Effect of stromal cell-derived factor-1/CXCR4 axis in neural stem cell transplantation for Parkinson’s disease

Previous studies have shown that neural stem cell transplantation has the potential to treat Parkinson’s disease,but its specific mechanism of action is still unclear.Stromal cell-derived factor-1 and its receptor,chemokine receptor 4(CXCR4),are important regulators of cell migration.We speculated that the CXCR4/stromal cell-derived factor 1 axis may be involved in the therapeutic effect of neural stem cell transplantation in the treatment of Parkinson’s disease.A Parkinson’s disease rat model was injected with 6-hydroxydopamine via the right ascending nigrostriatal dopaminergic pathway,and then treated with 5μL of neural stem cell suspension(1.5×104/L)in the right substantia nigra.Rats were intraperitoneally injected once daily for 3 days with 1.25 mL/kg of the CXCR4 antagonist AMD3100 to observe changes after neural stem cell transplantation.Parkinson-like behavior in rats was detected using apomorphine-induced rotation.Immunofluorescence staining was used to determine the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Using quantitative real-time polymerase chain reaction,the mRNA expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra were measured.In addition,western blot assays were performed to analyze the protein expression of stromal cell-derived factor-1 and CXCR4.Our results demonstrated that neural stem cell transplantation noticeably reduced apomorphine-induced rotation,increased the mRNA and protein expression of stromal cell-derived factor-1 and CXCR4 in the right substantia nigra,and enhanced the immunoreactivity of tyrosine hydroxylase,CXCR4,and stromal cell-derived factor-1 in the brain.Injection of AMD3100 inhibited the aforementioned effects.These findings suggest that the stromal cell-derived factor-1/CXCR4 axis may play a significant role in the therapeutic effect of neural stem cell transplantation in a rat model of Parkinson’s disease.This study was approved by the Animal Care and Use Committee of Kunming Medical University,China(approval No.SYXKK2015-0002)on April 1,2014.     

Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.     

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune modulation.One of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment.In the present study,immortalized microglial cells were pretreated with L.barbarum extract for 1 hour and then treated with oligomeric Aβfor 23 hours.The results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial cells.The results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.     

All roads lead to Rome-a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer’s disease

Age-related neurodegenerative disorders such as Alzheimer’s disease(AD)have become a critical public health issue due to the significantly extended human lifespan,leading to considerable economic and social burdens.Traditional therapies for AD such as medicine and surgery remain ineffective,impractical,and expensive.Many studies have shown that a variety of bioactive substances released by physical exercise(called“exerkines”)help to maintain and improve the normal functions of the brain in terms of cognition,emotion,and psychomotor coordination.Increasing evidence suggests that exerkines may exert beneficial effects in AD as well.This review summarizes the neuroprotective effects of exerkines in AD,focusing on the underlying molecular mechanism and the dynamic expression of exerkines after physical exercise.The findings described in this review will help direct research into novel targets for the treatment of AD and develop customized exercise therapy for individuals of different ages,genders,and health conditions.     

Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer’s disease

Numerous molecular mechanisms are being examined in an attempt to discover disease-modifying drugs to slow down the underlying neurodegeneration in Alzheimer’s disease.Recent studies have shown the beneficial effects of epidermal growth factor receptor inhibitors on the enhancement of behavioral and pathological sequelae in Alzheimer’s disease.Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer’s disease,there is no irrefutable neuroprotective evidence in well-established animal models using epidermal growth factor receptor inhibitors due to many un-explored downstream signaling pathways.This caused controversy about the potential involvement of epidermal growth factor receptor inhibitors in any prospective clinical trial.In this review,the mystery beyond the under-investigation of epidermal growth factor receptor in Alzheimer’s disease will be discussed.Furthermore,their molecular mechanisms in neurodegeneration will be explained.Also,we will shed light on SARS-COVID-19 induced neurological manifestations mediated by epidermal growth factor modulation.Finally,we will discuss future perspectives and under-examined epidermal growth factor receptor downstream signaling pathways that warrant more exploration.We conclude that epidermal growth factor receptor inhibitors are novel effective therapeutic approaches that require further research in attempts to be repositioned in the delay of Alzheimer’s disease progression.     

高效液相色谱法同时测定人血浆1'-羟基咪达唑仑与咪达唑仑含量

目的建立同时检测1’-羟基咪达唑仑和咪达唑仑血药浓度的高效液相色谱法。方法采用Zirchrom 反相柱(Kromasil C18， 250 mm×4.6 mm，5 μm)；柱温：40 ℃；流动相：醋酸铵水溶液-甲醇(35∶65，V/V)；流速：1.5 mL·min^-1，样品经碱化提取分离后，流动相溶解，在220 nm波长处检测，内标：地西泮溶液。结果1’-羟基咪达唑仑和咪达唑仑分别在0.005 ～0.100和0.01 ～0.20 μg·mL^-1范围内线性关系良好，最低检测浓度分别为0.002和0.003 μg·mL^-1。萃取回收率均＞95%，日内和日间RSD均＜5%。结论该方法专一性强、灵敏度高、简单可靠，可用于研究体内CYP3A4酶的活性。     

1例Bowen＇s病复发患者外阴切除术的护理

对1例Bowen＇s病复发患者行外阴切除术，术后6d切口一期愈合，住院21d康复出院，随访1年,无复发。提出术前做好心理护理、术前准备及外阴清洗；术后密切观察病情变化。加强外阴护理应出院指导，可提高手术治疗效果,避免复发。     

单侧多功能外固定“T”型架治疗新鲜股骨髁上骨折5例

我院骨科近两年用单侧多功能外固定支架中的“T”型架治疗股骨髁上骨折5例,骨折愈合情况较好,报道如下。1 临床资料1.1 一般资料 本组5例,男3例,女2例。年龄38～68岁,平均50.6岁。从受伤到手术时     

Peyronie''''s病研究新进展

Peyronie’s病是发生在阴茎海绵体白膜内，以无弹性的纤维斑块为特征的一种疾病。由此可导致阴茎勃起疼痛、勃起弯曲，严重者可造成性交困难或勃起功能障碍，给患者带来极大的痛苦。作者曾在1995年对该病的病因、病理与治疗研究进展作了综述。但随着医学科学的不断进步，特别是对分子生物学的研究，对该病的各个方面又有许多新的研究进展，现综述如下。