Integrative Medicine Commons^™

Kras Inhibitor That Simultaneously Inhibits Nucleotide Exchange Activity And Effector Engagement, Cynthia V Pagba, Amit K Gupta, Ali K Naji, Dharini Van Der Hoeven, Kelly Churion, Xiaowen Liang, Jacob Jakubec, Magnus Hook, Yan Zuo, Marisela Martinez De Kraatz, Jeffrey A Frost, Alemayehu A Gorfe

Faculty, Staff and Student Publications

We describe a small molecule ligand ACA-14 (2-hydroxy-5-{[(2-phenylcyclopropyl) carbonyl] amino} benzoic acid) as an initial lead for the development of direct inhibitors of KRAS, a notoriously difficult anticancer drug target. We show that the compound binds to KRAS near the switch regions with affinities in the low micromolar range and exerts different effects on KRAS interactions with binding partners. Specifically, ACA-14 impedes the interaction of KRAS with its effector Raf and reduces both intrinsic and SOS-mediated nucleotide exchange rates. Likely as a result of these effects, ACA-14 inhibits signal transduction through the MAPK pathway in cells expressing mutant KRAS and …

Bcl11b And Atoh8 Coordinate Cellular Plasticity For Reprogramming And Transformation, Mo-Fan Huang, Rachel Shoemaker, Dung-Fang Lee

Faculty, Staff and Student Publications

By dissecting and comparing the transcriptional trajectories and epigenomic traits of reprogramming and transforming cells at the single-cell resolution, Huyghe et al discovered Bcl11b and Atoh8, two key transcription factors controlling cell plasticity during pluripotent reprogramming and oncogenic transformation.

Remodeling Of The Plasma Membrane By Surface-Bound Protein Monomers And Oligomers: The Critical Role Of Intrinsically Disordered Regions, Mussie K Araya, Yong Zhou, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The plasma membrane (PM) of cells is a dynamic structure whose morphology and composition is in constant flux. PM morphologic changes are particularly relevant for the assembly and disassembly of signaling platforms involving surface-bound signaling proteins, as well as for many other mechanochemical processes that occur at the PM surface. Surface-bound membrane proteins (SBMP) require efficient association with the PM for their function, which is often achieved by the coordinated interactions of intrinsically disordered regions (IDRs) and globular domains with membrane lipids. This review focuses on the role of IDR-containing SBMPs in remodeling the composition and curvature of the PM. …

New Non-Fullerene Acceptor With Extended Conjugation Of Cyclopenta [2,1-B:3,4-B’] Dithiophene For Organic Solar Cells, Cheng Sun, Sanseong Lee, Changeun Choi, Soyeong Jeong, Juhui Oh, Ju-Hyeon Kim, Jaeyoung Kim, Ho Eon Baek, Hongkyu Kang, Soo-Young Jang, Hyun Ho Choi, Kwanghee Lee, Yun-Hi Kim

Faculty, Staff and Student Publications

Herein, we design and characterize 9-heterocyclic ring non-fullerene acceptors (NFAs) with the extended backbone of indacenodithiophene by cyclopenta [2,1-b:3,4-b'] dithiophene (CPDT). The planar conjugated CPDT donor enhances absorption by reducing vibronic transition and charge transport. Developed NFAs with different end groups shows maximum absorption at approximately 790-850 nm in film. Because of the electronegative nature of the end-group, the corresponding acceptors showed deeper LUMO energy levels and red-shifted ultraviolet absorption. We investigate the crystallinity, film morphology, surface energy, and electronic as well as photovoltaic performance. The organic photovoltaic cells using novel NFAs with the halogen end groups fluorine or chlorine …

Human Nop2/Nsun1 Regulates Ribosome Biogenesis Through Non-Catalytic Complex Formation With Box C/D Snornps, Han Liao, Anushri Gaur, Hunter Mcconie, Amirtha Shekar, Karen Wang, Jeffrey T Chang, Ghislain Breton, Catherine Denicourt

Faculty, Staff and Student Publications

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the …

Short Signature Rpob Gene Sequence To Differentiate Species In Mycobacterium Abscessus Group, Jian R Bao, Kileen L Shier, Ronald N Master, Robert S Jones, Richard B Clark

Faculty, Staff and Student Publications

Mycobacterium abscessus group (MAG) are rapidly growing acid-fast bacteria that consist of three closely related species: M. abscessus (Ma), M. bolletii (Mb), and M. massiliense (Mm). Differentiation of these species can be difficult but is increasingly requested owing to recent infectious outbreaks and their differential drug resistance. We developed a novel and rapid pyrosequencing method using short signature sequences (35 to 45 bp) at a hypervariable site in the rpoB gene to differentiate the three MAG species, along with M. chelonae (Mc), and M. immunogenum (Mi). This method was evaluated …

Mettl14-Mediated Epitranscriptome Modification Of Mn1 Mrna Promote Tumorigenicity And All-Trans-Retinoic Acid Resistance In Osteosarcoma, Hong-Bo Li, Gang Huang, Jian Tu, Dong-Ming Lv, Qing-Lin Jin, Jun-Kai Chen, Yu-Tong Zou, Dung-Fang Lee, Jing-Nan Shen, Xian-Biao Xie

Faculty, Staff and Student Publications

BACKGROUND: Osteosarcoma (OS) is the most common primary malignant bone tumor in adolescents. The molecular mechanism behind OS progression and metastasis remains poorly understood, which limits the effectiveness of current therapies. RNA N

METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS), dot blotting, and colorimetric ELISA were used to detect m

FINDINGS: We observed the abundance of m

INTERPRETATION: Our study revealed that METTL14 contributes to OS progression and ATRA resistance as an m

FUNDING: This work was supported by the National Natural Science Foundation of China (Grants 81972510 and 81772864).

The Use Of Second-Generation Antipsychotics And The Changes In Physical Growth In Children And Adolescents With Perinatally Acquired Hiv, Nan Xin, Jenni Durieux, Chunxia Yang, Suzanne Wolff, Hyun-Eui Kim, Andrew Dillin

Faculty, Staff and Student Publications

The mitochondrial unfolded protein response (UPRmt) is dedicated to promoting mitochondrial proteostasis and is linked to extreme longevity. The key regulator of this process is the transcription factor ATFS-1, which, upon UPRmt activation, is excluded from the mitochondria and enters the nucleus to regulate UPRmt genes. However, the repair proteins synthesized as a direct result of UPRmt activation must be transported into damaged mitochondria that had previously excluded ATFS-1 owing to reduced import efficiency. To address this conundrum, we analyzed the role of the import machinery when the UPRmt was induced. Using in vitro and in vivo analysis of mitochondrial …

Phosphatidylserine And Phosphatidylethanolamine Asymmetry Have A Negligible Effect On The Global Structure, Dynamics, And Interactions Of The Kras Lipid Anchor, Mussie K Araya, Alemayehu A Gorfe

Faculty, Staff and Student Publications

The intrinsically disordered C-terminus of the prominent oncogenic protein KRAS-4B (KRAS) selectively interacts and clusters with phosphatidylserine (PS) lipids in the plasma membrane (PM). This 11-residue segment, called tK, contains a polybasic domain (PBD) of six contiguous lysine residues and a farnesylated cysteine. Previous molecular dynamics (MD) simulation studies of tK in phosphatidylcholine (PC)/PS bilayers have suggested that backbone conformational dynamics modulate tK-PS interactions. These simulations have been conducted in symmetric membranes whereas the PM is compositionally asymmetric, with the inner leaflet, where KRAS is localized, being enriched with PS and phosphatidylethanolamine (PE) lipids. To examine if bilayer asymmetry affects …

A Telehealth-Delivered Tai Chi Intervention (Taichi4joint) For Managing Aromatase Inhibitor-Induced Arthralgia In Patients With Breast Cancer During Covid-19: Longitudinal Pilot Study, Sameh Gomaa, Carly West, Ana Maria Lopez, Tingting Zhan, Max Schnoll, Maysa Abu-Khalaf, Andrew B. Newberg, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Background: Estrogen receptor-positive breast cancer is the most common type of breast cancer in postmenopausal women. Aromatase inhibitors (AIs) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop arthralgia, often resulting in poor adherence and decreased quality of life.

Objective: The study is a single-arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability, and potential efficacy of TaiChi4Joint, a remotely delivered 12-week tai chi intervention designed to relieve AI-induced joint pain.

Methods: Women diagnosed with stage 0-III breast cancer who received an AI for at least 2 …

Medical Norm Of Psychiatric Misdiagnoses In Rare Disease Patients, Rachel Han

Publications and Research

Spring 2022 ENG 120 Student Final Research Paper on the medical norm of psychiatric misdiagnosis throughout the diagnostic journeys of rare disease patients. The idea of a norm was taken from Chimamanda Ngozi Adichie's Tedx Talk "The Danger of a Single Story". Paper discusses prevalence, harmful effects, and origin of this medical norm. Includes discussion of statistical data quoted relating to prevalence of rare diseases as well as anecdotal evidence of the severe ramifications of this norm. Discussion of how medically unexplained symptoms such as mysterious chronic pain often lead to the phenomenon of the psychogenic inference. Origins of this …

Role Of Emotional Intelligence In Job Performance Of Healthcare Providers Working In Public Sector Hospitals Of Pakistan, Nimra Zaman, Khalida Naz Memon, Faryal Zaman, Komal Zaman Khan, Shazia Rahman Shaikh

Journal of Mind and Medical Sciences

Objective. To determine the association between emotional intelligence (EI) and job performance (JP) of health care providers (HCPs). Methods. Healthcare professionals from various hospitals were chosen for a cross-sectional study. The survey was conducted using a three-part questionnaire including the demographic profile, Wong and Law Emotional Intelligence (EI) Scale, and an individual work performance (JP) questionnaire. The relationship of predictor variables on JP was sought by applying Chi-square test and multiple regression analysis. Results. About 43.3% of the 50.8% of participants who scored well on the EI scale also scored high on the JP scales. The remaining …

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 …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

D-Dimer Levels And Acute Pulmonary Embolism Development In Covid-19 Patients, Vural Ahmet, Kahraman Ahmet Nedim

Journal of Mind and Medical Sciences

Objective. To identify those who develop pulmonary embolism with Ddimer levels by evaluating pulmonary CT angiographies of patients who are followed up with suspicion of coronavirus disease 2019 (COVID-19). Methods. Patients who were followed up in a community hospital with suspicion of COVID-19 and underwent Pulmonary CT angiography examination were evaluated. Clinical and demographic parameters and DDimer values for patients with and without pulmonary embolism were evaluated in the pulmonary CT angiogram. Results. During the COVID-19 pandemic, Thorax CT examination was performed in our center for suspicion or follow-up of COVID-19 infection in 3396 patients. Pulmonary CT angiography was applied …

Study On The Formulation And Characterization Of A Photoprotective Cream Containing A New Synthetized Compound, Teodora Dalila Balaci, Emma Adriana Ozon, Daniela Luiza Baconi, Georgiana Nițulescu, Bruno Velescu, Cristian Bălălău, Ioana Păunică, Cătălina Ancuța Fița

Journal of Mind and Medical Sciences

Starting from a new organic sunscreen synthesized in our laboratory by the condensation of sodium salt of the p-aminosalicylic acid with 2,6 – dichloroacetanilide, efficient cosmetic formulation with broad photoprotective properties was obtained by using the new compound as organic UV filter, metal oxides as inorganic filters, and vegetable extracts, oils and other ingredients with emollient, protective, and moisturizing effect. After showing the lack of toxicity of the new compound, in order to reduce the amount of UV filter used, it was encapsulated into nanostructured lipid carriers (NLCs). The final cream has demonstrated good qualities for skin application, possessing suitable …

Oral Pathology Induced By Excess Or Deficiency Of Glucocorticoids In Adults, Rucsandra Elena Dănciulescu Miulescu, Loreta Guja, Bogdan Socea, Anca Dumitriu, Stana Paunica, Emil Ștefănescu

Journal of Mind and Medical Sciences

Oral manifestations are present both in Cushing's syndrome and in adrenal insufficiency. Possible oro-dental pathology in patients with Cushing's syndrome include jawbone loss, tooth loss, and periodontal diseases. Professional societies did not include Cushing's syndrome as being part of systemic diseases associated with loss of periodontal supporting tissues. The comorbidities of Cushing's syndrome such as obesity, osteoporosis, and diabetes are conditions that influence periodontal attachment apparatus. In patients with adrenal primary insufficiency, the most specific sign is the melanic pigmentation of the skin and mucosal surfaces due to increments of corticotropin and pro-opiomelanocortin peptide levels that occur as a result …

Compassion And Suppression In Caregivers: Twin Masks Of Tragedy And Joy Of Caring, Emanuele Maria Merlo, Sean M. Mcnabney, Fabio Frisone, Federica Sicari, Mihai Paunica, Catalina Motofei, Salvatore Settineri

Journal of Mind and Medical Sciences

Background: Compassionate caregiving is a critical skill for workers among the helping professions, but the degree of empathy required by caregivers can place high demands on their mental and emotional resources. While many professionals employ successful coping strategies to mitigate these stressors, others experience compassion fatigue or burnout from emotional exhaustion. The objective of this research was to evaluate the relationships between caregivers’ demographic/career variables, compassion satisfaction, compassion fatigue, and psychodynamic defense mechanisms such as suppression, repressive function, regression in the service of the Ego, and rationalization. Methods: Participants were 250 caregivers with 178 (71,2%) women and 72 men (28,8%) …

Lavender Aromatherapy: Ready For Prime-Time Office Use?, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

The editor-in-chief of Journal of Patient-Centered Research and Reviews comments on the perioperative use of lavender aromatherapy and its potential to relieve pain and anxiety during minor primary care office procedures.

N-Acetyl Cysteine May Support Dopamine Neurons In Parkinson's Disease: Preliminary Clinical And Cell Line Data., Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Jingli Cai, Xiatao Wei, Anthony J. Bazzan, Li Zhong, Brendan Bowen, Charles Intenzo, Lorraine Iacovitti, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).

METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult …

Modulation Of Body Weight By Intestinal Flora In Orphan Nuclear Receptor Shp-/- Mice, Ryan Mifflin

Williams Honors College, Honors Research Projects

The whole-body deletion of small heterodimer partner (SHP) in mice is associated with protection from diet-induced obesity and hepatic steatosis upon feeding of a western diet. This protection was reported to be mediated through decreases in hepatic gene expression for lipogenesis, as well as increases in gene expression for fatty acid oxidation. SHP has been known to regulate the expression of the CYP7A1 gene, encoding the rate-limiting enzyme for bile acid synthesis, thereby altering the bile acid pool. The effects of this altered bile acid profile on the gut microbiome are unknown, as some bacteria in the gut are responsible …