The Inhibitory Role of Hydrogen Sulfide in UII-Induced Cardiovascular Effects and the Underlying Signaling Pathways.

Urotensin II (UII) could increase blood pressure and heart rate via increased central reactive oxygen species (ROS) levels. We reported previously that hydrogen sulfide (HS) exerts an antihypertensive effect by suppressing ROS production. The aim of the current study is to further examine the effects of endogenous and exogenous HS on UII-induced cardiovascular effects by using an integrated physiology approach.

Activation of unfolded protein response overcomes Ibrutinib resistance in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most widespread type of non-Hodgkin lymphoma (NHL). As the most aggressive form of the DLBCL, the activated B-cell-like (ABC) subtype is often resistant to standard chemotherapies. Bruton's tyrosine kinase (BTK) inhibitor ibrutinib provides a potential therapeutic approach for the DLBCL but fails to improve the outcome in the phase III trial.

Upregulation of Nav1.6 expression in the rostral ventrolateral medulla of stress-induced hypertensive rats.

The rostral ventrolateral medulla (RVLM) plays a key role in mediating the development of stress-induced hypertension (SIH) by excitation and/or inhibition of sympathetic preganglionic neurons. The voltage-gated sodium channel Nav1.6 has been found to contribute to neuronal hyperexcitability.

The protective effects of electro-acupuncture in thoracic surgery on trauma stressed rats involve the rostral ventrolateral medulla and supraoptic nucleus.

The present study was designed to explore whether the rostral ventrolateral medulla (RVLM) and supraoptic nucleus (SON) were involved in the protective effects of electro-acupuncture (EA) in thoracic surgery on trauma-stressed rats. The rats were randomly divided into a non-stressed group (Control), surgical trauma-stressed group (Trauma), and Neiguan EA applied on the surgical trauma-stressed group (Trauma+EA-PC 6). RVLM neuron discharge was observed by using an in vivo electrophysiological method, and micro-dialysis combining high-performance liquid chromatography with fluorometric detection (HPLC-FD) was used to assess expression of amino acids in the RVLM.

2-(3-Benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ameliorates metabolic disorders in high-fat diet-fed mice.

Aim: Sterol-regulatory element binding proteins (SREBPs) are major transcription factors that regulate liver lipid biosynthesis. In this article we reported a novel synthetic compound 2-(3-benzoylthioureido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (ZJ001) that inhibited the SREBP-1c pathway, and effectively reduced hepatic lipid accumulation in diet-induced obesity (DIO) mice.

Methods: A luciferase reporter driven by an SRE-containing promoter transfected into HepG2 cells was used to discover the compound.

The urinary bladder of spontaneously hypertensive rat demonstrates bladder hypertrophy, inflammation, and fibrosis but not hyperplasia.

Aims: The present study aims to systemically characterize the factors that are associated with urinary bladder organ enlargement in spontaneously hypertensive rats (SHR).

Main Methods: We compared the SHR to age-matched normotensive Wistar-Kyoto (WKY) control rats in the levels of bladder pro-inflammatory factors, collagen expression (type I), and detrusor smooth muscle growth.

Key Findings: Our results showed that enhanced inflammatory responses and fibrosis were key factors that were closely associated with bladder wall thickening in SHR.

Simvastatin pretreatment protects cerebrum from neuronal injury by decreasing the expressions of phosphor-CaMK II and AQP4 in ischemic stroke rats.

Excitotoxicity and cytotoxic edema are the two major factors resulting in neuronal injury during brain ischemia and reperfusion. Ca2+/calmodulin-dependent protein kinase II (CaMK II), the downstream signal molecular of N-methyl-D-aspartate receptors (NMDARs), is a mediator in the excitotoxicity. Aquaporin 4 (AQP4), expressed mainly in the brain, is an important aquaporin to control the flux of water.

In vivo regulation of brain-derived neurotrophic factor in dorsal root ganglia is mediated by nerve growth factor-triggered Akt activation during cystitis.

The role of brain-derived neurotrophic factor (BDNF) in sensory hypersensitivity has been suggested; however the molecular mechanisms and signal transduction that regulate BDNF expression in primary afferent neurons during visceral inflammation are not clear. Here we used a rat model of cystitis and found that the mRNA and protein levels of BDNF were increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation. BDNF up-regulation in the L6 DRG was triggered by endogenous nerve growth factor (NGF) because neutralization of NGF with a specific NGF antibody reduced BDNF levels during cystitis.

Endogenous PI3K/Akt and NMDAR act independently in the regulation of CREB activity in lumbosacral spinal cord in cystitis.

The integral interaction of signaling components in the regulation of visceral inflammation-induced central sensitization in the spinal cord has not been well studied. Here we report that phosphoinositide 3-kinase (PI3K)-dependent Akt activation and N-methyl-d-aspartic acid receptor (NMDAR) in lumbosacral spinal cord independently regulate the activation of cAMP response element-binding protein (CREB) in vivo in a rat visceral pain model of cystitis induced by intraperitoneal injection of cyclophosphamide (CYP). We demonstrate that suppression of endogenous PI3K/Akt activity with a potent PI3K inhibitor LY294002 reverses CYP-induced phosphorylation of CREB, however, it has no effect on CYP-induced phosphorylation of NR1 at Ser(897) and Ser(896); conversely, inhibition of NMDAR in vivo with MK801 fails to block CYP-induced Akt activation but significantly attenuates CYP-induced CREB phosphorylation in lumbosacral spinal cord.

Novel small-molecule AMP-activated protein kinase allosteric activator with beneficial effects in db/db mice.

AMP-activated protein kinase (AMPK) is an energy sensor of metabolism that is an attractive therapeutic target for type 2 diabetes mellitus and metabolic syndrome. Using a homogeneous scintillation proximity assay (SPA), we identified a new small-molecule AMPK activator, ZLN024, which allosterically stimulated active AMPK heterotrimers and the inactive α1 subunit truncations α1 (1-394) and α1 (1-335) but not α1 (1-312). AMPK activation by ZLN024 requires the pre-phosphorylation of Thr-172 by at least one upstream kinase and protects AMPK Thr-172 against dephosphorylation by PP2Cα.

Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.

Studies have revealed that apelin is a novel multifunctional peptide implicated both in blood pressure (BP) regulation and cardiac function control. Evidence shows that apelin and its receptor (APJ) in the rostral ventrolateral medulla (RVLM) may play an important role in central BP regulation; however, its role is controversial and very few reports have shown the relationship between acupuncture and apelin. Our study aims to both investigate the apelinergic system role in stress-induced hypertension (SIH) and determine whether acupuncture therapy effects on hypertension involve the apelinergic system in the RVLM.

Novel small-molecule PGC-1α transcriptional regulator with beneficial effects on diabetic db/db mice.

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has been shown to influence energy metabolism. Hence, we explored a strategy to target PGC-1α expression to treat metabolic syndromes. We developed a high-throughput screening assay that uses the human PGC-1α promoter to drive expression of luciferase.

Up-regulation of brain-derived neurotrophic factor is regulated by extracellular signal-regulated protein kinase 5 and by nerve growth factor retrograde signaling in colonic afferent neurons in colitis.

Brain-derived neurotrophic factor (BDNF) plays an essential role in sensory neuronal activation in response to visceral inflammation. Here we report that BDNF up-regulation in the primary afferent neurons in the dorsal root ganglia (DRG) in a rat model of colitis is mediated by the activation of endogenous extracellular signal-regulated protein kinase (ERK) 5 and by nerve growth factor (NGF) retrograde signaling. At 7 days of colitis, the expression level of BDNF is increased in conventional neuronal tracing dye Fast Blue labeled primary afferent neurons that project to the distal colon.

Protective effects of electroacupuncture on cardiac function in rats subjected to thoracic surgery trauma.

The present study investigates the protective effects of electroacupuncture (EA) application on cardiac function, while simultaneously exploring the underlying neurobiological mechanisms, in rats that have experienced thoracic surgery-induced stress. Mean arterial and left intraventricular pressures were monitored as indicators of cardiac function. Meanwhile, the immunohistochemistry for c-Fos protein expression and electrophysiology in vitro in brain nuclei, known to regulate cardiac function, provide insights into the effects of EA on the central nervous system.

Activation of extracellular signal-regulated protein kinase 5 is essential for cystitis- and nerve growth factor-induced calcitonin gene-related peptide expression in sensory neurons.

Background: Cystitis causes considerable neuronal plasticity in the primary afferent pathways. The molecular mechanism and signal transduction underlying cross talk between the inflamed urinary bladder and sensory sensitization has not been investigated.

Results: In a rat cystitis model induced by cyclophosphamide (CYP) for 48 h, the mRNA and protein levels of the excitatory neurotransmitter calcitonin gene-related peptide (CGRP) are increased in the L6 dorsal root ganglia (DRG) in response to bladder inflammation.

Up-regulation of brain-derived neurotrophic factor in primary afferent pathway regulates colon-to-bladder cross-sensitization in rat.

Background: In humans, inflammation of either the urinary bladder or the distal colon often results in sensory cross-sensitization between these organs. Limited information is known about the mechanisms underlying this clinical syndrome. Studies with animal models have demonstrated that activation of primary afferent pathways may have a role in mediating viscero-visceral cross-organ sensitization.

Treadmill pre-training suppresses the release of glutamate resulting from cerebral ischemia in rats.

This study was designed to investigate the neuroprotective effect of treadmill pre-training against the over-release of glutamate resulting from cerebral ischemia. Sprague-Dawley rats underwent 2 weeks of treadmill run-training before cerebral ischemia was performed by middle cerebral artery occlusion. The level of glutamate in brain extracellular fluid was detected before, during and after ischemia/reperfusion.

Pre-ischemic treadmill training affects glutamate and gamma aminobutyric acid levels in the striatal dialysate of a rat model of cerebral ischemia.

Aims: Treadmill training has been shown to improve function in animal models and patients with cerebral ischemia. However, the neurochemical effects of this intervention on the ischemic brain have not been well studied. This study was designed to evaluate the effects of pre-ischemic treadmill training on the release of glutamate and gamma-aminobutyric acid (GABA) from the striatum in a rat middle cerebral artery occlusion (MCAO) model.

First-pass perfusion computed tomography: initial experience in differentiating adrenal adenoma from metastasis.

Objective: To differentiate adrenal adenoma from metastasis in patients using perfusion computed tomography (PCT) imaging.

Methods: Thirty-two patients with adrenal masses underwent first-pass PCT imaging. Of these patients, twenty-one were diagnosed with adrenal adenoma, and the others with metastases.

Differential expressions of nNOS and iNOS in the rostral ventrolateral medulla induced by electroacupuncture in acute myocardial ischemia rats.

Increasing lines of evidence has been accumulated that nitric oxide (NO) and nitric oxide synthase (NOS) distribute plentifully in the rostral ventrolateral medulla (RVLM) and contribute to cardiovascular regulation. In the present study, the expressions of neuronal and inducible isoform of NOS (nNOS and iNOS) were observed in the RVLM of acute myocardial ischemia (AMI) Wistar rats experienced electroacupuncture (EA) treatment, thereby the cardiovascular effects of NO in the RVLM were investigated and the mechanism of acupuncture effect on AMI was inferred. The results indicated that in the AMI rats, cardiac functions were markedly attenuated with high serum level of brain natriuretic peptide (BNP) and norepinephine (NE), the number of nNOS-immunoreactive cells and nNOS mRNA exprossion in the RVLM area were increased, while those of iNOS were lowered.

Effects of melatonin on blood pressure in stress-induced hypertension in rats.

Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise.