Single nucleotide polymorphisms in the GFR-related gene and the SNP-SNP interactions on the risk of diabetic kidney disease in Chinese Han population.

PURPOSE: Genetic susceptibility is an important pathogenic mechanism in diabetic kidney disease (DKD). However, the specific gene variant associated with DKD susceptibility remains unclear. Glomerular filtration rate (GFR), an important indicator for the process of DKD, has a heritable component. This study aimed to explore whether these GFR-related single nucleotide polymorphisms (SNPs) were associated with DKD. METHODS: GFR-related SNPs were collected from the Phenotype-Genotype Integrator (PheGenI) database. SNPs for population cohort analysis were selected following the criteria of complete records of eQTL and MAF > 5% in the Chinese Han population. Totally 498 subjects participated, including166 patients with DKD, 166 patients with T2DM, and 166 controls. The genotypes of SNPs were determined using a Sequenom MassARRAY system. Plink software was employed to analyze the SNP-SNP interactions. RESULTS: By screening the GFR-related SNPs recorded in the PheGenI database, four SNPs (rs1260326, rs17319721, rs35716097, and rs6420094) were finally selected to investigate the association with DKD. It was shown that one of the four SNPs was related to DKD. The G allele of SLC34A1 rs6420094 was associated with a decreased risk of DKD in DKD and T2DM groups (OR 0.716; P = 0.049). Genetic model analysis revealed that rs6420094 was a protective factor for DKD in T2DM in a dominant model and an additive model (P = 0.03; P = 0.032, respectively). Although rs17319721 was not associated with the risk of DKD, the SNP-SNP interactions between rs17319721 and rs6420094 predicted a significantly decreased risk of DKD (OR 0.464; P = 0.047). CONCLUSION: SLC34A1 rs6420094 was associated with a decreased DKD risk in the Chinese Han population. SNP-SNP interaction between rs17319721 and rs6420094 was associated with a lower risk of DKD.

Potential of Mitochondrial Ribosomal Genes as Cancer Biomarkers Demonstrated by Bioinformatics Results.

Next-generation sequencing and bioinformatics analyses have clearly revealed the roles of mitochondrial ribosomal genes in cancer development. Mitochondrial ribosomes are composed of three RNA components encoded by mitochondrial DNA and 82 specific protein components encoded by nuclear DNA. They synthesize mitochondrial inner membrane oxidative phosphorylation (OXPHOS)-related proteins and participate in various biological activities via the regulation of energy metabolism and apoptosis. Mitochondrial ribosomal genes are strongly associated with clinical features such as prognosis and foci metastasis in patients with cancer. Accordingly, mitochondrial ribosomes have become an important focus of cancer research. We review recent advances in bioinformatics research that have explored the link between mitochondrial ribosomes and cancer, with a focus on the potential of mitochondrial ribosomal genes as biomarkers in cancer.

Functional integration of newly generated neurons into striatum after cerebral ischemia in the adult rat brain.

BACKGROUND AND PURPOSE: Ischemic injury can induce neurogenesis in the striatum. Those newborn neurons can express glutamic acid decarboxylase and choline acetyltransferase, markers of GABAergic and cholinergic neurons, respectively. The present study investigated whether these GABAergic and cholinergic new neurons could differentiate into functional cells. METHODS: Retrovirus containing the EGFP gene was used to label dividing cells in striatal slices prepared from adult rat brains after middle cerebral artery occlusion. EGFP-targeted immunostaining and immunoelectron microscopy were performed to detect whether newborn neurons could anatomically form neuronal polarity and synapses with pre-existent neurons. Patch clamp recording on acute striatal slices of brains at 6 to 8 weeks after middle cerebral artery occlusion was used to determine whether the newborn neurons could display functional electrophysiological properties. RESULTS: EGFP-expressing (EGFP(+)) signals could be detected mainly in the cell body in the first 2 weeks. From the fourth to thirteenth weeks after their birth, EGFP(+) neurons gradually formed neuronal polarity and showed a time-dependent increase in dendrite length and branch formation. EGFP(+) cells were copositive for NeuN and glutamic acid decarboxylase (EGFP(+)-NeuN(+)-GAD(67)(+)), MAP-2, and choline acetyltransferase (EGFP(+)-MAP-2(+)-ChAT(+)). They also expressed phosphorylated synapsin I (EGFP(+)-p-SYN(+)) and showed typical synaptic structures comprising dendrites and spines. Both GABAergic and cholinergic newborn neurons could fire action potentials and received excitatory and inhibitory synaptic inputs because they displayed spontaneous postsynaptic currents in picrotoxin- and CNQX-inhibited manners. CONCLUSIONS: Ischemia-induced newly formed striatal GABAergic and cholinergic neurons could become functionally integrated into neural networks in the brain of adult rats after stroke.

Melatonin protects against MPTP/MPP+ -induced mitochondrial DNA oxidative damage in vivo and in vitro.

The effects of melatonin on the mitochondrial DNA (mtDNA) damage induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine ion (MPP(+)) were investigated both in vivo and in vitro. MPTP (24 mg/kg, s.c.) induced a rapid increase in the immunoreactivity of 8-hydroxyguanine (8-oxoG), a common biomarker of DNA oxidative damage, in the cytoplasm of neurons in the Substantia Nigra Compact of mouse brain. Melatonin preinjection (7.5, 15 or 30 mg/kg, i.p.) dose-dependently prevented MPTP-induced DNA oxidative damage. In SH-SY5Y cells, MPP(+) (1 mm) increased the immunoreactivity of 8-oxoG in the mitochondria at 1 hr and in the nucleus at 3 hr after treatment. Melatonin (200 microm) preincubation significantly attenuated MPP(+)-induced mtDNA oxidative damage. Furthermore, MPP(+) time-dependently increased the accumulation of mitochondrial oxygen free radicals (mtOFR) from 1 to 24 hr and gradually decreased the mitochondrial membrane potential (Psim) from 18 to 36 hr after incubation. At 72 hr after incubation, MPP(+) caused cell death in 49% of the control. However, melatonin prevented MPP(+)-induced mtOFR generation and Psim collapse, and later cell death. The present results suggest that cytoprotection of melatonin against MPTP/MPP(+)-induced cell death may be associated with the attenuation of mtDNA oxidative damage via inhibition of mtOFR generation and the prevention of Psim collapse.

Electroacupuncture enhances striatal neurogenesis in adult rat brains after a transient cerebral middle artery occlusion.

In this study, we investigated the effects of electroacupuncture (EA) on ischemia-induced neurogenesis in the striatum of adult rat brains with a 30-minute middle cerebral artery occlusion. Injection of bromodeoxyuridine (BrdU, 30 mg/kg, i.p., cell proliferation marker) and 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3',3',3' -tetramethylindocarbo-cyanine (DiI, 1 microg/ microl, i.c.v, lipophilic neuronal tracer) combined with multiple fluorescence immunostaining were used to determine whether the proliferated cells were newly generated neurons and where they originated from in the brain. We demonstrated that EA treatment (60 Hz 1 s and 2 Hz 3 s alternately at an intensity of 10 mA for 20 min on "Fengfu", GV.16 and "Jinsuo", GV.8) enhanced stroke-induced striatal neurogenesis in rat brains as follows: 1) EA increased the number of BrdU+ cells, indicating that it activates cell proliferation; 2) EA increased BrdU+/CRMP-4(+) (collapsing response mediated protein-4, immature neuron marker) and BrdU+/MAP-2(+) (microtubule-associated protein 2, mature neuron marker) cells, suggesting that it facilitates neurogenesis and maturation of newly generated neurons; 3) EA expanded the distribution of DiI-stained cells in the striatum. Moreover, most BrdU+/CRMP-4(+) or BrdU+/MAP-2(+) cells in the striatum were observed DiI+ staining. Thus, the results suggest that striatal newborn neurons mainly migrate from the cells lining ventricle. Therefore, we conclude that EA can improve neuronal regeneration, newborn neuron migration and their maturation in the striatum of adult rat brains after stroke.