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Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery

Asian Journal of Pharmaceutical Sciences 2018年第2期13卷 163-172页

作者： Wanling Liang Alan Y.L.Chan Michael Y.T.Chow fiona f.k.lo Yingshan Qiu Philip C.L.kwok Jenny k.W.Lam Department of Pharmacology and Pharmacy Li Ka Shing Faculty of Medicine The University of Hong Kong Advanced Drug Delivery Group Faculty of Pharmacy The University of Sydney

The therapeutic potential of small nucleic acids such as small interfering RNA(siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled formulation.In this study, spray freeze drying was employed to prepare dry powder of small nucleic acids.Mannitol and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope(SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 μm, and the aerosol performance study using next generation impactor(NGI) showed an emitted fraction(Ef) and fine particle fraction(fPf) of 91% and 28% respectively. This formulation(5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high Ef of 92.4%and a modest fPf of around 20%. further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.

关键词： Inhalation Pulmonary delivery Small interfering RNA Spray freeze drying

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Tau in the pancreas:understanding the link between type 2 diabetes mellitus and Alzheimer's disease

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Signal Transduction and Targeted Therapy 2024年第1期9卷 6-7页

作者： Wenlu Li Steffen Tiedt Eng H.lo Neuroprotection Research Laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA02129USA Consortium International pour la Recherche Circadienne sur l’AVC(CIRCA) BostonUSA Institute for Stroke and Dementia Research LMU University HospitalLMU MunichMunichGermany

A recent study published in Molecular Psychiatry proposes a cellular mechanism that may contribute to decreased insulin production in individuals with type 2 diabetes mellitus(T2DM).1 Using a combination of cell culture experiments,animal models and studies in T2DM patients,the authors show that an up-regulation of tau inβ-islet cells can inhibit pancreatic insulin secretion through changes in microtubule assembly.

关键词： T2DM Alzheimer tau

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Autolysosomal acidification impairment as a mediator for TNfR1 induced neuronal necroptosis in Alzheimer’s disease

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Neural Regeneration Research 2024年第9期19卷 1869-1870页

作者： Evridiki Asimakidou Richard Reynolds Anna M.Barron Chih Hung lo Department of Clinical Neurosciences University of CambridgeCambridgeUK Department of Brain Sciences Faculty of MedicineImperial College LondonLondonUK Lee kong Chian School of Medicine Nanyang Technological UniversitySingaporeSingapore

Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellular tau neurofibrillary tangles as well as progressive neuronal loss.Recent evidence has suggested that prolonged neuroinflammation with increased levels of cytokines,arising from neuronal injury,innate immune responses from glial cells,and peripheral inflammation,leads to neuronal death and AD progression.

关键词： Alzheimer death tau Aβ

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Mathematical Modeling of Cell Polarity Establishment of Budding Yeast

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Communications on Applied Mathematics and Computation 2024年第1期6卷 218-235页

作者： Yue Liu Jun Xie Hay-Oak Park Wing-Cheong lo Department of Mathematics City University of Hong KongTat Chee AvenueKowloonHong KongChina Department of Molecular Genetics The Ohio State UniversityColumbusOHUSA

The budding yeast Saccharomyces cerevisiae is a powerful model system for studying the cell polarity establishment.The cell polarization process is regulated by signaling molecules,which are initially distributed in the cytoplasm and then recruited to a proper location on the cell membrane in response to spatial cues or spontaneously.Polarization of these signaling molecules involves complex regulation,so the mathematical models become a useful tool to investigate the mechanism behind the process.In this review,we discuss how mathematical modeling has shed light on different regulations in the cell polarization.We also propose future applications for the mathematical modeling of cell polarization and morphogenesis.

关键词： Budding yeast Cdc42 Morphogenesis Septin Mathematical models

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Cellular zinc metabolism and zinc signaling:from biological functions to diseases and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 401-441页

作者： Bonan Chen Peiyao Yu Wai Nok Chan fuda Xie Yigan Zhang Li Liang kam Tong Leung kwok Wai lo Jun Yu Gary M.k.Tse Wei kang ka fai To Department of Anatomical and Cellular Pathology State Key Laboratory of Translational OncologyPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina State key Laboratory of Digestive Disease Institute of Digestive DiseaseThe Chinese University of Hong KongHong KongChina CUHk-Shenzhen Research Institute The Chinese University of Hong KongShenzhenChina Department of Pathology Nanfang Hospital and Basic Medical CollegeSouthern Medical UniversityGuangdong Province Key Laboratory of Molecular Tumor PathologyGuangzhouChina Institute of Biomedical Research Taihe HospitalHubei University of MedicineShiyanChina Department of Pediatrics The Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina

Zinc metabolism at the cellular level is critical for many biological processes in the body.A key observation is the disruption of cellular homeostasis,often coinciding with disease progression.As an essential factor in maintaining cellular equilibrium,cellular zinc has been increasingly spotlighted in the context of disease development.Extensive research suggests zinc’s involvement in promoting malignancy and invasion in cancer cells,despite its low tissue concentration.This has led to a growing body of literature investigating zinc’s cellular metabolism,particularly the functions of zinc transporters and storage mechanisms during cancer progression.Zinc transportation is under the control of two major transporter families:SLC30(ZnT)for the excretion of zinc and SLC39(ZIP)for the zinc intake.Additionally,the storage of this essential element is predominantly mediated by metallothioneins(MTs).This review consolidates knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression,with a special focus on cancer.We also compile a summary of clinical trials involving zinc ions.Given the main localization of zinc transporters at the cell membrane,the potential for targeted therapies,including small molecules and monoclonal antibodies,offers promising avenues for future exploration.

关键词： metabolism invasion involvement

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How Can Practitioners Support Citizen Volunteers in Disaster Risk Reduction? Insight from “Good and Ready” in Aotearoa New Zealand

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International Journal of Disaster Risk Science 2024年第3期15卷 374-387页

作者： lo?c Le Dé Steve Ronoh Ei Mon Thinn kyu Brigitte Rive School of Public Health and Interdisciplinary Studies Auckland University of Technology Pacific Health Research Centre Auckland University of Technology New Zealand Red Cross

Global and national policy frameworks emphasize the importance of people's participation and volunteers' role in disaster risk reduction. While research has extensively focused on volunteers in disaster response and recovery, less attention has been paid on how organizations involved in disaster risk management can support volunteers in leading and coordinating communitybased disaster risk reduction. In 2019, the New Zealand Red Cross piloted the Good and Ready initiative in Auckland,Aotearoa New Zealand, with the objective to empower local people in resilience building with a focus on volunteers and community participation. This research examined the positive and negative outcomes of Good and Ready and investigated volunteers' experiences in the disaster resilience initiative. It involved the codesign of a questionnaire-based survey using participatory methods with Good and Ready volunteers, the dissemination of the survey to gather volunteers' viewpoints, and a focus group discussion with participatory activities with Red Cross volunteers. The findings highlight that a key challenge lies in finding a balance between a program that provides flexibility to address contextual issues and fosters communities' ownership, versus a prescriptive and standardized approach that leaves little room for creativity and self-initiative. It pinpoints that supporting volunteers with technical training is critical but that soft skills training such as coordinating, communicating,or facilitating activities at the local level are needed. It concludes that the sustainability of Good and Ready requires understanding and meeting volunteers' motivations and expectations and that enhancing partnerships with local emergency management agencies would strengthen the program.

关键词： Community-based approach Disaster risk reduction New Zealand Participation Volunteers

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Post-fontan circulation hepatocellular carcinoma:Open and laparoscopic hepatectomy

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 90-93页

作者： karin kY Ho Wong Hoi She Simon HY Tsang kevin S lo Tan To Cheung Department of Surgery The University of Hong Kong102 Pok Fu Lam RoadHong KongChina Department of Anaesthesiology Queen Mary Hospital102 Pok Fu Lam RoadHong KongChina

To the Editor:fontan-associated liver disease shows increasing incidence as advances in pediatric cardiology have prolonged life expectancy in patients with single ventricle congenital heart defects[1].Their unique physiology and procedure-related sequelae present an increasingly relevant challenge in hepatic surgery.We hereby reported a series of patients suffering from hepatocellular carcinoma(HCC)who successfully underwent open and laparoscopic hepatectomy.

关键词： hepatocellular hepatectomy surgery

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Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration

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Neural Regeneration Research 2025年第4期20卷 1069-1076页

作者： Evridiki Asimakidou Eka Norfaishanty Saipuljumri Chih Hung lo Jialiu Zeng Department of Clinical Neurosciences University of CambridgeCambridgeUK School of Applied Science Republic PolytechnicSingaporeSingapore Lee kong Chian School of Medicine Nanyang Technological UniversitySingaporeSingapore

The interaction between metabolic dysfunction and inflammation is central to the development of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.Obesity-related conditions like type 2 diabetes and non-alcoholic fatty liver disease exacerbate this relationship.Peripheral lipid accumulation,particularly in the liver,initiates a cascade of inflammatory processes that extend to the brain,influencing critical metabolic regulatory regions.Ceramide and palmitate,key lipid components,along with lipid transporters lipocalin-2 and apolipoprotein E,contribute to neuroinflammation by disrupting blood–brain barrier integrity and promoting gliosis.Peripheral insulin resistance further exacerbates brain insulin resistance and neuroinflammation.Preclinical interventions targeting peripheral lipid metabolism and insulin signaling pathways have shown promise in reducing neuroinflammation in animal models.However,translating these findings to clinical practice requires further investigation into human subjects.In conclusion,metabolic dysfunction,peripheral inflammation,and insulin resistance are integral to neuroinflammation and neurodegeneration.Understanding these complex mechanisms holds potential for identifying novel therapeutic targets and improving outcomes for neurodegenerative diseases.

关键词： Alzheimer’s disease inflammatory cytokines insulin resistance lipid

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Solitary extraovarian primary peritoneal carcinoma with direct invasion into the liver,diaphragm and lung without peritoneal dissemination or distant metastasis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 322-325页

作者： Billy Ho Hung Cheung Wong Hoi She Siu Lun Ho Albert Chi Yan Chan Chung Mau lo Tan To Cheung Department of Surgery The University of Hong KongHong KongChina Department of Pathology The University of Hong KongHong KongChina

To the Editor:Extraovarian primary peritoneal carcinoma(EOPPC)is an uncommon malignancy with many similarities to epithelial ovarian carcinoma in histological,clinical,and etiological aspects[1].This phenomenon is explained by their common embryonal origin,in which both develop from the coelomic epithelium in the early embryological stage.Despite their similarities,the incidence of EOPPC is significantly lower than that of epithelial ovarian carcinoma(6.78 cases per million vs.120.5 cases per million)[1].

关键词： peritoneal invasion metastasis

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Indications of pro-inflammatory cytokines in laparoscopic and open liver resection for early-stage hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 257-264页

作者： kevin Tak-Pan Ng Li Pang Jia-Qi Wang Wong Hoi She Simon Hing-Yin Tsang Chung Mau lo kwan Man Tan To Cheung Department of Surgery HKU-SZH&School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina State key Laboratory of Liver Research The University of Hong KongHong KongChina

Background:Our clinical practice of laparoscopic liver resection(LLR)had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma(HCC)over open liver resection(OLR),but the underlying mechanisms are not clear.This study was to find out whether systemic inflammation plays an important role.Methods:A total of 103 patients with early-stage HCC under liver resection were enrolled(LLR group,n=53;OLR group,n=50).The expression of 9 inflammatory cytokines in patients at preoperation,postoperative day 1(POD1)and POD7 was quantified by Luminex Multiplex assay.The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR.Results:Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels.Compared to OLR,the POD1 levels of granulocytemacrophage colony-stimulating factor(GM-CSf),interleukin-6(IL-6),IL-8,and monocyte chemoattractant protein-1(MCP-1)in the LLR group were significantly lower.Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation.The levels of these cytokines were positively associated with postoperative liver injury,and the length of hospital stay.Importantly,a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection.Conclusions:Significantly lower level of GM-CSf,IL-6,IL-8,and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.

关键词： Laparoscopic liver resection Open liver resection Hepatocellular carcinoma Postoperative cytokines Inflammatory responses

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