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1. Ethnic and racial differences in children and young people with respiratory and neurological post-acute sequelae of SARS-CoV-2: an electronic health record-based cohort study from the RECOVER InitiativeResearch in context

Author

Suchitra Rao, Rodrigo Azuero-Dajud, Vitaly Lorman, Jeremy Landeo-Gutierrez, Kyung E. Rhee, Julie Ryu, C. Kim, Megan Carmilani, Rachel S. Gross, Sindhu Mohandas, Srinivasan Suresh, L. Charles Bailey, Victor Castro, Yalini Senathirajah, Shari Esquenazi-Karonika, Shawn Murphy, Steve Caddle, Lawrence C. Kleinman, Leah Castro-Baucom, Carlos R. Oliveira, Jonathan D. Klein, Alicia Chung, Lindsay G. Cowell, Charisse Madlock-Brown, Carol Reynolds Geary, Marion R. Sills, Lorna E. Thorpe, Jacqueline Szmuszkovicz, Kelan G. Tantisira, Ivan Diaz, Rachel Kenny, Parsa Mirhaji, Ravi Jhaveri, Marc Rosenman, Christopher Forrest, Beth Tarini, Hiroki Morizono, Nathan Pajor, W. Schuyler Jones, Kieler Curtis, Rishi Kamaleswaran, Nita Deshpande, Saul Blecker, Claudia Pulgarin, Marion Sills, Erin Hinkman, Dan Fort, Timothy Guthrie, Cynthia Chuang, Wenke Hwang, Dimitri Christakis, Daksha Ranade, Shannon Herring, Aaron Mishkin, Soledad Fernandez, Neena Thomas, Yuriy Bisyuk, Jyotsna Fuloria, Elizabeth Chrischilles, Boyd Knosp, Asa Oxner, Athanasios Tsalatsanis, Lindsay Cowell, Phillip Reeder, Stephen M. Downs, Brian Ostasiewski, Rainu Kaushal, Thomas Campion, Jessica Snowden, Katherine Irby, Paul Darden, Lexie Dixon, Danielle Evans, Connor Garbe, Laura Hobart-Porter, Lee Howard, Kathy Hummel, Hannah Krehbiel, Haley Spradlin, Phaedra Yount, Amy Elliott, Grace Adam, Jyoti Angal, Maria Barber, Katelynne Clark, Clayton Dos Reis, Mandy Freesemann, Christa Friedrich, Christine Hockett, Rachel Johannsen, Emily Johnson-Vonk, Cassidy Kaiser, Alexa Kruse, Jennifer Lang, Peter Lim, Meggie McCoy, Lorie Miller, Shelby Petereit (Cerkovnik), Jaime RiChard (Werpy), Jessica Seiler, Bret Sundleaf, Joshua Svendsen, Billy Trosper, Olivia Vermeulen, Scott Young, Aul Palumbo, Sean Dabney, Marie-Christine Fahrner, Torrey Gallagher, Karilyn Martini, Mary McNally, Sarah Vivensi Stiverson, Jessica Kosut, Venkataraman Balaraman, JoAnn Cheung, Travis K.F. Hong, Shanelle Kalua, Evan Minami, Andrea Siu, Micah Tong, Ronald J. Teufel, II, Andy Atz, Marina Dantas, Tyler Kasmarcak, Kreighton Milks, Judith Ross, Chijoke Ikomi, Marisa Meyer, Connie Nguyen, Gwen Pellicciotti, Thao-Ly Phan, Karen Ravin, Victoria Reynolds, Abigail Strang, Deepika Thacker, Dan Eckrich, Annabelle Goetter, Cheyenne Katz, Karen Kowal, Carol McDevitt, Emily Zimmerman, Genesis Agosto Roman, Akram Alshawabkeh, Ishwara Ayala Ortiz, Virginia Casey, Jose Cordero, Jocelyn De Jesus, Crystal Galan, Gredia Huerta-Montanez, Nilda Otero, Mayra Rivera Robles, Priscilla Roman, Genesis Roman, Zaira Rosario-Pabon, Xiodenis Santiago, Carmen Velez-Vega, Carlos Vergara, Daniel S. Hsia, Baylea Albarado, Tracey Allen, Allison Attuso, Taylor Ayers, Emily Bebler, Grace Bella, Alexa Bennett, John Brown, Alison Carville, Sydnie Darby, Kara Devall, Amber Dragg, Angela Elderedge, Elisabeth Fontenot, Greta Fry, Bethany Gildersleeve, Sara Goff, Lauren Harrington, Lisa Jones, Victoria Kaiser, Yejee Lee, Stephen Lee, Erin LeJeune, Robert Leonhard, Jennifer Levatino, Donald Lewis, Angrielle Lloyd, Ron Monce, Susannah Munro, Meghan Phillips, Blair Pucheu, Emily Rachal, Jennifer Rood, Stacey Roussel, Renee Rumsey, Connor Sanford, Monica Santos, Aryelle Stafford, Amy Thomassie, Celeste Waguespack, Katherine Walgamotte, Meredith Welch, Aubrey Windham, Michelle Stevenson, Tiffany Bell, Jackie Boyd, Soham Dasgupta, Sarah Deans, Katie Harris, Molly Hemmerle, Sarah King, Cameo McGuire, Brie Merten, Sarah Morris, Madison Ray, Brooklyn Reinhardt, Shellese Shemwell, Theresa Simeon, Katherine Walker, Sara Watson, Kathryn Weakley, Russell McCulloh, Johnathon Figliomeni, Laura Fischer, Denise Hoover, Megan Morse, Aleisha Nabower, Evan Roberts, Alice Sato, Joann Von Bon, Hengameh Raissy, David Archuleta, Rebecca Brito, Richard Campbell, Jude Chavez, Walter Dehority, Noella Garcia-Soberanez, Eve Gronert, Matthew Kadish, Jerry Larrabee, Debbie Lovato, Karen Luo, Noah Martinez, Analyse Merlino, Emily Reese, Sarah Ward, Kevin Wilson, Amanda Bogie, Ryan Brown, Ryan Butchee, Gina Fergeson, Ryan McKee, Brandon Mohler, Tiffany Moore, Valorie Owens, Sarah Stubbs, Timothy Van Wagoner, Kelly Cowan, Meghan Bethel, Laurie Chassereau, Thomas Lahiri, Lesley Cottrell, Lauren Lake, Kathy Moffett, Emily Polak, Sarah Stutler, Charlotte Workman, David Warburton, John C. Wood, Emma Carpenter, Isabelle Dhindsa, Samantha Mejia, Nelly Moghadam, Candice Mulder, Sharon O'Neil, Alisha Osornio, Adrian Rios, Sydney Rosen, Andrea Smith, Deeba Tabibi, Sharon Tang, Ariana Teame, Melissa Stockwell, Joshua Milner, Erika B. Rosenzweig, Brett Anderson, Tawanda Aquino, Elizabeth Berg, Marina Catallozzi, Wendy Chung, Tom Connors, Aliva De, Anny Diaz Perez, Michael DiLorenzo, Dani Dumitriu, Kanwal Farooqi, Michael Fremed, Sylvie Goldman, Kayla Kaplan, Usha Krishnan, Aimee Layton, Angela Lignelli-Dipple, Son McClaren, Jonathan Overdevest, Michelle Rodriguez, Jay Selman, Wendy Silver, Raul Silverio, Ana Valdez de Romero, Celibell Vargas, Alan Werzberger, Daniella Caputo, Camille Leggieri, Pamela Pretsch, Lawrence Kleinman, Sunanda Gaur, Lisa Cerracchio, Amber Folnagy, Maria Gennaro, Sherri Gzemski, Yue Hao, Simon Li, Sandee Moroso, Manette Ness-Cochinwala, Akhil Patel, Benjamin Richlin, Harsh Sharma, Damaris Soto, Christian Suarez, Bibiana Vargas Forero, Lynn Olson, Kristin Davis, Alexander Fiks, Miranda Griffith, Donna Harris, Everly Macario, Jennifer Steffes, Alessandra Torres, Rangaraj Selvarangan, Dithi Banerjee, Chris Day, Kelsye Howell, Megan Mains, Juan C. Salazar, William T. Zempsky, Emily Bean, Carlie DeFelice, Hassan El Chebib, Katherine W. Herbst, Stephanie Lesmes, Ian C. Michelow, Melissa Santos, Noah Schulman, Wilson D. Pace, Alicia Brooks-Greien, Karinne Colin, Christina M. Hester, Ariadna Juarez-Colunga, Brian Manning, Joel Shields, Jack Westfall, Daphne York, Judy Aschner, Katharine Clouser, Justine Griswold, Donna Lee, Amanda Nowakowski, Maryellen Riordan, Hulya Bukulmez, David Kaelber, Rozina Aamir, Mohammed Abuzahrieh, Nandini Bangalore, Alexis Brown, Wendy Dalton, Suzanne Fortuna, Judi Minium, Bonnie Rosolowski, Sheila M. Nolan, Amal Ahmed, Suzanne Braniecki, Montserrat Contreras, Allen Dozor, Supriya Jain, Suzanne Kaseta, Sankaran Krishnan, Zachary Messer, Armando Ramirez, Aalok Singh, Randy Williams, Kyung Rhee, Kelan Tantisira, Almary Akerlundh, Natacha Akshoomoff, Maria Arroyo, Wendy Barrientos, Rakesh Bhattacharjee, Bryant Y. Chao, Maricela Diaz, Sergio Garcia, Sonia Garcia, Guadalupe Gomez, Trinidad Herrera, Margarita Holguin, Manaswitha Khare, Elizabeth Kiernan, Jeremy Landeo Gutierrez, Ileana Matta, Sofia Reyes, Cinthia Sanchez, Andrea Schreck, Megan R. Warner, Uzma Hasan, Elizabeth Ricciardi, Vanessa Trespalacios, Vince Faustino, Matthew Kluko, Bryant Chao, Maria Glenn-Arroyo, Elizabeth A. Kiernan, Anika Madan, Lisa Ramos Vallejo, Cinthia E. Sanchez, Maira Suarez, Patricia Kinser, Amy Salisbury, Jocelyn Espinoza, Sara Moyer, Amy Rider, Sally Russell, Michael Schecter, Lindsey Stevenson, Cheryl R. Stein, Stephanie V. Caldas, Thomas Dylan Castro Ovalle, Anthony Chung, Jonathan S. Farkas, Maria Isidoro-Chino, Deniz Kesebir, Eugenia Kim, Ashley Quarless, Alan Schlechter, Ranjini Srinivasan, Viren D'Sa, Fatoumata Barry, Phoebe Burton, Rosa Cano Lorente, Caroline Cummins, Stephanie Wehbe, Sandra Brown, Anders Dale, Terry Jernigan, Susan Tapert, Jose Aguilar, David Benjamin, Natalie C. Buchbinder, Norma Castro, Brandy Emerson, Hugh Garavan, Jennifer Graves, Amanda Guerrero, Janosch Linkersdoerfer, Robert Schooley, Wes Thompson, Thanh Trinh, Ron Yang, Megan Herting, Elizabeth Sowell, Cynthia Cisneros, Lauren Goedde, Cedric Manlhiot, Raul Gonzalez, Angela Laird, Jorge Limia, Robin Aupperle, Martin Paulus, Melanie Curry, Nour S. El-Sabbagh, Kevin Gray, Lindsay Squeglia, Samuel Agbeh, Cori Herring, Brittany Mckenzie, Bonnie Nagel, Abby Espinoza, Anthony Hill, Angie Morales, Fiona Baker, Eva Muller-Oehring, Ian Colrain, Ingrid Durley, Mirella Dapretto, Lucina Uddin, Susan Bookheimer, Christina Caldera, Jennifer Dzul, Cinthia Zarate, Marie Banich, Paola Badilla, Jennifer Keith, G. Kumar, David Messinger, Katie Prazak, Sara Jo Nixon, Melanie Cardoso, Meagan Sullivan, Stephen Villard, Linda Chang, Thomas Ernst, Christine Cloak, Huajun Liang, Meghann C. Ryan, Mary Heitzerg, Jennifer Conley, Leonard Puttler, Monica Luciana, William Iacono, Aaron Schroeder, Duncan Clark, Doyeon (Dan) Kim, Megan Retucci, Edward Freedman, John Foxe, Sile Ni Mhurchu, Samantha Spallina, Erin McGlade, Deborah Yurgelun-Todd, Liz Bell, Kirsten Cline, Lauren Heinrich, Perry Renshaw, Alexandra Potter, Cass Barrett, Sofia Lozon, Samantha Spear, Christine Larson, Krista Lisdahl, Tory Clearwater, Christine Kaiver, Caitlin Nelson, Zach Paltzer, Bridgette Peteet, James Bjork, Mike Neale, Olive Calonge, Noah Slattery, Lisa Straub, Deanna Barch, Andrew Heath, Pamela Madden, Taylor Powell, Denise Schmitz, Dylan Gee, Boris Epie, Rebekah Hobbs, Alex Williams, Zhouran (Rick) Xiang, Julie Miller, Jane Newburger, Felicia Trachtenberg, Ayesha Amarnath, James Ambrosoli, Denise Artis, Sachin Bandari, Emily Birmingham, Lozan Eyob, Kerri Hayes, Chenwei Hu, Melissa Joyce, Valentina Kazlova, Iris Liu, Amanda Marshall, Devine Mbizdenyuy, P.J. Mu, Robin Rowe, Brooke Sayles, Mo Zhang, Pei-Ni Jone, Michael Carr, Lauren Goodell, Wantanabe Kar, Kathleen Van't Hof, Kristin Sexson, Elias Moussi, David Olukayode, Sandra Pena, Ricardo Pignatelli, Faridis Serrano, Sara Sexson Tejtel, Lara Shekerdemian, Audrey Dionne, Annette Baker, Sarah DeFerrantini, Thomas Giorgio, Numaira Khan, Simran Mahanta, MaryBeth Son, Matt Oster, Melissa Burnett, Kolby Sanders-Lewis, Sonia Chavez, Georgia Reis, Jackie Szmuszkovicz, Fariborz Behzadian, Carla Canas, Andrew Cheng, Mike Gawad, Paige Johnson, Alicia Kazarians, Anastasia Sarkissian, Brandi Scott, Consuelo Secules, Jennifer Su, Crystal Vargas, Jodie Votava-Smith, Sharon Wagner-Lees, Shuo Wang, Pierre Wong, Yamuna Sanil, Sanjeev Aggarwal, Aiman Almasnaah, Nirupama Kannikeswaran, Kathleen Meert, Gautam Singh, Priya Spencer, Nancy Sullivan, Sureja Sundaralingam, Vishnu Undyala, Emily Ward, Amanda Weber, Charmaine Williams Farr, Tamara Bradford, Marla Johnston, Matthew Elias, Alex Fiks, Chris Forrest, Dana Albizem, Susan Coffin, Therese Giglia, Katherine Lupton, Grace Marks, Tonia Morrison, Shawn O'Connor, Daniel Forsha, Jennifer Nelson, Rachel Sachdeva, Dara Watkins, Ashraf S. Harahsheh, Jordyn Britton, Alix Fetch, Anita Krishnan, Onais Tariq, Sean Lang, Marisa Almaguer, Jim Cnota, Lauryn Dugan, Elise Pickering, Kathleen Rathge, Elizabeth Mitchell, Christine Capone, Nilanjana Misra, Olga Shamailova, Mark Russell, Tammy Doman, Lori Harris, Keren Hasbani, Sagar Jani, Brian McCrindle, Jessica Bainton, Maryanne Chrisant, Doris Alaby, Norma Barton, Danielle Katz, Paulette Smith, Stephanie Handler, Joe Block, Regina Cole, Jennifer Maldonado, Kim McHugh, Andrew Atz, Megan Bickford, Jason Buckley, John Costello, Delany Dennis, Elizabeth Emrath-Zwick, Mary Freeman, Lanier Jackson, Madison Johnson, Elizabeth Mack, Scott Pletzer, Natasha Ruth, Carolyn Taylor, Sinai Zyblewski, Katrina Golub, Chanel Rojas, Korsin Rosalind, Chantal Sanchez, Shubhika Srivastava, Carol Prospero, Ed Williams, Varsha Zadokar, Arash Sabati, Kylie Domian, Ashley Herzberg, Sanjana Khanna, Todd Nowlen, Susan Park, Jade Porche, Samantha Stack, Dongngan Truong, Andrea Dunn, Lilly Fagatele, Emma Joyce, Linda Lambert, Kirsten Dummer, Sherrie Bandy, Jane Burns, Katheryn Crane, Sanjeet Hedge, Joan Pancheri, Adriana Tremoulet, Ronald Mark Payne, Mary Stumpf, Michael Portman, Hidemi Kajimoto, Camden Hebson, Krissie Hock, Onyekachukwu Osakwe, Jemylle Morato, Divya Shakti, Matt Kadish, Kavita Sharma, William Anguiano, Catherine Ikemba, Alejandra Lozano, Maria Martinez, Wendy Rojas, Lerraughn Morgan, Isaura Macias, Carl Owada, Mayra Rangel, and Michelle Sykes

Subjects
PEDSnet, PCORnet, Long COVID, Chronic COVID-19 syndrome, Late sequelae of COVID-19, Long-haul COVID, Medicine (General), R5-920
Abstract

Summary: Background: Children from racial and ethnic minority groups are at greater risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but it is unclear whether they have increased risk for post-acute sequelae of SARS-CoV-2 (PASC). Our objectives were to assess whether the risk of respiratory and neurologic PASC differs by race/ethnicity and social drivers of health. Methods: We conducted a retrospective cohort study of individuals

Published
2025
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2. The relationship between weight and pulmonary outcomes in overweight and obese people with cystic fibrosis: A retrospective observational study

Author

John J. Welter, Alison T. Lennox, Sankaran Krishnan, Christy Kim, Sheila Krishnan, Haley Thompson, Emily McAllister, Kristen Huang, Kasiemobi Nwaedozie, and Allen J. Dozor

Subjects
body mass index, forced expiratory volume in 1 s, forced vital capacity, pulmonary exacerbations, Medicine
Abstract

Abstract Background A major focus in cystic fibrosis (CF) care aims to increase weight gain. Rates of overweight and obese people with CF have gradually increased over the past decade. Obesity could be a risk for restriction of lung volumes and airway obstruction as well as increase rates of pulmonary exacerbations in people with CF. Aim To assess the relationship between weight categories and pulmonary outcomes in children and adults with CF. Methods Patients 6 years of age and older were categorized into weight categories based on the Centers for Disease Control and Prevention (CDC) definitions. A retrospective chart review was conducted to obtain lung function testing and other outcomes. Results One hundred five patients with a median age of 20.6 years were included in this analysis. 8.4%, 64%, 18%, and 10% of patients were underweight, normal/healthy weight, overweight, and obese, respectively. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (% predicted) did not differ between patients with weights in the normal range versus patients in the overweight/obese categories. Linear regression analysis showed a direct correlation between body mass index (BMI) and FEV1 that continued as BMI entered overweight and obese categories in both pediatric and adult patients. Overweight/obese patients did not have increased rates of pulmonary exacerbations compared to those in the normal/healthy weight category. Conclusion As CF therapies continue to improve, an increasing number of people with CF are exceeding the CDC's normal‐weight range. Gaining weight past the normal range does not appear to negatively impact pulmonary health of people with CF. If this trend of increased weight gain continues, it remains to be seen if it will eventually negatively affect lung health.

Published
2022
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3. TRPV4-mediated Mechanotransduction Regulates the Differentiation of Valvular Interstitial Cells to Myofibroblasts: Implications for Aortic Stenosis.

Author

Mukherjee P, Mahanty M, Dutta B, Rahaman SG, Sankaran KR, and Rahaman SO

Abstract

As aortic valve stenosis (AVS) progresses, the valve tissue also stiffens. This increase in tissue stiffness causes the valvular interstitial cells (VICs) to transform into myofibroblasts in response. VIC-to-myofibroblast differentiation is critically involved in the development of AVS. Herein, we investigated the role of mechanosensitive Ca 2+ -permeant transient receptor potential vanilloid 4 (Trpv4) channels in matrix stiffness- and transforming growth factor β1 (TGFβ1)-induced VIC-myofibroblast activation. We confirmed Trpv4 functionality in primary mouse wild-type VICs compared to Trpv4 null VICs using live Ca 2+ influx detection during application of its selective agonist and antagonist. Using physiologically relevant hydrogels of varying stiffness that respectively mimic healthy or diseased aortic valve tissue stiffness, we found that genetic ablation of Trpv4 blocked matrix stiffness- and TGFβ1-induced VIC-myofibroblast activation as determined by changes in morphology, alterations of expression of α-smooth muscle actin, and modulations of F-actin generation. Our results showed that N-terminal residues 30-130 in Trpv4 were crucial for cellular force generation and VIC-myofibroblast activation, while deletion of residues 1-30 had no noticeable negative effect on these processes. Collectively, these data suggest a differential regulatory role for Trpv4 in stiffness/TGFβ1-induced VIC-myofibroblast activation. Our data further showed that Trpv4 regulates stiffness/TGFβ1-induced PI3K-AKT activity that is required for VIC-myofibroblast differentiation and cellular force generation, suggesting a mechanism by which Trpv4 activity regulates VIC-myofibroblast activation. Altogether, these data identify a novel role for Trpv4 mechanotransduction in regulating VIC-myofibroblast activation, implicating Trpv4 as a potential therapeutic target to slow and/or reverse AVS development., Competing Interests: CONFLICT OF INTEREST: The authors declare that there are no conflicts of interest.

Published
2024
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4. Avocado-derived extracellular vesicles loaded with ginkgetin and berberine prevent inflammation and macrophage foam cell formation.

Author

Sharma S, Mahanty M, Rahaman SG, Mukherjee P, Dutta B, Khan MI, Sankaran KR, He X, Kesavalu L, Li W, and Rahaman SO

Subjects
Humans, Foam Cells, Macrophages, Lipoproteins, LDL, Berberine pharmacology, Persea, Atherosclerosis drug therapy, Atherosclerosis prevention & control, Biflavonoids
Abstract

Atherosclerosis, a chronic inflammatory disease of aorta, remains the major cause of morbidity and mortality among cardiovascular disease patients. Macrophage foam cell formation and inflammation are critically involved in early stages of atherosclerosis, hence chemopreventive targeting of foam cell formation by nutraceuticals may be a promising approach to curbing the progression of atherosclerosis. However, many nutraceuticals including berberine and ginkgetin have low stability, tissue/cell penetration and bioavailability resulting in inadequate chemotherapeutic effects of these nutraceuticals. We have used avocado-derived extracellular vesicles (EV) isolated from avocado (EV Avo ) as a novel carrier of nutraceuticals, in a strategy to alleviate the build-up of macrophage foam cells and expression of inflammatory genes. Our key findings are: (i) Avocado is a natural source of plant-derived EVs as shown by the results from transmission electron microscopy, dynamic light scattering and NanoBrook Omni analysis and atomic force microscopy; (ii) EV Avo are taken up by macrophages, a critical cell type in atherosclerosis; (iii) EV Avo can be loaded with high amounts of ginkgetin and berberine; (iv) ginkgetin plus berberine-loaded EV Avo (EV Avo(B+G) ) suppress activation of NFκB and NLRP3, and inhibit expression of pro-inflammatory and atherogenic genes, specifically Cd36, Tnfα, Il1β and Il6; (v) EV Avo(B+G) attenuate oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation and (vi) EV Avo(B+G) inhibit oxLDL uptake but not its cell surface binding during foam cell formation. Overall, our results suggest that using EV Avo as a natural carrier of nutraceuticals may improve strategies to curb the progression of atherosclerosis by limiting inflammation and pro-atherogenic responses., (© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Published
2024
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5. Thymoquinone mitigates obesity and diabetic parameters through regulation of major adipokines, key lipid metabolizing enzymes and AMPK/p-AMPK in diet-induced obese rats.

Author

Ramineedu K, Sankaran KR, Mallepogu V, Rendedula DP, Gunturu R, Gandham S, Md SI, and Meriga B

Abstract

The present study was designed to evaluate the anti-obesity and anti-hyperglycemic activity of Thymoquinone (ThyQ) isolated from Nigella sativa seeds. Male Wistar rats were randomly divided into five groups and fed either normal pellet diet or high-fat diet (HFD) for 18 weeks and water ad-libitum . Group I: normal pellet diet (NPD)-fed, Group II: high-fat diet (HFD)-fed, Group III: HFD-fed-ThyQ (20 mg)-treated, Group IV: HFD-fed-ThyQ (40 mg)-treated and Group V: HFD-fed-Orlistat (5 mg)-treated group. Intervention with ThyQ started from 12th week onwards to HFD-fed rats of group III and IV. ThyQ administration significantly ( p  < 0.01) mitigated body weight gain, blood glucose, insulin level, serum and liver lipids (except HDL) and improved glucose tolerance and insulin sensitivity as evaluated by oral glucose tolerance test (OGTT), homeostasis model assessment-insulin resistance (HOMA-IR) and insulin tolerance test (ITT). Furthermore, ThyQ significantly ( p  < 0.01) diminished serum aspartate transaminase (AST), alanine transaminase (ALT), acetyl-CoA carboxylase (ACC), plasma leptin, resistin and visfatin levels but enhanced lipoprotein lipase (LPL) and adiponectin levels. RT-PCR analysis demonstrated down-regulated mRNA expression of sterol regulatory element-binding proteins-1c (SREBP-1c), CCAAT/enhancer-binding protein-α (C/EBP-α) and fatty acid synthase (FAS) but upregulation of Insulin receptor substrate-1 (IRS-1).Western blot analysis displayed phosphorylation of adenosine monophosphate activated protein kinase (AMPK) in ThyQ-treated rats. Liver microtome sections of HFD-fed rats showed degenerated hepatocytes with high lipid stores while that of adipose tissue sections displayed large, fat-laden adipocytes, however, these histological changes were considerably attenuated in ThyQ-treated groups. Together these findings demonstrate that ThyQ can be a valuable therapeutic compound to potentially alleviate diet-induced obesity, hyperglycemia and insulin resistance., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03847-x., Competing Interests: Conflict of interestThere are no competing financial interests declared by the authors., (© King Abdulaziz City for Science and Technology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Published
2024
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6. Ursolic acid regulates key EMT transcription factors, induces cell cycle arrest and apoptosis in MDA-MB-231 and MCF-7 breast cancer cells, an in-vitro and in silico studies.

Author

Mallepogu V, Sankaran KR, Pasala C, Bandi LR, Maram R, Amineni UM, and Meriga B

Subjects
Humans, Female, MCF-7 Cells, Fibronectins, Transcription Factors, Cell Cycle Checkpoints, Epithelial-Mesenchymal Transition, Apoptosis, Cell Line, Tumor, Cell Proliferation, Breast Neoplasms metabolism
Abstract

Epithelial-mesenchymal transition (EMT) is a vital process in tumorigenesis and metastasis of breast cancer. In our quest to explore effective anticancer alternatives, ursolic acid (UA) was purified from Capparis zeylanica and investigated for its anticancer activity against MDA-MB-231 and MCF-7 breast cancer cells. The apparent anticancer activity of UA on MDA-MB-231 and MCF-7 cells was evident from IC50 values of 14.98 and 15.99 μg/mL, respectively, in MTT assay and also through enhanced generation of ROS. When MDA-MB-231 and MCF-7 cells were treated with 20 μg/mL UA, an absolute decrease in cell viability of 47.6% and 48.6%, enhancement of 1.35% and 1.10% in early apoptosis, and 21.90% and 21.35% in late apoptosis, respectively and G 0 /G 1 phase, S phase, G 2 /M phase cell cycle arrest was noticed. The gene expression studies revealed that UA could significantly (p < 0.001) downregulate the expression of EMT markers such as snail, slug, and fibronectin at molecular level. Further, the obtained in vitro results of snail, slug, and fibronectin were subjected to quantum-polarized-ligand (QM/MM) docking, which predicted that the in silico binding affinities of these three markers are in good correlation with strong hydrogen and van der Waal interactions to UA with -53.865, -48.971 and -40.617 MMGBSA (ΔG bind ) scores, respectively. The long-range molecular dynamics (50 ns) simulations have showed more consistency by UA. These findings conclude that UA inhibits breast cancer cells growth and proliferation through regulating the expression of key EMT marker genes, and thus UA is suggested as a potential anticancer agent., (© 2023 Wiley Periodicals LLC.)

Published
2023
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