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Full-Text Articles in Cells

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin Mar 2024

Nf-Κb As An Inducible Regulator Of Inflammation In The Central Nervous System, Sudha Anilkumar, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as …

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Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang Jan 2024

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

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Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang Jan 2024

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …

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Nanosecond Pulsed Electric Fields Increase Antibiotic Susceptibility In Methicillin-Resistant Staphylococcus Aureus, Alexandra E. Chittams-Miles, Areej Malik, Erin B. Purcell, Claudia Muratori Jan 2024

Nanosecond Pulsed Electric Fields Increase Antibiotic Susceptibility In Methicillin-Resistant Staphylococcus Aureus, Alexandra E. Chittams-Miles, Areej Malik, Erin B. Purcell, Claudia Muratori

Bioelectrics Publications

Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this …

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Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia Jan 2024

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

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Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo Jan 2024

Identification And Characterization Of Two Novel Kcnh2 Mutations Contributing To Long Qt Syndrome, Anthony Owusu-Mensah, Jacqueline Treat, Joyce Bernardi, Ryan Pfeiffer, Robert Goodrow, Bright Tsevi, Victoria Lam, Michel Audette, Jonathan M. Cordeiro, Makarand Deo

Electrical & Computer Engineering Faculty Publications

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the …

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Tailored Micromagnet Sorting Gate For Simultaneous Multiple Cell Screening In Portable Magnetophoretic Cell-On-Chip Platforms, Jonghwan Yoon, Yumin Kang, Hyeonseol Kim, Abbas Ali, Keonmok Kim, Sri Ramulu Torati, Mi-Young Im, Changyeop Jeon, Byeonghwa Lim, Cheolgi Kim Jan 2024

Tailored Micromagnet Sorting Gate For Simultaneous Multiple Cell Screening In Portable Magnetophoretic Cell-On-Chip Platforms, Jonghwan Yoon, Yumin Kang, Hyeonseol Kim, Abbas Ali, Keonmok Kim, Sri Ramulu Torati, Mi-Young Im, Changyeop Jeon, Byeonghwa Lim, Cheolgi Kim

Bioelectronics Publications

Conventional magnetophoresis techniques for manipulating biocarriers and cells predominantly rely on large-scale electromagnetic systems, which is a major obstacle to the development of portable and miniaturized cell-on-chip platforms. Herein, a novel magnetic engineering approach by tailoring a nanoscale notch on a disk micromagnet using two-step optical and thermal lithography is developed. Versatile manipulations are demonstrated, such as separation and trapping, of carriers and cells by mediating changes in the magnetic domain structure and discontinuous movement of magnetic energy wells around the circumferential edge of the micromagnet caused by a locally fabricated nano-notch in a low magnetic field system. The motion …

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On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski Dec 2023

On The Anti-Adipogenic Function Of Collagen Triple Helix Repeat-Containing Protein 1, Matthew E. Siviski

Electronic Theses and Dissertations

Adipogenesis is regulated by the coordinated activity of adipogenic transcription factors, including PPAR-gamma (PPARG) and C/EBP alpha (CEBPA). Thus, dysregulated adipogenesis predisposes adipose tissues to adipocyte hypertrophy and hyperplasia. We have previously reported that mice possessing a homozygous null gene mutation in collagen triple helix repeat-containing protein 1 (CTHRC1) have increased adiposity compared to wildtype mice, supporting the concept that CTHRC1 regulates body composition. Herein, we investigated the anti-adipogenic activity of CTHRC1. Using 3T3-L1 preadipocytes, we showed significantly reduced adipogenic differentiation in the presence of CTHRC1 commensurate to marked suppression of Cebpa and Pparg gene expression. In addition, CTHRC1 increased …

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Tumor Infiltrating Lymphocytes (Tils) Are A Prognosis Biomarker In Colombian Patients With Triple Negative Breast Cancer, Carlos A. Huertas-Caro, Mayra A. Ramírez, Laura Rey-Vargas, Lina María Bejarano-Rivera, Diego Felipe Ballen, Marcela Nuñez, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez Dec 2023

Tumor Infiltrating Lymphocytes (Tils) Are A Prognosis Biomarker In Colombian Patients With Triple Negative Breast Cancer, Carlos A. Huertas-Caro, Mayra A. Ramírez, Laura Rey-Vargas, Lina María Bejarano-Rivera, Diego Felipe Ballen, Marcela Nuñez, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with …

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The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl Nov 2023

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

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A Neurodevelopmental Perspective To Improve Innovation In Preventive Treatment Of Substance Use Disorders, Ismael Perez, John Vandeberg, Mario Gil Sep 2023

A Neurodevelopmental Perspective To Improve Innovation In Preventive Treatment Of Substance Use Disorders, Ismael Perez, John Vandeberg, Mario Gil

Research Symposium

Background: Midbrain dopaminergic neurons have been associated with substance use disorders (Blaess & Ang, 2015). Understanding their neurodevelopment during early stages of life is fundamental for innovating preventive care treatments. The animal model Monodelphis domestica has been proposed as an excellent candidate to study neurodevelopmental changes due to the ease of access to see changes in their embryonic development (Mate et al., 1994). The purpose of our study is to inform how brain cells, including and especially dopaminergic neurons, mature by quantifying their number during early development. Additionally, the study aims to compare different midbrain areas and track neurodevelopmental changes …

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Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal Sep 2023

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

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Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr Sep 2023

Candida-Induced Granulocytic Myeloid-Derived Suppressor Cells Are Protective Against Polymicrobial Sepsis, Shannon Esher Righi, Amanda J. Harriett, Elizabeth A. Lilly, Paul L. Fidel Jr., Mairi C. Noverr

School of Dentistry Faculty Publications

Polymicrobial intra-abdominal infections (IAI) can lead to life-threatening sepsis with significant morbidity and mortality, especially when pathogenic fungi are involved. We have employed an established clinically relevant mouse model of fungal/bacterial IAI and shown that immunization with low-virulence Candida species, that is, Candida dubliniensis, can induce responses that protect against sepsis via the suppression of lethal inflammation. This protection is dependent on long-lived Gr-1(+) polymorphonuclear leukocytes that display characteristics consistent with myeloid-derived suppressor cells (MDSCs) and trained innate immunity. Here we aimed to functionally and phenotypically characterize these protective Gr-1(+) leukocytes. Compared to nonimmunized control mice, we observed increased levels …

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Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke Aug 2023

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

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Pannexin3 In Exercise, Obesity, And Osteoarthritis, Brent Wakefield Aug 2023

Pannexin3 In Exercise, Obesity, And Osteoarthritis, Brent Wakefield

Electronic Thesis and Dissertation Repository

Pannexin 3 (PANX3), is a glycoprotein that oligomerizes to form mechano-sensitive channels expressed in musculoskeletal tissues, and has been identified as a potential target for the treatment of obesity and osteoarthritis (OA). Obesity and OA are two of the most prevalent diseases worldwide, leading to disability and even death. These conditions are thought to originate from a complex interaction between genetics, aging, sex, and modifiable lifestyle factors, such as exercise. Investigating the interactions between genetic and exercise may provide a more comprehensive, context-specific understanding of gene function. This thesis aimed to understand the interactions between PANX3 and exercise interventions on …

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Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart Jun 2023

Targeting Cgas/Sting Signaling-Mediated Myeloid Immune Cell Dysfunction In Time, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Graduate Studies Faculty Publications

Myeloid immune cells (MICs) are potent innate immune cells serving as first responders to invading pathogens and internal changes to cellular homeostasis. Cancer is a stage of altered cellular homeostasis that can originate in response to different pathogens, chemical carcinogens, and internal genetic/epigenetic changes. MICs express several pattern recognition receptors (PRRs) on their membranes, cytosol, and organelles, recognizing systemic, tissue, and organ-specific altered homeostasis. cGAS/STING signaling is a cytosolic PRR system for identifying cytosolic double-stranded DNA (dsDNA) in a sequence-independent but size-dependent manner. The longer the cytosolic dsDNA size, the stronger the cGAS/STING signaling activation with increased type 1 interferon …

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Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder Jun 2023

Systemic Review Of Clot Retraction Modulators, Alaina Guilbeau, Rinku Majumder

School of Graduate Studies Faculty Publications

Through a process termed clot retraction, platelets cause thrombi to shrink and become more stable. After platelets are activated via inside-out signaling, glycoprotein αIIbβIII binds to fibrinogen and initiates a cascade of intracellular signaling that ends in actin remodeling, which causes the platelet to change its shape. Clot retraction is also important for wound healing. Although the detailed molecular biology of clot retraction is only partially understood, various substances and physiological conditions modulate clot retraction. In this review, we describe some of the current literature pertaining to clot retraction modulators. In addition, we discuss compounds from Cudrania trucuspidata, Arctium lappa, …

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Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods Jun 2023

Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods

School of Medicine Faculty Publications

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. …

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Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan Jun 2023

Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Graduate Studies Faculty Publications

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …

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Control Of The Electroporation Efficiency Of Nanosecond Pulses By Swinging The Electric Field Vector Direction, Vitalii Kim, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Ruben M. L. Colunga Biancatelli, Andrei G. Pakhomov Jun 2023

Control Of The Electroporation Efficiency Of Nanosecond Pulses By Swinging The Electric Field Vector Direction, Vitalii Kim, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Ruben M. L. Colunga Biancatelli, Andrei G. Pakhomov

Bioelectrics Publications

Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing …

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Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang Apr 2023

Moerv14 Mediates The Intracellular Transport Of Cell Membrane Receptors To Govern The Appressorial Formation And Pathogenicity Of Magnaporthe Oryzae, Bin Qian, Xiaotong Su, Ziyuan Ye, Xinyu Liu, Muxing Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Magnaporthe oryzae causes rice blasts posing serious threats to food security worldwide. During infection, M. oryzae utilizes several transmembrane receptor proteins that sense cell surface cues to induce highly specialized infectious structures called appressoria. However, little is known about the mechanisms of intracellular receptor tracking and their function. Here, we described that disrupting the coat protein complex II (COPII) cargo protein MoErv14 severely affects appressorium formation and pathogenicity as the ΔMoerv14 mutant is defective not only in cAMP production but also in the phosphorylation of the mitogen-activated protein kinase (MAPK) MoPmk1. Studies also showed that either externally supplementing cAMP or …

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Triazole Compounds – Potentials In The Treatment Of Cystic Fibrosis, Maggie Taylor Mar 2023

Triazole Compounds – Potentials In The Treatment Of Cystic Fibrosis, Maggie Taylor

Undergraduate Research Conference

Cystic Fibrosis (CF) is a genetic disease that affects the respiratory and digestive system and is most common among Caucasians of Northern European origin. CF is caused by mutations in a membrane protein CFTR (Cystic Fibrosis Transmembrane-conductance Regulator). This mutation impairs the membrane protein’s chloride ion channel function. One of the most common CFTR mutations is the DF508 mutation that affects over 70% of CF cases. Our research has shown that the DF508-CFTR mutation can be partially reversed by physical and chemical means [Heda & Marino, BBRC, 271:659-664, 2000]. In cell lines expressing DF508-CFTR, synthetic anion carriers have shown to …

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Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee Mar 2023

Enhanced Ca2+-Channeling Complex Formation At The Er-Mitochondria Interface Underlies The Pathogenesis Of Alcohol-Associated Liver Disease, Themis Thoudam, Dipanjan Chanda, Jung Yi Lee, Min Kyo Jung, Ibotombi Singh Sinam, Byung Gyu Kim, Bo Yoon Park, Woong Hee Kwon, Hyo Jeong Kim, Myeongjin Kim, Chae Won Lim, Hoyul Lee, Yang Hoon Huh, Caroline A. Miller, Romil Saxena, Nicholas J. Skill, Nazmul Huda, Praveen Kusumanchi, Jing Ma, Zhihong Yang, Min Ji Kim, Ji Young Mun, Robert A. Harris, Jae Han Jeon, Suthat Liangpunsakul, In Kyu Lee

School of Medicine Faculty Publications

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 …

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Lipoprotein(A) In Atherosclerotic Cardiovascular Disease And Aortic Stenosis: A European Atherosclerosis Society Consensus Statement, Florian Kronenberg, Samia Mora, Erik S G Stroes, Brian Ference Ference Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, Marlys Koschinsky, Gilles Lambert, Salim S. Virani Feb 2023

Lipoprotein(A) In Atherosclerotic Cardiovascular Disease And Aortic Stenosis: A European Atherosclerosis Society Consensus Statement, Florian Kronenberg, Samia Mora, Erik S G Stroes, Brian Ference Ference Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, Marlys Koschinsky, Gilles Lambert, Salim S. Virani

Office of the Provost

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do …

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H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam Feb 2023

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

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Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang Feb 2023

Quitting Smoking After A Cancer Diagnosis Is Associated With High-Risk Neutrophil-To-Lymphocyte Ratio Among Tobacco Use-Related Cancer Survivors, You Lu, Katherine Kwong, James Wells, Andrea Edwards, Zhong Chen, Tung-Sung Tseng, Kun Zhang

School of Public Health Faculty Publications

Quitting smoking could potentially minimize the risk of a high neutrophil-to-lymphocyte ratio (NLR) among tobacco use-related (TUR) cancer survivors. A total of 1263 TUR cancer survivors aged 20 to 85 years old were investigated using data from the National Health and Nutritional Examination Survey 1999-2018. The primary outcome was the NLR, which was defined as having two levels: high-risk (≥ 3) and low-risk (< 3). The association between smoking cessation time and a high-risk NLR level was analyzed using weighted logistic regression models. Overall, the current smoking rate of TUR cancer survivors was found to be 21.7%. Older age (75 years above), gender and respiratory-related cancers are covariables associated with high risk of NLR levels for individual who identified as Non-Hispanic White (NHW). Non-Hispanic Black (NHB) (n = 27) who quit smoking after a cancer diagnosis were associated with the highest risk of a high NLR (OR 4.83, 95% CI 1.40-16.61, p = 0.01) compared to NHB nonsmokers (n = 139). These findings suggest that the risk of a high NLR level is strongly associated with the time of smoking cessation in NHB TUR cancer survivors. As a result, NHB TUR cancer survivors should quit smoking as soon as possible because the benefits of quitting smoking were observed over the 5 year period following smoking cessation.

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Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali Jan 2023

Frequency Of Von Willebrand Disease And Its Types: Data From A Tertiary Care Hospital Of Karachi, Pakistan, Jyoti Mohan Lal, Anila Rashid, Natasha Ali

Department of Pathology and Laboratory Medicine

Introduction: von Willebrand disease is the most common inherited bleeding disorder. It is classified into 3 main types, type I and III are quantitative defects whereas type II is qualitative defect which is further sub-classified in to II-A, II-B, II-M, II-N. The aim of the present study is to see frequency and types of von Willebrand disease in a tertiary care hospital of Karachi, Pakistan.
Materials and methods: This retrospective cross-sectional study was conducted in the section of Hematology and Transfusion Medicine, Department of Pathology and Laboratory Medicine, the Aga Khan University hospital, Karachi, from May 2020 to April 2021 …

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Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava Jan 2023

Inhibition Of Ribosome Assembly Factor Pno1 By Crispr/Cas9 Technique Suppresses Lung Adenocarcinoma And Notch Pathway: Clinical Application, Sanjit K. Roy, Shivam Srivastava, Andrew Hancock, Anju Shrivastava, Jason Morvant, Sharmila Shankar, Rakesh K. Srivastava

School of Medicine Faculty Publications

Growth is crucially controlled by the functional ribosomes available in cells. To meet the enhanced energy demand, cancer cells re-wire and increase their ribosome biogenesis. The RNA-binding protein PNO1, a ribosome assembly factor, plays an essential role in ribosome biogenesis. The purpose of this study was to examine whether PNO1 can be used as a biomarker for lung adenocarcinoma and also examine the molecular mechanisms by which PNO1 knockdown by CRISPR/Cas9 inhibited growth and epithelial–mesenchymal transition (EMT). The expression of PNO1 was significantly higher in lung adenocarcinoma compared to normal lung tissues. PNO1 expression in lung adenocarcinoma patients increased with …

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Relationship Of Abdominal Circumference And Trunk Length With Spinal Anesthesia Block Height In Geriatric Patients Undergoing Transurethral Resection Of Prostate, Muhammad Yahya, Aliya Ahmed, Iayla Fatima, Muhammad Nasir Jan 2023

Relationship Of Abdominal Circumference And Trunk Length With Spinal Anesthesia Block Height In Geriatric Patients Undergoing Transurethral Resection Of Prostate, Muhammad Yahya, Aliya Ahmed, Iayla Fatima, Muhammad Nasir

Department of Anaesthesia

Introduction: Spinal anesthesia is commonly used for various surgical procedures. Prediction of spinal anesthesia block height is always a challenging task for anesthetists. Higher than desired levels of spinal anesthesia blocks are associated with serious side effects, while inadequate block height does not provide satisfactory surgical anesthesia. In this study, we observed the relationship between the ratio of trunk length (TL) and square of the abdominal circumference (AC2) and spinal anesthesia sensory block height in geriatric patients undergoing transurethral resection of the prostate (TURP).
Material & Methods: This is a cross-sectional study conducted at the Aga Khan University …

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Testicular Choriocarcinoma With Small Bowel Metastasis And Active Gastrointestinal Bleeding, Asad Saulat Fatimi, Khizer Masroor Anns, Faheemullah Khan, Wasim Ahmed Memon, Junaid Iqbal, Muhammad Aman, Izaz Ahmad, Sahar Fatima Jan 2023

Testicular Choriocarcinoma With Small Bowel Metastasis And Active Gastrointestinal Bleeding, Asad Saulat Fatimi, Khizer Masroor Anns, Faheemullah Khan, Wasim Ahmed Memon, Junaid Iqbal, Muhammad Aman, Izaz Ahmad, Sahar Fatima

Medical College Documents

Testicular choriocarcinomas make up less than 1% of all germ-cell tumors and are highly malignant, attributable to hematogenous spread. While the most common sites of metastasis are the lungs and liver, metastatic spread to the gastrointestinal tract is rare wherein patients may present with GI distress or even an upper GI bleed. In this report, we present a case of known testicular choriocarcinoma in a 40-year-old male who presented to the emergency room with severe anemia and a suspected upper GI bleed.

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