医学最新文献

{"title":"Complement-dependent neuroinflammation in spinal cord injury: from pathology to therapeutic implications.","authors":"Hassan Saad, Bachar El Baba, Ali Tfaily, Firas Kobeissy, Juanmarco Gutierrez Gonzalez, Daniel Refai, Gerald R Rodts, Christian Mustroph, David Gimbel, Jonathan Grossberg, Daniel L Barrow, Matthew F Gary, Ali M Alawieh","doi":"10.4103/NRR.NRR-D-24-00116","DOIUrl":"10.4103/NRR.NRR-D-24-00116","url":null,"abstract":"<p><p>Spinal cord injury remains a major cause of disability in young adults, and beyond acute decompression and rehabilitation, there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population. Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation, a similar role for complement in spinal neuroinflammation is a focus of ongoing research. In this work, we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins, triggers of complement activation, and role of effector functions in the pathology. We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris, and or activation via antibody binding to damage-associated molecular patterns. Several effector functions of complement have been implicated in spinal cord injury, and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury. Following this pathophysiological review, we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects. This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury, to evaluate the phases of involvement of opsonins and anaphylatoxins, and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1324-1335"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Apolipoprotein A-I binding protein-mediated neuroprotection in glaucomatous neuroinflammation and neurodegeneration.","authors":"Sinwoo Hwang, Seunghwan Choi, Soo-Ho Choi, Keun-Young Kim, Yury I Miller, Won-Kyu Ju","doi":"10.4103/NRR.NRR-D-24-00221","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00221","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1414-1415"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis: a retrospective observational study.","authors":"Jieying Wu, Shan Ye, Xiangyi Liu, Yingsheng Xu, Dongsheng Fan","doi":"10.4103/NRR.NRR-D-23-01359","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-23-01359","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202505000-00032/figure1/v/2024-07-28T173839Z/r/image-tiff Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons. Early bilateral limb involvement significantly affects patients' daily lives and may lead them to be confined to bed. However, the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear. To address this issue, we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022. A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis. We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients. Multiple factor analyses revealed that higher upper motor neuron scores (hazard ratio [HR] = 1.05, 95% confidence interval [CI] = 1.01-1.09, P = 0.018), onset in the left limb (HR = 0.72, 95% CI = 0.58-0.89, P = 0.002), and a horizontal pattern of progression (HR = 0.46, 95% CI = 0.37-0.58, P < 0.001) were risk factors for a shorter interval until bilateral limb involvement. The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients. These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1505-1512"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational machinery and translation regulation in axon regeneration.","authors":"Homaira Nawabi, Stephane Belin","doi":"10.4103/NRR.NRR-D-24-00313","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00313","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1392-1394"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NECAB family of neuronal calcium-binding proteins in health and disease.","authors":"Diones Bueno, Michael K E Schäfer, Sudena Wang, Michael J Schmeisser, Axel Methner","doi":"10.4103/NRR.NRR-D-24-00094","DOIUrl":"10.4103/NRR.NRR-D-24-00094","url":null,"abstract":"<p><p>The N-terminal EF-hand calcium-binding proteins 1-3 (NECAB1-3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not well-characterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein-protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1236-1243"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.","authors":"Wenrui Qu, Xiangbing Wu, Wei Wu, Ying Wang, Yan Sun, Lingxiao Deng, Melissa Walker, Chen Chen, Heqiao Dai, Qi Han, Ying Ding, Yongzhi Xia, George Smith, Rui Li, Nai-Kui Liu, Xiao-Ming Xu","doi":"10.4103/NRR.NRR-D-23-01338","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-23-01338","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1467-1482"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of axon guidance molecules in the pathogenesis of epilepsy.","authors":"Zheng Liu, Chunhua Pan, Hao Huang","doi":"10.4103/NRR.NRR-D-23-01620","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-23-01620","url":null,"abstract":"<p><p>Current treatments for epilepsy can only manage the symptoms of the condition but cannot alter the initial onset or halt the progression of the disease. Consequently, it is crucial to identify drugs that can target novel cellular and molecular mechanisms and mechanisms of action. Increasing evidence suggests that axon guidance molecules play a role in the structural and functional modifications of neural networks and that the dysregulation of these molecules is associated with epilepsy susceptibility. In this review, we discuss the essential role of axon guidance molecules in neuronal activity in patients with epilepsy as well as the impact of these molecules on synaptic plasticity and brain tissue remodeling. Furthermore, we examine the relationship between axon guidance molecules and neuroinflammation, as well as the structural changes in specific brain regions that contribute to the development of epilepsy. Ample evidence indicates that axon guidance molecules, including semaphorins and ephrins, play a fundamental role in guiding axon growth and the establishment of synaptic connections. Deviations in their expression or function can disrupt neuronal connections, ultimately leading to epileptic seizures. The remodeling of neural networks is a significant characteristic of epilepsy, with axon guidance molecules playing a role in the dynamic reorganization of neural circuits. This, in turn, affects synapse formation and elimination. Dysregulation of these molecules can upset the delicate balance between excitation and inhibition within a neural network, thereby increasing the risk of overexcitation and the development of epilepsy. Inflammatory signals can regulate the expression and function of axon guidance molecules, thus influencing axonal growth, axon orientation, and synaptic plasticity. The dysregulation of neuroinflammation can intensify neuronal dysfunction and contribute to the occurrence of epilepsy. This review delves into the mechanisms associated with the pathogenicity of axon guidance molecules in epilepsy, offering a valuable reference for the exploration of therapeutic targets and presenting a fresh perspective on treatment strategies for this condition.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1244-1257"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin.","authors":"Meifeng Zheng, Borui Zhang, Sonata S Y Yau, Kwok-Fai So, Li Zhang, Haining Ou","doi":"10.4103/NRR.NRR-D-23-01101","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-23-01101","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202505000-00027/figure1/v/2024-07-28T173839Z/r/image-tiff Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy. Physical exercise enhances neurogenesis and synaptogenesis, and has been widely used for functional rehabilitation after stroke. In this study, we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia. We also examined the role of exercise-induced circulating factors in these effects. Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion. We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area, inhibited gliogenesis, protected synaptic proteins, and improved novel object and spatial memory function. Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise. Agonist activation of adiponectin receptors by AdipoRon mimicked the effects of exercise, while inhibiting receptor activation abolished the exercise effects. In summary, our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1445-1454"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate is a potentially harmful substitute for brain glucose fuel: consequences for metabolic restoration of neurotransmission.","authors":"Oliver Kann, Lennart Söder, Babak Khodaie","doi":"10.4103/NRR.NRR-D-24-00262","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-00262","url":null,"abstract":"","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":"20 5","pages":"1403-1404"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial therapies for spinal cord injury repair.","authors":"Carla S Sousa, Andreia Monteiro, António J Salgado, Nuno A Silva","doi":"10.4103/NRR.NRR-D-24-00061","DOIUrl":"10.4103/NRR.NRR-D-24-00061","url":null,"abstract":"<p><p>Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":"1293-1308"},"PeriodicalIF":5.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}