tbuckley/cabot-search huggingface dataset:
Cosmic chronometers: Is spaceflight a catalyst for biological ageing?
Authors: Manuela Campisi, Luana Cannella, Sofia Pavanello
Journal: Ageing Research Reviews (2024)

Astronauts returning from space missions often exhibit health issues mirroring age-related conditions, suggesting spaceflight as a potential driver of biological ageing and age-related diseases. To unravel the underlying mechanisms of these conditions, this comprehensive review explores the impact of the space "exposome" on the twelve hallmarks of ageing. Through a meticulous analysis encompassing both space environments and terrestrial analogs, we aim to decipher how different conditions influence ageing hallmarks. Utilizing PubMed, we identified 189 studies and 60 meet screening criteria. Research on biological ageing in space has focused on genomic instability, chronic inflammation, and deregulated nutrient sensing. Spaceflight consistently induces genomic instability, linked to prolonged exposure to ionizing radiation, triggers pro-inflammatory and immune alterations, resembling conditions in isolated simulations. Nutrient sensing pathways reveal increased systemic insulin-like growth-factor- 1. Microbiome studies indicate imbalances favoring opportunistic species during spaceflight. Telomere dynamics present intriguing patterns, with lengthening during missions and rapid shortening upon return. Despite a pro-ageing trend, some protective mechanisms emerge. Countermeasures, encompassing dietary adjustments, prebiotics, postbiotics, symbiotics, tailored exercises, meditation, and anti-inflammatory supplements, exhibit potential. Spaceflight's impact on ageing is intricate, with diverse findings challenging established beliefs. Multidisciplinary studies provide guidance for future research in this field.
A Divalent Chikungunya and Zika Nanovaccine with Thermostable Self‐Assembly Multivalent Scaffold LS‐SUMO
Authors: Qianlin Li, Jinsong Zhang, Qiang Deng, Conghui Liao, Jun Qian, Zeliang Chen, Jiahai Lu
Journal: Advanced Healthcare Materials (2024)

Abstract The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine‐induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS‐SUMO (SUMO, small ubiquitin‐likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS‐SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS‐SUMO conjugates produce CD4 + T cell‐mediated Th2‐biased responses and promote humoral immunity. Importantly, LS‐SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS‐SUMO is a powerful biotargeting nanoplatform with high‐yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.
Correspondence to “Oral immunotherapy in alpha‐gal red meat allergy: Could specific <scp>IgE</scp> be a potential biomarker in monitoring management?”
Authors: Yi‐Chen Chen, Yu‐Hsi Lin, Chi‐Tung Lu, Chin‐Yuan Yii, Pei‐Chi Chen, Su‐Boon Yong
Journal: Allergy (2024)

The authors have no relevant financial or non-financial interests to disclose. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges
Authors: Zhenwei Zhang, Linghui Hou, Dan Liu, Shenglin Luan, Min Huang, Linxiang Zhao
Journal: Acta Pharmaceutica Sinica B (2024)

For over two decades, the development of B-cell lymphoma-2 (Bcl-2) family therapeutics has primarily focused on anti-apoptotic proteins, resulting in the first-in-class drugs called BH3 mimetics, especially for Bcl-2 inhibitor Venetoclax. The pro-apoptotic protein Bcl-2-associated X protein (BAX) plays a crucial role as the executioner protein of the mitochondrial regulated cell death, contributing to organismal development, tissue homeostasis, and immunity. The dysregulation of BAX is closely associated with the onset and progression of diseases characterized by pathologic cell survival or death, such as cancer, neurodegeneration, and heart failure. In addition to conducting thorough investigations into the physiological modulation of BAX, research on the regulatory mechanisms of small molecules identified through biochemical screening approaches has prompted the identification of functional and potentially druggable binding sites on BAX, as well as diverse all-molecule BAX modulators. This review presents recent advancements in elucidating the physiological and pharmacological modulation of BAX and in identifying potentially druggable binding sites on BAX. Furthermore, it highlights the structural and mechanistic insights into small-molecule modulators targeting diverse binding surfaces or conformations of BAX, offering a promising avenue for developing next-generation apoptosis modulators to treat a wide range of diseases associated with dysregulated cell death by directly targeting BAX.
Biofabrication's Contribution to the Evolution of Cultured Meat
Authors: Franziska Brigitte Albrecht, Tilman Ahlfeld, Annemarie Klatt, Simon Heine, Michael Gelinsky, Petra Juliane Kluger
Journal: Advanced Healthcare Materials (2024)

Cultured Meat (CM) is a growing field in cellular agriculture, driven by the environmental impact of conventional meat production, which contributes to climate change and occupies ≈70% of arable land. As demand for meat alternatives rises, research in this area expands. CM production relies on tissue engineering techniques, where a limited number of animal cells are cultured in vitro and processed to create meat-like tissue comprising muscle and adipose components. Currently, CM is primarily produced on a small scale in pilot facilities. Producing a large cell mass based on suitable cell sources and bioreactors remains challenging. Advanced manufacturing methods and innovative materials are required to subsequently process this cell mass into CM products on a large scale. Consequently, CM is closely linked with biofabrication, a suite of technologies for precisely arranging cellular aggregates and cell-material composites to construct specific structures, often using robotics. This review provides insights into contemporary biomedical biofabrication technologies, focusing on significant advancements in muscle and adipose tissue biofabrication for CM production. Novel materials for biofabricating CM are also discussed, emphasizing their edibility and incorporation of healthful components. Finally, initial studies on biofabricated CM are examined, addressing current limitations and future challenges for large-scale production.
Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa
Authors: Xiao Liu, Yuyu Liu, Xiping Xu, Wenqian Huang, Yaru Yan, Yingxia Wang, Weisheng Tian, Ting Mo, Xiaoxue Cui, Jun Li, She-Po Shi, Pengfei Tu
Journal: Acta Pharmaceutica Sinica B (2024)

Enzymatic malonylation of natural glycosides provided a promising alternative method for drug-like malonylated glycosides supply. However, the catalytic potential and structural basis of plant malonyltransferase are far from being fully elucidated. This work identified a new malonyltransferase CtMaT1 from Cistanche tubulosa. It displayed unprecedented mono- and/or di-malonylation activity toward diverse glucosides with different aglycons. A "one-pot" system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated glucosides. Structural investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse glucosides. Additionally, it recognizes malonyl-CoA through strong electrotactic and hydrogen interactions. QM/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1, while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167, resulting in its high malonylation regiospecificity. Calculated energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates, emphasizing CtMaT1's preference for glucosides. Furthermore, a mutant CtMaT1H36A with notably increased di-malonylation activity was obtained. The underlying molecular mechanism was illuminated through MM/GBSA binding free energy calculation. This study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives, while also providing a versatile tool for enzymatic malonylation applications in pharmacology.
Cisplatin-based miRNA delivery strategy inspired by the circCPNE1/miR-330-3p pathway for oral squamous cell carcinoma
Authors: Hua-yang Fan, Ming-da Zhao, Hong-jie Jiang, Zhen-wei Yu, Yu-jiang Fan, Xin-hua Liang, Ya-ling Tang, Yong Sun
Journal: Acta Pharmaceutica Sinica B (2024)

Circular RNAs (circRNAs) are ideal biomarkers of oral squamous cell carcinoma (OSCC) because of their highly stable closed-loop structure, and they can act as microRNA (miRNA) sponges to regulate OSCC progression. By analyzing clinical samples, we identified circCPNE1, a dysregulated circRNA in OSCC, and its expression level was negatively correlated with the clinical stage of OSCC patients. Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1, which was then identified as a miR-330-3p sponge. MiR-330-3p was recognized as a tumor promoter in multiple studies, consistent with our finding that it could promote the proliferation, migration, and invasion of OSCC cells. These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression. Therefore, we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p (a miRNA inhibitory analog) via electrostatic interactions to form PP@miR nanoparticles (NPs). Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination (2/5), which confirmed the critical role of miR-330-3p in OSCC development. These findings provide a new perspective for the development of OSCC treatments.
Deep learning models across the range of skin disease
Authors: Kaushik P. Venkatesh, Marium M. Raza, Grace Nickel, Serena Wang, Joseph C. Kvedar
Journal: npj Digital Medicine (2024)

We explore the evolving landscape of diagnostic artificial intelligence (AI) in dermatology, particularly focusing on deep learning models for a wide array of skin diseases beyond skin cancer. We critically analyze the current state of AI in dermatology, its potential in enhancing diagnostic accuracy, and the challenges it faces in terms of bias, applicability, and therapeutic recommendations.
Multi-cohort validation of Ascore: an anoikis-based prognostic signature for predicting disease progression and immunotherapy response in bladder cancer
Authors: Tianlei Xie, Shan Peng, Shujun Liu, Minghao Zheng, Wenli Diao, Meng Ding, Yao Fu, Hongqian Guo, Wei Zhao, Junlong Zhuang
Journal: Molecular Cancer (2024)

Abstract Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore’s independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy ( P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.
Unveiling the impact of aging on BBB and Alzheimer's disease: Factors and therapeutic implications
Authors: Vinod Kumar Nelson, Niraj Kumar Jha, Mohana Vamsi Nuli, Saurabh Gupta, Sandeep Kanna, Reem M. Gahtani, Umme Hani, Arun Kumar Singh, Mosleh Mohammad Abomughaid, Ali M. Abomughayedh, Abdulmajeed G. Almutary, Danish Iqbal, Ayoub Al Othaim, S. Sabarunisha Begum, Fuzail Ahmad, Prabhu Chandra Mishra, Saurabh Kumar Jha, Shreesh Ojha
Journal: Ageing Research Reviews (2024)
Donor germ‐line variants associate with outcomes of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndromes
Authors: Paul L. Auer, Manzur Farazi, Tao Zhang, Jing Dong, Yung‐Tsi Bolon, Stephen R. Spellman, Wael Saber
Journal: American Journal of Hematology (2024)

Overall survival probability for MDS patients who underwent allo-HCT and were matched to donors that are wild-type (red) and heterozygous (blue) for the rs111224634 SNP.
Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling
Authors: Qing Zhao, Junjie Feng, Fubin Liu, Qianxin Liang, Manlin Xie, Jiaming Dong, Yanfang Zou, Jiali Ye, Guilong Liu, Yue Cao, Zhaodi Guo, Hongzhi Qiao, Lei Zheng, Kewei Zhao
Journal: Acta Pharmaceutica Sinica B (2024)

Although various anti-osteoporosis drugs are available, the limitations of these therapies, including drug resistance and collateral responses, require the development of novel anti-osteoporosis agents. Rhizoma Drynariae displays a promising anti-osteoporosis effect, while the effective component and mechanism remain unclear. Here, we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles (RDNVs) for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) by targeting estrogen receptor-alpha (ERα). RDNVs, a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation, exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model. RDNVs, effectively internalized by hBMSCs, enhanced proliferation and ERα expression levels of hBMSC, and promoted osteogenic differentiation and bone formation. Mechanistically, via the ERα signaling pathway, RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs, which are involved in regulating osteogenic differentiation. Further analysis revealed that naringin, existing in RDNVs, was the active component targeting ERα in the osteogenic effect. Taken together, our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.
Circulating cancer-specific CD8 T cell frequency is associated with response to PD-1 blockade in Merkel cell carcinoma
Authors: Thomas Pulliam, Saumya Jani, Lichen Jing, Heeju Ryu, Ana Jojic, Carolyn Shasha, Jiajia Zhang, Rima Kulikauskas, Candice Church, Charlie Garnett-Benson, Ted Gooley, Aude Chapuis, Kelly Paulson, Kellie N. Smith, Drew M. Pardoll, Evan W. Newell, David M. Koelle, Suzanne L. Topalian, Paul Nghiem
Journal: Cell Reports Medicine (2024)

Understanding cancer immunobiology has been hampered by difficulty identifying cancer-specific T cells. Merkel cell polyomavirus (MCPyV) causes most Merkel cell carcinomas (MCCs). All patients with virus-driven MCC express MCPyV oncoproteins, facilitating identification of virus (cancer)-specific T cells. We studied MCPyV-specific T cells from 27 patients with MCC using MCPyV peptide-HLA-I multimers, 26-color flow cytometry, single-cell transcriptomics, and T cell receptor (TCR) sequencing. In a prospective clinical trial, higher circulating MCPyV-specific CD8 T cell frequency before anti-PD-1 treatment was strongly associated with 2-year recurrence-free survival (75% if detectable, 0% if undetectable, p = 0.0018; ClinicalTrial.gov: NCT02488759). Intratumorally, such T cells were typically present, but their frequency did not significantly associate with response. Circulating MCPyV-specific CD8 T cells had increased stem/memory and decreased exhaustion signatures relative to their intratumoral counterparts. These results suggest that cancer-specific CD8 T cells in the blood may play a role in anti-PD-1 responses. Thus, strategies that augment their number or mobilize them into tumors could improve outcomes.
IL‐37 Modulates Myocardial Calcium Handling via the p‐STAT3/SERCA2a Axis in HF‐Related Engineered Human Heart Tissue
Authors: Dan Yin, Yong Liu, Bingqing Xue, Rui Ding, Gang Wang, Shutao Xia, Donghui Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Interleukin‐37 (IL‐37) is a potent anti‐inflammatory cytokine belonging to the IL‐1 family. This study investigates the regulatory mechanism and reparative effects of IL‐37 on HF‐related human induced pluripotent stem cells derived cardiomyocytes (hiPSC‐CMs) and engineered human heart tissue subjected to hypoxia and H 2 O 2 treatment. The contractile force and Ca 2+ conduction capacity of the tissue are assessed using a stretching platform and high‐resolution fluorescence imaging system. This investigation reveals that IL‐37 treatment significantly enhances cell viability, calcium transient levels, contractile force, and Ca 2+ conduction capacity in HF‐related hiPSC‐CMs and engineered human heart tissue. Notably, IL‐37 facilitates the upregulation of sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) through enhancing nuclear p‐STAT3 levels. This effect is mediated by the binding of p‐STAT3 to the SERCA2a promoter, providing a novel insight on the reparative potential of IL‐37 in HF. IL‐37 demonstrates its ability to enhance systolic function by modulating myocardial calcium handling via the p‐STAT3/SERCA2a axis in HF‐related engineered human heart tissue (as shown in schematic diagram).
Endoplasmic reticulum stress-related cancer-associated fibroblast confers adverse prognosis and therapeutic vulnerability in skull base chordoma
Authors: Mingxuan Li, Yujia Xiong, Jiwei Bai, Yazhuo Zhang
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Endoplasmic reticulum stress-related cancer-associated fibroblast confers adverse prognosis and therapeutic vulnerability in skull base chordoma Get access Mingxuan Li, Mingxuan Li Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (M.L., J.B., Y.Z.) Search for other works by this author on: Oxford Academic PubMed Google Scholar Yujia Xiong, Yujia Xiong Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Pathology, West China Hospital, Sichuan University, Chengdu, China Search for other works by this author on: Oxford Academic PubMed Google Scholar Jiwei Bai, Jiwei Bai Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Corresponding Authors: Yazhuo Zhang, MD, PhD, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China (zyztxzz@126.com); Jiwei Bai, MD, PhD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China (bai-12@163.com). Search for other works by this author on: Oxford Academic PubMed Google Scholar Yazhuo Zhang Yazhuo Zhang Beijing Neurosurgical Institute, Capital Medical University, Beijing, ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China Corresponding Authors: Yazhuo Zhang, MD, PhD, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China (zyztxzz@126.com); Jiwei Bai, MD, PhD, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China (bai-12@163.com). https://orcid.org/0000-0002-8583-2580 Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae007, https://doi.org/10.1093/neuonc/noae007 Published: 10 February 2024 Article history Corrected and typeset: 10 February 2024 Published: 10 February 2024
Corrigendum to “European society of clinical microbiology and infectious diseases guidelines on diagnosis and treatment of brain abscess in children and adults” [Clin Microbiol and Infect 30(1) (2024 Jan) 66–89 Doi: 10.1016/j.cmi.2023.08.016]
Authors: Jacob Bodilsen, Quintino Giorgio D'Alessandris, Hilary Humphreys, Mildred A. Iro, Matthias Klein, Katharina Last, Inmaculada López Montesinos, Pasquale Pagliano, Oğuz Reşat Sipahi, Rafael San-Juan, Pierre Tattevin, Majda Thurnher, Rogelio de J. Treviño-Rangel, Matthijs C. Brouwer
Journal: Clinical Microbiology and Infection (2024)