Hsien Lee, Hidehiro Yamane, Jinfang Zhu, Alan Sher, Ronald N Germain, William E Paul
Conventional CD4(+) T cells are composed of naïve, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells under steady state. Naïve and pathogen-specific memory cells play key roles in adaptive immunity, whereas the homeostatic mechanisms regulating the generation of MP cells and their biological functions are unclear. We show that MP cells are autonomously generated from peripheral naïve cells in the absence of infectious stimulation in a T cell receptor (TCR)- and CD28-dependent manner...
June 16, 2017: Science Immunology
https://www.readbyqxmd.com/read/28780479/q-twist-analysis-of-patients-with-metastatic-castrate-naive-prostate-cancer-treated-by-androgen-deprivation-therapy-with-or-without-docetaxel-in-the-randomised-phase-iii-getug-afu-15-trial
#8
P Marino, P Sfumato, F Joly, K Fizazi, S Oudard, S Culine, M Habibian, J-M Boher, G Gravis
BACKGROUND: Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. PATIENTS AND METHODS: This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients...
August 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28776581/decreased-brain-ph-as-a-shared-endophenotype-of-psychiatric-disorders
#9
Hideo Hagihara, Vibeke S Catts, Yuta Katayama, Hirotaka Shoji, Tsuyoshi Takagi, Freesia L Huang, Akito Nakao, Yasuo Mori, Kuo-Ping Huang, Shunsuke Ishii, Isabella A Graef, Keiichi I Nakayama, Cynthia Shannon Weickert, Tsuyoshi Miyakawa
Although the brains of patients with schizophrenia and bipolar disorder exhibit decreased brain pH relative to those of healthy controls upon postmortem examination, it remains controversial whether this finding reflects a primary feature of the diseases or is a result of confounding factors such as medication and agonal state. To date, systematic investigation of brain pH has not been undertaken using animal models, which can be studied without confounds inherent in human studies. In the present study, we first reevaluated the pH of the postmortem brains of patients with schizophrenia and bipolar disorder by conducting a meta-analysis of existing datasets from ten studies...
August 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28772243/daphnoretin-modulates-differentiation-and-maturation-of-human-dendritic-cells-through-down-regulation-of-c-jun-n-terminal-kinase
#10
Chien-An Chen, Chien-Kuo Liu, Ming-Ling Hsu, Chih-Wen Chi, Chun-Chuan Ko, Jian-Syun Chen, Cheng-Ta Lai, Hen-Hong Chang, Tzung-Yan Lee, Yuen-Liang Lai, Yu-Jen Chen
Daphnoretin, an active constituent of Wikstroemia indica C.A. Meys, has been shown possessing anti-cancer activity. In this study, we examined the effect of daphnoretin on differentiation and maturation of human myeloid dendritic cells (DCs). After treatment with daphnoretin (0, 1.1, 3.3, 10 and 30μM) to initiate monocytes, the recovery rate of DCs was reduced in a dose-dependent manner. The mature DCs differentiated in the presence of daphnoretin had fewer and shorter dendrites. Daphnoretin modulated DCs differentiation and maturation in terms of lower expression of CD1a, CD40, CD83, DC-SIGN, and HLA-DR...
July 31, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28771778/new-onset-or-transition-of-disease-state-of-psoriatic-arthritis-during-treatment-with-ustekinumab-a-single-center-retrospective-study
#11
Akihiko Asahina, Yoshinori Umezawa, Mami Momose, Hiromi Honda, Koichi Yanaba, Hidemi Nakagawa
Ustekinumab (UST) is a treatment option for psoriatic arthritis (PsA), but recent observations indicate that some psoriatic patients may experience new onset of PsA or worsening of pre-existent PsA. We retrospectively analyzed all cases of psoriasis vulgaris (PsV) and PsA treated with UST in our facility between 2011 and 2015. PsA developed in eight out of 179 PsV patients, mostly later than 8 months after initiation of UST. It was generally not severe, and none had received tumor necrosis factor (TNF)-α inhibitors previously, indicating that the possibility of unmasking pre-existing subclinical arthritis is minimal...
August 3, 2017: Journal of Dermatology
https://www.readbyqxmd.com/read/28765697/eight-week-ledipasvir-sofosbuvir-in-non-cirrhotic-treatment-na%C3%A3-ve-hepatitis-c-genotype-1-patients-with-hepatitis-c-virus-rna-6-million-single-center-real-world-effectiveness-and-safety
#12
Nyan L Latt, Beshoy T Yanny, Derenik Gharibian, Rita Gevorkyan, Amandeep K Sahota
AIM: To evaluate sustained viral response (SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus (HCV) patients with RNA < 6 million IU/mL. METHODS: We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir (LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/mL. Primary outcome was an achievement of SVR at 12 wk after treatment...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28764206/analysis-of-survival-data-challenges-and-algorithm-based-model-selection
#13
REVIEW
Kaushik Sarkar, Ranadip Chowdhury, Aparajita Dasgupta
Survival data is a special form of time to event data that is often encountered while modelling risk. The classical Cox proportional hazard model, that is popularly used to analyse survival data, cannot be used for modelling risk when the proportional hazard assumption is violated or when there is recurrent time to event data. In this context we conducted this narrative review to develop an algorithm for selection of advanced methods of analysing survival data in the above-mentioned situations. Findings were synthesized from literature retrieved from searches of Pubmed, Embase, and Google Scholar...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28761088/shift-of-emt-gradient-in-3d-spheroid-mscs-for-activation-of-mesenchymal-niche-function
#14
Sohee Jeon, Ho-Sun Lee, Ga-Young Lee, Gyeongsin Park, Tae-Min Kim, Jihye Shin, Cheolju Lee, Il-Hoan Oh
Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in clinical trials, their variable and heterogeneous supporting activity pose major challenges. While three-dimensional (3D) MSC cultures are emerging as alternative approaches, key changes in cellular characteristics during 3D-spheroid formation remain unclear. Here, we show that MSCs in 3D spheroids undergo further progression towards the epithelial-mesenchymal transition (EMT), driven by upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753790/positive-pelvic-lymph-nodes-in-prostate-cancer-harbor-immune-suppressor-cells-to-impair-tumor-reactive-t-cells
#15
Vidit Sharma, Haidong Dong, Eugene Kwon, R Jeffrey Karnes
The impact of prostate cancer (PCa) metastases on pelvic lymph nodes in local antitumor immunity remains unknown. We prospectively enrolled ten hormone therapy-naïve men undergoing salvage pelvic lymph node dissection (sPLND) and analyzed their peripheral blood (PB) and positive pelvic lymph nodes (PPLNs) with PCa metastases for tumor-reactive CD8(+) T cells and myeloid-derived suppressor cells (MDSCs) using flow cytometry. MDSCs were stratified into CD14(+) monocytic and CD14(-) granulocytic types. PD-L1/2 expression was also analyzed for MDSCs...
September 21, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28753462/micrornas-and-rna-binding-protein-regulators-of-micrornas-in-the-control-of-pluripotency-and-reprogramming
#16
REVIEW
Jing Hao, Fei-Fei Duan, Yangming Wang
Post-transcriptional and translational regulations play essential roles during cellular reprogramming and in the maintenance and differentiation of pluripotent stem cells (PSCs). MicroRNAs (miRNAs) control cell cycle, glycolysis, chromatin state, survival and pluripotency of ESCs. Likewise, many miRNAs assist or act as a barrier for the generation of induced pluripotent stem cells (iPSCs). Recent studies also reveal exciting new directions on miRNA functions in regulating the switch between naive and primed pluripotent states as well as the establishment of totipotent-like state...
July 25, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28747210/the-medical-food-souvenaid-affects-brain-phospholipid-metabolism-in-mild-alzheimer-s-disease-results-from-a-randomized-controlled-trial
#17
Anne Rijpma, Marinette van der Graaf, Marieke M Lansbergen, Olga Meulenbroek, Aysun Cetinyurek-Yavuz, John W Sijben, Arend Heerschap, Marcel G M Olde Rikkert
BACKGROUND: Synaptic dysfunction contributes to cognitive impairment in Alzheimer's disease and may be countered by increased intake of nutrients that target brain phospholipid metabolism. In this study, we explored whether the medical food Souvenaid affects brain phospholipid metabolism in patients with Alzheimer's disease. METHODS: Thirty-four drug-naive patients with mild Alzheimer's disease (Mini Mental State Examination score ≥20) were enrolled in this exploratory, double-blind, randomized controlled study...
July 26, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28746311/prolonged-mek1-2-suppression-impairs-the-developmental-potential-of-embryonic-stem-cells
#18
Jiho Choi, Aaron J Huebner, Kendell Clement, Ryan M Walsh, Andrej Savol, Kaixuan Lin, Hongcang Gu, Bruno Di Stefano, Justin Brumbaugh, Sang-Yong Kim, Jafar Sharif, Christopher M Rose, Arman Mohammad, Junko Odajima, Jean Charron, Toshi Shioda, Andreas Gnirke, Steven Gygi, Haruhiko Koseki, Ruslan I Sadreyev, Andrew Xiao, Alexander Meissner, Konrad Hochedlinger
Concomitant activation of the Wnt pathway and suppression of Mapk signalling by two small molecule inhibitors (2i) in the presence of leukaemia inhibitory factor (LIF) (hereafter termed 2i/L) induces a naive state in mouse embryonic stem (ES) cells that resembles the inner cell mass (ICM) of the pre-implantation embryo. Since the ICM exists only transiently in vivo, it remains unclear how sustained propagation of naive ES cells in vitro affects their stability and functionality. Here we show that prolonged culture of male mouse ES cells in 2i/L results in irreversible epigenetic and genomic changes that impair their developmental potential...
July 26, 2017: Nature
https://www.readbyqxmd.com/read/28741622/in-vivo-detection-of-cpp-115-target-engagement-in-human-brain
#19
Andrew P Prescot, Steven R Miller, Gary Ingenito, Rebekah S Huber, Douglas G Kondo, Perry F Renshaw
CPP-115, a next-generation γ-amino butyric acid (GABA)-aminotransferase (AT) inhibitor, shows comparable pharmacokinetics, improved safety and tolerability, and a more favorable toxicity profile when compared to vigabatrin. The pharmacodynamic characteristics of CPP-115 remain to be evaluated. The present study employed state-of-the-art proton magnetic resonance spectroscopy techniques to measure changes in brain GABA+ (the composite resonance of GABA, homocarnosine, and macromolecules) concentrations in healthy subjects receiving oral daily doses of CPP-115 or placebo...
July 25, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28740264/prdm15-safeguards-naive-pluripotency-by-transcriptionally-regulating-wnt-and-mapk-erk-signaling
#20
Slim Mzoughi, Jingxian Zhang, Delphine Hequet, Shun Xie Teo, Haitong Fang, Qiao Rui Xing, Marco Bezzi, Michelle Kay Yi Seah, Sheena L M Ong, Eun Myoung Shin, Heike Wollmann, Esther S M Wong, Muthafar Al-Haddawi, Colin L Stewart, Vinay Tergaonkar, Yuin-Han Loh, N Ray Dunn, Daniel M Messerschmidt, Ernesto Guccione
The transcriptional network acting downstream of LIF, WNT and MAPK-ERK to stabilize mouse embryonic stem cells (ESCs) in their naive state has been extensively characterized. However, the upstream factors regulating these three signaling pathways remain largely uncharted. PR-domain-containing proteins (PRDMs) are zinc-finger sequence-specific chromatin factors that have essential roles in embryonic development and cell fate decisions. Here we characterize the transcriptional regulator PRDM15, which acts independently of PRDM14 to regulate the naive state of mouse ESCs...
July 24, 2017: Nature Genetics
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