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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam center for Cognitive Neurology and Alzheimer’s disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第9期20卷 2556-2570页

作者： Yongting Lv Hongfu Li department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina department of Medical Genetics and center for Rare disease Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina Nanhu Brain-Computer Interface Institute HangzhouZhejiang Province

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely *** principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial *** biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even *** these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and *** light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and ***,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal *** fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration *** DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related *** is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease *** the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable *** review summarizes the lat

关键词： amyotrophic lateral sclerosis biomarker blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain prognosis TAR DNA-binding protein 43

Application of virtual reality technology improves the functionality of brain networks in individuals experiencing pain

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World Journal of Clinical Cases 2025年第3期13卷 66-68页

作者： Takahiko Nagamine department of Psychiatric internal medicine Sunlight Brain Research CenterHofu 7470066YamaguchiJapan

Medical procedures are inherently invasive and carry the risk of inducing pain to the mind and ***,efforts have been made to alleviate the discomfort associated with invasive medical procedures through the use of virtual reality(VR)*** has been demonstrated to be an effective treatment for pain associated with medical procedures,as well as for chronic pain conditions for which no effective treatment has been *** precise mechanism by which the diversion from reality facilitated by VR contributes to the diminution of pain and anxiety has yet to be ***,the provision of positive images through VR-based visual stimulation may enhance the functionality of brain *** salience network is diminished,while the default mode network is ***,the medial prefrontal cortex may establish a stronger connection with the default mode network,which could result in a reduction of pain and *** research into the potential of VR technology to alleviate pain could lead to a reduction in the number of individuals who overdose on painkillers and contribute to positive change in the medical field.

关键词： Virtual reality Pain Anxiety Salience network Default mode network

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

Summary of the current guidelines for managing iatrogenic colorectal perforations and the evolving role of endoluminal vacuum therapy

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World Journal of Clinical Cases 2025年第6期13卷 1-8页

作者： Ahmed Tawheed Ibrahim Halil Bahcecioglu Mehmet Yalniz Mubin Ozercan Ali Cagri Oral Mohamed El-Kassas department of Endemic medicine Faculty of MedicineHelwan UniversityCairo 11795Egypt department of Gastroenterology Firat UniversityElazig 23119Türkiye Liver disease Research center College of MedicineKing Saud UniversityRiyadh 7805Saudi Arabia

Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal *** the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic *** recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased *** incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe ***,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case *** editorial provides an overview of the current guidelines for the management of iatrogenic colorectal *** insights are from the perspectives of endoscopists and *** also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency *** also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.

关键词： Colon Rectum Iatrogenic colonic perforation Colonoscopy Guidelines Endovacuum Endolumical vacuum therapy Endoscopic management

Septic shock due to cytomegalovirus colitis associated with rituximab use:A case report

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World Journal of Virology 2025年第1期14卷 118-123页

作者： Siddharth Patel Jordan Jay Prutha Pathak Mc Anto Antony Mrudula Thiriveedi department of internal medicine Decatur Morgan HospitalDecaturAL 35601United States department of medicine Alabama College of Osteopathic MedicineDothanAL 36303United States department of internal medicine North Alabama Medical CenterFlorenceAL 35630United States department of Endocrinology Diabetes and MetabolismMedical University of South Carolina/AnMed CampusAndersonSC 29621United States

BACKGROUND Cytomegalovirus(CMV)infections can cause significant morbidity and mortality in immunocompromised *** targets dysfunctional *** rituximab(RTX)therapy can cause B-lymphocyte dysfunction,increasing CMV ***,CMV infections present with critical illness such as septic *** SUMMARY A 64-year-old African American woman presented with generalized weakness and non-bloody watery diarrhea of 4-6 weeks *** did not have nausea,vomiting or,abdominal *** had been on monthly RTX infusions for neuromyelitis *** was admitted for septic shock due to *** investigations suggested pancytopenia and serology detected significantly elevated CMV *** treatment led to disease *** This case illustrates an extremely rare case of CMV colitis associated with RTX use presenting with septic *** suspicion for rare opportunistic infections is imperative in individuals with long-term RTX use.

关键词： Cytomegalovirus colitis Rituximab use Immunocompromised status Septic shock Pancytopenia Case report

Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of internal medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public Health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

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Neural Regeneration Research 2025年第11期20卷 3113-3123页

作者： Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki department of Clinical Neuroscience Karolinska InstituteStockholmSweden department of Neurology Karolinska University HospitalStockholmSweden department of Molecular medicine and Surgery Karolinska InstituteStockholmSweden center for Diabetes Academic Specialist CenterStockholmSweden center for Neurology Academic Specialist CenterStockholmSweden

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic *** data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular *** insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological *** contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

关键词： brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling neurodegeneration Parkinson's disease targeted therapy

Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

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World Journal of Gastroenterology 2012年第39期18卷 5589-5594页

作者： Tae Yoon Lee Young Koog Cheon Chan Sup Shim Young Deok Cho digestive disease center Department of Internal MedicineKonkuk University Medical CenterKonkuk University School of MedicineSeoul 143-729South Korea Institute for digestive Research and digestive disease center Soonchunhyang University College of MedicineSeoul 140-743South Korea

AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

关键词： Bile duct cancer Palliative endoscopic stent-ing Photodynamic therapy Outcome