tbuckley/cabot-search huggingface dataset:
Current Challenges and Future Directions in the Assessment of Glucocorticoid Status
Authors: Sophie A Clarke, Pei Chia Eng, Alexander N Comninos, Katharine Lazarus, Sirazum Choudhury, Christie Tsang, Karim Meeran, Tricia M Tan, Waljit S Dhillo, Ali Abbara
Journal: Endocrine Reviews (2024)

Abstract Glucocorticoid (GC) hormones are secreted in a circadian and ultradian rhythm and play a critical role in maintaining physiological homeostasis, with both excess and insufficient GC associated with adverse effects on health. Current assessment of GC status is primarily clinical, often in conjunction with serum cortisol values, which may be stimulated or suppressed depending on the GC disturbance being assessed. In the setting of extreme perturbations in cortisol levels ie, markedly low or high levels, symptoms and signs of GC dysfunction may be overt. However, when disturbances in cortisol GC status values are less extreme, such as when assessing optimization of a GC replacement regimen, signs and symptoms can be more subtle or nonspecific. Current tools for assessing GC status are best suited to identifying profound disturbances but may lack sensitivity for confirming optimal GC status. Moreover, single cortisol values do not necessarily reflect an individual's GC status, as they are subject to inter- and intraindividual variation and do not take into account the pulsatile nature of cortisol secretion, variation in binding proteins, or local tissue concentrations as dictated by 11beta-hydroxysteroid dehydrogenase activity, as well as GC receptor sensitivity. In the present review, we evaluate possible alternative methods for the assessment of GC status that do not solely rely on the measurement of circulating cortisol levels. We discuss the potential of changes in metabolomic profiles, micro RNA, gene expression, and epigenetic and other novel biomarkers such as growth differentiating factor 15 and osteocalcin, which could in the future aid in the objective classification of GC status.
IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial
Authors: Glenn M. Chertow, Anna Marie Chang, G. Michael Felker, Mark Heise, Elena Velkoska, Bengt Fellström, David M. Charytan, Regina Clementi, C. Michael Gibson, Shaun G. Goodman, Meg Jardine, Adeera Levin, Yuliya Lokhnygina, Jenny Mears, Roxana Mehran, Peter Stenvinkel, Angela Yee-Moon Wang, David C. Wheeler, Carmine Zoccali, Paul M. Ridker, Kenneth W. Mahaffey, Pierluigi Tricoci, Myles Wolf
Journal: Nature Medicine (2024)

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l
Functional Integration of Synthetic Cells into 3D Microfluidic Devices for Artificial Organ‐On‐Chip Technologies
Authors: Niki Hakami, Anna Burgstaller, Ning Gao, Angela Rutz, Stephen Mann, Oskar Staufer
Journal: Advanced Healthcare Materials (2024)

Microfluidics plays a pivotal role in organ-on-chip technologies and in the study of synthetic cells, especially in the development and analysis of artificial cell models. However, approaches that use synthetic cells as integral functional components for microfluidic systems to shape the microenvironment of natural living cells cultured on-chip are not explored. Here, colloidosome-based synthetic cells are integrated into 3D microfluidic devices, pioneering the concept of synthetic cell-based microenvironments for organs-on-chip. Methods are devised to create dense and stable networks of silica colloidosomes, enveloped by supported lipid bilayers, within microfluidic channels. These networks promote receptor-ligand interactions with on-chip cultured cells. Furthermore, a technique is introduced for the controlled release of growth factors from the synthetic cells into the channels, using a calcium alginate-based hydrogel formation within the colloidosomes. To demonstrate the potential of the technology, a modular plug-and-play lymph-node-on-a-chip prototype that guides the expansion of primary human T cells by stimulating receptor ligands on the T cells and modulating their cytokine environment is presented. This integration of synthetic cells into microfluidic systems offers a new direction for organ-on-chip technologies and suggests further avenues for exploration in potential therapeutic applications.
Biomedical application of materials for external auditory canal: History, challenges, and clinical prospects
Authors: Yang Xu, Zhongwu Bei, Mei Li, Lin Ye, Bingyang Chu, Yu Zhao, Zhiyong Qian
Journal: Bioactive Materials (2024)

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.
Emerging paradigms and recent progress in targeting ErbB in cancers
Authors: Nicolas Stoup, Maxime Liberelle, Nicolas Lebègue, Isabelle Van Seuningen
Journal: Trends in Pharmacological Sciences (2024)

The epidermal growth factor receptor (EGFR) family is a class of transmembrane proteins, highly regarded as anticancer targets due to their pivotal role in various malignancies. Standard cancer treatments targeting the ErbB receptors include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs). Despite their substantial survival benefits, the achievement of curative outcomes is hindered by acquired resistance. Recent advancements in anti-ErbB approaches, such as inhibitory peptides, nanobodies, targeted-protein degradation strategies, and bispecific antibodies (BsAbs), aim to overcome such resistance. More recently, emerging insights into the cell surface interactome of the ErbB family open new avenues for modulating ErbB signaling by targeting specific domains of ErbB partners. Here, we review recent progress in ErbB targeting and elucidate emerging paradigms that underscore the significance of EGF domain-containing proteins (EDCPs) as new ErbB-targeting pathways.
Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial
Authors: Helen M. Colhoun, Ildiko Lingvay, Paul M. Brown, John Deanfield, Kirstine Brown-Frandsen, Steven E. Kahn, Jorge Plutzky, Koichi Node, Alexander Parkhomenko, Lars Rydén, John P. H. Wilding, Johannes F. E. Mann, Katherine R. Tuttle, Thomas Idorn, Naveen Rathor, A. Michael Lincoff
Journal: Nature Medicine (2024)

Abstract The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide ( n = 8,803) versus placebo ( n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial. The incidence of the pre-specified main composite kidney endpoint (death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent estimated glomerular filtration rate (eGFR) &lt; 15 ml min −1 1.73 m − 2 , persistent ≥50% reduction in eGFR or onset of persistent macroalbuminuria) was lower with semaglutide (1.8%) versus placebo (2.2%): hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.63, 0.96; P = 0.02. The treatment benefit at 104 weeks for eGFR was 0.75 ml min −1 1.73 m − 2 (95% CI 0.43, 1.06; P &lt; 0.001) overall and 2.19 ml min −1 1.73 m − 2 (95% CI 1.00, 3.38; P &lt; 0.001) in patients with baseline eGFR &lt;60 ml min −1 1.73 m − 2 . These results suggest a benefit of semaglutide on kidney outcomes in individuals with overweight/obesity, without diabetes. ClinicalTrials.gov identifier: NCT03574597 .
Smartphone application versus written material for smoking reduction and cessation in individuals undergoing low-dose computed tomography (LDCT) screening for lung cancer: a phase II open-label randomised controlled trial
Authors: Sanna Iivanainen, Antti Kurtti, Viktor Wichmann, Heidi Andersen, Antti Jekunen, Riitta Kaarteenaho, Tuula Vasankari, Jussi P Koivunen
Journal: The Lancet Regional Health - Europe (2024)
Re: Michael Baboudjian, Romain Diamand, Alessandro Uleri, et al. Does Overgrading on Targeted Biopsy of Magnetic Resonance Imaging–visible Lesions in Prostate Cancer Lead to Overtreatment? Eur Urol. In press. https://doi.org/10.1016/j.eururo.2024.02.003
Authors: Andrew J. Vickers
Journal: European Urology (2024)
Developing MiR‐133a Zipper Nanoparticles for Targeted Enhancement of Thermogenic Adipocyte Generation
Authors: Sang Ah Yi, Thanapat Pongkulapa, Sarah Nevins, Li Ling Goldston, Meizi Chen, Ki‐Bum Lee
Journal: Advanced Healthcare Materials (2024)

Existing delivery methods for RNAi therapeutics encounter challenges, including stability, specificity, and off-target effects, which restrict their clinical effectiveness. In this study, a novel miR-133a zipper nanoparticle (NP) system that integrates miRNA zipper technology with rolling circle transcription (RCT) to achieve targeted delivery and specific regulation of miR-133a in adipocytes, is presented. This innovative approach can greatly enhance the delivery and release of miR-133a zippers, increasing the expression of thermogenic genes and mitochondrial biogenesis. he miR-133a zipper NP is utilized for the delivery of miRNA zipper-blocking miR-133a, an endogenous inhibitor of Prdm16 expression, to enhance the thermogenic activity of adipocytes by modulating their transcriptional program. Inhibition of miR-133a through the miR-133a zipper NP leads to more significant upregulation of thermogenic gene expression (Prdm16 and Ucp1) than with the free miR-133a zipper strand. Furthermore, miR-133a zipper NPs increase the number of mitochondria and induce heat production, reducing the size of 3D adipose spheroids. In short, this study emphasizes the role of RNA NPs in improving RNAi stability and specificity and paves the way for broader applications in gene therapy. Moreover, this research represents a significant advancement in RNAi-based treatments, pointing toward a promising direction for future therapeutic strategies.
A Randomized Phase 2 Trial of Felzartamab in Antibody-Mediated Rejection
Authors: Katharina A Mayer, Eva Schrezenmeier, Matthias Diebold, Philip F Halloran, Martina Schatzl, Sabine Schranz, Susanne Haindl, Silke Kasbohm, Alexander Kainz, Farsad Eskandary, Konstantin Doberer, Uptal D Patel, Jaideep S Dudani, Heinz Regele, Nicolas Kozakowski, Johannes Kläger, Rainer Boxhammer, Kerstin Amann, Elisabeth Puchhammer-Stöckl, Hannes Vietzen, Julia Beck, Ekkehard Schütz, Aylin Akifova, Christa Firbas, Houston N Gilbert, Bilgin Osmanodja, Fabian Halleck, Bernd Jilma, Klemens Budde, Georg A Böhmig
Journal: New England Journal of Medicine (2024)

Antibody-mediated rejection is a leading cause of kidney-transplant failure. The targeting of CD38 to inhibit graft injury caused by alloantibodies and natural killer (NK) cells may be a therapeutic option.
Topical Nanoliposomal Collagen Delivery for Targeted Fibril Formation by Electrical Stimulation
Authors: Albertus Ivan Brilian, Sang Ho Lee, Agustina Setiawati, Chang Ho Kim, Soo Ryeon Ryu, Hyo‐Jin Chong, Yejin Jo, Hayan Jeong, Bong‐Gun Ju, Oh‐Sun Kwon, Giyoong Tae, Kwanwoo Shin
Journal: Advanced Healthcare Materials (2024)

Abstract Collagen is a complex, large protein molecule that presents a challenge in delivering it to the skin due to its size and intricate structure. However, conventional collagen delivery methods are either invasive or may affect the protein's structural integrity. This study introduces a novel approach involving the encapsulation of collagen monomers within zwitterionic nanoliposomes, termed Lip‐Cols, and the controlled formation of collagen fibrils through electric fields (EF) stimulation. The results reveal the self‐assembly process of Lip‐Cols through electroporation and a pH gradient change uniquely triggered by EF, leading to the alignment and aggregation of Lip‐Cols on the electrode interface. Notably, Lip‐Cols exhibit the capability to direct the orientation of collagen fibrils within human dermal fibroblasts. In conjunction with EF, Lip‐Cols can deliver collagen into the dermal layer and increase the collagen amount in the skin. The findings provide novel insights into the directed formation of collagen fibrils via electrical stimulation and the potential of Lip‐Cols as a non‐invasive drug delivery system for anti‐aging applications.
Hydrogel Coatings of Implants for Pathological Bone Repair
Authors: Mengqing Li, Youzhun Fan, Maofei Ran, Haoyan Chen, Jien Han, Jinxia Zhai, Zhengao Wang, Chengyun Ning, Zhifeng Shi, Peng Yu
Journal: Advanced Healthcare Materials (2024)

Hydrogels are well-suited for biomedical applications due to their numerous advantages, such as excellent bioactivity, versatile physical and chemical properties, and effective drug delivery capabilities. Recently, hydrogel coatings have developed to functionalize bone implants which are biologically inert and cannot withstand the complex bone tissue repair microenvironment. These coatings have shown promise in addressing unique and pressing medical needs. This review begins with the major functionalized performance and interfacial bonding strategy of hydrogel coatings, with a focus on the novel external field response properties of the hydrogel. Recent advances in the fabrication strategies of hydrogel coatings and their use in the treatment of pathologic bone regeneration are highlighted. Finally, challenges and emerging trends in the evolution and application of physiological environment-responsive and external electric field-responsive hydrogel coatings for bone implants are discussed.
Autoantibodies Targeting Nephrin in Podocytopathies
Authors: Felicitas E Hengel, Silke Dehde, Moritz Lassé, Gunther Zahner, Larissa Seifert, Annabel Schnarre, Oliver Kretz, Fatih Demir, Hans O Pinnschmidt, Florian Grahammer, Renke Lucas, Lea Maxima Mehner, Tom Zimmermann, Anja M Billing, Jun Oh, Adele Mitrotti, Paola Pontrelli, Hanna Debiec, Claire Dossier, Manuela Colucci, Francesco Emma, William E Smoyer, Astrid Weins, Franz Schaefer, Nada Alachkar, Anke Diemert, Julien Hogan, Elion Hoxha, Thorsten Wiech, Markus M Rinschen, Pierre Ronco, Marina Vivarelli, Loreto Gesualdo, Nicola M Tomas, Tobias B Huber
Journal: New England Journal of Medicine (2024)

Minimal change disease and primary focal segmental glomerulosclerosis in adults, along with idiopathic nephrotic syndrome in children, are immune-mediated podocytopathies that lead to nephrotic syndrome. Autoantibodies targeting nephrin have been found in patients with minimal change disease, but their clinical and pathophysiological roles are unclear.
β1 integrins regulate cellular behaviour and cardiomyocyte organization during ventricular wall formation
Authors: Lianjie Miao, Yangyang Lu, Anika Nusrat, Luqi Zhao, Micah Castillo, Yongqi Xiao, Hongyang Guo, Yu Liu, Preethi Gunaratne, Robert J Schwartz, Alan R Burns, Ashok Kumar, C Michael DiPersio, Mingfu Wu
Journal: Cardiovascular Research (2024)

Abstract Aims The mechanisms regulating the cellular behaviour and cardiomyocyte organization during ventricular wall morphogenesis are poorly understood. Cardiomyocytes are surrounded by extracellular matrix (ECM) and interact with ECM via integrins. This study aims to determine whether and how β1 integrins regulate cardiomyocyte behaviour and organization during ventricular wall morphogenesis in the mouse. Methods and results We applied mRNA deep sequencing and immunostaining to determine the expression repertoires of α/β integrins and their ligands in the embryonic heart. Integrin β1 subunit (β1) and some of its ECM ligands are asymmetrically distributed and enriched in the luminal side of cardiomyocytes, and fibronectin surrounds cardiomyocytes, creating a network for them. Itgb1, which encodes the β1, was deleted via Nkx2.5Cre/+ to generate myocardial-specific Itgb1 knockout (B1KO) mice. B1KO hearts display an absence of a trabecular zone but a thicker compact zone. The levels of hyaluronic acid and versican, essential for trabecular initiation, were not significantly different between control and B1KO. Instead, fibronectin, a ligand of β1, was absent in the myocardium of B1KO hearts. Furthermore, B1KO cardiomyocytes display a random cellular orientation and fail to undergo perpendicular cell division, be organized properly, and establish the proper tissue architecture to form trabeculae. Mosaic clonal lineage tracing showed that Itgb1 regulates cardiomyocyte transmural migration and proliferation autonomously. Conclusion β1 is asymmetrically localized in the cardiomyocytes, and some of its ECM ligands are enriched along the luminal side of the myocardium, and fibronectin surrounds cardiomyocytes. β1 integrins are required for cardiomyocytes to attach to the ECM network. This engagement provides structural support for cardiomyocytes to maintain shape, undergo perpendicular division, and establish cellular organization. Deletion of Itgb1 leads to loss of β1 and fibronectin and prevents cardiomyocytes from engaging the ECM network, resulting in failure to establish tissue architecture to form trabeculae.
Nanozyme‐Incorporated Microneedles for the Treatment of Chronic Wounds
Authors: Zhiyuan Hu, Jie Shan, Yuyu Cui, Liang Cheng, Xu‐Lin Chen, Xianwen Wang
Journal: Advanced Healthcare Materials (2024)

Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti-inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research.
A Dual‐Function CD47‐Targeting Nano‐Drug Delivery System Used to Regulate Immune and Anti‐Inflammatory Activities in the Treatment of Atherosclerosis
Authors: Huanhuan Wang, Runze Zhao, Lei Peng, Ao Yu, Yongjian Wang
Journal: Advanced Healthcare Materials (2024)

Atherosclerosis is a primary contributor to cardiovascular disease. Current studies have highlighted the association between the immune system, particularly immune cells, and atherosclerosis, although treatment options and clinical trials remain scarce. Immunotherapy for cardiovascular disease is still in its infancy. Bruton's tyrosine kinase (BTK), widely expressed in various immune cells, represents a promising therapeutic target for atherosclerosis by modulating the anti-inflammatory function of immune cells. This study introduces a polydopamine-based nanocarrier system to deliver the BTK inhibitor, ibrutinib, to atherosclerotic plaques with an active targeting property via an anti-CD47 antibody. Leveraging polydopamine's pH-sensitive reversible disassembly, the system offers responsive, controlled release within the pathologic microenvironment. This allows precise and efficient ibrutinib delivery, concurrently inhibiting the activation of the NF-κB pathway in B cells and the NLRP3 inflammasome in macrophages within the plaques. This treatment also modulates both the immune cell microenvironment and inflammatory conditions in atherosclerotic lesions, thereby conveying promising therapeutic effects for atherosclerosis in vivo. This strategy also provides a novel option for atherosclerosis treatment.
AAV-mediated gene therapy for sialidosis
Authors: Diantha van de Vlekkert, Huimin Hu, Jason A. Weesner, Leigh E. Fremuth, Scott A. Brown, Meifen Lu, Elida Gomero, Yvan Campos, Heather Sheppard, Alessandra d’Azzo
Journal: Molecular Therapy (2024)

Sialidosis (mucolipidosis I) is a glycoprotein storage disease, clinically characterized by a spectrum of systemic and neurological phenotypes. The primary cause of the disease is deficiency of the lysosomal sialidase NEU1, resulting in accumulation of sialylated glycoproteins/oligosaccharides in tissues and body fluids. Neu1
Targeted Macrophage Re‐Programming: Synergistic Therapy With Methotrexate and RELA siRNA Folate‐Liposome in RAW264.7 Cells and Arthritic Rats
Authors: Simran Nasra, Dhiraj Bhatia, Ashutosh Kumar
Journal: Advanced Healthcare Materials (2024)

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and destruction. Current treatments, such as Methotrexate (MTX), though effective, often face limitations such as high plasma C