tbuckley/cabot-search huggingface dataset:
Photoperiod and metabolic health: evidence, mechanism, and implications
Authors: Prashant Regmi, Morag Young, Gabriela Minigo, Natalie Milic, Prajwal Gyawali
Journal: Metabolism (2023)

Circadian rhythms are evolutionarily programmed biological rhythms that are primarily entrained by the light cycle. Disruption of circadian rhythms is an important risk factor for several metabolic disorders. Photoperiod is defined as total duration of light exposure in a day. With the extended use of indoor/outdoor light, smartphones, television, computers, and social jetlag people are exposed to excessive artificial light at night increasing their photoperiod. Importantly long photoperiod is not limited to any geographical region, season, age, or socioeconomic group, it is pervasive. Long photoperiod is an established disrupter of the circadian rhythm and can induce a range of chronic health conditions including adiposity, altered hormonal signaling and metabolism, premature ageing, and poor psychological health. This review discusses the impact of exposure to long photoperiod on circadian rhythms, metabolic and mental health, hormonal signaling, and ageing and provides a perspective on possible preventive and therapeutic approaches for this pervasive challenge.
Immunotoxicity Evaluation of Trihalophenolic Disinfection By-Products in Mouse and Human Mononuclear Macrophage Systems: The Role of RNA Epitranscriptomic Modification in Mammalian Immunity
Authors: Min Qin, Linyuan Huang, Meishuang Li, Tianye Shao, Jun Zhang, Xiaoqin Jiang, Chenlu Shao, Chengsi Zhao, Yang Pan, Qing Zhou, Yong Wang, Xiao-Min Liu, Jingfan Qiu
Journal: Environmental Health Perspectives (2023)

2,4,6-Trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodophenol (TIP) are three widely detected trihalophenolic disinfection by-products (DBPs). Previous studies have mainly focused on the carcinogenic risk and developmental toxicity of 2,4,6-trihalophenols. Very little is known about their immunotoxicity in mammals.
Author correction to ‘Discovery and identification of EIF2AK2 as a direct key target of berberine for anti-inflammatory effects’ [Acta Pharmaceutica Sinica B 13 (2023) 2138–2151]
Authors: Wei Wei, Qingxuan Zeng, Yan Wang, Xixi Guo, Tianyun Fan, Yinghong Li, Hongbin Deng, Liping Zhao, Xintong Zhang, Yonghua Liu, Yulong Shi, Jingyang Zhu, Xican Ma, Yanxiang Wang, Jiandong Jiang, Danqing Song
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2022.12.009.].
Quantitative Integration of Mode of Action Information in Dose–Response Modeling and POD Estimation for Nonmutagenic Carcinogens: A Case Study of TCDD
Authors: Qiran Chen, Yun Zhou, Chao Ji, James E. Klaunig, Kan Shao
Journal: Environmental Health Perspectives (2023)

Traditional dose–response assessment applies different low-dose extrapolation methods for cancer and noncancer effects and assumes that all carcinogens are mutagenic unless strong evidence suggests otherwise. Additionally, primarily focusing on one critical effect, dose–response modeling utilizes limited mode of action (MOA) data to inform low-dose risk.
Is Kidney Function Associated with Age-Related Macular Degeneration?
Authors: Can Can Xue, Ralene Sim, Miao Li Chee, Marco Yu, Ya Xing Wang, Tyler Hyungtaek Rim, Park Kyu Hyung, Kang Se Woong, Su Jeong Song, Vinay Nangia, Songhomitra Panda-Jonas, Ning Li Wang, Jie Hao, Qing Zhang, Kai Cao, Mariko Sasaki, Sei Harada, Takebayashi Toru, Kawasaki Ryo, Rajiv Raman, Janani Surya, Rehana Khan, Mukharram Bikbov, Ian Y. Wong, Chui Ming Gemmy Cheung, Jost B. Jonas, Ching-Yu Cheng, Yih-Chung Tham
Journal: Ophthalmology (2023)

Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium.
Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers
Authors: Xumei Ouyang, Yu Liu, Ke Zheng, Zhiqing Pang, Shaojun Peng
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Nanoscale drug delivery systems (nDDS) have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects. Although several nDDS have been successfully approved for clinical use up to now, biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment. Polyethylene glycol (PEG)-modification (or PEGylation) has been regarded as the gold standard for stabilising nDDS in complex biological environment. However, the accelerated blood clearance (ABC) of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications. Zwitterionic polymer, a novel family of anti-fouling materials, have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility. Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues. More impressively, zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution, pressure gradients, impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications. The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS, which could facilitate their better clinical translation. Herein, we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlying mechanisms. Finally, prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.
Biomarkers of early SARS-CoV-2 infection before the onset of respiratory symptoms
Authors: Ooiean Teng, Amy May Lin Quek, Tuong Minh Nguyen, Suqing Wang, Isabel Xue Qi Ng, Lorivie Fragata, Firdaus Begum Mohd-Abu-Bucker, Paul Anantharajah Tambyah, Raymond Chee Seong Seet
Journal: Clinical Microbiology and Infection (2023)
bFGF-releasing biodegradable nanoparticles for effectively engrafting transplanted hepatocyte sheet
Authors: Kenichi Nagase, Marin Nagaoka, Yuto Nakano, Rie Utoh
Journal: Journal of Controlled Release (2023)

Hepatic tissue engineering has been applied for the treatment of intractable liver diseases, and hepatocyte sheets are promising for this purpose. However, hepatocyte sheets have poor survival after transplantation because of their high metabolic activity. In this study, we aimed to develop basic fibroblast growth factor (bFGF)-releasing nanoparticles to prolong the survival of hepatocyte sheets after transplantation. The nanoparticles were prepared by electrospraying a bFGF-dispersed poly(D,l-lactide-co-glycolide) emulsion. bFGF-loaded PLGA nanoparticles can be developed by optimizing the applied electrospray voltage and the oil:water ratio of the emulsion. The prepared nanoparticles exhibited prompt release at the initial duration and continuous gradual release at the subsequent duration. Hepatocyte sheet engraftment was evaluated by transplanting hepatocyte sheets containing the prepared nanoparticles into rats. The hepatocyte sheets with the prepared nanoparticles exhibited longer survival than those without the bFGF nanoparticles or solution owing to the local and continuous release of bFGF from the nanoparticles and the subsequent enhanced angiogenesis at the transplantation site. These results indicated that the prepared bFGF-releasing nanoparticles can enhance the efficiency of hepatocyte sheet transplantation. The developed bFGF-releasing nanoparticles would be useful for the transplantation of cellular tissue with post-transplantation survival challenges.
Nogo-A neutralization in the central nervous system with a blood-brain barrier-penetrating antibody
Authors: Sandrine Joly, Gilles Augusto, Baya Mdzomba, Ivo Meli, Monique Vogel, Andrew Chan, Vincent Pernet
Journal: Journal of Controlled Release (2023)

The poor penetration of monoclonal antibodies (mAb) across the blood-brain barrier (BBB) impedes the development of regenerative therapies for neurological diseases. For example, Nogo-A is a myelin-associated protein highly expressed in the central nervous system (CNS) whose inhibitory effects on neuronal plasticity can be neutralized with direct administration of 11C7 mAb in CNS tissues/fluids, but not with peripheral administrations such as intravenous injections. Therefore, in the present study, we engineered a CNS-penetrating antibody against Nogo-A by combining 11C7 mAb and the single-chain variable fragment (scFv) of 8D3, a rat antibody binding transferrin receptor 1 (TfR) and mediating BBB transcytosis (11C7-scFv8D3). The binding of 11C7-scFv8D3 to Nogo-A and to TfR/CD71 was validated by capture ELISA and Biolayer Interferometry. After intravenous injection in mice, capture ELISA measurements revealed fast plasma clearance of 11C7-scFv8D3 concomitantly with brain and spinal cord accumulation at levels up to 19 fold as high as those of original 11C7 mAb. 11C7-scFv8D3 detection in the parenchyma indicated effective blood-to-CNS transfer. A single dose of 11C7-scFv8D3 induced stronger activation of the growth-promoting AkT/mTOR/S6 signaling pathway than 11C7 mAb or control antibody. Taken together, our results show that BBB-crossing 11C7-scFv8D3 engages Nogo-A in the mouse CNS and stimulates neuronal growth mechanisms.
Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier
Authors: Dongsheng Bai, Jiawei Zhao, Runde Wang, Jiaying Du, Chen Zhou, Chunyang Gu, Yuxiang Wang, Lulu Zhang, Yue Zhao, Na Lu
Journal: Acta Pharmaceutica Sinica B (2023)

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment, significantly curtailing the efficacy of these treatments and, in some cases, resulting in fatal consequences. Despite identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis, the paucity of effective treatments for such damage is evident. In our study, we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells, thereby fortifying the integrity of the intestinal mucus barrier. This enhanced barrier function serves to resist microbial invasion and subsequently reduces the inflammatory response. Importantly, this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy drugs. Mechanistically, E. copr up-regulates the expression of AUF1, leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet cells. An especially significant finding is that E. copr activates the AhR pathway, thereby promoting the expression of AUF1. In summary, our results strongly indicate that E. copr enhances the intestinal mucus barrier, effectively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUF1 pathway, consequently enhancing Muc2 mRNA stability.
Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy
Authors: Duoyang Fan, Xiaohui Liu, Yueming Ren, Ziheng Luo, Yanbing Li, Jie Dong, Seraphine V. Wegner, Fei Chen, Wenbin Zeng
Journal: Acta Pharmaceutica Sinica B (2023)

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G–) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G– bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.
Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy
Authors: Mark S. Humayun, Dennis O. Clegg, Margot S. Dayan, Amir H. Kashani, Firas M. Rahhal, Robert L. Avery, Hani Salehi-Had, Sanford Chen, Clement Chan, Neal Palejwala, April Ingram, Debbie Mitra, Britney O. Pennington, Cassidy Hinman, Mohamed A. Faynus, Jeffrey K. Bailey, Lincoln V. Johnson, Jane S. Lebkowski
Journal: Ophthalmology (2023)
Pseudomonas aeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID/ISARPAE Group
Authors: Antonio Oliver, Estrella Rojo-Molinero, Jorge Arca-Suarez, Yeşim Beşli, Pierre Bogaerts, Rafael Cantón, Cansu Cimen, Peter D. Croughs, Olivier Denis, Christian G. Giske, Tíscar Graells, Te-Din Daniel Huang, Bogdan I. Iorga, Onur Karatuna, Béla Kocsis, Andreas Kronenberg, Carla López-Causapé, Surbhi Malhotra-Kumar, Luis Martínez Martínez, Annarita Mazzariol, Sylvain Meyer, Thierry Naas, Daan W. Notermans, Jesús Oteo-Iglesias, Torunn Pedersen, Mateja Pirš, Patricia Poeta, Laurent Poirel, Spyros Pournaras, Arnfinn Sundsfjord, Dora Szabó, Arjana Tambić-Andrašević, Rossitza Vatcheva-Dobrevska, Astra Vitkauskienė, Katy Jeannot
Journal: Clinical Microbiology and Infection (2023)

Pseudomonas aeruginosa, a ubiquitous opportunistic pathogen considered one of the paradigms of antimicrobial resistance, is among the main causes of hospital-acquired and chronic infections associated with significant morbidity and mortality. This growing threat results from the extraordinary capacity of P. aeruginosa to develop antimicrobial resistance through chromosomal mutations, the increasing prevalence of transferable resistance determinants (such as the carbapenemases and the extended-spectrum β-lactamases), and the global expansion of epidemic lineages. The general objective of this initiative is to provide a comprehensive update of P. aeruginosa resistance mechanisms, especially for the extensively drug-resistant (XDR)/difficult-to-treat resistance (DTR) international high-risk epidemic lineages, and how the recently approved β-lactams and β-lactam/β-lactamase inhibitor combinations may affect resistance mechanisms and the definition of susceptibility profiles.
IL-10 dampens antitumor immunity and promotes liver metastasis via PD-L1 induction
Authors: Ahmad Mustafa Shiri, Tao Zhang, Tanja Bedke, Dimitra E. Zazara, Lilan Zhao, Jöran Lücke, Morsal Sabihi, Antonella Fazio, Siwen Zhang, Daniele V.F. Tauriello, Eduard Batlle, Babett Steglich, Jan Kempski, Theodora Agalioti, Mikołaj Nawrocki, Yang Xu, Kristoffer Riecken, Imke Liebold, Leonie Brockmann, Leonie Konczalla, Lidia Bosurgi, Baris Mercanoglu, Philipp Seeger, Natalie Küsters, Panagis M. Lykoudis, Asmus Heumann, Petra C. Arck, Boris Fehse, Philipp Busch, Rainer Grotelüschen, Oliver Mann, Jakob R. Izbicki, Thilo Hackert, Richard A. Flavell, Nicola Gagliani, Anastasios D. Giannou, Samuel Huber
Journal: Journal of Hepatology (2023)

The liver is one of the organs most commonly affected by metastasis. The presence of liver metastases has been reported to be responsible for an immunosuppressive microenvironment and diminished immunotherapy efficacy. Herein, we aimed to investigate the role of IL-10 in liver metastasis and to determine how its modulation could affect the efficacy of immunotherapy in vivo.
Hypoxia-induced galectin-8 maintains stemness in glioma stem cells via autophagy regulation
Authors: Dan Liu, Hongtao Zhu, Lidong Cheng, Ran Li, Xiaoyu Ma, Jing Wang, Junwen Wang, Suojun Zhang, Yingjie Li, Kai Shu, Xingjiang Yu, Chuanzhou Li
Journal: Neuro-Oncology (2023)

Abstract Background Glioma stem cells (GSCs) are the root cause of relapse and treatment resistance in glioblastoma (GBM). In GSCs, hypoxia in the microenvironment is known to facilitate the maintenance of stem cells, and evolutionally conserved autophagy regulates cell homeostasis to control cell population. The precise involvement of autophagy regulation in hypoxic conditions in maintaining the stemness of GSCs remains unclear. Methods The association of autophagy regulation and hypoxia was first assessed by in silico analysis and validation in vitro. Glioma databases and clinical specimens were used to determine galectin-8 (Gal-8) expression in GSCs and human GBMs, and the regulation and function of Gal-8 in stemness maintenance were evaluated by genetic manipulation in vitro and in vivo. How autophagy was stimulated by Gal-8 under hypoxia was systematically investigated. Results Hypoxia enhances autophagy in GSCs to facilitate self-renewal, and Gal-8 in the galectin family is specifically involved and expressed in GSCs within the hypoxic niche. Gal-8 is highly expressed in GBM and predicts poor survival in patients. Suppression of Gal-8 prevents tumor growth and prolongs survival in mouse models of GBM. Gal-8 binds to the Ragulator-Rag complex at the lysosome membrane and inactivates mTORC1, leading to the nuclear translocation of downstream TFEB and initiation of autophagic lysosomal biogenesis. Consequently, the survival and proliferative activity of GSCs are maintained. Conclusions Our findings reveal a novel Gal-8-mTOR-TFEB axis induced by hypoxia in the maintenance of GSC stemness via autophagy reinforcement, highlighting Gal-8 as a candidate for GSCs-targeted GBM therapy.
A quasi-experimental study of a bundled diagnostic stewardship intervention for ventilator-associated pneumonia
Authors: Owen R. Albin, Jonathan P. Troost, Louis Saravolatz, Michael P. Thomas, Robert C. Hyzy, Mark A. Konkle, Andrew J. Weirauch, Robert P. Dickson, Krishna Rao, Keith S. Kaye
Journal: Clinical Microbiology and Infection (2023)
Development of antibody‐drug conjugates in cancer: Overview and prospects
Authors: Dan‐Yun Ruan, Hao‐Xiang Wu, Qi Meng, Rui‐Hua Xu
Journal: Cancer Communications (2023)

Abstract In recent years, remarkable breakthroughs have been reported on antibody‐drug conjugates (ADCs), with 15 ADCs successfully entering the market over the past decade. This substantial development has positioned ADCs as one of the fastest‐growing domains in the realm of anticancer drugs, demonstrating their efficacy in treating a wide array of malignancies. Nonetheless, there is still an unmet clinical need for wider application, better efficacy, and fewer side effects of ADCs. An ADC generally comprises an antibody, a linker and a payload, and the combination has profound effects on drug structure, pharmacokinetic profile and efficacy. Hence, optimization of the key components provides an opportunity to develop ADCs with higher potency and fewer side effects. In this review, we comprehensively reviewed the current development and the prospects of ADC, provided an analysis of marketed ADCs and the ongoing pipelines globally as well as in China, highlighted several ADC platforms and technologies specific to different pharmaceutical enterprises and biotech companies, and also discussed the new related technologies, possibility of next‐generation ADCs and the directions of clinical research.
Develop quantitative FRET (qFRET) technology as a high-throughput universal assay platform for basic quantitative biomedical and translational research and development
Authors: Jiayu Liao
Journal: Med-X (2023)

Abstract Protein–protein interactions and enzyme-catalyzed reactions are the fundamental processes in life, and the quantification and manipulation, kinetics determination, and ether activation or inhibition of these processes are critical for fully understanding physiological processes and discovering new medicine. Various methodologies and technologies have been developed to determine the parameters of these biological and medical processes. However, due to the extreme complexity of these processes, current methods and technologies can only determine one or a few parameters. The recent development of quantitative Förster resonance energy transfer (qFRET) methodology combined with technology aims to establish a high-throughput assay platform to determine protein interaction affinity, enzymatic kinetics, high-throughput screening, and pharmacological parameters using one assay platform. The FRET assay is widely used in biological and biomedical research in vitro and in vivo and provides high-sensitivity measurement in real time. Extensive efforts have been made to develop the FRET assay into a quantitative assay to determine protein–protein interaction affinity and enzymatic kinetics in the past. However, the progress has been challenging due to complicated FRET signal analysis and translational hurdles. The recent qFRET analysis utilizes cross-wavelength correlation coefficiency to dissect the sensitized FRET signal from the total fluorescence signal, which then is used for various biochemical and pharmacological parameter determination, such as K D , K cat , K M , K i , IC 50, and product inhibition kinetics parameters. The qFRET-based biochemical and pharmacological parameter assays and qFRET-based screenings are conducted in 384-well plates in a high-throughput assay mode. Therefore, the qFRET assay platform can provide a universal high-throughput assay platform for future large-scale protein characterizations and therapeutics development. Graphical Abstract
Take a walk on the KRAB side
Authors: Olga Rosspopoff, Didier Trono
Journal: Trends in Genetics (2023)

When this article was first published, the images for Figures 2–4 were inadvertently misplaced. Figure 3 appeared as Figure 2; Figure 4 appeared as Figure 3; and Figure 2 appeared as Figure 4. The correctly matched figure numbers and images are shown below, and the article has been updated accordingly.
The genetic landscape of age-related hearing loss
Authors: Yuzuru Ninoyu, Rick A. Friedman
Journal: Trends in Genetics (2023)

Age-related hearing loss (ARHL) is a prevalent concern in the elderly population. Recent genome-wide and phenome-wide association studies (GWASs and PheWASs) have delved into the identification of causative variants and the understanding of pleiotropy, highlighting the polygenic intricacies of this complex condition. While recent large-scale GWASs have pinpointed significant SNPs and risk variants associated with ARHL, the detailed mechanisms, encompassing both genetic and epigenetic modifications, remain to be fully elucidated. This review presents the latest advances in association studies, integrating findings from both human studies and model organisms. By juxtaposing historical perspectives with contemporary genomics, we aim to catalyze innovative research and foster the development of novel therapeutic strategies for ARHL.