Search

Metabolic remodeling in cardiomyocytes is deeply associated with the pathogenesis of heart failure (HF). Glutaminolysis is an anaplerotic pathway that incorporates α-ketoglutarate (αKG) derived from glutamine into the tricarboxylic acid (TCA) cycle. It is well known that cancer cells depend on glutamine for their increased energy demand and proliferation; however, the physiological roles of glutamine metabolism in failing hearts remain unclear. To investigate the regulatory mechanisms and biological effects of glutamine metabolism in oxidative stress-induced failing myocardium. The intracellular levels of glutamine, glutamate, and αKG were significantly decreased by H 2 O 2 stimulation in rat neonatal cardiomyocytes (RNCMs). To better understand the metabolic flux in failing myocardium, we performed a stable isotope tracing study and found that glutaminolysis was upregulated in RNCMs under oxidative stress. Consistent with this, the enzymatic activity of glutaminase (Gls), which converts glutamine to glutamate, was augmented in RNCMs treated with H 2 O 2. These findings suggest that glutamine anaplerosis is enhanced in cardiomyocytes under oxidative stress to compensate for the reduction of αKG. Furthermore, the inhibition of Gls reduced cardiac cell viability, ATP production, and glutathione (GSH) synthesis in RNCMs with H 2 O 2 stimulation. Finally, we evaluated the effects of αKG on failing myocardium and observed that dimethyl α-ketoglutarate (DMKG) suppressed oxidative stress-induced cell death likely due to the enhancement of intracellular ATP and GSH levels. Our study demonstrates that under oxidative stress, glutaminolysis is upregulated to compensate for the loss of αKG and its replenishment into the TCA cycle, thereby exerting cardioprotective effects by maintaining ATP and GSH levels. Modulation of glutamine metabolism in failing hearts might provide a new therapeutic strategy for HF. Image 1 • Glutaminolysis is upregulated in cardiomyocytes under oxidative stress. • Cardiac glutamine anaplerosis contributes to increased ATP and GSH synthesis. • αKG maintains ATP and GSH levels in cardiomyocytes under oxidative stress. • Cardiac glutaminolysis improves cell viability under oxidative stress. [ABSTRACT FROM AUTHOR]

Acute dietary nitrate (NO 3 −) supplementation can increase [NO 3 −], but not nitrite ([NO 2 −]), in human skeletal muscle, though its effect on [NO 3 −] and [NO 2 −] in skin remains unknown. In an independent group design, 11 young adults ingested 140 mL of NO 3 −-rich beetroot juice (BR; 9.6 mmol NO 3 −), and 6 young adults ingested 140 mL of a NO 3 −-depleted placebo (PL). Skin dialysate, acquired through intradermal microdialysis, and venous blood samples were collected at baseline and every hour post-ingestion up to 4 h to assess dialysate and plasma [NO 3 −] and [NO 2 −]. The relative recovery rate of NO 3 − and NO 2 − through the microdialysis probe (73.1% and 62.8%), determined in a separate experiment, was used to estimate skin interstitial [NO 3 −] and [NO 2 −]. Baseline [NO 3 −] was lower, whereas baseline [NO 2 −] was higher in the skin interstitial fluid relative to plasma (both P < 0.001). Acute BR ingestion increased [NO 3 −] and [NO 2 −] in the skin interstitial fluid and plasma (all P < 0.001), with the magnitude being smaller in the skin interstitial fluid (e.g., 183 ± 54 vs. 491 ± 62 μM for Δ[NO 3 −] from baseline and 155 ± 190 vs. 217 ± 204 nM for Δ[NO 2 −] from baseline at 3 h post BR ingestion, both P ≤ 0.037). However, due to the aforementioned baseline differences, skin interstitial fluid [NO 2 −] post BR ingestion was higher, whereas [NO 3 −] was lower relative to plasma (all P < 0.001). These findings extend our understanding of NO 3 − and NO 2 − distribution at rest and indicate that acute BR supplementation increases [NO 3 −] and [NO 2 −] in human skin interstitial fluid. • [NO 3 −] and [NO 2 −] in skin interstitial fluid was assessed using microdialysis. • Basal [NO 3 −] is lower in skin interstitial fluid relative to plasma. • Basal [NO 2 −] is higher in skin interstitial fluid compared with plasma. • Dietary nitrate (NO 3 −) increases [NO 3 −] and [NO 2 −] in skin interstitial fluid. [ABSTRACT FROM AUTHOR]

Cryotherapy is one of the most common treatments for trauma or fatigue in the field of sports medicine. However, the molecular biological effects of acute cold exposure on skeletal muscle remain unclear. Therefore, we used zebrafish, which have recently been utilized as an animal model for skeletal muscle, to comprehensively investigate and selectively clarify the time-course changes induced by cryotherapy. Zebrafish were exposed intermittently to cold stimulation three times for 15 min each. Thereafter, skeletal muscle samples were collected after 15 min and 1, 2, 4, and 6 h. mRNA sequencing revealed the involvement of trim63a , fbxo32 , fbxo30a , and klhl38b in "protein ubiquitination" from the top 10 most upregulated genes. Subsequently, we examined the time-course changes of the four genes by quantitative PCR, and their expression peaked 2 h after cryotherapy and returned to baseline after 6 h. Moreover, the proteins encoded by trim63a and fbxo32 (muscle-specific RING finger protein 1 [MuRF1] and muscle atrophy F-box, respectively), which are known to be major genes encoding E3 ubiquitin ligases, were examined by western blotting, and MuRF1 expression displayed similar temporal changes as trim63a expression. These findings suggest that acute cold exposure transiently upregulates E3 ubiquitin ligases, especially MuRF1; thus, cryotherapy may contribute to the treatment of trauma or fatigue by promoting protein processing. • Acute cold stress affected the expression of multiple genes, mainly those related to E3 ubiquitin ligases. • The increase in gene expression was transiently induced, peaking at 2 h after cold exposure and returning to baseline by 6 h. • In particular, the protein expression of MuRF1 (encoded by trim63a) was significantly increased. • Cryotherapy may contribute to recovery from trauma or fatigue by promoting the processing of damaged or unfolded proteins. [ABSTRACT FROM AUTHOR]

Ninety-two bifidobacterial strains were obtained from the faeces of 5 baby common marmosets, three known species Bifidobacterium aesculapii , Bifidobacterium callithricos and Bifidobacterium reuteri and 4 novel putative bifidobacterial species were retrieved. The occurrence of bifidobacteria in non-human primate babies is described for the first time. [ABSTRACT FROM AUTHOR]

Abstract: A millet alcoholic beverage that is made primarily from glutinous rice or millet is a traditional drink of indigenous Taiwanese tribes. In this study, we used both culture-dependent and culture-independent methods to analyse the diversity of the lactic acid bacteria (LAB) that are present during the process of millet alcohol fermentation, including during starter preparation and brewing. Based on random amplified polymorphic DNA (RAPD)-PCR fingerprinting profiles, 147 LAB isolates were identified and categorised into 38 groups. Phylogenetic analyses of 16S rRNA, phenylalanyl-tRNA synthase alpha subunit (pheS) and RNA polymerase alpha subunit (rpoA) gene sequences identified representative strains from each of the 38 groups as belonging to the following ten species: Enterococcus faecium group, Lactobacillus brevis, Lactococcus garvieae, Lactococcus lactis, Leuconostoc carnosum, Leuconostoc (Leu.) mesenteroides, Pediococcus pentosaceus, Pediococcus stilesii, Weissella cibaria and Weissella soli. The results of the LAB species diversity studies were confirmed using 16S rRNA gene-based denaturing gradient gel electrophoresis (PCR-DGGE), which showed that P. pentosaceus was mainly involved in the fermentation in both the starter preparation and at the brewing stage. However, L. brevis, Leu. mesenteroides and P. stilesii were the predominant LAB strains found during the brewing stage. [Copyright &y& Elsevier]

Abstract: We used culture- and molecular-biology-based methods to investigate the diversity of lactic acid bacteria (LAB) in the ethnic chevon (goat) meat products chartayshya, jamma and arjia of the Western Himalayas. In six chartayshya, six jamma and four arjia samples, LAB were the predominant microbial component involved in the fermentation of these samples, and the total LAB population in arjia (7.8 ± 0.1 log cfu g−1; mean ± SD) was significantly higher (P < 0.05) than in chartayshya (6.9 ± 0.1 log cfu g−1) and jamma (7.5 ± 0.1 log cfu g−1). We identified 53 LAB samples by 16S rRNA and phenylalanyl-tRNA synthase (pheS) genes sequencing. The LAB isolates were identified as Enterococcus durans, Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Leuconostoc citreum, Leuconostoc mesenteroides, Pediococcus pentosaceus, and Weissella cibaria. These results revealed that there is a high level of diversity of LAB in the Himalayan ethnic preserved meat products. [Copyright &y& Elsevier]