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https://www.readbyqxmd.com/read/27926992/inherited-diseases-caused-by-mutations-in-cathepsin-protease-genes
#1
REVIEW
Stephanie Ketterer, Alejandro Gomez-Auli, Larissa E Hillebrand, Agnese Petrera, Anett Ketscher, Thomas Reinheckel
Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays six out of the fifteen human proteases called "cathepsins" have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926970/management-of-endometriosis-involving-the-urinary-tract
#2
Mobolaji O Ajao, Jon I Einarsson
Endometriosis is a common cause of infertility and disabling pelvic pain in reproductive age women. The most widely accepted theory of its pathogenesis is the retrograde flow of menstrual products, although extra-abdominal and extrapelvic diagnoses have been made. After the pelvic peritoneum and gynecologic structures, the most commonly affected sites are the lower gastrointestinal and urinary tracts. When the urinary tract is involved, the bladder is the predominant site, followed by the ureters. The focus of this seminar will thus be these two anatomic sites...
December 7, 2016: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/27926944/targeting-neutrophils-to-prevent-malaria-associated-acute-lung-injury-acute-respiratory-distress-syndrome-in-mice
#3
Michelle K Sercundes, Luana S Ortolan, Daniela Debone, Paulo V Soeiro-Pereira, Eliane Gomes, Elizabeth H Aitken, Antonio Condino Neto, Momtchilo Russo, Maria R D' Império Lima, José M Alvarez, Silvia Portugal, Claudio R F Marinho, Sabrina Epiphanio
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting in the lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion of DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and that these mice recapitulate various aspects of the human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion and hypoxemia. Herein, we investigated the role of neutrophils in the pathogenesis of malaria-associated ALI/ARDS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926940/inflammasome-independent-nlrp3-restriction-of-a-protective-early-neutrophil-response-to-pulmonary-tularemia
#4
Sivakumar Periasamy, Hongnga T Le, Ellen B Duffy, Heather Chin, Jonathan A Harton
Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926730/integrin-yap-taz-jnk-cascade-mediates-atheroprotective-effect-of-unidirectional-shear-flow
#5
Li Wang, Jiang-Yun Luo, Bochuan Li, Xiao Yu Tian, Li-Jing Chen, Yuhong Huang, Jian Liu, Dan Deng, Chi Wai Lau, Song Wan, Ding Ai, King-Lun Kingston Mak, Ka Kui Tong, Kin Ming Kwan, Nanping Wang, Jeng-Jiann Chiu, Yi Zhu, Yu Huang
The Yorkie homologues YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif, also known as WWTR1), effectors of the Hippo pathway, have been identified as mediators for mechanical stimuli. However, the role of YAP/TAZ in haemodynamics-induced mechanotransduction and pathogenesis of atherosclerosis remains unclear. Here we show that endothelial YAP/TAZ activity is regulated by different patterns of blood flow, and YAP/TAZ inhibition suppresses inflammation and retards atherogenesis...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926540/the-novel-interleukin-1-cytokine-family-members-in-inflammatory-diseases
#6
Madelaine Hahn, Silke Frey, Axel J Hueber
PURPOSE OF REVIEW: This review provides an update on the new interleukin-1 (IL-1) cytokine family members in inflammatory diseases with focus on recent findings concerning the family members IL-36, IL-37, and IL-38 and their different expression patterns. RECENT FINDINGS: The IL-1 cytokines are known to be involved in many different inflammatory and autoimmune diseases. The latest IL-1 family members, IL-36, IL-37, and IL-38 have been shown to be differently regulated during course of disease...
December 6, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27926530/the-association-between-serum-uric-acid-and-glaucoma-severity-in-primary-angle-closure-glaucoma-a-retrospective-case-control-study
#7
Shengjie Li, Mingxi Shao, Binghua Tang, Aiping Zhang, Wenjun Cao, Xinghuai Sun
Uric acid (UA) is a major antioxidant molecule and has been hypothesized to have a protective effect on the central nervous system against oxidative damage. We prospectively investigated the serum concentration of UA in primary angle closure glaucoma (PACG), and explored the association between serum concentration of UA and the severity of PACG. Using a retrospective case-control study design, 886 PACG subjects and 994 control subjects who attended the Eye & ENT Hospital of Fudan University, were eligible for this study...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926525/apoptosis-linked-gene-2-promotes-breast-cancer-growth-and-metastasis-by-regulating-the-cytoskeleton
#8
Juan Qin, Dengwen Li, Yunqiang Zhou, Songbo Xie, Xin Du, Ziwei Hao, Ruming Liu, Xinqi Liu, Min Liu, Jun Zhou
Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926512/depression-of-oncogenecity-by-dephosphorylating-and-degrading-bcr-abl
#9
Miao Gao, Zheng-Lan Huang, Kun Tao, Qing Xiao, Xin Wang, Wei-Xi Cao, Min Xu, Jing Hu, Wen-Li Feng
Aberrant phosphorylation and overexpression of BCR-ABL fusion protein are responsible for the main pathogenesis in chronic myeloid leukemia (CML). Phosphorylated BCR-ABL Y177 recruits GRB2 adaptor and triggers leukemic RAS-MAPK and PI3K-AKT signals. In this study, we engineered a SPOA system to dephosphorylate and degrade BCR-ABL by targeting BCR-ABL Y177. We tested its effect on BCR-ABL phosphorylation and expression, as well as cell proliferation and apoptosis in CML cells. We found that SPOA remarkably dephosphorylated BCR-ABL Y177, prevented GRB2 recruitment, and uncoupled RAS-MAPK and PI3K-AKT signals...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926504/the-immunomodulatory-effects-of-tnf-%C3%AE-inhibitors-on-human-th17-cells-via-ror%C3%AE-t-histone-acetylation
#10
Yi-Ching Lin, Yu-Chih Lin, Cheng-Chin Wu, Ming-Yii Huang, Wen-Chan Tsai, Chih-Hsing Hung, Po-Lin Kuo
The presence of interleukin (IL)-17-related cytokines correlates with rheumatoid arthritis (RA) pathogenesis. Epigenetic modifications, including histone acetylation, regulate gene expression in RA pathogenesis. Tumour necrosis factor-alpha (TNF-α) inhibitors such as etanercept and adalimumab, represent a breakthrough in RA treatment. We aimed to investigate the effects of etanercept and adalimumab on human Th17-polarized cells and the possible intracellular regulators of these effects, including the Th17-specific transcription factors signal transducer, activator of transcription 3 (STAT3), retinoid-related orphan receptor γ-T (RORγt) and epigenetic modification...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#11
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925785/accelerating-scientific-advancement-for-pediatric-rare-lung-disease-research-report-from-a-national-institutes-of-health-nhlbi-workshop-september-3-and-4-2015
#12
Lisa R Young, Bruce C Trapnell, Kenneth D Mandl, Daniel T Swarr, Jennifer A Wambach, Carol J Blaisdell
Pediatric rare lung disease (PRLD) is a term that refers to a heterogeneous group of rare disorders in children. In recent years, this field has experienced significant progress marked by scientific discoveries, multicenter and interdisciplinary collaborations, and efforts of patient advocates. Although genetic mechanisms underlie many PRLDs, pathogenesis remains uncertain for many of these disorders. Furthermore, epidemiology and natural history are insufficiently defined, and therapies are limited. To develop strategies to accelerate scientific advancement for PRLD research, the NHLBI of the National Institutes of Health convened a strategic planning workshop on September 3 and 4, 2015...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27925688/rare-deleterious-pard3-variants-in-the-apkc-binding-region-are-implicated-in-the-pathogenesis-of-human-cranial-neural-tube-defects-via-disrupting-apical-tight-junction-formation
#13
Xiaoli Chen, Yu An, Yonghui Gao, Liu Guo, Lei Rui, Hua Xie, Mei Sun, Siv Lam Hung, Xiaoming Sheng, Jizhen Zou, Yihua Bao, Hongyan Guan, Bo Niu, Zandong Li, Richard H Finnell, James F Gusella, Bai-Lin Wu, Ting Zhang
Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial NTD susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, p<0.05, OR = 3...
December 7, 2016: Human Mutation
https://www.readbyqxmd.com/read/27925643/primary-and-secondary-hemophagocytic-lymphohistiocytosis-have-different-patterns-of-t-cell-activation-differentiation-and-repertoire
#14
Sandra Ammann, Kai Lehmberg, Udo Zur Stadt, Gritta Janka, Anne Rensing-Ehl, Christian Klemann, Maximilian Heeg, Sebastian Bode, Ilka Fuchs, Stephan Ehl
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome characterized by hyperactivation of lymphocytes and histiocytes. T cells play a key role in HLH pathogenesis, but their differentiation pattern is not well characterized in patients with active HLH. We compared T-cell activation patterns between patients with familial HLH (1°HLH), 2°HLH without apparent infectious trigger (2°HLH) and 2°HLH induced by a viral infection (2°V-HLH). Polyclonal CD8(+) T cells are highly activated in 1°HLH and 2°V-HLH, but less in 2°HLH as assessed by HLA-DR expression and marker combination with CD45RA, CCR7, CD127, PD-1 and CD57...
December 7, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27925632/sepsis-induces-telomere-shortening-a-potential-mechanism-responsible-for-delayed-pathophysiological-events-in-sepsis-survivors
#15
Naara Mendes Oliveira, Ester C S Rios, Thais Martins de Lima, Vanessa Jacob Victorino, Hermes Barbeiro, Fabiano Pinheiro da Silva, Csaba Szabo, Francisco Garcia Soriano
Sepsis survivors suffer from additional morbidities, including higher disk of readmissions, nervous system disturbances and cognitive dysfunction, and increased mortality, even several years after the initial episode of sepsis. In many ways, the phenotype of sepsis survivors resembles the phenotype associated with accelerated aging. Since telomere shortening is a hallmark of aging, we investigated whether sepsis also leads to telomere shortening. Male balb/c mice were divided into two groups: the control group received 100 μl of normal saline intraperitoneally; the sepsis group received 15 mg/kg of bacterial lipopolysaccharide i...
December 5, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27925197/factor-xa-signaling-contributes-to-the-pathogenesis-of-inflammatory-diseases
#16
REVIEW
Safieh Ebrahimi, Sara Rezaei, Parvaneh Seiri, Mikhail Ryzhikov, Seyed Issac Hashemy, Seyed Mahdi Hassanian
The coagulation protease Factor Xa (FXa) triggers a variety of signaling pathways through activation of protease-activated receptors (PARs) and non-PAR receptors. FXa-mediated signaling is strongly implicated in the pathogenesis of several inflammatory diseases including fibrosis, cardiovascular diseases and cancer. Thus, targeting of FXa can have great clinical significance in terms of the treatment of these disorders. This review summarizes the current knowledge about the mechanism of FXa signaling in cellular and animal systems under (patho)physiological conditions for a better understanding and hence a better management of FXa-induced disorders...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925193/systemic-and-local-adipose-tissue-in-knee-osteoarthritis
#17
REVIEW
Elisa Belluzzi, Hamza El Hadi, Marnie Granzotto, Marco Rossato, Roberta Ramonda, Veronica Macchi, Raffaele De Caro, Roberto Vettor, Marta Favero
Osteoarthritis is a common chronic joint disorder affecting older people. The knee is the major joint affected. The symptoms of osteoarthritis include limited range of motion, joint swelling, and pain causing disability. There are no disease modifying drugs available, and treatments are mainly focused on pain management. Total knee replacement performed at the end stage of the disease is considered the only cure available. It has been found that obese people have an increased risk to develop not only knee but also hand osteoarthritis...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27925050/fetal-thrombotic-vasculopathy-a-case-report-and-literature-review
#18
Ana Berquo Peleja, Silvio Martinelli, Renata Lopes Ribeiro, Roberto Eduardo Bittar, Regina Schultz, Rossana Pulcineli Vieira Francisco
Introduction: Fetal thrombotic vasculopathy is a recently described placental alteration with varying degrees of involvement and often associated with adverse perinatal outcomes. The diagnosis is made histologically and therefore is postnatal, which makes it a challenge in clinical practice. Method: Case report and review of literature on the subject. Results: The present case refers to a pregnant woman presenting fetal growth restriction, with poor obstetrical past, and sent late to our service...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27925039/metaplastic-squamous-cell-carcinoma-of-the-breast-a-case-report-and-literature-review
#19
Luciana Graziano, Paschoal Graziano, Almir Galvão Vieira Bitencourt, Daniel Bernal Soto, Alexandre Hiro, Cíntia Camillo Nunes
Metaplastic tumors are rare and represent a heterogeneous group of neoplasms showing dominant areas of non-glandular differentiation. Etiology and pathogenesis of this type of lesion in the breast is uncertain. The most common sources of metastatic squamous cell carcinoma of the breast are lung, esophagus, cervix, and urinary bladder. Squamous cell carcinomas may present clinically with inflammation and average size greater than breast adenocarcinoma. As for imaging studies, mammography shows no typical findings and ultrasound can show a complicated cyst or an inflammatory process, among the differential diagnoses...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27924915/serum-uric-acid-is-independently-and-linearly-associated-with-risk-of-nonalcoholic-fatty-liver-disease-in-obese-chinese-adults
#20
Chang-Qin Liu, Chun-Mei He, Ning Chen, Dongmei Wang, Xiulin Shi, Yongwen Liu, Xin Zeng, Bing Yan, Suhuan Liu, Shuyu Yang, Xiaoying Li, Xuejun Li, Zhibin Li
The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25...
December 7, 2016: Scientific Reports
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