tbuckley/cabot-search huggingface dataset:
Targeting PARG induces tumor cell growth inhibition and antitumor immune response by reducing phosphorylated STAT3 in ovarian cancer
Authors: Antons Martincuks, Chunyan Zhang, Theresa Austria, Yi-Jia Li, Rui Huang, Nicole Lugo Santiago, Adrian Kohut, Qianqian Zhao, Rosemarie Martinez Borrero, Binghui Shen, Mihaela Cristea, Edward W Wang, Mihae Song, Lorna Rodriguez-Rodriguez, Hua Yu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Ovarian cancer is the most lethal gynecological malignancy, with limited treatment options after failure of standard therapies. Despite the potential of poly(ADP-ribose) polymerase inhibitors in treating DNA damage response (DDR)-deficient ovarian cancer, the development of resistance and immunosuppression limit their efficacy, necessitating alternative therapeutic strategies. Inhibitors of poly(ADP-ribose) glycohydrolase (PARG) represent a novel class of inhibitors that are currently being assessed in preclinical and clinical studies for cancer treatment. Methods By using a PARG small-molecule inhibitor, COH34, and a cell-penetrating antibody targeting the PARG’s catalytic domain, we investigated the effects of PARG inhibition on signal transducer and activator of transcription 3 (STAT3) in OVCAR8, PEO1, and Brca1 -null ID8 ovarian cancer cell lines, as well as in immune cells. We examined PARG inhibition-induced effects on STAT3 phosphorylation, nuclear localization, target gene expression, and antitumor immune responses in vitro, in patient-derived tumor organoids, and in an immunocompetent Brca1 -null ID8 ovarian mouse tumor model that mirrors DDR-deficient human high-grade serous ovarian cancer. We also tested the effects of overexpressing a constitutively activated STAT3 mutant on COH34-induced tumor cell growth inhibition. Results Our findings show that PARG inhibition downregulates STAT3 activity through dephosphorylation in ovarian cancer cells. Importantly, overexpression of a constitutively activated STAT3 mutant in tumor cells attenuates PARG inhibitor-induced growth inhibition. Additionally, PARG inhibition reduces STAT3 phosphorylation in immune cells, leading to the activation of antitumor immune responses, shown in immune cells cocultured with ovarian cancer patient tumor-derived organoids and in immune-competent mice-bearing mouse ovarian tumors. Conclusions We have identified a novel antitumor mechanism underlying PARG inhibition beyond its primary antitumor effects through blocking DDR in ovarian cancer. Furthermore, targeting PARG activates antitumor immune responses, thereby potentially increasing response rates to immunotherapy in patients with ovarian cancer.
SIMULTANEOUS WATCHMAN AND ATRIAL SEPTAL DEFECT CLOSURE IN SETTING OF SIGNIFICANT GASTROINTESTINAL BLEEDING
Authors: Daniel Pak, Patrick May, Roi Altit, Abdalrahman Assaassa, Joshua Malinis, Suleiman Khreshi, Kartikeya Kaul, Saad Hussain
Journal: Journal of the American College of Cardiology (2024)
PROPIONIC ACIDEMIA: A RARE ETIOLOGY OF ADVANCED HEART FAILURE WARRANTING AN UNCOMMON SOLUTION
Authors: Ellen Kelly, Swaiman Singh, Philip Spencer, Adrian daSilva-deAbreu, Juan Crestanello, Sudhir S. Kushwaha, Robert P. Frantz, Barry A. Boilson
Journal: Journal of the American College of Cardiology (2024)
LEAD MALFUNCTION AND DISRUPTION OF CARDIAC RESYNCHRONIZATION THERAPY (CRT) DUE TO MINERALIZATION - A COMPLICATION OF ASIA SYNDROME DUE TO GLUTEAL BIOPOLYMER INJECTIONS
Authors: Jesse N. Medina, Stacey C. Regis, Renan Prado, Ryan Severdija, Rahul Sheth, Rosario Colombo, Chaitra Mohan, Assaf Tzur, Mrudula Munagala
Journal: Journal of the American College of Cardiology (2024)
THE WATCHMEN AND A TUNNEL: DEPLOYMENT OF TWO WATCHMAN FLX AND PFO CLOSURE IN A PATIENT WITH ATRIAL FIBRILLATION AND COR PULMONALE
Authors: Jerry Lipinski, Kishan Padalia, Theresa Thai, Gurmukh Kainth, Charles Tharp, Andrew Prouse, Lohit Garg, Syed Rafay Ali Sabzwari, Amneet Sandhu, Alexis Z. Tumolo, Paul D. Varosy, Wendy S. Tzou, Johannes von Alvensleben, Ryan G. Aleong, Matthew Michael Zipse, John Jason West, Joseph Burke
Journal: Journal of the American College of Cardiology (2024)
LEFT ATRIAL MASS AS A RARE PRESENTATION FOR A SILENT ATRIAL-ESOPHAGEAL FISTULA AFTER ATRIAL FIBRILLATION ABLATION THERAPY
Authors: Aneeza Jamshed, Ayesha Abbasi, Alejandro Nieto Dominguez, Imran Naeem Aziz, Yousra Khalid, Manoj Kumar, Mahir Yilmaz, Ufuk Vardar, Sadichhya Karki, Aviral Vij, Rohan Gajjar
Journal: Journal of the American College of Cardiology (2024)
BEST MATERNAL AND FETAL CARE PRACTICES FOR HYPERTROPHIC CARDIOMYOPATHY
Authors: Luis Alonso Hernandez Mejia, Nitheesha Ganta, Arianne Clare C. Agdamag, Phoo Pwint Nandar, Jeffrey S. Bennett, Justin Lappen, Katherine Singh, Tanisha Mishra, Karlee K. Hoffman
Journal: Journal of the American College of Cardiology (2024)
INSANE IN THE MEMBRANE: THE ROLE OF CATHETERIZATION IN THE DIAGNOSIS OF A SUBAORTIC MEMBRANE
Authors: Rebecca Kocak, Christina Romano, Cara Joseph, Meer Fakhry, William Meeks, Ninad M. Zaman, Muhammad Mohyuddin, Hata Mujadzic, Gabrielle Rhinehart, Patrick Anthony Xavier Hall
Journal: Journal of the American College of Cardiology (2024)
NATURAL SURVIVOR OF UNIVENTRICULAR HEART PHYSIOLOGY'S MISFORTUNES
Authors: Fabio Akio Nishijuka, David Duarte, maria cola, Beny Binensztok, Bianca De Almeida Teodoro, Maria Gabriela Pimenta Dos Santos, Aloan Carlos Lemos Ferraz, Nathalia Valle, Lorreine Ferreira, Cíntia Mattoso, Luiza Nobre, Regis Oliveira, Thaissa Monteiro
Journal: Journal of the American College of Cardiology (2024)
LEFT VENTRICULAR NONCOMPACTION CARDIOMYOPATHY WITH MYOCARDITIS IN A YOUNG MALE: A CASE REPORT OF AN UNCOMMON OVERLAP
Authors: Azeem H. Rathore, Leela Krishna Teja Boppana, Anh Do, Nimeh Najjar, Dinesh Kadariya, Khadeeja Esmail
Journal: Journal of the American College of Cardiology (2024)
THE DEADLIEST CATCH: MYOCARDITIS FROM SALMONELLA ENTERITIS
Authors: Abhinav Karan, Mohamed E. Abdul Qader, Hui Jun Guo, Samantha Isern, Avni Agrawal, Aarav Mohanlal, Kaitlyn Romero, Alexander Black, Dinesh Kadariya, Luis Ortega Paz
Journal: Journal of the American College of Cardiology (2024)
PERCUTANEOUS INTERVENTION OF LVAD OUTFLOW GRAFT OBSTRUCTION AND THROMBOSIS
Authors: Andrew Takla, Mohamed Eid, Akshay Joshi, Moghniuddin Mohammed, Fahad Eid, Kirolus Sourial, Mostafa Zaalouk, Mostafa Elbanna, Mostafa Najim, Abdallah Bitar
Journal: Journal of the American College of Cardiology (2024)
THE CASE OF THE MISSING CORONARY: AN ANOMALOUS ORIGIN OF THE RIGHT CORONARY ARTERY ARISING FROM THE PULMONARY ARTERY
Authors: Afif Hossain, Baoqiong Liu, Paul Y. Lee, Vinesh Jonnala, Kyrollos G. Saad, Omar Elkattawy, Aysha Hussain, Shriya Patel, Mina Ghbrial, Joshua Greendyk, Soyi Sarkar, Sabino R. Torre
Journal: Journal of the American College of Cardiology (2024)
SEVERE AORTIC REGURGITATION POST-TRANSCATHETER AORTIC VALVE REPLACEMENT LINKED TO SINUS OF VALSALVA PSEUDOANEURYSM
Authors: Omofolarin Babayale, Nada Hafez, Astha Prasai, Hina Ukrani, Andrew Takla, Bipul Baibhav, Mallory Balmer-Swain
Journal: Journal of the American College of Cardiology (2024)
PERSISTING AORTIC DISSECTION AND CHRONIC DIC: MONITORING AND MANAGEMENT OF A RARE COMPLICATION
Authors: Prem Parajuli, Kristina Shum, Nimesh Khanal, Bidhya Timilsina, Bharosha Bhattarai, Apil Dawadi, Sijan Basnet, Aniruddha Singh
Journal: Journal of the American College of Cardiology (2024)
ALL THAT GLITTERS IS NOT GOLD: ATRIOVENTRICULAR NODAL REENTRANT TACHYCARDIA MASQUERADING AS A VENTRICULAR TACHYCARDIA IN AN ISCHEMIC HEART DISEASE PATIENT
Authors: Somto Tagbo Nwaedozie, Jacob Obholz, Deepa Soodi, Elliot A. Hwang, Param P. Sharma, Weijia Wang
Journal: Journal of the American College of Cardiology (2024)
MINOCA VS MYOPERICARDITIS: A DIAGNOSTIC CHALLENGE IN A MIDDLE INCOME COUNTRY
Authors: Jose Valdez, Saray Maria Perez Alegria, Lairyn Halpay, Grisel Onelia Canahuate, Eunices Tavarez, Damarys Samboy Turbi, Pura M. Henriquez
Journal: Journal of the American College of Cardiology (2024)
HEART UNDER SIEGE: NAVIGATING CARDIAC TAMPONADE WITH BIVENTRICULAR HEART FAILURE IN THE SETTING OF SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: Sacide S. Ozgur, Muhammad Adil Afzal, Nida Ansari, Rachel Abboud, Yezin F. Shamoon, Sherif Elkattawy, Fayez E. Shamoon
Journal: Journal of the American College of Cardiology (2024)
A RARE CASE OF APIXABAN-INDUCED HYPERSENSITIVITY SKIN RASH IN THE CRITICAL CARE UNIT
Authors: Abdul-Fatawu Osman, Blessing Eze, Malak Tahsin, Sammudeen Ibrahim, Sajithaa Varadarasa, Abeeha Naqvi, Habib Rahban, Kelly Wesselhoff, Andrew Boshara, Bimal Padaliya, Robert Roberts, Namit Rohant
Journal: Journal of the American College of Cardiology (2024)
WORKUP AND MANAGEMENT OF A NEW NONISCHEMIC CARDIOMYOPATHY WITH ABCDES: AORTIC VALVE VEGETATION, BLOOD CULTURES NEGATIVE, CVA, DETERIORATING VALVES, EOSINOPHILS AND EMBOLI
Authors: Amy Rechenberg, Mahrukh F. Akram, Laura Franey
Journal: Journal of the American College of Cardiology (2024)
COMPLETE RECOVERY AFTER ECMO IN THE SETTING OF CARDIAC ARREST FROM RVOT PERFORATION DURING PULMONARY EMBOLISM THROMBECTOMY IN A PATIENT WITH MAYTHURNER SYNDROME
Authors: Laura Muller, Dhiran Verghese, Elsy Viviana Navas, Mazen Albaghdadi, Stephen E. D'Orazio
Journal: Journal of the American College of Cardiology (2024)
IDENTIFICATION OF ANOMALOUS RETRO-AORTIC CIRCUMFLEX CORONARY ARTERY IN TRANSTHORACIC ECHOCARDIOGRAM: RETRO-AORTIC ANOMALOUS CORONARY (RAC) SIGN
Authors: Prem Parajuli, Nimesh Khanal, Bidhya Timilsina, Bharosha Bhattarai, Arjun Basnet, Apil Dawadi, Robert Dendall, Aniruddha Singh
Journal: Journal of the American College of Cardiology (2024)
A RARE COMPLICATION OF SURGICAL MITROAORTIC CONTINUITY REPAIR - A MULTIMODAL APPROACH
Authors: Ximena Latapi Ruiz Esparza, Sarai Hernandez Pastrana, Aranzazu Vanessa Alegria Saldivar, Oscar-Ulises Preciado-Gutierrez, Nitzha Andrea Najera-Rojas, Rafael Sanez, Alejandro Sierra, Luis Alejandro Soliz Uriona, Rodrigo Gopar-Nieto, Jose Luis Briseño De La Cruz, Diego Araiza Garaygordobil, Hector Gonzalez-Pacheco, Alexandra Arias-Mendoza, Daniel Sierra
Journal: Journal of the American College of Cardiology (2024)
SEVERE REGURGITATION OF THE NATIVE MITRAL VALVE DUE TO BRUCELLA ENDOCARDITIS
Authors: Dominic J. Vacca, Hata Mujadzic, Ninad M. Zaman, Rebecca Kocak, William Meeks, Meer Fakhry, Gabrielle Rhinehart, Muhammad Mohyuddin, Meghan L. Businaro
Journal: Journal of the American College of Cardiology (2024)
CARDIAC FIBROELASTOMA MIMICKING BRUGADA SYNDROME AND ACUTE ANTERIOR STEMI IN A GERIATRIC FEMALE PATIENT
Authors: Mohammad Alshami, Mohannad Al Akeel, Huthaifah Aburumman, Ahmed Kassem Abdallah, Manar H. Jbara, Vijay K. Ramu
Journal: Journal of the American College of Cardiology (2024)
A CARDIAC PLOT TWIST: BICUSPID AORTIC VALVE UNVEILS COARCTATION
Authors: Tala A. Haddad, Hashim AlHammouri, Nora Abuammouneh, Zaid Al-Abed, Mahmoud Qeshta, Hanna K. Al-Makhamreh
Journal: Journal of the American College of Cardiology (2024)
IMPACT OF BALLOON PULMONARY ANGIOPLASTY ON VENTILATORY INEFFICIENCY IN OPERABLE CTEPH - A CASE REPORT
Authors: Alexis Coulis, Vladimir Lakhter, Ahmed Sadek, Amine Nasri, Anjali Vaidya, PAUL FORFIA, Riyaz Bashir, Estefania Oliveros Soles
Journal: Journal of the American College of Cardiology (2024)
MULTI-MODALITY IMAGING ANALYSIS OF A RIGHT VENTRICULAR LESION IN THE SETTING OF METASTATIC LEIOMYOSARCOMA
Authors: Andrew Sagalov, Abubaker Kallan, Michael Obregon, Samie M. Gilani, Shruti Hegde, Abhishek Kalidas Kulkarni, Momin Siddique
Journal: Journal of the American College of Cardiology (2024)
HEMODYNAMIC ASSESSMENT AND MANAGEMENT OF CONCURRENT HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY AND SEVERE AORTIC STENOSIS
Authors: Samuel B. Jackson, Dhananjay Chatterjee, Aleesha Shaik, Aditya R. Goud, Daniel Cruz, Negeen Shahandeh, Pratyaksh Srivastava
Journal: Journal of the American College of Cardiology (2024)
UTILIZATION OF TRANSTHORACIC ECHOCARDIOGRAM FOR THE ASSESSMENT OF MINIMALLY INVASIVE INTERVENTION IN SEVERE MITRAL STENOSIS AND REGURGITATION
Authors: Priyanka Bhagat-Raj, Anisha Pareddy, John Dayco, Abdalaziz Awadelkarim, Tiffany T. Le, Fadi Kathawa, Parnal Kapadia
Journal: Journal of the American College of Cardiology (2024)
GHOST BUSTERS, PARADOXICAL BUSTERS, OR CLOT BUSTERS? AN ETIOPATHOGENESIS ANALYSIS OF A DEVIOUS STEMI CONFOUNDED BY THROMBOLYTICS
Authors: Sheena Amin, Hanyuan Shi, Max Biondi, Daniel Feldman, Hannah Bensimhon, Daniel Robert Storms
Journal: Journal of the American College of Cardiology (2024)
AN INDOLENT CASE OF GIANT CELL MYOCARDITIS PRESENTING WITH VENTRICULAR TACHYCARDIA
Authors: Nicolette Friedman, Tanesha Beebe-Peat, Sean D. Till, Vall Vinaithirthan, Jay Vance, Sherrie Khadanga, Joseph F. Winget
Journal: Journal of the American College of Cardiology (2024)
ANOMALOUS ORIGIN OF RIGHT CORONARY ARTERY FROM PROXIMAL LEFT ANTERIOR DESCENDING ARTERY: AN INCIDENTAL FINDING
Authors: Marlon Rivera Boadla, Azka Naeem, Nava Sharma, Asiya Batool, Arsalan Talib Hashmi, Omair A. Khan, Syed Mohammad Mazhar Uddin
Journal: Journal of the American College of Cardiology (2024)
Regulation of BCR-mediated Ca <sup>2+</sup> mobilization by MIZ1-TMBIM4 safeguards IgG1 <sup>+</sup> GC B cell–positive selection
Authors: Lingling Zhang, Amparo Toboso-Navasa, Arief Gunawan, Abdouramane Camara, Rinako Nakagawa, Katja Finsterbusch, Probir Chakravarty, Rebecca Newman, Yang Zhang, Martin Eilers, Andreas Wack, Pavel Tolar, Kai-Michael Toellner, Dinis Pedro Calado
Journal: Science Immunology (2024)

The transition from immunoglobulin M (IgM) to affinity-matured IgG antibodies is vital for effective humoral immunity. This is facilitated by germinal centers (GCs) through affinity maturation and preferential maintenance of IgG + B cells over IgM + B cells. However, it is not known whether the positive selection of the different Ig isotypes within GCs is dependent on specific transcriptional mechanisms. Here, we explored IgG1 + GC B cell transcription factor dependency using a CRISPR-Cas9 screen and conditional mouse genetics. We found that MIZ1 was specifically required for IgG1 + GC B cell survival during positive selection, whereas IgM + GC B cells were largely independent. Mechanistically, MIZ1 induced TMBIM4, an ancestral anti-apoptotic protein that regulated inositol trisphosphate receptor (IP3R)–mediated calcium (Ca 2+ ) mobilization downstream of B cell receptor (BCR) signaling in IgG1 + B cells. The MIZ1-TMBIM4 axis prevented mitochondrial dysfunction–induced IgG1 + GC cell death caused by excessive Ca 2+ accumulation. This study uncovers a unique Ig isotype–specific dependency on a hitherto unidentified mechanism in GC-positive selection.
SHIFTING OF CALCIUM WITH TAVI CAUSING SUBACUTE CRITICAL LEFT MAIN CORONARY ARTERY STENOSIS REQUIRING CABG
Authors: Abdallah Masri, David Nery, Dilanthy R. Annappah, Yan Naung Htay, Sharan Rufus Ponniah, Basharat Ahmad
Journal: Journal of the American College of Cardiology (2024)
IMPELLA 5.5 PLUS 70 DAYS EQUALS SUCCESSFUL HEART-LIVER TRANSPLANT
Authors: Jenna Skowronski, William R. Barrington, Nicholas Faraci, Edward Horn, Ryan Rivosecchi, Veronica Garvia, Pyongsoo Yoon, David Kaczorowski, Gavin W. Hickey
Journal: Journal of the American College of Cardiology (2024)
JUNGLE JUICE INDUCED MYOCARDIAL INJURY: CHRONIC USE AND NEW VARIATIONS IN NITRITE PRODUCTS
Authors: Matthew Baer, James Choi, Vahid Namdarizandi, Michael Gurin, Marija Petrovic, Kirtipal Bhatia, Loba Alam, Devika Aggarwal, Sandra Maria Soler
Journal: Journal of the American College of Cardiology (2024)
PATIENT SELECTION PROTOCOL FOR OUTPATIENT PERCUTANEOUS CLOSURE OF THE LEFT ATRIAL APPENDAGE IN THE CONTEXT OF ATRIAL FIBRILLATION WITH CONTRAINDICATION FOR ANTICOAGULATION
Authors: Juan Carlos Vega, Mauricio Vanegas, Randall Quiros Fallas, Vladimir Poutvinski Poutvinska
Journal: Journal of the American College of Cardiology (2024)
PERCUTANEOUS LEFT ATRIAL APPENDAGE OCCLUSION IN MITRAL VALVE DISEASE: A NATIONWIDE READMISSION DATABASE ANALYSIS
Authors: Rafey Feroze, Waqas Ullah, Puneet Kang, Tabitha N. Lobo, Sung-Han Yoon, Luis Augusto Dallan, Steven Filby
Journal: Journal of the American College of Cardiology (2024)
UNCHARTED TERRITORY: CONSIDERING HEART TRANSPLANT IN ADULT CONGENITAL HEART DISEASE WITH PROTEIN LOSING ENTEROPATHY AND HYPOGAMMAGLOBINEMIA
Authors: Neeja Patel, Elizabeth Dente, Nguyen Pham, Joseph Isaac Wong, Megan Pelter, Jenica Thangathurai, Mario Deng, Gentian Lluri, Andrew D. Watson
Journal: Journal of the American College of Cardiology (2024)
PERCUTANEOUS CORONARY INTERVENTION OF TRAUMATIC RIGHT CORONARY ARTERY OCCLUSION FROM A HIGH VELOCITY AIR RIFLE PELLET IN AN ADOLESCENT MALE
Authors: Vandan D. Upadhyaya, Abbas Alshami, Steven Imburgio, Palak Patel, Anas Alrefaee, Deepak Singh, Madhav Upadhyaya
Journal: Journal of the American College of Cardiology (2024)
GLOBAL BURDEN OF CARDIOVASCULAR DISEASE ATTRIBUTABLE TO SMOKING, 1990-2019; AN ANALYSIS OF 2019 GLOBAL BURDEN OF DISEASE STUDY
Authors: Abdul Mannan Khan Minhas, Michael D. Shapiro, Mahboob Alam, Salim S. Virani, Christie M. Ballantyne, Dmitry Abramov
Journal: Journal of the American College of Cardiology (2024)
EXPLORING UNCOMMON SYNCOPE: A CASE OF ISOLATED CARDIAC SARCOIDOSIS
Authors: Christopher Luna Estrella, Eddiana Colon, Alfonso Corral, Rafaelina Lopez, Luz Mendez, Carolina Tejada, Kristy Collado, José Abel Camilo Figueroa, Yomary Campos, Maria Lopez, Derys Valerio
Journal: Journal of the American College of Cardiology (2024)
Identification of cells of leukemic stem cell origin with non-canonical regenerative properties
Authors: Cameron G. Hollands, Allison L. Boyd, Xueli Zhao, Jennifer C. Reid, Charisa Henly, Amro ElRafie, David Boylan, Emily Broder, Olivia Kalau, Paige Johnson, Alyssa Mark, Jamie McNicol, Anargyros Xenocostas, Tobias Berg, Ronan Foley, Michael Trus, Brian Leber, Alejandro Garcia-Horton, Clinton Campbell, Mickie Bhatia
Journal: Cell Reports Medicine (2024)

Despite most acute myeloid leukemia (AML) patients entering remission following chemotherapy, outcomes remain poor due to surviving leukemic cells that contribute to relapse. The nature of these enduring cells is poorly understood. Here, through temporal single-cell transcriptomic characterization of AML hierarchical regeneration in response to chemotherapy, we reveal a cell population: AML regeneration enriched cells (RECs). RECs are defined by CD74/CD68 expression, and although derived from leukemic stem cells (LSCs), are devoid of stem/progenitor capacity. Based on REC in situ proximity to CD34-expressing cells identified using spatial transcriptomics on AML patient bone marrow samples, RECs demonstrate the ability to augment or reduce leukemic regeneration in vivo based on transfusion or depletion, respectively. Furthermore, RECs are prognostic for patient survival as well as predictive of treatment failure in AML cohorts. Our study reveals RECs as a previously unknown functional catalyst of LSC-driven regeneration contributing to the non-canonical framework of AML regeneration.
Gut bacteria-driven homovanillic acid alleviates depression by modulating synaptic integrity
Authors: Mingliang Zhao, Zhenxing Ren, Aihua Zhao, Yajun Tang, Junliang Kuang, Mengci Li, Tianlu Chen, Shouli Wang, Jieyi Wang, Huiheng Zhang, Jijun Wang, Tianhong Zhang, Jiahui Zeng, Xiaohua Liu, Guoxiang Xie, Penghong Liu, Ning Sun, Tianhao Bao, Tongtong Nie, Jingchao Lin, Ping Liu, Yuanyi Zheng, Xiaojiao Zheng, Tiemin Liu, Wei Jia
Journal: Cell Metabolism (2024)

The gut-brain axis is implicated in depression development, yet its underlying mechanism remains unclear. We observed depleted gut bacterial species, including Bifidobacterium longum and Roseburia intestinalis, and the neurotransmitter homovanillic acid (HVA) in individuals with depression and mouse depression models. Although R. intestinalis does not directly produce HVA, it enhances B. longum abundance, leading to HVA generation. This highlights a synergistic interaction among gut microbiota in regulating intestinal neurotransmitter production. Administering HVA, B. longum, or R. intestinalis to mouse models with chronic unpredictable mild stress (CUMS) and corticosterone (CORT)-induced depression significantly improved depressive symptoms. Mechanistically, HVA inhibited synaptic autophagic death by preventing excessive degradation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 proteins, protecting hippocampal neurons' presynaptic membrane. These findings underscore the role of the gut microbial metabolism in modulating synaptic integrity and provide insights into potential novel treatment strategies for depression.
Tissue-specific nonheritable influences drive endometrial immune system variation
Authors: Jonna Bister, Iva Filipovic, Dan Sun, Ylva Crona-Guterstam, Martin Cornillet, Andrea Ponzetta, Jakob Michaëlsson, Sebastian Gidlöf, Martin A. Ivarsson, Benedikt Strunz, Niklas K. Björkström
Journal: Science Immunology (2024)

Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the contribution of these factors to immune system variability in tissues remains unexplored. The human uterus undergoes constant regeneration and is exposed to distinct environmental factors. To assess uterine immune system variation, we performed a system-level analysis of endometrial and peripheral blood immune cells in monozygotic twins. Although most immune cell phenotypes in peripheral blood showed high genetic heritability, more variation was found in endometrial immune cells, indicating a stronger influence by environmental factors. Cytomegalovirus infection was identified to influence peripheral blood immune cell variability but had limited effect on endometrial immune cells. Instead, hormonal contraception shaped the local endometrial milieu and immune cell composition with minor influence on the systemic immune system. These results highlight that the magnitude of human immune system variation and factors influencing it can be tissue specific.
AS03 adjuvant enhances the magnitude, persistence, and clonal breadth of memory B cell responses to a plant-based COVID-19 vaccine in humans
Authors: Lilit Grigoryan, Yupeng Feng, Lorenza Bellusci, Lilin Lai, Bushra Wali, Madison Ellis, Meng Yuan, Prabhu S. Arunachalam, Mengyun Hu, Sangeeta Kowli, Sheena Gupta, Sofia Maysel-Auslender, Holden T. Maecker, Hady Samaha, Nadine Rouphael, Ian A. Wilson, Alberto C. Moreno, Mehul S. Suthar, Surender Khurana, Stéphane Pillet, Nathalie Charland, Brian J. Ward, Bali Pulendran
Journal: Science Immunology (2024)

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4 + T cell and memory B cell responses. Antigen-specific CD4 + T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response.
A CASE OF INCIDENTAL FINDING OF A LARGE ASD WITH SHUNTING AND SEVERE PULMONARY HYPERTENSION IN ASYMPTOMATIC 58-YEAR-OLD PATIENT WHO PRESENTED WITH STROKE LIKE SYMPTOMS
Authors: Michael Morgan, Vikas Yellapu, David Allen, Eluwana A.D.T. Amaratunga, Kashyap Shah
Journal: Journal of the American College of Cardiology (2024)