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Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2024年第13期30卷 1899-1910页

作者： Ante Tonkic Marko Kumric Ivna Akrapovic Olic Doris Rusic Piero Marin Zivkovic Daniela Supe Domic Zeljko Sundov Ivan Males Josko Bozic biology of Neoplasms University of Split School of MedicineSplit 21000Croatia department of Pathophysiology University of Split School of MedicineSplit 21000Croatia department of Gastroenterology University Hospital of SplitSplit 21000Croatia department of Pharmacy University of Split School of MedicineSplit 21000Croatia department of Medical Laboratory Diagnostics University Hospital of SplitSplit 21000Croatia department of Health Studies University of SplitSplit 21000Croatia department of Internal medicine University of Split School of MedicineSplit 21000Croatia department of Surgery University Hospital of SplitSplit 21000Croatia

BACKGROUND Population of patients with inflammatory bowel disease(IBD)is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and ***-differentiation factor-15(GDF-15)is often overexpressed under stress conditions,such as inflammation,malignancies,heart failure,myocardial ischemia,and many *** To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple *** additional aim was to determine possible associations between GDF-15 and multiple clinical,anthropometric and laboratory parameters in patients with *** This cross-sectional study included 90 adult patients diagnosed with IBD,encompassing both Crohn’s disease(CD)and ulcerative colitis(UC),and 67 healthy age-and sex-matched *** patients underwent an extensive workup,including colonoscopy with subsequent histopathological *** activity was assessed by two independent gastroenterology consultants specialized in IBD,employing well-established clinical and endoscopic scoring ***-15 serum concentrations were determined following an overnight fasting,using electrochemiluminescence *** In patients with IBD,serum GDF-15 concentrations were significantly higher in comparison to the healthy controls[800(512-1154)pg/mL vs 412(407-424)pg/mL,P<0.001],whereas no difference in GDF-15 was found between patients with CD and UC[807(554-1451)pg/mL vs 790(509-956)pg/mL,P=0.324].Moreover,multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age,sex,and C-reactive protein levels(P=0.016 and P=0.049,respectively).Finally,an association between GDF-15 and indices of anemia was ***,negative correlations were found between GDF-15 and serum iron levels(r=-0.248,P=0.021),as well as GDF-15 and hemoglobin(r=-0.351,P=0.021).Accordingly,in comparison to I

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Growth-differentiation factor-15 Anemia Extraintestinal manifestations

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Top Five Stories of the Cellular Landscape and Therapies of Atherosclerosis:Current Knowledge and Future Perspectives

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Current Medical Science 2024年第1期44卷 1-27页

作者： Qi PAN Cheng CHEN Yue-jin YANG State Key Laboratory of cardiovascular Disease Department of CardiologyFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China

Atherosclerosis(AS)is characterized by impairment and apoptosis of endothelial cells,continuous systemic and focal inflammation and dysfunction of vascular smooth muscle cells,which is documented as the traditional cellular ***,the mechanisms appear much more complicated than we thought since a bulk of studies on efferocytosis,transdifferentiation and novel cell death forms such as ferroptosis,pyroptosis,and extracellular trap were *** of novel pathological cellular landscapes provides a large number of therapeutic *** the other side,the unsatisfactory therapeutic effects of current treatment with lipid-lowering drugs as the cornerstone also restricts the efforts to reduce global AS *** cell-or nanoparticle-based strategies spurred a lot of attention due to the attractive therapeutic effects and minimized adverse *** the complexity of pathological changes of AS,attempts to develop an almighty medicine based on single mechanisms could be theoretically *** this review,the top stories in the cellular landscapes during the initiation and progression of AS and the therapies were summarized in an integrated perspective to facilitate efforts to develop a multi-targets strategy and fill the gap between mechanism research and clinical *** future challenges and improvements were also discussed.

关键词： atherosclerosis transdifferentiation extracellular traps efferocytosis stem cell nanoparticles

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New evidence for the epigenetic regulation of skeletal stem cells

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Science Bulletin 2024年第13期69卷 2004-2006页

作者： Liming Zhao Jun Xiao Charles K.F.Chan Institute for Stem Cell biology and Regenerative medicine Stanford University School of MedicineStanford CA 94305USA department of Surgery Division of Plastic and Reconstructive SurgeryStanford University School of MedicineStanford CA 94305USA department of Orthopaedic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Skeletal stem cells(SSCs)are crucial for skeletal development and regeneration,yet the epigenetic regulation of these cells remains poorly *** studies have delineated the epigenetic landscape across the developmental trajectory of SSCs,highlighting the involvement of Ptip in regulating SSC *** skeletal system undergoes dynamic remodeling throughout *** stem cells(SSCs),residing within the skeleton and lineage-restricted,serve as a cellular reserve to foster development and maintain skeletal *** categorized within the broader mesenchymal stromal/stem cells(MSCs).

关键词： skeletal involvement maintain

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Connecting cellular mechanisms and extracellular vesicle cargo in traumatic brain injury

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Neural Regeneration Research 2024年第10期19卷 2119-2131页

作者： Nikita Ollen-Bittle Austyn D.Roseborough Wenxuan Wang Jeng-liang D.Wu Shawn N.Whitehead department of Anatomy and Cell biology Western UniversityLondonONCanada Schulich School of medicine and Dentistry Western UniversityLondonONCanada Deparment of Clinical Neurological Sciences Western UniversityLondonONCanada

Traumatic brain injury is followed by a cascade of dynamic and complex events occurring at the cellular level. These events include: diffuse axonal injury, neuronal cell death, blood-brain barrier break down, glial activation and neuroinflammation, edema, ischemia, vascular injury, energy failure, and peripheral immune cell infiltration. The timing of these events post injury has been linked to injury severity and functional outcome. Extracellular vesicles are membrane bound secretory vesicles that contain markers and cargo pertaining to their cell of origin and can cross the blood-brain barrier. These qualities make extracellular vesicles intriguing candidates for a liquid biopsy into the pathophysiologic changes occurring at the cellular level post traumatic brain injury. Herein, we review the most commonly reported cargo changes in extracellular vesicles from clinical traumatic brain injury samples. We then use knowledge from animal and in vitro models to help infer what these changes may indicate regrading cellular responses post traumatic brain injury. Future research should prioritize labeling extracellular vesicles with markers for distinct cell types across a range of timepoints post traumatic brain injury.

关键词： axonal injury biomarkers blood-brain barrier chronic traumatic encephalopathy extracellular vesicles glial activation neuroinflammation traumatic brain injury

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Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

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Molecular Plant 2024年第6期17卷 884-899页

作者： Liping Zeng Maria Fernanda Gomez Mendez Jingzhe Guo Jishan Jiang Bailong Zhang Hao Chen Brandon Le Haiyan Ke Katayoon Dehesh department of Botany and Plant Sciences Institute of Integrative Genome BiologyUniversity of CaliforniaRiversideRiversideCA 92521USA School of medicine University of CaliforniaRiversideRiversideCA 92521USA

Stress-induced retrograde signal transmission from the plastids to the nucleus has long puzzled plant *** address this,we performed a suppressor screen of the ceh1 mutant,which contains elevated 2-C-methyl-d-erythritol-2,4-cyclopyrophosphate(MEcPP)levels,and identified the gain-of-function mutant impα-9,which shows reversed dwarfism and suppressed expression of stress-response genes in the ceh1 background despite heightened *** genetic and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in Arabidopsis SKP1-like 1(ASK1)abundance,a pivotal component in the proteasome degradation *** increase in ASK1 prompts the degradation of IMPα-***,we uncovered a protein-protein interaction between IMPα-9 and TPR2,a transcriptional co-suppressor and found that a reduction in IMPα-9 levels coincides with a decrease in TPR2 ***,the interaction between IMPα-9 and TPR2 was disrupted in impα-9 mutants,highlighting the critical role of a single amino acid alteration in maintaining their *** of their interaction results in the reversal of MEcPP-associated *** immunoprecipitation coupled with sequencing analyses revealed that TPR2 binds globally to stress-response genes and suggested that IMPα-9 associates with the *** function together to suppress the expression of stress-response genes under normal conditions,but this suppression is alleviated in response to stress through the degradation of the suppressing *** biological relevance of our discoveries was validated under high light stress,marked by MEcPP accumulation,elevated ASK1 levels,IMPα-9 degredation,reduced TPR2 abundance,and subsequent activation of a network of stress-response *** summary,our study collectively unveils fresh insights into plant adaptive mechanisms,highlighting intricate interactions among retrograde signaling,the proteasome,and nuclear transport machinery.

关键词： plastidial retrograde signal MEcPP ASK1 impα-9 TPR2

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Current knowledge for the risk factors of early permanent pacemaker implantation following transcatheter aortic valve replacement and what is next for the primary prevention?

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World Journal of Cardiology 2024年第2期16卷 54-57页

作者： Gen-Min Lin Wei-Chun Huang Chih-Lu Han department of medicine Hualien Armed Forces General HospitalHualien 970Taiwan cardiovascular Center Kaohsiung Veterans General HospitalKaohsiung 81346Taiwan department of medicine Taipei Veterans General HospitalTaipei 112Taiwan

In this editorial,we comprehensively summarized the preoperative risk factors of early permanent pacemaker implantation after transcatheter aortic valve replacement(TAVR)among patients with severe aortic stenosis from several renowned clinical studies and focused on the primary prevention of managing the modifiable factors,e.g.,paroxysmal atrial fibrillation before the TAVR.

关键词： Permanent pacemaker implantation Transcatheter aortic valve replacement Interventricular conduction delay Diabetes Supraventricular arrhythmia

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Rheum palmatum L. and Salvia miltiorrhiza Bge. Alleviates Acute Pancreatitis by Regulating Th17 Cell Differentiation: An Integrated Network Pharmacology Analysis, Molecular Dynamics Simulation and Experimental Validation

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Chinese Journal of Integrative medicine 2024年第5期30卷 408-420页

作者： FENG Min-chao LUO Fang HUANG Liang-jiang LI Kai CHEN Zu-min LI Hui YAO Chun QIN Bai-jun CHEN Guo-zhong The First Clinical Medical College Guangxi University of Traditional Chinese MedicineNanning 530000China Guangxi Key Laboratory of Molecular biology of Traditional Chinese medicine and Preventive medicine Nanning 530000China Graduate School Guangxi University of Traditional Chinese MedicineNanning 530000China department of Gastroenterology the First Affiliated Hospital of Guangxi University of Traditional Chinese MedicineNanning 530023China

Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics ***, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.

关键词： Rheum palmatum L. Salvia miltiorrhiza Bge. molecular docking simulation network pharmacology acute pancreatitis Th17 cell differentiation

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Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm

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World Journal of Cardiology 2024年第2期16卷 58-63页

作者： Amedeo Tirandi Elisa Schiavetta Elia Maioli Fabrizio Montecucco Luca Liberale department of Internal medicine University of GenoaGenoa 16132Italy IRCCS Ospedale Policlinico San Martino Genoa–Italian Cardiovascular NetworkGenoa 16132Italy

Myeloproliferative neoplasms(MPN)are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem *** are clinically classifiable into four main diseases:chronic myeloid leukemia,essential thrombocythemia,polycythemia vera,and primary *** pathologies are closely related to cardio-and cerebrovascular diseases due to the increased risk of arterial thrombosis,the most common underlying cause of acute myocardial *** evidence shows that the classical Virchow triad(hypercoagulability,blood stasis,endothelial injury)might offer an explanation for such ***,patients with MPN might have a higher number and more reactive circulating platelets and leukocytes,a tendency toward blood stasis because of a high number of circulating red blood cells,endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal *** abnormal cancer cells,especially when associated with the JAK2V617F mutation,tend to proliferate and secrete several inflammatory *** sustains a pro-inflammatory state throughout the *** direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus ***,MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.

关键词： Inflammation Myeloproliferative neoplasm Acute coronary syndrome Myocardial infarction Thrombosis Cancer

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M^(6)A modification in cardiovascular disease:With a focus on programmed cell death

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Genes & Diseases 2024年第5期11卷 272-284页

作者： Wen Li Yao Liu Ruiyan Xu Yuan Zong Lu He Jun Hu Guohua Li Institute of cardiovascular Disease Key Laboratory for Arteriosclerology of Hunan ProvinceHunan International Scientific and Technological Cooperation Base of Arteriosclerotic DiseaseDepartment of PathophysiologyMOE Key Lab of Rare Pediatric DiseasesHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China department of cardiovascular medicine The Second Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China department of Obstetrics and Gynecology The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China department of cardiovascular Surgery The Second Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China

N^(6)-methyladenosine(m^(6)A)methylation is one of the most predominant internal RNA modifications in eukaryotes and has become a hot spot in the field of epigenetics in recent *** diseases(CVDs)are a leading cause of death *** evidence demonstrates that RNA modifications,such as the m^(6)A modification,are associated with the development and progression of many diseases,including *** increasing body of studies has indicated that programmed cell death(PCD)plays a vital role in ***,the molecular mechanisms underlying m^(6)A modification and PCD in CVDs remain poorly ***,elaborating on the highly complex connections between the m^(6)A mechanisms and different PCD signaling pathways and clarifying the exact molecular mechanism of m^(6)A modification mediating PCD have significant meaning in developing new strategies for the prevention and therapy of *** is great potential for clinical application.

关键词： Apoptosis Autophagy cardiovascular diseases Ferroptosis N^(6)-methyladenosine Programmed cell death Pyroptosis

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Going only half the way:cell cycle exit after the G1 restriction point

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Signal Transduction and Targeted Therapy 2024年第1期9卷 1-2页

作者： Lisa Muller Tony Gutschner Mechthild Hatzfeld department of Pathobiochemistry Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany department of RNA biology and Pathogenesis Institute of Molecular MedicineMartin Luther University Halle-WittenbergCharles Tanford Protein Research CenterHalleGermany

In a recent article published in Nature,James *** et *** that cyclin A2 levels determine whether cells will make an entrance into mitosis or whether cells will leave the cell cycle after having passed the G1/restriction(R)-point implicating that the decision is fully reversible(Fig.1).This ground-breaking study could impact future approaches for cancer treatment by targeting the mitotic clock.

关键词： point cycle

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