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Role of N-formyl peptide receptor 2 in germinal matrix hemorrhage:an intrinsic review of a hematoma resolving pathway

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Neural Regeneration Research 2024年第2期19卷 350-354页

作者： Jerry Flores Jiping Tang department of Physiology&pharmacology Loma Linda University School of MedicineLoma LindaCAUSA

Germinal matrix hemorrhage is one of the leading causes of morbidity,mortality,and acquired infantile hydrocephalus in preterm infants in the United States,with little progress made in its clinical *** clots have been shown to elicit secondary brain injury after germinal matrix hemorrhage,by disrupting normal cerebrospinal fluid circulation and absorption after germinal matrix hemorrhage causing post-hemorrhagic hydrocephalus *** evidence suggests that rapid hematoma resolution is necessary to improve neurological outcomes after hemorrhagic *** articles have demonstrated the beneficial effects of stimulating the polarization of microglia cells into the M2 phenotype,as it has been suggested that they play an essential role in the rapid phagocytosis of the blood clot after hemorrhagic models of stroke.N-formyl peptide receptor 2(FPR2),a G-protein-coupled receptor,has been shown to be neuroprotective after ***2 activation has been associated with the upregulation of phagocytic macrophage clearance,yet its mechanism has not been fully *** literature suggests that FPR2 may play a role in the stimulation of scavenger receptor *** receptor CD36 plays a vital role in microglia phagocytic blood clot clearance after germinal matrix ***2 has been shown to phosphorylate extracellular-signal-regulated kinase 1/2(ERK1/2),which then promotes the transcription of the dual-specificity protein phosphatase 1(DUSP1)*** this review,we present an intrinsic outline of the main components involved in FPR2 stimulation and hematoma resolution after germinal matrix hemorrhage.

关键词： AnxA1 FPR2 GMH hematoma resolution hemorrhagic stroke M1 M2 microglia polarization microglia phagocytosis

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Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA department of pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA department of medicine University of Rochester School of Medicine and DentistryRochesterNYUSA department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pathology and Laboratory medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

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Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

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World Journal of Gastroenterology 2024年第18期30卷 2387-2390页

作者： Aleksandra Boldys Lukasz Buldak department of Internal medicine and Clinical pharmacology School of Medicine in KatowiceMedical University of SilesiaKatowice 40-752Poland

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within *** redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated *** is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic *** challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic ***,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid ***,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic *** is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

关键词： Metabolic dysfunction-associated steatotic liver disease Diagnostics Pathophysiology of metabolic dysfunction-associated steatotic liver disease Therapy of metabolic dysfunction-associated steatotic liver disease Therapeutic innovations

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Na^(+)/K^(+)-ATPase:ion pump,signal transducer,or cytoprotective protein,and novel biological functions

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Neural Regeneration Research 2024年第12期19卷 2684-2697页

作者： Songqiang Huang Wanting Dong Xiaoqian Lin Jinsong Bian department of pharmacology Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and DiseasesSchool of MedicineSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina department of pharmacology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into ***,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell ***^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of *** re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological ***,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell *** recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's *** of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these *** this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell ***,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related *** potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.

关键词： antibody biological functions cellular communication electrochemical gradient ion balance ion channels Na^(+)/K^(+)-ATPase neurological diseases neurotransmitter release signal transduction

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CRISPR-Cas9 gene editing strengthens cuproptosis/chemodynamic/ferroptosis synergistic cancer therapy

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4059-4072页

作者： Xiaoyu Wu Zijun Bai Hui Wang Hanqing Wang Dahai Hou Yunzhu Xu Guanqun Wo Haibo Cheng Dongdong Sun Weiwei Tao department of Surgical Oncology Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029China school of Integrated medicine Nanjing University of Chinese MedicineNanjing 210023China Jiangsu Collaborative Innovation Center of Traditional Chinese medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjing 210023China school of pharmacology Nanjing University of Chinese MedicineNanjing 210023China school of pharmacology Ningxia Medical UniversityYinchuan 750004China

Copper-based nanomaterials demonstrate promising potential in cancer *** efficiently triggers a Fenton-like reaction and further consumes the high level of glutathione,initiating chemical dynamic therapy(CDT)and ***,a newly identified cell death modality that represents a great prospect in cancer therapy,is ***,active homeostatic systems rigorously keep copper levels within cells exceptionally low,which hinders the application of cooper nanomaterials-based ***,a novel strategy of CRISPR-Cas9 RNP nanocarrier to deliver cuprous ions and suppress the expression of copper transporter protein ATP7A for maintaining a high level of copper in cytoplasmic fluid is *** Cu2O and organosilica shell would degrade under the high level of glutathione and weak acidic environment,further releasing RNP and *** liberated Cut triggered a Fenton-like reaction for CDT and partially transformed to Cu2t,consuming intracellular GSH and initiating cuproptosis and ferroptosis ***,the release of RNP effectively reduced the expression of copper transporter ATP7A,subsequently increasing the accumulation of cooper and enhancing the efficacy of CDT,cuproptosis,and *** tumor microenvironment responsive multimodal nanoplatform opens an ingenious avenue for colorectal cancer therapy based on gene editing enhanced synergistic cuproptosis/CDT/ferroptosis.

关键词： GSH-and pH-responsive Effective copper delivery CRISPR-Cas9 ATP7A Cuproptosis Chemodynamic Ferroptosis Synergistic therapy

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Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke

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Stroke & Vascular Neurology 2024年第4期9卷 367-379,I0022-I0031页

作者： Tianchi Tang Li-bin Hu Chao Ding Zhihua Zhang Ning Wang Tingting Wang Hang Zhou Siqi Xia Linfeng Fan Xiong-jie Fu Feng Yan Xiangnan Zhang Gao Chen Jianru Li department of Neurosurgery Zhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 2NeurosurgeryZhejiang University School of Medicine Second Affiliated HospitalHangzhouZhejiangChina 3Zhejiang University School of MedicineHangzhouZhejiangChina 4Zhejiang University Department of PharmacologyHangzhouZhejiangChina

Background Ischaemic stroke triggers neuronal mitophagy,while the involvement of mitophagy receptors in ischaemia/reperfusion(I/R)injury-induced neuronal mitophagy remain not fully ***,we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1(FUNDC1)and its modulation in neuronal mitophagy induced by I/R *** Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I/R injury,including transient middle cerebral artery occlusion(tMCAO)in vivo and oxygen glucose deprivation/reperfusion in *** outcomes of mice with two genotypes were *** mitophagy was analysed both in vivo and in *** of FUNDC1 and its regulator Src were *** impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist *** To our surprise,FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type *** neuronal mitophagy could be activated by I/R injury,FUNDC1 deletion did not disrupt neuronal *** activation of FUNDC1,represented by dephosphorylation of Tyr18,was detected in the early stages(within 3hours)of neuronal I/R injury;however,phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages(after 6hours),accompanied by a decrease in FUNDC1-light chain 3 *** inactivation of FUNDC1 was associated with Src activation,represented by phosphorylation of Tyr416,which changed in parallel with the level of phosphorylated FUNDC1(Tyr18)during neuronal I/R ***,FUNDC1-mediated mitophagy in neurons under I/R conditions can be rescued by pharmacological inhibition of *** FUNDC1 is inactivated by Src during the later stage(after 6hours)of neuronal I/R injury,and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.

关键词： FUNDC1 involvement injury

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CRABP1-mediated non-canonical retinoic acid signaling in motor neurons and neural stem cells

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Neural Regeneration Research 2024年第6期19卷 1169-1170页

作者： Li-Na Wei department of pharmacology University of Minnesota Medical SchoolMinneapolisMNUSA

Retinoic acid(RA),the active metabolite of vitamin A(the retinoids),elicits a wide spectrum of biological activities critical to the development and health of most of the organ systems including the nervous systems(Corcoran et al.,2002).The effects of RA are mediated by two very distinct pathways;the first is manifested in the nucleus by binding to a large family of nuclear RA receptors(RARs)to regulate proper expression of RAtargeted genes.

关键词： canonical spectrum critical

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From the dust:extracellular vesicles as regulators of development and neuroregeneration

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Neural Regeneration Research 2024年第5期19卷 933-934页

作者： Leon G.Coleman Jr The university of North Carolina at Chapel Hill School of MedicineDepartment of PharmacologyBowles Center for Alcohol StudiesChapel HillNCUSA

First impressions can have a lasting *** science,this can be especially problematic,because our lack of understanding often causes us to mislabel and thus ignore important biological *** this vein,extracellular vesicles(EVs)were once considered to be“cellular dust”.Similar to the previous concept of“junk DNA”to describe protein non-coding regions,EVs are far more than just cellular *** fact,EVs are emerging as key mediators of intracellular communication across nearly all biological *** includes peripheral immune responses(e.g.,arthropathies and sepsis),intra-organ communication(Seim et al.,2023),and a host of other physiological and pathological states(Figure 1A and B).

关键词： Figure extracellular

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Twisted fiber microfluidics:a cutting-edge approach to 3D spiral devices

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Microsystems & Nanoengineering 2024年第1期10卷 193-202页

作者： Shunsuke Kato Daniel W.Carlson Amy Q.Shen Yuanyuan Guo department of Electrical Information and Physics EngineeringSchool of EngineeringTohoku UniversityAoba-kuSendai 980-8579 MiyagiJapan Micro/Bio/Nanofluidics Unit Okinawa Institute of Science and TechnologyOnnaKunigami-gun 904-0495 OkinawaJapan Frontier Research Institute for Interdisciplinary Sciences(FRIS) Tohoku UniversityAoba-kuSendai 980-0845 MiyagiJapan Graduate school of Biomedical Engineering Tohoku UniversityAoba-kuSendai 980-8579 MiyagiJapan department of Physiology Graduate School of MedicineTohoku UniversityAoba-kuSendai 980-8575 MiyagiJapan

The development of 3D spiral microfluidics has opened new avenues for leveraging inertial focusing to analyze small fluid volumes,thereby advancing research across chemical,physical,and biological *** traditional straight microchannels rely solely on inertial lift forces,the novel spiral geometry generates Dean drag forces,eliminating the necessity for external fields in fluid ***,fabricating 3D spiral microfluidics remains a labor-intensive and costly endeavor,hindering its widespread ***,conventional lithographic methods primarily yield 2D planar devices,thereby limiting the selection of materials and geometrical *** address these challenges,this work introduces a streamlined fabrication method for 3D spiral microfluidic devices,employing rotational force within a miniaturized thermal drawing process,termed as *** innovation allows for rapid prototyping of twisted fiber-based microfluidics featuring versatility in material selection and heightened geometric *** validate the performance of these devices,we combined computational modeling with microtomographic particle image velocimetry(uTPiM)to comprehensively characterize the 3D flow *** results corroborate the presence of a steady secondary flow,underscoring the effectiveness of our *** 3D spiral microfluidics platform paves the way for exploring intricate microflow dynamics,with promising applications in areas such as drug delivery,diagnostics,and lab-on-a-chip systems.

关键词： thereby straight twisted

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Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 613-624页

作者： Akitoshi Sano Jun Inoue Eiji Kakazu Masashi Ninomiya Mio Tsuruoka Kosuke Sato Masazumi Onuki Satoko Sawahashi Keishi Ouchi Atsushi Masamune Division of Gastroenterology Tohoku University Graduate School of MedicineSendaiMiyagiJapan department of Liver Disease The Research Center for Hepatitis and ImmunologyNational Center for Global Health and MedicineIchikawaChibaJapan

Background and Aims:Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma(HCC).Given their diverse physiological activities,we hypothesized that plasma fatty acids might influence the progression of *** study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with ***:In this singlecenter retrospective study,we registered 516 cases and analyzed 414 cases of liver cirrhosis and *** skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar *** cutoff value for sarcopenia followed the criteria set by the Japan Society of *** acid concentrations were measured by gas ***:Fatty acid levels,particularly omega-3(n-3)polyunsaturated fatty acid(PUFA),were lower in patients with poor liver function(Child-Pugh grade B/C)and were negatively correlated with the albumin-bilirubin score(p<0.0001).The prognosis of HCC patients with low PUFA levels was significantly *** the different fatty acid fractions,only n-3 PUFAs significantly correlated with skeletal muscle mass index(p=0.0026).In the multivariate analysis,the n-3 PUFA level was an independent variable associated with sarcopenia(p=0.0006).Conclusions:A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

关键词： Liver cirrhosis Hepatocellular carcinoma Sarcopenia Skeletal Muscle Fatty Acids Omega-3 polyunsaturated fatty acids

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