[Reconstructing January-June precipitation in Southeastern Shanxi over the past 296 years inferred from tree-ring records of Pinus tabuliformis]. / åŸºäºŽæ²¹æ¾æ ‘è½®é‡å»ºæ™‹ä¸œå—åœ°åŒºè¿‘296年来1­6月降水变化.

The study of regional historical climate change is limited by the availability of observational data, which is not conducive to understanding long-term climate change. In this study, we used the tree-ring cores of Pinus tabuliformis to establish a tree ring width chronology (RES) from the southeast Shanxi Province, and analyzed the relationship between precipitation and tree-ring width chronology. The results showed that the residual chronology had a good correlation (r=0.636, n=59, P<0.01) with January-June precipitation. A linear regression was used to reconstruct the January-June precipitation for the southeastern Shanxi Province, which accounts for 40.4% of the instrumental precipitation variation during 1724-2019. Dry conditions occurred during 1742-1771, 1830-1848, 1872-1894, 1917-1945, 1961-1981, and 1990-2019, while the periods of 1727-1741, 1772-1829, 1849-1871, 1895-1916 were relatively wet. There were 10 extremely dry years and six extremely wet years during the period from 1724 to 2019. The longest dry periods were 1742-1771 and 1990-2019, while the longest wet period was 1772-1829. Results of spatial climate correlation analyses with gridded land surface data showed that the precipitation reconstruction contained a strong regional precipitation signal for southeast Shanxi Province. Power spectrum analysis of the precipitation reconstruction showed remarkable 2.3, 3.2-3.3, 3.7-3.8, 6.3-6.7, 8.3-8.7 years cycles for the past 296 years, the 2.3 year cycle corresponds to the 'quasi-two-year pulsation', and the 3.2-3.3, 3.7-3.8 and 6.3-6.7 year cycles might have a certain relationship with ENSO. Results of the spatial correlation analysis showed that the reconstructed precipitation series could better represent precipitation changes in the study area.

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients.

BACKGROUND: At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM: To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS: Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS: Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION: The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

[Effects of microbial agents on bacterial community composition during swine manure composting]. / å¾®ç”Ÿç‰©èŒå‰‚å¯¹çŒªç²ªå †è‚¥ä¸­ç»†èŒç¾¤è½ç»“æž„çš„å½±å“.

The process of swine manure and wheat straw aerobic composting was examined, with exogenous microbial agents being added in treatment group. The physicochemical properties were measured by conventional methods, and bacterial community characteristics were investigated by high throughput sequencing analysis. Exogenous microbial agents increased high-temperature duration, reduced pH value at the end of fermentation stage, augmented total nitrogen content, reduced C/N ratio. Results from principal component analysis showed that microbial agents affected the stability of bacterial community during composting. At the phylum level, the relative abundance of Firmicutes, Proteobacteria, and Chloroflexi was higher in the treatment group. At the class level, the relative abundance of Clostridia, Alphaproteobacteria, and Gammaproteobacteria in the treatment group were higher at the mesophilic and thermophilic phases. At the family level, Peptostreptococcaceae, Clostridiaceae_1, and Halanaerobiaceae of the Clostridia and Micromonosporaceae in the treatment group were higher at the mesophilic and thermophilic phases. Halocella was significantly positively correlated with exogenous microbial agents, while Ammoniibacillus was significantly negatively correlated with it. It suggested that microbial agents significantly changed the physicochemical properties and bacterial community structure during swine composting.

Morin exerts protective effects on encephalopathy and sepsis-associated cognitive functions in a murine sepsis model.

Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3ß activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aß deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.

Caspase-1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia.

AIMS: The involvement of pyroptosis in ischemic stroke remains to be established. Therefore, we used the specific pyroptosis inhibitor Vx765 as an experimental intervention target in a murine model of stroke. METHODS: A total of 564 C57BL/6 mice were subjected to photothrombotic procedures and treated via gavage with Vx765 at 1-hour post-ischemia. We subsequently assessed the expression of Gasdermin D (GSDMD), inflammasomes, caspase-1, and interleukin-1ß (IL-1ß) using immunofluorescence (IF) and Western blot (WB) analyses. We also examined ultrastructural changes of cortical neurons with transmission electron microscopy (TEM) and measured infarct volumes dynamically by magnetic resonance imaging (MRI). Moreover, we evaluated the neurologic deficits by modified neurological severity scores, the rotarod test, and Treadscan. RESULTS: Elevated expression of GSDMD and GSDMD p30, the pore-forming subunit, was evident in the peri-ischemic region on days one and three post-ischemia. The neuronal plasma, nuclear, and mitochondrial membranes showed ultrastructural damage at day three post-stroke. Elevated expression of inflammasomes, caspase-1, and IL-1ß was also present on days one and three post-injury. There were significant differences between Vx765-treated and vehicle groups in mean infarct volumes (14.36 vs 21.52 mm3 ; 12.34 vs 18.56 mm3 ; 4.13 vs 10.06 mm3 ; P < .05 at day one, three, and seven post-surgery, respectively). Mice treated with Vx765 showed better motor recovery as assessed by serial behavior tests and had better neuronal survival, which was attributable to pyroptosis inhibition, as illustrated by downregulated expression of the effector protein GSDMD, inflammasomes, caspase-1, and IL-1ß. Besides, treatment with Vx765 preserved neuronal membrane structures after the ischemic injury. CONCLUSIONS: Pyroptosis emerges as an important pathway for neuronal death in an acute ischemic stroke. Vx765, a low molecular weight drug that has proven safe in clinical epilepsy trials, has potential therapeutic value for cerebral ischemia by targeting the canonical inflammasome pathway of pyroptosis.

FK866 attenuates sepsis-induced acute lung injury through c-jun-N-terminal kinase (JNK)-dependent autophagy.

AIMS: Increasing evidence indicates that FK866, a specific noncompetitive nicotinamide phosphoribosyl transferase inhibitor, exhibits a protective effect on acute lung injury (ALI). Autophagy plays a pivotal role in sepsis-induced ALI. However, the contribution of autophagy and the underlying mechanism by which FK866-confered lung protection remains elusive. Herein, we aimed to study whether FK866 could alleviate sepsis-induced ALI via the JNK-dependent autophagy. MAIN METHODS: Male C57BL/6 mice were subjected to cecal ligation and puncture (CLP) to establish the polymicrobial sepsis mice model, and treated with FK866 (10 mg/kg) at 24, 12 and 0.5 h before the CLP procedure. The lung protective effects were measured by lung histopathology, tissue edema, vascular leakage, inflammation infiltration, autophagy-related protein expression and JNK activity. A549 cells were stimulated with LPS (1000 ng/ml) to generate the ALI cell model, and pretreated with FK866 or SP600125 for 30 min to measure the autophagy-related protein expression and JNK activity. KEY FINDINGS: Our results demonstrated that FK866 reduced lung injury score, tissue edema, vascular leakage, and inflammatory infiltration, and upregulated autophagy. The protective effect of autophagy conferred by FK866 on ALI was further clarified by using 3-methyladenine (3MA) and rapamycin. Additionally, the activity of JNK was suppressed by FK866, and inhibition of JNK promoted autophagy and showed a benefit effect. SIGNIFICANCE: Our study indicates that FK866 protects against sepsis-induced ALI by induction of JNK-dependent autophagy. This may provide new insights into the functional mechanism of NAMPT inhibition in sepsis-induced ALI.

Brief Mindfulness Meditation Improves Emotion Processing.

Mindfulness-based interventions have previously been shown to have positive effects on psychological well-being. However, the time commitment, teacher shortage, and high cost of classic mindfulness interventions may have hindered efforts to spread the associated benefits to individuals in developing countries. Brief mindfulness meditation (BMM) has recently received attention as a way to disseminate the benefits of mindfulness-based interventions. Most existing BMM methods are adaptations of the classic approach. Few studies have investigated the mechanisms underlying the beneficial effects of BMM. We developed a 15-min BMM named JW2016, which is based on the core concepts of mindfulness, Anapanasati (breath meditation of Buddhist Vipassana), our practical experience, and the results of scientific reports on meditation. We investigated the effects of this BMM on mood and emotion processing in an effort to create an effective, convenient, safe, and standardized BMM method that could benefit individuals with limited time or money to devote to meditation. Forty-six healthy participants (aged 18-25 years) were randomly allocated to the BMM group (n = 23) or the emotional regulation education (ERE) control group (n = 23). Forty-two of the study participants cooperated fully in all measurements and interventions (one time daily for seven consecutive days). Mood was measured with the Centre for Epidemiological Studies-Depression scale (CES-D) and the State Anxiety Inventory (SAI). Emotion processing was evaluated by assessing performance on an emotion intensity task, an emotional memory task, and an emotional dot-probe task. After intervention, the BMM group, but not the ERE group, showed a significant decreases in emotional intensity in response to positive as well as negative emotional stimuli, response time for emotional memory, and duration of attention bias toward negative emotional stimuli. Negative effects on mood state were found in the ERE group but not in the BMM group. This study demonstrated that BMM may improve aspects of emotion processing such as emotion intensity, emotional memory, and emotional attention bias. JW2016 BMM may be an effective, convenient, safe and standardized way to help practitioners remain focused and peaceful without any negative effect on emotion.

Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.

Sepsis-associated encephalopathy (SAE) manifested clinically in acute and long-term cognitive impairments and associated with increased morbidity and mortality worldwide. The potential pathological changes of SAE are complex and remain to be elucidated. Pyroptosis, a novel programmed cell death, is executed by caspase-1-cleaved GSDMD N-terminal (GSDMD-NT) and we investigated it in peripheral blood immunocytes of septic patients previously. Here, a caspase-1 inhibitor VX765 was treated with CLP-induced septic mice. Novel object recognition test indicated that VX765 treatment reversed cognitive dysfunction in septic mice. Elevated plus maze, tail suspension test and open field test revealed that depressive-like behaviors of septic mice were relieved. Inhibited caspase-1 suppressed the expressions of GSDMD and its cleavage form GSDMD-NT, and reduced pyroptosis in brain at day 1 and day 7 after sepsis. Meantime, inhibited caspase-1 mitigated the expressions of IL-1ß, MCP-1 and TNF-α in serum and brain, diminished microglia activation in septic mice, and reduced sepsis-induced brain-blood barrier disruption and ultrastructure damages in brain as well. Inhibited caspase-1 protected the synapse plasticity and preserved long-term potential, which may be the possible mechanism of cognitive functions protective effects of septic mice. In conclusion, caspase-1 inhibition exerts brain-protective effects against SAE and cognitive impairments in a mouse model of sepsis.

Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model.

Increasing evidence demonstrates that pyroptosis, pro-inflammatory programmed cell death, is linked to acute lung injury (ALI). Dihydromyricetin (DHM) has been reported to exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation in vascular endothelial cells. However, the effects of DHM on NLRP3 inflammasome-induced pyroptosis in ALI remain elusive. In the present study, male BALB/c mice were subjected to cecal ligation and puncture (CLP), and DHM (50, 100, 150 mg/kg) was orally administered (once per day, for 3 days) 2 h after CLP. After 72 h, lung histopathology was examined, and the wet/dry (W/D) ratio, inflammatory infiltration, total protein concentration, total cell, and neutrophil counts were detected. Myeloperoxidase (MPO), interleukin (IL)-6, TNF-α, IL-1ß, and IL-18 levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, the expression of NLRP3 signaling pathway proteins were detected by Western blotting. The results revealed that in BALF, DHM (150 mg/kg) treatment significantly reduced the CLP-induced lung histopathological injury, inflammatory cell infiltration, total cell and neutrophil number, and total protein and albumin concentration. DHM treatment significantly inhibited the CLP-induced NLRP3 inflammasome pathway (NLRP3, ASC, caspase-1, gasdermin D (Gsdmd), IL-1ß, and IL-18). In conclusion, these results demonstrate that DHM protects against CLP-induced ALI by inhibiting NLRP3 inflammasome activation and subsequent pyroptosis.

Anterior Subcutaneous Transposition of the Ulnar Nerve Affects Elbow Range of Motion: A Mean 13.5 Years of Follow-up.

BACKGROUND: Surgical decompression of the ulnar nerve is effective for cubital tunnel syndrome. However, deep approaches may result in iatrogenic elbow stiffness. This long-term study was to evaluate the range of motion (ROM) of the elbow and functional outcomes after anterior subcutaneous transposition. METHODS: A total of 115 patients (78 male and 37 female; mean age: 46.6 years) who underwent anterior subcutaneous transposition of the ulnar nerve between 2001 and 2005 were evaluated retrospectively; mean follow-up was 13.5 years. Elbow ROM was measured as flexion arc, flexion, and extension preoperatively and at the final follow-up, and compared via a mixed analysis of variance adjusting for age. Neuropathy was assessed preoperatively using a modified McGowan neuropathy grade and postoperatively using modified Wilson-Krout criteria. An ordinal logistic regression analysis used postoperative modified Wilson-Krout criteria as the outcome and preoperative factors as predictors. RESULTS: Preoperative McGowan grades were Grade 1 in 14 patients (12.2%), Grade 2A in 28 (24.3%), Grade 2B in 53 (46.1%), and Grade 3 in 20 (17.4%) patients. Postoperatively, 66 patients (57.4%) had excellent results, 26 (22.6%) had good results, 16 (13.9%) had fair results, and 7 (6.1%) had poor results at the final follow-up, as per the Wilson-Krout criteria. There were no complications. Pre- and postoperative elbow ROM was significantly decreased in patients with previous trauma or surgery of the elbow compared with those without (P < 0.05). Anterior subcutaneous transposition of the ulnar nerve did not significantly affect elbow ROM regardless of previous trauma or surgical history nor preoperative ROM (P > 0.05), after adjusting for age. Patients with prolonged symptoms prior to surgery and worse neuropathy tended to have less satisfactory functional outcomes (P < 0.05), after adjusting for covariates. CONCLUSIONS: Anterior subcutaneous transposition of the ulnar nerve is an effective and reliable treatment of cubital tunnel syndrome with satisfactory outcomes and minimal effect on elbow ROM.

Effect of recurrent severe hypoglycemia on cognitive performance in adult patients with diabetes: A meta-analysis.

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus (DM) patients with episodes of recurrent severe hypoglycemia, by using meta-analysis to synthesize data across studies. PubMed, EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia. Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method. Effect sizes, which are the standardized differences between the experimental group and the control group, were calculated. Of the 853 studies, 7 studies met the inclusion criteria. Compared with control subjects, the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients, and poor performance of processing speed in type 2 DM patients. There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence, executive function, processing speed and psychomotor efficiency. Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia, whereas general intelligence, executive function, and psychomotor efficiency are spared.

Effect of Recurrent Severe Hypoglycemia on Cognitive Performance in Adult Patients with Diabetes: A Meta-analysis / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the existence and extent of cognitive impairment in adult diabetes mellitus (DM) patients with episodes of recurrent severe hypoglycemia,by using meta-analysis to synthesize data across studies.PubMed,EMBASE and Cochrane library search engines were used to identify studies on cognitive performance in DM patients with recurrent severe hypoglycemia.Random-effects meta-analysis was performed on seven eligible studies using an inverse-variance method.Effect sizes,which are the standardized differences between the experimental group and the control group,were calculated.Of the 853 studies,7 studies met the inclusion criteria.Compared with control subjects,the adult DM patients with episodes of recurrent severe hypoglycemia demonstrated a significantly lowered performance on memory in both types of DM patients,and poor performance of processing speed in type 2 DM patients.There was no significant difference between adult DM patients with and those without severe hypoglycemia in other cognitive domains such as general intelligence,executive function,processing speed and psychomotor efficiency.Our results seem to confirm the hypothesis that cognitive dysfunction is characterized by worse memory and processing speed in adult DM patients with a history of recurrent severe hypoglycemia,whereas general intelligence,executive function,and psychomotor efficiency are spared.

TPPU protects tau from H2O2-induced hyperphosphorylation in HEK293/tau cells by regulating PI3K/AKT/GSK-3ß pathway.

Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3ß) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects. However, little is known about the role of sEH in tau phosphorylation. The present study investigated the role of a sEH inhibitor, 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl] urea (TPPU), on H2O2-induced tau phosphorylation and the underlying signaling pathway in human embryonic kidney 293 (HEK293)/Tau cells. We found that the cell viability was increased after TPPU treatment compared to control in oxidative stress. Western blotting and immunofluorescence results showed that the levels of phosphorylated tau at Thr231 and Ser396 sites were increased in H2O2-treated cells but dropped to normal levels after TPPU administration. H2O2 induced an obvious decreased phosphorylation of GSK-3ß at Ser9, an inactive form of GSK-3ß, while there were no changes of phosphorylation of GSK-3ß at Tyr216. TPPU pretreatment maintained GSK-3ß Ser 9 phosphorylation. Moreover, Western blotting results showed that TPPU upregulated the expression of p-Akt. The protective effects of TPPU were found to be inhibited by wortmannin (WT, a specific PI3K inhibitor). In conclusion, these results suggested that the protective effect of TPPU on H2O2-induced oxidative stress is associated with PI3K/Akt/GSK-3ß pathway.

SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.

Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and ß-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.

Silencing PP2A inhibitor by lenti-shRNA interference ameliorates neuropathologies and memory deficits in tg2576 mice.

Deficits of protein phosphatase-2A (PP2A) play a crucial role in tau hyperphosphorylation, amyloid overproduction, and synaptic suppression of Alzheimer's disease (AD), in which PP2A is inactivated by the endogenously increased inhibitory protein, namely inhibitor-2 of PP2A (I2(PP2A)). Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration. By infusion of lentivirus-shRNA targeting I2(PP2A) (LV-siI2(PP2A)) into hippocampus and frontal cortex of 11-month-old tg2576 mice, we demonstrated that expression of LV-siI2(PP2A) decreased remarkably the elevated I2(PP2A) in both mRNA and protein levels. Simultaneously, the PP2A activity was restored with the mechanisms involving reduction of the inhibitory binding of I2(PP2A) to PP2A catalytic subunit (PP2AC), repression of the inhibitory Leu309-demethylation and elevation of PP2AC. Silencing I2(PP2A) induced a long-lasting attenuation of amyloidogenesis in tg2576 mice with inhibition of amyloid precursor protein hyperphosphorylation and ß-secretase activity, whereas simultaneous inhibition of PP2A abolished the antiamyloidogenic effects of I2(PP2A) silencing. Finally, silencing I2(PP2A) could improve learning and memory of tg2576 mice with preservation of several memory-associated components. Our data reveal that targeting I2(PP2A) can efficiently rescue Aß toxicities and improve the memory deficits in tg2576 mice, suggesting that I2(PP2A) could be a promising target for potential AD therapies.

Lithium attenuates scopolamine-induced memory deficits with inhibition of GSK-3ß and preservation of postsynaptic components.

Cholinergic dysfunction plays a crucial role in the memory deterioration of Alzheimer's disease, but the molecular mechanism is not fully understood. By employing a widely recognized cholinergic dysfunction rat model that was produced by intraperitoneal injection of scopolamine, we investigated the mechanisms underlying scopolamine-induced memory deficits. We found that scopolamine caused spatial learning and memory deficits that involved activation of glycogen synthase kinase-3ß (GSK-3ß) and impairments of dendrite arborization and spine formation/maturation associated with alterations of AMPAR, Homer1, and CREB. Pretreatment by intraperitoneal injection of lithium, an inhibitor of GSK-3, for one week prevented the synaptic changes and the learning and memory deficits induced by scopolamine. Lithium treatment also activated cholineacetyltransferase and inhibited acetylcholinesterase, which might have also contributed to the improved memory. Our findings suggest that GSK-3ß may be a key molecular mediator of cholinergic synaptic dysfunction, and that inhibition of GSK-3ß by lithium may be promising in protecting cholinergic synaptic functions.

Anxiolytic-like effect of α-asarone in mice.

The effects of α-asarone in four assays predictive of anxiolytic activity in male mice were studied, with diazepam as a positive anxiolytic control. The use of the elevated plus-maze test revealed that diazepam (2 mg/kg) or α-asarone (3.5 mg/kg) increased the percentage of entries into open arms and of the time spent on open arms. In the light/dark transition test, as with 2 mg/kg diazepam, 7 mg/kg α-asarone increased the time spent in the light area and the number of transitions between the two compartments. In the novel food consumption test, α-asarone (3.5, 7 and 14 mg/kg) caused significant increases in food intake during 5 min as well as diazepam (0.5 mg/kg). In the marble burying test, α-asarone also produced a significant inhibition of marble burying at doses of 14 and 28 mg/kg, as did diazepam (5 mg/kg). Thus, these findings indicated that α-asarone exhibited an anxiolytic-like effect. Further studies will be required to assess the generality of the present findings to other species and behavioral paradigms.

Vitamin E modulates cigarette smoke extract-induced cell apoptosis in mouse embryonic cells.

Vitamin E (VE) can effectively prevent occurrence of lung cancer caused by passive smoking in mice. However, whether VE prevents smoking-induced cytotoxicity remains unclear. In this study, a primary culture of embryonic lung cells (ELCs) was used to observe the cytotoxic effects of cigarette smoke extract (CSE), including its influence on cell survival, cell cycle, apoptosis, and DNA damage, and also to examine the effects of VE intervention on CSE-induced cytotoxicity. Our results showed that CSE could significantly inhibit the survival of ELCs with dose- and time-dependent effects. Furthermore, CSE clearly disturbed the cell cycle of ELCs by decreasing the proportion of cells at the S and G2/M phases and increasing the proportion of cells at the G0/G1 phase. CSE promoted cell apoptosis, with the highest apoptosis rate reaching more than 40%. CSE also significantly caused DNA damage of ELCs. VE supplementation could evidently inhibit or reverse the cytotoxic effects of CSE in a dose- and time-dependent manner. The mechanism of CSE effects on ELCs and that of VE intervention might involve the mitochondrial pathway of cytochrome c-mediated caspase activation. Our study validate that VE plays a clearly protective effect against CSE-induced cytotoxicity in mouse embryonic lung cells.

Monoacylglycerol lipase (MAGL) knockdown inhibits tumor cells growth in colorectal cancer.

OBJECTIVES: Obesity has been reported to increase the risk of colorectal cancer, which may due to aberrant lipid metabolism. And recently findings of monoacylglycerol lipase provide a novel evidence in the correlation of obesity and cancer. So in this study, we investigated the effect of MAGL in regulation of tumor growth in colorectal cancer. METHODS: MAGL expression in tumor tissues was estimated, and then JZL184 and siRNA were used to knockdown the expression of MAGL in colorectal cancer cells. Cell viability and invasion were detected to estimate the influence of MAGL knocked down in vitro and vivo. Then cell proliferation, apoptosis, cell cycle transition and screening of candidate genes were performed for further exploring of the effect mediated by MAGL knocked down. RESULTS: It was noted that the expression of MAGL was highly elevated in tumor tissues, however, it was found only significantly correlated with the BMI index. Tumor cells' growth and invasion was significantly inhibited in vitro and in vivo induced by pharmacological and siRNA mediated MAGL knocked down. Cell proliferation was reduced and apoptosis was increased. And two target genes Cyclin D1 and Bcl-2 seemed to be repressed by MAGL knocked down. CONCLUSIONS: This study demonstrated colorectal cancer cells growth can be inhibited via knockdown of MAGL, which manipulate tumor cells proliferation and apoptosis by downregulation of Cyclin D1 and Bcl-2. It provides a novel therapeutic target in treatment of colorectal cancer and a further support for the correlation of obesity and colorectal cancer.

[Study on PLB induction and proliferation of Dendrobium officinale].

OBJECTIVE: To study on the optimal medium ingredients for PLB induction and proliferation of Dendrobium officinale. METHODS: Seed embryos of Dendrobium officinale were cultivated in MS medium as the basic medium, along with different plant hormones like 6-BA, NAA,2,4-D and KT or their combinations added with organic additives like PE, BE, AE and CM. RESULTS: BA and NAA combination was not conductive to germination and the germination ratio was even lower than that of MS medium; 10% PE and CM was beneficial to PLB induction; 2,4-D was not conductive to growth and proliferation; A certain concentration of BA, KT and NAA was beneficial to PLB proliferation; KT at 1.0 mg/L recorded the highest 40 d PLB proliferation times at 9.0; PE, CM and AE could promote the PLB proliferation at different levels, among which 10% CM was the most effective. CONCLUSION: The optimized medium ingredients suitable for PLB induction are MS +10% CM +1.0g/L AC; The optimized medium ingredients suitable for PLB proliferation are MS + 1.0 mg/L KT + 0.2 mg/L NAA + 10% CM.