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Melanoma in a patient with previously unrecognized Birt-Hogg-Dubé syndrome

JAAD Case Reports 2019年第11期5卷 947-952页

作者： Nowsheen, Somaira Hand, Jennifer L. Gibson, Lawrence E. el-Azhary, Rokea A. Mayo Clinic Medical Scientist Training Program Mayo Clinic Rochester MN United States Department of Dermatology Mayo Clinic Rochester MN United States Department of Pediatrics and Adolescent Medicine Mayo Clinic Rochester MN United States Department of Clinical Genomics Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States

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Reasons for delayed spinal cord decompression in individuals with traumatic spinal cord injuries in Iran:A qualitative study from the perspective of neurosurgeons

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Chinese Journal of Traumatology 2021年第6期24卷 356-359页

作者： Masoud SohrabiAsl Zahra Ghodsi Roya Habibi Arejan Zahra Azadmanjir Mahdi Sharif-Alhoseini Moein Khormali Maryam Shojaei Abbas Rahimiforoushani Alireza Khoshnevisan Alexander R.Vaccaro Michael G.Fehlings Vafa Rahimi-Movaghar Sina Trauma and Surgery Research Center Tehran University of Medical SciencesTehranIran Rehabilitation Office State Welfare Organization of IranTehranIran Health Information Management Department Tehran University of Medical Sciences Department of Epidemiology and Biostatistics School of Public HealthTehran University of Medical SciencesTehranIran Department of Neurosurgery Shariati HospitalTehran University of Medical SciencesTehran Iran Department of Orthopaedics and Neurosurgery Thomas Jefferson University and the Rothman InstitutePhiladelphiaPAUSA Department of Surgery University of TorontoSenior Scientist Krembil Brain Institute and McEwen Centre for Regenerative MedicineToronto Western HospitalUniversity Health NetworkCanada Universal Scientific Education and Research Network(USERN) TehranIran Institute of Biochemistry and Biophysics University of TehranTehranIran Visiting Professor Spine ProgramUniversity of TorontoTorontoCanada Brain and Spinal Cord Injury Research Center Neuroscience InstituteTehran University of Medical SciencesTehranIran

Purpose:The median time from the event leading to the spinal cord injury(SCI)to the time of decompressive surgery is estimated to be 6.9 days in Iran,which is much longer than the proposed ideal time(less than 24 h)in published *** current qualitative study aimed to determine the reasons for the observed decompression surgery delay in Iran from the perspective of ***:This qualitative study is designed to perform content analysis on the gathered data from face-to-face semi-structured interviews with 12 Iranian ***:The findings of the current study suggest that patient-related factors constitute more than half of the codes extracted from the ***,the type of injury,presence of polytrauma,and surgeons’’wrong attitude are the main factors causing delayed spinal cord decompression in Iranian patients from the perspective of *** notable factors include delay in transferring patients to the trauma center,delay in availability of necessary equipment,and scarce medical ***:In the perspective of neurosurgeons,the type of injury,presence of polytrauma,and surgeons’’wrong attitude are the leading reasons for delayed decompressive surgery of individuals with SCI in Iran.

关键词： Spinal cord injuries Decompression Surgical Neurosurgeons Iran Qualitative research

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Engineered BMP2/BMP7 extracellular vesicles induce autocrine BMP release driving SMAD phosphorylation to promote bone formation

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NPJ Regenerative medicine 2025年第1期10卷 26页

作者： Zeji Du Skylar A Rizzo Tiffany L Sarrafian Monique S Bagwell Ryan C Mahlberg Ashley Amontree Paige Schiebel Dinah M Tauferner Zoe S LeBrasseur Tyra A Witt Mary Nagel Kyla A Boyd Humberto De Vitto Matthew L Hillestad Paul G Stalboerger Matthew T Houdek Rafael J Sierra Atta Behfar Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Center for Regenerative Medicine Rochester MN USA. Mayo Clinic Medical Scientist Training Program Rochester MN USA. Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN USA. Mayo Clinic Department of Virology and Gene Therapy Mayo Clinic Rochester MN USA. Mayo Clinic Department of Cardiovascular Medicine Rochester MN USA. Mayo Clinic Department of Orthopedic Medicine Rochester MN USA. Van Cleve Cardiac Regenerative Medicine Program Mayo Clinic Center for Regenerative Medicine Rochester MN USA. behfar.atta@mayo.edu. Mayo Clinic Department of Molecular Pharmacology and Experimental Therapeutics Mayo Clinic Rochester MN USA. behfar.atta@mayo.edu. Mayo Clinic Department of Cardiovascular Medicine Rochester MN USA. behfar.atta@mayo.edu. Marriott Heart Disease Research Program Mayo Clinic Rochester MN USA. behfar.atta@mayo.edu.

In the United States, impaired bone healing impacts ~600,000 patients annually. Bone morphogenetic protein 2 (rhBMP2) therapy is impeded by low bone quality and adverse effects. Here, mesenchymal stem cells, engineered to produce BMP2 and BMP2/7 containing extracellular vesicles (BMP2-EV and BMP2/7-EV), provided an alternative means of stimulating bone formation. BMP2-EV and BMP2/7-EV drove increased calcium deposition and alkaline phosphatase activity; with increase in osterix, RUNX2, osteocalcin, and osteopontin documenting osteoblast differentiation. BMP2/7-EV induced SMAD phosphorylation and calcium deposition, was inhibited by DMH1, a BMP I receptor inhibitor, demonstrating BMP receptor dependence. BMP2 and BMP7 extracellular vesicle encapsulation was confirmed with preserved potency following treatment with BMP antagonist, Noggin. Application of BMP2/7-EV in a rat calvarial defect model demonstrated enhanced bone formation on micro-computed tomography and histopathologic analysis, equaling rhBMP2. BMP2/7-EV mediated bone formation here highlights EVs as a unique modality for delivery of tailored polyvalent regenerative biotherapies.

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Common AAV gene therapy vectors show nonselective transduction of ex vivo human brain tissue

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Molecular Therapy Methods & Clinical Development 2025年第2期33卷

作者： JP McGinnis Joshua Ortiz-Guzman Maria Camila Guevara Sai Mallannagari Benjamin D.W. Belfort Suyang Bao Snigdha Srivastava Maria Morkas Emily Ji Angela Addison Evelyne K. Tantry Sarah Chen Ying Wang Zihong Chen Kalman A. Katlowitz Jeffrey J. Lange Melissa M. Blessing Carrie A. Mohila M. Cecilia Ljungberg Guillermo Aldave Benjamin R. Arenkiel Department of Neurosurgery Baylor College of Medicine Houston TX 77030 USA Jan and Dan Duncan Neurological Research Institute Texas Children’s Hospital Houston TX 77030 USA Department of Molecular and Human Genetics Baylor College of Medicine Houston TX 77030 USA Medical Scientist Training Program Baylor College of Medicine Houston TX 77030 USA Development Disease Models & Therapeutics Graduate Program Baylor College of Medicine Houston TX 77030 USA Stowers Institute for Medical Research Kansas City MO 64110 USA Department of Pathology Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA Department of Pediatrics Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA Department of Neurosurgery Texas Children’s Hospital Baylor College of Medicine Houston TX 77030 USA

The ability to deliver a therapeutic sequence to a specific cell type in the human brain would make possible innumerable therapeutic options for some of our most challenging diseases; however, studies on adeno-associated virus (AAV) vector tropism have generally relied on animal models with limited translational utility. For this reason, establishing the tropism of common adeno-associated virus (AAV) vectors in living human brain tissue serves as an important baseline for further optimization, as well as a determination of human brain cell types transduced by clinically approved gene therapy vectors AAV2 and AAV9. We have adapted an ex vivo organotypic model to evaluate AAV transduction properties in living slices of human brain tissue. Using fluorescent reporter expression and single-nucleus RNA sequencing, we found that common AAV vectors show broad transduction of normal cell types, with protein expression most apparent in astrocytes; this work introduces a pipeline for identifying and optimizing AAV gene therapy vectors in human brain samples.

关键词： gene therapy human brain AAV AAV tropism human brain organotypic slice culture

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Modular, Topographically Patterned, Biomimetic Poly(Ethylene Glycol) Hydrogels as Customized Scaffolds for Organoid Culture

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SSRN 2020年

作者： Wilson, Reid L. Swaminathan, Ganesh Ettayebi, Khalil Bomidi, Carolyn Zeng, Xi-Lei Blutt, Sarah E. Estes, Mary K. Grande-Allen, K. Jane Department of Bioengineering Rice University 6100 Main Street HoustonTX77005 United States Strand Life Sciences Department of Molecular Virology and Microbiology Baylor College of Medicine 1 Baylor Plaza HoustonTX77030 United States Medical Scientist Training Program Baylor College of Medicine 1 Baylor Plaza HoustonTX77030 United States

The recent development of stem cell-derived, organotypic in vitro models, known as organoids, has revolutionized our ability to study important biological processes in vitro. However, their continued development is limited by the failure of the hydrogel matrices in which they are grown to adequately replicate the tissue-specific ECM cues they experience in their native in vivo environment. Here, we present a highly customizable, modular hydrogel scaffold that can incorporate tissue-specific cues from the extracellular matrix. We demonstrate that these scaffolds can be functionalized with a wide variety of cell adhesion molecules, including peptides and full-length proteins, and can support the attachment and growth of intestinal epithelials organoids, a model organoid system. We also found that these scaffolds can be patterned with large, high-aspect ratio topographical features that mimic anatomical structures (such as intestinal villi) found in vivo. Finally, we show that organoids cultured on these hydrogel scaffolds retain their capacity for multi-lineage differentiation and their ability to model enteric infections. Together, these findings are an excellent proof-of-concept that such hydrogel scaffolds can facilitate the development of organoid models of many organ systems and improve our ability to study a variety of important developmental and pathological processes. © 2020, The Authors. All rights reserved.

关键词： Peptides

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A Cell-Free Antigen Processing System Reveals Factors Critical for HIV-1 Epitope Dominance and Informs Vaccine Design

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SSRN 2021年

作者： Sengupta, Srona Reed, Madison C. Yu, Jeanna Zhang, Josephine Kim, Aeryon Boronina, Tatiana N. Welsh, Robin A. Yang, Weiming Timmons, Andrew E. Wrabl, James O. Hoh, Rebecca Cole, Robert N. Deeks, Steve Siliciano, Janet D. Siliciano, Robert F. Sadegh-Nasseri, Scheherazade Department of Medicine Johns Hopkins University School of Medicine BaltimoreMD21205 United States Department of Pathology Johns Hopkins University School of Medicine BaltimoreMD21205 United States Department of Inflammation and Oncology Genome Analysis Unit Amgen Research Amgen Inc. South San FranciscoCA94080 United States Mass Spectrometry and Proteomics Facility Department of Biological Chemistry Johns Hopkins University School of Medicine BaltimoreMD21205 United States Department of Biology Johns Hopkins University BaltimoreMD21218 United States Department of Medicine University of California San Francisco San FranciscoCA94143 United States Howard Hughes Medical Institute BaltimoreMD21205 United States The Graduate Program in Immunology Medical Scientist Training Program Johns Hopkins University School of Medicine BaltimoreMD21205 United States

Distinct CD4+T cell epitopes have been associated with spontaneous control of HIV-1 replication, but analysis of antigen-dependent factors that influence epitope selection is lacking. To examine these factors, we used a cell-free antigen processing system that incorporates soluble HLA-DR (DR1), HLA-DM (DM), and cathepsins along with full-length protein antigens for epitope identification by LC-MS/MS. HIV-1 Gag, Pol, Env, Vif, Nef, Tat, and Rev were examined using this system. We identified 35 novel epitopes, including glycopeptides. Epitopes from smaller HIV-1 proteins with crystal structures mapped to regions of low protein stability and higher solvent accessibility. HIV-1 antigens associated with limited CD4+T cell responses were processed efficiently, while some protective epitopes were inefficiently processed. 66% of epitopes obtained from cell-free processing induced memory CD4+T cell responses in HIV-1+ donors, including 10 of 19 novel epitopes. Thus, an in vitro processing system can identify novel HIV-1 epitopes and reveal factors influencing epitope dominance. © 2021, The Authors. All rights reserved.

关键词： Epitopes

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Structural and Biophysical Analysis of the Calcium-Activated Chloride Channel Regulator 1 (CLCA1) VWA Domain Suggests Mode of TMEM16A Engagement

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SSRN 2019年

作者： Berry, Kayla N. Brett, Tom J. Immunology Program and Medical Scientist Training Program Department of Internal Medicine Division of Pulmonary and Critical Care Department of Cell Biology and Physiology Department of Biochemistry and Molecular Biophysics Washington University School of Medicine St. LouisMO63110 United States

The secreted protein calcium-activated chloride channel regulator 1 (CLCA1) utilizes a von Willebrand Factor type A domain (VWA) to bind to and potentiate the calcium activated chloride channel TMEM16A. To gain insight into this unique potentiation mechanism, we determined the 2.0 Å crystal structure of human CLCA1 VWA bound to Ca2+, the first CLCA family structure reported. The structure reveals the metal ion dependent adhesion site (MIDAS) in a high-affinity "open" conformation, engaging in crystal contacts that likely mimic how CLCA1 engages TMEM16A. The CLCA1 VWA contains a disulfide bond between α3 and α4 in close proximity to the MIDAS that is invariant in the CLCA family and unique in VWA structures. Further biophysical studies indicate that CLCA1 VWA is preferably stabilized by Mg2+ over Ca2+ and that a6 atypically extends from the VWA core. Finally, an analysis of TMEM16A structures suggests residues likely to mediate interaction with CLCA1 VWA. © 2019, The Authors. All rights reserved.

关键词： Glycoproteins

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Regulation of stem and progenitor cells in the adrenal cortex

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Current Opinion in Endocrine and Metabolic Research 2019年 8卷 66-71页

作者： Finco, Isabella Mohan, Dipika R. Hammer, Gary D. Lerario, Antonio Marcondes Department of Internal Medicine Division of Metabolism Endocrinology and Diabetes University of Michigan Ann Arbor MI United States Medical Scientist Training Program University of Michigan Ann Arbor MI United States Doctoral Program in Cancer Biology University of Michigan Ann Arbor MI United States Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI United States Rogel Cancer Center University of Michigan Ann Arbor MI United States Department of Cell & Developmental Biology University of Michigan Ann Arbor MI United States

The adrenal cortex is an endocrine organ comprised of three histological zones, the outermost zona glomerulosa, the intermediate zona fasciculata, and the innermost zona reticularis. High plasticity of the adrenal gland is supported by pools of stem and progenitor cells that are deployed to sustain physiological and homeostatic demands. In recent decades, exciting new discoveries elucidating the identity, function, and fate of these cell populations have emerged. In this review, we describe paracrine and endocrine signaling loops that are crucial for adrenal biology, focusing on recent studies unpacking the enigmatic nature of adrenal stem and progenitor cell populations. © 2019 Elsevier Ltd

关键词： Adrenal cortex Endocrine signaling Progenitor cells Signaling pathways Stem cells

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Real-World Experiences With Yoga on Cancer-Related Symptoms in Women With Breast Cancer

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Global Advances In Health and Medicine 2021年第1期10卷

作者： Patel, Shruti R Zayas, Jacqueline Medina-Inojosa, Jose R Loprinzi, Charles Cathcart-Rake, Elizabeth J Bhagra, Anjali Olson, Janet E Couch, Fergus J Ruddy, Kathryn J Department of Internal Medicine Mayo Clinic Rochester MN United States Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic School of Medicine and the Mayo Clinic Medical Scientist Training Program Rochester MN United States Department of Cardiovascular Medicine Mayo Clinic Rochester MN United States Department of Medical Oncology Mayo Clinic Rochester MN United States Department of Medical Oncology University of Missouri Kansas City MO United States Department of Health Sciences Research Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States

Purpose: Integrative therapies such as yoga are potential treatments for many psychological and physical symptoms that occur during and/or after treatment for cancer. The purpose of the current study was to evaluate the patient-perceived benefit of yoga for symptoms commonly experienced by breast cancer survivors. Methods: 1,049 breast cancer survivors who had self-reported use of yoga on a follow up survey, in an ongoing prospective Mayo Clinic Breast Disease Registry (MCBDR), received an additional mailed yoga-focused survey asking about the impact of yoga on a variety of symptoms. Differences between pre- and post- scores were assessed using Wilcoxon Signed Rank Test. Results: 802/1,049 (76%) of women who were approached to participate, consented and returned the survey. 507/802 (63%) reported use of yoga during and/or after their cancer diagnosis. The vast majority of respondents (89.4%) reported some symptomatic benefit from yoga. The most common symptoms that prompted the use of yoga were breast/chest wall pain, lymphedema, and anxiety. Only 9% of patients reported that they had been referred to yoga by a medical professional. While the greatest symptom improvement was reported with breast/chest wall pain and anxiety, significant improvement was also perceived in joint pain, muscle pain, fatigue, headache, quality of life, hot flashes, nausea/vomiting, depression, insomnia, lymphedema, and peripheral neuropathy, (all p-values <0.004). Conclusion: Data supporting the use of yoga for symptom management after cancer are limited and typically focus on mental health. In this study, users of yoga often reported physical benefits as well as mental health benefits. Further prospective studies investigating the efficacy of yoga in survivorship are warranted. © The Author(s) 2021.

关键词： breast cancer complementary and alternative medicine survivorship symptom control yoga

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New strategies for applying targeted therapies to adrenocortical carcinoma

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Current Opinion in Endocrine and Metabolic Research 2019年 8卷 72-79页

作者： Mohan, Dipika R. Lerario, Antonio Marcondes Finco, Isabella Hammer, Gary D. Medical Scientist Training Program University of Michigan Ann Arbor MI United States Doctoral Program in Cancer Biology University of Michigan Ann Arbor MI United States Department of Internal Medicine Division of Metabolism Endocrinology and Diabetes University of Michigan Ann Arbor MI United States Department of Molecular and Integrative Physiology University of Michigan Ann Arbor MI United States Department of Cell & Developmental Biology University of Michigan Ann Arbor MI United States University of Michigan Rogel Cancer Center University of Michigan Ann Arbor MI United States

Adrenocortical carcinoma (ACC) is a rare, aggressive, and frequently deadly cancer. Up to 75% of all patients will eventually develop metastatic disease, and our current medical therapies for ACC provide limited — if any — survival benefit. These statistics highlight a crucial need for novel approaches. Recent studies performing comprehensive molecular profiling on ACC have illuminated that ACC comprises three clinically distinct molecular subtypes, bearing differential regulation of the cell cycle, epigenetics, Wnt/β-catenin signaling, PKA signaling, steroidogenesis, and immune cell biology. Furthermore, these studies have spurred the development of molecular subtype–based biomarkers, contextualized outcomes of recent clinical trials, and advanced our understanding of the underlying biology of adrenocortical homeostasis and cancer. In this review, we describe these findings and their implications for new strategies to apply targeted therapies to ACC. © 2019 Elsevier Ltd

关键词： ACC Adrenocortical carcinoma Biomarkers Genomics Targeted therapy

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