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NLRP3 inflammasome plays a vital role in the pathogenesis of age-related diseases in the eye and brain

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Neural Regeneration Research 2024年第7期19卷 1425-1426页

作者： Jack Jonathan Maran Odunayo Omolola Mugisho Buchanan Ocular therapeutics Unit Department of OphthalmologyNew Zealand National Eye CentreUniversity of AucklandAucklandNew Zealand

Key points:With aging,there is increased nucleotide-binding oligomerization domain-(NOD-)like receptor(NLR) protein-3(NLRP3) activation in neural and ocular *** of the NLRP3 inflammasome appears to be a common denominator in the pathogenesis of age-related diseases of the eye and *** inhibition of the NLRP3 inflammasome may be a potent therapy for preventing the development and progression of age-related eye and brain diseases.

关键词： NLRP3 pathogenesis inflam

Current and future trends in whole genome sequencing in cancer

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Cancer Biology & Medicine 2024年第1期21卷 16-20页

作者： Yuki Katsuya department of Experimental therapeutics National Cancer Center Hospital5-1-1 TsukijiChuo-kuTokyo 104-0045Japan

Cancer remains a formidable global health challenge affecting millions of lives *** decades,conventional cancer treatments used a one-size-fits-all approach,overlooking the intricate genetic variations that drive *** emergence of cancer genomics has ushered in a new era of personalized and targeted cancer *** Human Genome Project,which was launched in 1990 and completed in 2003。

关键词： cancer Cancer annually

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration Research 2024年第4期19卷 747-753页

作者： Peter H.King department of Neurology and Center for Neurodegeneration and Experimental therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical Center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda department of Medical Oncology Showa UniversityTokyo 1428555Japan department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic ***,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently *** SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe *** tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated *** RAS or BRAF mutations were *** Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was *** drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly ***,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse *** Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

Viral and nonviral nanocarriers for in vivo CRISPR-based gene editing

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Nano Research 2024年第10期17卷 8904-8925页

作者： Zhongyuan Guo Audrey T.Zhu Ronnie H.Fang Liangfang Zhang Aiiso Yufeng Li Family department of Chemical and Nano Engineering University of California San DiegoLa JollaCA 92093USA Division of Host-Microbe Systems and therapeutics Department of PediatricsUniversity of California San DiegoLa JollaCA 92093USA

The continued development of clustered regularly interspaced short palindromic repeats(CRISPR)technology has the potential to greatly impact clinical medicine,particularly for disease diagnosis and *** high demand for the in vivo delivery of CRISPR-based therapies,significant challenges *** include rapid degradation by enzymes,inefficient disease site targeting,and the risk of undesired off-target *** platforms,with their tailorable properties,have been engineered to efficiently package CRISPR payloads in various formats,including as plasmid DNA,mRNA,and ribonucleoprotein complexes,for in vivo *** them,recombinant adeno-associated viruses,virus-like particles,and lipid nanoparticles have displayed exceptional *** review will discuss the development of these and other nanocarriers for in vivo CRISPR-based genome editing.

关键词： clustered regularly interspaced short palindromic repeats(CRISPR) in vivo gene editing nanocarriers recombinant adeno-associated viruses(rAAVs) virus-like particle(VLP) lipid nanoparticle(LNP)

Initial decrease in the lipoprotein(a)level is a novel prognostic biomarker in patients with acute coronary syndrome

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World Journal of Cardiology 2024年第6期16卷 329-338页

作者： Yasuhiko Saeki Jun Sawaguchi Satori Akita Taka-aki Takamura Kosuke Fujibayashi Minoru Wakasa Hironobu Akao Michihiko Kitayama Yasuyuki Kawai Kouji Kajinami department of Cardiology Kanazawa Medical UniversityUchinada 9200293Japan Trans-catheter Cardiovascular therapeutics Kanazawa Medical UniversityUchinada 9200293Japan

BACKGROUND Lipoprotein(a)[Lp(a)]is a causal risk factor for atherosclerotic cardiovascular diseases;however,its role in acute coronary syndrome(ACS)remains *** To investigate the hypothesis that the Lp(a)levels are altered by various conditions during the acute phase of ACS,resulting in subsequent cardiovascular *** From September 2009 to May 2016,377 patients with ACS who underwent emergent coronary angiography,and 249 who completed≥1000 d of follow-up were ***(a)levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention(PCI)to 48 h after *** primary endpoint was the occurrence of major adverse cardiac events(MACE;cardiac death,other vascular death,ACS,and non-cardiac vascular events).RESULTS The mean circulating Lp(a)level decreased significantly from pre-PCI(0 h)to 12 h after(19.0 mg/dL to 17.8 mg/dL,P<0.001),and then increased significantly up to 48 h after(19.3 mg/dL,P<0.001).The changes from 0 to 12 h[Lp(a)Δ0-12]significantly correlated with the basal levels of creatinine[Spearman’s rank correlation coefficient(SRCC):-0.181,P<0.01]and Lp(a)(SRCC:-0.306,P<0.05).Among the tertiles classified according to Lp(a)Δ0-12,MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups(66.2%vs 53.6%,P=0.034).A multivariate analysis revealed that Lp(a)Δ0-12[hazard ratio(HR):0.96,95%confidence interval(95%CI):0.92-0.99]and basal creatinine(HR:1.13,95%CI:1.05-1.22)were independent determinants of subsequent *** Circulating Lp(a)levels in patients with ACS decreased significantly after emergent PCI,and a greater decrease was independently associated with a worse prognosis.

关键词： Lipoprotein(a) Acute coronary syndrome Percutaneous coronary intervention Major adverse cardiac events Prognosis

Sexual dimorphism of G protein-coupled receptor signaling in the brain

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Neural Regeneration Research 2024年第8期19卷 1635-1636页

作者： Sara Aljoudi Hamdan Hamdan Khaled S.Abd-Elrahman department of Physiology and Immunology College of Medicine and Health SciencesKhalifa UniversityAbu DhabiUnited Arab Emirates Healthcare Engineering Innovation Center(HEIC) Khalifa UniversityAbu DhabiUnited Arab Emirates department of Anesthesiology Pharmacology and Therapeuticsand Djavad Mowafaghian Center for Brain HealthUniversity of British ColumbiaVancouverBCCanada department of Pharmacology and therapeutics College of Medicine and Health ScienceKhalifa UniversityAbu DhabiUnited Arab Emirates department of Pharmacology and Toxicology Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by *** and Drug Administration-approved *** of the preclinical research to understand the pharmacology of... 详细信息

关键词： drugs clinical targeted

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of Digestive Disease and department of Medicine and therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage–bone interface

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The Innovation 2024年第2期5卷 88-97页

作者： Yijian Zhang Duo Li Yang Liu Liuqi Peng Dongdong Lu Pinpin Wang Dongxu Ke Huilin Yang Xuesong Zhu Changshun Ruan department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Research Center for Human Tissue and organ Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Novaprint therapeutics Suzhou Co. Ltd.Room 605B1 BuildingBioBayNo.218 Xinghu StreetSuzhou Industrial ParkSuzhou 215000China

Reconstruction of osteochondral(OC)defects represents an immense challenge due to the need for synchronous regeneration of special stratified *** revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure;however,their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are ***,inspired by natural OC bilayer features,anisotropic bicellular living hydrogels(ABLHs)simultaneously embedding articular cartilage progenitor cells(ACPCs)and bone mesenchymal stem cells(BMSCs)in stratified layers were precisely fabricated via two-channel extrusion *** optimum formulation of the 7%GelMA/3%AlgMA hydrogel bioink was demonstrated,with excellent printability at room temperature and maintained high cell ***,the chondrogenic ability of ACPCs and the osteogenic ability of BMSCs were demonstrated in vitro,confirming the inherent differential spatial regulation of ABLHs.

关键词： printing stratified boost