[Expression changes of RNA m6A regulators in mouse cerebellum affected by hypobaric hypoxia stimulation].

Objective: To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment. Methods: Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella. Results: Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced (P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella (P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice (P<0.05). Conclusions: Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

[Effects of RNA M6A demethylase ALKBH5 gene deficiency on morphology and function of cerebellum in aged mice].

Objective: To investigate the effects of RNA m6A demethylase ALKBH5 gene deficiency on cerebellar morphology and function in the aged mice, and to explore the role of ALKBH5 in cerebellar degeneration. Methods: Western blot was performed to detect the protein level of ALKBH5 in the cerebellum of wild-type mice of various ages. The expression of NeuN, Calbindin-D28K, MAP2, GFAP and other proteins in the cerebella of middle-aged (12-month-old) and aged (18-month-old) wild-type mice and ALKBH5-/- mice was examined using immunohistochemistry. The balance beam test and gait analysis were performed to test the balance ability and motor coordination of the mice. Results: With aging of the mice, the expression of ALKBH5 in the cerebellum increased gradually in an age-dependent manner. In the aged mice, but not middle-aged mice, the body weight, whole brain weight and cerebellum weight of ALKBH5-/- mice decreased by 15%, 10% and 21%, respectively (P<0.05). The expression of ALKBH5 in the Purkinje cells was much higher than that in other types of neural cells. Correspondingly, ALKBH5-deficiency caused 40% reduction in the number of Purkinje cells, as well as the length and density of neuronal dendrites in the aged mice (P<0.01). In addition, the time for the aged ALKBH5-/- mice to pass the balance beam was 70% longer than that of the wild type mice of the same age, with unstable gaits (P<0.01). Conclusions: Gene deficiency of RNA m6A demethylase ALKBH5 causes cerebellar atrophy, Purkinje neuron loss and damage in the aged mice. These changes eventually affect mice's motor coordination and balance ability. These results suggest that imbalanced RNA m6A methylation may lead to neurodegenerative lesions in the cerebellum of mice.

[Four cases of acute ethylene glycol poisoning].

Ethylene glycol is the main component of antifreeze, due to its special sweetness, it is easy to cause misuse. In this paper, the clinical data of 4 cases of acute ethylene glycol poisoning admitted to Beijing Chao-Yang Hospital from August 2016 to August 2021 were retrospectively analyzed to explore the clinical characteristics of acute ethylene glycol poisoning cases. Early and accurate assessment of the disease and early hemodialysis treatment is the key to cure acute ethylene glycol poisoning.

[Expression of heterogeneous nuclear ribonucleo-protein A2B1 in mouse cerebellar development and human medulloblastoma].

Objective: To investigate the expression and potential role of heterogeneous nuclear ribonucleo-protein A2B1 (HNRNPA2B1) in mouse cerebellar development and the significance of HNRNPA2B1 in human medulloblastoma. Methods: The data of HNRNPA2B1 RNA expression in mouse and human cerebella were obtained from databases. Western blot and immunohistochemical staining were performed to detect the protein level of HNRNPA2B1 in mouse cerebella at different ages. The expression level of HNRNPA2B1 in control human cerebellum and medulloblastoma was detected by immunohistochemical staining. m6A-IP-qPCR method was applied to confirm whether HNRNPA2B1 RNA in Daoy cells was modified with m6A.Western blot was used to detect the effect of MG132 treatment on the HNRNPA2B1 protein level in Daoy cells. Results: The level of HNRNPA2B1 protein in postnatal mouse cerebella was higher than that in adult mouse cerebella, with weak HNRNPA2B1 staining in external granular cells while strong staining in mature Purkinje cells and molecular layer. Compared with control normal human cerebella, the RNA expression level of HNRNPA2B1 increased in medulloblastoma, while immunohistochemical staining showed that the mean intensity of HNRNPA2B1 decreased in medulloblastoma. HNRNPA2B1 RNA in medulloblastoma and Daoy cells was modified by m6A. The HNRNPA2B1 protein level in Daoy cells increased upon MG132 treatment. Conclusions: HNRNPA2B1 is dynamically expressed during mouse cerebellar development. Compared with normal human cerebella, HNRNPA2B1 is significantly up-regulated at transcriptional level but obviously down-regulated at translational level in medulloblastoma. These results indicate that HNRNPA2B1 may be involved in cerebellar development process and medulloblastoma tumorigenesis. The m6A methylation in HNRNPA2B1 transcript and protein ubiquitin-proteasome pathway may account for the down-regulation of HNRNPA2B1 at protein level.

PCL/EUG scaffolds with tunable stiffness can regulate macrophage secretion behavior.

Osteoarthritis (OA) is a prevalent joint disorder worldwide. Recent studies suggested that macrophages play an important role in the progression of OA. However, the detailed pathology related to macrophages is still ambiguous, especially where related to mechanotransduction. In this study, polycaprolactone (PCL) and Eucommia Ulmoides Gum (EUG) composite scaffolds were first fabricated by electrospinning. The stiffness of as-fabricated scaffolds was altered by adjusting the PCL-to-EUG ratio. The mechanical properties, structural characteristics and chemical composition of the scaffolds were investigated using various materials characterization techniques. The results show that stiffness of the scaffolds was in the same range as that of cartilage tissues with OA. Confocal microscopy and reverse transcription-polymerase chain reaction (RT-PCR) were performed to investigate the macrophages cultured on the scaffolds. Significant morphological changes of cells were observed on PCL/EUG scaffolds with different stiffness. The expression of inflammatory and fibrosis-related cytokines increases as scaffold stiffness decreases, similar to the trend observed in OA progression.

[Expression of protein phosphatase 2AC in the brain of mice and Alzheimer's patients].

Objective: To investigate the biological functions of protein phosphatase 2AC(PP2AC) in the brain, and to detect its spatio-temporal expression and its involvement in neurological disorders in the brains of mice and Alzheimer's patients. Methods: Western blot was used to evaluate the expression level of PP2AC in different organs. Immunohistochemical staining was performed to detect the in situ expression levels of PP2AC in the brains of mice and patients, and the pathological changes were confirmed in the brains of patients with Alzheimer's disease. Results: Among all the tested organs in adult mouse, the expression of PP2AC protein was the highest in the brain. From embryonic day 18.5 to postnatal 2-year-old mice, PP2AC exhibited spatio-temporal specific expression in the brains. Furthermore, an age-dependent increased expression in the cerebral cortex at both protein and RNA levels was observed. Compared to control group, PP2AC protein expression was lower in the frontal cortex of Alzheimer's patients. Conclusions: The spatio-temporal specific expression profiles of PP2AC in mouse brain implicate its biological significance. Its diminished expression in the frontal cortex of Alzheimer's disease patients implies that PP2AC plays a potential role in the pathogenesis of Alzheimer's disease.

[The clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China: A Meta analysis].

Objective:To systematically review the clinical efficacy of coblation tonsillectomy and conventional tonsillectomy in China. Method:Randomized controlled trials (RCT) of coblation tonsillectomy and conventional tonsillectomy were searched and retrieved through online databases (PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Library, CBM, CNKI, VIP, WanFang, SUMsearch and Google search engine) and related literatures were reviewed up to 30 April, 2017. Two investigators independently screened literatures,extracted data and evaluated the risk of bias assessment tools for RCT using the Version 5.1.0 of Cochrane Handbook for Systematic Reviews of Interventions. Then, Meta analysis was performed using RevMan 5.3 software provided by the Cochrane Collaboration. Result:A total of 32 RCTs involving 3 197 tonsillectomy patients were included. The results of meta-analysis showed that: the operation time (MD=-17.03, 95%CI -19.78 to -14.28, P＜0.00 001), intraoperative blood loss (MD=-27.00, 95%CI -30.44 to -23.56, P＜0.00 001), postoperative pain in 24 hours (MD=-2.00, 95%CI -2.65 to -1.35, P＜0.00 001), time needed to regain the normal diet (MD=-2.01, 95%CI -2.60 to -1.42, P＜0.00001), formation time of white membrane (MD=-2.44, 95%CI -3.96 to -0.93, P=0.002) of patients in the coblation tonsillectomy group were all significantly lower than the conventional tonsillectomy group; while the exfoliation time of white membrane (MD=2.02, 95%CI 0.65 to 3.39, P=0.004) in the coblation tonsillectomy group was significantly longer than the conventional tonsillectomy group. Conclusion:Current evidence shows that, compared with the conventional tonsillectomy group, the coblation tonsillectomy group can significantly shorten the operation time, decrease intraoperative blood loss, alleviate postoperative pain degree during 24 hours, regain the normal diet early and form white membrane early, but delaye the exfoliation time of white membrane. Due to the limited kinds of literature and quality of the included studies, the above conclusions still need to be verified by carrying out more large scale samples and high quality randomized controlled trials (RCTs) studies.

WITHDRAWN: PCL/EUG scaffolds with tunable stiffness can regulate macrophage secretion behavior.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.pbiomolbio.2018.05.008. The duplicate article has therefore been withdrawn.

[Correlation between Mic60 haploid insufficiency and cardiac aging in mouse].

Objective: To investigate the role of Mic60 in cardiac aging. Methods: Wild-type and Mic60(+ /-) male mice at age of 4-6 months (young group, n=6) and 18-20 months (aged group, n=9) were used. H&E and Masson staining of frozen and paraffin sections were subjected to morphologic evaluation of the cardiac tissue samples. SA-ß-Gal staining was utilized to detect the activity of senescence-associated ß-galactosidase. Western blot was performed to detect the expression of Mic60 and p21 in cardiac tissues. Results: Expression of Mic60 in mouse cardiac tissue increased in an age-dependent manner. Haploid insufficiency of Mic60 resulted in an increased left ventricular wall thickness [(1.32±0.09) mm vs.(1.12±0.09) mm, P<0.05], cardiomyocyte hypertrophy[(474.9±27.6) µm(2) vs.(358.8±48.7) µm(2), P<0.05] and interstitial fibrosis [ (38.24±7.58) ×10(3)µm(2) vs.(25.81±4.12)×10(3)µm(2,) P<0.05], increased activity of SA-ß-Gal (2.26±0.24 vs.0.25±0.05, P<0.01) and higher expression of p21 (P<0.01) in aged mouse cardiac tissue, but not in young mice. Conclusion: Haploid insufficiency of Mic60 leads to cardiac hypertrophy, interstitial fibrosis, increased activity of SA-ß-Gal and higher expression of p21 in aged cardiac tissue in mice, suggesting that Mic60 may prevent cardiac aging.

Paternal treadmill exercise enhances spatial learning and memory related to hippocampus among male offspring.

Both epidemiologic and laboratory studies suggest that parents can shape their offspring's development. Recently, it has been shown that maternal exercise during pregnancy benefits the progeny's brain function. However, little is known regarding the influence of paternal exercise on their offspring's phenotype. In this study we attempt to determine the effects of 6 weeks paternal treadmill exercise on spatial learning and memory and the expression of brain-derived neurotrophic factor (BDNF) and reelin in their male offspring. Sibling males were divided into two groups: the control (C) and the exercise group (E). The mice in the E group were exercised on a motor-driven rodent treadmill for 5 days per week for 6 weeks. After 6 weeks of exercise, the male mouse was mated with its sibling female. After weaning, male pups underwent behavioral assessment (Open field and Morris water maze tests). Immunohistochemistry staining, real time-PCR and western blot were performed to determine hippocampal BDNF and reelin expression of the male pups after behavior tasks. Our results showed that paternal treadmill exercise improved the spatial learning and memory capability of male pups, which was accompanied by significantly increased expression of BDNF and reelin, as compared to those of C group. Our results provide novel evidence that paternal treadmill exercise can enhance the brain functions of their F1 male offspring.

Association between XPD Lys751Gln polymorphism and risk of head and neck cancer: a meta-analysis.

Several studies have investigated the association between Lys751Gln polymorphism in the xeroderma pigmentosum group D (XPD) gene and risk of head and neck cancer; however, the published results are conflicting. We conducted a meta-analysis that comprised 15 published case-control studies examining the association of head and neck cancer risk with XPD Lys751Gln polymorphism in different populations, based on the data identified in Medline up to November 2010. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association. Overall, significantly elevated head and neck cancer risk was associated with XPD Lys751Gln polymorphism when all studies were pooled into the meta-analysis [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.12, 95%CI = 1.03-1.22, P < 0.01, heterogeneity P = 0.11]. In the subgroup analysis by ethnicity, borderline significantly increased risk was found for Europeans [(Gln/Gln + Lys/Gln) vs Lys/Lys: OR = 1.11, 95%CI = 1.00-1.23, P < 0.05]. In conclusion, our meta-analysis demonstrated that XPD Lys751Gln polymorphism could be a prediction marker for risk of head and neck cancer.