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Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

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Neural Regeneration Research 2025年第1期20卷 205-206页

作者： Sarah Fullam Sean O’Dowd Antoinette O’Connor Department of Neurology Tallaght University HospitalDublinIreland Academic unit of Neurology Trinity College DublinIreland

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of *** evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic *** the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for ***,the expensive and invasive nature of these tests limits their scalability.

关键词： Blood Alzheimer diagnosis

Ginsenoside Rg1 Attenuates Isoflurane-induced Caspase-3 Activation via Inhibiting Mitochondrial Dysfunction

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Biomedical and Environmental Sciences 2015年第2期28卷 116-126页

作者： MIAO Hui Hui ZHEN Yu DING Guan Nan HONG Fang Xiao XIE Zhong Cong TIAN Ming Beijing Friendship Hospital Capital Medical University Geriatric anesthesia Research unit Department of Anesthesia Critical Care and Pain Medicine Massachusetts General Hospital and Harvard Medical School

Objective The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rgl is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rgl can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction. Methods We investigated the effects of ginsenoside Rgl at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naive and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein （APP）（H4-APP cells）. For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore （mPTP） and adenosine-5＇-triphosphate （ATP） levels. We employed Western blot analysis, chemiluminescence, and flowcytometry. Results Here we show that pretreatment with 50 μmol/L ginsenoside Rgl for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 μmol/L ginsenoside Rgl for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naive and H4-APP cells. Conclusion These data suggest that ginsenoside Rgl may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rgl in preventing and treating isoflurane-induced neurotoxicity.

关键词： Ginsenoside Rgl Isoflurane Neurotoxicity Mitochondrial dysfunction

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Early respiratory complications after liver transplantation

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World Journal of Gastroenterology 2013年第48期19卷 9271-9281页

作者： Paolo Feltracco Cristiana Carollo Stefania Barbieri Tommaso Pettenuzzo Carlo Ori Department of Medicine Anesthesia and Intensive Care Unit Padova University Hospital35128 Padova Italy

The poor clinical conditions associated with end-stage cirrhosis,pre-existing pulmonary abnormalities,and high comorbidity rates in patients with high Model for End-Stage Liver Disease scores are all well-recognized factors that increase the risk of pulmonary complications after orthotopic liver transplantation(OLT)*** intraoperative and postoperative events,such as fluid overload,massive transfusion of blood products,hemodynamic instability,unexpected coagulation abnormalities,renal dysfunction,and serious adverse effects of reperfusion syndrome,are other factors that predispose an individual to postoperative respiratory *** advances in surgical techniques and anesthesiological management,the lung may still suffer throughout the perioperative period from various types of injury and ventilatory impairment,with different clinical *** complications after OLT can be classified as infectious or *** effusion,atelectasis,pulmonary edema,respiratory distress syndrome,and pneumonia may contribute considerably to early morbidity and mortality in liver transplant *** is of paramount importance to accurately identify lung disorders because infectious pulmonary complications warrant speedy and aggressive treatment to prevent diffuse lung injury and the risk of evolution into multisystem organ *** review discusses the most common perioperative factors that predispose an individual to postoperative pulmonary complications and these complications’early clinical manifestations after OLT and influence on patient outcome.

关键词： Respiratory complications Postoperative respiratory failure Liver transplantation Postoperative edema Post-transplant pneumonia

Nonintubated thoracic surgery: a lead role or just a walk on part?

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Chinese Journal of Cancer Research 2014年第5期26卷 507-510页

作者： Tommaso C.Mineo Federico Tacconi Thoracic Surgery Division Research Unit on Non-General Anesthesia in Thoracic Surgery00133Tor Vergata University

With the advent of the patient-centered health care concept, thoracic surgeons of the modern era are called to minimize at most the overall invasiveness of their performances, while increasing safety and effectiveness as much as possible. This need has driven an outstanding development of minimallyinvasive surgical approaches, which are now the standard to perform a broad spectrum of thoracic operations. A recent and fascinating evolution in this field is represented by the increasing interest toward the use of so-called ＂nonintubated＂ anesthesia protocol, which are expected to provide a further improvement in postsurgical outcomes （1-8）.

关键词： a lead role or just a walk on part Nonintubated thoracic surgery

Divergent expression of bacterial wall sensing toll-like receptors 2 and 4 in colorectal cancer

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World Journal of Gastroenterology 2017年第26期23卷 4831-4838页

作者： Karoliina Paarnio Sara Vayrynen Kai Klintrup Pasi Ohtonen Markus J Makinen Jyrki Makela Tuomo J Karttunen Oulu University Hospital and Medical Research Center Oulu Research unit of Surgery Anesthesia and Intensive CareUniversity of Oulu Cancer and Translational Medicine Research unit University of Oulu

To characterize the expression of toll-like receptors (TLR) 2 and 4 in colorectal cancer (CRC) and in normal colorectal mucosa. METHODSWe analysed tissue samples from a prospective series of 118 unselected surgically treated patients with CRC. Sections from formalin fixed, paraffin embedded specimens were analysed for TLR2 and TLR4 expression by immunohistochemistry. Two independent assessors evaluated separately expression at the normal mucosa, at the invasive front and the bulk of the carcinoma, and in the lymph node metastases when present. Expression levels in different locations were compared and their associations with clinicopathological features including TNM-stage and the grade of the tumour and 5-year follow-up observations were analysed. RESULTSNormal colorectal epithelium showed a gradient of expression of both TLR2 and TLR4 with low levels in the crypt bases and high levels in the surface. In CRC, expression of both TLRs was present in all cases and in the major proportion of tumour cells. Compared to normal epithelium, TLR4 expression was significantly weaker but TLR2 expression stronger in carcinoma cells. Weak TLR4 expression in the invasive front was associated with distant metastases and worse cancer-specific survival at 5 years. In tumours of the proximal colon the cancer-specific survival at 5 years was 36.9% better with strong TLR4 expression as compared with those with weak expression (P = 0.044). In contrast, TLR2 expression levels were not associated with prognosis. Tumour cells in the lymph node metastases showed higher TLR4 expression and lower TLR2 expression than cells in primary tumours. CONCLUSIONTumour cells in CRC show downregulation of TLR4 and upregulation of TLR2. Low expression of TLR4 in the invasive front predicts poor prognosis and metastatic disease.

关键词： Colorectal Cancer Toll-like receptor 2 Toll-like receptor 4 Inflammation Prognosis

Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural Regeneration Research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.R.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.R.Wayne Moore Jack P.Antel Neuroimmunology unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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Neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： Paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique Santamaría Clinical Neuroproteomics unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:Neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

Dexmedetomidine mitigates isoflurane-induced neurodegeneration in fetal rats during the second trimester of pregnancy

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Neural Regeneration Research 2017年第8期12卷 1329-1337页

作者： Zhi-yuan Su Qing Ye Xian-bao Liu Yu-zhong Chen Hong Zhan Shi-yuan Xu Department of anesthesia The Third Affiliated Hospital of Guangzhou Medical University Department of anesthesia Zhujiang Hospital of Southern Medical University

Dexmedetomidine has significant neuroprotective effects. However, whether its protective effects can reduce neurotoxicity caused by isoflurane in fetal brain during the second trimester of pregnancy remains unclear. In this study, timed-pregnancy rats at gestational day 14 spontaneously inhaled 1.5% isoflurane for 4 hours, and were intraperitoneally injected with dexmedetomidine at dosages of 5, 10, 20, and 20 μg/kg 15 minutes before inhalation and after inhalation for 2 hours. Our results demonstrate that 4 hours after inhaling isoflurane, 20 μg/kg dexmedetomidine visibly mitigated isoflurane-induced neuronal apoptosis, reversed downregulation of brain-derived neurotrophic factor expression, and lessened decreased spatial learning and memory ability in adulthood in the fetal rats. Altogether, these findings indicate that dexmedetomidine can reduce neurodegeneration induced by isoflurane in fetal rats during the second trimester of pregnancy. Further, brain-derived neurotrophic factor participates in this process.

关键词： nerve regeneration dexmedetornidine isoflurane fetal rat apoptosis brain-derived neurotrophic factor behavior neuroprotection neurodegeneration neural regeneration