Cell viability and dopamine secretion of 6-hydroxydopamine-treated PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells

In the present study, PC12 cells induced by 6-hydroxydopamine as a model of Parkinson＇s Disease, were used to investigate the protective effects of bone marrow-derived mesenchymal stem cells bone marrow-derived mesenchymal stem cells against 6-hydroxydopamine-induced neurotoxicity and to verify whether the mechanism of action relates to abnormal a-synuclein accumulation in cells Results showed that co-culture with bone marrow-derived mesenchymal stem cells enhanced PC12 cell viability and dopamine secretion in a cell dose-dependent manner. MitoLight staining was used to confirm that PC12 cells co-cultured with bone marrow-derived mesenchymal stem cells demonstrate reduced levels of cell apoptosis. Immunocytochemistry and western blot analysis found the quantity of α-synuclein accumulation was significantly reduced in PC12 cell and bone marrow-derived mesenchymal stem cell co-cultures. These results indicate that bone marrow-derived mesenchymal stem cells can attenuate 6-hydroxydopamine-induced cytotoxicity by reducing abnormal α-synuclein accumulation in PC12 cells.

Ghrelin alleviates 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells

Ghrelin is a neuropeptide that has various physiological functions and has been demonstrated to be neuroprotective in a number of neurological disease models.However,the underlying mechanisms of ghrelin in Parkinson’s disease remain largely unexplored.The current study aimed to study the effects of ghrelin in a 6-hydroxydopamine(6-OHDA)-induced Parkinson’s disease model and evaluate the potential underlying mechanisms.In the present study,we treated an SH-SY5 Y cell model with 6-OHDA,and observed that pretreatment with different concentrations of ghrelin(1,10,and 100 nM)for 30 minutes relieved the neurotoxic effects of 6-OHDA,as revealed by Cell Counting Kit-8 and Annexin V/propidium iodide(PI)apoptosis assays.Reverse transcription quantitative polymerase chain reaction and western blot assay results demonstrated that 6-OHDA treatment upregulatedα-synuclein and lincRNA-p21 and downregulated TG-interacting factor 1(TGIF1),which was predicted as a potential transcription regulator of the gene encodingα-synuclein(SNCA).Ghrelin pretreatment was able to reverse the trends caused by 6-OHDA.The Annexin V/PI apoptosis assay results revealed that inhibiting eitherα-synuclein or lincRNA-p21 expression with small interfering RNA(siRNA)relieved 6-OHDA-induced cell apoptosis.Furthermore,inhibiting lincRNA-p21 also partially upregulated TGIF1.By retrieving information from a bioinformatics database and performing both double luciferase and RNA immunoprecipitation assays,we found that lincRNA-p21 and TGIF1 were able to form a double-stranded RNA-binding protein Staufen homolog 1(STAU1)binding site and further activate the STAU1-mediated mRNA decay pathway.In addition,TGIF1 was able to transcriptionally regulateα-synuclein expression by binding to the promoter of SNCA.The Annexin V/PI apoptosis assay results showed that either knockdown of TGIF1 or overexpression of lincRNA-p21 notably abolished the neuroprotective effects of ghrelin against 6-OHDA-induced neurotoxicity.Collectively,these findings suggest that ghrelin exerts neuroprotective effects against 6-OHDA-induced neurotoxicity via the lincRNA-p21/TGIF1/α-synuclein pathway.

Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson’s disease

Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson’s disease using 6-hydroxydopamine. When SH-SY5 Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson’s disease and in a mouse model of Parkinson’s disease. Next, we pretreated cell models of Parkinson’s disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson’s disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor downregulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase(PI3 K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulinlike growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3 K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson’s disease treatment.

Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson＇s disease models

Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson＇s disease animal models.They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra,but also satisfy the requirements for iron deposition.However,few studies have compared the characteristics of these two models by magnetic resonance imaging.In this study,rat models of Parkinson＇s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra.At 1,2,4,and 6 weeks after injection,coronal whole-brain T2-weighted imaging,transverse whole-brain T2-weighted imaging,and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2＊ values at the injury site.The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group.In the 6-hydroxydopamine group,the fractional anisotropy value was decreased,but T2＊ values were increased on the right side of the substantia nigra at 1 week.Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods,while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson＇s disease over long periods.

Reduced glutathione alleviates the toxic effect of 6-hydroxydopamine on bone marrow stromal cells

We studied the effect of reduced glutathione on bone marrow stromal cells （BMSCs） treated with 6-hydroxydopamine （6-OHDA）, which shows a toxic effect on dopaminergic neurons. The proliferation of BMSCs treated with 6-OHDA decreased, while that of BMSCs treated with reduced glutathione increased. The proliferation of BMSCs treated with both 6-OHDA and reduced glutathione was significantly higher compared with that treated with 6-OHDA alone. These findings indicate that reduced glutathione alleviates the toxic effect of 6-OHDA on BMSCs.

Dimethyl sulfide,a metabolite of the marine microorganism,protects SH-SY5Y cells against 6-hydroxydopamine and MPP~＋-induced apoptosis

Dimethyl sulfide(DMS)has been historically recognized as a metabolite of the marine microorganism or a disgusting component for the smell of halitosis patients.In our recent study,DMS has been identified as a cytoprotectant that protects against oxidative-stress induced cell death and aging.We found that at near-physiological concentrations,DMS reduced reactive oxygen species(ROS)in cultured PC12 cells and alleviated oxidative stress.The radical-scavenging capacity of DMS at near-physiological concentration was equivalent to endogenous methionine(Met)-centered antioxidant defense.Methionine sulfoxidereductase A(MsrA),the key antioxidant enzyme in Met-centered defense,bound to DMS and promoted its antioxidant capacity via facilitating the reaction of DMS with ROS through a sulfonium intermediate at residues Cys72,Tyr103,Glu115,followed by the release of dimethyl sulfoxide(DMSO).MTT assay and trypan blue test indicated that supplement of DMS exhibited cytoprotection against 6-hydroxydopamine and MPP+induced cell apoptosis.Furthermore,Msr A knockdown abolished the cytoprotective effect of DMS at near-physiological concentrations.The present study reveals new insight into the potential therapeutic value of DMS in Parkinson disease.

Protective Effect of Immaturue Bitter Orange(Citrus aurantium L.)Flavonoids Extracts on PC12 Cell Injury Induced by 6-Hydroxydopamine

To study the neuro protective effect of flavonoids extracts from immature bitter orange(Citrus aurantium L.),the PC12 cells treated with 6-hydroxydopamine(6-OHDA)were used as the Parkinson’s disease(PD)model.To determine the optimal dose of 6-OHDA for constructing a PD model,PC12 cells were incubated with different concentrations of 6-OHDA for 24 h.After 24 h incubation,PC12 cells of drug groups were added 6-OHDA and different concentrations of flavonoids extracts were measured cell viability by CCK8 for selecting effective concentration of flavonoids extracts;the ROS level was determined using flow cytometry;the levels of MDA,CAT,SOD and GSH-Px were assayed by Colorimetric kit for oxidative stress investigation.Compared with the model group,PC12 cell viability was significantly enhanced(P<0.05),the levels of ROS and MDA were reduced significantly(P<0.05),and the activities of SOD,CAT and GSH-Px were significantly enhanced(P<0.05)in drug groups.In conclusion,immature bitter orange flavonoids extracts could protect PC12 cells against 6-OHDA-induced oxidative stress.

Feasibility of establishing model of Parkinson disease by injecting 6-hydroxydopamine at different parts of the nigrostriatal pathway in the brain of rats

BACKGROUND： Previous researches found that animal models with Parkinson disease （PD） could be established by injecting 6-hydroxydopamine （6-OHDA） into medial forebrain bundle （MFB）, substantia nigra compacta （SNC） and caudate-putamen complex （CPU） of the nigrostriatal pathway. OBJECTIVE ： To compare behavioral, biochemica 6-OHDA injections in the areas of MFB, SNC and DESIGN： Controlled observational study and histological properties of these rats undergoing the CPU respectively. SEI-IING： Department of Neurology, First Affiliated Hospital of Guangxi Medical University MATERIALS： A total of 64 adult female SD rats weighing 180-230 g were provided by the Animal Experimental Center of Guangxi Medical University. 6-OHDA （Sigma Company, USA）; Brain solid positioner （Standard model 51600, Stoelting Co., IL, USA）; rotational monitoring of little animal （type QL-1, USA）; high liquid chromatography （HLC, Waters Company）. METHOOS： The experiment was carried out in the Medical Experimental Center of Guangxi Medical University from February to December 2005. ① According to digital table, 64 SD rats were divided into MFB group, SNC group, CPU group and control group with 16 in each group. On the basis of the brain atlas of Paxinos, rats in the first three groups were injected with 5 μL 6-OHDA into right MFB （0 mm of line of incisor tooth, A/P 4.4 mm, L/R 1.2 mm, ON -7.8 mm）, SNC （line of incisor tooth just equal to horizon, A/P -4.8 mm, L/R 1.6 mm, ON -7.8 mm） and CPU （0 mm of line of incisor tooth, A/P 1.2 mm, L/R 2.7 mm, ON -5.4 mm）, respectively. The rats in control group were injected with 5 μL ascorbic acid solution （2 g/L）. One week after operation, 0.1 g/L apomorphine （Apo, 0.05 mg/kg） was subcutaneously injected into neck and then rotational behavior induced by Apo was recorded once a week for 8 weeks. The PD models were considered successful only when rotational times more than or equal to 7 times per minute. Eight weeks after operation, micro-perfusion was used to obtain micro-perfusate in bilateral CPU and contents of 3,4-dihydroxyphenylacetic acid （3,4-DOPAC） and homovanillic acid （HVA） were also measured. In addition, amount of tyrosine hydroxylase positive cells （TH＊） in SNC was counted with immuno- histochemical staining. MAIN OUTCOME MEASURES ： ① Successful rate of PD models; ② contents of dopamine and its metabolite in MFB, SNC and CPU groups and TH＊ amount. RESULTS： All 64 SD rats were involved in the final analysis. ③ Successful rate and rotational behavior： One week after operation, there were 6 successful models both in SNC and MFB groups; in the 2^nd week, there were 6 both in SNC and MFB groups and 1 in CPU group; in the 3^nd week, there were 1 in MFB group and 3 in CPU group; in the 4^nd week, there were 3 in CPU group. Otherwise, no successful case was found out in the next 3 weeks. Abnormal rotational behavior was not observed in control group. Four weeks after operation, successful rates were 81% （13/16） in MFB group, 75% （12/16） in SNC group and 44% （7/16） in CPU group.② Contents of 3, 4-DOPAC and HVA： Eight weeks after operation, contents in the SNC area of the injured side were lower than those on non-lesion side （P 〈 0.01）.③Changes of TH＋ amount： Eight weeks after operation, TH＋ amount in the SNC area of the lesion side was lower than that on non-lesion side （P 〈 0.01 ）. CONCLUSION： Injecting 6-OHDA into MFB, SNC and CPU can damage dopaminergic cells and establish successful PD models.

Aged Garlic Extract Reduces ROS Production and Cell Death Induced by 6-Hydroxydopamine through Activation of the Nrf2-ARE Pathway in SH-SY5Y Cells

Many degenerative or pathological processes, such as aging, cancer and coronary heart disease, are related to reactive oxygen species (ROS) and radical-mediated reactions. We examined the effectiveness of aged garlic extract (AGE), a garlic preparation rich in water-soluble cysteinyl moieties, for protection of cells from ROS produced by 6-hydroxy-dopamine (6-OHDA) using human neuroblastoma SH-SY5Y cells. Concomitant treatment of cells with AGE (2 and 4 mg/ml) showed the dose-dependent protective effect on the cell death induced by 6-OHDA. In addition, the AGE treatment significantly suppressed the increase of ROS generation by 6-OHDA. Furthermore, the protective effect of AGE was accompanied by activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway and the increase of mRNAs of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1. These two enzymes are important in the cellular antioxidant system. These results indicated that AGE protected cells from ROS damage by not only capturing ROS directly but also activating the cellular antioxidant system by stimulating antioxidant gene expression via the Nrf2-ARE pathway. The present study suggested that AGE may be useful for prevention and treatment of cell damage caused by ROS.

Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease

Objective Curcumin is a plant polyphenolic compound and a major component of spice turmeric （Curcuma longa）. It has been reported to possess free radical-scavenging, iron-chelating, and anti-inflammatory properties in dif- ferent tissues. Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine （6-OHDA）-induced neurotoxicity in vitro. The present study aimed to explore this neuroprotective effect in the 6-OHDA-lesioned rat model of Parkinson＇s disease in vivo. Methods Rats were given intragastric curcumin for 24 days. 6-OHDA lesioning was conducted on day 4 of curcumin treatment. Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection, tyrosine hydroxylase （TH）-containing neurons by immunohistochemistry, and iron-containing cells by Perls＇ iron staining. Results The dopamine content in the striatum and the number of TH-immunoreactive neurons decreased after 6-OHDA treatment. Curcumin pretreatment reversed these changes. Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells, which was dramatically decreased by curcumin pretreatment. Conclusion The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.

Antagonistic effect of 6-hydroxydopamine (6-OHDA) on generation of immunosuppressive protein of stress in the rat

Neonatal rats were injected with 6-hydroxydopamine (6-OHDA) for chemical sympa-thectomy. The rats were treated with restraint stress when they grew up to 56 d. It has been found that the generation of immunosuppressive protein of stress (ISPS) is significantly reduced, suggesting that peripheral sympathetic nerve plays an important role in mediating the generation of ISPS.

Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo

Background:Abnormal expression of major histocompatibility complex class I(MHC-I)is increased in dopaminergic(DA)neurons in the substantia nigra(SN)in Parkinson’s disease(PD).Low-molecular-mass protein 7(β5i)is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells.Methods:In this study,we investigated the role of β5i in DA neurons using a 6-hydroxydopamine(6-OHDA)model in vitro and vivo.Results:We showed that 6-OHDA upregulatedβ5i expression in DA neurons in a concentration-and time-dependent manner.Inhibition and downregulation ofβ5i induced the expression of glucose-regulated protein(Bip)and exacerbated 6-OHDA neurotoxicity in DA neurons.The inhibition of β5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA.β5i also activated transporter associated with antigen processing 1(TAP1)and promoted MHC-I expression on DA neurons.Conclusion:Taken together,our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.

17~45岁肥胖门诊患者的6分钟步行试验距离参考方程研究

背景 目前6分钟步行试验(6MWT)已经被广泛用于评估肥胖人群的运动能力,并为制订干预措施提供了参考依据。国外已有研究提出了其他人群的6MWT距离参考方程,但中国17~45岁且BMI≥30 kg/m^(2)肥胖受试者的6MWT距离参考方程研究较少。目的 为17~45岁门诊肥胖受试者制订6MWT距离参考方程,并评估其影响因素。方法 根据美国胸科学会指南,前瞻性选取2022年6月—2023年9月于江苏省苏北人民医院内分泌科肥胖门诊部就诊的143名年龄17~45岁且BMI≥30 kg/m^(2)的成年人(71名男性和72名女性),进行人体测量和6MWT。采用逐步多元回归模型建立6MWT距离参考方程,将新建立的6MWT距离参考方程与现有的预测方程进行比较。结果 143名受试者的平均6MWT距离为(506.1±49.8)m,其中男性平均6MWT距离为(515.7±50.1)m,大于女性的平均6MWT距离(496.6±47.9)m(P<0.05)。在年龄段17~23岁、24~30岁、31~37岁以及38~45岁中,男性与女性6MWT距离比较,差异均有统计学意义(P<0.05)。男性受试者的体质量、BMI、最大心率(HR_(max))、心率差(ΔHR)、腰围、舒张压差(ΔDBP)、Borg量表评分差(ΔBorg)与6MWT距离相关(P<0.05),女性受试者的体质量、BMI、腰围与6MWT距离相关(P<0.05)。以步进的方法将潜在的影响因素纳入多元线性回归方程中,最终建立6MWT距离参考公式:男性y=494.463+1.414×ΔHR-3.903×BMI+0.874×HR_(max),R^(2)=0.429,女性y=670.448+0.299×ΔHR-4.342×BMI-0.195×HR_(max),R^(2)=0.312。结论 17~45岁门诊肥胖受试者中,男性的平均6MWT距离长于女性,且在不同年龄段均有显著差异。男性的体质量、BMI、HR_(max)、ΔHR、腰围、ΔDBP、ΔBorg与6MWT距离相关,女性的体质量、BMI、腰围、ΔSBP与6MWT距离相关。通过多元线性回归分析,为男性和女性分别建立了预测6MWT距离的参考方程,这些公式可能为评估个体的体能水平提供有价值的参考。

金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性理论研究

NO_(2)是空气污染物的主要成分之一,设计和开发高效的气敏传感器对NO_(2)进行检测具有重要意义.本工作利用基于密度泛函理论(DFT)的第一性原理计算方法对不同过渡金属原子形成的金属二聚体和氮共掺杂石墨烯(Gra)M_(2)N_(6)-Gra(M=Cr-Cu)的NO_(2)吸附特性进行了研究.结果表明,NO_(2)分子与M_(2)N_(6)-Gra之间均存在明显的化学吸附作用.其中,Ni_(2)N_(6)-Gra和Cu_(2)N_(6)-Gra体系具备较为适中的恢复时间(分别约为5秒和14分钟),这意味着这两个体系是开发新型NO_(2)气敏材料的潜在候选者.其它体系(M_(2)N_(6)-Gra,M=Cr-Co)强的吸附作用导致恢复时间过长,从而使得它们不适合作为NO_(2)气敏材料.这一研究不仅有望为设计和开发性能优异的新型NO_(2)气敏材料提供有益理论指导,还将有益于人们深入认识M_(2)N_(6)-Gra材料的NO_(2)电催化合成NO或NH 3性能.

定向电场下W_(6)C_(6)团簇的超卤素调制及非线性光学特性

本文采用密度泛函(DFT)方法研究了定向外电场(OEEF)对W_(6)C_(6)团簇几何结构、电子性质以及非线性光学响应(NLO)的影响.计算结果表明W_(6)C_(6)的结构在一定OEEF强度下可以保持稳定.OEEF可以增大W_(6)C_(6)团簇的电子亲和能(EA值),且在特定强度下,OEEF可以将W_(6)C_(6)团簇转变为超卤素.通过对EA值的非线性拟合可以实现对W_(6)C_(6)团簇的连续调制.进一步对不同外电场下W_(6)C_(6)团簇的最高占据分子轨道(HOMO)和最低未占据分子轨道(LUMO)能级进行分析,发现OEEF降低了W_(6)C_(6)团簇LUMO能级是其EA值增大的主因.此外,OEEF可以显著增大W_(6)C_(6)团簇的平均极化率和第一超极化率,尤其是第一超极化率,改变其非线性光学性质.

Salidroside Protects Against 6-Hydroxydopamine-Induced Cytotoxicity by Attenuating ER Stress

Parkinson＇s disease （PD） is a neurodegenera- tive disease characterized by a persistent decline of dopaminergic （DA） neurons in the substantia nigra pars compacta. Despite its frequency, effective therapeutic strategies that halt the neurodegenerative processes are lacking, reinforcing the need to better understand the molecular drivers of this disease. Importantly, increasing evidence suggests that the endoplasmic reticulum （ER） stress-induced unfolded protein response is likely involved in DA neuronal death. Salidroside, a major compound isolated from Rhodiola rosea L., possesses potent anti- oxidative stress properties and protects against DA neu- ronal death. However, the underlying mechanisms are not well understood. In the present study, we demonstrate that salidroside prevents 6-hydroxydopamine （6-OHDA）- induced cytotoxicity by attenuating ER stress. Further- more, treatment of a DA neuronal cell line （SN4741） and primary cortical neurons with salidroside significantly reduced neurotoxin-induced increases in cytoplasmic reactive oxygen species and calcium, both of which cause ER stress, and cleaved caspase-12, which is responsible for ER stress-induced cell death. Together, these results sug- gest that salidroside protects SN4741 cells and primary cortical neurons from 6-OHDA-induced neurotoxicity by attenuating ER stress. This provides a rationale for the investigation of salidroside as a potential therapeutic agent in animal models of PD.

Wnt3a protects SH-SY5Y cells against 6-hydroxydopamine toxicity by restoration of mitochondria function

Background:Wnt/β-catenin signal has been reported to exert cytoprotective effects in cellular models of several diseases,including Parkinson’s disease(PD).This study aimed to investigate the neuroprotective effects of actived Wnt/β-catenin signal by Wnt3a on SH-SY5Y cells treated with 6-hydroxydopamine(6-OHDA).Methods:Wnt3a-conditioned medium(Wnt3a-CM)was used to intervene dopaminegic SH-SY5Y cells treated with 6-OHDA.Cell toxicity was determined by cell viability and lactate dehydrogenase leakage(LDH)assay.The mitochondria function was measured by the mitochondrial membrane potential,while oxidative stress was monitored with intracellular reactive oxygen species(ROS).Western blot analysis was used to detect the expression of GSK3β,β-catenin as well as Akt.Results:Our results showed that 100μM 6-OHDA treated for 24 h significantly decreased cell viability and mitochondrial transmembrane potential,reduced the level ofβ-catenin and p-Akt,increased LDH leakage,ROS production and the ratio of p-GSK3β(Tyr216)to p-GSK3β(Ser9).However,Wnt3a-conditioned medium reversing SH-SY5Y cells against 6-OHDA-induced neurotoxicity by reversing these changes.Conclusions:Activating of Wnt/β-catenin pathway by Wnt3a-CM attenuated 6-OHDA-induced neurotoxicity significantly,which related to the inhibition of oxidative stress and maintenance of normal mitochondrial function.

血清淀粉样蛋白A、白介素6、肿瘤坏死因子α及微小RNA在脓毒症并发急性肾损伤患儿中的表达及预后评估价值研究

背景 急性肾损伤(AKI)是脓毒症常见并发症,机体免疫-炎症指标是预测脓毒症并发AKI患儿预后的常用指标,目前从微小RNA(miR)方面评估的研究较少,有待临床探究。目的 探究血清淀粉样蛋白A(SAA)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)及miR在脓毒症并发AKI患儿中的表达,并分析其对预后的评估价值。方法 选取2020年3月—2023年3月平顶山市第一人民医院收治的100例脓毒症并发AKI患儿为观察组,另选取同期80例单纯脓毒症患儿为对照组。收集患者一般资料,酶联免疫吸附试验(ELISA)检测血清SAA、IL-6、TNF-α水平,采用实时荧光定量PCR法检测miR-21-3p、miR-182-5p、miR-128-3p相对表达量。比较两组序贯性器官功能衰竭(SOFA)评分、急性生理与慢性健康(APACHEⅡ)评分。采用Pearson相关性检验分析血清SAA、IL-6、TNF-α及miR水平与SOFA、APACHEⅡ评分的相关性。绘制受试者工作特征(ROC)曲线探究血清SAA、IL-6、TNF-α及miR水平对脓毒症并发AKI患儿死亡的预测价值并计算ROC曲线下面积(AUC)。结果 观察组SOFA评分、APACHEⅡ评分、血清SAA、IL-6、TNF-α、miR-21-3p、miR-182-5p、miR-128-3p水平均高于对照组(P<0.05)。住院28 d后观察组74例患儿生存,26例患儿死亡。生存患儿血清SAA、IL-6、TNF-α、miR-21-3p、miR-182-5p、miR-128-3p均低于死亡患儿(P<0.05)。血清SAA、IL-6、TNF-α、miR-21-3p、miR-182-5p、miR-128-3p与SOFA、APACHEⅡ评分均呈正相关(P<0.05)。ROC曲线结果显示联合预测的AUC为0.926(95%CI=0.856~0.969,P<0.05)。结论 脓毒症并发AKI患儿血清SAA、IL-6、TNF-α、miR-21-3p、miR-182-5p、miR-128-3p异常高表达,临床检测各项指标水平对患儿预后评估有较高价值及预警作用。

Electronic structure and ultraviolet spectra of p-C_(6)H_(4)-C_(20)

Geometry optimization of p-C_(6)H_(4)-connected cyclo[20]carbon(p-C_(6)H_(4)-C_(20))was carried out at M062X/6-311G(d,p)level,three kinds of bond orders(Mayer,Laplacian,and Wiberg),electron-hole distributions,localized orbital locators(LOL),and infrared(IR)spectrum were also performed at the same level.Based on TD-DFT M062X/6-311G(d,p)method,the first 20 excited states and ultraviolet(UV)spectra of p-C_(6)H_(4)-C_(20) were calculated.Calculation results of π-electron delocalization analyses prove thatπ-electron delocalization of p-C_(6)H_(4)-C_(20) is more likely to occur on shorter C-C bonds rather than longer C-C bonds,and inside/outside of the ring plane rather than above/below the ring plane.Two absorption peaks of p-C_(6)H_(4)-C_(20) locate at about 319 nm and 236 nm,respectively.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.