Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity.

BACKGROUND: Considerable evidence has shown that neuroinflammation and oxidative stress play an important role in the pathophysiology of postoperative cognitive dysfunction (POCD) and other progressive neurodegenerative disorders. Increasing evidence suggests that acetaminophen (APAP) has unappreciated antioxidant and anti-inflammatory properties. However, the impact of APAP on the cognitive sequelae of inflammatory and oxidative stress is unknown. The objective of this study is to explore whether APAP could have neuroprotective effects on lipopolysaccharide (LPS)-induced cognitive impairment in mice. METHODS: A mouse model of LPS-induced cognitive impairment was established to evaluate the neuroprotective effects of APAP against LPS-induced cognitive impairment. Adult C57BL/6 mice were treated with APAP half an hour prior to intracerebroventricular microinjection of LPS and every day thereafter, until the end of the study period. The Morris water maze was used to assess cognitive function from postinjection days 1 to 3. Animal behavioural tests as well as pathological and biochemical assays were performed to evaluate LPS-induced hippocampal damage and the neuroprotective effect of APAP. RESULTS: Mice treated with LPS exhibited impaired performance in the Morris water maze without changing spontaneous locomotor activity, which was ameliorated by treatment with APAP. APAP suppressed the accumulation of pro-inflammatory cytokines and microglial activation induced by LPS in the hippocampus. In addition, APAP increased SOD activity, reduced MDA levels, modulated glycogen synthase kinase 3ß (GSK3ß) activity and elevated brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Moreover, APAP significantly decreased the Bax/Bcl-2 ratio and neuron apoptosis in the hippocampus of LPS-treated mice. CONCLUSIONS: Our results suggest that APAP may possess a neuroprotective effect against LPS-induced cognitive impairment and inflammatory and oxidative stress via mechanisms involving its antioxidant and anti-inflammatory properties, as well as its ability to inhibit the mitochondrial permeability transition (MPT) pore and the subsequent apoptotic pathway.

Novel Electrochemical Raman Spectroscopy Enabled by Water Immersion Objective.

Electrochemical Raman spectroscopy is a powerful molecular level diagnostic technique for in situ investigation of adsorption and reactions on various material surfaces. However, there is still a big room to improve the optical path to meet the increasing request of higher detection sensitivity and spatial resolution. Herein, we proposed a novel electrochemical Raman setup based on a water immersion objective. It dramatically reduces mismatch of the refractive index in the light path. Consequently, significant improvement in detection sensitivity and spatial resolution has been achieved from both Zemax simulation and the experimental results. Furthermore, the thickness of electrolyte layer could be expanded to 2 mm without any influence on the signal collection. Such a thick electrolyte layer allows a much normal electrochemical response during the spectroelectrochemical investigations of the methanol oxidation.

Androgenesis, gynogenesis, and parthenogenesis haploids in cucurbit species.

Haploids and doubled haploids are critical components of plant breeding. This review is focused on studies on haploids and double haploids inducted in cucurbits through in vitro pollination with irradiated pollen, unfertilized ovule/ovary culture, and anther/microspore culture during the last 30 years, as well as comprehensive analysis of the main factors of each process and comparison between chromosome doubling and ploidy identification methods, with special focus on the application of double haploids in plant breeding and genetics. This review identifies existing problems affecting the efficiency of androgenesis, gynogenesis, and parthenogenesis in cucurbit species. Donor plant genotypes and surrounding environments, developmental stages of explants, culture media, stress factors, and chromosome doubling and ploidy identification are compared at length and discussed as methodologies and protocols for androgenesis, gynogenesis, and parthenogenesis in haploid and double haploid production technologies.

Vitamin C alleviates LPS-induced cognitive impairment in mice by suppressing neuroinflammation and oxidative stress.

Neuroinflammation is believed to be one of the primary causes of cognitive impairment. Previous studies showed that the antioxidant vitamin C (Vit C) performs many beneficial functions such as immunostimulant and anti-inflammatory actions, but its role in inflammatory cognitive impairment is unclear. In the current study, we investigated the effect and possible mechanism of action of Vit C in lipopolysaccharide (LPS)-induced cognitive impairment. Intracerebroventricular LPS-induced memory impairment was used as the model for neuroinflammatory cognitive dysfunction. Vit C was administered by intracerebroventricular microinjection 30 min prior to LPS exposure. It was found that Vit C significantly protected animals from LPS-induced memory impairment as evidenced by improved performance in the Morris water maze and novel object recognition tests without changes in spontaneous locomotor activity. Vit C pretreatment inhibited the activation of microglia and the production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). Furthermore, Vit C pretreatment markedly decreased the malondialdehyde (MDA) level, increased superoxide dismutase (SOD) activity, and modulated the Bax/Bcl-2 ratio and p-p38 MAPK activation in the hippocampus of LPS-treated mice. Together, these results suggest that vitamin C pretreatment could protect mice from LPS-induced cognitive impairment, possibly through the modulation of oxidative stress and inflammatory responses.

[Choline improves lipopolysaccharide-induced central nervous system inflammatory response and cognitive dysfunction in mice].

OBJECTIVE: To assess the effect of choline in ameliorating lipopolysaccharide (LPS)-induced central nervous system inflammation and cognitive deficits in mice and explore the underlying mechanism. METHODS: Seventy-two mice were randomized into saline control group, LPS group, choline intervention group and choline control group. In the latter two groups, the mice received pretreatment with intraperitoneal injections of choline (40 mg/kg, 3 times daily for 3 consecutive days) prior to microinjection of LPS into the lateral cerebral ventricle to induce central nervous system inflammation; in saline and LPS groups, the mice were pretreated with saline in the same manner before intraventicular injection of artificial cerebrospinal fluid. Choline treatment was administered in the mice till the end of the experiment. The locomotor activity and spatial learning and memory capacity of the mice were examined. The expressions of Iba1 protein and proinflammatory cytokines (TNF-α and IL-ß) I the hippocampal dentate gyrus, and the expressions of α 7nAchR, p38 MAPK and phosphorylated p38 MAPK in the hippocampus of the mice were detected. RESULTS: Water maze test showed that compared with the saline control group, the mice in LPS group exhibited significantly reduced platform crossings (P<0.05), which was significantly increased by choline pretreatment (P<0.05). The mice pretreated with LPS expressed obviously increased levels of IBA-1 protein, TNF-α, and IL-1ß in the hippocampus (P<0.01), and choline pretreatment significantly lowered the expressions of IBA-1 protein and IL-1ß (P<0.05). The phosphorylation level of p38 MAPK increased significantly after LPS pretreatment (P<0.05), and was reduced by choline pretreatment (P<0.05); α 7nAchR expression increased significantly in choline intervention group as compared with that in the other 3 groups (P<0.05). CONCLUSION: Choline can probably antagonize LPS-induced hippocampal p38 MAPK phosphorylation in mice via the α 7nAchR signaling pathway to protective against LPS-induced neuroinflammation and cognitive impairment in mice.

Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice.

Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery is highly associated with POCD. Phosphodiesterase-4 (PDE4) is an enzyme that specifically hydrolyses cyclic adenosine monophosphate (cAMP), which plays an important role during neuroinflammation and the process of learning and memory. However, the role of PDE4 in the development of POCD remains unclear. Male 14-month-old C57BL/6 mice received carotid artery exposure to mimic POCD. First, we evaluated cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were investigated. Then, we used rolipram, a PDE4 inhibitor, to block the effects of PDE4. The cognitive performance of the mice and the expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, elevation of pro-inflammatory cytokines, and reduction in the expression of p-CREB, PSD95 and cAMP levels after surgery. The expression of PDE4B and PDE4D in the hippocampus decreased following blocking of PDE4 by rolipram. Meanwhile, rolipram attenuated the cognitive impairment and the elevation of pro-inflammatory cytokines induced by surgery. Moreover, rolipram reversed the reduction of p-CREB and PSD95. These results indicate that PDE4 subtype overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.

[Cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma].

BACKGROUND & OBJECTIVE: Abnormal expression of genes is related to development and progression of hepatocellular carcinoma (HCC); however, the detailed mechanism is unclear yet because the known genetic information is not sufficient at present. This study was to explore cloning and identification of fibrinogen gamma polypeptide (FGG) gene differentially expressed in human hepatocellular carcinoma. METHODS: The suppression subtractive hybridization was used to obtain subtracted cDNA products of HCC, then the products were cloned by T/A method. The differential expression of gene in HCC was identified by DNA sequencing analysis, Northern blot analysis, rapid amplification of cDNA end (RACE), and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Firstly, a cDNA fragment of 787 nucleotides was screened from the subtracted cDNA clones, and it was further discovered that the expression of the cDNA fragment was higher significantly in human hepatocellular carcinoma cell strains of SMMC-7721 and HepG2 than in normal hepatocytes by Northern blot analysis. The RACE was carried out and the gene of 1 597 bp containing polyA in 3'end was obtained, which has an entire open reading frame encoding 437 amino acids. Homology analysis showed that this was a gene encoding human FGG. RT-PCR analysis of FGG showed that the amplification of cancerous tissues, especially in metastasis of HCC, was raised as compared to that of adjacent non-cancerous tissues. CONCLUSION: Overexpression of FGG was discovered in SMMC-7721 and HepG2 cells. The up-regulation of FGG may be associated with the pathogenesis of HCC.

[Association of p53, PCNA expression and trace element content in esophageal mucosa].

BACKGROUND & OBJECTIVE: There were abnormal changes of trace element in esophageal cancer patient's hair and serum in the high risk area. But it was still unknown that the relationship between p53 and proliferating cell nuclear antigen(PCNA) expression and the trace element content in varied esophageal mucosa. This study was designed to probe the relationship of trace element content and p53 mutation, PCNA expression in esophgeal mucosa. METHODS: Esophageal biopsy specimen of 151 cases were divided into four groups (normal, esophagitis, dysplasia, and early carcinoma). The quantitative determination of trace element was performed was performed by using X-ray energy spectrometry and the detection of PCNA expression and p53 mutation was performed by using S-P immunohistochemistry method. RESULTS: The contents of Zn, Se, Mo, were 1.74 +/- 0.32, 1.53 +/- 0.64, 0.58 +/- 0.21, 0.20 +/- 0.08; 0.15 +/- 0.06, 0.10 +/- 0.03, 0.04 +/- 0.02, 0; 4.73 +/- 1.31, 3.45 +/- 1.19, 3.51 +/- 1.32, 2.51 +/- 1.04; respectively in four groups. There was a significant difference in varied histological typies(P < 0.05). The contents of Cu/Zn, Ni were 0.57 +/- 0.17, 0.89 +/- 0.18, 2.45 +/- 0.48, 2.92 +/- 1.08; 0.45 +/- 0.05, 1.27 +/- 0.11, 2.46 +/- 0.24, 2.58 +/- 0.33; respectively, which increased gradually in pace with upgrade of esophageal lesions, with significant difference (P < 0.05). The postive rates of p53 and PCNA were 0, 46.15%, 100%; 31.19%, 84.62%, 100% respectively in normal esophageal epithelium, dysplasia, and early carcinoma, with significant difference (P < 0.01), and had significant correlation to trace element. CONCLUSION: The content variation of Zn, Se, Mo, Cu, Ni could be possessed of certain effect on p53 mutation and PCNA overexpression of esophageal epithelium in the high risk area.