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Uveitis-Mediated Immune Cell Invasion Through The Extracellular Matrix Of The Lens Capsule, JodiRae DeDreu, Sonali Pal-Ghosh, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko 2022 Thomas Jefferson University

Uveitis-Mediated Immune Cell Invasion Through The Extracellular Matrix Of The Lens Capsule, Jodirae Dedreu, Sonali Pal-Ghosh, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule ...


Monitoring The Systemic Immune System To Understand And Improve The Efficacy Of Immunotherapy For Metastatic Osteosarcoma, justin edward markel 2022 West Virginia University

Monitoring The Systemic Immune System To Understand And Improve The Efficacy Of Immunotherapy For Metastatic Osteosarcoma, Justin Edward Markel

Graduate Theses, Dissertations, and Problem Reports

Osteosarcoma (OS) is a complex tumor with no effective targeted therapies due to its genomic heterogeneity and pleomorphism. The immune response it creates, particularly against metastatic lesions, is considerable; however, various suppressive mechanisms induced by the tumor prohibit its effectiveness. The presence of infiltrating lymphocytes suggests that therapeutic disinhibition through checkpoint blockade could increase antitumor immunity, though none have been successful in clinical trials. The complexities of the immune response to OS tumors have yet to be unraveled; however, there is evidence to suggest that cell-mediated immunity (CMI, specifically T cells, Natural Killer [NK] cells, and myeloid-lineage cells [MLCs]) plays ...


Sox10 Requirement For Melanoma Tumor Growth Is Due, In Part, To Immune-Mediated Effects, Sheera Rosenbaum, Manoela Tiago, Signe Caksa, Claudia Capparelli, Timothy J. Purwin, Gaurav Kumar, McKenna Glasheen, Danielle Pomante, Daniel Kotas, I Chervoneva, A E Aplin 2021 Thomas Jefferson University

Sox10 Requirement For Melanoma Tumor Growth Is Due, In Part, To Immune-Mediated Effects, Sheera Rosenbaum, Manoela Tiago, Signe Caksa, Claudia Capparelli, Timothy J. Purwin, Gaurav Kumar, Mckenna Glasheen, Danielle Pomante, Daniel Kotas, I Chervoneva, A E Aplin

Department of Cancer Biology Faculty Papers

Developmental factors may regulate the expression of immune modulatory proteins in cancer, linking embryonic development and cancer cell immune evasion. This is particularly relevant in melanoma because immune checkpoint inhibitors are commonly used in the clinic. SRY-box transcription factor 10 (SOX10) mediates neural crest development and is required for melanoma cell growth. In this study, we investigate immune-related targets of SOX10 and observe positive regulation of herpesvirus entry mediator (HVEM) and carcinoembryonic-antigen cell-adhesion molecule 1 (CEACAM1). Sox10 knockout reduces tumor growth in vivo, and this effect is exacerbated in immune-competent models. Modulation of CEACAM1 expression but not HVEM elicits modest ...


The Effect Of Cancer Cachexia Progression On The Feeding Regulation Of Skeletal Muscle Protein Turnover, Brittany R. Franch 2021 University of Tennessee Health Science Center

The Effect Of Cancer Cachexia Progression On The Feeding Regulation Of Skeletal Muscle Protein Turnover, Brittany R. Franch

Theses and Dissertations (ETD)

Cancer cachexia is defined as the unintentional loss of skeletal muscle mass with or without fat loss that cannot be reversed by conventional nutritional support. Cachexia occurs in ~20% of cancer patients. More specifically, 50% of lung cancer patients, the most common cancer worldwide, develop cachexia. Cachexia occurs most often in lung and gastrointestinal cancers, whereas breast and prostate have the lowest rate of cachexia. Cancer-induced cachexia disrupts skeletal muscle protein turnover (decreasing protein synthesis and increasing protein degradation). Skeletal muscle’s capacity for protein synthesis is highly sensitive to local and systemic stimuli that are controlled by mTORC1 and ...


The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer 2021 Goethe University

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 ...


A Spatial Model Of Hepatic Calcium Signaling And Glucose Metabolism Under Autonomic Control Reveals Functional Consequences Of Varying Liver Innervation Patterns Across Species, Aalap Verma, Alexandra Manchel, Rahul Narayanan, Jan B. Hoek, Babatunde A Ogunnaike, Rajanikanth Vadigepalli 2021 Thomas Jefferson University

A Spatial Model Of Hepatic Calcium Signaling And Glucose Metabolism Under Autonomic Control Reveals Functional Consequences Of Varying Liver Innervation Patterns Across Species, Aalap Verma, Alexandra Manchel, Rahul Narayanan, Jan B. Hoek, Babatunde A Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Rapid breakdown of hepatic glycogen stores into glucose plays an important role during intense physical exercise to maintain systemic euglycemia. Hepatic glycogenolysis is governed by several different liver-intrinsic and systemic factors such as hepatic zonation, circulating catecholamines, hepatocellular calcium signaling, hepatic neuroanatomy, and the central nervous system (CNS). Of the factors regulating hepatic glycogenolysis, the extent of lobular innervation varies significantly between humans and rodents. While rodents display very few autonomic nerve terminals in the liver, nearly every hepatic layer in the human liver receives neural input. In the present study, we developed a multi-scale, multi-organ model of hepatic metabolism ...


Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph 2021 Thomas Jefferson University

Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the ...


Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu 2021 Zhengzhou University

Mirna-30e Downregulation Increases Cancer Cell Proliferation, Invasion And Tumor Growth Through Targeting Rps6kb1, Lin Wang, Xiang-Bo Ji, Li-Hong Wang, Zhong-Kun Xia, Yun-Xia Xie, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang, Ling-Zhi Liu

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Human esophagus carcinoma (EC) is one of the most common malignant tumors, especially in Africa and Asia including China. In EC initiation and progression, genetic and epigenetic aberrations have been reported to play a major role, but the underlying molecular mechanisms are largely unknown. In this study, the miR-30e levels were analyzed in human EC tissues and TCGA databases, and the results demonstrated that miR-30e expression in EC tissues was significantly decreased compared to adjacent normal tissues. To further investigate the role of miR-30e in cancer cells, we found that forced expression of miR-30e dramatically inhibited cell proliferation, invasion, tube ...


An Investigative Analysis Of Underlying Alzheimer’S Disease Pathology: Understanding The Pathology Of Neurofibril Tangles, William Barker 2021 Liberty University

An Investigative Analysis Of Underlying Alzheimer’S Disease Pathology: Understanding The Pathology Of Neurofibril Tangles, William Barker

Senior Honors Theses

Researchers familiar with Alzheimer’s Disease (AD) refer to two common pathological hallmarks: β-amyloid plaques and Neurofibril Tangles (NFTs). The development of these pathologies are the leading theory to explain the cause of cognitive decline and dementia-like symptoms of individuals with AD. The literature supports the theory that NFTs are caused by the hyperphosphorylation of the precursor tau protein. However, the mechanism that causes this hyperphosphorylation is still unknown. This review seeks to evaluate the normal function of tau then analyze and expound upon the current research concerning the underlying mechanisms for the hyperphosphorylation of tau observed in Neurofibril Tangles ...


Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari 2021 University of Tennessee Health Science Center

Role Of Smad2 And Smad3 On Adipose Tissue Development And Function, Roshan Kumari

Theses and Dissertations (ETD)

Introduction: Obesity and its associated metabolic syndrome are major medical problems worldwide including United States. Adipose tissue is the primary site of energy storage, playing important roles in health. Adipose tissue also has other critical functions, producing adipocytokines and contributing to normal nutrient metabolism, which in turn play important roles in satiety, inflammation, and total energy homeostasis. Activin A and activin B play important roles in maintaining body composition and energy homeostasis. This dissertation highlights the role of activin/SMADs signaling in adipose tissue development, function, and maintenance.

SMAD2/3 proteins are downstream mediators of transforming growth factor-β (TGFβ) family ...


The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato 2021 Thomas Jefferson University

The Role Of Hgf/Met Signaling In Metastatic Uveal Melanoma, Ryota Tanaka, Mizue Terai, Eric R Londin, Takami Sato

Department of Medical Oncology Faculty Papers

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To ...


Retinoic Acid Fluctuation Activates An Uneven, Direction-Dependent Network-Wide Robustness Response In Early Embryogenesis, Madhur Parihar, Liat Bendelac-Kapon, Michal Gur, Tali Abbou, Abha Belorkar, Sirisha Achanta, Keren Kinberg, Rajanikanth Vadigepalli, Abraham Fainsod 2021 Thomas Jefferson University

Retinoic Acid Fluctuation Activates An Uneven, Direction-Dependent Network-Wide Robustness Response In Early Embryogenesis, Madhur Parihar, Liat Bendelac-Kapon, Michal Gur, Tali Abbou, Abha Belorkar, Sirisha Achanta, Keren Kinberg, Rajanikanth Vadigepalli, Abraham Fainsod

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Robustness is a feature of regulatory pathways to ensure signal consistency in light of environmental changes or genetic polymorphisms. The retinoic acid (RA) pathway, is a central developmental and tissue homeostasis regulatory signal, strongly dependent on nutritional sources of retinoids and affected by environmental chemicals. This pathway is characterized by multiple proteins or enzymes capable of performing each step and their integration into a self-regulating network. We studied RA network robustness by transient physiological RA signaling disturbances followed by kinetic transcriptomic analysis of the recovery during embryogenesis. The RA metabolic network was identified as the main regulated module to achieve ...


M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun 2021 Xi'an Jiaotong University

M6a Associated Tsuc7 Inhibition Contributed To Erlotinib Resistance In Lung Adenocarcinoma Through A Notch Signaling Activation Dependent Way, Kai Li, Zi-Yang Peng, Shan Gao, Qing-Shi Wang, Rui Wang, Xiang Li, Guo-Dong Xiao, Jing Zhang, Hong Ren, Shou-Ching Tang, Xin Sun

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: The small tyrosine kinase inhibitors (TKIs) subversively altered the lung cancer treatments, but patients will inevitably face the therapy resistance and disease recurrence. We aim to explore the potential roles of non-coding RNAs in sensitizing the TKIs effects.

Methods: Multiple cellular and molecular detections were applied to confirm the mechanistic regulations and intracellular connections.

Results: We explored the specific gene features of candidates in association with resistance, and found that m6A controlled the stemness of EMT features through METTL3 and YTHDF2. The miR-146a/Notch signaling was sustained highly activated in a m6A dependent manner, and the m6A regulator of ...


Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic 2021 UNIVERSITY OF KRAGUJEVAC, FACULTY OF MEDICAL SCIENCES, DEPARTMENT OF GENETICS, SERBIA

Therapeutic Efficacy Of Mesenchymal Stem Cells For Cardiovascular Diseases, Dragana Radoje Miloradovic, Dragica Radoje Pavlovic, Miodrag Bozidar Stojkovic, Sanja Bratislav Bojic, Vladislav Bogdan Volarevic, Marina Milosav Gazdic Jankovic, Biljana Tomislav Ljujic

Journal of Mind and Medical Sciences

Despite the improvements in pharmacological and surgical treatments, cardiovascular diseases (CVDs) are the number one cause of death worldwide. During the last two decades, the search for new therapies has been revolutionized with the growing knowledge of stem cell biology. Due to their huge differentiation capacity and paracrine effects, mesenchymal stem cells (MSCs) are a promising tool for the treatment of CVDs. The encouraging outcomes of preclinical studies using MSCs as a treatment for diseased myocardium have set the scene for worldwide clinical trials. In this review, we overview either complete or ongoing clinical trials using MSCs for the therapy ...


Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan 2021 Thomas Jefferson University

Cell-Based Therapies For Retinal Diseases: A Review Of Clinical Trials And Direct To Consumer "Cell Therapy" Clinics, John Hinkle, Raziyeh Mahmoudzadeh, Ajay E. Kuriyan

Wills Eye Hospital Papers

Background: The retinal pigment epithelium (RPE) is implicated in the pathophysiology of many retinal degenerative diseases. This cell layer is also an ideal target for cell-based therapies. Several early phase clinical trials evaluating cell therapy approaches for diseases involving the RPE, such as age-related macular degeneration and Stargardt's macular dystrophy have been published. However, there have also been numerous reports of complications from unproven "cell therapy" treatments marketed by "cell therapy" clinics. This review aims to outline the particular approaches in the different published clinical trials for cell-based therapies for retinal diseases. Additionally, the controversies surrounding experimental treatments offered ...


Gβγ Regulates Mitotic Golgi Fragmentation And G2/M Cell Cycle Progression., Kalpana Rajanala, Lauren M. Klayman, Philip B. Wedegaertner 2021 Thomas Jefferson University

Gβγ Regulates Mitotic Golgi Fragmentation And G2/M Cell Cycle Progression., Kalpana Rajanala, Lauren M. Klayman, Philip B. Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

Heterotrimeric G proteins (αβγ) function at the cytoplasmic surface of a cell's plasma membrane to transduce extracellular signals into cellular responses. However, numerous studies indicate that G proteins also play noncanonical roles at unique intracellular locations. Previous work has established that G protein βγ subunits (Gβγ) regulate a signaling pathway on the cytoplasmic surface of Golgi membranes that controls the exit of select protein cargo. Now, we demonstrate a novel role for Gβγ in regulating mitotic Golgi fragmentation, a key checkpoint of the cell cycle that occurs in the late G2 phase. We show that small interfering RNA-mediated depletion ...


Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei 2021 Portland State University

Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei

University Honors Theses

Trained immunity is long-term innate immune memory induced by a primary stimulus, which leads to hyper-inflammation upon secondary stimulation with a homologous or heterologous ligand. Trained immunity is mediated by epigenetic and metabolic reprogramming of the target cell and leads to modification of gene expression and cellular function. Classically, trained immunity is initiated by β-glucans, an inflammatory molecule found on the exterior of fungal species. Interestingly, our lab has recently described that dietary fatty acids can initiate trained immunity, working through similar pathways as β-glucans. Specifically, our data show that a pre-treatment with a specific dietary saturated fatty acid (SFA ...


Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez 2021 Seton Hall University

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic ...


Comparative Analysis Of Proteomics Biomarkers Associated With Residual Ridge Resorption Induced By Denture Wear, Rohana Ahmad, Ainin Sofia Mohamad Napi, Tong Wah Lim, Su Keng Tan, Saiful Anuar Karsani, Musalmah Mazlan, Lay Kek Teh, Steven M. Morgano, Nadim Z. Baba 2021 Center of Restorative Dentistry Studies, Faculty of Dentistry, Universiti Teknologi MARA, Selangor 47000, Malaysia

Comparative Analysis Of Proteomics Biomarkers Associated With Residual Ridge Resorption Induced By Denture Wear, Rohana Ahmad, Ainin Sofia Mohamad Napi, Tong Wah Lim, Su Keng Tan, Saiful Anuar Karsani, Musalmah Mazlan, Lay Kek Teh, Steven M. Morgano, Nadim Z. Baba

Makara Journal of Health Research

Background: The biochemical bone turnover markers for residual ridge resorption (RRR) are unclear. Therefore, the present study aimed to determine the biochemical bone turnover markers associated with RRR by comparing proteomics between the compressed mucosa of denture wearers and the non-compressed mucosa of non-denture wearers.

Methods: The mucosal specimens of 11 complete-denture wearers were obtained from the alveolar ridge during surgical implant exposure for implant-retained overdentures. All denture wearers had been edentulous and worn dentures for at least 5 years. The tissues of 11 non-denture wearers were taken from the ridge during minor preprosthetic surgery. The mucosal proteins were extracted ...


Scrna Seq Analysis Of Ebv+ Associated Gastric Cancer, Eric Wang 2021 Western University

Scrna Seq Analysis Of Ebv+ Associated Gastric Cancer, Eric Wang

Undergraduate Student Research Internships Conference

No abstract provided.


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