Percutaneous kyphoplasty in the treatment of Kümmell disease in lumbar scoliosis:A case report

BACKGROUND Due to mechanical imbalance in the spine,elderly scoliosis patients tend to develop vertebral fracture nonunion,i.e.,Kümmell disease,when osteoporotic vertebral compression fractures occur.However,accompanying vertebral rotational deformities make surgical procedures challenging risky.Such patients are usually compelled to undergo conservative treatment and there are very few reports on minimally invasive surgeries for them.We first-time report a patient with Kümmell disease and lumbar scoliosis treated with percutaneous kyphoplasty(PKP)under O-arm guidance.CASE SUMMARY An 89-year-old female was admitted to the hospital due to delayed low back pain after a fall.She was diagnosed with Kümmell disease based on physical and radiologic examinations.The patient experienced severe scoliosis and subsequently underwent O-arm-guided kyphoplasty,resulting in a significant alleviation of low back pain.CONCLUSION PKP has good efficacy in treating Kümmell disease.However,surgical risks are elevated in scoliosis patients with Kümmell disease due to the abnormal anatomical structure of the spine.O-arm assisted operations play a crucial role in decreasing surgical risks.

Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

椎体后凸成形术治疗骨质疏松性Kümmell's病

目的:探讨球囊扩张椎体后凸成形术治疗骨质疏松性Kümmell's病的疗效。方法:2007年1月～2009年10月对12例骨质疏松性Kümmell's病患者行球囊扩张椎体后凸成形术治疗。男3例,女9例;年龄61～87岁,平均69.9岁;背部疼痛病史1个月～2年,平均2.7个月。测量术前、术后2d及末次随访时站立位X线片椎体前缘高度,并采用视觉模拟评分(VAS)及Oswestry功能障碍指数(ODI)综合评估手术疗效。结果:3例发生骨水泥渗漏,但未出现临床症状。病椎前缘高度由术前平均31.4%恢复至术后68.7%,VAS及ODI评分由术前平均8.9分、87.5%改善至术后平均2.4分、30.9%,差异均有统计学意义(P<0.01);随访6～36个月,平均19.7个月,末次随访时病椎前缘高度为67.1%,VAS和ODI分别为2.2分和26.7%,与术后2d时比较差异均无统计学意义(P>0.05)。结论:球囊扩张椎体后凸成形术是治疗骨质疏松性Kümmell's病的有效方法之一。

椎体后凸成形术治疗Kümmell's病疗效观察

目的观察经皮球囊扩张椎体后凸成形术（percutaneous kyphoplasty,PKP）治疗老年Kümmell＇s病的临床疗效。方法自2010年7月至2014年2月采用经皮球囊扩张椎体后凸成形术治疗老年骨质疏松性Kümmell＇s病21例,男性10例,女性11例;年龄61-82岁,平均69.2岁。测量比较术前、术后1周及末次随访时侧位X线片病椎椎体高度变化及Cobb角变化,根据疼痛视觉模拟评分（visual analogue scale,VAS）进行评估。结果 21例患者手术成功,术后1周及末次随访VAS评分、病椎椎体高度及Cobb角均较术前明显改善,差异有统计学意义（P〈0.05）;术后1周与末次随访之间差异无统计学意义（P〉0.05）。结论 PKP是治疗无神经压迫损伤Kümmell＇s病安全有效的方法。

应用过伸位CT重建预判椎体强化术治疗Ⅲ期可复型kümmell's病

目的 探讨过伸位CT重建在经皮强化术治疗Ⅲ期可复型kümmell＇s病中的价值。方法 回顾性分析骨质疏松椎体压缩骨折患者中的Ⅲ期可复型kümmell＇s病患者19例,男7例,女12例,年龄59~88岁,平均（74.6±9.2）岁。其中T（10）1例,T（11）3例,T（12）8例,L（1）5例,L（2）1例,L（4）1例。术前均行脊柱X线片、过伸位CT、MRI等影像学检查,所有患者均采用椎体强化术治疗。记录术前、术后第7天及末次随访时的疼痛视觉模拟（VAS）评分、Oswestry功能障碍指数（ODI）、伤椎前缘及中间高度、病椎局部矢状Cobb角,记录手术并发症。结果 19例患者均顺利完成手术,无严重手术并发症发生,4例患者出现少量骨水泥椎间隙渗漏,2例沿椎体前方骨壁裂隙渗漏,未出现临床症状。18例患者获随访,随访时间7~42个月,平均（22±13.5）个月。术后第7天及末次随访与术前相比,椎体高度得到恢复,后凸畸形角度显著改善,VAS及ODI评分明显下降（P〈0.05）;术后1周与末次随访差异无统计学意义（P〉0.05）。随访期间3例患者出现邻近椎体骨折,再次行椎体强化术后痊愈。结论 应用过伸位CT重建预判Ⅲ期可复型kümmell＇s病,对指导经皮椎体强化术治疗Ⅲ期kümmell＇s病有较高的临床价值。

Role of calbindin-D28K in estrogen treatment for Parkinson’s disease

Studies have shown that estrogen has neuroprotective effects on the nigrostriatal system. The present study established a Parkinson＇s disease model in C57BL/6 mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrapyridine. The mice were subjected to 1713 estradiol injection into the lateral ventricle. Immunofluorescence double staining showed that estrogen increased tyrosine hydroxylase and calbindin-D28K expression and co-expression in dopaminergic neurons of midbrain substantia nigra pars compacta of model mice. Behavior experiments showed that estrogen improved swimming and hanging behaviors in this mouse model of Parkinson＇s disease.

Strategy for prevention of hip fractures in patients with Parkinson's disease

Hypovitaminosis D and K due to malnutrition or sunlight deprivation,increased bone resorption due to immobilization,low bone mineral density(BMD)and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Parkinson’s disease.The purpose of the present study was to clarify the efficacy of interventions intended to prevent hip fractures in elderly patients with Parkinson’s disease.Pub Med was used to search the literature for randomized controlled trials(RCTs)regarding Parkinson’s disease and hip fractures.The inclusion criteria were 50 or more subjects per group and a study period of 1 year or longer.Five RCTs were identified and the relative risk and95%confidence interval were calculated for individual RCTs.Sunlight exposure increased serum hydroxyvitamin D[25(OH)D]concentration,improved motor function,decreased bone resorption and increased BMD.Alendronate or risedronate with vitamin D supplementation increased serum 25(OH)D concentration,strongly decreased bone resorption and increased BMD.Menatetrenone(vitamin K2)decreased serum undercarboxylated osteocalcin concentration,decreased bone resorption and increased BMD.Sunlight exposure(men and women),menatetrenone(women),alendronate and risedronate with vitamin D supplementation(women)significantly reduced the incidence of hip fractures.The respective RRs(95%confidence intervals)according to the intention-to-treat analysis were 0.27(0.08,0.96),0.13(0.02,0.97),0.29(0.10,0.85)and 0.20(0.06,0.68).Interventions,including sunlight exposure,menatetrenone and oral bisphosphonates with vitamin D supplementation,have a protective effect against hip fractures elderly patients with Parkinson’s disease.

Treatment of Kümmell’s disease with sequential infusion of bone cement:A retrospective study

BACKGROUND Percutaneous vertebroplasty(PVP)is an effective method for the treatment of neurologically intact Kümmell’s disease,but bone cement leakage during surgery is a problem that deserves attention.AIM To reduce bone cement leakage and evaluate the effect of the sequential infusion of bone cement during PVP for the treatment of stage I or II Kümmell’s disease.METHODS Patients with Kümmell’s disease treated in our hospital from September 2015 to September 2018 were retrospectively analyzed.Patients meeting the inclusion and exclusion criteria were divided into two groups:Traditional single infusion and sequential infusion(SI).The visual analog scale(VAS)and Oswestry disability index(ODI)were evaluated and compared,and duration of operation,bone cement content and complications were recorded.RESULTS Forty-five patients were included in this study;there were 24 in the traditional single infusion group and 21 in the SI group.The VAS and ODI were significantly different for both groups when compared pre-and postoperatively,whereas the differences between 1 wk postoperatively and at the final follow-up were not statistically.When the VAS and ODI of the two groups were compared,there were no significant differences at any time point.The leakage rate of bone cement was significantly lower in the SI group(14.3%,3 of 21)than that in the traditional single infusion group(41.7%,10 of 24).CONCLUSION SI in unipedicular PVP is a safe and effective procedure for neurologically intact Kümmell’s disease,and this technique could decrease the incidence of bone cement leakage.

The Role of RP105 in Cardiovascular Disease through Regulating TLR4 and PI3K Signaling Pathways

Raidoprotective 105(RP105)was first discovered on the surface of mouse B cells and it has been demonstrated that RP105 can function as an inflammatory regulator in cardiovascular disease(CVD),such as myocardial ischemic reperfusion injury(MI/RI),atherosclerosis and myocardial infarction(MI).As a member of Toll-like receptor(TLR)homolog which is capable of regulating toll-like receptor(TLR4)signaling pathway,RP105 is implicated in various biological processes.Mounting evidence suggests that RP105 regulates the function of TLR4 and phosphoinositide 3-kinase(PI3K)signaling pathways.Here,we review the effect of RP105 on CVD through regulating TLR4/PI3K signaling pathways.

The MORC2 p.S87L mutation reduces proliferation of pluripotent stem cells derived from a patient with the spinal muscular atrophy-like phenotype by inhibiting proliferation-related signaling pathways

Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.

Schwann cells differentiated from skin-derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson’s disease

Autophagy has been shown to play an important role in Parkinson’s disease.We hypothesized that skin-derived precursor cells exhibit neuroprotective effects in Parkinson’s disease through affecting autophagy.In this study,6-hydroxydopamine-damaged SH-SY5Y cells were pretreated with a culture medium containing skin-derived precursors differentiated into Schwann cells(SKP-SCs).The results showed that the SKP-SC culture medium remarkably enhanced the activity of SH-SY5Y cells damaged by 6-hydroxydopamine,reduced excessive autophagy,increased tyrosine hydroxylase expression,reducedα-synuclein expression,reduced the autophagosome number,and activated the PI3K/AKT/mTOR pathway.Autophagy activator rapamycin inhibited the effects of SKP-SCs,and autophagy inhibitor 3-methyladenine had the opposite effect.These findings confirm that SKP-SCs modulate the PI3K/AKT/mTOR pathway to inhibit autophagy,thereby exhibiting a neuroprotective effect in a cellular model of Parkinson’s disease.This study was approved by the Animal Ethics Committee of Laboratory Animal Center of Nantong University(approval No.S20181009-205)on October 9,2018.

Expression of calbindin D28K in substantia nigra of model rats with Parkinson disease

BACKGROUND： Previous researches suggested that expression level of calbindin D28K mRNA decreased in substantia nigra （SN） of model rats with Parkinson disease （PD）, and this might be related to the decrease of anti-degeneration potentials of dopaminergic neurons. OBJECTIVE： To observe expression changes of calbindin D28K in SN dopaminergic neurons during their degeneration and death in midbrain of PD model rats. DESIGN： Completely randomized grouping design SETTING： Department of Neurobiology, Xuzhou Medical College MATERIALS＂ A total of 92 healthy male SD rats, with the age of 3 months, weighing 200-250 g, were selected from Experimental Animal Center of Xuzhou Medical College [certification： SCXK （su） 2003-0003]. Calbindin D28K（CB）, tyroxine hydroxylase （TH）, ABC kit, 6-hydroxydopamine （6-OHDA） and Nissl dyes were provided by Sigma Company, and sheep serum was provided by Beijing Zhongshan Company. METHODS： The experiment was carried out in the Neurobiological Center of Xuzhou Medical College from October 2003 to October 2004. ① With lot method, rats were divided into blank control group （n=28）, experimental control group （n=-28） and experimental group （n=36）. Rats in experimental group were injected with 6-OHDA at right corpus striatum for PD modeling; rats in experimental control group were injected with saline at the same site; rats in blank control group did not give any injections.② On the 7^th, 14^th, 21^st and 28^th days, SN segments on right midbrain from every 5 rats in experimental group were fixed, embedded with paraffin and cut into successively coronary pieces. Rats in other two groups were treated with the same methods and then stained with Nissl to show neuronal form. Meanwhile, CB and TH antibodies staining with immunohistochemistry were used to show CB containing dopaminergic neurons and dopaminergic neurons, and cells were calculated and observed under optic microscope. ③ On the 14^th and 28^th days, every 4 rats in experimental group and every 4 rats in control group were selected to obtain their brains and separate SN on the injured side. Western blot was used to detect expression of calbindin D28K, protein band was scanned with imaging equipment, and data were analyzed with LabWorks software. MAIN OUTCOME MEASURES：① On the 7^th, 14^th, 21^st and 28^th days, Nissl staining results of SN neurons and immunohistochemical staining results of CB and TH antibodies; ② On the 14^th and 28^th days, Western blot results of calbindin D28K in SN neurons, RESULTS; Among 92 rats, 2 rats in experimental group died after 1 day due to 6-OHDA injection and other 90 rats were involved in the final analysis. ①Nissl staining results： On the 7^th day of 6-OHDA injection, most neuronal somas on right SN pars compacta were shown as deep pycnosis or lysis breakage; on the 14^th and 21^st days, amount of neurons was decreased remarkably; on the 28^th day, most neurons in SN pars compacta disappeared. ② Results of immunohistochemical staining： Amount of positive neurons of calbindin D28K in right SN pars compacta was not changed on the 7^th day after 6-OHDA injection; on the 14^th day, the amount was higher in experimental group than that in both control groups （P 〈 0.01） and was decreased till the 21^st day, but it was still higher than that in the two control groups （P 〈 0.05）; on the 28^th day, positive neurons of calbindin D28K nearly disappeared, and the amount was lower than that in the two control groups （P 〈 0.01）. In addition, on the 7^th day after 6-OHDA injection into corpus striatum, positive TH neurons decreased 24% in right SN, and there was significant difference from that in control groups; on the 14^th, 21^st and 28^th days, positive TH neurons decreased 37%, 46% and 64%, respectively. ③ Western blot results： On the 14＇h day after 6-OHDA injection into corpus striatum, expression of calbindin D28K in right SN was higher in experimental group than that in both control groups （P 〈 0.05）; however, on the 28^th day, the expression was lower than that in the two control groups （P 〈 0.01 ）. CONCLUSION ： During degeneration and death of dopaminergic neurons, CB expression in SN pars compacta increases firstly and decreased gradually.

肝豆状核变性患者角膜K-F环与临床病情程度关系探讨

目的分析不同角膜K-F环分级的肝豆状核变性(WD)患者肝功能变化及其对治疗应答的影响。方法2016年2月~2022年12月联勤保障部队第九一医院眼科就诊或会诊的WD患者63例,在裂隙灯显微镜下检查进行K-F环分级。给予所有患者D-青霉胺治疗2~6个月。结果在63例WD患者中,发现角膜K-F环1级8例,2级14例,3级41例;临床肝型35例,脑型16例,其他类型5例和混合型7例,肝型、脑型、其他型和混合型患者角膜K-F环3级占比分别为62.9%、75.0%、60.0%和57.1%,各组间无显著性差异(P>0.05);在治疗6月末,22例角膜K-F环3级肝型患者血清总胆红素和谷丙转氨酶水平分别为(38.3±5.4)μmol/L和(92.4±10.5)U/L,显著高于9例2级患者【分别为(25.9±8.8)μmol/L和(46.5±11.3)U/L,P<0.05】或4例1级患者【分别为(16.3±3.2)μmol/L和(36.4±5.7)U/L,P<0.05】,而血清白蛋白和銅蓝蛋白水平分别为(26.4±6.4)g/L和(90.8±18.6)mg/L,显著低于2级患者【分别为(42.7±8.2)g/L和(187.5±13.4)mg/L,P<0.05】或1级患者【(46.9±10.1)g/L和(224.3±25.9)mg/L,P<0.05】。结论角膜K-F环3级的WD患者可能病情重,对治疗应答差,应予以特别关注和处理。

Percutaneous vertebroplasty versus percutaneous kyphoplasty for the treatment of delayed post-traumatic vertebral body collapse(Kümmell’s disease) in Chinese patients: a systematic review and meta-analysis

Objective: To compare the clinical efficacy between percutaneous vertebroplasty(PVP) and percutaneous kyphoplasty(PKP) in the treatment of Kümmell's disease in Chinese patients.Methods: The studies using randomized controlled trials to compare clinical efficacy between PVP and PKP in the treatment of Kümmell's disease in Chinese patients were retrieved from Embase, Pubmed, Central, Cinahl, PQDT, CNKI, CQVIP, Wanfang Data, and CBM(from September 2008 to September 2018). Keywords for both Chinese and English search were: percutaneous vertebroplasty, PVP, percutaneous kyphoplasty, PKP, and Kümmell's disease. A total of 132 articles were retrieved based on the search strategy through online database searching and manual searching. Finally, one foreign report and seven Chinese reports were included. After extracting the data, statistical software Review Manager 5.3 was used for data analysis.Results: Through comparison, Cobb angle(95% CI [0.54, 4.42), P = 0.01] and Oswestry Dysfunction Index(ODI)(95% CI [0.21, 2.15], P= 0.02) of PKP group was smaller than that of PVP group. Postoperative anterior vertebral body height of the PKP group was better than PVP group(95% CI [-1.27,-0.66], P < 0.001]. However, the PVP group had shorter operation time than PKP group(95% CI [-13.48,-7.43), P = 0.001]. In the other outcome measures, including Visual Analogue Scale(VAS) score(95% CI [-0.04, 0.27), P = 0.15), cement volume(95% CI [-0.82, 0.32], P = 0.39) and cement leakage(95% CI [0.90, 2.76], P = 0.11), there was no significant differences between the two procedures.Conclusions: At this stage, there is sufficient evidence to support that PKP is better than PVP in the treatment of Kümmell's disease in Chinese patients. Although PVP surgery requires much less operation time, PKP has better postoperative radiological results and lower ODI. Moreover, both of them had similar clinical results(e.g., analgesic effects, cement dosage, and leakage rate). Further evidence is dependent on the emergence of randomized controlled trials with higher quality and larger sample sizes in the future.

维生素K治疗神经退行性疾病的分子机制与临床研究进展

目的 总结维生素K治疗神经退行性疾病的分子机制与临床研究进展。方法 采用文献分析法,检索PubMed和中国知网数据库中自建库起至2024年2月有关维生素K治疗神经退行性疾病的文献,以蛋白质错误折叠、线粒体功能障碍、氧化应激、神经炎症和铁死亡为切入点,梳理维生素K治疗神经退行性疾病的分子机制。结果与结论 维生素K通过影响蛋白聚集及自噬的调控,可改善线粒体功能,减少氧化应激、神经炎症、铁死亡等的发生,逆转细胞或动物模型的神经退行性疾病病理过程。

Indirubin alleviates retinal neurodegeneration through the regulation of PI3K/AKT signaling

Retinal neurodegenerative disease is a leading cause of blindness among the elderly in developed countries,including glaucoma,diabetic retinopathy,traumatic optic neuropathy and optic neuritis,etc.The current clinical treatment is not very effective.We investigated indirubin,one of the main bioactive components of the traditional Chinese medicine Danggui Longhui Pill,in the present study for its role in retinal neurodegeneration.Indirubin exhibited no detectable tissue toxicity in vivo or cytotoxicity in vitro.Moreover,indirubin improved visual function and ameliorated retinal neurodegeneration in mice after optic nerve crush injury in vivo.Furthermore,indirubin reduced the apoptosis of retinal ganglion cells induced by oxidative stress in vitro.In addition,indirubin significantly suppressed the increased production of intracellular reactive oxygen species and the decreased activity of superoxide dismutase induced by oxidative stress.Mechanically,indirubin played a neuroprotective role by regulating the PI3K/AKT/BAD/BCL-2 signaling.In conclusion,indirubin protected retinal ganglion cells from oxidative damage and alleviated retinal neurodegeneration induced by optic nerve crush injury.The present study provides a potential therapeutic medicine for retinal neurodegenerative diseases.

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

Mechanism of stilbene glycosides on apoptosis of SH-SY5Y cells via regulating PI3K/AKT signaling pathway

Objective:To investigate the effects of stilbene glycoside(TSG)on okadaic acid-induced apoptosis in human neuroblastoma cells(SH-SY5Y)via the PI3K/AKT pathway.Methods:The optimal concentration of OA was screened by CCK-8 assay,and SH-SY5Y cells were divided into control group,model group,TSG group,LY294002 group and LY294002+TSG group.The proliferation and apoptosis in each group were detected by CCK-8 and TUNEL assays;Western blotting method and real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of PI3K,P-PI3K(Y607),AKT,P-AKT(Ser473),Bcl-2 and Bax proteins.The relative protein expression was represented by P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax gray ratio.Results:CCK-8 screened the optimal concentration of OA as 40 nmol/L.Compared with the control group,the model group increased relative cell viability,decreased apoptosis rate,the pathway and apoptotic proteins expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were decreased,and the mRNA expression levels of PI3K,AKT and Bcl-2 were decreased.Bax mRNA expression level increased(P<0.05);Compared with model group,TSG group increased relative cell viability,decreased apoptosis rate,increased protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT,Bcl-2/Bax,and increased mRNA expression levels of PI3K,AKT,and Bcl-2.Bax mRNA expression decreased(P<0.05),LY294002 group decreased relative cell viability,increased apoptosis rate,P-PI3K(Y607)/PI3K protein expression levels were significantly decreased(P<0.05),P-AKT(Ser473)/AKT and Bcl-2/Bax protein expression levels were significantly decreased,but there was no statistical significance,PI3K,AKT and Bcl-2 mRNA expression levels were decreased,and Bax mRNA expression levels were increased(all P<0.05);Compared with LY294002 group,LY294002+TSG group increased relative cell viability,decreased apoptosis rate,and the protein expression levels of P-PI3K(Y607)/PI3K,P-AKT(Ser473)/AKT and Bcl-2/Bax were increased.The mRNA expression levels of PI3K,AKT,Bcl-2 were increased,Bax was decreased(all P<0.05).Conclusion:Stilbene glycoside may alleviate okadaic acid-induced apoptosis in SH-SY5Y cells by interfering with the PI3K/AKT signaling pathway,which in turn regulates the expression of apoptotic factors such as Bcl-2 and Bax.

Research progress on the correlation between ion channel and excitability of striatum neurons in Parkinson's disease

Parkinson's disease(PD)is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain,however the pathogenesis is unclear.There is a correlation between the excitability of striatal neurons and PD.Ion channels are important to maintain membrane potential and regulate excitability of neurons,while ionic mechanisms for modulation of neurons excitability are not fully understood.This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD.In order to find new targets to treatment PD by intervening ion channels.