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Nanoparticles for the treatment of spinal cord injury

Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang Chen Wang Yanlian Yang Ling Zhu Xinzhi Sun department of Orthopedic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina department of Orthopedic surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Laparoscopic ultrasonography as an alternative to intraoperative cholangiography during laparoscopic cholecystectomy

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World Journal of Gastroenterology 2017年第29期23卷 5438-5450页

作者： Alexandra Dili Claude Bertrand Unit of Digestive Endocrine and General Surgery Department of Surgery University Hospital - Godinne Université catholique de Louvain

To assess the role of laparoscopic ultrasound (LUS) as a substitute for intraoperative cholangiography (IOC) during cholecystectomy. METHODSWe present a MEDLINE and PubMed literature search, having used the key-words “laparoscopic intraoperative ultrasound” and “laparoscopic cholecystectomy”. All relevant English language publications from 2000 to 2016 were identified, with data extracted for the role of LUS in the anatomical delineation of the biliary tract, detection of common bile duct stones (CBDS), prevention or early detection of biliary duct injury (BDI), and incidental findings during laparoscopic cholecystectomy. Data for the role of LUS vs IOC in complex situations (i.e., inflammatory disease/fibrosis) were specifically analyzed. RESULTSWe report data from eighteen reports, 13 prospective non-randomized trials, 5 retrospective trials, and two meta-analyses assessing diagnostic accuracy, with one analysis also assessing costs, duration of the examination, and anatomical mapping. Overall, LUS was shown to provide highly sensitive mapping of the extra-pancreatic biliary anatomy in 92%-100% of patients, with more difficulty encountered in delineation of the intra-pancreatic segment of the biliary tract (73.8%-98%). Identification of vascular and biliary variations has been documented in two studies. Although inflammatory disease hampered accuracy, LUS was still advantageous vs IOC in patients with obscured anatomy. LUS can be performed before any dissection and repeated at will to guide the surgeon especially when hilar mapping is difficult due to fibrosis and inflammation. In two studies LUS prevented conversion in 91% of patients with difficult scenarios. Considering CBDS detection, LUS sensitivity and specificity were 76%-100% and 96.2%-100%, respectively. LUS allowed the diagnosis/treatment of incidental findings of adjacent organs. No valuable data for BDI prevention or detection could be retrieved, even if no BDI was documented in the reports analyzed. L

关键词： Intraoperative ultrasound Laparoscopic cholecystectomy Bile duct injury Choledocolithiasis Biliary anomalies

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Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

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Neural Regeneration Research 2025年第6期20卷 1749-1763页

作者： Tian Qin Yuxin Jin Yiming Qin Feifei Yuan Hongbin Lu Jianzhong Hu Yong Cao Chengjun Li department of Spine surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina department of Sports Medicine Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

关键词： corticospinal tract remodeling epigenetic regulations locomotor cortex m^(6)A modification methyltransferase 14 protein(METTL14) mitogen-activated protein kinase neural regeneration spinal cord injury syringin TRIB2

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Specific CYP450 Genotypes in the Chinese Population Affect Sorafenib Toxicity in HBV/HCV-associated Hepatocellular Carcinoma Patients

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Biomedical and Environmental Sciences 2018年第8期31卷 586-595页

作者： GUO Xing Gang WANG Zhi Heng DONG Wei HE Xu Dong LIU Fu Chen LIU Hui The Third department of Hepatic surgery Eastern Hepatobiliary Surgery Hospital Second Military Medical University Respiratory and endocrine department The People's Hospital of Wuwei County

Objective The purpose of this study was to screen for frequencies of different CYP450 genotypes in the Chinese population and explore the relationship between sorafenib toxicity and CYP450 polymorphism. Methods A total of 600 peripheral blood samples were obtained from two groups for this study. The first group of 300 samples were from Chinese patients with HBV/HCV-associated HCC, while the remaining 300 samples were from a healthy population of recruited subjects. Allele-specific PCR and long-fragment gene sequencing was used to identify the frequencies of CYP450 polymorphism. Aflatoxin-induced HCC rat models expressing CYP3A4*1, CYP3A5*3, CYP2C19*2, and CYP2D6*10 were established and treated with sorafenib at certain time points. Hepatic and renal function, along with plasma concentration of sorafenib, were monitored regularly. Results The most common forms of CYP mutations in the Chinese population were identified. The levels of sorafenib plasma concentration, as well as damage to hepatic and renal function in aflatoxin-induced HCC rat models varied significantly across the different CYP genotypes. Conclusion The mutational frequencies of CYP3A5, CYP3A4, CYP2C19, and CYP2D6 genotypes varied among different ethnic groups and populations. Individuals with CYP3A5*3 demonstrated minimal sorafenib metabolism, which led to severe hepatic and renal damage. Inter-individual variability in sorafenib-toxicity may be interpreted by CYP450 genetic polymorphisms, suggesting that identification of CYP polymorphism within a certain population should be considered in sorafenib therapy.

关键词： Sorafenib Hepatocellular carcinoma CYP450 polymorphism Inter-individual adverse events

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Multifocal intraportal invasion of breast carcinoma diagnosed by laparoscopy-assisted liver biopsy

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World Journal of Gastroenterology 2005年第15期11卷 2360-2363页

作者： Tomoki Nakajima Satoru Sekoguchi Taichirou Nishikawa Hidetaka Takashima Tadashi Watanabe Masahito Minami Yoshito Itoh Naruhiko Mizuta Hiroo Nakajima Takeshi Mazaki Akio Yanagisawa Takeshi Okanoue Molecular Gastroenterology and Hepatology endocrine surgery Surgical Pathology

Hepar lobatum carcinomatosum (HLC) is defined as an acquired hepatic deformity consisting of an irregularly lobulated hepatic contour caused by intravascular infiltration of metastatic carcinoma. To date, only nine cases of HLC have been reported in the literature. We report a case of a 68-year-old woman showing hepatic metastasis of breast carcinoma in radiologically unidentified form. Initially, she received left partial mastectomy for breast cancer but solid hepatic metastases were identified in S2 and S6, 9 mo after surgery. Then, they responded to chemotherapy and radiologically disappeared. After radiological disappearance of the liver tumors, the patient's blood chemistry showed abnormal liver function. A CT scan demonstrated heterogeneous enhancement effect in the liver in the late phase,suggesting uneven hepatic blood supply. Hepatic deformity was not obvious. Laparoscopy revealed a slightly deformed liver surface with multiple indentations and shallow linear depressions. Furthermore, a wide scar was observed on the surface of S2 possibly at the site where the metastatic tumor existed before chemotherapy. Liver biopsy from the wide scar lesion showed intraportal tumor thrombi with desmoplastic change. Because of its similarity to the histology of the original breast cancer, we concluded that the hepatic functional abnormalities and slightly deformed liver surface were derived from the circulatory disturbance caused by microscopic tumor thrombi. Besides, since the wide scar was located at the site of the pre-existing tumor,it is probable that chemotherapy was an important cause of fibrous scarring as a result of tumor regression. These morphologic findings are compatible with those of ***-assisted liver biopsy was useful to make definite diagnosis, even though the hepatic deformity was radiologically undetectable.

关键词： Metastatic breast cancer Hepar lobatum carcinomatosum Laparoscopy

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Heparin improves organ microcirculatory disturbances in caerulein-induced acute pancreatitis in rats

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World Journal of Gastroenterology 2004年第17期10卷 2553-2556页

作者： Marek Dobosz Lucjanna Mionskowska Stanislaw Ha■ Sebastian Dobrowolski Dariusz Dymecki Zdzislaw Wajda department of General and Gastroenterological surgery St.Vincent a'Paulo HospitalGdyniaPoland department of General Transplant and Endocrine SurgeryMedical University of Gda■skPoland

AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute *** aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler *** interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined *** administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.

关键词： Acute Disease Animals Anticoagulants Caerulein Hematocrit Heparin Male Microcirculation Pancreas Pancreatitis Rats Rats, Wistar Research Support, Non-U.S. Gov't Splanchnic Circulation

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Resection of the primary tumor in stage Ⅳ breast cancer

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World Journal of Clinical Oncology 2014年第2期5卷 82-85页

作者： Tadahiko Shien Hiroyoshi Doihara department of Breast and endocrine surgery Okayama University Hospital

Stage Ⅳ breast cancer refers to breast cancer that has already metastasized to distant regions when initially diagnosed. Treatment for stage Ⅳ is intended to "prolong survival and palliate symptoms". Resection of a primary tumor is considered to be "effective only at alleviating chest symptoms and providing local control" in spite of the advances of imaging examination and medication for breast cancer. Molecular target and endocrine drugs are very effective and useful to tailor-make a treatment strategy according to breast cancer subtypes. Positron emission tomography-computed tomography can detect and diagnose the very small metastases and recurrences which can potentially be cured even if they are distant metastases. Recently, many retrospective studies have reported the survival benefit of surgery for breast cancer patients with metastases and some clinical trials which confirm the surgical prognostic benefit for them have started to enrol patients. The goal of treatment has to be clearly identified:increase the patient's survival time, provide local control or perform histology to determine the cancer's properties. The best evidence is absolutely essential to treat patients who need surgery at the right time. We need to evaluate the treatment strategy, including primary resection for stage Ⅳ breastcancer particularly, and find new evidence by prospective analysis.

关键词： Breast cancer Metastasis surgery Survival StageⅣ Clinical trial

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Laparoscopic distal pancreatectomy: Up-to-date and literature review

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World Journal of Gastroenterology 2012年第38期18卷 5329-5337页

作者： Maurizio Iacobone Marilisa Citton Donato Nitti Minimally Invasive endocrine surgery Unit Department of Surgical Oncological and Gastroenterological Sciences University of Padua 35128 Padova Italy

Pancreatic surgery represents one of the most challenging areas in digestive surgery. In recent years, an increasing number of laparoscopic pancreatic procedures have been performed and laparoscopic distal pancreatectomy (LDP) has gained world-wide acceptance because it does not require anastomosis or other reconstruction. To date, English literature reports more than 300 papers focusing on LDP, but only 6% included more than 30 patients. Literature review confirms that LDP is a feasible and safe procedure in patients with benign or low grade malignancies. Decreased blood loss and morbidity, early recovery and shorter hospital stay may be the main advantages. Several concerns still exist for laparoscopic pancreatic adenocarcinoma excision. The individual surgeon determines the technical conduction of LDP, with or without spleen preservation; currently robotic pancreatic surgery has gained diffu- sion. Additional researches are necessary to determine the best technique to improve the procedure results.

关键词： Pancreas resection Laparoscopic distal pancreatectomy Left pancreatectomy Open pan- createctomy Pancreatic fistula Splenectomy Spleen- preserving technique

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Microglia lactylation in relation to central nervous system diseases

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Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina department of Clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK department of Orthopedics(Spine surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina department of Pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina department of Clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system ***,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative *** has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of *** is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various *** review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting ***,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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