Medicine and Health Sciences Commons^™

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Free Fatty Acid Treatment Alters Autophagy During Mouse Preimplantation Embryo Development, Zuleika C. L. Leung

Electronic Thesis and Dissertation Repository

Obesity-induced hyperlipidemia is one of the main factors for female infertility. Hyperlipidemia, specifically with high levels of palmitic acid (PA) and oleic acid (OA), interferes with preimplantation development. Autophagy is essential in early embryo development but, it is unknown whether hyperlipidemia affects autophagic mechanisms in preimplantation embryos. It was hypothesized that PA will alter autophagy in preimplantation mouse embryos and that the subsequent effects will be reversed by OA. PA impaired blastocyst development by arresting embryos at the 8-cell stage. PA also elevated early embryo autophagy by increasing autophagosome formation, decreasing maturation, and disrupting degradation. Co-treatment with OA showed developmental …

Autophagy Regulation By Lipid Factors With Implications For Parkinson's Disease, Alejandro Soto-Avellaneda

Boise State University Theses and Dissertations

Parkinson’s disease is the second most common neurodegenerative disorder. It is characterized by the death of dopaminergic neurons in the substantia nigra and a series of debilitating motor symptoms. Macroautophagy (hereafter referred to as autophagy) is a cellular process by which cells degrade proteins, lipids, organelles or dysfunctional components. Autophagy is thought to play an important role in Parkinson’s disease, because it is the only cellular process known to remove large protein aggregates, such as those seen in Parkinson’s disease pathology. Historically, a large body of work has focused on reporting on protein effectors of autophagy, and regulation of autophagy …

Autophagy, Apoptosis, The Unfolded Protein Response, And Lung Function In Idiopathic Pulmonary Fibrosis, Pawan Sharma, Javad Alizadeh, Maya Juarez, Afshin Samali, Andrew J Halayko, Nicholas J Kenyon, Saeid Ghavami, Amir A Zeki

Center for Translational Medicine Faculty Papers

Autophagy, apoptosis, and the unfolded protein response (UPR) are fundamental biological processes essential for manifold cellular functions in health and disease. Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary disorder associated with aging that has limited therapies, reflecting our incomplete understanding. We conducted an observational study linking molecular markers of cell stress response pathways (UPR: BiP, XBP1; apoptosis: cleaved caspase-3; autophagy: LC3β) in lung tissues from IPF patients and correlated the expression of these protein markers to each subject's lung function measures. We hypothesized that changes in lung tissue expression of apoptosis, autophagy, and UPR markers correlate with …

Apigenin Ameliorates Hepatic Lipid Accumulation By Activating The Autophagy-Mitochondria Pathway, Man Chen Hsu, Bei Chia Guo, Po-An Hu, Chia Hui Chen, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Apigenin, a flavonoid isolated from plants, provides protection against non-alcoholic fatty liver disease. However, the mechanism by which apigenin decreases lipid accumulation in the liver is unclear. In this study, we investigated the molecular mechanism underlying the beneficial effect of apigenin on the hepatic deregulation of lipid metabolism. Oleic acid (OA)-induced lipid accumulation in human hepatoma cells (Huh7 cells) was used as an in vitro model. Western blot analysis was used for evaluating protein expression. Oil red O staining, Nile red staining, and conventional assay kits were used to assess the level of lipids. Immunocytochemistry was performed to observe mitochondrial …

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 …

Nucleocytoplasmic Expression Of Autophagy-Related Protein 7 In Psoriasis, Ahmed E. Tahoun, Mohammed A. Basha, Rehab M. Samaka, Wafaa A. Shehata

Menoufia Medical Journal

Objective The aim of this study was to evaluate the role of autophagy-related protein 7 (Atg7) in psoriasis. Background Despite psoriasis being a common skin disorder, the exact pathogenic mechanism of psoriasis is still not fully understood. Abnormal autophagy is now established to be associated with pathogenesis of some skin disorders. Atg7 plays a central role in the machinery of the autophagy. Materials and methods This prospective case-control study included 30 patients with chronic plaque psoriasis, either lesional or perilesional, and 20 age-matched and sex-matched apparently normal participants as a control group. All cases were immunohistochemically stained for Atg7 antibody. …

Does Beclin 1 Have A Role In Basal Cell Carcinoma?, Alaa H. Marey, Dania N. Abo Elros, Rehab M. Samaka, Tarek M. Rageh

Menoufia Medical Journal

Objective To evaluate the role of Beclin 1 in basal cell carcinoma (BCC). Background BCC is the most common kind of skin cancer with increased incidence. Autophagy is considered an intracellular homeostatic pathway that is related to cancer and other diseases. Beclin 1 is a specific marker for autophagy. Patients and methods This An Ambidirectional Cohort Study was conducted on 77 cases with BCC and 20 age-matched and sex-matched apparently healthy participants. All sections were immunohistochemical stained for Beclin 1 antibody. Results Significant absolute Beclin 1 cytoplasmic localization in epidermis and dermis of control group was noted, whereas in BCC, …

Atg16l1 As A Novel Biomarker And Autophagy Gene For Diabetic Retinopathy., Xinxiao Gao, Yunhui Du, Wayne Bond Lau, Yu Li, Siquan Zhu, Xin-Liang Ma

Department of Emergency Medicine Faculty Papers

Objective: Accumulating evidence suggests the critical role of autophagy in the pathogenesis of diabetic retinopathy (DR). In the current study, we aim to identify autophagy genes involved in DR via microarray analyses.

Methods: Gene microarrays were performed to identify differentially expressed lncRNAs/mRNAs between normal and DR retinas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of lncRNA-coexpressed mRNAs were used to determine the related pathological pathways and biological modules. Real-time polymerase chain reactions (PCR) were conducted to validate the microarray analyses.

Results: A total of 2474 significantly dysregulated lncRNAs and 959 differentially expressed mRNAs were identified in the …

The Mitochondrial Permeability Transition: Nexus Of Aging, Disease And Longevity., Hagai Rottenberg, Jan B. Hoek

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca²⁺ and NAD⁺. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy …

Repurposing Niclosamide For Targeting Pancreatic Cancer By Inhibiting Hh/Gli Non-Canonical Axis Of Gsk3Β, Jyoti B. Kaushal, Rakesh Bhatia, Ranjana K. Kanchan, Pratima Raut, Surya Mallapragada, Quan P. Ly, Surinder K. Batra, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive …

Post-Translational Modification And Degradation Mechanisms Of The Aryl Hydrocarbon Receptor, Yujie Yang

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor first discovered to be activated by exogenous ligands, such as dioxins, and helps promote downstream gene (e.g. CYP1A1) transcription to metabolize the toxicants. With the reports of various AHR targets genes, the expression levels and activities of AHR have been implicated in many physiological and pathological situations. Understanding how AHR protein level is regulated would provide more information to target AHR. AHR stays in the cytosol in the absence of ligand in a complex with HSP90, p23 and XAP2. After ligand activation, AHR translocates into the nucleus, fulfilling its transactivation function …

Human Monocyte-Derived Macrophage Responses To M. Tuberculosis Differ By The Host’S Tuberculosis, Diabetes Or Obesity Status, And Are Enhanced By Rapamycin, Blanca I. Restrepo, Arshad Khan, Vipul K. Singh, Erica De Leon, Genesis P. Aguillón-Durán, Eder Ledezma-Campos, David H. Canaday, Chinnaswamy Jagannath

School of Medicine Publications and Presentations

Human macrophages play a major role in controlling tuberculosis (TB), but their anti-mycobacterial mechanisms remain unclear among individuals with metabolic alterations like obesity (TB protective) or diabetes (TB risk). To help discern this, we aimed to: i) Evaluate the impact of the host’s TB status or their comorbidities on the anti-mycobacterial responses of their monocyte-derived macrophages (MDMs), and ii) determine if the autophagy inducer rapamycin, can enhance these responses. We used MDMs from newly diagnosed TB patients, their close contacts and unexposed controls. The MDMs from TB patients had a reduced capacity to activate T cells (surrogate for antigen presentation) …