βAR-mTOR-lipin1 pathway mediates PKA-RIIβ deficiency-induced adipose browning.

Enhancing white adipose tissue (WAT) browning combats obesity. The RIIβ subunit of cAMP-dependent protein kinase (PKA) is primarily expressed in the brain and adipose tissue. Deletion of the hypothalamic RIIβ gene centrally induces WAT browning, yet the peripheral mechanisms mediating this process remain unexplored.

Temporospatial effects of acyl-ghrelin on activation of astrocytes after ischaemic brain injury.

The protective mechanisms of astrocyte signalling are based on the release of neurotrophic factors and the clearing of toxic substances in the early stages of cerebral ischaemia. However, astrocytes are also responsible for the detrimental effects that occur during the later stages of ischaemia, in which glial scars are formed, thereby impeding neural recovery. Acyl-ghrelin has been found to be neuroprotective after stroke, although the influence of acyl-ghrelin on astrocytes after ischaemic injury is yet to be clarified.

Ghrelin Promotes Cortical Neurites Growth in Late Stage After Oxygen-Glucose Deprivation/Reperfusion Injury.

Acyl ghrelin, a novel brain-gut peptide, is an endogenous ligand for the growth hormone secretagogue receptor. Accumulated research data have shown that acyl ghrelin exercises a significant neuroprotective effect against cerebral ischemia/reperfusion (I/R) injury in animal models and in cultured neurons during the acute phase, usually, 1 day after cerebral ischemia. The chronic effects of acyl ghrelin 1 week after brain ischemia remain largely unknown.

Unravel a neuroactive sHA sulfation pattern with neurogenesis activity by a library of defined oligosaccharides.

Sulfated hyaluronic acid (sHA) is chemically synthetic mimetic of glycosaminoglycan (GAG) presenting promising biological functions. Specific sulfation pattern, termed as sulfation code plays critical roles in regulating the binding mode between GAG and proteins. As a structural analogue of chondroitin sulfate (CS), sHA bears much higher molecular weight and is nearly free of other proteoglycan contaminants.

Activation of the Nuclear Receptor Fxr Improves Intestinal Cell Tolerance to Ischemia-Reperfusion Injury.

The farnesoid X receptor (FXR) plays an important role in bile acid metabolism, intestinal homeostasis, and intestinal ischemia-reperfusion (I/R) injury. We aimed to clarify the potential effects of FXR on intestinal epithelial cell tolerance to intestinal I/R injury and reveal the underlying mechanisms. An intestinal I/R injury model was established by the occlusion of the superior mesenteric artery for ischemia for 1 h, followed by reperfusion for 4 h in C57BL/6 (wild type [WT]) and FXR mice.

[Movement Control of Striatum Neural Pathway].

Striatum is the central structure controlling movement. It plays a pivotal role in the regulation of voluntary movement, unconscious movement, muscle tone, posture adjustment and fine movement. Dysfunction of striatum causes a variety of movement disorders ranging from the hypokinetic disorders with increased muscle tone, such as Parkinson's disease, to the hyperkinetic disorders with decreased muscle tone, such as Huntington's disease.

[Leptin Signalings and Leptin Resistance].

Leptin plays a critical role in the regulation of energy balance and metabolic homeostasis. Impairment of leptin function is closely involved in the pathogenesis of obesity, diabetes mellitus and some other metabolic diseases. Leptin initiates intracellular signal transductions in the leptin-receptor-expressing neurons in the central nervous system to exert its physiological functions.

Chitosan Oligosaccharides Inhibit/Disaggregate Fibrils and Attenuate Amyloid β-Mediated Neurotoxicity.

Alzheimer's disease (AD) is characterized by a large number of amyloid-β (Aβ) deposits in the brain. Therefore, inhibiting Aβ aggregation or destabilizing preformed aggregates could be a promising therapeutic target for halting/slowing the progression of AD. Chitosan oligosaccharides (COS) have previously been reported to exhibit antioxidant and neuroprotective effects.

Genetic analysis of dTSPO, an outer mitochondrial membrane protein, reveals its functions in apoptosis, longevity, and Ab42-induced neurodegeneration.

The outer mitochondrial membrane (OMM) protein, the translocator protein 18 kDa (TSPO), formerly named the peripheral benzodiazepine receptor (PBR), has been proposed to participate in the pathogenesis of neurodegenerative diseases. To clarify the TSPO function, we identified the Drosophila homolog, CG2789/dTSPO, and studied the effects of its inactivation by P-element insertion, RNAi knockdown, and inhibition by ligands (PK11195, Ro5-4864). Inhibition of dTSPO inhibited wing disk apoptosis in response to γ-irradiation or H2O2 exposure, as well as extended male fly lifespan and inhibited Aβ42-induced neurodegeneration in association with decreased caspase activation.

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis.

14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen-glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons.

Chitosan oligosaccharides protect rat primary hippocampal neurons from oligomeric β-amyloid 1-42-induced neurotoxicity.

β-Amyloid peptide (Aβ), the major component of senile plaques in patients with Alzheimer's disease (AD), is believed to facilitate the progressive neurodegeneration that occurs in this disease. Mounting natural compounds are proved to be potential candidates for the prevention and treatment of AD. Chitosan oligosaccharides (COSs), the enzymatic hydrolysates of chitosan, have been reported to possess diverse biological activities.

CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro.

Aβ-40 Y10F increases βfibrils formation but attenuates the neurotoxicity of amyloid-β peptide.

Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. The tyrosine residue (Tyr-10) is believed to be important in Aβ-induced neurotoxicity due to the formation of tyrosyl radicals. To reduce the likelihood of cross-linking, here we designed an Aβ-40 analogue (Aβ-40 Y10F) in which the tyrosine residue was substituted by a structurally similar residue, phenylalanine.

Depletion of tissue factor suppresses hepatic metastasis and tumor growth in colorectal cancer via the downregulation of MMPs and the induction of autophagy and apoptosis.

Tissue factor (TF) is a significant risk factor for hepatic metastasis in patients with colorectal cancer (CRC). However, the mechanism by which TF promotes hepatic metastasis in CRC remains elusive. In this study, we first confirmed that TF expression was significantly correlated with lymph node metastasis, hepatic metastasis and TNM staging in clinical CRC samples, and found that TF expression in colon cancer cell lines was correlated with the invasion ability.

Influence of fasting, insulin and glucose on ghrelin in the dorsal vagal complex in rats.

The dorsal vagal complex (DVC) is an important site in which ghrelin plays an orexigenic role. However, the relationship between ghrelin expression in DVC and the energy status of the organism is unclear, as well as the role of the vagus nerve in this process. In this study, ghrelin expression in DVC neurons of rats was detected, then levels of ghrelin expression were observed under the conditions of regular diet, fasting, high blood glucose, low blood glucose, and following subdiaphragmatic vagotomy and vagus nerve electrostimulation.

Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats.

Ethnopharmacological Relevance: Kirenol is a diterpenoid compound purified from the Chinese Herba Siegesbeckiae. Siegesbeckiae has been employed for the treatment of arthritis for centuries, its safety and efficacy are documented through a long history of human use.

Aim Of The Study: To investigate the effects on collagen-induced arthritis (CIA) and anti-inflammatory mechanism of kirenol.

High glucose stimulates TNFα and MCP-1 expression in rat microglia via ROS and NF-κB pathways.

Aim: To investigate whether high glucose stimulates the expression of inflammatory cytokines and the possible mechanisms involved.

Methods: ELISA and real-time PCR were used to determine the expression of the inflammatory factors, and a chemiluminescence assay was used to measure the production of reactive oxygen species (ROS).

Results: Compared to low glucose (10 mmol/L), treatment with high glucose (35 mmol/L) increased the secretion of tumor necrosis factor (TNF)α and monocyte chemotactic protein-1 (MCP-1), but not interleukin (IL)-1β and IL-6, in a time-dependent manner in primary cultured rat microglia.

Ghrelin protects cortical neuron against focal ischemia/reperfusion in rats.

Ghrelin is a novel brain-gut peptide and the endogenous ligand of growth hormone secretagogue receptor 1a (GHSR-1a). Evidences have been shown that ghrelin inhibited cell apoptosis in cardiocytes, endotheliocytes, osteoblasts, and so on. Recently, it was reported that ghrelin inhibited neuronal apoptosis of hypothalamus and hippocampus.

Ghrelin inhibits apoptosis signal-regulating kinase 1 activity via upregulating heat-shock protein 70.

Ghrelin is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), which has been originally isolated from rat stomach. It has been reported that ghrelin inhibited apoptosis in several cells, such as cardiomyocytes, endothelial cells, adipocyte, adrenal zona glomerulosa cells, pancreatic beta-cells, osteoblastic MC3T3-E1 cells, intestinal epithelial cells and hypothalamic neurons. However, it is unknown whether heat-shock protein 70 (HSP70) or apoptosis signal-regulating kinase 1 (ASK1) is the important target molecule which mediates the anti-apoptotic effects of ghrelin.

CART peptide promotes the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor.

The neuropeptide cocaine- and amphetamine-regulated transcript (CARTp) plays a role in various physiological processes. CARTp is highly expressed in rat hippocampus and can promote the survival and differentiation of neurons in primary hippocampal cell cultures. However, little is known about the neurotrophic mechanism of CARTp on the hippocampal neuron.

Ghrelin-containing neuron in cerebral cortex and hypothalamus linked with the DVC of brainstem in rat.

Ghrelin is a newly discovered brain-gut peptide and an endogenous ligand for growth hormone secretagogues receptor (GHS-R). Ghrelin and GHS-R present extensively in central and peripheral tissues such as stomach, brain and other organs of rodent and human, which suggest it has multiple biological effects. It has been reported that ghrelin has significant role in the regulation of energy homeostasis, food intake and appetite.

Role of the central interleukin-1 in stress responses.

The molecules of interleukin-1 (IL-1) system are widely distributed in central nervous system. As a classical pro-inflammatory factor, central IL-1 has diverse biological functions and plays a pivotal role in a number of important physiological and pathophysiological processes. During the past few years, particular attentions have been directed to the stress mediator actions of central IL-1.

[Progress in central interleukin-1 system and its signaling pathway].

Central interleukin-1 (IL-1 ) system is a relatively independent system which is composed of IL-1 and other molecules associated with IL-1 in functions or structures. The knowledge of central IL-1 system in the constitution and function have been extended with the discovery of new members and its function, the extensive and intensive research on intracellular signaling pathways, as well as the relationship among those molecules. This paper reviews the recent findings in the study of central IL-1 system, which comprises the new members, new signaling molecules, new biological functions, and the effects in the processes of physiology and pathophysiology.

Effects of ghrelin on the proliferation and secretion of splenic T lymphocytes in mice.

Ghrelin, a novel gut--brain peptide predominantly produced by the stomach, displays strong growth hormone (GH)-releasing activity mediated by the hypothalamus-pituitary GH secretagogue receptor (GHS-R). Recently, the ghrelin receptor has also been detected in peripheral systems including immune tissues, suggesting that ghrelin may play an important role in the regulation of immune function. In this paper, we assessed the presence and function of the ghrelin receptor in murine splenic T cells.

[Central interleukin-1beta involved in modulation of motor behavior in novelty stress rats].

Objective: To investigate the effect of central interleukin-1beta (IL-1beta) on motor behavioral responses in novelty stress rats.

Methods: The novelty stress was elicited by novel environmental stimuli with novelty stress box. The intracerebrolventricular (ICV) cannula and microinjection were performed with rat brain stereotaxic system.