基于小分子识别的光电化学传感器用于组氨酸检测

血清中组氨酸(His)水平异常变化可能与多种疾病相关,因此检测His具有重要的临床意义。光电化学(PEC)传感具有灵敏度高、操作简单、价格低廉和易于微型化等优点,是一种有潜力的临床检测手段。由于缺乏合适的识别机制,到目前为止PEC传感器用于His检测仍未见报道。本研究提出以小分子探针作为识别单元构建光电化学传感界面的方法,通过探针与His之间的特异性反应提高传感器的选择性。因此,构建的光电化学传感器具有较好的选择性、稳定性和重现性,可用于生物样品中His的定量检测。

Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas:A Report of Two Cases and Literature Review

The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.

Tetrahydroxy Stilbene Glucoside Ameliorates Cognitive Impairments and Pathology in APP/PS1 Transgenic Mice

Cognitive impairment is the main clinical manifestation of Alzheimer's disease(AD),and amyloid-β(AB)deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains.This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside(TSG)on cognitive function in APP/PS 1 mice during long-term administration.Here,we treated APP/PS1 model mice of AD with different doses of TSG(50 mg/kg and 100 mg/kg)for 5 to 17 months by gavage,and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests,and investigated the possible mechanisms by immunohistochemistry and Western blotting.Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test.Furthermore,Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique.Finally,Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβplaque deposition in the cortex and hippocampus of mice.These results reveal the beneficial effects of TSG in APP/PSI-AD mice,which may be associated with the reduction of Aβdeposits in the brain.

Cornel Iridoid Glycoside Regulates Modification of Tau and Alleviates Synaptic Abnormalities in Aged P301S Mice

Alzheimer’s disease(AD),also defined as a tauopathology,is a common neurodegenerative disease.Hyper-phosphorylation,cleavage or truncation,and aggregation of tau contribute to AD.Thus,targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD.This study understood how cornel iridoid glycoside(CIG)affects tau post-translational modifications and synaptic abnormalities.The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month.Hyperphosphorylated and truncated tau,synapse-associated proteins and glutamatergic receptors were all detected using Western blotting.The interactions between Morroniside(MOR)or Loganin(LOG)and tau were detected using Autodock and Surface Plasmon Resonance(SPR).The effects of CIG on the aggregation of tau were investigated using a cell-free system.CIG attenuated tau hyperphosphorylation at Thr205,Ser212,Ser262,Thr231 and Ser235(AT180),but had no effect on tau truncation in the brains of 10-month old P301S mice.Binding free energies and interactions revealed that MOR and LOG bound with tau.We also found that CIG upregulated synapse-associated proteins such as PSD-95,syntaxin1A and synaptotagmin.In addition,CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels.CIG improves post-translational modification of tau as well as synaptic abnormalities.The data presented here reveal that CIG may be used in the treatment of AD.

Morroniside antagonizes tau hyperphosphorylation against neurodegeneration:a cell culture study

OBJECTIVE Protein phosphatase 2A(PP2A),a major protein phosphatase,have been reported to be involved in the microtubule-associated protein tau hyperphosphorylation and aggregation in Alzheime disease(AD).Morroniside(MOR)is the isolated component from Cornus officinalis Sieb.et Zucc.The present study is to investigate the inhibitory effect of MOR on tau hyperphosphorylation and the underlying mechanisms.METHODS SK-N-SH cells were pretreated with MOR 50-200μmol·L-1 for 24 hand then treated with okadaic acid(OA)(20nmol·L-1)for 6h to induce tau hyperphosphorylation by inhibiting PP2A activity.To determine whether the inhibitory effect of MOR on tau hyperphosphorylation was dependent on PP2A directly,we transfected PP2Ac siRNA into HEK293 cells.Cell morphology was visualized under contrast microscope.Western blotting was used to measure the expressions of phosphorylated tau,total tau,Protein phosphatase-2A(PP2A),phosphorylated PP2 Aat Tyr307(P-PP2A),demethylated PP2 Aat Leu309(DM-PP2A),protein phosphatase methylesterase 1(PME-1),Leucine carboxyl methyltransferase 1(LCMT-1),phosphorylated Src at Tyr416 and Tyr529,total Src,glycogen synthase kinase-3β(GSK-3β)and phospho-GSK3β(Ser9).The activity of PP2 A was measured by aprotein phosphatases activity assay kit.RESULTS Compared with the control,the OA-treated cells became retracted and rounded up and their tau phosphorylation levels at pSer199/202,pT205,pT212,pS214,pT217 markedly increased.Pretreatment with MOR improved the cellular morphology and reduced OA-induced tau hyperphosphorylation.In addition,MOR treatment increased PP2 Aactivity accompanied by a decrease of DM-PP2 Aand P-PP2 Aexpression.MOR decreased PME-1expression and the ratio of PME/LCMT-1.Furthermore,MOR treatment altered the level of Src phosphorylated at Tyr416,which can regulate phosphorylation of PP2 A.PP2Ac siRNA could inhibit PP2Ac expression and induce tau hyperphosphorylation.MOR had no effect on PP2Ac expression,correspondingly,didn′t affect tau hyperphosphorylation in PP2Ac siRNA transfected HEK293 cells.CONCLUSION Morroniside attenuates OA-induced tau hyperphosphorylation through regulating PP2Ac posttranslational modification.MOR is a potential protein phosphatase 2A activator which might be a therapeutic drug for AD and other tau pathology-related degenerative diseases.

Shenqi Xingnao Granules ameliorates cognitive impairments and Alzheimer’s disease-like pathologies in APP/PS1 mouse model

Objective:Alzheimer’s disease(AD)is along with cognitive decline due to amyloid-β(Aβ)plaques,tau hyperphospho rylation,and neuron loss.Shenqi Xingnao Granules(SQXN),a traditional Chinese medicine,significantly ameliorated the cognitive function and daily living abilities of patients with AD.However,till date,no study has investigated the mechanism of action of SQXN on AD.The present study aimed to verify the effects of SQXN treatment on cognitive impairments and AD-like pathologies in APP/PS1 mice.Methods:Four-month-old APP/PS1 transgenic(Tg)mice were randomly divided into a model group and SQXN-treated(3.5,7,14 g/kg per day)groups.Learning-memory abilities were determined by Morris water maze and object recognition test.All mice were sacrificed and the brain samples were collected after 75 d.The soluble Aβcontents were detected by Elisa kit;The levels of expression of NeuN,APP,phosphorylated tau and related protein were measured by Western blotting;The inflammation factors were detected by the proinflammatory panel kit.Results:Four-month-old APP/PS1 mice were administered SQXN by oral gavage for 2.5 months.Using the Morris water maze tests and Novel object recognition,we found that SQXN restored behavioral deficits in the experimental group of Tg mice when compared with the controls.SQXN also inhibited neuronal loss(NeuN marker).SQXN treatment decreased soluble Aβ42 through inhibiting the expression of sAPPβand BACE-1 without regulating full-length amyloid precursor protein(FL APP).Insulin degrading enzyme(IDE),the Aβdegrading enzyme,were increased by SQXN.In addition,SQXN reduced hyperphosphorylated tau protein levels and prevented excessive activation of p-GSK-3βin the brain of APP/PS1 mice.Compared with APP/PS1 transgenic negative mice,IFN-γ,IL-1β,IL-2,IL-4,IL-5,IL-6,IL-12 p70,KC/GRO and TNF-αwere not obviously changed in the brain of 6.5-month-old APP/PS1 transgenic(Tg)mice.However,SQXN could inhibited the expression of IL-2.Conclusion:These results demonstrate that SQXN ameliorates the cognitive impairments in APP/PS1 mice.The possible mechanisms involve its inhibition of neuronal loss,soluble Aβdeposition,tau hyperphosphorylation and inflammation.