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Non-pancreatic hyperlipasemia:A puzzling clinical entity

World Journal of Gastroenterology 2024年第19期30卷 2538-2552页

作者： Krisztina Eszter Feher David Tornai Zsuzsanna Vitalis Laszlo Davida Nora Sipeki Maria Papp Division of Gastroenterology Department of Internal MedicineFaculty of MedicineUniversity of DebrecenDebrecen H-4032Hajdu-BiharHungary Kalman Laki doctoral School of biomedical and Clinical sciences Faculty of MedicineUniversity of DebrecenDebrecen H-4032Hungary

BACKGROUND Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis(AP)but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism.This non-pancreatic hyperlipasemia(NPHL)is puzzling for attending physicians during the diagnostic procedure for AP.It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it.A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.AIM To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.METHODS A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal(ULN)was prospectively evaluated over 31 months.Patients were identified using daily electronic laboratory reports developed to support an ongoing observational,multicenter,prospective cohort study called the EASY trial(ISRCTN10525246)to establish a simple,easy,and accurate clinical scoring system for early prognostication of AP.Diagnosis of NPHL was established based on≥3×ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.RESULTS A total of 808 patients[male,n=420(52%);median age(IQR):65(51-75)years]were diagnosed with≥3×ULN serum lipase levels.A total of 392 patients had AP,whereas 401 had NPHL with more than 20 different etiologies.Sepsis and acute kidney injury(AKI)were the most prevalent etiologies of NPHL(27.7%and 33.2%,respectively).The best discriminative cut-off value for lipase was≥666 U/L(sensitivity,71.4%;specificity,88.8%).The presence of AKI or sepsis negatively affected the diagnostic performance of lipase.NPHL was associated with a higher in-hospital mortalit

关键词： Non-pancreatic hyperlipasemia Acute pancreatitis Glycoprotein 2 Acute kidney injury Sepsis Mortality

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Perspectives for delivery of therapeutics by extravasation of biodegradable microspheres in the brain

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Neural Regeneration Research 2024年第5期19卷 969-970页

作者： Anne-Eva van der Wijk Ed VanBavel Amsterdam UMC location University of Amsterdam Department of Biomedical Engineering and PhysicsAmsterdamThe Netherlands Amsterdam Neuroscience Neurovascular Disorders ProgramAmsterdamThe Netherlands Amsterdam Cardiovascular sciences Microcirculation ProgramAmsterdamThe Netherlands

Development of therapeutics for brain diseases has remained challenging,in particular due to the difficulty of passing the blood-brain barrier.As a result,the current arsenal of therapeutics targeting the brain is limited to small,lipid-soluble drugs and there is a lack of options for treating neuroblastomas,Alzheimer’s disease,and many other devastating pathologies.Despite the advances in strategies for crossing the blood-brain barrier such as the use of nanoparticles(Hersh et al.,2022;Duan et al.,2023),such delivery systems have not yet reached clinical practice.Therefore,novel platforms for the transport of therapeutics across the blood-brain barrier remain highly desired.This specifically holds for large molecules such as monoclonal antibodies and recombinant proteins,as well as nucleotide-based therapeutics and cell therapies.Research efforts in this field are increasing exponentially,with thousands of publications in the last few years.

关键词： therapeutics holds spite

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NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

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Neural Regeneration Research 2024年第9期19卷 1961-1966页

作者： Napissara Boonpraman Sun Shin Yi BK21 four program Department of Medical SciencesSoonchunhyang UniversityAsanSouth Korea Department of biomedical Laboratory Science Soonchunhyang UniversityAsanSouth Korea iConnectome Co.Ltd.CheonanSouth Korea

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

关键词： Alzheimer’s disease astrocytes mitochondrial dysfunction myeloperoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases osteopontin Parkinson’s disease reactive oxygen species

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You had me at PELO:a"Ribosome Rescuer"induces NLR inflammasome assembly

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Cellular & Molecular Immunology 2024年第1期21卷 1-2页

作者： Zoie Magri Alexander Poltorak Graduate program in Immunology Tufts Graduate School of Biomedical Sciences136 Harrison AvenueBostonMA02111USA Department of Immunology Tufts University School of MedicineBostonMA02111USA

Pyroptosis,an inflammatory form of programmed cell death,eliminates a niche where pathogens replicate,providing overall benefits to a host.When left uncontrolled,pyroptosis can lead to severe pathology.Overactive pyroptotic activation has been implicated in neuroinflammation,cardiovascular disease,acute respiratory distress syndrome(ARDS),and many other diseases[1,2,3].Because of its multiple and permanent consequences,pyroptosis is a highly regulated signaling pathway.Major regulators of pyroptosis are NLR inflammasomes,which are activated by various“danger”signals such as ATP.

关键词： inflam NLR distress

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Inflammatory bowel disease(ulcerative colitis type)severity shows inverse correlation with semen parameters and testosterone levels

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Asian Journal of Andrology 2024年第2期26卷 155-159页

作者： Darmadi Darmadi Cennikon Pakpahan Rajender Singh Ankur Saharan Wanly Syahrizal Pasaribu Hermansyah Hermansyah Andri Rezano Department of Internal Medicine Faculty of MedicineUniversitas Sumatera UtaraMedan 20155Indonesia Andrology Study program Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Department of biomedical sciences Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Division of Endocrinology Central Drug Research InstituteLucknowUtar Pradesh 226031India Amity University LucknowUttar Pradesh 226010India Department of biomedical sciences Faculty of MedicineUniversitas PadjadjaranSumedang 45363Indonesia

Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual dysfunction.Although the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and fertility.To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,Indonesia.The patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these groups.In addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient grouping.Sperm concentration,motility,and morphology were found to decline significantly with an increase in IBD severity.Without classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,P<0.0001),rapid progressive motility(r=-0.660,P<0.0001),free testosterone(r=-0.732,P<0.0001),and total testosterone(r=-0.721,P<0.0001),and positivecorrelations with immotile sperm(r=0.660,P<0.0001),abnormal morphology(r=0.657,P<0.0001),and sex hormone-binding globulin(SHBG;r=0.278,P=0.002).Sperm concentration,motility,and morphology declined significantly with the severity of IBD.This study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.

关键词： inflammatory bowel disease reproductive health sexual health sperm parameter testosterone

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Three-dimensional morphological and fluorescent imaging of zebrafish with a continuous-rotational light-sheet microscope

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Journal of Innovative Optical Health sciences 2024年第2期17卷 59-66页

作者： Dongmin Zhang Guang Yang Yao Tan Chong Chen Jie Zhang Hui Li School of biomedical Engineering(Suzhou)Division of Life sciences and Medicine University of Science and Technology of China Hefei 230041 P.R.China Suzhou Institute of biomedical Engineering and Technology Chinese A cademy of sciences Suzhou Jiangsu 215163P.R.China

Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.

关键词： Light-sheet microscope zebrafish blood vessels morphology

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Tumor microenvironment-activatable neuropeptide-drug conjugates enhanced tumor penetration and inhibition via multiple delivery pathways and calcium deposition

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Chinese Chemical Letters 2024年第4期35卷 292-297页

作者： Yi Cao Xiaojiao Ge Yuanyuan Wei Lulu He Aiguo Wu Juan Li Ningbo Key Laboratory of biomedical Imaging Probe Materials and Technology Zhejiang International Cooperation Base of Biomedical Materials Technology and ApplicationChinese Academy of Sciences(CAS)Key Laboratory of Magnetic Materials and DevicesNingbo Cixi Institute of Biomedical EngineeringZhejiang Engineering Research Center for Biomedical MaterialsNingbo Institute of Materials Technology and EngineeringChinese Academy of SciencesNingbo 315201China University of Chinese Academy of sciences Beijing 100049China Advanced Energy Science and Technology Guangdong Laboratory Huizhou 516000China

Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.

关键词： Neuropeptide-drug conjugate Tumor penetration Calcium deposition Tumor inhibition Triple-negative breast cancer

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of biomedical Engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Shanghai World Foreign Language Academy Beijing Advanced Innovation Center for biomedical Engineering School of Engineering MedicineBeihang University Beijing Key Lab of Cryo-biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, etc.Opportunities to translate LM materials into medicine and obstacles encountered in practices are discussed.Following that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

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Recent advances in small-scale hydrogel-based robots for adaptive biomedical applications

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Nano Research 2024年第2期17卷 649-662页

作者： Mingzhe Nie Qilong Zhao Xuemin Du Institute of biomedical&Health Engineering Shenzhen Institute of Advanced Technology(SIAT)Chinese Academy of Sciences(CAS)Shenzhen 518055China

Small-scale robots,ranging in size from micrometers to centimeters,have gained significant attention in the biomedical field.However,conventional small-scale robots made of rigid materials encounter challenges in adapting themselves to the soft tissues and complicated environments of human body.Compared to the rigid counterpart,small-scale hydrogel-based robots hold great promises due to their tissue-like low modulus,outstanding biocompatibility and accessible stimuli-responsive capabilities.These attributes offer small-scale hydrogel-based robots with multimodal locomotion and reinforced functions,further enhancing the adaptability in manipulation and tasks execution for various biomedical applications.In this review,we present recent advances in small-scale hydrogel-based robots.We first summarize the design principles of small-scale hydrogel-based robots including materials,fabrication techniques and manipulation strategies,then highlighting their upgraded functions and adaptive biomedical applications.Finally,we discuss existing challenges and future perspectives for small-scale hydrogel-based robots.

关键词： small-scale robot hydrogel locomotion multi-function adaptability

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Gas-generating polymersomes-based amplified photoimmunotherapy for abscopal effect and tumor metastasis inhibition

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Chinese Chemical Letters 2024年第6期35卷 456-461页

作者： Chenlu Huang Xinyu Yang Qingyu Yu Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

Due to the heterogeneity of tumors,single phototherapy cannot completely ablate tumors and inhibit tumor metastasis.To overcome these,we formulated targeted and multifunctional polymersomes ABC@ICGIMQ-LHRH(AIRL)that encapsulated Toll-like receptor(TLR)7/8 agonist imiquimod(IMQ)and photosensitizer indocyanine green(ICG)in the hydrophobic layer as well as bubble-generator NH_(4)HCO_(3) in the hydrophilic cavity to inhibit the growth of primary and distant tumors,and prevent tumor metastasis through synergistic photoimmunotherapy.The AIRL polymersomes exhibited uniform and stable size,and high drug encapsulation efficiency,acid/reduction/laser responsiveness,excellent photothermal conversion efficiency,effective reactive oxygen species generation,high tumor accumulation.AIRL could be effectively internalized by dendritic cells(DCs),achieve lysosome escape and enhance DCs maturation.The synergistic photoimmunotherapy via AIRL polymersomes remarkably promoted the differentiation and activation of T cells,elevated strong systemic immune response to eradicate primary tumors and inhibit the growth of distant tumors.Simultaneously,the endurable immunological memory prevented tumor metastasis,which provided a promising nanoplatform for the combination therapy of cancer.

关键词： Polymersomes Phototherapy Immunotherapy TLR 7/8 agonist Gas-generating

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