To address the impact of cellular origin on acute myeloid leukemia (AML), we generated an inducible transgenic mouse model for MLL-AF9-driven leukemia. MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion. In vivo, 20% LT-HSC-derived AML were particularly aggressive with extensive tissue infiltration, chemoresistance, and expressed genes related to epithelial-mesenchymal transition...
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Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular...
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In fragile X syndrome (FXS), CGG repeat expansion greater than 200 triplets is believed to trigger FMR1 gene silencing and disease etiology. However, FXS siblings have been identified with more than 200 CGGs, termed unmethylated full mutation (UFM) carriers, without gene silencing and disease symptoms. Here, we show that hypomethylation of the FMR1 promoter is maintained in induced pluripotent stem cells (iPSCs) derived from two UFM individuals. However, a subset of iPSC clones with large CGG expansions...
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Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate...
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Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these...
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Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show...
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Human studies on the role of mannose-binding lectin (MBL) in patients with invasive candidiasis have yielded conflicting results. We investigated the influence of MBL and other lectin pathway proteins on Candida colonization and intra-abdominal candidiasis (IAC) in a cohort of high-risk patients.; Prospective observational cohort study of 89 high-risk intensive-care unit (ICU) patients. Levels of lectin pathway proteins at study entry and six MBL2 single-nucleotide polymorphisms were analyzed by...
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Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling...
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MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4...
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BACKGROUND: Treatment to restore sinus rhythm among patients with atrial fibrillation (AF) has limited long-term success rates. Gene expression profiling may provide new insights into AF pathophysiology. OBJECTIVE: To identify biomarkers and improve our understanding of AF pathophysiology by comparing whole blood gene expression before and after electrical cardioversion (ECV). METHODS: In 46 patients with persistent AF that underwent ECV, whole blood samples were collected 1-2 hours before and 4...
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Premature atherosclerosis and thrombotic complications are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the high incidence of these complications cannot be explained by traditional risk factors alone, suggesting direct effects of an activated immune system on hemostasis. The unexpected nucleotide sequence homology between SLE patient-derived autoantibodies against complement C1q (Fab anti-C1q) and von Willebrand factor (VWF) led us to investigate...
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INTRODUCTION: Left atrial (LA) enlargement is an important risk factor for incident stroke and a key determinant for the success of rhythm control strategies in patients with atrial fibrillation (AF). However, factors associated with LA volume in AF patients remain poorly understood. METHODS: Patients with paroxysmal or persistent AF were enrolled in this study. Real time 3-D echocardiography was performed in all participants and analyzed offline in a standardized manner. We performed stepwise backward...
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OBJECTIVE: Candida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking. DESIGN: We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4 cell counts as the patients at...
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Duemila arance al giorno: è la 'bomba' di vitamina C che può aiutare a sconfiggere i tumori, potenziando l'attività anticancro del sistema immunitario e rendendo più efficaci e meglio...
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Jialin Qu, Peng Huang, Lin Zhang, Yang Qiu, Huan Qi, Aijing Leng, Dong Shang
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Wei Zhang, Hojat Veisi, Reyhaneh Sharifi, Delafarin Salamat, Bikash Karmakar, Malak Hekmati, Saba Hemmati, Zhiyong Zhang, Qiang Su, Mohammad Mahdi Zangeneh
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Mohamed A. Abdel-Naby, W.M. Abu El-Wafa, G.E.M. Salim
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Jeng Hua Beh, Teck Hock Lim, Jin Hau Lew, Jau Choy Lai
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Xiaoying Luo, Jinling Li, Wenli Yan, Ru Liu, Tao Yin, Juan You, Hongying Du, Shanbai Xiong, Yang Hu
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Rui Wang, Shang Wang, Yan Xu, Xiaowei Yu
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Luca Massaccesi, Emiliano Laudadio, Giovanna Mobbili, Cristina Minnelli, Roberta Galeazzi
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Guangtao Song, Benjin Xu, Huigang Shi, Yong Zhang, Dejiu Zhang, Xintao Cao, Zengrui Liu, Ran Guo, Yan-Zhong Guan, Yanhui Chu, Xinzheng Zhang, Jizhong Lou, Yan Qin
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Maopeng Wang, Tingting Fu, Jiayi Hao, Letian Li, Mingyao Tian, Ningyi Jin, Linzhu Ren, Chang Li
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Pankaj Jha
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Kiran Jyoti, Garima Malik, Monika Chaudhary, Monika Sharma, Manish Goswami, Om Prakash Katare, Shashi Bala Singh, Jitender Madan
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Reihaneh Sorourian, Amir Eghbal Khajehrahimi, Mehrnoosh Tadayoni, Mohammad Hossein Azizi, Mohammad Hojjati
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Marwa Hamdi, Rim Nasri, Ikram Ben Amor, Suming Li, Jalel Gargouri, Moncef Nasri
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Sana Qausain, Faez Iqbal Khan, Dakun Lai, Md. Imtaiyaz Hassan, Mohd Basheeruddin, Neesar Ahmed, Md. Khurshid Alam Khan
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Publication date: Available online 30 May 2020Source: International Journal of Biological MacromoleculesAuthor(s): Nele Mullens, Gontran Sonet, Eva Decru, Massimiliano Virgilio, Snoeks Jos, Emmanuel Vreven
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Publication date: Available online 30 May 2020Source: Cancer CellAuthor(s): Abbie S. Ireland, Alexi M. Micinski, David W. Kastner, Bingqian Guo, Sarah J. Wait, Kyle B. Spainhower, Christopher C. Conley, Opal S. Chen, Matthew R. Guthrie, Danny Soltero, Yi Qiao, Xiaomeng Huang, Szabolcs Tarapcsák, Siddhartha Devarakonda, Milind D. Chalishazar, Jason Gertz, Justin C. Moser, Gabor Marth, Sonam Puri, Benjamin L. Witt
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Publication date: Available online 30 May 2020Source: Journal of Infection and ChemotherapyAuthor(s): Yuki Ohno, Akihiro Nakamura, Eriko Hashimoto, Nobuyoshi Noguchi, Gaku Matsumoto, Saori Fukuda, Noriyuki Abe, Shuji Matsuo, Masaru Komatsu
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Abstract Cryptotanshinone (CPT) is an efficacious acne treatment, while niosomal hydrogel is a known effective topical drug delivery system that produces a minimal amount of irritation. Three-dimensional (3D) printing technologies have the potential to improve the field of personalized acne treatment. Therefore, this study endeavored to develop a 3D-printed niosomal hydrogel (3DP-NH) containing CPT as a topical delivery system for acne therapy. Specifically, CPT-loaded niosomes...
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Abstract The aim of this present study was to investigate the ability of different dissolution methods to predict the in vivo performance of efonidipine hydrochloride (EFH). The solid dispersions of EFH were prepared by solvent evaporation method with HPMC-AS as matrix and urea as a pH adjusting agent. The paddle method, the open-loop, and the closed-loop flow-through cell methods were studied. In the study, Weibull’s model was the best fit to explain release profiles. The pharmacokinetics...
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Our findings revealed a novel mechanism that the proinflammatory cytokines IL‐1β and TNF‐α modulate corneal epithelial wound healing via the p16Ink4a‐p‐STAT3 signaling. Abstract The proinflammatory cytokines interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α) are involved in the corneal inflammatory response and wound healing following corneal injuries. However, the mechanism by which proinflammatory cytokines modulate corneal epithelial wound healing remains unclear. In this study,...
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This review summarizes and analyzes the updated information on the regulation of sortilin expression and its trafficking function. Recent advances in the regulation of sortilin expression and function, and its related mechanisms will help the ongoing research related to sortilin and promote future clinical application via sortilin intervention. Abstract This review summarizes and analyzes the updated information on the regulation of sortilin expression and its trafficking function. Evidence indicates...
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Publication date: Available online 31 May 2020Source: International Journal of Oral and Maxillofacial SurgeryAuthor(s): W. Powcharoen
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Publication date: Available online 30 May 2020Source: Cancer Treatment ReviewsAuthor(s): Aung M. Tun, Stephen M. Ansell
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Publication date: Available online 30 May 2020Source: Cancer Treatment ReviewsAuthor(s): Luigi Mele, Vitale del Vecchio, Davide Liccardo, Claudia Prisco, Melanie Schwerdtfeger, Nirmal Robinson, Vincenzo Desiderio, Virginia Tirino, Gianpaolo Papaccio, Marcella La Noce
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