Endogenous corticotropin-releasing factor potentiates the excitability of presympathetic neurons in paraventricular nucleus via activation of its receptor 1 in spontaneously hypertensive rats.

It is well established that increased excitability of the presympathetic neurons in the hypothalamic paraventricular nucleus (PVN) during hypertension leads to heightened sympathetic outflow and hypertension. However, the mechanism underlying the overactivation of PVN presympathetic neurons remains unclear. This study aimed to investigate the role of endogenous corticotropin-releasing factor (CRF) on the excitability of presympathetic neurons in PVN using Western blot, arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA) recording, CRISPR/Cas9 technique and patch-clamp technique. The results showed that CRF protein expression in PVN was significantly upregulated in spontaneously hypertensive rats (SHRs) compared with normotensive Wistar-Kyoto (WKY) rats. Besides, PVN administration of exogenous CRF significantly increased RSNA, heart rate and ABP in WKY rats. In contrast, knockdown of upregulated CRF in PVN of SHRs inhibited CRF expression, led to membrane potential hyperpolarization, and decreased the frequency of current-evoked firings of PVN presympathetic neurons, which were reversed by incubation of exogenous CRF. Perfusion of rat brain slices with artificial cerebrospinal fluid containing CRF receptor 1 (CRFR1) blocker, NBI-35965, or CRF receptor 2 (CRFR2) blocker, Antisauvagine-30, showed that blocking CRFR1, but not CRFR2, hyperpolarized the membrane potential and inhibited the current-evoked firing of PVN presympathetic neurons in SHRs. However, blocking CRFR1 or CRFR2 did not affect the membrane potential and current-evoked firing of presympathetic neurons in WKY rats. Overall, these findings indicate that increased endogenous CRF release from PVN CRF neurons enhances the excitability of presympathetic neurons via activation of CRFR1 in SHRs.

Paenibacillus susongensis sp. nov., a mineral-weathering bacterium.

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated M327(T), was isolated from the weathered surfaces of rock (mica schist) from Susong, Anhui Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain M327(T) belonged to the genus Paenibacillus and was related most closely to Paenibacillus terrigena A35(T) (98.6 % similarity) and Paenibacillus selenitireducens ES3-24(T) (98.3 %). Strain M327(T) contained meso-diaminopimelic acid in the cell wall and MK-7 as the major menaquinone. The main fatty acids of strain M327(T) were anteiso-C15 : 0 and iso-C16 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unknown aminophospholipids and an unknown lipid. The total DNA G+C content of strain M327(T) was 48.6 mol%. Based on the low level of DNA-DNA relatedness (ranging from 26.6 to 33.1 %) to these type strains of species of the genus Paenibacillus and unique phenotypic characteristics, it is suggested that strain M327(T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus susongensis sp. nov. is proposed. The type strain is M327(T) ( = CCTCC AB 2014058(T) = LMG 28236(T) = JCM 19951(T)).

Dyella jiangningensis sp. nov., a γ-proteobacterium isolated from the surface of potassium-bearing rock.

A Gram-stain-negative, aerobic, motile with one polar flagellum γ-proteobacterium, designated strain SBZ3-12(T), was isolated from surfaces of weathered potassic trachyte. Phylogenetic analysis of this strain based on 16S rRNA gene sequences showed that it was most closely related to Dyella japonica XD53(T) (97.9% 16S rRNA gene sequence similarity), Dyella terrae JS14-6(T) (97.7%), Dyella soli JS12-10(T) (97.5%) and Dyella koreensis BB4(T) (97.0%). The DNA G+C content of strain SBZ3-12(T) was 64.0 mol%. In addition, iso-C(17:1)ω9c, iso-C(15:0) and iso-C(16:0) were the major cellular fatty acids and ubiquinone Q-8 was the predominant respiratory quinone. The low DNA-DNA relatedness values between strain SBZ3-12(T) and recognized species of the genus Dyella and the many phenotypic properties supported the classification of strain SBZ3-12(T) as a representative of a novel species of the genus Dyella, for which the name Dyella jiangningensis sp. nov. is proposed. The type strain is SBZ3-12(T) ( =CCTCC AB 2012160(T) =KACC 16539(T) =DSM 26119(T)).

CIHH protects the heart against left ventricular remodelling and myocardial fibrosis by balancing the renin-angiotensin system in SHR.

AIM: The aim of our study was to clarify the cardioprotection of chronic intermittent hypobaric hypoxia (CIHH) and the underlying mechanism in spontaneously hypertensive rats (SHR). MAIN METHODS: Adult male rats were divided into normal blood pressure Wistar-Kyoto rats (WKY) control (WKY-CON), WKY rats with CIHH treatment (WKY-CIHH), SHR control (SHR-CON) and SHR with CIHH treatment (SHR-CIHH) groups. SHR-CIHH and WKY-CIHH rats were subjected to hypobaric hypoxia simulating 4000-m altitude for 35 days, 5 h per day. Arterial blood pressure and cardiac function parameters, including ejection fraction, fractional shortening and left ventricular (LV) wall thickness, were evaluated. Cardiac pathomorphology and myocardial fibrosis were determined. The expression of angiotensin-converting enzyme (ACE), ACE2, Ang II, Ang1-7, AT1 receptor, Mas receptor, IL-6, TNF-α，IL-10, SOD and MDA were assayed in myocardium. KEY FINDINGS: CIHH significantly decreased arterial blood pressure, alleviated LV hypertrophy, and improved cardiovascular function in SHR (P < 0.05-0.01). Also, CIHH protected SHR heart against morphological changes and fibrosis. In addition, CIHH significantly down-regulated the ACE/Ang II/AT1 receptor axis and up-regulated the ACE2/Ang1-7/Mas axis of renin-angiotensin system (RAS) in SHR (P < 0.05-0.01). CIHH significantly reduced IL-6, TNF-α, and MDA levels, but increased IL-10 and SOD in SHR myocardium (P < 0.05-0.01). SIGNIFICANCE: The CIHH treatment protected the heart of SHR against LV remodelling and myocardial fibrosis, which might be carried out through a balance in the ACE/Ang II/AT1 axis and the ACE2/Ang1-7/Mas axis of the RAS to reduce inflammation, and inhibit oxidative stress.

Chronic intermittent hypobaric hypoxia attenuates skeletal muscle ischemia-reperfusion injury in mice.

AIM: The aim of this study was to investigate the protective effect of chronic intermittent hypobaric hypoxia (CIHH) against skeletal muscle ischemia-reperfusion (IR) injury and to determine the underlying mechanism. MAIN METHODS: C57BL/6 mice were randomly divided into 3 groups: skeletal muscle IR injury group (IR), CIHH pretreatment following IR group (IR + CIHH), and sham operation group (Sham). The skeletal muscle IR injury model was induced by the unilateral application of a tourniquet on a hind limb for 3 h and then releasing it for 24 h. CIHH pretreatment simulating a 5000-m altitude was applied 6 h per day for 28 days. The functional and morphological performance of IR-injured gastrocnemius muscle was evaluated using contraction force, H&E staining, and transmission electron microscopy. IR injury-induced CD68+ macrophage infiltration was assessed by immunofluorescence. TNFα levels in serum and muscle were measured by ELISA and western blotting, respectively. Apoptosis was examined by TUNEL staining and Cleaved Caspase-3 protein expression. KEY FINDINGS: Acute IR injury resulted in reduced contraction tension, morphological destruction, macrophage infiltration, increased TNFα levels, and apoptosis in gastrocnemius muscle. CIHH pretreatment significantly ameliorated contraction function and morphological performance in IR-injured skeletal muscle. In addition, CIHH pretreatment resulted in marked decreases in CD68+ macrophage infiltration, TNFα levels, and apoptosis. SIGNIFICANCE: These data demonstrated that CIHH has a protective effect against acute IR injury in skeletal muscle via inhibition of inflammation and apoptosis.