ER-residential Nogo-B accelerates NAFLD-associated HCC mediated by metabolic reprogramming of oxLDL lipophagy.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity.

Cardioprotective effects of monocyte locomotion inhibitory factor on myocardial ischemic injury by targeting vimentin.

Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide produced by Entamoeba histolytica, has anti-inflammatory function and protective effect on ischemic stroke. In this study, we evaluated the effect of MLIF on myocardial ischemia. Mice were subjected to ischemia/reperfusion by occlusion of the left anterior descending artery (LAD).

EF1A1/HSC70 Cooperatively Suppress Brain Endothelial Cell Apoptosis via Regulating JNK Activity.

Aims: In our previous study, eEF1A1 was identified to be a new target for protecting brain ischemia injury, but the mechanism remains largely unknown. In this study, we screened the downstream cellular protein molecules interacted with eEF1A1 and found mechanism of eEF1A1 in brain ischemia protection.

Methods And Results: Through co-immunoprecipitation and mass spectrometry for searching the interaction of proteins with eEF1A1 in bEnd3 cells, HSC70 was identified to be a binding protein of eEF1A1, which was further validated by Western blot and immunofluorescence.

MLIF Alleviates SH-SY5Y Neuroblastoma Injury Induced by Oxygen-Glucose Deprivation by Targeting Eukaryotic Translation Elongation Factor 1A2.

Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide, has been shown to exert potent anti-inflammatory effects in ischemic brain injury. In this study, we investigated the neuroprotective action of MLIF against oxygen-glucose deprivation (OGD)-induced injury in human neuroblastoma SH-SY5Y cells. MTT assay was used to assess cell viability, and flow cytometry assay and Hoechst staining were used to evaluate apoptosis.

Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response.

Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly.

Determination of an unstable pentapeptide, monocyte locomotion inhibitory factor, in dog blood by LC-MS/MS: application to a pharmacokinetic study.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and established for the quantitative determination of monocyte locomotion inhibitory factor, a pentapeptide (Met-Gln-Cys-Asn-Ser) produced by Entamoeba histolytica in axenic culture, in dog blood. The main challenge was the chemical and enzymatic instability of the peptide which was successfully overcome. After a simple protein precipitation, MLIF was separated from AS-5 (Met-Gln-Gly-Asn-Ser), acted as an internal standard, on a Gemini C18 column (5 μm, 50 mm × 4.

miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis.

The tumour stroma is an active participant during cancer progression. Stromal cells promote tumour progression and metastasis through multiple mechanisms including enhancing tumour invasiveness and angiogenesis, and suppressing immune surveillance. We report here that miR-126/miR-126(*), a microRNA pair derived from a single precursor, independently suppress the sequential recruitment of mesenchymal stem cells and inflammatory monocytes into the tumour stroma to inhibit lung metastasis by breast tumour cells in a mouse xenograft model.

3β,5α,6β-Oxygenated sterols from the South China Sea gorgonian Muriceopsis flavida and their tumor cell growth inhibitory activity and apoptosis-inducing function.

Three new polyhydroxysterols, named muriflasteroids A-C (1-3) were isolated from the South China Sea gorgonian Muriceopsis flavida, together with sixteen known analogs, cholest-3β,5α,6β-triol,3β-acetate (4), 5α-methoxycholest-3β,6β-diol (5), (22E)-cholest-22-en-3β,5α,6β-triol (6), cholest-3β,5α,6β-triol (7), (22E)-24-norcholest-22-en-3β,5α,6β-triol (8), (22E,24S)-ergost-22-en-3β,5α,6β-triol (9), ergost-24(28)-en-3β,5α,6β-triol (10), (22E)-cholest-7,22-dien-3β,5α,6β-triol (11), cholest-7-en-3β,5α,6β-triol (12), (22E)-24-norcholest-7,22-dien-3β,5α,6β-triol (13), ergost-7,24(28)-dien-3β,5α,6β-triol (14), (22E,24R)-ergost-7,22-dien-3β,5α,6β-triol (15), (22E)-cholest-22-en-1β,3β,5α,6β-tetrol (16), (22E)-24-norcholest-22-en-1β,3β,5α,6β-tetrol (17), cholest-1β,3β,5α,6β-tetrol (18), and (24ξ)-ergost-1β,3β,5α,6β-tetrol (19). The structures of the new compounds were elucidated by detailed spectroscopic analysis in combination with comparison of reported data. All the compounds are reported for the first time from the animal.

Therapeutic effects of astragaloside IV on myocardial injuries: multi-target identification and network analysis.

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb used for cardiovascular diseases (CVD). In this work, we investigated the therapeutic mechanisms of AGS-IV at a network level by computer-assisted target identification with the in silico inverse docking program (INVDOCK). Targets included in the analysis covered all signaling pathways thought to be implicated in the therapeutic actions of all CVD drugs approved by US FDA.

MicroRNA-1 inhibits proliferation of hepatocarcinoma cells by targeting endothelin-1.

Aims: MicroRNA-1 (miR-1) has been demonstrated as a tumor-suppressive miRNA, which shows a down-regulated pattern in several human malignancies including hepatocellular carcinoma (HCC). However, the pathophysiologic roles of miR-1 and their mechanisms in HCC tumorigenesis are still not totally elucidated.

Main Methods: Pre-miR-1 was cloned into pSuper plasmid to overexpress the miR-1 in hepatoma cells.

CD133(+)CXCR4(+) colon cancer cells exhibit metastatic potential and predict poor prognosis of patients.

Background: Colorectal cancer (CRC), which frequently metastasizes to the liver, is one of the three leading causes of cancer-related deaths worldwide. Growing evidence suggests that a subset of cells exists among cancer stem cells. This distinct subpopulation is thought to contribute to liver metastasis; however, it has not been fully explored in CRC yet.

A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway.

Background And Purpose: Ischemic stroke is a major cause of death worldwide but lacks viable treatment or treatment targets. Monocyte locomotion inhibitory factor (MLIF) is a small heat-stable pentapeptide produced by Entamoeba histolytica in axenic culture, which is supposed to protect the brain from ischemic injury; the mechanism, however, remains unknown. In this study, we further investigated the mechanism underlying the protective role of MLIF in brain ischemia.

Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway.

Objective: Stroke is a leading cause of mortality and disability. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme in mammalian nicotinamide adenine dinucleotide (NAD)(+) biosynthesis and contributes to cell fate decisions. However, the role of Nampt in brain and stroke remains to be investigated.

MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells.

Background: Endothelin-1 (ET-1) is considered to be one of the most potent and long-lasting vasoconstrictive peptides, but the mechanisms on the regulation of ET-1 expression are not fully understood.

Method And Results: In this study, we found that microRNA (miR)-125a-5p and miR-125b-5p are highly expressed in vascular endothelial cells (VECs), which can be regulated by oxidized low-density lipoprotein (oxLDL). To explore the function of miR-125a/b-5p in VECs, we examined the roles of potential targets of miR-125a/b-5p that could influence endothelium function.

The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway.

Intracellular nucleic acid sensors detect microbial RNA and DNA and trigger the production of type I interferon. However, the cytosolic nucleic acid-sensing system remains to be fully identified. Here we show that the cytosolic nucleic acid-binding protein LRRFIP1 contributed to the production of interferon-beta (IFN-beta) induced by vesicular stomatitis virus (VSV) and Listeria monocytogenes in macrophages.

NDRG2 induced by oxidized LDL in macrophages antagonizes growth factor productions via selectively inhibiting ERK activation.

During atherogenesis, macrophage foam cells produce prodigious growth factors, cytokines, and chemokines, which play the central roles in inflammatory process in atherosclerotic plaque formation. In the present study, we identified a new protein marker, N-Myc downstream-regulated protein 2 (NDRG2), which is significantly up-regulated in oxidized low density lipoprotein (oxLDL) treated macrophages and in human atherosclerotic plaques. Over-expression and siRNA knockdown studies showed that NDRG2 is a negative regulator of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) productions in macrophages.

Lentiviral vector-mediated siRNA knockdown of SR-PSOX inhibits foam cell formation in vitro.

Aim: To investigate the expression of scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXC chemokine ligand 16 (CXCL16) in the human monocyte-derived cell line THP-1, and the effect of lentiviral vectors for the stable delivery of SR-PSOX/CXCL16 short hairpin RNA on foam cell formation.

Methods: A lentiviral expression vector containing enhanced green fluorescence protein (GFP) and SR-PSOX small interfering RNA (siRNA) (Lenti-SR-PSOXsi), or the control siRNA (Lenti-NC) gene was constructed. A human monocyte-derived cell line THP-1 was transfected with a different multiplicity of infection (MOI) of Lenti-SR-PSOXsi or Lenti-NC, and cultured to obtain stably-transfected THP- 1KD and THP-1NC cells.

Adenovirus viral interleukin-10 inhibits adhesion molecule expressions induced by hypoxia/reoxygenation in cerebrovascular endothelial cells.

Aim: To investigate the effects of recombinant adenovirus encoding viral interleukin-10 (vIL-10), a potent anti-inflammatory cytokine, on adhesion molecule expressions and the adhesion rates of leukocytes to endothelial cells in cerebrovascular endothelial cells injured by hypoxia/reoxygenation (H/R).

Methods: A recombinant adenovirus expressing vIL-10 (Ad/vIL-10 (or the green fluorescent protein (Ad/GFP) gene was constructed. A cerebrovascular endothelial cell line bEnd.

Adenoviral gene transfer of viral interleukin-10 protects cerebrovascular impairment induced by lysophosphatidylcholine.

Cerebrovascular disease is a significant cause of morbidity and mortality in the world. Inflammatory processes induce several pathological responses such as atherosclerosis, which have fundamental roles in stroke in the etiology of ischemic cerebrovascular disease and the pathophysiology of cerebral ischemia. Viral interleukin-10 (vIL-10), a potential anti-inflammatory cytokine, has been studied extensively.

Effects of Ginkgo biloba extract on expressions of IL-1beta, TNF-alpha, and IL-10 in U937 foam cells.

This study is to investigate the protein and mRNA expressions of pro-inflammatory and anti-inflammatory cytokines in U937 foam cells and effects of Ginkgo biloba extract (GbE) on the cytokines. U937 cells were cultured with different concentrations of GbE (0.1, 1, and 10 microg x L(-1)), and stimulated by 100 mg x L(-1) oxidized low density lipoprotein (ox-LDL) for 24 h.

Protective effects of Guizhi-Fuling-Capsules on rat brain ischemia/reperfusion injury.

Previous studies revealed that Guizhi-Fuling-Capsules (GZFLC), a traditional Chinese medical (Kampo) formulation composed of five kinds of medicinal plants, Cinnamomum cassia BLUME (Cinnamomi Cortex), Paeonia lactiflora PALL. (Peonies Radix), Paeonia suffruticosa ANDREWS (Moutan Cortex), Prunus persica BATSCH (Persicae Semen), and Poria cocos WOLF (Hoelen), exerts a protective effect against vascular injury and has a protective effect against glutamate- or nitro oxide-mediated neuronal damage. In the present study, the effect of GZFLC in a rat in vivo model of focal cerebral ischemia and reperfusion was investigated.

Modulation of signal transducers and activators of transcription (STAT) factor pathways during focal cerebral ischaemia: a gene expression array study in rat hippocampus after middle cerebral artery occlusion.

1. Signal transducers and activators of transcription (STAT) factors are a family of transcription factors that mediate intracellular signalling initiated at cytokine cell surface receptors and transmitted to the nucleus. In the present study, we determined the global changes in STAT gene expression in the hippocampus of rats after focal cerebral ischaemia and reperfusion using microarray analysis.

Regulation of Nogo-B expression in the lesion of aortic aneurysms.

1. Our previous study showed that Nogo-B was highly expressed in endothelial cells and downregulated in endothelial cells following induction by lysophosphatidylcholine, which contributed to atherosclerotic lesions. However, the role of Nogo-B in the development of aortic aneurysms remains unclear.

Timosaponin B-II improves memory and learning dysfunction induced by cerebral ischemia in rats.

Sapogenins from Anemarrhenae asphodeloides was reported to improve the learning and memory abilities. In this study, we investigated the effect of Timosaponin B-II(TB-II), a purified extract from A. asphodeloidesb on rat vascular dementia (VD) produced by transient (2h) middle cerebral artery occlusion.

RNA interference for HIF-1alpha inhibits foam cells formation in vitro.

Macrophage-derived foam cells in atherosclerotic lesions are generally thought to play a major role in the pathology of the disease. Hypoxia-inducible factor-1alpha (HIF-1alpha) was recently found to play an important role in atherosclerosis. Here we applied RNA interference to study the role of HIF-1alpha in foam cell formation in vitro.