tbuckley/cabot-search huggingface dataset:
Current developments of gene therapy in human diseases
Authors: Fanfei Liu, Ruiting Li, Zilin Zhu, Yang Yang, Fang Lu
Journal: MedComm (2024)

Gene therapy has witnessed substantial advancements in recent years, becoming a constructive tactic for treating various human diseases. This review presents a comprehensive overview of these developments, with a focus on their diverse applications in different disease contexts. It explores the evolution of gene delivery systems, encompassing viral (like adeno-associated virus; AAV) and nonviral approaches, and evaluates their inherent strengths and limitations. Moreover, the review delves into the progress made in targeting specific tissues and cell types, spanning the eye, liver, muscles, and central nervous system, among others, using these gene technologies. This targeted approach is crucial in addressing a broad spectrum of genetic disorders, such as inherited lysosomal storage diseases, neurodegenerative disorders, and cardiovascular diseases. Recent clinical trials and successful outcomes in gene therapy, particularly those involving AAV and the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins, are highlighted, illuminating the transformative potentials of this approach in disease treatment. The review summarizes the current status of gene therapy, its prospects, and its capacity to significantly ameliorate patient outcomes and quality of life. By offering comprehensive analysis, this review provides invaluable insights for researchers, clinicians, and stakeholders, enriching the ongoing discourse on the trajectory of disease treatment.
Role of hydrogen sulfide in health and disease
Authors: Yu‐Qing Jin, Hang Yuan, Ya‐Fang Liu, Yi‐Wen Zhu, Yan Wang, Xiao‐Yi Liang, Wei Gao, Zhi‐Guang Ren, Xin‐Ying Ji, Dong‐Dong Wu
Journal: MedComm (2024)

In the past, hydrogen sulfide (H
Recryopreservation impairs blastocyst implantation potential via activated endoplasmic reticulum stress pathway and induced apoptosis
Authors: Meng Wang, Juepu Zhou, Rui Long, Yuehan Li, Limin Gao, Ruolin Mao, Xiangfei Wang, Na Guo, Lei Jin, Lixia Zhu
Journal: MedComm (2024)

Recryopreservation (recryo) is occasionally applied in clinical, while the underlying mechanism of impaired clinical outcomes after recryo remains unclear. In this study, frozen embryo transfer (FET) cycles of single blastocyst transfer in an academic reproductive medicine center were enrolled. According to the number of times blastocysts experienced cryopreservation, they were divided into the cryopreservation (Cryo) group and the Recryo group. Donated human blastocysts were collected and detected for mechanism exploration. It was found that recryo procedure resulted in impaired blastocyst developmental potential, including decreased implantation rate, reduced biochemical pregnancy rate, declined clinical pregnancy rate, higher early miscarriage rate, and lower live birth rate. Moreover, recryo led to impaired trophectoderm (TE) function, exhibiting lower human chorionic gonadotropin levels 12 days after FET. In addition, single-cell RNA sequencing showed that the expression of genes involved in cell adhesion and embryo development were altered. More specifically, activated endoplasmic reticulum (ER) pathway and induced apoptosis were further verified by immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay involving in the recryo procedure. In conclusion, recryo could interfere with the process of blastocyst implantation by impairing TE function, affecting blastocyst adhesion, activating ER stress pathway and inducing apoptosis. It provides caution to embryologists about the potential risk of recryopreservation.
MPGAN: Multi Pareto Generative Adversarial Network for the denoising and quantitative analysis of low-dose PET images of human brain
Authors: Yu Fu, Shunjie Dong, Yanyan Huang, Meng Niu, Chao Ni, Lequan Yu, Kuangyu Shi, Zhijun Yao, Cheng Zhuo
Journal: Medical Image Analysis (2024)
Fusion Event Mediated by IS903B between Chromosome and Plasmid in Two MCR-9- and KPC-2-Co-Producing Klebsiella pneumoniae Isolates
Authors: Ruishan Liu, Yingying Chen, Hao Xu, Huanran Zhang, Yi Liu, Xiaojing Liu, Haowei Ye, Mantao Chen, Beiwen Zheng
Journal: Drug Resistance Updates (2024)

Herein, we first isolated two MCR-9- and KPC-2-co-producing K. pneumoniae isolates. Notably, we observed a fusion event between the chromosome and plasmid, mediated by IS903B, in these two strains. This cointegration of chromosomes and plasmids introduces a new mode of transmission for antimicrobial resistance genes.
Targeting tumor microenvironment with photodynamic nanomedicine
Authors: Suraj Kumar Modi, Pragyan Mohapatra, Priya Bhatt, Aishleen Singh, Avanish Singh Parmar, Aniruddha Roy, Vibhuti Joshi, Manu Smriti Singh
Journal: Medicinal Research Reviews (2024)

Photodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third-generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface-modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT-induced hypoxia, disrupting the blood vascular networks in tumor tissues-vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. We propose that a synergistic outlook will help to address challenges such as deep-seated tumors, metastasis, or relapse and would lead to robust PDT response in patients.
Natural and synthetic 5‐(3′‐indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules
Authors: Jing‐Rui Liu, En‐Yu Jiang, Otgonpurev Sukhbaatar, Wei‐Hua Zhang, Ming‐Zhi Zhang, Guang‐Fu Yang, Yu‐Cheng Gu
Journal: Medicinal Research Reviews (2024)

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.
Re: Laura Elst, Gino Philips, Kaat Vandermaesen, et al. Single-cell Atlas of Penile Cancer Reveals TP53 Mutations as a Driver of an Aggressive Phenotype, Irrespective of Human Papillomavirus Status, and Provides Clues for Treatment Personalization. Eur Urol. 2024;86:114–27
Authors: Jan Hrudka, Petr Waldauf, Radoslav Matěj
Journal: European Urology (2024)
Re: Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-specific Membrane Antigen–Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-center, Prospective, Single-arm Trial
Authors: Alice C M Thomson, David Chen, Elio Mazzone, Yao Zhu, Marlon Perera, Declan G Murphy
Journal: European Urology (2024)
Comparative genomics supports ecologically induced selection as a putative driver of banded penguin diversification
Authors: Fabiola León, Eduardo Pizarro, Daly Noll, Luis R Pertierra, Patricia Parker, Marcela P A Espinaze, Guillermo Luna-Jorquera, Alejandro Simeone, Esteban Frere, Gisele Dantas, Robin Cristofari, Omar E Cornejo, Rauri C K Bowie, Juliana A Vianna
Journal: Molecular Biology and Evolution (2024)

Abstract The relative importance of genetic drift and local adaptation in facilitating speciation remains unclear. This is particularly true for seabirds, who can disperse over large geographic distances, providing opportunities for intermittent gene flow among distant colonies that span the temperature and salinity gradients of the oceans. Here, we delve into the genomic basis of adaptation and speciation of banded penguins, Galápagos (Spheniscus mendiculus), Humboldt (S. humboldti), Magellanic (S. magellanicus) and African penguins (S. demersus), by analyzing 114 genomes from the main 16 breeding colonies. We aim to identify the molecular mechanism and genomic adaptive traits that have facilitated their diversifications. Through positive selection and gene family expansion analyses, we identified candidate genes that may be related to reproductive isolation processes mediated by ecological thermal niche divergence. We recover signals of positive selection on key loci associated with spermatogenesis, especially during the recent peripatric divergence of the Galápagos penguin from the Humboldt penguin. High temperatures in tropical habitats may have favored selection on loci associated with spermatogenesis to maintain sperm viability, leading to reproductive isolation among young species. Our results suggest that genome-wide selection on loci associated with molecular pathways that underpin thermoregulation, osmoregulation, hypoxia, and social behavior appear to have been crucial in local adaptation of banded penguins. Overall, these results contribute to our understanding of how the complexity of biotic, but especially abiotic, factors, along with the high dispersal capabilities of these marine species, may promote both neutral and adaptive lineage divergence even in the presence of gene flow.
A validated estimate of visceral adipose tissue volume in relation to cancer risk
Authors: Yujia Lu, Yu Chen Zhao, Kuangyu Liu, Alaina Bever, Ziyi Zhou, Kai Wang, Zhe Fang, Georgios Polychronidis, Yuchen Liu, Liyuan Tao, Barbra A Dickerman, Edward L Giovannucci, Mingyang Song
Journal: JNCI Journal of the National Cancer Institute (2024)

Despite the recognized role of visceral adipose tissue in carcinogenesis, its independent association with cancer risk beyond traditional obesity measures remains unknown because of limited availability of imaging data.
The Immunological and Pharmacokinetic Evaluation of Lipid-PLGA Hybrid Nanoparticle-Based Oxycodone Vaccines
Authors: Debra L Walter, Yuanzhi Bian, He Hu, Fatima A Hamid, Kobra Rostamizadeh, Jennifer R Vigliaturo, Riley DeHority, Marion Ehrich, Scott Runyon, Marco Pravetoni, Chenming Zhang
Journal: Biomaterials (2024)
The atopic dermatitis patient journey: insights from a qualitative study
Authors: Fanny C Kpenou, Carle Paul, Julien Seneschal, Nicolas Andreu, Sébastien Barbarot, Marie Tauber, Pierre-André Natella, Jason Shourick, Khaled Ezzedine
Journal: British Journal of Dermatology (2024)

This qualitative study aimed to explore adults’ experiences with atopic dermatitis (AD) and gain insight into their expectations regarding healthcare, in order to improve their wellbeing. Data from 21 interviews were analysed. Participants reported a significant burden due to the psychosocial impact of AD, encompassing emotional distress and daily life impediments. Factors influencing treatment satisfaction among patients with AD extend beyond clinical efficacy. Dermatological care should consider patients’ preferences within treatment plans through a holistic approach to ensure satisfaction with their therapeutic regimen. We therefore encourage efforts to promote collaborative discussions between patients and physicians to improve treatment satisfaction.
Time-restricted feeding ameliorates non-alcoholic fatty liver disease through modulating hepatic nicotinamide metabolism via gut microbiota remodeling
Authors: Ruijia Feng, Wenchao Yang, Weiqi Feng, Xiuyi Huang, Meifeng Cen, Guiyan Peng, Wenrui Wu, Zhecun Wang, Yexiang Jing, Ting Long, Yunchong Liu, Zilun Li, Guangqi Chang, Kan Huang
Journal: Gut Microbes (2024)

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, lacking specific therapeutic strategies. Time-restricted feeding (TRF) regimen demonstrated beneficial effects in NAFLD; however, the underlying mechanisms remain unclear. In this study, we established a NAFLD mouse model through a high-fat diet (HFD) and implemented the 16:8 TRF regimen for a duration of 6 weeks. We demonstrated that TRF remarkably alleviated hepatic steatosis in HFD mice. Of note, aldehyde oxidase 1 (AOX1), a key enzyme in hepatic nicotinamide (NAM) catabolism, exhibited apparent upregulation in response to HFD, leading to abnormal accumulation of N-Methyl-6-pyridone-3-carboxamide (N-Me-6-PY, also known as 2PY) and N-Methyl-4-pyridone-5-carboxamide (N-Me-4-PY, also known as 4PY), whereas it was almost restored by TRF. Both N-Me-6-PY and N-Me-4-PY promoted de novo lipogenesis and fatty acid uptake capacities in hepatocyte, and aggravated hepatic steatosis in mice either fed chow diet or HFD. In contrast, pharmacological inhibition of AOX1 was sufficient to ameliorate the hepatic steatosis and lipid metabolic dysregulation induced by HFD. Moreover, transplantation of fecal microbiota efficiently mimicked the modulatory effect of TRF on NAM metabolism, thus mitigating hepatic steatosis and lipid metabolic disturbance, suggesting a gut microbiota-dependent manner. In conclusion, our study reveals the intricate relationship between host NAM metabolic modification and gut microbiota remodeling during the amelioration of NAFLD by TRF, providing promising insights into the prevention and treatment of NAFLD.
Targeting endothelial KCa channels in vivo restores arterial and endothelial function in type 2 diabetic rats
Authors: Ramesh C Mishra, Darrell D Belke, Latika Singh, Heike Wulff, Andrew P Braun
Journal: Metabolism (2024)

This study tested the hypothesis that administration of the KCa channel activator SKA-31 restores endothelium-dependent vasodilation in vivo in Type 2 Diabetic (T2D) rats.
A Non‐Metallic Nanozyme Ameliorates Pulmonary Hypertension Through Inhibiting ROS/TGF‐β1 Signaling
Authors: Ruxia Liu, Ting Zhou, Xinsheng Li, Quan Zou, Jiaojiao Yu, Jingjing Ye, Wenhui Wang, Yan Zhou, Shao‐Kai Sun
Journal: Advanced Healthcare Materials (2024)

Pulmonary hypertension (PH) is a life-threatening cardiovascular disease with a lack of effective treatment options. Nanozymes, though promising for PH therapy, pose safety risks due to their metallic nature. Here, a non-metallic nanozyme is reported for the treatment of monocrotaline (MCT)-induced PH with a therapeutic mechanism involving the ROS/TGF-β1 signaling. The synthesized melanin-polyvinylpyrrolidone-polyethylene glycol (MPP) nanoparticles showcase ultra-small size, excellent water solubility, high biocompatibility, and remarkable antioxidant capacity. The MPP nanoparticles are capable of effectively eliminating ROS in isolated pulmonary artery smooth muscle cells (PASMCs) from PH rats, and significantly reduce PASMC proliferation and migration. In vivo results from a PH model demonstrate that MPP nanoparticles significantly increase pulmonary artery acceleration time, decrease wall thickening and PCNA expression in lung tissues, as evidenced by echocardiograpy, histology and immunoblot analysis. Additionally, MPP nanoparticles treatment improve running capacity, decrease Fulton index, and attenuate right ventricular fibrosis in MCT-PH rats by using treadmill test, picrosirius red, and trichrome Masson staining. Further transcriptomic and biochemical analyses reveal that inhibiting ROS-driven activation of TGF-β1 in the PA is the mechanism by which MPP nanoparticles exert their therapeutic effect. This study provides a novel approach for treating PH with non-metallic nanozymes based on a well-understood mechanism.
Phototactic/Photosynthetic/Magnetic‐Powered <i>Chlamydomonas Reinhardtii</i>‐Metal‐Organic Frameworks Micro/Nanomotors for Intelligent Thrombolytic Management and Ischemia Alleviation
Authors: Chia‐Che Chiang, Chia‐Hung Liu, Lekshmi Rethi, Hieu Trung Nguyen, Andrew E.‐Y. Chuang
Journal: Advanced Healthcare Materials (2024)

Thrombosis presents a critical health threat globally, with high mortality and incidence rates. Clinical treatment faces challenges such as low thrombolytic agent bioavailability, thrombosis recurrence, ischemic hypoxia damage, and neural degeneration. This study developed biocompatible Chlamydomonas Reinhardtii micromotors (CHL) with photo/magnetic capabilities to address these needs. These CHL micromotors, equipped with phototaxis and photosynthesis abilities, offer promising solutions. A core aspect of this innovation involves incorporating polysaccharides (glycol chitosan (GCS) and fucoidan (F)) into ferric Metal-organic frameworks (MOFs), loaded with urokinase (UK), and subsequently self-assembled onto the multimodal CHL, forming a core-shell microstructure (CHL@GCS/F-UK-MOF). Under light-navigation, CHL@GCS/F-UK-MOF is shown to penetrate thrombi, enhancing thrombolytic biodistribution. Combining CHL@GCS/F-UK-MOF with the magnetic hyperthermia technique achieves stimuli-responsive multiple-release, accelerating thrombolysis and rapidly restoring blocked blood vessels. Moreover, this approach attenuates thrombi-induced ischemic hypoxia disorder and tissue damage. The photosynthetic and magnetotherapeutic properties of CHL@GCS/F-UK-MOF, along with their protective effects, including reduced apoptosis, enhanced behavioral function, induced Heat Shock Protein (HSP), polarized M2 macrophages, and mitigated hypoxia, are confirmed through biochemical, microscopic, and behavioral assessments. This multifunctional biomimetic platform, integrating photo-magnetic techniques, offers a comprehensive approach to cardiovascular management, advancing related technologies.
Targeting Osteoblast‐Osteoclast Cross‐Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats
Authors: Jiancheng Zheng, Xiaoyan Li, Fangke Zhang, Changwei Li, Xingkai Zhang, Fei Wang, Jin Qi, Wenguo Cui, Lianfu Deng
Journal: Advanced Healthcare Materials (2024)

Abstract Balancing osteoblast‐osteoclast (OB‐OC) cross‐talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross‐talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin‐specific protease 26 (USP26) is shown to coordinate OB‐OC cross‐talk by independently regulating β‐catenin and Iκb‐α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA‐loaded lipid nanoparticles (mRNA@LNP) within MMPs‐responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB‐OC cross‐talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell‐to‐cell cross‐talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.
H<sub>2</sub>O<sub>2</sub>‐Activatable Liposomal Nanobomb Capable of Generating Hypoxia‐Irrelevant Alkyl Radicals by Photo‐Triggered Cascade Reaction for High‐Performance Elimination of Biofilm Bacteria
Authors: Ke Yang, Li Wang, Jinyi Chen, Zefeng Wang, Junqin Li, Xi Chen, Shuting Fu, Luo Hai, Le Deng, Dinggeng He
Journal: Advanced Healthcare Materials (2024)

Abstract High H 2 O 2 levels are widely present at the infection sites or in the biofilm microenvironment. Herein, hemin with peroxidase‐like catalytic activity and its substrate, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), are simultaneously introduced into a liposomal nanoparticle containing thermosensitive 2,2′‐azobis[2‐(2‐imidazolin‐2‐yl) propane] dihydrochloride (AIBI)‐loaded bovine serum albumin (BAG), rationally constructing an H 2 O 2 ‐activatable liposomal nanobomb (Lipo@BHA) for combating biofilm‐associated bacterial infections with high performance. In the presence of H 2 O 2 , hemin can catalyze the conversion of ABTS into its oxidized form (ABTS· + ) with strong near‐infrared (NIR) absorption, which produces photonic hyperpyrexia to cause the decomposition of AIBI into oxygen‐independent alkyl radicals (·R) and nitrogen (N 2 ) microbubbles. The former not only directly damage bacterial cells but also significantly accelerates the oxidization of ABTS to ABTS· + for augmenting photothermal‐triggered generation of ·R. Interestingly, the released N 2 can induce transient cavitation to rupture lysosomal nanoparticle and improve the biofilm permeability, thereby enhancing the antibiofilm effect of Lipo@BHA. The proposed Lipo@BHA exhibits satisfactory multi‐mode combination antibacterial properties. Through endogenous H 2 O 2 ‐activated cascade reaction, Lipo@BHA achieves remarkable hypoxia‐irrelevant ·R therapy of biofilm‐associated wound infections with low cytotoxicity and good in vivo biosafety. Therefore, this work presents a versatile H 2 O 2 ‐activatable cascade ·R generation strategy for biofilm‐specific therapeutic applications.
The Dawn of a New Pharmaceutical Epoch: Can AI and Robotics Reshape Drug Formulation?
Authors: Pauric Bannigan, Riley J. Hickman, Alán Aspuru‐Guzik, Christine Allen
Journal: Advanced Healthcare Materials (2024)

Abstract Over the last four decades, pharmaceutical companies’ expenditures on research and development have increased 51‐fold. During this same time, clinical success rates for new drugs have remained unchanged at about 10 percent, predominantly due to lack of efficacy and/or safety concerns. This persistent problem underscores the need to innovate across the entire drug development process, particularly in drug formulation, which is often deprioritized and under‐resourced.