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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

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ImSpiRE: image feature-aided spatial resolution enhancement method

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Science China Life Sciences 2025年第1期 272-283页

作者： Yuwei Hua Yizhi Zhang Zhenming Guo Shan Bian Yong Zhang State Key Laboratory of Cardiovascular diseases and Medical Innovation center Institute for Regenerative MedicineDepartment of NeurosurgeryShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji University

The resolution of most spatially resolved transcriptomic technologies usually cannot attain the single-cell level, limiting their applications in biological discoveries. Here, we introduce ImSpiRE, an image feature-aided spatial resolution enhancement method for in situ capturing spatial transcriptome. Taking the information stored in histological images, ImSpiRE solves an optimal transport problem to redistribute the expression profiles of spots to construct new transcriptional profiles with enhanced resolution, together with extending the gene expression profiles into unmeasured regions. Applications to multiple datasets confirm that ImSpiRE can enhance spatial resolution to the subspot level while contributing to the discovery of tissue domains, signaling communication patterns, and spatiotemporal characterization.

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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

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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

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital center for disease Control and Prevention of Sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan center for disease Control and Prevention Office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Healthcare utilization and costs associated with gastroparesis

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World Journal of Gastroenterology 2017年第24期23卷 4428-4436页

作者： Vaibhav Wadhwa Dhruv Mehta Yash Jobanputra Rocio Lopez Prashanthi N Thota Madhusudhan R Sanaka Department of internal medicine Fairview HospitalCleveland Clinic Department of internal medicine Westchester Medical Center Department of Gastroenterology and Hepatology Digestive Disease InstituteCleveland Clinic center for Advanced Endoscopy Digestive Disease InstituteCleveland Clinic

To use a national database of United States hospitals to evaluate the incidence and costs of hospital admissions associated with gastroparesis. METHODSWe analyzed the National Inpatient Sample Database (NIS) for all patients in whom gastroparesis (ICD-9 code: 536.3) was the principal discharge diagnosis during the period, 1997-2013. The NIS is the largest publicly available all-payer inpatient care database in the United States. It contains data from approximately eight million hospital stays each year. The statistical significance of the difference in the number of hospital discharges, length of stay and hospital costs over the study period was determined by regression analysis. RESULTSIn 1997, there were 3978 admissions with a principal discharge diagnosis of gastroparesis as compared to 16460 in 2013 (P < 0.01). The mean length of stay for gastroparesis decreased by 20 % between 1997 and 2013 from 6.4 d to 5.1 d (P < 0.001). However, during this period the mean hospital charges increased significantly by 159 % from $13350 (after inflation adjustment) per patient in 1997 to $34585 per patient in 2013 (P < 0.001). The aggregate charges (i.e., “national bill”) for gastroparesis increased exponentially by 1026 % from $50456642 ± 4662620 in 1997 to $568417666 ± 22374060 in 2013 (P < 0.001). The percentage of national bill for gastroparesis discharges (national bill for gastroparesis/total national bill) has also increased over the last 16 years (0.0013% in 1997 vs 0.004% in 2013). During the study period, women had a higher frequency of gastroparesis discharges when compared to men (1.39/10000 vs 0.9/10000 in 1997 and 5.8/10000 vs 3/10000 in 2013). There was a 6-fold increase in the discharge diagnosis of gastroparesis amongst type 1 DM and 3.7-fold increase amongst type 2 DM patients over the study period (P < 0.001). CONCLUSIONThe number of inpatient admissions for gastroparesis and associated costs have increased significantly over the last 16 years. Inpatient cost

关键词： Inpatient admission rates Gastroparesis Cancer epidemiology National inpatient database

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Effectiveness of contrast-enhanced harmonic endoscopic ultrasound for the evaluation of solid pancreatic masses

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World Journal of Gastroenterology 2014年第2期20卷 518-524页

作者： Jin-Seok Park Hyung Kil Kim Byoung Wook Bang Sang Gu Kim Seok Jeong Don Haeng Lee digestive disease center Department of Internal MedicineInha University School of MedicineIncheon 400-711South Korea

AIM:To evaluate the usefulness of contrast-enhanced harmonic endoscopic ultrasound(CH-EUS)in differentiating between pancreatic adenocarcinomas and other pancreatic ***:This retrospective cohort study evaluated90 patients who were seen between November 2010and May *** these patients had solid pancreatic masses that had a hypoechoic appearance on *** patients underwent CH-EUS to evaluate this diagnostic method’s *** mass lesions observed on CH-EUS were classified into three categories based on their echo intensity:hypoenhanced,isoenhanced,and hyperenhanced *** adjusted the sensitivity and the specificity of each category for detecting *** also estimated the accuracy of CH-EUS by comparing it to a pathological ***:Of the 90 patients,62 had a pancreatic ***-seven out of 62 pancreatic adenocarcinomas showed a hypoenhanced pattern on *** sensitivity was 92%,the specificity 68%and the accuracy approximately 82%.The area under the curve of the receiver operating characteristic analysis for CH-EUS was *** is a significant association between the hypoenhanced pattern on CH-EUS and pancreatic duct adenocarcinoma(χ2=35.264,P<0.001).In pathological examinations,the number of specimens for EUS-fine needle aspiration(EUS-FNA)was considered insufficient for diagnosis in three patients,and in two patients,the results were reported to be negative for *** masses in all five patients revealed a hypoenhanced pattern with *** patients were diagnosed with pancreatic adenocarcinoma based on the pathology results of a biopsy,and the remaining two patients were clinically diagnosed with ***:CH-EUS is useful for distinguishing between pancreatic adenocarcinoma and other pancreatic *** a pancreatic mass shows a hypoenhanced pattern on CH-EUS but involves either insufficient samples or negative results with EUS-FNA,clinicians might consider perfo

关键词： Pancreas neoplasm Endoscopic ultrasound SonoVue Contrast media Microbubbles

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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

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Case of Fitz-Hugh-Curtis syndrome in male without presentation of sexually transmitted disease

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World Journal of Clinical Cases 2015年第11期3卷 965-969页

作者： Haram Yi Chan Sup Shim Gyu Won Kim Jung Seok Kim In Zoo Choi Department of internal medicine Sahmyook Seoul Hospital Global digestive disease center Department of Internal Medicine Konkuk University Medical Center

Fitz-Hugh-Curtis syndrome is a type of perihepatitis that causes liver capsular infection without infecting the hepatic parenchyma or pelvis. Fitz-Hugh-Curtis syndrome is known to occur commonly in women of childbearing age who do not use oral contraceptives and have sexual partners older than 25 years of age. However, the syndrome has been reported to occur rarely in males. The clinical symptoms are right upper quadrant pain and tenderness, and pleuritic right sided chest pain. The clinical presentation is similar in male and female. We experienced a case of Fitz-HughCurtis syndrome in a 60-year-old man with the chief complaint of right upper quadrant abdominal pain. Despite a previous history of gonorrhea, we have also described our experiences of improved symptoms and recovery with allopathic medicines and have thereby reported the present case with a literature review.

关键词： Male Right upper quadrant pain Fitz-Hugh-Curtis syndrome Perihepatitis Sexually transmitted disease Liver capsular infection

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Metabolic reprogramming: a new option for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao Wang Yi Li Kesi Shi Yuang Zhang Haibin Xu Xuesong Zhang Jingkai Wang Qixin Chen Chengzhen Liang Department of Orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Orthopedics Research Institute of Zhejiang University Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor System disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research center of Motor System disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s Hospital KailiGuizhou ProvinceChina Department of Orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they *** the ongoing development of various therapies for spinal cord injuries,their effectiveness remains ***,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic *** this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic *** spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic ***,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial *** metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of *** rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell *** available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord *** further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

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