Mechanism of action of non-coding RNAs and traditional Chinese medicine in myocardial fibrosis: Focus on the TGF-ß/Smad signaling pathway.

Cardiac fibrosis is a serious public health problem worldwide that is closely linked to progression of many cardiovascular diseases (CVDs) and adversely affects both the disease process and clinical prognosis. Numerous studies have shown that the TGF-ß/Smad signaling pathway plays a key role in the progression of cardiac fibrosis. Therefore, targeted inhibition of the TGF-ß/Smad signaling pathway may be a therapeutic measure for cardiac fibrosis. Currently, as the investigation on non-coding RNAs (ncRNAs) move forward, a variety of ncRNAs targeting TGF-ß and its downstream Smad proteins have attracted high attention. Besides, Traditional Chinese Medicine (TCM) has been widely used in treating the cardiac fibrosis. As more and more molecular mechanisms of natural products, herbal formulas, and proprietary Chinese medicines are revealed, TCM has been proven to act on cardiac fibrosis by modulating multiple targets and signaling pathways, especially the TGF-ß/Smad. Therefore, this work summarizes the roles of TGF-ß/Smad classical and non-classical signaling pathways in the cardiac fibrosis, and discusses the recent research advances in ncRNAs targeting the TGF-ß/Smad signaling pathway and TCM against cardiac fibrosis. It is hoped, in this way, to give new insights into the prevention and treatment of cardiac fibrosis.

Characterization and functional analysis of two novel 3-hydroxy-3-methylglutaryl-coenzyme A reductase genes (GbHMGR2 and GbHMGR3) from Ginkgo biloba.

Terpene trilactones (TTLs) are the main secondary metabolites of Ginkgo biloba. As one of the rate-limiting enzymes in the mevalonic acid (MVA) pathway of TTL biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the 3-hydroxy-3-methylglutaryl coenzyme A to form MVA. In this study, two cDNA sequences of HMGR genes, namely, GbHMGR2 and GbHMGR3, were cloned from G. biloba. The protein sequences of GbHMGR2 and GbHMGR3, which contain several functional domains, were analyzed. Regulatory elements related to light, hormone, and stress response were detected in the promoter regions of GbHMGR2 and GbHMGR3. The catalytic activity of these genes was verified by a functional complement experiment in yeast. Quantitative real-time PCR (qRT-PCR) showed the distinct expression patterns of the two genes in different organs. The TTL contents in the organs were detected by high-performance liquid chromatography- evaporative light scattering detector. GbHMGR2 and GbHMGR3 were responded to cold, dark, methyl jasmonate (MJ), abscisic acid (ABA), salicylic acid (SA), and ethephon (Eth) treatments. The TTL contents were also regulated by cold, dark, MJ, ABA, SA, and Eth treatment. In conclusion, GbHMGR2 and GbHMGR3 may participate in the MVA pathway of TTL biosynthesis.

Moderating effects of music on resting state networks.

Resting state networks (RSNs) are spontaneous, synchronous, low-frequency oscillations observed in the brains of subjects who are awake but at rest. A particular RSN called the default mode network (DMN) has been shown to exhibit changes associated with neurological disorders such as temporal lobe epilepsy or Alzheimer's disease. Previous studies have also found that differing experimental conditions such as eyes-open versus eyes-closed can produce measurable changes in the DMN. These condition-associated changes have the potential of confounding the measurements of changes in RSNs related to or caused by disease state(s). In this study, we use fMRI measurements of resting-state connectivity paired with EEG measurements of alpha rhythm and employ independent component analysis, undirected graphs of partial spectral coherence, and spatiotemporal regression to investigate the effect of music-listening on RSNs and the DMN in particular. We observed similar patterns of DMN connectivity in subjects who were listening to music compared with those who were not, with a trend toward a more introspective pattern of resting-state connectivity during music-listening. We conclude that music-listening is a valid condition under which the DMN can be studied.

A spectral graphical model approach for learning brain connectivity network of children's narrative comprehension.

Narrative comprehension is a fundamental cognitive skill that involves the coordination of different functional brain regions. We develop a spectral graphical model with model averaging to study the connectivity networks underlying these brain regions using fMRI data collected from a story comprehension task. Based on the spectral density matrices in the frequency domain, this model captures the temporal dependency of the entire fMRI time series between brain regions. A Bayesian model averaging procedure is then applied to select the best directional links that constitute the brain network. Using this model, brain networks of three distinct age groups are constructed to assess the dynamic change of network connectivity with respect to age.