Neurofibrillary tangles in Alzheimer＇s disease： elucidation of the molecular mechanism by immunohistochemistry and tau protein phospho-proteomics

As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.

S100 PROTEIN-POSITIVE DENDRITIC CELLS AND THE SIGNIFICANCE OF THEIR DENSITY IN GASTRIC PRECANCEROUS LESIONS

Quantitative analysis of dendritic cells (DC’s) was carried out in tissue specimens of normalgastric mucosa (n=15),gastric ulcer (n=19),chronic atrophic gastritis (n=28),and gastriccarcinoma (n=65) by ABC immunostaining with S100 protein antibody.Significant increasein DC number were observed in chronic atrophic gastritis with type Ⅲ intestinal metaplasiaand/or grade Ⅱ,Ⅲ dysplasia.The result suggests that DC’s are potentially capable opresenting neoantigens associated with malignant transformation at the precancerous stagewhen malignant morphological changes have not yet taken place.Combined with routinediagnostic methods,the serial monitoring of DC density in gastric mucosa may be usefulin the follow-up of premalignant lesions in the stomach and the diagnosis of early gastriccarcinoma.

S100 protein expression during induced Schwann cell-like cell differentiation of rat bone marrow mesenchymal cells in vitro

BACKGROUND： S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells （MSCs） that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE： To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING： This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS： The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS： MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES： S100 protein and mRNA expression. RESULTS： MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION： MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.

The S100 protein family and its application in cardiac diseases

The S100 protein family is the largest group of EF-hand signaling proteins in humans. The members of the S100 protein family are expressed in many tissues and play different functions. Many diseases are related to S100 proteins, which function as new biochemical markers especially in cardiac diseases. The most studied members, protein S100Β and protein S100A1, exhibit activities in cardiac diseases, and these immunohistochemical expressions or serum levels have been used in predicting neurologic outcome after resuscitation of cardiac arrest or recovery of cardioprotective function.

Role of Notoginsenoside Rg1 in Improving Spatial Cognitive Ability and Lowering Phosphorylation Level of Tau Protein in AD Model Rats

[Objectives] To study the effects and mechanism of notoginsenoside Rg1 on the spatial learning and memory and phosphorylated tau protein in the AD( Alzheimer's Disease) model rat. [Methods]The AD model rat was replicated by injection of Aβ_(25-35) in the left lateral ventricles of SD rats. The low dose( 25 mg/kg),middle dose( 50 mg/kg) and high dose( 100 mg/kg) notoginsenoside Rg1 was used for intragastric administration,respectively,two times every day. After 4 weeks,the Morris water maze test was done to detect the learning and memory capacity,and the immunoblotting,immunohistochemical methods were used to detect the changes in the phosphorylation level and distribution of tau protein in hippocampus of the rats. [Results] After the intracerebroventricular injection of Aβ_(25-35),the learning and memory capacity of the model rats was significantly lower than the learning and memory capacity of the normal control rats. The immunoblotting test results showed that the phosphorylation level of tau protein threonine 231 site( Thr231) in hippocampus was significantly increased,and the nonphosphorylation level was significantly decreased. The morphological testing results showed that the phosphorylation level of tau protein Thr231 of AD model rats was increased markedly in region of DG,CA1 and CA3 of the hippocampus. The intervention of the middle dose notoginsenoside Rg1 could significantly improve the learning and memory capacity of the model rats in Morris water maze. The notoginsenoside Rg1 in three different doses could all reduce the phosphorylation level of tau protein Thr231 in the hippocampal DG,CA1,CA3 regions,and there were no significant differences among the three doses. [Conclusions]The notoginsenoside Rg1 could improve Aβ_(25-35)-induced spatial learning and memory impairment of the AD model rats,and decreased the phosphorylation level of tau protein in hippocampus.

Effects of Propofol combined with remifentanil on the levels of MBP,NSE and S100B protein,D-D and inflammatory factors in patients with acute craniocerebral trauma

Objective: To investigate the effects of Propofol combined with remifentanil on serum levels of MBP, NSE and S100B protein, D-D and inflammatory factors in patients with acute craniocerebral trauma. Methods: A total of 100 patients were selected with traumatic brain injury who underwent emergency surgery from August 2014 to May 2017 in our hospital, then randomly divided them into the control group and the experimental group, 50 cases each. The control group received isoflurane combined with remifentanil to maintain anesthesia, and the experimental group received propofol and remifentanil to maintain anesthesia. The inflammatory factors and the levels of MBP, NSE, S100B and D-D in the two groups before and after anesthesia (T0), 1H (T1) and postoperative 1H (T2) were detected and compared. Results: There was no significant difference between the two groups in the levels of TNF-α. The serum level of hs-CRP in two groups of T1, T2 increased significantly, the difference was statistically significant compared with T0, in the experimental group, serum level of hs-CRP at T1 and T2 was significantly higher than the control group, the difference was statistically significant. Conclusion: Propofol combined with remifentanil anesthesia for acute craniocerebral trauma can maintain the balance of inflammatory cytokine levels during the perioperative period, inhibit the elevation of serum MBP, NSE, S100B protein and D-D levels, reduce brain cell damage. It has a good protective effect on brain cells and is worthy of clinical application.

Tau protein,phosphorylated tau protein,and beta-amyloid 42 levels in patients with neurodegenerative diseases complicated by cognitive deficits A non-randomized,concurrent,case-control investigation

BACKGROUND： The differential diagnosis of many neurodegenerative disorders depends primarily on clinical symptoms together with imaging methods. Recently, increased importance has been placed on the use of biomarkers for diagnosing various neurodegenerative disorders. OBJECTIVE： To assess the feasibility of tau-protein, phosphorylated tau-protein, beta-amyloid 42 （Aβ42）, and 14-3-3 protein as biomarkers for diagnosing several neurodegenerative diseases complicated by cognitive deficits. DESIGN, TIME AND SETTING： A non-randomized, concurrent, case-control investigation was performed in three medical centers in the Czech Republic （Department of Neurology at the University Hospital in Hradec Kralove, Department of Neurology at the 2rd Medical Faculty, and the University Hospital Motol） between October 2000 and November 2006. PARTICIPANTS： Eighteen patients with probable AIzheimer＇s disease, 4 patients with Creutzfeldt-Jakob disease, 10 patients with frontotemporal dementia, 9 patients with clinically isolated syndrome suggestive of multiple sclerosis, and 7 patients with multiple sclerosis, as well as 38 race-, nationality-, and age-matched cognitively intact controls, were included in the study. Diagnoses were established based on the following criteria： the criteria for Alzheimer＇s disease proposed by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer＇s Disease and Related Disorders Association, WHO criteria for Creutzfeldt-Jakob disease, Neary criteria for frontotemporal dementia, and McDonald＇s criteria for multiple sclerosis. All included patients were confirmed to suffer from various degrees of dementia. METHODS： Enzyme-linked immunosorbent assay was used to measure concentrations of tau-protein, phosphorylated tau-protein, and Aβ42 in cerebrospinal fluid （CSF） samples collected by standard lumbar puncture from each patient. Moreover, 14-3-3 protein was assessed by Western blot in CSF of Creutzfeldt-Jakob disease patients. Cognitive status was assessed using the Mini Mental Scale Examination （MMSE） in all subjects. MAIN OUTCOME MEASURES： Establishment of biomarkers with greatest specificity and sensitivity for the investigated disorders according to Receiver Operating Characteristic curves, which were based on values from patients and controls; correlation between concentrations of given biomarkers and demographic parameters, diagnosis, duration of disease, and level of cognitive deficit. RESULTS： Increased concentrations of total tau protein and phosphorylated tau protein, and decreased levels of Aβ42, in CSF of Alzheimer＇s disease patients reached the required sensitivity/specificity ratio of 80% or greater. A marked elevation in CSF concentrations of total tau protein showed even greater sensitivity than 14-3-3 protein in Creutzfeldt-Jakob disease. There was no association between selected biomarkers and frontotemporal dementia or multiple sclerosis. Phosphorylated tau-protein was the only biomarker that noticeably correlated with MMSE scores for Alzheimer＇s disease.CONCLUSION： Levels of total tau protein, phosphorylated tau protein, and A!342 in the CSF could differentiate patients with Alzheimer＇s disease and Creutzfeldt-Jakob disease from healthy controls and patients with other neurodegenerative disorders. The diversity of absolute values demonstrates the necessity to establish a specific standard for each laboratory.

The β-amyloid protein induces S100β expression in rat hippocampus through a mechanism that involves IL-1

Objective To explore the effect of β-amyloid protein (Aβ) on S100β expression in rat hippocampus and its mechanisms. Methods At 7 days after bilateral stereotaxis injection of different dose of fibrillar Aβ 25-35 and interluekin-1 receptor antagonist (IL-1ra) into the rat CA1 region, the learning and memory abilities of rats were tested with passive avoidance task. Amyloid deposition was detected by using Congo red staining technique. Nissl staining and immunohistochemical techniques were used to analyze the number of neurons, and GFAP and the S100β expression in hippocampal CA1 region , respectively. Results After fibrillar Aβ injection, the step-through latency of rats was significantly shortened compared to that of the control group. The GFAP positive astrocytes were found surrounding amyloid deposition. Neuronal loss occurred in the pyramidal cell layer of CA1 region. The number of S100β positive cells in Aβ-treated group was significantly increased compared with that in the control group. After IL-1ra injection, the number of S100β positive cells was significantly decreased. Conclusion Intrahippocampal injection of Aβ 25-35 could cause similar pathologic changes of Alzheimer’s disease. Aβ 25-35 was capable of up-regulating S100β expression in a dose-dependent manner. The injection of IL-1ra could attenuate the effect of Aβ on S100β expression.

Amyloid precursor-like protein 2 C-terminal fragments upregulate S100A9 gene and protein expression in BV2 cells

The murine microglial cell line BV2 has neuroprotective effects, but is toxic to neurons by secret-ing inlfammatory cytokines, and is an important target in the treatment of nerve inlfammation and neurodegenerative diseases. In the present study, we observed the effects of transfecting three amyloid precursor-like protein 2 （APLP2） C-terminal fragments （CTFs; C57, C50 and C31） in the pEGFP-N1 vector on S100A9 expression in BV2 cells. Reverse transcription-PCR, western blot assay and immunocytochemistry revealed that S100A9 protein and mRNA expression was greater in BV2 cells after CTF transfection than after mock transfection with an empty vector. Furthermore, transfection of full-length APLP2-751 resulted in low levels of S100A9 protein ex-pression. Our results show that APLP2-CTFs upregulate S100A9 protein and mRNA expression in BV2 cells, and identify a novel pathway involved in neuronal injury and apoptosis, and repair and protection in Alzheimer’s disease.

Soluble Structure of CLIC and S100 Proteins Investigated by Atomic Force Microscopy

The ability to visualise proteins in their native environment and discern information regarding stoichiometry is of critical importance when studying protein interactions and function. We have used liquid cell atomic force microscopy (AFM) to visualise proteins in their native state in buffer and have determined their molecular volumes. The human proteins S100A8, S100A9, S100A12 and CLIC1 were used in this investigation. The effect of oxidation on the protein structure of CLIC1 was also investigated and we found that CLIC1 multimerisation could be discerned by AFM, which supports similar findings by other methods. We have found good correlation between the molecular volumes measured by AFM and the calculated volumes of the individual proteins. This method allows for the study of single soluble proteins under physiological conditions and could potentially be extended to study the structure of these proteins when located within a membrane environment.

Preparation of Polyclonal Antisera of Dairy Cow S100A12 Protein

[Objective] This study aimed to prepare dairy cow anti-S100A12 antisem and develop a highly effective and sensitive immunological detection reagent for further investigation of the functions of dairy cow S100A12. [Method] Purified S100A12 protein was respectively emulsified with Freund＇s complete adjuvant and Freund＇s incomplete adjuvant as the antigen for immunizing New Zealand white rabbits to prepare the polyclonal antisera. The titer was detected using agar double diffusion assay and indirect enzyme-linked immunoserbent assay （ELISA） and the specificity was determined with Western Blot. [ Result ] The titer of anti- S100A12 antisera was 1： 8 as determined by agar double diffusion assay and over 1：409 600 by ELISA. Western Blot result showed that the polyclonal antisera could be specifically combined with S100A12 protein. [ Conclusion] The results indicated that anti-S100A12 polyclonal antibody with high fiter and high specificity was successfully obtained, which provided a novel tool for further investigation of the functions of S100A12 gene.

APPLICATION OF HMB－45 MONOCLONAL ANTIBODY AND S100 PROTEIN IN THE IMMUNOHISTOCHEMICAL DIAGNOSIS OF MELANOMA

We tested a variety of fixed embedded sections of malignant tumors with HMB-45 MoAband S-100 polyclonal antibody.The results showed that RMB-45 was a highly sensitive and specificantibody for recongnizing melanoma on fixed paraffin-embedded tissue sections, it reacted with 96.6percent of melanomas tested(all primary and 6 of 7 metastatic lesions)Both pigmented and nonpigmeated melanomas were recongnized.Malignant tumors of epithelial,lymphoid and mesenchymal origin were all negative.Although antibody to S-100 protien quite sensitive,it was not melanome-specific and it reached with all melanomas including the one metastatic melanoma that did not react withHMB-45,it we also positive in one of five lymphomas and one of three sarcomas.AdditionallyHMB-45 reacted with junctional nevi and componentes of compound neai and not with intradermalnevi and the dermal components of compound nevi.

Change and significance of serum inflammatory factors,NSE,S100 protein and stress hormone levels in patients with craniocerebral injury

Objective: To investigate the change and significance of serum inflammatory factors, neuron specific enolase (NSE), S100 protein and stress hormone levels in patients with brain diseases. Methods: A total of 115 patients with craniocerebral injury were selected as the observation group, according to the Glasgow Coma Scale (GCS), they were divided into light-sized group (n=38), middle-sized group (n=40) and severe-sized group (n=37), at the same time the other 120 healthy subjects were selected as the control group. The levels of serum inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and procalcitonin (PCT)], neuron specific enolase (NSE), S100 protein and the stress hormone cortisol [(COR), adrenocorticotropic hormone (ACTH), β-endorphin (β-EP)] of both groups were compared. Results: The levels of TNF-α, PCT, NSE, S100, COR, ACTH and β-EP in the observation group were (145.73±19.24) ng/L, (2.41±0.64) ng/mL, (38.11±12.28) ng/mL, (0.87±0.32) μg/L, (818.87±121.14) nmol/L, (107.38±13.94) ng/L, (126.74±39.04) ng/mL, which were significantly higher than control group, the difference was statistically significant;Comparison of indexes among the observation group, NF-α, PCT, NSE, S100, COR, ACTH and β-EP levels in the middle-sized group and severe-sized group were significantly higher than those in the light-sized group, and the levels in the severe-sized group were significantly higher than those of the middle-sized group, the difference was statistically significant. Conclusion:The levels of Serum inflammatory factors, NSE, S100 protein and stress hormone were significantly increased in patients with craniocerebral injury, the level was related to the degree of traumatic brain injury, which could be used as an important indicator to assess the severity of the disease.

Immunoexpression of Cathepsin D and S100A4 Protein and Their Molecular Subtyptes in Canine Mammary Carcinomas

Cathepsin D (CD), a lysosomal protease, and S100A4 protein, a calcium binding motif, are considered to be involved in metastasis in various human cancers. No data regarding such proteins are available for canine mammary carcinomas (CMCs). Accordingly, their expression in association with known factors of prognosis was investigated in this study. For that, 66 surgically resected CMCs were submitted to an immunohistochemical evaluation using anti CD, S100A4 protein, HER2, estrogen receptor α, cytokeratin 5, and p63 antibodies, further characterizing the tumors' molecular subtype. An increase in S100A4 immunoexpression by neoplastic luminal mammary cells was associated with an infiltrative tumor mode of growth, consequently leading us to conclude that S100A4 protein could be related to progression in CMCs. Additionally, the occurrence of the luminal A molecular subtype was associated with the complex histotype in CMCs. Although we have demonstrated that changes in S100A4 protein immunoexpression occurs in CMCs, further studies are needed to determine whether this represents important independent biomarkers for CMCs.

Effect of salvia miltiorrhiza and ligustrazine hydrochloride injection combined with hydroxyethyl starch injection on serum BNP, Hcy, MMP-2, S100B protein and hemorheology in patients with acute cerebral watershed infarction

Objective:To study the effect of salvia miltiorrhiza and ligustrazine hydrochloride injection combined with hydroxyethyl starch injection on serum BNP, Hcy, MMP-2, S100B protein and hemorheology in patients with acute cerebral watershed infarction.Methods:A total of 90 patientswith acute cerebral watershed infarction in our hospital from August 2014 to December 2016 were enrolled in this study. The subjects were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group was treated with hydroxyethyl starch injection, the treatment group was treated withsalvia miltiorrhiza and ligustrazine hydrochloride injection combined with hydroxyethyl starch injection, and both the two groups were treated for 2 weeks. The serum BNP, Hcy, MMP-2, S100B protein and hemorheology of the two groups before and after treatments were compared.Results:There were no significantly differences of the serum BNP, Hcy, MMP-2, S100B protein and hemorheology of the two groups before treatment. The serum BNP, Hcy, MMP-2, S100B proteinlevels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group after treatment were significantly lower than the control group. The PV, Lr, Mr, Hr and RE of the two groups after treatment were significantly lower than before treatment, and that of the treatment group after treatment were significantly lower than the control group.Conclusion:Salvia miltiorrhiza and ligustrazine hydrochloride injection combined with hydroxyethyl starch injectioncan significantlyimprovetheneurological function and hemorheology, reduce inflammation of the patients with acute cerebral watershed infarction, and it was worthy clinical application.

亚低温对颅脑损伤后血清S-100_β蛋白含量影响的实验研究

目的 观察亚低温治疗对颅脑损伤后患者血清S - 10 0 β蛋白含量变化的影响 ,揭示亚低温保护脑的可能机制。方法 4 6例重型颅脑损伤患者随机分成常温治疗组和亚低温治疗组 ,分别予以常温治疗和亚低温治疗。两组均于伤后 6h、2 4h、3d、7d等各时间点测定血清S - 10 0 β蛋白含量 ,并与 10名健康成年人正常对照组血清S - 10 0 β蛋白含量比较 ,观察亚低温治疗后颅脑损伤患者血清S - 10 0 β蛋白含量的变化。 结果 ①伤后各时间点两组颅脑损伤患者血清S - 10 0 β蛋白含量明显高于正常对照组 (P <0 0 1) ,但两组间S - 10 0 β蛋白含量在伤后 6h无显著性差异 (P >0 0 5 )。②亚低温治疗后各时点亚低温治疗组血清S - 10 0 β蛋白含量低于常温治疗组 ,且差异有统计学意义 (P <0 0 1) ,而且出院时预后也较常温治疗组为佳。结论 亚低温治疗能够降低颅脑损伤患者血清S - 10 0 β含量 ,其脑保护作用可能与亚低温能减轻S - 10 0

S100β对重症肺炎患者预后评估的价值

目的:探讨S100β对重症肺炎患者预后的评估价值。方法:以出院作为研究的观察终点,对2021年5月至2023年10月期间中山大学附属第一医院急诊科收治的107例重症肺炎患者的资料进行回顾性分析,根据S100β的血清学浓度分为阴性组和阳性组,根据患者出院存活状态分为存活组及死亡组,用GCS评分评估患者入院时神志,用CURB-65评分、SOFA评分、APACHEⅡ评分、PSI指数评估重症肺炎患者病情严重程度,采用出院时存活情况、机械通气时间(天)、去甲肾上腺素剂量(mg)、CRRT时间(天)评估重症肺炎患者预后。结果:107例重症肺炎患者中S100β阳性组的患者48人(44.9%),阴性患者59人(55.1%)。S100β阳性患者GCS评分低于S100β阴性患者,SOFA评分高于S100β阴性患者。S100β阳性组的患者住院期间机械通气时间、去甲肾上腺素使用剂量、CRRT治疗时长均高于S100β阴性患者。S100β阳性组的患者院内死亡率(62.5%)显著高于S100β阴性患者的(23.7%)。S100β联合SOFA评分及APACHEⅡ评分预测重症肺炎预后时,能辅助原有评分,提高诊断的特异性。结论:重症肺炎患者脑损伤发生率较高,可达44.9%,S100β能反映重症肺炎患者的病情严重程度,是预测重症肺炎患者预后不良的独立危险因素。

Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase Ⅳ protein levels in Alzheimer's disease model rats

Genistein has a neuroprotective effect in Alzheimer＇s disease, but its mechanism of action needs further clarification. Accumulating evidence suggests that excessive phosphorylation of tau protein causes production of neurofibrillary tangles, which is one of the main pathological characteristics of Alzheimer＇s disease, and tau protein can be phosphorylated by calcium/calmodulin dependent protein kinase IV （CAMK4）. After 7 days of pre-administration of genistein （90 mg/kg）, an Alzheimer＇s disease rat model was established using an intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide （25-35）. The rat was then continu- ously administered genistein （90 mg/kg） for 42 days. The Morris water maze test, western blotting and hematoxylin-eosin staining results showed that genistein significantly decreased the escape latency and increased the number of times crossing the platform, reduced p-tau, CALM, CAMKK1 and p-CAMK4 protein levels in the hippocampus, and alleviated hippocampal neuron damage. These findings indicate that genistein may play a neuroprotective role in Alzheimer＇s disease through regulating CAMK4 to modulate tau hyperphosphorylation. Key

Natural polyphenols effects on protein aggregates in Alzheimer＇s and Parkinson＇s prion-like diseases

Alzheimer＇s and Parkinson＇s diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer＇s disease, α-synuclein and synphilin-1 for Parkinson＇s disease. Drugs currently proposed to treat these pathologies do not prevent neurodegenerative processes and are mainly symptomatic therapies. Molecules inducing inhibition of aggregation or disaggregation of these proteins could have beneficial effects, especially if they have other beneficial effects for these diseases. Thus, several natural polyphenols, which have antioxidative, anti-inflammatory and neuroprotective properties, have been largely studied, for their effects on protein aggregates found in these diseases, notably in vitro. In this article, we propose to review the significant papers concerning the role of polyphenols on aggregation and disaggregation of amyloid peptide, tau, α-synuclein, synphilin-1, suggesting that these compounds could be useful in the treatments in Alzheimer＇s and Parkinson＇s diseases.