Translational Medical Research Commons^™

Nur77 Mitigates Endothelial Dysfunction Through Activation Of Both Nitric Oxide Production And Anti-Oxidant Pathways, Lin Lu, Soohwa Jang, Jiaqi Zhu, Qing Qin, Lijun Sun, Jianxin Sun

Center for Translational Medicine Faculty Papers

BACKGROUND: Nur77 belongs to the member of orphan nuclear receptor 4A family that plays critical roles in maintaining vascular homeostasis. This study aims to determine whether Nur77 plays a role in attenuating vascular dysfunction, and if so, to determine the molecular mechanisms involved.

METHODS: Both Nur77 knockout (Nur77 KO) and Nur77 endothelial specific transgenic mice (Nur77-Tg) were employed to examine the functional significance of Nur77 in vascular endothelium in vivo. Endothelium-dependent vasodilatation to acetylcholine (Ach) and reactive oxygen species (ROS) production was determined under inflammatory and high glucose conditions. Expression of genes was determined by real-time PCR and western blot …

Pkcε Activator Protects Hippocampal Microvascular Disruption And Memory Defect In 3×Tg-Alzheimer's Disease Mice With Cerebral Microinfarcts, Huaixing Wang, Zongxiu Zhang, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

BACKGROUND: Current evidence suggests that microvessel disease is involved in Alzheimer's disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.

METHODS: To induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 …

Interleukin 31 Receptor Α Promotes Smooth Muscle Cell Contraction And Airway Hyperresponsiveness In Asthma, Santhoshi Akkenepally, Dan Yombo, Sanjana Yerubandi, Geereddy Bhanuprakash Reddy, Deepak Deshpande, Francis Mccormack, Satish Madala

Center for Translational Medicine Faculty Papers

Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and goblet cell hyperplasia. Multiple cytokines, including IFNγ, IL-4, and IL-13 are associated with asthma; however, the mechanisms underlying the effects of these cytokines remain unclear. Here, we report a significant increase in the expression of IL-31RA, but not its cognate ligand IL-31, in mouse models of allergic asthma. In support of this, IFNγ, IL-4, and IL-13 upregulated IL-31RA but not IL-31 in both human and mice primary airway smooth muscle cells (ASMC) isolated from the airways of murine and human lungs. Importantly, the loss of IL-31RA …

Reactive Oxygen Species Behaving Badly: Oxidized Phosphatidylcholines Corrupt Ca2+ Signaling In Airway Smooth Muscle, Deepak A. Deshpande, Raymond B. Penn

Center for Translational Medicine Faculty Papers

No abstract provided.

Editorial: Debates In Cardiovascular Pharmacology And Drug Discovery: 2022, Keman Xu, Fatma Saaoud, Ying Shao, Yifan Lu, Xiaohua Jiang, Sheng Wu, Jianxin Sun, Filipe Fernades Conti, Laisel Martinez, Roberto Vazquez-Padron, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

No abstract provided.

Reclaiming The Balance: Blocking Glutamine Uptake To Restrain Pulmonary Fibrosis, Gang Liu, Ross Summer

Center for Translational Medicine Faculty Papers

No abstract provided.

Epicutaneous Sensitization To The Phytocannabinoid Β-Caryophyllene Induces Pruritic Inflammation, Saadet Inan, Sara J Ward, Citlalli T Baltazar, Gabrielle A. Peruggia, Elham Javed, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

In recent years, there has been increased accessibility to cannabis for recreational and medicinal use. Incidentally, there has been an increase in reports describing allergic reactions to cannabis including exacerbation of underlying asthma. Recently, multiple protein allergens were discovered in cannabis, yet these fail to explain allergic sensitization in many patients, particularly urticaria and angioedema. Cannabis has a rich chemical profile including cannabinoids and terpenes that possess immunomodulatory potential. We examined whether major cannabinoids of cannabis such as cannabidiol (CBD) and the bicyclic sesquiterpene beta-caryophyllene (β-CP) act as contact sensitizers. The repeated topical application of mice skin with β-CP at …

Proteomics-Based Approach For Detailing The Allergenic Profile Of Cannabis Chemotypes, Cali Loblundo, Jenna Severa, Gabrielle A Peruggia, Kristina Reid Black, Suman Chandra, Hemant Lata, Mahmoud Elsohly, Martin D Chapman, Deepak A. Deshpande, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

Allergic sensitization to cannabis is an emerging public health concern and is difficult to clinically establish owing to lack of standardized diagnostic approaches. Attempts to develop diagnostic tools were largely hampered by the Schedule I restrictions on cannabis, which limited accessibility for research. Recently, however, hemp was removed from the classified list, and increased accessibility to hemp allows for the evaluation of its practical clinical value for allergy diagnosis. We hypothesized that the proteomic profile is preserved across different cannabis chemotypes and that hemp would be an ideal source of plant material for clinical testing. Using a proteomics-based approach, we …

Abaloparatide Maintains Normal Rat Blood Calcium Level In Part Via 1,25-Dihydroxyvitamin D/Osteocalcin Signaling Pathway, Yanmei Yang, Wei-Ju Louis Tseng, Bin Wang

Center for Translational Medicine Faculty Papers

The PTH-related peptide(1-34) analog, abaloparatide (ABL), is the second anabolic drug available for the treatment of osteoporosis. Previous research demonstrated that ABL had a potent anabolic effect but caused hypercalcemia at a significantly lower rate. However, the mechanism by which ABL maintains the stability of blood calcium levels remains poorly understood. Our in vivo data showed that ABL treatment (40 µg/kg/day for 7 days) significantly increased rat blood level of 1,25-dihydroxyvitamin D [1,25-(OH)2D] without raising the blood calcium value. ABL also significantly augmented the carboxylated osteocalcin (Gla-Ocn) in the blood and bone that is synthesized by osteoblasts, and increased noncarboxylated …

Comparison Of The Biological Basis For Non-Hiv Transmission To Hiv-Exposed Seronegative Individuals, Disease Non-Progression In Hiv Long-Term Non-Progressors And Elite Controllers, Joseph Hokello, Priya Tyagi, Shelly Dimri, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons …

Crosstalk Between Diacylglycerol Kinase And Protein Kinase A In The Regulation Of Airway Smooth Muscle Cell Proliferation, Miguel Angel Hernandez-Lara, Santosh Kumar Yadav, Stanley Conaway, Sushrut D. Shah, Raymond B. Penn, Phd, Deepak A. Deshpande, Phd

Center for Translational Medicine Faculty Papers

Background: Diacylglycerol kinase (DGK) regulates intracellular signaling and functions by converting diacylglycerol (DAG) into phosphatidic acid. We previously demonstrated that DGK inhibition attenuates airway smooth muscle (ASM) cell proliferation, however, the mechanisms mediating this effect are not well established. Given the capacity of protein kinase A (PKA) to effect inhibition of ASM cells growth in response to mitogens, we employed multiple molecular and pharmacological approaches to examine the putative role of PKA in the inhibition of mitogen-induced ASM cell proliferation by the small molecular DGK inhibitor I (DGK I).

Methods: We assayed cell proliferation using CyQUANT™ NF assay, protein expression …

The Effects Of Dual Iqos And Cigarette Smoke Exposure On Airway Epithelial Cells: Implications For Lung Health And Respiratory Disease Pathogenesis, Pritam Saha, Siddhi Jain, Ipsita Mukherjee, Samir R. Panda, Amir A. Zeki, V.G.M. Naidu, Pawan Sharma

Center for Translational Medicine Faculty Papers

Background Cigarette smoking remains a primary cause of chronic lung diseases. After a steady decline, smoking rates have recently increased especially with the introduction of newer electronic nicotine delivery devices, and it is also emerging that dual- or poly-product usage is on the rise. Additionally, with the introduction of IQOS (a heated tobacco product) globally, its impact on human health needs to be investigated. In this study we tested if dual exposure (cigarette smoke (CS)+IQOS) is detrimental to lung epithelial cells when compared with CS or IQOS exposure alone.

Methods Human airway epithelial cells (BEAS-2B) were exposed to either CS, …

Comparing Performance Of Spectral Image Analysis Approaches For Detection Of Cellular Signals In Time-Lapse Hyperspectral Imaging Fluorescence Excitation-Scanning Microscopy, Marina Parker, Naga S. Annamdevula, Donald Pleshinger, Zara Ijaz, Josephine Jalkh, Raymond Penn, Deepak Deshpande, Thomas C. Rich, Silas J. Leavesley

Center for Translational Medicine Faculty Papers

Hyperspectral imaging (HSI) technology has been applied in a range of fields for target detection and mixture analysis. While HSI was originally developed for remote sensing applications, modern uses include agriculture, historical document authentication, and medicine. HSI has also shown great utility in fluorescence microscopy. However, traditional fluorescence microscopy HSI systems have suffered from limited signal strength due to the need to filter or disperse the emitted light across many spectral bands. We have previously demonstrated that sampling the fluorescence excitation spectrum may provide an alternative approach with improved signal strength. Here, we report on the use of excitation-scanning HSI …

Mst1-Mediated Phosphorylation Of Nur77 Improves The Endometrial Receptivity In Human And Mice, Xinyu Cai, Yue Jiang, Zhiwen Cao, Mei Zhang, Na Kong, Lina Yu, Yedong Tang, Shuangbo Kong, Wenbo Deng, Haibin Wang, Jianxin Sun, Lijun Ding, Ruiwei Jiang, Haixiang Sun, Guijun Yan

Center for Translational Medicine Faculty Papers

Background: Successful embryo implantation requires the attachment of a blastocyst to the receptive endometrial epithelium, which was disturbed in the women with recurrent implantation failure (RIF). Endometrial β3-integrin was the most important adhesion molecule contributing to endometrial receptivity in both humans and mice. Nur77 has been proven indispensable for fertility in mice, here we explore the role of Nur77 on embryo-epithelial adhesion and potential treatment to embryo implantation failure.

Methods: The expression and location of Mst1 and Nur77 in endometrium from fertile women and RIF patients were examined by IHC, qRT-PCR and Western blotting. In vitro kinase assay following with …

An Entosis-Like Process Induces Mitotic Disruption In Pals1 Microcephaly Pathogenesis, Noelle A Sterling, Jun Young Park, Raehee Park, Seo-Hee Cho, Seonhee Kim

Center for Translational Medicine Faculty Papers

Entosis is cell cannibalism utilized by tumor cells to engulf live neighboring cells for pro- or anti-tumorigenic purposes. It is unknown whether this extraordinary cellular event can be pathogenic in other diseases such as microcephaly, a condition characterized by a smaller than normal brain at birth. We find that mice mutant for the human microcephaly-causing gene Pals1, which exhibit diminished cortices due to massive cell death, also exhibit nuclei enveloped by plasma membranes inside of dividing cells. These cell-in-cell (CIC) structures represent a dynamic process accompanied by lengthened mitosis and cytokinesis abnormalities. As shown in tumor cells, ROCK inhibition completely …

Cocaine Sensitizes The Cd4+ T Cells For Hiv Infection By Co-Stimulating Nfat And Ap-1, Adhikarimayum Lakhikumar Sharma, Dylan Shafer, Daniel Netting, Mudit Tyagi

Center for Translational Medicine Faculty Papers

The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4+ T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV …

Piperine Attenuates Cigarette Smoke-Induced Oxidative Stress, Lung Inflammation, And Epithelial-Mesenchymal Transition By Modulating The Sirt1/Nrf2 Axis, Pritam Saha, Sneha Durugkar, Siddhi Jain, P A Shantanu, Samir R Panda, Aishwarya Jala, Sharad Gokhale, Pawan Sharma, V G M Naidu

Center for Translational Medicine Faculty Papers

Piperine (PIP) is a major phytoconstituent in black pepper which is responsible for various pharmacological actions such as anti-inflammatory, antioxidant, and antitumor activity. To investigate the effects and mechanisms of PIP on cigarette smoke (CS)-induced lung pathology using both in-vitro and in-vivo models. BEAS-2B and A549 cells were exposed to CS extract (CSE) for 48 h; BALB/c mice were exposed to CS (9 cigarettes/day, 4 days) to induce features of airway disease. PIP at doses of (0.25, 1.25, and 6.25 µM, in vitro; 1 and 10 mg/kg, in vivo, i.n) and DEX (1 µM, in vitro; 1 mg/kg, in vivo, …

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

Regulation Of Oxidative Phosphorylation Of Liver Mitochondria In Sepsis, Pierre Eyenga, Benjamin Rey, Lilia Eyenga, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

The link between liver dysfunction and decreased mitochondrial oxidative phosphorylation in sepsis has been clearly established in experimental models. Energy transduction is plastic: the efficiency of mitochondrial coupling collapses in the early stage of sepsis but is expected to increase during the recovery phases of sepsis. Among the mechanisms regulating the coupling efficiency of hepatic mitochondria, the slipping reactions at the cytochrome oxidase and ATP synthase seem to be a determining element, whereas other regulatory mechanisms such as those involving proton leakage across the mitochondrial membrane have not yet been formally proven in the context of sepsis. If the dysfunction …

Akt Inhibition In The Central Nervous System Induces Signaling Defects Resulting In Psychiatric Symptomatology, Apostolia-Maria Tsimberidou, Antonis Skliris, Alan Valentine, Jamie Shaw, Ursula Hering, Henry Hiep Vo, Tung On Chan, Roger S Armen, Jeffrey R Cottrell, Jen Q Pan, Philip N Tsichlis

Center for Translational Medicine Faculty Papers

Background: Changes in the expression and activity of the AKT oncogene play an important role in psychiatric disease. We present translational data assessing the role of AKT in psychiatric symptoms.

Methods: (1) We assessed the protein activity of an AKT3 mutant harboring a PH domain mutation (Q60H) detected in a patient with schizophrenia, the corresponding AKT1 mutant (Q61H), and wild-type AKT1 and AKT3 transduced in AKT-null mouse fibroblasts and modeled the Q61H mutation onto the crystal structure of the Akt1 PH domain. (2) We analyzed the results of earlier genome-wide association studies to determine the distribution of schizophrenia-associated single-nucleotide polymorphisms …

Aorta In Pathologies May Function As An Immune Organ By Upregulating Secretomes For Immune And Vascular Cell Activation, Differentiation And Trans-Differentiation-Early Secretomes May Serve As Drivers For Trained Immunity, Yifan Lu, Yu Sun, Keman Xu, Fatma Saaoud, Ying Shao, Charles Drummer, Sheng Wu, Wenhui Hu, Jun Yu, Satya P Kunapuli, John R Bethea, Roberto I Vazquez-Padron, Jianxin Sun, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

To determine whether aorta becomes immune organ in pathologies, we performed transcriptomic analyses of six types of secretomic genes (SGs) in aorta and vascular cells and made the following findings: 1) 53.7% out of 21,306 human protein genes are classified into six secretomes, namely, canonical, caspase 1, caspase 4, exosome, Weibel-Palade body, and autophagy; 2) Atherosclerosis (AS), chronic kidney disease (CKD) and abdominal aortic aneurysm (AAA) modulate six secretomes in aortas; and Middle East Respiratory Syndrome Coronavirus (MERS-CoV, COVID-19 homologous) infected endothelial cells (ECs) and angiotensin-II (Ang-II) treated vascular smooth muscle cells (VSMCs) modulate six secretomes; 3) AS aortas upregulate …

Pkcε Activation Restores Loss Of Pkcε, Manganese Superoxide Dismutase, Vascular Endothelial Growth Factor, And Microvessels In Aged And Alzheimer's Disease Hippocampus, Guetchyn Millien, Huaixing Wang, Zongxiu Zhang, Dan L Alkon, Jarin Hongpaisan

Center for Translational Medicine Faculty Papers

Vascular endothelial dysfunction and capillary loss are currently considered to be a primary phenotype of normal human aging and Alzheimer's disease (AD). Activation of protein kinase C (PKCε) improves several molecular, cellular, physiological, and behavioral endpoints, yet it is not known whether a loss of PKCε activity occurs in the microvascular endothelium in aged and AD hippocampi, whether this loss contributes to microvascular change, or whether activation of PKCε protects against microvascular damage, an early change that induces age-associated memory defect and AD. We investigated the effect of the PKCε activation on microvascular loss in the hippocampus, important for memory …

Abi1 Mediates Airway Smooth Muscle Cell Proliferation And Airway Remodeling Via Jak2/Stat3 Signaling, Ruping Wang, Yinna Wang, Guoning Liao, Bohao Chen, Reynold A. Panettieri, Jr., Raymond B. Penn, Albany Medical College

Center for Translational Medicine Faculty Papers

Asthma is a complex pulmonary disorder with multiple pathological mechanisms. A key pathological feature of chronic asthma is airway remodeling, which is largely attributed to airway smooth muscle (ASM) hyperplasia that contributes to thickening of the airway wall and further drives asthma pathology. The cellular processes that mediate ASM cell proliferation are not completely elucidated. Using multiple approaches, we demonstrate that the adapter protein Abi1 (Abelson interactor 1) is upregulated in ∼50% of ASM cell cultures derived from patients with asthma. Loss-of-function studies demonstrate that Abi1 regulates the activation of Jak2 (Janus kinase 2) and STAT3 (signal transducers and activators …

29 M 6 A-Rna Methylation (Epitranscriptomic) Regulators Are Regulated In 41 Diseases Including Atherosclerosis And Tumors Potentially Via Ros Regulation - 102 Transcriptomic Dataset Analyses, Ming Liu, Keman Xu, Fatma Saaoud, Ying Shao, Ruijing Zhang, Yifan Lu, Yu Sun, Charles Drummer Iv, Li Li, Sheng Wu, Satya P Kunapuli, Gerard J Criner, Jianxin Sun, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

Center for Translational Medicine Faculty Papers

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; …

Ovarian Cancer G Protein-Coupled Receptor 1 Inhibits A549 Cells Migration Through Casein Kinase 2Α Intronless Gene And Neutral Endopeptidase, Adhikarimayum Lakhikumar Sharma, Puyam Milan Meitei, Takhellambam Chanu Machathoibi, Naorem Tarundas Singh, Thiyam Ramsing Singh, Lisam Shanjukumar Singh

Center for Translational Medicine Faculty Papers

Background: We have previously reported that a new intronless gene for casein kinase 2α (CK2α), CSNK2A3, is expressed in human cells. The promoter of the well-known CK2α, CSNK2A1, displays characteristics of a housekeeping gene, whereas CSNK2A3 has a characteristic of a regulated promoter with two TATA boxes and a CAAT box. GPR68, a family of the G protein-coupled receptors, is also known as ovarian cancer G protein-coupled receptor 1 (OGR1). In the current study, we analyzed the roles of CK2α genes and neutral endopeptidase (NEP), a key enzyme that influences a variety of malignancies, in the OGR1-induced inhibition of A549 …

Retraction Note: Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury, Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer

Center for Translational Medicine Faculty Papers

The Authors have retracted this Article. Afer publication of this Article, concerns have been raised about irregularities in the western blot data. In particular, the following bands appear to be duplicated: – Fig. 1e HFD/p-Src lane 1 and 3; – Fig. 4c NCD/Ve-cadherin lane 1 and 3 – Fig. 5e HFD+APN/ICAM-1 lane 1 and 2 – Fig. 5f HFD/beta-catenin lane 2 and HFD+APN/beta-catenin lane 1 – Fig. S1d HFD/beta-catenin all lanes – Fig. S4c NCD/beta-catenin lane 1 and 3. Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. Te Authors …

Crossroads Of Drug Abuse And Hiv Infection: Neurotoxicity And Cns Reservoir, Shilpa Sonti, Kratika Tyagi, Amit Pande, René Daniel, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Drug abuse is a common comorbidity in people infected with HIV. HIV-infected individuals who abuse drugs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A modest proportion of HIV-infected individuals develop HIV-associated neurocognitive issues, the severity of which further increases with drug abuse. Moreover, the tendency of the virus to go into latency in certain cellular reservoirs again complicates the elimination of HIV and HIV-associated illnesses. Antiretroviral therapy (ART) successfully decreased the overall viral load in infected people, yet it does not effectively eliminate the virus from all latent reservoirs. Although ART increased …

Micro-Computed Tomographic Analysis Of The Shaping Ability Of Xp-Endo Shaper In Oval-Shaped Distal Root Canals Of Mandibular Molars, Ane Poly, Wei-Ju Louis Tseng, Fernando Marques, Frank Carsten Setzer, Bekir Karabucak

Center for Translational Medicine Faculty Papers

Objective: To compare the shaping ability of the XP-endo Shaper (XPS) system to the ProTaper Next (PTN) system in oval-shaped distal root canals.

Methods: From 12 mandibular molars, distal roots with moderately curved single oval canals were randomly assorted to be instrumented with XPS (experimental group) or PTN (control group) and then scanned using micro-computed tomography [Scan 1]. The root canals of the XPS samples were prepared following the manufacturer's instructions using 15 insertions (XPS15) and rescanned [Scan 2]. An additional 10 insertions to the working length were applied, totalling 25 insertions (XPS25), and the roots were rescanned again [Scan …

Hiv-1 Persistence In The Cns: Mechanisms Of Latency, Pathogenesis And An Update On Eradication Strategies., Shilpa Sonti, Adhikarimayum Lakhikumar Sharma, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Despite four decades of research into the human immunodeficiency virus (HIV-1), a successful strategy to eradicate the virus post-infection is lacking. The major reason for this is the persistence of the virus in certain anatomical reservoirs where it can become latent and remain quiescent for as long as the cellular reservoir is alive. The Central Nervous System (CNS), in particular, is an intriguing anatomical compartment that is tightly regulated by the blood-brain barrier. Targeting the CNS viral reservoir is a major challenge owing to the decreased permeability of drugs into the CNS and the cellular microenvironment that facilitates the compartmentalization …

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 …