高效液相色谱法测定α-硫辛酸绿茶片中α-硫辛酸的含量

目的 建立α-硫辛酸绿茶片中α-硫辛酸的含量测定方法。方法 利用高效液相色谱(HPLC)技术,采用Alltima C_(18)柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.1%磷酸溶液(55∶45),流速为1.0 mL·min^(-1),检测波长为215 nm,柱温为30℃。结果 α-硫辛酸在102.6~307.7μg·mL^(-1)与峰面积呈良好的线性关系,相关系数(r)为1.000;精密度、重复性和稳定性考察RSD均小于2.0%;3个浓度的加样回收率为98.44%~100.2%,RSD值均小于1.0%。结论 该方法准确、简单、快速,能够用于α-硫辛酸绿茶片中α-硫辛酸的含量测定。

α-硫辛酸联合依帕司他对2型糖尿病伴糖尿病周围神经病变患者肌电图、血清炎症因子及血流变学的影响

目的探讨α-硫辛酸联合依帕司他治疗2型糖尿病(T2DM)伴糖尿病周围神经病变(DPN)患者的效果,并分析其对肌电图、血清炎症因子和血流变学指标的影响。方法按照随机数字表法将2021年9月至2023年9月广西科技大学第一附属医院收治的84例T2DM合并DPN患者分为对照组(给予依帕司他治疗)和观察组(给予α-硫辛酸联合依帕司他治疗),各42例。比较两组患者肌电图指标、炎症因子和血流变学指标。结果治疗后,两组患者正中和腓总神经的运动神经传导速度(MCV)和感觉神经传导速度(SCV)水平均升高,且观察组均高于对照组(均P<0.05)。治疗后,两组患者超敏C反应蛋白(hs-CRP)和白细胞介素-6(IL-6)水平均较治疗前降低,且观察组均低于对照组(P<0.05)。治疗后,两组患者全血高切黏度、全血低切黏度和血浆黏度均低于治疗前,且观察组均低于对照组(均P<0.05)。结论给予T2DM合并DPN患者α-硫辛酸联合依帕司他治疗的效果显著,可有效提高神经传导速度,抑制炎症反应,调节血流变学。

18β-glycyrrhetinic acid inhibits proliferation of gastric cancer cells through regulating the miR-345-5p/TGM2 signaling pathway

BACKGROUND Gastric cancer(GC)is a common gastrointestinal malignancy worldwide.Based on cancer-related mortality,the current prevention and treatment strategies for GC still show poor clinical results.Therefore,it is important to find effective drug treatment targets.AIM To explore the molecular mechanism of 18β-glycyrrhetinic acid(18β-GRA)regulating the miR-345-5p/TGM2 signaling pathway to inhibit the proliferation of GC cells.METHODS CCK-8 assay was used to determine the effect of 18β-GRA on the survival rate of GES-1 cells and AGS and HGC-27 cells.Cell cycle and apoptosis were detected by flow cytometry,cell migration was detected by a wound healing assay,the effect of 18β-GRA on subcutaneous tumor growth in BALB/c nude mice was investigated,and the cell autophagy level was determined by MDC staining.TMT proteomic analysis was used to detect the differentially expressed autophagy-related proteins in GC cells after 18β-GRA intervention,and then the protein-protein interaction was predicted using STRING(https://string-db.org/).MicroRNAs(miRNAs)transcriptome analysis was used to detect the miRNA differential expression profile,and use miRBase(https://www.mirbase/)and TargetScan(https://www.targetscan.org/)to predict the miRNA and complementary binding sites.Quantitative real-time polymerase chain reaction was used to detect the expression level of miRNA in 18β-GRA treated cells,and western blot was used to detect the expression of autophagy related proteins.Finally,the effect of miR-345-5p on GC cells was verified by mir-345-5p overexpression.RESULTS 18β-GRA could inhibit GC cells viability,promote cell apoptosis,block cell cycle,reduce cell wound healing ability,and inhibit the GC cells growth in vivo.MDC staining results showed that 18β-GRA could promote autophagy in GC cells.By TMT proteomic analysis and miRNAs transcriptome analysis,it was concluded that 18β-GRA could down-regulate TGM2 expression and up-regulate miR-345-5p expression in GC cells.Subsequently,we verified that TGM2 is the target of miR-345-5p,and that overexpression of miR-345-5p significantly inhibited the protein expression level of TGM2.Western blot showed that the expression of autophagy-related proteins of TGM2 and p62 was significantly reduced,and LC3II,ULK1 and AMPK expression was significantly increased in GC cells treated with 18β-GRA.Overexpression of miR-345-5p not only inhibited the expression of TGM2,but also inhibited the proliferation of GC cells by promoting cell apoptosis and arresting cell cycle.CONCLUSION 18β-GRA inhibits the proliferation of GC cells and promotes autophagy by regulating the miR-345-5p/TGM2 signaling pathway.

Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice

Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Alpha lipoic acid protects lens from H_2O_2-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes

Objective:To determine whether alpha lipoic acid（LA）can effectively protect lenses from hydrogen peroxide（H2O2）-induced cataract.Methods:Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2,0.2 mM of H2O2 plus 0.5 mM.1.0 mM.or 2.0 mM of LA for 24 h.Cataract was assessed using cross line grey scale measurement.Superoxide dismutase（SOD）.glutathione（GSH-Px）.lactate dehydrogenase（LDH）. and maloudialdehyde（MDA）activity or level in lens homogenates was measured.Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling（TUNEL） Assay.Results:A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens’ epithelial cells,but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis.Furthermore.0.2 mM ol H2O2 significantly decreased SOD.GSH-Px,and LDH activity and significant increased MDA level in the lens,but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2.One mM of LA was found to be the most effective. Conclusions:LA can protect lens from H2O2-induced cataract.LA exerts protective effects through inhibition of lens’ epithelial cell apoptosis and activation of anti-oxidative enzymes.

Lipoic acid suppresses portal endotoxemia-induced steatohepatitis and pancreatic inflammation in rats

AIM: To examine the effect of α-lipoic acid (LA) on mild portal endotoxemia-induced steatohepatitis and associated pancreatic abnormalities in fructose-fed rats. METHODS: Rats were randomly assigned into two groups with a regular or 60% fructose-enriched diet for 8 wk. After fructose feeding for 4 wk, rats were further divided into four subgroups: with intraportal saline (F PV ), with intraportal saline plus administration of LA (F PV + LA ), with lipopolysaccharide (LPS) infusion (F PLPS ), and with LPS infusion plus administration of LA (F PLPS + LA ). Rats were treated with LPS using intraportal infusion while LA was administered orally. Metabolite levels, superoxide levels, inflammatory markers, malondialdehyde content, glutathione content and toll-like receptor 4 (TLR4 ) gene expression were all measured using standard biochemical techniques. Pancreatic insulin secretion was evaluated by a hyperglycemic clamp technique. Histology of liver and pancreas tissues were evaluated using hematoxylin and eosin staining and immunohistochemistry. RESULTS: Fructose-induced elevation in plasma C-reactive protein, amylase, superoxide, white blood cell count as well as in hepatic and pancreatic contents of malondialdehyde, tumor necrosis factor alpha and interleukin-6 were increased in animals treated with LPS and reversed with LA administration. The augmented hepatic gene expression of TLR4 in fructose-fed rats was further increased in those with intraportal LPS infusion, which was partially reversed by LA administration. Pathological examination showed inflammatory changes and leukocyte infiltration in hepatic and pancreatic islets of animals treated with LPS but were rarely observed in those with LA treatment. In addition to affects on the liver, impaired pancreatic insulin secretion seen in fructose-fed rats was deteriorated in with LPS treatment and partially reversed with LA administration. CONCLUSION: These data suggest LA could significantly suppress mild portal-endotoxemia but not fructoseinduced liver and pancreatic abnormalities in a rodent model for metabolic syndrome.

补充胍基乙酸和α-硫辛酸对绵羊瘤胃微生物和代谢物的影响

【目的】探究饲粮中添加胍基乙酸(guanidine acetic acid, GAA)和α-硫辛酸(alpha-lipoic acid, LA)对绵羊瘤胃微生物和代谢物的影响。【方法】选取24只体重相近、体质良好的健康杜湖杂交公羊,随机分为4组,分别为对照组(CTL,饲喂基础饲粮)、GAA组(基础饲粮中添加1 500 mg/kg GAA)、LA组(基础饲粮中添加600 mg/kg LA)和MIX组(基础饲粮中添加1 500 mg/kg GAA和600 mg/kg LA),正试期60 d。试验结束后采集瘤胃液,利用16S rRNA基因测序和非靶向代谢组学检测瘤胃菌群及其代谢物。【结果】在绵羊瘤胃液菌群门水平上,与对照组相比,GAA和MIX组帕特斯菌门(Patescibacteria)的丰度显著上调(P<0.05);LA和MIX组疣微菌门(Verrucomicrobiota)的丰度显著下调(P<0.05)。在绵羊瘤胃液菌群属水平上,与对照组相比,LA组奎因氏菌属(Quinella)的丰度显著降低(P<0.05);各试验组糖单胞菌属(Candidatus_Saccharimonas)的丰度显著升高(P<0.05),图氏杆菌属(Turicibacter)的丰度显著降低(P<0.05);GAA组隆氏菌科UCG-001属(Veillonellaceae_UCG-001)的丰度显著降低(P<0.05);MIX组瘤胃艾氏梭菌属(Eubacterium_Ruminantium_group)的丰度显著降低(P<0.05)。绵羊瘤胃菌群代谢途径分析显示,GAA组的差异代谢物11-羟基过氧十八碳二烯酸、8-甲氧基犬尿氨酸等主要参与色氨酸代谢通路;LA组的差异代谢物1-磷酸鞘氨醇、二氢神经酰胺等主要参与鞘脂信号通路和鞘脂类代谢通路;MIX组的差异代谢物8-甲氧基犬尿氨酸、单磷酸鸟苷、3-甲基吲哚等主要参与色氨酸代谢通路。【结论】饲粮中单独添加GAA或LA以及组合添加均能够调节绵羊瘤胃微生物群落组成和代谢功能。该结果有助于揭示GAA和LA作为添加剂的深层次原理。

Protective effects of lipoic acid-niacin dimers against blue light-induced oxidative damage to retinal pigment epithelium cells

AIM: To evaluate the protective effects of lipoic acid-niacin(N2 L) dimers against blue light(BL)-induced oxidative damage to human retinal pigment epithelium(hRPE) cells in vitro.METHODS: h RPE cells were divided into a control group(CG), a BL group, an N2 L plus BL irradiation group, an α-lipoic acid(ALA) plus BL group, an ALA-only group, and an N2 L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium(MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy. Reactive oxygen species formation was assayed by flow cytometry. The expression levels of the apoptosis-related proteins BCL-2 associated X protein(BAX), B-cell leukmia/lymphoma 2(BCL-2), and caspase-3 were quantified by Western blot analysis.RESULTS: BL exposure with a light density of 4±0.5 mW/cm2 exceeding 6 h caused hRPE toxicity, whereas treatment with a high dose of N2 L(100 mol/L) or ALA(150 mol/L) maintained cell viability at control levels. BL exposure caused vacuole-like degeneration, mitochondrial swelling, and reduced microvillus formation;however, a high dose of N2 L or ALA maintained the ultrastructure of hRPE cells and their organelles. High doses of N2 L and ALA also protected hRPE cells from BL-induced apoptosis, which was confirmed by Western blot analysis: BCL-2 expression significantly increased, while BAX and caspase-3 expression slightly decreased compared to the CG.CONCLUSION: High-dose N2 L treatment(>100 mol/L) can reduce oxidative damage in degenerating hRPE cells exposed to BL with an efficacy similar to ALA.

Effect of SP-A/B in lipoic acid on acute paraquat poisoning

BACKGROUND: This study was undertaken to observe the concentration of SP-A/B and the pulmonary surfactant in the lung tissue of rats with acute lung injury/acute respiratory distress syndrome caused by paraquat poisoning after the treatment of metabolic antioxidant-lipoic acid and whether its influence was related to TNF-α.METHODS: Sixty-six male Sprage-Dawley rats were randomly divided into three groups: normal control group(NS group), 6 rats; paraquat poisoning group(PQ group), 30 rats; and paraquat+lipoic acid treatment group(LA group), 30 rats. The rats in the PQ and LA groups were subdivided into 3-, 6-, 12-, 24-, 48-hour subgroups, with 6 rats in each group. After the rats were sacrificed, lung tissue from the same part was taken from the rats. After HE staining, histological changes were observed in the tissue under a light microscope. Lung tissue was also taken to test the levels of superoxide dismutase(SOD) and malondialdehyde(MDA). Whole blood(0.8 mL) without anticoagulant was drawn from the tail vein of rats for the determination of the TNF-α level. The total RNA of the lung tissue was collected, and the Rt-PCR method was used to measure the levels of SP-A and SP-B mRNA.RESULTS: HE staining showed that histopathological changes were milder in the LA group than in the PQ group. There were significant differences in MDA and SOD levels between different intervals both in intergroups and intragroups except the 3-hour subgroup(P<0.01). Likewise, the significant differences in the levels of TNF-α were also present between the three groups and between different intervals(P<0.01). The significant differences in SP-A mRNA and SP-B mRNA amplification ratio were seen between the three groups at the same intervals(P<0.01), but the differences between different intervals in the PQ group were statistically significant(P<0.05). The differences between different intervals in the LA group were statistically significant(P<0.01).CONCLUSION: Lipoic acid in acute paraquat poisoning could diminish lung tissue damage by regulating directly tumor necrosis factor and indirectly the content of pulmonary surfactant so as to reduce pulmonary edema, improve lung compliance, and finally protect lung tissues.

α-硫辛酸在微囊藻毒素-LR诱导草鱼卵巢细胞损伤中的作用

为研究α-硫辛酸(Alpha lipoic acid,α-LA)在微囊藻毒素-LR(Microcystin-LR,MC-LR)诱导水生动物毒性效应中的保护作用,本研究以草鱼卵巢(Grass carp ovary,GCO)细胞为研究对象,检测分析了不同浓度α-LA以及α-LA与MC-LR共同暴露对GCO细胞活力的影响,随后根据测定的结果设置对照组(不添加MC-LR和α-LA)、125μmol·L^(-1)α-LA组、24μmol·L^(-1)MC-LR组及125μmol·L^(-1)α-LA+24μmol·L^(-1)MC-LR组,检测分析了α-LA在缓解MC-LR对GCO细胞活性、氧化应激以及炎症方面的影响。结果表明:与对照组相比,24μmol·L^(-1)MC-LR可诱导乳酸脱氢酶(LDH)活性和丙二醛(MDA)含量显著上升,同时显著抑制谷胱甘肽(GSH)活性(P<0.05),当MC-LR处理组中加入125μmol·L^(-1)α-LA后,与MC-LR单独暴露组相比,LDH活性和MDA含量均显著下降(P<0.05),但GSH活性却显著上升(P<0.05)。对氧化相关基因分析发现,与对照组相比,24μmol·L^(-1)MC-LR可显著降低SOD1、CAT和GST基因的表达量(P<0.05),当125μmol·L^(-1)α-LA与24μmol·L^(-1)MC-LR共同作用于GCO细胞后,与MC-LR单独暴露组相比,联合暴露组的GST基因的表达量显著上升(P<0.05),但SOD1和CAT两个基因的表达变化不显著(P>0.05)。此外,对炎症因子进行分析发现,MC-LR单独暴露组TNFα和IL11基因的相对表达水平显著高于对照组(P<0.05),但联合暴露组中的TNFα和IL11基因的相对表达水平却显著低于MC-LR单独暴露组(P<0.05)。研究结果表明,α-LA可缓解MC-LR诱导的氧化应激,提高细胞活力,抑制GCO细胞炎症的发生,从而减弱MC-LR对GCO细胞的损伤。

胍基乙酸和α-硫辛酸对绵羊生长性能、血液指标及肉品质的影响

试验旨在探究日粮中添加胍基乙酸(guanidine acetic acid,GAA)和α-硫辛酸(α-lipoic acid,LA)对绵羊生长性能、血液指标及肉品质的影响,选择体重相近、体质良好的健康公绵羊24只,随机分为4组,分别为对照组(饲喂基础日粮)、胍基乙酸组(基础日粮中添加1500 mg/kg胍基乙酸)、α-硫辛酸组(基础日粮中添加600 mg/kgα-硫辛酸)和混合组(基础日粮中添加1500 mg/kg胍基乙酸和600 mg/kgα-硫辛酸),试验期60 d,测定生长性能、血液指标、屠宰性能指标及肉品质指标。结果表明:α-硫辛酸组和混合组的平均日采食量显著高于对照组(P<0.05);胍基乙酸组血液中的谷草转氨酶和尿素含量显著高于对照组(P<0.05);对照组的白细胞介素-6含量显著高于其他3组(P<0.05);胍基乙酸组丙二醛含量显著低于对照组(P<0.05);混合组的肝脏指数显著高于对照组、胍基乙酸组和α-硫辛酸组(P<0.05);肉品质方面,对照组的剪切力显著高于胍基乙酸组、α-硫辛酸和混合组(P<0.05);对照组的肌肉蛋白质含量显著低于胍基乙酸组、α-硫辛酸组和混合组(P<0.05),对照组的肌肉脂肪含量显著高于α-硫辛酸组和混合组(P<0.05);α-硫辛酸组和混合组的肌肉氮含量显著高于对照组(P<0.05);胍基乙酸组的癸酸(C10∶0)、肉豆蔻烯酸(C14∶1)、十五碳烯酸(C15∶1)、棕榈油酸(C16∶1)、十七碳烯酸(C17∶1)等均显著高于对照组(P<0.05)。综上所述,α-硫辛酸提高了绵羊的采食量,降低了绵羊肌肉的剪切力,提高了肌肉嫩度,胍基乙酸提高了肌肉中脂肪酸含量。

MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.

Post-Marketing Surveillance of Fixed Dose Combination of Methylcobalamin, Alpha Lipoic Acid, Folic Acid, Biotin, Benfotiamine &Vitamin B6-Nutripathy for the Management of Peripheral Neuropathy

Background: Peripheral neuropathy is a commonly encountered troublesome condition which is often disabling & worsens when left untreated. Traditional neuropathic pain medications primarily provide symptomatic relief;however, the pathogenesis of nerve damage remains unresolved. Extensive literature survey reveals that patients with peripheral neuropathy experience significant benefits with the use of B-vitamins like methylcobalamin (B12), folic acid (B9), biotin (B7), benfotiamine (B1) and pyridoxine (B6). The other well documented antineuropathic agents include alpha lipoic acid, glutathione, omega fatty acids, myoinositol, certain trace elements, etc. Materials and Methods: A multicentre, prospective, open-label, non-comparative clinical study was carried out in 497 patients with peripheral neuropathy. A fixed dose combination of methylcobalamin, alpha lipoic acid (ALA), folic acid, biotin, benfotiamine & vitamin B6 capsule was orally administered once daily for 12 weeks. Results: Treatment led to significant reduction from baseline score in various neuropathy symptoms from the 4th week itself. After 12 weeks of treatment, the mean pain score declined by 78.0%, numbness by 92.1% and muscle weakness by 96.9%. Also, there was 96.0% & 99.2% reduction in tingling & burning sensation respectively. No serious adverse events were reported.Conclusion: The current study confirms that fixed dose combination of methylcobalamin, ALA, folic acid, biotin, benfotiamine & vitamin B6 is effective & well tolerated in the management of peripheral neuropathy.

Self-Assembled Monolayer of Lipoic Acid on Gold and Its Application to Rapid Determination of 2, 3, 7, 8-Tetrachlorodibenzo-p-Dioxin

Lipoic acid (LA) has received great attention in the area of gold surface functionalization. In this study, LA was employed as a linker for the attachment of antibody to the gold surface of surface plasmon resonance (SPR) chip. By using this chip in a homemade SPR immunosensor, low molecular weight compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) can be detected at a low level of 0.01 ng/mL. There is a good linear relationship(R2 =0.943 1) between the results of SPR biosensor and enzyme-linked immunosorbent assay(ELISA).

Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats

Objective To investigate the alterations in auditory brainstem evoked responses (ABRs) and the changes of carboplatin-induced ototoxicity in the cochlear oxidant/antioxidant systems and otoprotection by an antioxidant lipoate. Methods Male wistar rats were divided into four groups and treated as follows: 1) vehicle (saline) control, 2) carboplatin (256 mg/kg, i.p.), 3) lipoate (100 mg/kg, i.p.), 4) lipoate + carboplatin. Post-treatment ABRs were performed after four days and rats were sacrificed with their cochleae harvested and analyzed. Results Carboplatin significantly elevated ABR threshold above the pretreatment thresholds. Lipoate+carboplatin treated rats showed decreased elevation of hearing threshold. Carboplatin significantly depleted cochlear reduced to oxizized glutathione (GSH/GSSG) ratio, whereas lipoate+carboplatin treatment increased GSH/GSSG ratio. Carboplatin significantly decreased cochlear copper zinc-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) activities and enzyme protein expressions and a significant increase in Mn-SOD activity, protein expression and malondialdehyde (MDA) level. Cochlear antioxidant enzyme activities, enzyme protein expressions and MDA level were partially restored in lipoate+carboplatin treated rats, compared to carboplatin alone. Conclusion Carboplatin-induced ototoxicity is related to impairment of cochlear antioxidant system and otoprotection conferred by lipoate is associated with partial sparing of the cochlear antioxidant defense system.

木丹颗粒联合α-硫辛酸与甲钴胺治疗糖尿病周围神经病变疗效及对血清同型半胱氨酸、神经传导速度影响研究

目的 探讨对糖尿病周围神经病变(diabetic peripheral neuropathy,DPN)患者采用木丹颗粒联合α-硫辛酸、甲钴胺治疗的临床效果。方法 选取2019年1月—2020年10月在该院治疗的96例DPN患者为研究对象,采用随机数字表法将其分为对照组和研究组,每组48例。两组患者均给予甲钴胺和α-硫辛酸治疗,研究组在此基础上联合木丹颗粒进行治疗,观察并比较两组患者治疗前后左腓神经、左腓总神经、右腓神经和右腓总神经传导速度,多伦多临床评分系统(TCSS)评分,血清同型半胱氨酸(Hcy)和氧化应激指标[超敏C反应蛋白(hs-CRP)、血清超氧化物歧化酶(SOD)]水平,血液流变学指标水平;两组患者治疗后治疗效果及不良反应发生率。结果 (1)治疗前,两组患者神经传导速度比较差异无统计学意义(P>0.05);治疗后,两组患者神经传导速度较本组治疗前均提高(P<0.05),且研究组各项神经传导速度均快于对照组(P<0.05)。(2)治疗前,两组患者神经症状、感觉功能和神经反射三方面TCSS评分比较差异无统计学意义(P>0.05);治疗后两组患者三方面TCSS评分较本组治疗前均降低(P<0.05),且研究组三方面TCSS评分均低于对照组(P<0.05)。(3)治疗后,研究组治疗总有效率(93.75%)高于对照组(77.08%),差异有统计学意义(P<0.05)。(4)治疗前,两组患者血清Hcy、hs-CRP和SOD水平比较差异无统计学意义(P>0.05);治疗后,两组患者Hcy和hs-CRP水平较本组治疗前均降低(P<0.05),SOD水平较本组治疗前均升高(P<0.05),且研究组与对照组比较差异有统计学意义(P<0.05)。(5)治疗前,两组患者血浆黏度、红细胞体积、纤维蛋白原、全血低切黏度和全血高切黏度5项血液流变学指标水平比较差异无统计学意义(P>0.05);治疗后,两组患者5项血液流变学指标水平较本组治疗前均降低(P<0.05),且研究组水平均低于对照组(P<0.05)。(6)研究组不良反应发生率(22.92%)与对照组(18.75%)比较差异无统计学意义(P>0.05)。结论 α-硫辛酸、甲钴胺和木丹颗粒3种药物联合治疗DPN可以有效改善神经感知异常症状,提高神经传导速度,降低Hcy水平,提高临床治疗效果并保障患者治疗的安全性,联合用药临床价值较高。

Effects of alprostadil combined with lipoic acid on clinical efficacy, hemodynamics, fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot

ObjectiveTo investigate the effects of alprostadil combined with lipoic acid on clinical efficacy,hemodynamics,fibronectin and plasma D-dimer in elderly patients with type 2 diabetic foot.Methods Ninety-six elderly patients with type 2 diabetic foot hospitalized in Department of Endocrinology,Xining First People's Hospital from January 2017 to June 2019 were selected as the study subjects.They were divided into control group(48 cases)and case group(48 cases)by random number table method.The control group was treated with lipoic acid,and the case group was treated with Alprostadil for injection on the basis of the control group.The clinical efficacy,clinical symptom score,ulcer healing,hemodynamics of dorsal artery of foot,fibronectin and plasma D-two dimer in two groups were observed.Results The total effective rate of the case group was 95.83%,which was significantly higher than that of the control group(83.33%).The difference was statistically significant(P<0.05).After treatment,the pain,swelling,claudication,numbness score,ulcer area,wound PH value,plasma D-dimer level of the two groups were lower than those before treatment,and the oxygen partial pressure,blood flow velocity,vascular diameter,Resistance index(RI),pulsation index(PI)and fibronectin levels of the two groups were higher than those before treatment,the difference was statistically significant(P<0.05).The improvement of clinical efficacy,ulcer healing,dorsal pedal artery hemodynamics,fibronectin and plasma D-dimer levels in the case group were significantly better than those in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).ConclusionsAlprostadil combined with lipoic acid has significant clinical effect on elderly patients with type 2 diabetic foot.It can correct the abnormal hemodynamics of dorsal pedal artery,promote the healing of foot ulcer,increase the content of fibronectin ulcer tissue,reduce the level of plasma D-dimer and improve the high coagulation state.It has high efficiency and safety.It is worthy of clinical application.Further promotion.

α-硫辛酸联合前列地尔治疗对糖尿病足患者微血管生成、氧化应激及创面愈合的影响

目的 探究α-硫辛酸联合前列地尔治疗对糖尿病足(DF)患者微血管生成、氧化应激及创面愈合的影响。方法 采用随机数字表法将98例DF患者分为联合组(49例)和对照组(49例)。对照组接受前列地尔治疗,联合组接受α-硫辛酸联合前列地尔治疗。比较两组患者临床疗效、创面微血管生成情况、氧化应激反应及创面愈合情况。结果 联合组临床总有效率95.91%显著高于对照组的81.63%(P<0.05)。治疗1个月后,两组血管内皮生长因子(VEGF)水平显著高于治疗前、内皮抑素(ES)水平显著低于治疗前,联合组VEGF(135.28±13.58)ng/L显著高于对照组的(103.29±12.39)ng/L、ES(41.06±4.59)ng/ml显著低于对照组的(49.68±5.12)ng/ml(P<0.05)。治疗1个月后,两组超氧化物歧化酶(SOD)水平显著高于治疗前、丙二醛(MDA)水平显著低于治疗前,联合组SOD(92.77±10.25)U/ml显著高于对照组的(86.29±9.21)U/ml、MDA(2.29±0.94)μmol/L显著低于对照组的(2.97±1.06)μmol/L(P<0.05)。联合组创面愈合时间(16.28±3.12)d显著短于对照组的(21.58±4.05)d,创面愈合率(76.29±10.39)%显著高于对照组的(54.95±11.28)%(P<0.05);治疗1个月后,两组创周肿势评分均低于本组治疗前,联合组创周肿势评分(0.93±0.34)分显著低于对照组的(1.17±0.41)分(P<0.05)。结论 α-硫辛酸联合前列地尔治疗DF患者较前列地尔单药治疗的临床效果更显著,促进微血管生成,改善氧化应激反应,促进创面愈合。

Protective Roles of α-lipoic Acid in Rat Model of Mitochondrial DNA4834bp Deletion in Inner Ear

The protective roles of α-lipoic acid in the rat model of mitochondrial DNA (mtDNA) 4834bp deletion in inner ear were investigated. Forty female Wistar rats at 4 weeks of age were divided into four groups: group A (D-galactose group, n=10), group B (D-galactose+α-lipoic acid group, n=10), group C (α-lipoic acid group, n=10), and group D (control group, n=10). Auditory brainstem response (ABR) was used to detect the hearing threshold. Colorimetry was used to analyze activity of superoxide dismutase (SOD) and concentration of malondialdehyde (MDA). The percentage of mtDNA4834bp deletion in inner ear was identified by real-time PCR. There was no significant difference in ABR threshold shift among all groups. The percentage of mtDNA4834bp deletion in group A was higher than that in other groups, but there was no significant difference in percentage of mtDNA4834bp deletion among groups B, C, and D. The activity of SOD in group A was lower than that in other groups. The concentration of MDA in group A was higher than that in other groups. It was concluded that there was no significant hearing loss when the percentage of mtDNA4834bp deletion was lower than 12.5%. α-Lipoic acid could prevent the reactive oxygen species (ROS)-induced mtDNA4834bp deletion in inner ear of rats.

18β-glycyrrhetinic acid promotes gastric cancer cell autophagy and inhibits proliferation by regulating miR-328-3p/signal transducer and activator of transcription 3

BACKGROUND Gastric cancer(GC)is one of the most common cancer types worldwide,and its prevention and treatment methods have garnered much attention.As the active ingredient of licorice,18β-glycyrrhetinic acid(18β-GRA)has a variety of pharmacological effects.The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC,in order to provide effective ideas for the clinical prevention and treatment of GC.AIM To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells.METHODS Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs(miRNAs)in GC cells after 18β-GRA intervention.Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability,cell colony formation ability was detected by the clone formation assay,and flow cytometry was used to detect the cell cycle and apoptosis.A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells.Tumor tissue morphology was observed by hematoxylin and eosin staining,and microtubule-associated protein light chain 3(LC3)expression was detected by immunohistochemistry.TransmiR,STRING,and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3(STAT3)-related information.Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction(qPCR)and the expression levels of STAT3,phosphorylated STAT3(p-STAT3),and LC3 were detected by western blot analysis.The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system.AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label.LC3 was labeled and autophagy flow was observed under a confocal laser microscope.RESULTS The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells(P=4.51E-06).Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability,arrested the cell cycle in the G0/G1 phase,promoted cell apoptosis,and inhibited the growth of subcutaneous tumors in BALB/c nude mice(P<0.01).No obvious necrosis was observed in the tumor tissue in the negative control group(no drug intervention or lentivirus transfection)and vector group(the blank vector for lentivirus transfection),and more cells were loose and necrotic in the miR-328-3p group.Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3,and STAT3 was closely related to autophagy markers such as p62.After overexpressing miR-328-3p,the expression level of STAT3 mRNA was significantly decreased(P<0.01)and p-STAT3 was downregulated(P<0.05).The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT33’untranslated regions of the wild-type reporter vector group was significantly decreased(P<0.001).Overexpressed miR-328-3p combined with bafilomycin A1(Baf A1)was used to detect the expression of LC3 II.Compared with the vector group,the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated(P<0.05),and compared with the Baf A1 group,the expression level of LC3 II in the overexpressed miR-328-3p+Baf A1 group was upregulated(P<0.01).The expression of LC3 II was detected after intervention of 18β-GRA in GC cells,and the results were consistent with the results of miR-328-3p overexpression(P<0.05).Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis(P<0.001).qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention(P<0.05).Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention(P<0.05).CONCLUSION 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway.