Accumulating evidence has indicated that intestinal microbiota is involved in the development of various human diseases, including cardiovascular diseases (CVDs). In the recent years, both human and ...animal experiments have revealed that alterations in the composition and function of intestinal flora, recognized as gut microflora dysbiosis, can accelerate the progression of CVDs. Moreover, intestinal flora metabolizes the diet ingested by the host into a series of metabolites, including trimethylamine N‐oxide, short chain fatty acids, secondary bile acid and indoxyl sulfate, which affects the host physiological processes by activation of numerous signalling pathways. The aim of this review was to summarize the role of gut microbiota in the pathogenesis of CVDs, including coronary artery disease, hypertension and heart failure, which may provide valuable insights into potential therapeutic strategies for CVD that involve interfering with the composition, function and metabolites of the intestinal flora.
Sarcopenia is an age‐related disease characterized by disturbed homeostasis of skeletal muscle, leading to a decline in muscle mass and function. Loss of muscle mass and strength leads to falls and ...fracture, and is often accompanied by other geriatric diseases, including osteoporosis, frailty and cachexia, resulting in a general decrease in quality of life and an increase in mortality. Although the underlying mechanisms of sarcopenia are still not completely understood, there has been a marked improvement in the understanding of the pathophysiological changes leading to sarcopenia in recent years. The role of microRNAs (miRNAs), especially, has been clearer in skeletal muscle development and homeostasis. miRNAs form part of a gene regulatory network and have numerous activities in many biological processes. Intervention based on miRNAs may develop into an innovative treatment strategy to conquer sarcopenia. This review is divided into three sections: firstly, the latest understanding of the pathogenesis of sarcopenia is summarized; secondly, increasing evidence for the involvement of miRNAs in the regulation of muscle quantity or quality and muscle homeostasis is highlighted; and thirdly, the possibilities and limitations of miRNAs as a treatment for sarcopenia are explored.
DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of ...chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2'-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. The deposition of m6dA is associated with increased genome-wide occupancy of the mammalian m6dA methyltransferase, N6amt1, and this correlates with extinction-induced gene expression. The accumulation of m6dA is associated with transcriptional activation at the brain-derived neurotrophic factor (Bdnf) P4 promoter, which is required for Bdnf exon IV messenger RNA expression and for the extinction of conditioned fear. These results expand the scope of DNA modifications in the adult brain and highlight changes in m6dA as an epigenetic mechanism associated with activity-induced gene expression and the formation of fear extinction memory.
DNA forms conformational states beyond the right-handed double helix; however, the functional relevance of these noncanonical structures in the brain remains unknown. Here we show that, in the ...prefrontal cortex of mice, the formation of one such structure, Z-DNA, is involved in the regulation of extinction memory. Z-DNA is formed during fear learning and reduced during extinction learning, which is mediated, in part, by a direct interaction between Z-DNA and the RNA-editing enzyme Adar1. Adar1 binds to Z-DNA during fear extinction learning, which leads to a reduction in Z-DNA at sites where Adar1 is recruited. Knockdown of Adar1 leads to an inability to modify a previously acquired fear memory and blocks activity-dependent changes in DNA structure and RNA state-effects that are fully rescued by the introduction of full-length Adar1. These findings suggest a new mechanism of learning-induced gene regulation that is dependent on proteins that recognize alternate DNA structure states, which are required for memory flexibility.
Enzymatic extraction of arabinoxylans (AXs) is an attractive and environmentally friendly extraction option, in which technical considerations (yield and purity) have been coupled with environmental ...concerns. Amano HC 90 and Cellulase were combined to evaluate their interactive effects on AX extraction from destarched, deproteinised bran (DSDPB). A response surface methodology was used to obtain the optimal extraction conditions. The experimental data fit well with the predicted values and the model adequately represented the actual relationship among the measured parameters. The extraction yield and AX content in the extract under optimal conditions (double-enzyme dose of 920 U/g, pH of 3.0, extraction temperature of 35.0 °C; extraction time of 6 h; and DSDPB to liquid ratio of 1:30) were 40.73 ± 0.09% and 75.88 ± 0.11%, respectively. The double-enzymatic extraction method of AX from fresh corn fibre was more efficient than the chemical method.
The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. ...Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro. In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis.
Fibroblast growth factor 1 (FGF1) is thought to exert protective and regenerative effects on neurons following spinal cord injury (SCI), although the mechanism of these effects is not well ...understood. The use of FGF1 as a therapeutic agent is limited by its lack of physicochemical stability and its limited capacity to cross the blood‐spinal cord barrier. Here, we demonstrated that overexpression of FGF1 in spinal cord following SCI significantly reduced tissue loss, protected neurons in the ventricornu, ameliorated pathological morphology of the lesion, dramatically improved tissue recovery via neuroprotection, and promoted axonal regeneration and remyelination both in vivo and in vivo. In addition, the autophagy and the expression levels of PRDX1 (an antioxidant protein) were induced by AAV‐FGF1 in PC12 cells after H2O2 treatment. Furthermore, the autophagy levels were not changed in PRDX1‐suppressing cells that were treated by AAV‐FGF1. Taken together, these results suggest that FGF1 improves functional recovery mainly through inducing PRDX1 expression to increase autophagy and anti‐ROS activity after SCI.
Combining with a static random-access memory (SRAM) and resistive memory (RRAM), an improved 8T2R nonvolatile SRAM (nvSRAM) memory cell is proposed in this study. With differential mode, a pair of ...1T1R RRAM is added to 6T SRAM storage node. By optimizing the connection and layout scheme, the power consumption is reduced and the data stability is improved. The nvSRAM memory cell is realized with UMC CMOS 28 nm 1p9m process. When the power supply voltage is 0.9 V, the static noise/read/write margin is 0.35 V, 0.16 V, and 0.41 V, respectively. The data storage/restoration time is 0.21 ns and 0.18 ns, respectively, with an active area of 0.97 μm2.
Combining the advantages of low-power consumption of static random access memory (SRAM) with high stability and nonvolatile of resistive memory (RRAM), an improved 8T2R nonvolatile SRAM (nvSRAM) ...memory cell was proposed in this paper. In order to solve the problem that data cannot be stored when SRAM is powered off, RRAM technology was introduced into SRAM to realize an SRAM with nonvolatile function. The differential mode was adopted to improve the data restoration speed. Meanwhile, a pre-decoding technology was proposed to realize fast address decoding, and a voltage-mode sensitive amplifier was used to achieve fast amplification of two bit lines, so as to improve the reading speed of the memory. An 8kb nvSRAM was implemented with a CMOS 28 nm 1P9M process. The simulation results show that when the power supply voltage was 0.9 V, the static/read/write noise margin was 0.35 V, 0.16 V and 0.41 V, respectively. The data storage time was 0.21 ns, and restoration time was 0.18 ns. The time for the whole system to read 1 bit of data was 5.2 ns.
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