Changes in Histamine Receptors (H1, H2, and H3) Expression in Rat Medial Vestibular Nucleus and Flocculus after Unilateral Labyrinthectomy: Histamine Receptors in Vestibular Compensation

Vestibular compensation is the process of behavioral recovery following peripheral vestibular lesion. In clinics, the histaminergic medicine is the most widely prescribed for the treatment of vertigo and motion sickness, however, the molecular mechanisms by which histamine modulates vestibular function remain unclear. During recovery from the lesion, the modulation of histamine receptors in the medial vestibular nucleus (MVN) and the flocculus may play an important role. Here with the means of quantitative real-time PCR, western blotting and immunohistochemistry, we studied the expression of histamine receptors (H1, H2, and H3) in the bilateral MVN and the flocculus of rats on the 1st, 3rd, and 7th day following unilateral labyrinthectomy (UL). Our results have shown that on the ipsi-lesional flocculus the H1, H2 and H3 receptors mRNA and the protein increased significantly on the 1st and 3rd day, with compare of sham controls and as well the contralateral side of UL. However, on the 7th day after UL, this expression returned to basal levels. Furthermore, elevated mRNA and protein levels of H1, H2 and H3 receptors were observed in the ipsi-lesional MVN on the 1st day after UL compared with sham controls and as well the contralateral side of UL. However, this asymmetric expression was absent by the 3rd post-UL. Our findings suggest that the upregulation of histamine receptors in the MVN and the flocculus may contribute to rebalancing the spontaneous discharge in bilateral MVN neurons during vestibular compensation.     

Decreased Leukocyte Telomere Length (LTL) Is Associated with Stroke but Unlikely to Be Causative

Aims

Interindividual variability in telomere length is highly heritable. Leukocyte telomere length (LTL) shortening has been shown to be associated with the process of atherosclerosis. But whether the inheritance of LTL is related to stroke is still unclear. The aim of this study was to test if telomere shortening was associated with stroke and whether this association was mainly due to inheritance or acquired cardiovascular risk factors.

Methods

Our study was focused on stroke in patients and their siblings. 450 subjects were recruited into this study: 150 patients with ischemic stroke as case group, 150 siblings of patients free of stroke (sibling group) and 150 healthy people as normal control. LTL was measured by real-time Polymerase Chain Reactions. The association between LTL and the cardiovascular risk factors was also determined.

Results

A significant decrease of LTL was found in case group when comparing with sibling (0.92±0.77 vs 1.68±1.24, p<0.001) and normal groups (0.92±0.77 vs 1.95±1.07, p<0.001), but no significant difference was found between sibling group and healthy control (p = 0.330). Shorter telomere length was independently associated with hypertension (p = 0.029, OR = 2.189, 95%CI:1.084–4.421), recent social pressure (p = 0.001, OR = 3.121, 95%CI:1.597–6.101), age (p = 0.004, OR = 1.055, 95%CI:1.017–1.093), HDL (p = 0.022, OR = 0.227, 95%CI:0.064–0.810) and diabetes (p = 0.018, OR = 3.174, 95%CI:1.221–8.252). Additionally, shortened length of telomere (p = 0.017, OR = 3.996, 95%CI:1.283–12.774) was an independent risk biomarker for stroke among case and sibling groups.

Conclusion

The present study has demonstrated that decreased LTL might be associated with ischemic stroke but unlikely to be causative.     

Altered Pattern of Spontaneous Brain Activity in the Patients with End-Stage Renal Disease: A Resting-State Functional MRI Study with Regional Homogeneity Analysis

Purpose

To investigate the pattern of spontaneous neural activity in patients with end-stage renal disease (ESRD) with and without neurocognitive dysfunction using resting-state functional magnetic resonance imaging (rs-fMRI) with a regional homogeneity (ReHo) algorithm.

Materials and Methods

rs-fMRI data were acquired in 36 ESRD patients (minimal nephro-encephalopathy [MNE], n = 19, 13 male, 37±12.07 years; non-nephro-encephalopathy [non-NE], n = 17, 11 male, 38±12.13 years) and 20 healthy controls (13 male, 7 female, 36±10.27 years). Neuropsychological (number connection test type A [NCT-A], digit symbol test [DST]) and laboratory tests were performed in all patients. The Kendall''s coefficient of concordance (KCC) was used to measure the regional homogeneity for each subject. The regional homogeneity maps were compared using ANOVA tests among MNE, non-NE, and healthy control groups and post hoc t -tests between each pair in a voxel-wise way. A multiple regression analysis was performed to evaluate the relationships between ReHo index and NCT-A, DST scores, serum creatinine and urea levels, disease and dialysis duration.

Results

Compared with healthy controls, both MNE and non-NE patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-NE, MNE patients showed decreased ReHo in the right inferior parietal lobe (IPL), medial frontal cortex (MFC) and left precuneus (PCu). The NCT-A scores and serum urea levels of ESRD patients negatively correlated with ReHo values in the frontal and parietal lobes, while DST scores positively correlated with ReHo values in the bilateral PCC/precuneus, MFC and inferior parietal lobe (IPL) (all P<0.05, AlphaSim corrected). No significant correlations were found between any regional ReHo values and disease duration, dialysis duration and serum creatinine values in ESRD patients (all P>0.05, AlphaSim corrected).

Conclusion

Diffused decreased ReHo values were found in both MNE and non-NE patients. The progressively decreased ReHo in the default mode network (DMN), frontal and parietal lobes might be trait-related in MNE. The ReHo analysis may be potentially valuable for elucidating neurocognitive abnormalities of ESRD patients and detecting the development from non-NE to MNE.     

从国家自然科学基金项目资助看植物科学态势

通过对2010-2015年度国家自然科学基金委员会生命科学部植物学学科资助的各类项目进行统计分析,总结了植物学学科资助的整体概况,详细分析了各类科学基金项目的资助特点、在不同分支学科和领域中的分布以及获资助排名前列的依托单位,并展望了我国未来植物学学科的发展趋势。     

Autophagy promotes ferroptosis by degradation of ferritin

Macroautophagy/autophagy is an evolutionarily conserved degradation pathway that maintains homeostasis. Ferroptosis, a novel form of regulated cell death, is characterized by a production of reactive oxygen species from accumulated iron and lipid peroxidation. However, the relationship between autophagy and ferroptosis at the genetic level remains unclear. Here, we demonstrated that autophagy contributes to ferroptosis by degradation of ferritin in fibroblasts and cancer cells. Knockout or knockdown of Atg5 (autophagy-related 5) and Atg7 limited erastin-induced ferroptosis with decreased intracellular ferrous iron levels, and lipid peroxidation. Remarkably, NCOA4 (nuclear receptor coactivator 4) was a selective cargo receptor for the selective autophagic turnover of ferritin (namely ferritinophagy) in ferroptosis. Consistently, genetic inhibition of NCOA4 inhibited ferritin degradation and suppressed ferroptosis. In contrast, overexpression of NCOA4 increased ferritin degradation and promoted ferroptosis. These findings provide novel insight into the interplay between autophagy and regulated cell death.     

FUNDC1 is a novel mitochondrial-associated-membrane (MAM) protein required for hypoxia-induced mitochondrial fission and mitophagy

Mitochondria need to be fragmented prior to engulfment by phagophores, the precursors to autophagosomes. However, how these 2 processes are finely regulated and integrated is poorly understood. We have shown that the outer mitochondrial membrane protein FUNDC1 is a novel mitochondrial-associated membrane (MAM) protein, enriched at the MAM by interacting with the ER resident protein CANX (calnexin) under hypoxia. As mitophagy proceeds, it dissociates from CANX and preferably recruits DNM1L/DRP1 to drive mitochondrial fission in response to hypoxic stress. In addition, knocking down of FUNDC1, DNM1L or CANX in hypoxic cells increases the number of elongated mitochondria and also reduces the colocalization of autophagosome and mitochondria, thus preventing mitophagy. These findings identify FUNDC1 as a molecular hub integrating mitochondrial fission and mitophagy at the MAM in response to hypoxia.     

Probiotic properties of Enterococcus strains isolated from traditional naturally fermented cream in China

The purpose of this study was to evaluate the probiotic properties of Enterococcus strains isolated from traditional naturally fermented cream in China. Four Enterococcus isolates showed high cholesterol removal ability in media were identified as Enterococcus durans (KLDS 6.0930 and 6.0933) and Enterococcus faecalis (KLDS 6.0934 and 6.0935) by 16S rRNA and pheS gene sequences, respectively, and selected for further evaluation. In order to assess the probiotic potential and safety of these strains, the property of four Enterococcus strains were examined, including acid and bile tolerance, adherence to Caco‐2 cells and antibiotics susceptibility. All four strains showed potential cholesterol assimilation, de‐conjugation of bile salts and/or cholesterol degradation to remove cholesterol in vitro. In addition, the potential effect of E. durans KLDS 6.0930 on serum cholesterol levels was evaluated in Sprague‐Dawley rats. After 4 weeks administration, compared with rats fed a high‐cholesterol diet without lactic acid bacteria supplementation, there was a significant (P < 0.05) decrease in the total cholesterol and low‐density lipoprotein cholesterol levels in the serum of rats treated with KLDS 6.0930. Furthermore, total bile acid level in the feces was significantly (P < 0.05) increased after KLDS 6.0930 administration. These observations suggested that the strain E. durans KLDS 6.0930 may be used in the future as a good candidate for lowering human serum cholesterol levels.     

Identification of a Highly Conserved Epitope on Avian Influenza Virus Non-Structural Protein 1 Using a Peptide Microarray

Avian influenza virus (AIV) non-structural protein 1 (NS1) is a multifunctional protein. It is present at high levels in infected cells and can be used for AIV detection and diagnosis. In this study, we generated monoclonal antibody (MAb) D7 against AIV NS1 protein by immunization of BALB/c mice with purified recombinant NS1 protein expressed in Escherichia coli. Isotype determination revealed that the MAb was IgG₁/κ-type subclass. To identify the epitope of the MAb D7, the NS1 protein was truncated into a total of 225 15-mer peptides with 14 amino acid overlaps, which were spotted for a peptide microarray. The results revealed that the MAb D7 recognized the consensus DAPF motif. Furthermore, the AIV NS1 protein with the DAPF motif deletion was transiently expressed in 293T cells and failed to react with MAb D7. Subsequently, the DAPF motif was synthesized with an elongated GSGS linker at both the C- and N-termini. The MAb D7 reacted with the synthesized peptide both in enzyme-linked immunosorbent assay (ELISA) and dot-blot assays. From these results, we concluded that DAPF motif is the epitope of MAb D7. To our knowledge, this is the first report of a 4-mer epitope on the NS1 protein of AIV that can be recognized by MAb using a peptide microarray, which is able to simplify epitope identification, and that could serve as the basis for immune responses against avian influenza.