Therapeutic utility of human umbilical cord-derived mesenchymal stem cells-based approaches in pulmonary diseases:Recent advancements and prospects

Pulmonary diseases across all ages threaten millions of people and have emerged as one of the major public health issues worldwide.For diverse disease con-ditions,the currently available approaches are focused on alleviating clinical symptoms and delaying disease progression but have not shown significant therapeutic effects in patients with lung diseases.Human umbilical cord-derived mesenchymal stem cells(UC-MSCs)isolated from the human UC have the capacity for self-renewal and multilineage differentiation.Moreover,in recent years,these cells have been demonstrated to have unique advantages in the treatment of lung diseases.We searched the Public Clinical Trial Database and found 55 clinical trials involving UC-MSC therapy for pulmonary diseases,including coronavirus disease 2019,acute respiratory distress syndrome,bron-chopulmonary dysplasia,chronic obstructive pulmonary disease,and pulmonary fibrosis.In this review,we summarize the characteristics of these registered clinical trials and relevant published results and explore in depth the challenges and opportunitiesfaced in clinical application.Moreover,the underlying mole-cular mechanisms involved in UC-MSC-based therapy for pulmonary diseases are also analyzed in depth.In brief,this comprehensive review and detailed analysis of these clinical trials can be expected to provide a scientific reference for future large-scale clinical application.

Progress in the generation of spinal cord organoids over the past decade and future perspectives

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Nanoparticles for the treatment of spinal cord injury

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.

Liposomes as versatile agents for the management of traumatic and nontraumatic central nervous system disorders:drug stability,targeting efficiency,and safety

Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.

c-Abl kinase at the crossroads of healthy synaptic remodeling and synaptic dysfunction in neurodegenerative diseases

Our ability to learn and remember depends on the active formation,remodeling,and elimination of synapses.Thus,the development and growth of synapses as well as their weakening and elimination are essential for neuronal rewiring.The structural reorganization of synaptic complexes,changes in actin cytos keleton and organelle dynamics,as well as modulation of gene expression,determine synaptic plasticity.It has been proposed that dys regulation of these key synaptic homeostatic processes underlies the synaptic dysfunction observed in many neurodegenerative diseases.Much is known about downstream signaling of activated N-methyl-D-aspartate andα-amino-3-hydroxy-5-methyl-4-isoazolepro pionate receptors;howeve r,other signaling pathways can also contribute to synaptic plasticity and long-lasting changes in learning and memory.The non-receptor tyrosine kinase c-Abl(ABL1)is a key signal transducer of intra and extracellular signals,and it shuttles between the cyto plasm and the nucleus.This review focuses on c-Abl and its synaptic and neuronal functions.Here,we discuss the evidence showing that the activation of c-Abl can be detrimental to neurons,promoting the development of neurodegenerative diseases.Nevertheless,c-Abl activity seems to be in a pivotal balance between healthy synaptic plasticity,regulating dendritic spines remodeling and gene expression after cognitive training,and synaptic dysfunction and loss in neurodegenerative diseases.Thus,c-Abl genetic ablation not only improves learning and memory and modulates the brain genetic program of trained mice,but its absence provides dendritic spines resiliency against damage.Therefo re,the present review has been designed to elu cidate the common links between c-Abl regulation of structural changes that involve the actin cytos keleton and organelles dynamics,and the transc riptional program activated during synaptic plasticity.By summarizing the recent discove ries on c-Abl functions,we aim to provide an overview of how its inhibition co uld be a potentially fruitful treatment to improve degenerative outcomes and delay memory loss.

An expert consensus on the evaluation and treatment of acute thoracolumbar spine and spinal cord injury in China

This is an expert consensus on the evaluation and treatment of thoracolumbar spinal injury, estab- lished from February 2009 to July 2010. The expert consensus consists mainly of six parts with a total of 54 recommendations including the overview （one item）; pre-hospital care （one item）; evaluation and diagnosis （13 items）; treatment （23 items）; prevention and treatment of major com- plications （12 items）; and rehabilitation （four items）. This is the first time that Chinese experts have published a consensus on spine and spinal cord injury. The expert consensus was established based on Delphi methods, literature analysis, and clinical experiences. Each recommendation is supported by and was interpreted using multi-level evidences. The level of agreement with the rec- ommendation among the panel members was assessed as either low, moderate, or strong. Each panel member was asked to indicate his or her level of agreement on a 5-point scale, with ＂1＂ cor- respondJng to neutrality and ＂5＂ representJng maxJmum agreement. Scores were aggregated across the panel members and an arithmetic mean was calculated. This mean score was then translated into low, moderate, or strong. After all of the votes were collected and calculated, the results showed no low-level recommendations, 10 moderate-level recommendations, and 44 strong-level recom- mendations. An expert consensus was reached and was recognized by Chinese spine surgeons. Wide-scale adoption of these recommendations is urgent in the management of acute thora- columbar spine and spinal cord injury in a broader attempt to create a standard evaluation and treatment strategy for acute thoracolumbar spine and spinal cord injury in China.

The clinical rehabilitation of spine and spinal cord disorders: detection and evaluation using SPECT/CT

Spine-related disorders are caused by several factors including （1） spinal nerve/visceral nerve stimulation by perivertebral aseptic inflammation, （2） spinal nerve/visceral nerve compression by injured periverterbal soft tissue, dislocated perivertebral small joint, and proliferative/degenerative tissue and, （3） secondary damage to the spinal cord, peripheral nerve, vessels and autonomic nerve, which further stimulate nerve root sheath and surround- ing pain-carrying nerve fibers. In many cases, the source of pain cannot be detected by standard image modalities. Particularly in anatomically complex regions like the spine, SPECT/CT can be helpful for some aspects by intro- ducing a metabolical dimension to the classical way of morphology-based diagnostic. The aim of the present review was to give an overview of the adoption of SPECT/CT in a clinical spine-focused setting.

Potential contribution of pedicle screw design to loosening rate in patients with degenerative diseases of the lumbar spine:An observational study

BACKGROUND The majority of published data report the results of biomechanical tests of various design pedicle screw performance.The clinical relevance and relative contribution of screw design to instrumentation stability have been insufficiently studied.AIM To estimate the contribution of screw design to rate of pedicle screw loosening in patients with degenerative diseases of the lumbar spine.METHODS This study is a prospective evaluation of 175 patients with degenerative diseases and instability of the lumbar spine segments.Participants underwent spinal instrumentation employing pedicle screws with posterior only or transforaminal interbody fusion.Follow-up was for 18 mo.Patients with signs of pedicle screw loosening on computed tomography were registered;logistic regression analysis was used to identify the factors that influenced the rate of loosening.RESULTS Parameters included in the analysis were screw geometry,type of thread,external and internal screw diameter and helical pitch,bone density in Hounsfield units,number of levels fused,instrumentation without anterior support,laminectomy,and unilateral and bilateral total facet joint resection.The rate of screw loosening decreased with the increment in outer diameter,decrease in core diameter and helical pitch.The rate of screw loosening correlated positively with the number of fused levels and decreasing bone density.Bilateral facet joint removal significantly favored pedicle screw loosening.The influence of other factors was insignificant.CONCLUSION Screw parameters had a significant impact on the loosening rate along with bone quality characteristics,the number of levels fused and the extensiveness of decompression.The significance of the influence of screw parameters was comparable to those of patient-and surgery-related factors.Pedicle screw loosening was influenced by helical pitch,inner and outer diameter,but screw geometry and thread type were insignificant factors.

Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases:a systematic review and meta-analysis

Although there are challenges in treating traumatic central nervous system diseases,mesenchymal stem cell-de rived extracellular vesicles(MSC-EVs) have recently proven to be a promising non-cellular the rapy.We comprehensively evaluated the efficacy of mesenchymal stem cell-de rived extracellular vesicles in traumatic central nervous system diseases in this meta-analysis based on preclinical studies.Our meta-analysis was registered at PROSPERO(CRD42022327904,May 24,2022).To fully retrieve the most relevant articles,the following databases were thoro ughly searched:PubMed,Web of Science,The Cochrane Library,and Ovid-Embase(up to April 1,2022).The included studies were preclinical studies of mesenchymal stem cell-derived extracellular vesicles for traumatic central nervous system diseases.The Systematic Review Centre for Laboratory Animal Experimentation(SYRCLE)’s risk of bias tool was used to examine the risk of publication bias in animal studies.After screening 2347studies,60 studies were included in this study.A meta-analysis was conducted for spinal co rd injury(n=52) and traumatic brain injury(n=8).The results indicated that mesenchymal stem cell-derived extracellular vesicles treatment prominently promoted motor function recovery in spinal co rd injury animals,including rat Basso,Beattie and Bresnahan locomotor rating scale scores(standardized mean difference [SMD]:2.36,95% confidence interval [CI]:1.96-2.76,P <0.01,I2=71%) and mouse Basso Mouse Scale scores(SMD=2.31,95% CI:1.57-3.04,P=0.01,I2=60%) compared with controls.Further,mesenchymal stem cell-de rived extracellular vesicles treatment significantly promoted neurological recovery in traumatic brain injury animals,including the modified N eurological Severity Score(SMD=-4.48,95% CI:-6.12 to-2.84,P <0.01,I2=79%) and Foot Fault Test(SMD=-3.26,95% CI:-4.09 to-2.42,P=0.28,I2=21%) compared with controls.Subgroup analyses showed that characteristics may be related to the therapeutic effect of mesenchymal stem cell-de rived extra cellular vesicles.For Basso,Beattie and Bresnahan locomotor rating scale scores,the efficacy of allogeneic mesenchymal stem cell-derived extracellular vesicles was higher than that of xenogeneic mesenchymal stem cell-derived extracellular vesicles(allogeneic:SMD=2.54,95% CI:2.05-3.02,P=0.0116,I2=65.5%;xenogeneic:SMD:1.78,95%CI:1.1-2.45,P=0.0116,I2=74.6%).Mesenchymal stem cellde rived extracellular vesicles separated by ultrafiltration centrifugation combined with density gradient ultra centrifugation(SMD=3.58,95% CI:2.62-4.53,P <0.0001,I2=31%) may be more effective than other EV isolation methods.For mouse Basso Mouse Scale scores,placenta-derived mesenchymal stem cell-de rived extracellular vesicles worked better than bone mesenchymal stem cell-derived extracellular vesicles(placenta:SMD=5.25,95% CI:2.45-8.06,P=0.0421,I2=0%;bone marrow:SMD=1.82,95% CI:1.23-2.41,P=0.0421,I2=0%).For modified Neurological Severity Score,bone marrow-derived MSC-EVs worked better than adipose-derived MSC-EVs(bone marrow:SMD=-4.86,95% CI:-6.66 to-3.06,P=0.0306,I2=81%;adipose:SMD=-2.37,95% CI:-3.73 to-1.01,P=0.0306,I2=0%).Intravenous administration(SMD=-5.47,95% CI:-6.98 to-3.97,P=0.0002,I2=53.3%) and dose of administration equal to 100 μg(SMD=-5.47,95% CI:-6.98 to-3.97,P <0.0001,I2=53.3%)showed better res ults than other administration routes and doses.The heterogeneity of studies was small,and sensitivity analysis also indicated stable results.Last,the methodological quality of all trials was mostly satisfactory.In conclusion,in the treatment of traumatic central nervous system diseases,mesenchymal stem cell-derived extracellular vesicles may play a crucial role in promoting motor function recovery.

An Analysis of the Hoarse Speech Signals by the Three Mass Model of Vocal Cords *

A three mass model of vocal cords as well as mathematical expression of the model are discussed. Different kinds of typical hoarse speech due to laryngeal diseases are simulated on microcomputer and the effects of different pathological factors of vocal cords on model parameters are studied. Some typical spectrum distribution of the simulated speech signals are given. Moreover, hoarse speech signals of some typical cases are analyzed by the methods of digital signal processing, including FFT, LPC, Cepstrum technique, Pseudocolor encoding, etc. The experiment results show that the three mass model analysis of vocal cords is an efficient method for analysis of hoarse speech signals.

Eff ects of early standardized enteral nutrition on preventing acute muscle loss in the acute exacerbation of chronic obstructive pulmonary disease patients with mechanical ventilation

BACKGROUND:To investigate the eff ects of early standardized enteral nutrition(EN)on the crosssectional area of erector spine muscle(ESMcsa),plasma growth diff erentiation factor-15(GDF-15),and 28-day mortality of acute exacerbation of chronic obstructive pulmonary disease(AECOPD)patients with invasive mechanical ventilation(MV).METHODS:A total of 97 AECOPD patients with invasive MV were screened in the ICUs of the First People's Hospital of Lianyungang.The conventional EN group(stage Ⅰ)and early standardized EN group(stage Ⅱ)included 46 and 51 patients,respectively.ESMcsa loss and GDF-15 levels on days 1 and 7 of ICU admission and 28-day survival rates were analyzed.RESULTS:On day 7,the ESMcsa of the early standardized EN group was significantly higher than that of the conventional EN group,while the plasma GDF-15 levels were significantly lower than those in the conventional EN group(ESMcsa:28.426±6.130 cm^(2) vs.25.205±6.127 cm^(2);GDF-15:1661.608±558.820 pg/mL vs.2541.000±634.845 pg/mL;all P<0.001).The 28-day survival rates of the patients in the early standardized EN group and conventional EN group were 80.40%and 73.90%,respectively(P=0.406).CONCLUSION:ESMcsa loss in AECOPD patients with MV was correlated with GDF-15 levels,both of which indicated acute muscular atrophy and skeletal muscle dysfunction.Early standardized EN may prevent acute muscle loss and intensive care unit-acquired weakness(ICU-AW)in AECOPD patients.

Electroacupuncture promotes the recovery of motor neuron function in the anterior horn of the injured spinal cord

Acupuncture has been shown to lessen the inflammatory reaction after acute spinal cord injury and reduce secondary injury.However,the mechanism of action remains unclear.In this study,a rat model of spinal cord injury was established by compressing the T8-9 segments using a modified Nystrom method.Twenty-four hours after injury,Zusanli（ST36）,Xuanzhong（GB39）,Futu（ST32）and Sanyinjiao（SP6）were stimulated with electroacupuncture.Rats with spinal cord injury alone were used as controls.At 2,4 and 6 weeks after injury,acetylcholinesterase（ACh E）activity at the site of injury,the number of medium and large neurons in the spinal cord anterior horn,glial cell line-derived neurotrophic factor（GDNF）m RNA expression,and Basso,Beattie and Bresnahan locomotor rating scale scores were greater in the electroacupuncture group compared with the control group.These results demonstrate that electroacupuncture increases ACh E activity,up-regulates GDNF m RNA expression,and promotes the recovery of motor neuron function in the anterior horn after spinal cord injury.

Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea- tures of 36 cases of inflammatory demyelinating pseudotumer in the spinal cord were retrospec- tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensofimotor disorder. Among them, six cases were misdiagnosed as having intrame- dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologically confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were common. Magnetic resonance imaging revealed edema and space-occupying lesions to varying degrees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like reinforcement （open-loop sign）. Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re- sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement （open-ring sign） on magnetic resonance imaging is the predominant property of inflammatory de- myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional patho- logical properties.

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND： Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE： To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN： Case analysis. SETTING： Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS： A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5 - 108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS： Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187 - 1 059 ng/L and normal value of serum homocysteine was 5 - 15μ mol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES： （1） Levels of blood routine, serum vitamin B12 and homocysteine; （2） results of neuroelectrophysiological examination; （3） results of MRI examination of spinal cord; （4） prognosis. RESULTS： Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. （1） Clinical manifestations： All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs （5 cases）, unstable gait （3 cases）, limb asthenia （4 cases）, limb numbness combined with light asthenia （5 cases）, limb numbness combined with unskillful activity （3 cases）, and limb numbness combined with unstable gait （1 case）. （2） Experimental results： Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of bomocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. （3） Results of neuroelectrophysiological examination： Among all patients, 95% （20/21） patients had abnormal sensory-evoked potential, 89% （8/9） patients had abnormal motor evoked potential, 67% （10/15） patients had abnormal nerve conduction, 13% （2/15） patients had neurogenic muscle injury showed by electromyography （EMG）, 70% （7/10） patients had abnormal brain-stem auditory evoked potential, and 40% （4/10） patients had abnormal visual evoked potential. （4） Results of MRI examination of spinal cord： MRI examination demonstrated that 40% （6/15） patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B I2 therapy. CONCLUSION： Nervous system lesion caused by vitamin B 12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin BI2. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.

Cortical transcriptome analysis after spinal cord injury reveals the regenerative mechanism of central nervous system in CRMP2 knock-in mice

Recent studies have shown that mutation at Ser522 causes inhibition of collapsin response mediator protein 2(CRMP2) phosphorylation and induces axon elongation and partial recovery of the lost sensorimotor function after spinal cord injury(SCI).We aimed to reveal the intracellular mechanism in axotomized neurons in the CRMP2 knock-in(CRMP2KI) mouse model by performing transcriptome analysis in mouse sensorimotor cortex using micro-dissection punching system.Prior to that, we analyzed the structural pathophysiology in axotomized or neighboring neurons after SCI and found that somatic atrophy and dendritic spine reduction in sensorimotor cortex were suppressed in CRMP2KI mice.Further analysis of the transcriptome has aided in the identification of four hemoglobin genes Hba-a1, Hba-a2, Hbb-bs, and Hbb-bt that are significantly upregulated in wild-type mice with concomitant upregulation of genes involved in the oxidative phosphorylation and ribosomal pathways after SCI.However, we observed substantial upregulation in channel activity genes and downregulation of genes regulating vesicles, synaptic function, glial cell differentiation in CRMP2KI mice.Moreover, the transcriptome profile of CRMP2KI mice has been discussed wherein energy metabolism and neuronal pathways were found to be differentially regulated.Our results showed that CRMP2KI mice displayed improved SCI pathophysiology not only via microtubule stabilization in neurons, but also possibly via the whole metabolic system in the central nervous system, response changes in glial cells, and synapses.Taken together, we reveal new insights on SCI pathophysiology and the regenerative mechanism of central nervous system by the inhibition of CRMP2 phosphorylation at Ser522.All these experiments were performed in accordance with the guidelines of the Institutional Animal Care and Use Committee at Waseda University, Japan(2017-A027 approved on March 21, 2017;2018-A003 approved on March 25, 2018;2019-A026 approved on March 25, 2019).

Discussion on the Diseases Relating to Spine

ＤｉｓｃｕｓｓｉｏｎｏｎｔｈｅＤｉｓｅａｓｅｓＲｅｌａｔｉｎｇｔｏＳｐｉｎｅ￥ＬｉＺｕｍｏ（ＧｕａｎｇＡｎＭｅｎＨｏｓｐｉｔａｌ，ＣｈｉｎａＡｃａｄｅｍｙｏｆＴＣＭ，Ｂｅｉｊｉｎｇ１０００５３．Ｃｈｉｎａ）Ｔｈｅｇｒｅａｔａｄｖａｎｃｅｓｈａｖｅｂｅ...

Observation of Therapeutic Effect with Hand Treating the Spine Relative Disease

ＯｂｓｅｒｖａｔｉｏｎｏｆＴｈｅｒａｐｅｕｔｉｃＥｆｆｅｃｔｗｉｔｈＨａｎｄＴｒｅａｔｉｎｇｔｈｅＳｐｉｎｅＲｅｌａｔｉｖｅＤｉｓｅａｓｅ￥Ｗａｎｇｗｅｉｊｕｎ（ＴｈｅＣｌｉｎｉｃｏｆＴｈｅＧｅｎｅｒａｌＯｆｆｉｃｅｏｆＩｎｖｅｓｔｉｇａｔｉｏｎＴｅ...

Neurotrophic fragments as therapeutic alternatives to ameliorate brain aging

Aging is a global phenomenon and a complex biological process of all living beings that introduces various changes.During this physiological process,the brain is the most affected organ due to changes in its structural and chemical functions,such as changes in plasticity and decrease in the number,diameter,length,and branching of dendrites and dendritic spines.Likewise,it presents a great reduction in volume resulting from the contraction of the gray matter.Consequently,aging can affect not only cognitive functions,including learning and memory,but also the quality of life of older people.As a result of the phenomena,various molecules with notable neuroprotective capacity have been proposed,which provide a therapeutic alternative for people under conditions of aging or some neurodegenerative diseases.It is important to indicate that in recent years the use of molecules with neurotrophic activity has shown interesting results when evaluated in in vivo models.This review aims to describe the neurotrophic potential of molecules such as resveratrol(3,5,4′-trihydroxystilbene),neurotrophins(brain-derived neurotrophic factor),and neurotrophic-type compounds such as the terminal carboxyl domain of the heavy chain of tetanus toxin,cerebrolysin,neuropeptide-12,and rapamycin.Most of these molecules have been evaluated by our research group.Studies suggest that these molecules exert an important therapeutic potential,restoring brain function in aging conditions or models of neurodegenerative diseases.Hence,our interest is in describing the current scientific evidence that supports the therapeutic potential of these molecules with active neurotrophic.

Blunt dopamine transmission due to decreased GDNF in the PFC evokes cognitive impairment in Parkinson’s disease

Studies have found that the absence of glial cell line-derived neurotrophic factor may be the primary risk factor for Parkinson’s disease. However, there have not been any studies conducted on the potential relationship between glial cell line-derived neurotrophic factor and cognitive performance in Parkinson’s disease. We first performed a retrospective case-control study at the Affiliated Hospital of Xuzhou Medical University between September 2018 and January 2020 and found that a decreased serum level of glial cell line-derived neurotrophic factor was a risk factor for cognitive disorders in patients with Parkinson’s disease. We then established a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and analyzed the potential relationships among glial cell line-derived neurotrophic factor in the prefrontal cortex, dopamine transmission, and cognitive function. Our results showed that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex weakened dopamine release and transmission by upregulating the presynaptic membrane expression of the dopamine transporter, which led to the loss and primitivization of dendritic spines of pyramidal neurons and cognitive impairment. In addition, magnetic resonance imaging data showed that the long-term lack of glial cell line-derived neurotrophic factor reduced the connectivity between the prefrontal cortex and other brain regions, and exogenous glial cell line-derived neurotrophic factor significantly improved this connectivity. These findings suggested that decreased glial cell line-derived neurotrophic factor in the prefrontal cortex leads to neuroplastic degeneration at the level of synaptic connections and circuits, which results in cognitive impairment in patients with Parkinson’s disease.

Minimally invasive procedures on the lumbar spine

Degenerative disease of the lumbar spine is a common and increasingly prevalent condition that is often implicated as the primary reason for chronic low back pain and the leading cause of disability in the western world. Surgical management of lumbar degenerative disease has historically been approached by way of open surgical procedures aimed at decompressing and/or stabilizing the lumbar spine. Advances in technology andsurgical instrumentation have led to minimally invasive surgical techniques being developed and increasingly used in the treatment of lumbar degenerative disease. Compared to the traditional open spine surgery, minimally invasive techniques require smaller incisions and decrease approach-related morbidity by avoiding muscle crush injury by self-retaining retractors, preventing the disruption of tendon attachment sites of important muscles at the spinous processes, using known anatomic neurovascular and muscle planes, and minimizing collateral soft-tissue injury by limiting the width of the surgical corridor. The theoretical benefits of minimally invasive surgery over traditional open surgery include reduced blood loss, decreased postoperative pain and narcotics use, shorter hospital length of stay, faster recover and quicker return to work and normal activity. This paper describes the different minimally invasive techniques that are currently available for the treatment of degenerative disease of the lumbar spine.