AVIAN DISEASES
·
2025
·
IF 1.3
Du Xiaowen,Zeng Mengting,Yang Wenzhuo,Jiang Yuting,Huang Guangyu,Ding Shiping,Jiang Danli,Yuan Zhaoxia
For decades, infectious bronchitis (IB), caused by the infectious bronchitis virus (IBV), has posed a significant threat to poultry health and is mainly controlled by vaccines. However, the currently available commercial vaccines do not provide adequate protection against new IBV strains that emerge due to ongoing evolution. Therefore, new antiviral strategies need to be explored. Cepharanthine (CEP), tetrandrine (TET), and berbamine hydrochloride (BBM) are natural plant-derived bis-benzylisoquinoline alkaloids (BBAs) with proven antiviral activities against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), porcine epidemic diarrhea virus (PEDV), and other viruses. Despite this, their potential antiviral activities against IBV remain unknown. As a proof-of-concept study, we aimed to investigate the inhibitory effects of CEP, TET, and BBM on the laboratory-adapted IBV Beaudette strain in Vero cells and of CEP in chicken embryos. Our research demonstrated that CEP, TET, and BBM effectively suppressed IBV infection in Vero cells, with CEP showing a particularly high selective index of 309.6. These compounds dose-dependently decreased IBV RNA levels and N protein expression and lowered intracellular and extracellular viral titers. Notably, CEP also exhibited antiviral activity against IBV infection in chicken embryos, resulting in reduced mortality and fewer lesions. While these findings highlight the potential of CEP, TET, and BBM as candidates for further development, further studies are required to evaluate their efficacy against field-prevalent IBV strains (e.g., Massachusetts, QX-like) and clarify the specific antiviral mechanisms.
研究领域:
病毒学
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药物开发
·
兽医学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2026
·
IF 8.5
Cao Kai,Xie Jun,Liang Xiaohan,Li Yanqing,Gong Hui,Luo Haiming
Hyperphosphorylation of tau is a key pathological hallmark of Alzheimer's disease and is closely associated with cognitive impairment. Passive immunotherapy targeting hyperphosphorylated tau is a promising approach to inhibit tau pathology. However, the blood-brain barrier restricts antibodies from reaching the central nervous system and exerting their therapeutic effects. Here, we developed an intranasal biomacromolecule delivery strategy for the treatment of Alzheimer's disease using dendritic mesoporous silica nanoparticles modified with hyaluronic acid as a drug carrier. Ten-month-old C57BL/6J mice, htau mice, and 5×FAD mice were intranasally administered 100 μg of hyaluronic acid-dendritic mesoporous silica nanoparticles@4B1 (antibody dose), and brain tissues were collected to evaluate antibody delivery efficiency. Using this delivery system, the anti-p-tau 396,404 antibody 4B1 was efficiently delivered to the brains of 5×FAD mice, with an enrichment of 7.31% ± 0.18% ID/g. Entry of the 4B1 antibody into the brain ameliorated tauopathy in Alzheimer's disease model mice, reduced neuronal loss and neuroinflammation caused by tau pathology, and reversed cognitive dysfunction. These findings suggest that the nasal delivery strategy based on hyaluronic acid-responsive release is an effective method for delivering antibody biomacromolecules to the central nervous system, showing high efficiency of antibody entry into brain tissue and intracellular delivery. Our findings also demonstrate the role of p-tau 396,404 in passive immunotherapy for Alzheimer's disease, suggesting that immunotherapy targeting p-tau 396,404 is a promising strategy for ameliorating Alzheimer's disease pathology, inhibiting the aggregation of hyperphosphorylated tau, and alleviating neurological damage and cognitive dysfunction.
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DOI
高影响因子
Neural Regeneration Research
·
2025
·Vol. 21
·期 7
·3122
·
IF 6.7
Liang Yu,Xi Deshuang,Teng Yilin,Liu Pan,Feng Yanbing,Huang Qiumei,Gao Ming,Zong Shaohui
Export Rat nerve growth factor and total flavonoids from hawthorn leaf contribute to the recovery of neurological function after spinal cord injury, including traumatic, non-traumatic spinal cord injuries. However, it remains challenging to efficiently deliver nerve growth factor and total flavonoids from hawthorn leaf to spinal cord injury sites, ensure their sustained release, and minimize further damage. In the present study, we chose a biocompatible and biodegradable gelatin as the substrate, which was crosslinked with the natural biological crosslinker genipin to form a gelatin–genipin hydrogel carrier for the slow release of nerve growth factor and total flavonoids from hawthorn leaf in spinal cord injury sites. The prepared gelatin–genipin hydrogel had good injectable properties and photothermal effects. Furthermore, when the hydrogel with 2% genipin, 200 ng/mL nerve growth factor, and 320 μg/mL total flavonoids from hawthorn leaf was combined with near infrared irradiation, there was a slow release of total flavonoids from hawthorn leaf and nerve growth factor, reduced oxidative stress, an improved inflammatory microenvironment, and accelerated angiogenesis and axonal regeneration via inhibition of the nuclear factor kappa-B signaling pathway, thereby promoting recovery from spinal cord injury. Collectively, our results indicate that this new hydrogel may improve the prognosis of spinal cord injury, and may represent a new strategy for treating spinal cord injury.
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DOI
高影响因子
Neural Regeneration Research
·
2025
·
IF 6.7
Ma Yangguang,Liu Yi,Pan Dongsheng,Zhang Jiawei,Liang Zhuowen,Wang Yi,Hu Xueyu,Wang Zhe,Ding Tan
The blood–spinal cord barrier is crucial for preserving homeostasis of the central nervous system. After spinal cord injury, autophagic flux within endothelial cells is disrupted, compromising the integrity of the blood–spinal cord barrier. This disruption facilitates extensive infiltration of inflammatory cells, resulting in exacerbated neuroinflammatory responses, neuronal death, and impaired neuronal regeneration. Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function. However, the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated. In this study, we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment. Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice, promoting recovery of hindlimb motor function. Using microvascular endothelial bEnd.3 cells subjected to oxygen–glucose deprivation, we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway. Additionally, photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood–spinal cord barrier. Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway, thereby promoting repair of the blood–spinal cord barrier following spinal cord injury.
研究领域:
神经科学
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再生医学
·
细胞生物学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2024
·Vol. 19
·期 12
·2708
·
IF 5.9
Fang He,Li Mengjie,Yang Jingchen,Ma Shunping,Zhang Li,Yang Hongqi,Tang Qiongyan,Cao Jing,Yang Weimin
Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.
研究领域:
神经科学
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药理学
·
分子生物学
·
神经病学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2024
·
IF 5.9
Li Tong,Xing Hui-Min,Qian Hai-Dong,Gao Qiao,Xu Sheng-Lan,Ma Hua,Chi Zai-Long
Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
研究领域:
神经科学
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干细胞生物学
·
眼科学
·
分子生物学
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DOI
PubMed
高影响因子
AVIAN DISEASES
·
2024
·
IF 1.3
Pang Xiaoyue,Qiu Wenyue,Zhang Xinting,Huang Jianjia,Zhou Shuilian,Wang Rongmei,Tang Zhaoxin,Su Rongsheng
Acute myocardial injury (AMI) induced by lipopolysaccharide (LPS) can cause cardiovascular dysfunction and lead to death in poultry. Traditional antibiotic therapy has been found to have many limitations and negative effects. Asiatic acid (AA) is a naturally occurring pentacyclic triterpenoid that is extracted from Centella asiatica and has anti-inflammatory, antioxidant, and anticancer pharmacological properties. Previously, we studied the effect of AA on LPS-induced liver and kidney injury; however, the impact of AA on LPS-induced AMI remained unclear. Sixty 1-day-old broilers were randomly divided into control group, LPS group, LPS + AA 15 mg/kg group, LPS + AA 30 mg/kg group, LPS + AA 60 mg/kg group, and control + AA 60 mg/kg group. The histopathology of cardiac tissues was detected by hematoxylin and eosin (H&E) staining. The mRNA and protein expressions related to mitochondrial dynamics and mitophagy were detected by quantitative real-time PCR, western blot, immunofluorescence, and immunohistochemistry. Disorganized myocardial cells and fractured myocardial fibers were found in the LPS group, and obvious red-blood-cell filling can be seen in the gaps between the myocardial fibers in the low-dose AA group. Nevertheless, the medium and high dose of AA obviously attenuated these changes. Our results showed that AA significantly restored the mRNA and protein expressions related to mitochondrial dynamic through further promoting mitophagy. This study revealed the effect of AA on LPS-induced AMI in broilers. Mechanically, AA regulated mitochondrial dynamic homeostasis and further promoted mitophagy. These novel findings indicate that AA may be a potential drug for LPS-induced AMI in broilers.
研究领域:
药理学
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心脏病学
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兽医学
·
分子生物学
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DOI
PubMed
高影响因子
Neural Regeneration Research
·
2025
·
IF 6.7
Gu Xinyi,Huang Chen,Wang Shen,Deng Jin,Guo Shuhang,Yin Xiaofeng
To perform various functions in the body, skeletal muscle is controlled and coordinated as a whole by nerves. However, there has been little research into whether the nerve control characteristics of different muscles are different, and the importance of these potential differences. In the present study, we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles. We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways. In terms of spatial distribution patterns, sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons. In addition, the neuronal innervation of limb muscles exhibited four different characteristics: sympathetic neuron-rich muscle, sensory neuron-rich muscle, neuron-sparse muscle, and motor neuron-rich muscle. Sensory neuron density was mainly associated with muscle contractile structure and cell pH, whereas sympathetic neuron density was associated with protein kinase activity, muscle vasculature, muscle calcium-dependent protein kinase activity, lipid transport, and vesicle release. Motor neuron density was mainly associated with protein kinase activity, cell adhesion, oxidoreductase activity, and exocytosis. These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions, thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.
研究领域:
神经科学
·
肌肉生理学
·
系统生物学
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分子生物学
·
解剖学
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产品关联
DOI
PubMed
高影响因子
Neural Regeneration Research
·
2024
·Vol. 20
·期 4
·1164
·
IF 5.9
Wang Pengfei,Bi Yuewei,Li Min,Chen Jiazhi,Wang Zhuyong,Wen Huantao,Zhou Ming,Luo Minjie,Zhang Wangming
Long-term levodopa administration can lead to the development of levodopa-induced dyskinesia. Gamma oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced dyskinesia. Currently, studies have reported increased oscillation power in cases of levodopa-induced dyskinesia. However, little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced dyskinesia. Furthermore, the role of the dopamine D3 receptor, which is implicated in levodopa-induced dyskinesia, in movement disorder-related changes in neural oscillations is unclear. We found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s disease. Furthermore, levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components, as well as bidirectional primary motor cortex (M1) ↔ dorsolateral striatum gamma flow. Administration of PD128907 (a selective dopamine D3 receptor agonist) induced dyskinesia and excessive gamma oscillations with a bidirectional M1 ↔ dorsolateral striatum flow. However, administration of PG01037 (a selective dopamine D3 receptor antagonist) attenuated dyskinesia, suppressed gamma oscillations and cortical gamma aperiodic components, and decreased gamma causality in the M1 → dorsolateral striatum direction. These findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity, and that it has potential as a therapeutic target for levodopa-induced dyskinesia.
研究领域:
神经科学
·
药理学
·
帕金森病
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DOI
高影响因子
Neural Regeneration Research
·
2024
·Vol. 21
·期 1
·365
·
IF 5.9
Zeng Fanzhuo,Li Yuxin,Li Xiaoyu,Gu Xinyang,Cao Yue,Cheng Shuai,Tian He,Mei Rongcheng,Mei Xifan
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited. Microglia is the resident immune cells of the central nervous system, play a critical role in spinal cord injury. Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors. However, excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars, which hinder axonal regeneration. Despite this, the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood. To elucidate the role of microglia in spinal cord injury, we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia. We observed that sustained depletion of microglia resulted in an expansion of the lesion area, downregulation of brain-derived neurotrophic factor, and impaired functional recovery after spinal cord injury. Next, we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia. We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function. Additionally, brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury. Furthermore, through using specific transgenic mouse lines, TMEM119, and the colony-stimulating factor 1 receptor inhibitor PLX73086, we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages. In conclusion, our findings suggest the critical role of microglia in the formation of protective glial scars. Depleting microglia is detrimental to recovery of spinal cord injury, whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
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DOI
高影响因子
Neural Regeneration Research
·
2026
·
IF 6.7
Wu Jinting,Hao Peng,Duan Hongmei,Zhao Wen,Gao Yudan,Cui Zhiqiang,Yang Zhaoyang,Li Xiaoguang
Activation and neuronal differentiation of endogenous neural stem/progenitor cells within the hippocampal neurogenic niche (a neurogenic region) of the adult mammalian brain are considered potential bases for restoration of cognitive and memory functions. However, following traumatic cortical brain injury (i.e., injuries in a non-neurogenic region), the local microenvironment becomes hostile due to the presence of inhibitory factors such as inflammation, edema, and hypoxic–ischemic stress. These conditions hinder the migration and subsequent neuronal differentiation of activated neural stem/progenitor cells into the injured cortex. Numerous recent studies have confirmed that biomaterials can improve the microenvironment of the injured area and promote nerve regeneration. In this study, we report the findings obtained by injecting a biodegradable chitosan–gelatin–collagen gel into the cortical lesion area. We observed that the chitosan–gelatin–collagen gel established a permissive microenvironment for neural repair by suppressing inflammation and scar infiltration while promoting neovascularization. Thus, it enabled activated endogenous “seed” cells, i.e., neural stem/progenitor cells, to migrate into the cortical lesion area and generate new neurons and thereby facilitate functional recovery. These findings represent a novel biomaterial-based therapeutic strategy for the treatment of traumatic cortical brain injury, stroke, and other neurological disorders.
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF PHYSIOLOGY
·
2023
·Vol. 66
·期 6
·437
·
IF 1.8
Fan Wenbo,Zhou Jianwu
Parkinson's disease (PD) is recognized as a degenerative and debilitating neurodegenerative disorder. The novel protective role of icariside II (ICS II) as a plant-derived flavonoid compound in neurodegenerative diseases has aroused much attention. Herein, the definite impacts of ICS II on the process of PD and the relevant action mechanism were studied. Human neuroblastoma SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium ion (MPP + ) to construct the PD cell model. MTT assay and flow cytometry analysis, respectively, appraised cell viability and apoptosis. Caspase 3 Activity Assay examined caspase 3 activity. Corresponding kits examined oxidative stress levels. BODIPY 581/591 C11 assay evaluated lipid reactive oxygen species. Iron Assay Kit assessed iron content. Western blot tested the expression of apoptosis-, ferroptosis- and Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling-associated proteins. Molecular docking verified the binding of ICS II with Keap1. The existing experimental results unveiled that ICS II elevated the viability whereas reduced the apoptosis, oxidative stress, and ferroptosis in MPP + -treated SK-N-SH cells in a concentration-dependent manner. Furthermore, ICS II declined Keap1 expression while raised Nrf2, heme oxygenase 1, and GPX4 expression. In addition, ICS II had a strong binding with Keap1 and Nrf2 inhibitor ML385 partially abolished the suppressive role of ICS II in MPP + -triggered apoptosis, oxidative stress, and ferroptosis in SK-N-SH cells. To summarize, ICS II might inhibit apoptosis, oxidative stress, and ferroptosis in the MPP + -stimulated PD cell model, which might be due to the activation of Keap1/Nrf2/GPX4 signaling.
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PubMed
高影响因子
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