Upregulation of HDAC9 in hippocampal neurons mediates depression-like behaviours by inhibiting ANXA2 degradation.

Major depressive disorder (MDD) is a pervasive and devastating mental disease. Broad spectrum histone deacetylase (HDAC) inhibitors are considered to have potential for the treatment of depressive phenotype in mice. However, due to its non-specific inhibition, it has extensive side effects and can not be used in clinical treatment of MDD. Therefore, finding specific HDAC subtypes that play a major role in the etiology of MDD is the key to develop corresponding specific inhibitors as antidepressants in the future. Copy number variation in HDAC9 gene is thought to be associated with the etiology of some psychiatric disorders. Herein, we found that HDAC9 was highly expressed in the hippocampus of chronic restraint stress (CRS) mouse model of depression. Upregulation of HDAC9 expression in hippocampal neurons of mice induced depression-like phenotypes, including anhedonia, helplessness, decreased dendritic spine density, and neuronal hypoexcitability. Moreover, knockdown or knockout of HDAC9 in hippocampal neurons alleviated depression-like phenotypes caused by chronic restraint stress (CRS) in WT mice. Importantly, using immunoprecipitation-mass spectrometry (IP-MS), we further found that Annexin A2 (ANXA2) was coupled to and deacetylated by HDAC9. This coupling resulted in the inhibition of ubiquitinated ANXA2 degradation and then mediates depression-like behavior. Overall, we discovered a previously unrecognized role for HDAC9 in hippocampal neurons in the pathogenesis of depression, indicating that inhibition of HDAC9 might be a promising clinical strategy for the treatment of depressive disorders.

The role of class IIa histone deacetylases in regulating endothelial function.

Vascular endothelial cells (ECs) are monolayer cells located in the inner layer of the blood vessel. Endothelial function is crucial in maintaining local and systemic homeostasis and is precisely regulated by sophisticated signaling pathways and epigenetic regulation. Endothelial dysfunctions are the main factors for the pathophysiological process of cardiovascular and cerebrovascular diseases like atherosclerosis, hypertension, and stroke. In these pathologic processes, histone deacetylases (HDACs) involve in epigenetic regulation by removing acetyl groups from lysine residues of histones and regulating downstream gene expression. Among all HDACs, Class IIa HDACs (HDAC4, 5, 7, 9) contain only an N-terminal regulatory domain, exert limited HDAC activity, and present tissue-specific gene regulation. Here, we discuss and summarize the current understanding of this distinct subfamily of HDACs in endothelial cell functions (such as angiogenesis and immune response) with their molecular underpinnings. Furthermore, we also present new thoughts for further investigation of HDAC inhibitors as a potential treatment in several vascular diseases.

Annexin A2 promotes angiogenesis after ischemic stroke via annexin A2 receptor - AKT/ERK pathways.

Promoting angiogenesis to restore circulation to the ischemic tissue is still an important therapeutic target in stroke. Our group and others previously reported that the Ca2+-regulated, phospholipid-and membrane-binding protein-Annexin A2 (ANXA2) functions in cerebrovascular integrity and retinal neoangiogenesis. Here, we hypothesized that ANXA2 may regulate angiogenesis after stroke, ultimately improve neurological outcomes. Compared with wild type (WT) mice, the density of microvessels in brain and the number of new vessels sprouting from aortic ring were significantly increased in Anxa2 knock-in (Anxa2 KI) mice. After focal cerebral ischemia, proliferation of brain endothelial cells in Anxa2 KI mice was significantly elevated at 7 days post-stroke, which further improved behavioral recovery. To assess the pro-angiogenic mechanisms of ANXA2, we used brain endothelial cells cultures to investigate its effects on cell tube-numbers and migration. Recombinant ANXA2 increased tube-numbers and migration of brain endothelial cells either under normal condition or after oxygen glucose deprivation (OGD) injury. Co-immunoprecipitation experiments demonstrated that these protective effects of recombinant ANXA2 were regulated by interaction with ANXA2 receptor (A2R), a protein found in cancer cells that can interact with ANXA2 to promote cell migration and proliferation, and the ability of ANXA2-A2R to activate AKT/ERK pathways. Inhibition of AKT/ERK diminished recombinant ANXA2-induced angiogenesis in vitro. Taken together, our study indicates that ANXA2 might be involved in angiogenesis after ischemic stroke. Further investigation of ANXA2-A2R will provide a new therapeutic target for stroke.

Classical HDACs in the regulation of neuroinflammation.

Neuroinflammation is a key factor of the pathology of various neurological diseases (brain injury, depression, neurodegenerative diseases). It is a complex and orderly process that relies on various types of glial cells and peripheral immune cells. Inhibition of neuroinflammation can reduce the severity of neurological diseases. The initiation, progression, and termination of inflammation require gene activation, epigenetic modification, transcriptional translation, and post-translational regulation, all of which are tightly regulated by different enzymes. Epigenetics refers to the regulation of epigenetic gene expression by epigenetic changes (DNA methylation, histone modification, and non-coding RNAs such as miRNA) that are not dependent on changes in gene sequence and are heritable. Histone deacetylases (HDACs) are a group of important enzymes that regulate epigenetics. They can remove the acetyl group on the lysine ϵ-amino group of the target protein, thereby affecting gene transcription or altering protein activity. HDACs are involved in the regulation of immunity and inflammation. HDAC inhibitor (HDACi) has also become a new hotspot in the research of anti-inflammatory drugs. Therefore, the aim of the current review is to discuss and summarize the role and mechanism of different HDACs in neuroinflammation and the corresponding role of HDACi in neurological diseases, and to providing new ideas for future research on neuroinflammation-related diseases and drug development.

Evaluation of Subjective Sleep Disturbances in Cancer Patients: A Cross-Sectional Study in a Radiotherapy Department.

Background: The factors associated with sleep disturbances in cancer patients remains unclear. This study aimed to explore the prevalence of sleep disorders and predictors associated with sleep disturbance in cancer patients from a radiotherapy department. Methods: Patients with cancers were recruited before the start of radiotherapy from our institution between January 2019 and February 2020. Pittsburgh Sleep Quality Index (PSQI) scale was used to assess sleep quality. Descriptive statistics, Chi-square test, and multivariate logistic regression analysis were used to conduct statistical analysis. Results: A total of 330 eligible patients were included. Of them, 38.3% (n = 127) had the globe PSQI score >7, indicating that they suffered from sleep disorders. Patients with lung cancer (45.2%) were more likely to suffer from sleep disturbance, followed by cervical cancer (43.8%), nasopharyngeal carcinoma (41.7%), esophageal cancer (41.5%), breast cancer (37.7%), and colorectal cancer (30%). With regard to the PSQI components, the mean sleep duration was 8 h, 20.3% (n = 67) of them reported poor subjective sleep quality, 6.1% (n = 20) needed medication to improve sleep, and 53.6% (n = 177) suffered daytime dysfunction. Multivariate logistic regression models showed body mass index (BMI) ≥ 20 kg/m2 [odds ratio (OR) 0.599, 95% confidence interval (CI) 0.329-0.948, P = 0.031] and the receipt of surgery (OR 0.507, 95% CI 0.258-0.996, P = 0.048) were the significant favorable predictors for sleep disturbance, while age, gender, marital status, education level, comorbidity, metastasis status, diagnostic status, and cancer type were not significantly associated with sleep disturbance. Conclusions: Approximately 40% of the cancer patients suffer from sleep disturbance before the start of radiotherapy. Patients with BMI ≥ 20 kg/m2 and receiving surgery are less likely to develop sleep disturbance in comparison with others.

Carvacryl acetate, a semisynthetic monoterpenic ester obtained from essential oils, provides neuroprotection against cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.

Carvacryl acetate (CA) is a semisynthetic monoterpenic ester obtained from essential oils, and it exerts an antioxidation effect. The purpose of our study was to investigate whether CA could provide neuroprotection against oxidative stress caused by cerebral ischemia-reperfusion injury (CIRI) and elucidate the underlying mechanism. Middle cerebral artery occlusion (MCAO)-induced damage was established in Sprague Dawley (SD) rats and PC12 cells were exposed to hydrogen peroxide (H2O2) to imitate oxidative stress damage. TTC, HE and Nissl staining were used to observe the pathological morphology of lesions. The contents of ROS and MDA, and the activity of SOD were measured to reflect the level of oxidative stress. In addition, the TUNEL method was used to assess injuries in vitro, and the expression of Nrf2 was determined by immunohistochemical staining and western blot analysis. Importantly, we constructed and validated Nrf2 knockdown PC12 cells to confirm the key role of Nrf2 in the neuroprotective effect of CA against oxidative stress injuries. CA alleviated CIRI in rats with MCAO, as shown by brain tissue pathophysiology. The contents of ROS and MDA were reduced, and the SOD activity was augmented by the simultaneous promotion of Nrf2 expression. In addition, the H2O2-induced injury in Nrf2-knockdown PC12 cells was more serious than it was in control cells, and CA-mediated neuroprotection was exclusively inhibited by the knock down of Nrf2 in PC12 cells. In conclusion, it is shown here that CA has the effect of relieving cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.

Mini-Review: The Non-Immune Functions of Toll-Like Receptors.

Toll-like receptors (TLRs) are a family of highly conserved pattern recognition receptors that can recognize both pathogen-associated molecular patterns and danger-associated molecular patterns. These receptors are important in the activation of the innate immune system and play a role in shaping the adaptive immune system. For years, the expression of TLRs in the brain has been proposed to contribute to the immunological protection of the central nervous system. However, emerging studies have provided increasing evidence of non-immune functions of TLRs and suggest that these receptors may participate in more complex processes that extend beyond the regulation of the innate immune response. In this review, we highlight the expression of TLRs in non-immune cells and epitomize TLR non-immune functions. We aim to reveal the novel roles of TLRs that are distinct from their traditional functions in immunity. Negative regulatory approaches used to study TLR signaling pathways are also discussed, providing potential directions for further studies.

Nrf2 mediates the protective effect of edaravone after chlorpyrifos-induced nervous system toxicity.

We aim to confirm the impairment of chlorpyrifos (CPF) in PC12 cells, evaluate the protective effect of edaravone on CPF-induced injury, and try to unravel its underlying mechanism perspective from Nrf2 signaling pathway. Viability of PC12 cells treated with CPF and edaravone (Ed) were evaluated by MTT assay. Cell apoptosis was observed by the Hoechst 33342 stain. The level of reactive oxygen species (ROS), the content of malondialdehyde (MDA), and the activity of superoxide dismutase (SOD) were detected to evaluate the oxidative stress injury. The expression of Nrf2 was detected by Western blot; profoundly, RNA interference was conducted to construct Nrf2 gene knockdown PC12 cells and to uncover its underlying mechanism. MTT results showed CPF injured PC12 cells in a concentration-dependent manner. Increased ROS and MDA content, decreased total SOD activity, or even apoptosis were occurred in PC12 cells when treated with CPF. Interestingly, CPF-induced cell injury was conspicuously reversed after Ed administration. Nrf2 signaling pathway was activated after Ed treatment and the neuroprotective effect of Ed was not significant in cells after Nrf2 gene knockdown. In conclusion, Ed exerts neuroprotective effect on CPF-induced oxidative stress injury and its mechanism was correlated with the Nrf2 signaling pathway.

Insulin is a potential antioxidant for diabetes-associated cognitive decline via regulating Nrf2 dependent antioxidant enzymes.

PURPOSE: To investigate the neuroprotective effects of insulin on diabetic encephalopathy and its mechanism. EXPERIMENTAL AND APPROACH: The diabetic model was established by injection of streptozotocin. Behavior examinations were conducted by the Morris water maze. Histopathological alterations were detected by HE staining. ROS, CAT levels and SOD activity were measured using a microplate reader. In vitro, the viability of wild type and knock-down PC12 cells was detected by MTT assay, the morphology of cells was monitored under a microscope. The subcellular distribution of Nrf2 was observed by western blotting and immunohistochemistry. KEY RESULTS: Evident oxidative stress injury was observed in diabetic rats and H2O2-induced PC12 cells. Insulin not only protect diabetic rat from oxidative stress injury but also significantly inhibited H2O2-induced apoptosis and intracellular ROS in cells. In addition, the level of malondialdehyde was reduced, and the activities of superoxide dismutase, catalase and glutathione peroxidase were augmented in both diabetic rats and PC12 cells. Interestingly, insulin promoted the translocation of Nrf2 into the nucleus and activation of downstream antioxidant protein expression. Further, the Nrf2 knockdown cells suffered more serious H2O2-induced damage than the wild PC12 cells. Moreover, insulin had no significant protective effect on knockdown cells with H2O2-damage. CONCLUSION AND IMPLICATIONS: Collectively, our results suggested that insulin significantly inhibited neuronal damage through the Nrf2 signaling pathway, which regulates endogenous oxidant-antioxidant balance, therefore, insulin may be a potential protective agent for the treatment of oxidative stress-induced diabetic encephalopathy.

Edaravone, a free radical scavenger, protects neuronal cells' mitochondria from ischemia by inactivating another new critical factor of the 5-lipoxygenase pathway affecting the arachidonic acid metabolism.

To investigate the neuroprotective effect of edaravone was dependent on 5-lipoxygenase (5-LOX) signalling pathway or not. Middle cerebral artery occlusion (MCAO) and oxygen glucose deprivation (OGD) were established in SD rats and PC12 cells to mimic ischemic injury. In vivo, edaravone can significantly reduce neurological deficit scores, infarct volume, ROS level and expression of 5-LOX. For in vitro experiment, reduced viability, cell death which occurred via necrosis and apoptosis were shown after OGD and even severer in OGD-reperfusion (OGD-R). Interestingly, edaravone (0.01, 0.1, 1 µmol/L) and caffeic acid (5-LOX inhibitor) can dramatically attenuate OGD/OGD-R injuries. Profoundly, mitochondrial transmembrane potential was ameliorated and cristae membranes (detected by electron microscope) were swollen in OGD/OGD-R cells; however, edaravone preserved the normal ultrastructure of mitochondria and reduced ROS. Astonishingly, immunohistochemistry analyses showed that 5-LOX was first located in the cytosol, dendrites and nuclei of control cells and then translocated to the nuclear membrane after OGD/OGD-R, which indicated the activation of 5-LOX pathway. Edaravone and caffeic acid can inhibit 5-LOX translocation to the nuclear membrane after OGD/OGD-R and reduce cysteinyl leukotrienes (CysLTs), which are metabolites of 5-LOX. Our results are the first to indicate that the protective action of edaravone may function, at least in part, by inhibiting 5-LOX activation, maintaining the ultrastructure and integrated function of mitochondria, thus protecting neuronal cells from ischemia. Furthermore, the instability of mitochondria may be another critical factor in 5-LOX activation.

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Infected State of Human Alveolar type Ⅱ Epithelial Cells / 中山大学学报(医学科学版)

[Objective]To investigate the effect of human umbilical cord mesenchymal stem cells on infected state of human alve?olar type Ⅱ epithelial cells.[Methods]Human alveolar type Ⅱ epithelial cells A549(1×105/mL)2 mL and PA(3×104 CFU/mL)2 mL has grown after 6 hours,add hUCMSC(1 × 106/mL)2 mL as the experimental group,add equal amounts of phosphate buffer (PBS)for infection,A549 and PBS and the medium has grown as the control group. A549 cells morphological changes between the compared groups(Transmission electron microscope,TEM),A549 cell viability(new CCK-8 cell proliferation assay Kit),A549 cells apoptosis(Annexin V-FITC/PI double staining flow cytometry)and the expression of A549 pulmonary surfactant A(SP-A) (Western blot).[Results]Transmission electron microscope cell morphology observation displayed ,infection group A549 cell dam?aged obviously,cell quality appeared empty bubble degeneration,chromatin height agglutination,visible apoptosis bodies;experi?ment group cell package film structure full,nuclear film full,nucleolus obviously,nuclear chromatin electronic density low,chroma? tin uniform,no apoptotic bodies;control group A549 cell structure full,membrane surface micro-fluff rich,nuclear film full,nucle?ar week clearance structure normal,chromatin uniform;infection group and control group compared,Infection group A549 cell sur?vival significantly reduced[(70.35±2.89)% and(97.37±2.07)%,n=3,P<0.01],apoptosis rate significantly increased[(8.63%± 0.16)%and(2.55±0.11)%,n=3,P<0.01],In the infected group,PA could damage A549 cells and decrease the amount of SP-A ex?pression(n=5,P<0.05). In the experiment group,the protective effect of hUCMSC on the A549 cells after infection may increase the expression of SP-A(n=5,P<0.05);[Conclusions]HUCMSC inhibits the infection of A549 cells apoptosis and protection of A549 cells secrete SP-A.

Epigenetic suppression of hippocampal BDNF mediates the memory deficiency induced by amyloid fibrils.

Accumulating evidences demonstrated that epigenetic modification of the expression of specific genes contributed to the pathogenesis of neurological disorders with dementia, including Alzheimer's disease (AD). Emerging reports also found the reduction of hippocampal brain-derived neurotrophic factor (BDNF) in the patients and rodent models of AD, while the mechanism and functional significance remain debated. The present study aims to study the epigenetic mechanism underlying the BDNF reduction and its functional significance in the rats with hippocampal infusion of amyloid fibrils. In the rats injected with amyloid fibrils, significant decreases of BDNF expression and the mRNA of Bdnf exon VI were found in the hippocampal CA1 area. Significantly increased hippocampal HDAC2 expression and its occupancy in the promoter region of Bdnf exon VI were also observed, thus contributing to the histone H3 deacetylation and BDNF suppression in the hippocampal CA1 in the rats injected with amyloid fibrils. Inhibition of HDAC2 activity by trichostatin A substantially recovered the histone H3 acetylation in the promoter region of Bdnf exon VI and BDNF expression, thus mitigating the synaptic dysfunction and memory deficiency induced by amyloid fibrils. These results elucidate the epigenetic mechanism underlying the BDNF reduction induced by amyloid fibrils, and provided novel insights into the pathogenic mechanism of Alzheimer's disease.

Diaporine, a novel endophyte-derived regulator of macrophage differentiation.

Diaporine (1), an unprecedented symmetric polyketide, was characterized from the endophytic fungus. The structure was determined by extensive spectroscopic analyses. Diaporine can inhibit significantly the differentiation of macrophages and has potential to induce conversion from the M2 to the M1 phenotype, in addition to regulation of the TLR4-MAPK signal pathway and PPARγ activity.

Platelet glycoprotein IIIa gene polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population.

OBJECTIVES: To study the relationship between platelet glycoprotein IIIa gene (GP IIIa) polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population. METHODS: Four hundred fifty very elderly Chinese people receiving aspirin therapy were enrolled in the study. Patients who underwent arachnoid acid-induced platelet aggregation were then divided into two groups based on their resistance to aspirin: aspirin-resistant (AR) group (n=236) and aspirin-sensitive (AS) group (n=214). The Leu33Pro polymorphism of the GP IIIa gene was scanned by polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: In the AR group, 224 participants had the A1/A1 genotype and 12 had the A1/A2 genotype. All patients in the AS group had the A1/A1 genotype. Thus, there was significant difference between these two groups in the genotype distribution (p<0.05). CONCLUSION: The genetic polymorphism of the GP IIIa gene was associated with AR in a very elderly Chinese population.

Alprostadil plays a protective role in contrast-induced nephropathy in the elderly.

PURPOSE: To evaluate the protective effects of alprostadil on contrast-induced nephropathy (CIN) in elderly patients. METHODS: We randomized 370 patients into the control or alprostadil group. The patients in the control group were injected with 100 ml sterile saline and the patients in the alprostadil group with alprostadil (0.4 µg/kg/day) in 100 ml sterile saline before and after iohexol-enhanced (100 ml) computed tomography (CT). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (CysC), and creatinine clearance (Ccr) were analyzed or calculated. ΔScr and ΔCysC were determined by the changes between baseline and highest Scr and CysC levels. The standard for CIN was a postdose Scr increase >44.2 µmol/l or >25 % over baseline. RESULTS: In the control group, peak Scr (P < 0.05) and ΔScr (P < 0.01) were higher than those in the alprostadil group. The postdose CysC at 24 h (P < 0.05), 48 h (P < 0.05), and 72 h (P < 0.05), peak CysC (P < 0.01), and ΔCysC (P < 0.05) in the control group were higher than those in the alprostadil group. The incidence of CIN in the control group was 22.2 %, which was higher than in the alprostadil group (9.1 %, P < 0.01). Subgroup analyses in patients with advanced age (≥ 80 years), concomitant hypertension or diabetes, and abnormal baseline renal function (Ccr ≤ 60 ml/min) showed that the alprostadil group had lower ΔScr and ΔCysC than the control group after contrast-enhanced CT examination in all four subgroups (P < 0.05 or P < 0.01). CONCLUSIONS: In this cohort of older patients undergoing contrast CT, the use of alprostadil reduced the incidence of CIN.

The relationship between glucose excursion and cognitive function in aged type 2 diabetes patients.

OBJECTIVE: Evidence suggests that type 2 diabetes (T2DM) is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. METHODS: A total of 248 aged T2DM patients wore a continuous glucose monitoring system (CGMS) for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions (MAGE) and mean of daily difference (MODD). All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination (MMSE). The relationship between MAGE and MODD and performance on these cognitive tests was assessed. RESULTS: The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. CONCLUSION: Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.

Hyperinsulinemia, insulin resistance and cognitive decline in older cohort.

OBJECTIVE: Type 2 diabetes has been recently recognized as an important risk factor for cognitive decline of patients with Alzheimer's disease (AD). But the roles of hyperinsulinemia (HI) and insulin resistance (IR) in the development of AD are still controversial. This study was designed to evaluate whether HI or IR influenced the cognitive functions of older cohort. METHODS: The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose (FBG) and fasting insulin (FINS) were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. RESULTS: In our study, there were 180 participants with HI and 148 without HI, and 192 with IR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model 1 adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. CONCLUSION: HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.

[The effect of adiponectin on human periodontal ligament fibroblasts in vitro].

PURPOSE: To investigate the expression of adiponectin receptor in periodontal tissues and the effect of adiponectin with different concentrations on the proliferation of human periodontal ligament fibroblast cells. METHODS: Ten human healthy premolars extracted for orthodontic reasons were collected. The primary cells were isolated from human periodontal ligament and cultured by tissue block method,then passaged when the cells completely covered the bottom of petri dish. The expression of AdipoR1 and AdipoR2 in human periodontal ligament fibroblasts was detected by RT-PCR. Adiponectin (0,5,10,20ng/µL) was added to petri dish in which the cells were incubated for 24 hours.The cells were then incubated with adiponectin for 7 days,and determined by MTT assay.SPSS16.0 software package was used for statistical analysis. RESULTS: By immunocytochemical method,the cells were stained positively to antibodies against vimentin,and negatively to antibodies against cytokeratin,indicating that they were external embryo mesenchymal cells ,without epithelial cell mixation. Agarose gel electrophoresis showed Adipo R2 was positively expressed in human periodontal ligament fibroblasts. MTT assay showed that proper doses of adiponectin could promote proliferation of human periodontal ligament fibroblasts (P<0.05).The number of adherent cells of group C or group D was significantly greater than that of group A after 24 hours(P<0.05); Group B, group C,and group D had significantly more adherent cells than group A after 96 hours and 168 hours (P<0.05). CONCLUSIONS: Adiponectin receptor 2 is expressed in the periodontal tissues.The proper doses of adiponectin could promote proliferation of human periodontal ligament fibroblasts.

[Clinical diagnosis and treatment in an outbreak of Fasciola gigantica infection in Yunnan Province].

OBJECTIVE: To carry out clinical diagnosis and treatment of Fasciola gigantica infection during an outbreak in Yunnan Province. METHODS: Data on epidemiology, diagnosis and treatment were collected from 27 patients. A questionnaire survey to the patients and partial villagers was carried out including history of raw food-eating and pet-raising. Animal feces were collected and examined by precipitation method and eggs incubation method. Cattle from two patients families were dissected to find Fasciola infection. Serum samples from patients, family members, and villagers were detected. Possible intermediate snails were collected from the vicinity of streams and ponds in 15 villages where patients lived. RESULTS: The earliest onset of symptoms among the patients was on March 10, 2011 and the last case was on January 10, 2012. The clinical manifestations were mainly fever with unknown reason, decreasing hemoglobin, increasing eosinophils, and hepatosplenomegaly. No parasite eggs were found in feces. Antibodies against F. gigantica were positive by ELISA in 23 patients. Fasciola eggs were then found in 4 patients' feces on February 16, 2012. F. gigantica eggs and adults were found in the hepatobiliary system of dissected cattle. Triclabendazole [10 mg/(kg x d) x2 d] was administered orally for the patients and the clinical symptoms eased. Snails including Physa acuta, Radix swinhoei and Galba pervia were collected and cercariae were found in only one snail. CONCLUSION: An outbreak of F. gigantica infection has been confirmed and the diagnosed cases effectively treated with triclabendazole.

The relationship between glucose excursion and cognitive function in aged type 2 diabetes patients / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Evidence suggests that type 2 diabetes (T2DM) is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients.</p><p><b>METHODS</b>A total of 248 aged T2DM patients wore a continuous glucose monitoring system (CGMS) for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions (MAGE) and mean of daily difference (MODD). All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination (MMSE). The relationship between MAGE and MODD and performance on these cognitive tests was assessed.</p><p><b>RESULTS</b>The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history.</p><p><b>CONCLUSION</b>Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.</p>