Article
Gastroenterology & Hepatology
Omar Y. Mousa, Brian D. Juran, Bryan M. McCauley, Mette N. Vesterhus, Trine Folseraas, Coleman T. Turgeon, Ahmad H. Ali, Erik M. Schlicht, Elizabeth J. Atkinson, Chang Hu, Denise Harnois, Elizabeth J. Carey, Andrea A. Gossard, Devin Oglesbee, John E. Eaton, Nicholas F. LaRusso, Gregory J. Gores, Tom H. Karlsen, Konstantinos N. Lazaridis
Summary: In patients with PSC, alterations in plasma BA consistent with cholestasis, UDCA treatment, and IBD were observed. BA profiles were able to predict future hepatic decompensation, demonstrating the clinical potential of BA profiling for use in clinical trials.
Article
Multidisciplinary Sciences
Rolf Reiter, Mehrgan Shahryari, Heiko Tzschatzsch, Dieter Klatt, Britta Siegmund, Bernd Hamm, Jurgen Braun, Ingolf Sack, Patrick Asbach
Summary: The study assessed spatial heterogeneity of hepatic fibrosis in PSC and viral hepatitis using MR elastography, finding significantly increased fibrosis heterogeneity in PSC compared to viral hepatitis. There was no significant difference in shear-wave speed between PSC and viral hepatitis, indicating potential for enhanced diagnosis based on spatial heterogeneity patterns revealed by MRI.
SCIENTIFIC REPORTS
(2021)
Article
Gastroenterology & Hepatology
Jonathon J. Graham, Sujit Mukherjee, Muhammad Yuksel, Rebeca Sanabria Mateos, Tengfei Si, Zhenlin Huang, Xiahong Huang, Hadil Abu Arqoub, Vishal Patel, Mark McPhail, Yoh Zen, Nigel Heaton, Maria Serena Longhi, Michael A. Heneghan, Rodrigo Liberal, Diego Vergani, Giorgina Mieli-Vergani, Yun Ma, Bu'Hussain Hayee
Summary: The study found that the gut homing hypothesis is not the primary driver of PSC, and aberrant recruitment of gut-derived T cells to the liver is also seen in other chronic liver diseases. This finding provides a new understanding of the pathogenesis of PSC and CLD.
Article
Pathology
Kevin De Muynck, Bart Vanderborght, Federico F. De Ponti, Eva Gijbels, Sophie Van Welden, Martin Guilliams, Charlotte L. Scott, Alain Beschin, Mathieu Vinken, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Lindsey Devisscher
Summary: Primary sclerosing cholangitis (PSC) is a chronic immune-mediated liver disease characterized by bile duct strictures and fibrosis. The role of hepatic macrophages (MFs) in PSC pathogenesis is unclear. This study found that resident Kupffer cells (ResKCs) were depleted during chronic liver injury, while infiltrating monocyte-derived cells (MoKCs) were enriched during the acute phase of PSC. Depletion of KCs did not affect disease outcomes. These findings provide new insights into the heterogeneity of MFs in PSC and suggest that resident and activated KCs do not play a major role in disease progression.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Gastroenterology & Hepatology
Christina Villard, Ingalill Friis-Liby, Fredrik Rorsman, Karouk Said, Anna Warnqvist, Martin Cornillet, Stergios Kechagias, Nils Nyhlin, Marten Werner, Izabella Janczewska, Therese Hagstrom, Emma Nilsson, Annika Bergquist
Summary: This study prospectively evaluated the effectiveness of yearly MRI/MRCP surveillance in detecting cholangiocarcinoma (CCA) in patients with primary sclerosing cholangitis (PSC) and found it to be ineffective in detecting cancer early enough to support long-term survival. Personalized follow-up strategies and improved diagnostic methods for PSC-related CCA are needed.
JOURNAL OF HEPATOLOGY
(2023)
Article
Gastroenterology & Hepatology
Brian J. Wentworth, Rachita Khot, Stephen H. Caldwell
Summary: Primary sclerosing cholangitis (PSC) poses challenges in diagnosis, management, and progression due to its heterogeneity. Updated practice guidance by major liver disease associations addresses some of these challenges, but fails to thoroughly discuss daily clinical dilemmas. This review aims to delve into controversial topics including the use of ursodeoxycholic acid, normalization of alkaline phosphatase, consideration of PSC variants and mimickers, and the implications of continuous hepatobiliary malignancy screening. Of particular concern is the potential long-term adverse effects of repeated exposure to gadolinium-containing contrast in PSC patients who undergo frequent magnetic resonance imaging scans.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Review
Gastroenterology & Hepatology
Areej Mazhar, Mark W. Russo
Summary: This systematic review analyzed 40 studies on prognostic tests for PSC, comprising a total of 16,094 subjects. Non-invasive tests were associated with transplant-free survival and reduced risk of hepatobiliary cancers, but the consistency of cut-off values for alkaline phosphatase varied among studies. The Mayo Risk Score (MRS) is the most studied prognostic model, although the UK-PSC score and PREsTo showed better test performance. Further studies are needed to compare these models.
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Gastroenterology & Hepatology
Qiaoyan Liu, Bo Li, Yikang Li, Yiran Wei, Bingyuan Huang, Jubo Liang, Zhengrui You, You Li, Qiwei Qian, Rui Wang, Jun Zhang, Ruiling Chen, Zhuwan Lyu, Yong Chen, Mingxia Shi, Xiao Xiao, Qixia Wang, Qi Miao, Jing-Yuan Fang, Merrill Eric Gershwin, Min Lian, Xiong Ma, Ruqi Tang
Summary: Comparative analysis of gut microbiome and metabolome in IgG4-SC and PSC patients revealed distinct host-microbe interactions that may contribute to disease pathogenesis, highlighting the uniqueness of IgG4-SC.
Article
Gastroenterology & Hepatology
John E. Eaton, Christopher L. Welle, Zeinab Bakhshi, Shannon P. Sheedy, Ilkay S. Idilman, Gregory J. Gores, Charles B. Rosen, Julie K. Heimbach, Timucin Taner, Denise M. Harnois, Keith D. Lindor, Nicholas F. LaRusso, Andrea A. Gossard, Konstantinos N. Lazaridis, Sudhakar K. Venkatesh
Summary: This study aimed to evaluate the diagnostic performances and prognostic implications of ultrasound and MRI-based perihilar cholangiocarcinoma (CCA) detection among patients with primary sclerosing cholangitis (PSC). Results showed that MRI was superior to ultrasound for the detection of early-stage CCA in PSC patients, and identifying CCA before symptom onset with MRI was associated with improved outcomes.
Article
Gastroenterology & Hepatology
Yevgeniy Gindin, Chuhan Chung, Zhaoshi Jiang, Jing Zhu Zhou, Jun Xu, Andrew N. Billin, Robert P. Myers, Zachary Goodman, Abdolamir Landi, Michael Houghton, Richard M. Green, Cynthia Levy, Kris V. Kowdley, Christopher L. Bowlus, Andrew J. Muir, Michael Trauner
Summary: RNA sequencing of liver tissue from patients with Primary Sclerosing Cholangitis (PSC) identified biological pathways independent of fibrosis that were associated with clinical events. Removing the effect of fibrosis revealed alterations in the unfolded protein response, which were linked to liver-related complications in PSC. The top pathways identified were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling.
Review
Biochemistry & Molecular Biology
Ji-Won Park, Jung-Hee Kim, Sung-Eun Kim, Jang Han Jung, Myoung-Kuk Jang, Sang-Hoon Park, Myung-Seok Lee, Hyoung-Su Kim, Ki Tae Suk, Dong Joon Kim
Summary: Cholangiopathies are various biliary diseases that affect the biliary epithelium and can lead to cholestasis and liver cirrhosis. Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the most important progressive cholangiopathies in adults, with research focusing on genetic risk, epigenetic changes, dysregulated mucosal immunity, and altered biliary epithelial cell function. Understanding the molecular pathogenesis of these diseases can help clinicians prevent and treat them more effectively.
Article
Gastroenterology & Hepatology
Daniel E. Radford-Smith, Emmanuel A. Selvaraj, Rory Peters, Michael Orrell, Jonathan Bolon, Daniel C. Anthony, Michael Pavlides, Kate Lynch, Alessandra Geremia, Adam Bailey, Emma L. Culver, Fay Probert
Summary: Serum metabolomic profiling has the potential to accurately distinguish between PSC and IgG4-SC, improve the diagnosis of IgG4-RD, and differentiate IgG4-SC from PSC.
LIVER INTERNATIONAL
(2022)
Article
Gastroenterology & Hepatology
Naga Chalasani, Raj Vuppalanchi, Craig Lammert, Samer Gawrieh, Jerome V. Braun, Jiali Zhuang, Arkaitz Ibarra, David A. Ross, Michael Nerenberg, Stephen R. Quake, John J. Sninsky, Shusuke Toden
Summary: This study characterized the circulating transcriptome of primary sclerosing cholangitis (PSC) using cell-free messenger RNA (cf-mRNA) sequencing. Differential expression analysis identified 1407 dysregulated genes in PSC and found common genes involved in liver pathophysiology. A diagnostic classifier based on liver-specific genes was developed to distinguish PSC from healthy controls.
HEPATOLOGY COMMUNICATIONS
(2023)
Review
Medicine, General & Internal
Yu Huang, Shuai Zhang, Jie-Feng Weng, Di Huang, Wei-Li Gu
Summary: This review summarizes the underlying mechanisms of PSC pathogenesis caused by the dysbiosis of microbiota and the newly reported information regarding cholangiocytes in PSC. It also introduces recently reported in vitro and in vivo models for studying the pathogenesis of PSC.
Article
Gastroenterology & Hepatology
Nora Cazzagon, Ester Gonzalez-Sanchez, Haquima El-Mourabit, Dominique Wendum, Dominique Rainteau, Lydie Humbert, Christophe Corpechot, Olivier Chazouilleres, Lionel Arrive, Chantal Housset, Sara Lemoinne
Summary: In patients with primary sclerosing cholangitis (PSC), the gallbladder status affects bile acid homeostasis and disease features. Evidence suggests less bile acid toxicity in patients with enlarged gallbladders and increased disease severity in those who had undergone cholecystectomy. In a mouse model of PSC, cholecystectomy worsened cholangitis and liver fibrosis. Overall, the gallbladder plays a protective role in PSC.
Article
Dentistry, Oral Surgery & Medicine
Maria R. Mang de la Rosa, Ayse Safaltin, Paul -Georg Jost-Brinkmann, Annette Aigner, Petra Julia Koch
Summary: The study aimed to compare the transfer accuracy of five different surgical guides (SGs) for orthodontic mini-implants (OMIs) in the anterior palate. Ten maxillary patient models and corresponding lateral cephalograms were virtually matched to plan the OMI position. Three 3D-printed and two conventional SGs were manufactured, and a total of 96 OMIs were transferred and compared. The results showed that conventional SGs had higher accuracy compared to 3D-printed SGs, but the latter can still provide sufficient accuracy for palatal OMI placement.
ANGLE ORTHODONTIST
(2023)
Review
Pharmacology & Pharmacy
Priyanga Ranasinghe, Melisande L. Addison, James W. Dear, David J. Webb
Summary: Post-transcriptional gene silencing can be achieved through siRNA therapy, which uses synthetic short double-stranded RNA molecules to specifically target and degrade mRNA transcripts. This technology offers advantages such as broad targeting capabilities and long-lasting effects. However, challenges in terms of pharmacokinetics and pharmacodynamics have been addressed through chemical modification and delivery systems. Several siRNA therapies have been approved for clinical use, but further advancements are needed to target organs beyond the liver and reach special sites.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Michael Karimov, Marlene Scherer, Heike Franke, Alexander Ewe, Achim Aigner
Summary: A three-dimensional tissue slice air-liquid interface (ALI) culture model was developed for nanoparticle testing, which showed clearer differences in transfection efficacy and cytotoxicity compared to 2D cell culture. This model allows for the evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment, providing a cost-effective and time-saving alternative.
BIOTECHNOLOGY JOURNAL
(2023)
Article
Chemistry, Medicinal
Lukas Heyder, Phil M. M. Hochban, Corey Taylor, Florent Chevillard, Christof Siefker, Christian Iking, Hannes Borchardt, Achim Aigner, Gerhard Klebe, Andreas Heine, Peter Kolb, Wibke E. Diederich
Summary: In this study, fragment-sized hits binding to Pim-1 kinase were optimized using a combination of computational, synthetic, and crystallographic expertise. The resulting potent ligands target rarely-targeted regions of Pim-1 kinase with affinities in the nanomolar range. The combination of computational and experimental approaches successfully developed a novel molecular scaffold for inhibition of Pim-1 kinase, targeting specific surface regions that have been less frequently investigated.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Entomology
Nagalapura Ramakrishnappa Prasannakumar, Vala Keshava Rao, Nagendraiah Jyothi, Sarikonda Saroja, Ankanahalli Naranayanashetty Lokesha, Govindaraju Ramkumar
Summary: Aphids, thrips, whiteflies, mealy bugs, and mites can cause significant crop losses. This study found that extracts from the seeds of Annona squamosa and Sapindus mukorossi have insecticidal properties against these pests, making them potential botanicals for safe pest management in organic farming.
JOURNAL OF APPLIED ENTOMOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Shinan Geng, Mengqin Guo, Guiting Zhan, Dingwen Shi, Liyun Shi, Lu Gan, Yanbing Zhao, Xiangliang Yang
Summary: A NIR light-triggered dePEGylation/ligand-presenting strategy based on thermal decomposition of azo bonds is developed in this study. It overcomes the PEG dilemma and improves tumor targeting and drug delivery by enhancing cellular uptake and tumor accumulation.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Chemistry, Multidisciplinary
Anisha D'Souza, Saeideh Nozohouri, Benjamin S. Bleier, Mansoor M. Amiji
Summary: Nucleic acid-based therapeutic molecules have great potential for treating diseases in the CNS, but delivering them to the brain's target cells and sub-cellular compartments is a challenge. This review discusses the challenges and recent advances in cellular and sub-cellular delivery using various mechanisms and routes of administration.
PHARMACEUTICAL RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Thomas Foster, Michael Lewkowicz, Christina Quintas, Corina Mihaela Ionescu, Melissa Jones, Susbin Raj Wagle, Bozica Kovacevic, Elaine Y. M. Wong, Armin Mooranian, Hani Al-Salami
Summary: Hearing loss is a significant issue worldwide, and gene delivery and nanoencapsulation technology may provide effective means for treatment.
Article
Oncology
Luis Alberto Bravo-Vazquez, Natalia Frias-Reid, Ana Gabriela Ramos-Delgado, Sofia Madeline Osorio-Perez, Hania Ruth Zlotnik-Chavez, Surajit Pathak, Antara Banerjee, Anindya Bandyopadhyay, Asim K. Duttaroy, Sujay Paul
Summary: MicroRNAs and long non-coding RNAs play a crucial role in the development and progression of pancreatic cancer. Their dysregulation is associated with chemoresistance and tumor growth, and they have the potential to be used as biomarkers for accurate diagnosis and as therapeutic targets.
TRANSLATIONAL ONCOLOGY
(2023)
Review
Cell Biology
Abdul Fatah A. Samad, Mohd Farizal Kamaroddin
Summary: MicroRNA has the potential to regulate genetic pathways and has been explored as a therapeutic tool. However, there are challenges such as off-target effects, immunogenicity, and delivery platforms. Recently, innovative approaches have been developed to address these issues. Nevertheless, dosage remains an uncertainty for miRNA administration.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Review
Materials Science, Biomaterials
Longyi Zhu, Jun Luo, Kewei Ren
Summary: Nucleic acid nanotechnology, with its high editability, easy synthesis, and modification, has emerged as a powerful tool in biosensing and nanomedicine. This review summarizes recent progress in the design and functional mechanisms of nucleic acid-based artificial nano-vectors, particularly for the delivery of exogenous siRNA and antisense oligonucleotides. Various types of DNA and RNA-based nanocarriers are introduced, along with enhanced targeting strategies to improve delivery efficacy. The potential challenges and outlook for nucleic acid-based artificial nanocarriers are also highlighted.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Clinical Neurology
Frauke Stascheit, Annette Aigner, Philipp Mergenthaler, Benjamin Hotter, Sarah Hoffmann, Sophie Lehnerer, Christian Meisel, Andreas Meisel
Summary: This study aimed to evaluate the association between Nfl and neuromuscular destruction and disease severity in MG patients. Serum samples from MG patients and controls were analyzed and compared. The results showed that sNfl levels were higher in MG patients compared to controls, but were not consistently associated with disease severity. Thus, sNfl is not a suitable biomarker for monitoring individual disease progression in MG patients.
FRONTIERS IN NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sewon Lim, Jinhyuk Park, Seung-Eun Chong, Sungwhan Kim, Yoonhwa Choi, So Hee Nam, Yan Lee
Summary: In this study, we substituted hydrophobic amino acids in the SAP(E) sequence with cysteine to enhance the cell penetrating activity and cargo conjugation. The cysteine substitution significantly improved the cell penetrating activity and showed lower co-localization with acidic endosomes or lysosomes compared to the positively-charged TAT. The cysteine handle of SAP(E)-7C allowed the conjugation and release of cargo drugs, demonstrating its potential as a useful module for CPP-based drug delivery.
Article
Public, Environmental & Occupational Health
Madlen Schranz, T. Sonia Boender, Timo Greiner, Theresa Kocher, Birte Wagner, Felix Greiner, Jonas Bienzeisler, Michaela Diercke, Linus Grabenhenrich, Annette Aigner, Alexander Ullrich
Summary: During the COVID-19 pandemic in Germany, there was a significant decrease in the number of patients seeking emergency care, especially during the first and second waves. The decrease was more prominent among younger age groups and less severe cases. This decrease in emergency department consultations is important to understand in order to ensure that patients receive the necessary care during future pandemics or public health crises.
Article
Clinical Neurology
Frederik Bartels, Birgit Baumgartner, Annette Aigner, Graham Cooper, Astrid Blaschek, Eva Maria Wendel, Annikki Bertolini, Michael Karenfort, Matthias Baumann, Robert Cleaveland, Andreas Wegener-Panzer, Steffen Leiz, Michela Salandin, Peter Krieg, Tobias Reindl, Markus Reindl, Carsten Finke, Kevin Rostasy
Summary: This observational cohort study found that patients with acute disseminated encephalomyelitis (ADEM) showed reduced brain volume at onset and over time, with a more pronounced reduction in brain volume for MOG-negative patients compared to MOG-positive patients, and relapsing MOG-positive patients showed additional brain volume loss.
NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION
(2023)