Acid-sensing ion channel 1a promotes alcohol-associated liver disease in mice via regulating endoplasmic reticulum autophagy.

Alcohol-associated liver disease (ALD) is a hepatocyte dysfunction disease caused by chronic or excessive alcohol consumption, which can lead to extensive hepatocyte necrosis and even liver failure. Currently, the pathogenesis of ALD and the anti-ALD mechanisms have not been fully elucidated yet. In this study, we investigated the effects of endoplasmic reticulum autophagy (ER-phagy) in ALD and the role of acid-sensing ion channel 1a (ASIC1a) in ER stress-mediated ER-phagy.

LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury.

Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that have little or no coding potential. LncRNAs function as key regulators in diverse physiological and pathological processes. However, the roles of lncRNAs in lipopolysaccharide (LPS)-induced acute liver injury (ALI) are still elusive.

Hepatocyte-derived MANF mitigates ethanol-induced liver steatosis in mice via enhancing ASS1 activity and activating AMPK pathway.

Hepatic steatosis plays a detrimental role in the onset and progression of alcohol-associated liver disease (ALD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved protein related to the unfolded protein response. Recent studies have demonstrated that MANF plays an important role in liver diseases.

Targeted delivery of edaravone by liposomes for the treatment of ischemic stroke.

To construct an edaravone-encapsulated liposomes (EDV-LIPs) formulation against acute ischemic stroke. EDV-LIPs were prepared by the film dispersion method. The biosafety was evaluated both and by flow cytometry and the histological staining method.

An Alternatively Spliced Variant of METTL3 Mediates Tumor Suppression in Hepatocellular Carcinoma.

Many post-transcriptional mRNA processing steps play crucial roles in tumorigenesis and the progression of cancers, such as N6-methyladenosine (mA) modification and alternative splicing. Upregulation of methyltransferase-like 3 (METTL3), the catalytic core of the mA methyltransferase complex, increases mA levels and results in significant effects on the progression of hepatocellular carcinoma (HCC). However, alternative splicing of METTL3 has not been fully investigated, and the functions of its splice variants remain unclear.

Prp5-Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription.

Transcription and pre-mRNA splicing are coupled to promote gene expression and regulation. However, mechanisms by which transcription and splicing influence each other are still under investigation. The ATPase Prp5p is required for pre-spliceosome assembly and splicing proofreading at the branch-point region.

Folic acid modified FeO nanoclusters by a one-step ultrasonic technique for drug delivery and MR imaging.

Multifunctional nanoclusters based on FeO nanoparticles for magnetic resonance imaging (MRI) and drug delivery are reported here. At first, oleic acid (OA)-coated FeO nanoparticles were prepared. Then block copolymer Pluronic F127 or folic acid (FA) conjugated-Pluronic F127 was used to modify the hydrophobic nanoparticles to become hydrophilic FeO@F127 nanoclusters facile ultrasonic treatment.

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway.

Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms.

The oncogenic impact of RNF2 on cell proliferation, invasion and migration through EMT on mammary carcinoma.

Mammary carcinoma (MC) is one of most common malignancy in women, and ring finger protein 2 (RNF2) possesses various roles in vast human tumors. In MC tissues as well as in cell lines RNF2 exhibited high expression, had significant association with tumor size, lymph node status, TNM stage, patients' poor survival, and promoted cell proliferation, colony formation, cell migration and invasion of MC cell lines which was mediated by downregulation of E-cadherin protein. These data reveal that RNF2 protein plays a vital role in the development of MC and may be a potential therapy target of MC.

Dexmedetomidine Promotes SH-SY5Y Cell Resistance Against Impairment of Iron Overload by Inhibiting NF-κB Pathways.

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further.

Facile fabrication of water-dispersible nanocomposites based on hexa--hexabenzocoronene and FeO for dual mode imaging (fluorescent/MR) and drug delivery.

The facile fabrication of multifunctional nanocomposites (FeO/HBC@F127) consisting of superparamagnetic FeO nanoparticles and fluorescent organic hexa--hexabenzocoronene (HBC) molecules incorporated in block copolymer diacylphospholipid-polyethyleneglycol F127 have been demonstrated for dual mode imaging (fluorescent/MR) and drug delivery. The obtained nanocomposites were water-dispersible, stable and biocompatible, as confirmed by dynamic light scattering (DLS) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Relativity measurements showed a relaxivity ( ) of 214.

Xanthatin induces apoptosis by activating endoplasmic reticulum stress in hepatoma cells.

Hepatocellular carcinoma (HCC) has high incidence and mortality in patients with chronic liver diseases worldwide. However, there are limited chemotherapeutic agents for HCC in clinic. Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancers, but little is known about its effects on HCC and the underlying mechanism.

Activator protein‑1 is a novel regulator of mesencephalic astrocyte‑derived neurotrophic factor transcription.

Mesencephalic astrocyte‑derived neurotrophic factor (MANF) is an endoplasmic reticulum stress‑inducible protein, which has been suggested to be upregulated in inflammatory diseases; however, how inflammation regulates its transcription remains unclear. Activator protein‑1 (AP‑1), which is a transcription factor complex composed of c‑Fos and c‑Jun, is activated during the inflammatory process. The present study aimed to investigate whether the AP‑1 complex regulates MANF transcription.

Mesencephalic Astrocyte-Derived Neurotrophic Factor Prevents Traumatic Brain Injury in Rats by Inhibiting Inflammatory Activation and Protecting the Blood-Brain Barrier.

Background: Our previous studies have shown that mesencephalic astrocyte-derived neurotrophic factor (MANF) provides a neuroprotective effect against ischemia/reperfusion injury and is also involved in inflammatory disease models. This study investigates the potential role and mechanism of MANF in acute brain damage after traumatic brain injury (TBI).

Methods: The model of TBI was induced by Feeney free falling methods with male Sprague-Dawley rats.

Lactoferrin modified graphene oxide iron oxide nanocomposite for glioma-targeted drug delivery.

Targeting delivery of drugs in a specific manner represents a potential powerful technology in gliomas. Herein, we prepared a multifunctional targeted delivery system based on graphene oxide (GO) that contains a molecular bio-targeting ligand and superparamagnetic iron oxide nanoparticles on the surface of GO for magnetic targeting. Superparamagnetic FeO nanoparticles was loaded on the surface of GO via chemical precipitation method to form GO@FeO nanocomposites.

MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats.

As an endoplasmic reticulum (ER) stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI) technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury.

Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.

Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2.

Activated macrophage-like synoviocytes are resistant to endoplasmic reticulum stress-induced apoptosis in antigen-induced arthritis.

Objective: To explore the characteristic expression of endoplasmic reticulum (ER) stress protein in antigen-induced arthritis models and the role of ER stress in arthritis.

Methods: Effective animal models of rheumatoid arthritis in rabbits and rats were induced by methylated bovine serum albumin and Freund's complete adjuvant. Pathological changes were assessed by magnetic resonance imaging and histological analysis.

Peroxisome proliferator-activated receptor-α activation protects against endoplasmic reticulum stress-induced HepG2 cell apoptosis.

Live ischemia-reperfusion injury is associated with endoplasmic reticulum (ER) stress-induced apoptosis. Activation of peroxisome proliferator-activated receptor-α (PPARα) may inhibit hepatocyte apoptosis induced by oxidative stress and protect against liver injury. This study aimed to investigate the effects of PPARα activation, through a specific agonist, on ER stress-induced apoptosis in human liver hepatocellular carcinoma (HepG2) cells.

Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection.

Cerebral ischemia-induced accumulation of unfolded proteins in vulnerable neurons triggers endoplasmic reticulum (ER) stress. Arginine-rich, mutated in early stage tumors (ARMET) is an ER stress-inducible protein and upregulated in the early stage of cerebral ischemia. The purposes of this study were to investigate the characteristics and implications of ARMET expression induced by focal cerebral ischemia.

Enhanced expression of the decoy receptor IL-13Ralpha2 in macrophages of Schistosoma japonicum-infected mice.

Background: Type 2 cytokine interleukin (IL)-13 and its decoy receptor, IL-13 receptor (R) alpha2 appear to play a major role in tissue fibrosis of schistosomiasis and asthma. IL-13 is a key regulator of the extracellular matrix (ECM). It is known to signal to cells by binding to the IL-13Ralpha1, which then heterodimerizes with IL-4Ralpha.

[Expression of a novel metastasis-inducing protein human anterior gradient-2 (AGR2) in breast cancer and its clinical and prognostic significance].

Objective: To investigate the expression of a novel metastasis-inducing protein human anterior gradient-2 (AGR2) in breast cancer and its clinical and prognostic significance.

Methods: AGR2 expression was assessed in 160 cases of breast cancer and 20 cases of benign breast diseases by immunohistochemistry using tissue chip technology. In addition the expression of ERa, PR and c-erbB-2 in breast cancer was also evaluated.