Rebamipide attenuates alcohol-induced gastric epithelial cell injury by inhibiting endoplasmic reticulum stress and activating autophagy-related proteins.

Apoptosis of gastric mucosa epithelial cells caused by the abuse of alcohol produces injury to the gastric mucosa and acute or chronic gastritis. In recent years, it has been demonstrated that endoplasmic reticulum stress (ERS) is involved in mediating apoptosis, and that autophagy has a protective effect on survival of cells. Rebamipide is a gastric mucosal protectant used to treat gastritis and stomach ulcers. In this study, ethanol was used to overstimulate gastric mucosal epithelial cells and gavage mice. It was found that 400 mmol/L ethanol overstimulation could activate ERS and induce apoptosis (control vs ethanol treatment: 15.24 ± 1.10% vs 33.80 ± 1.47%, P < 0.001); but could not activate the autophagy pathway. Rebamipide intervention can reduce apoptosis rate (20.78 ± 1.63%), and significantly inhibit the activation of ERS and the active ERS-related downstream NF-κB signaling pathway. Additionally, rebamipide can activate the expression of autophagy-related pathway proteins and increase the expression of p-ERK and p-p38. In addition, rebamipide relieved oxidative stress after an ethanol insult. In the present study, molecular evidence of rebamipide inhibition of ERS and regulation of the protein expression of autophagy pathway components were produced using an acute alcoholic gastric mucosal injury model. This model provides a new approach for investigating the effects of rebamipide treatment on alcohol-induced gastric mucosal damage.

Ubiquitin-specific protease USP34 controls osteogenic differentiation and bone formation by regulating BMP2 signaling.

The osteogenic differentiation of mesenchymal stem cells (MSCs) is governed by multiple mechanisms. Growing evidence indicates that ubiquitin-dependent protein degradation is critical for the differentiation of MSCs and bone formation; however, the function of ubiquitin-specific proteases, the largest subfamily of deubiquitylases, remains unclear. Here, we identify USP34 as a previously unknown regulator of osteogenesis. The expression of USP34 in human MSCs increases after osteogenic induction while depletion of USP34 inhibits osteogenic differentiation. Conditional knockout of Usp34 from MSCs or pre-osteoblasts leads to low bone mass in mice. Deletion of Usp34 also blunts BMP2-induced responses and impairs bone regeneration. Mechanically, we demonstrate that USP34 stabilizes both Smad1 and RUNX2 and that depletion of Smurf1 restores the osteogenic potential of Usp34-deficient MSCs in vitro Taken together, our data indicate that USP34 is required for osteogenic differentiation and bone formation.

Characteristics and response of mouse bone marrow derived novel low adherent mesenchymal stem cells acquired by quantification of extracellular matrix.

PURPOSE: The aim of present study was to identify characteristic and response of mouse bone marrow (BM) derived low-adherent bone marrow mesenchymal stem cells (BMMSCs) obtained by quantification of extracellular matrix (ECM). MATERIALS AND METHODS: Non-adherent cells acquired by ECM coated dishes were termed low-adherent BMMSCs and these cells were analyzed by in vitro and in vivo methods, including colony forming unit fibroblast (CFU-f), bromodeoxyuridine (BrdU), multi-potential differentiation, flow cytometry and transplantation into nude mouse to measure the bone formation ability of these low-adherent BMMSCs. Titanium (Ti) discs with machined and anodized surfaces were prepared. Adherent and low-adherent BMMSCs were cultured on the Ti discs for testing their proliferation. RESULTS: The amount of CFU-f cells was significantly higher when non-adherent cells were cultured on ECM coated dishes, which was made by 7 days culturing of adherent BMMSCs. Low-adherent BMMSCs had proliferation and differentiation potential as adherent BMMSCs in vitro. The mean amount bone formation of adherent and low-adherent BMMSCs was also investigated in vivo. There was higher cell proliferation appearance in adherent and low-adherent BMMSCs seeded on anodized Ti discs than machined Ti discs by time. CONCLUSION: Low-adherent BMMSCs acquired by ECM from non-adherent cell populations maintained potential characteristic similar to those of the adherent BMMSCs and therefore could be used effectively as adherent BMMSCs in clinic.

Helicobacter pylori CagA and gastric carcinogenesis.

OBJECTIVES: This study aimed to demonstrate the tyrosine phosphorylation motif (TPM) and 3' region structure of the Helicobacter pylori CagA gene as well as its SHP-2 binding activity in AGS cells and relation to gastric carcinogenesis. METHODS: Sixteen clinical isolate H. pylori strains from eight duodenal ulcer and eight gastric adenocarcinoma patients were studied for CagA repeat sequence EPIYA motifs, C-terminal structure, and western blot analysis of CagA protein expression, translocation, and SHP-2 binding in AGS cells. RESULTS: Except for strain 547, all strains from the gastric adenocarcinoma patients were positive for CagA by PCR and had three EPIYA copy motifs. Western blotting showed that all strains were positive for CagA protein expression (100%), CagA protein translocation (100%), and SHP-2 binding (100%). CagA protein expression was significantly higher in the gastric adenocarcinoma patients than in the duodenal ulcer patients (P=0.0023). CagA protein translocation and SHP-2 binding in the gastric adenocarcinoma patients were higher than those in the duodenal ulcer patients, but no significant differences were found between the two groups (P=0.59, P=0.21, respectively). CONCLUSIONS: The TPMs and 3' region structures of the H. pylori CagA gene in the duodenal ulcer and gastric adenocarcinoma patients have no significant differences.

[Tumor-like inflammatory demyelinating diseases of the central nervous system with relapse onset: a case report and review].

Here we report the clinical, radiological and neuropathological findings of a patient with tumor-like inflammatory demyelinating diseases of the central nervous system.The patient was a 51-year-old man with a four-month history of inflammatory pseudotumor and no other significant medical history, who presented to our hospital recurrent relapse numbness and weakness of his right extremities, dysarthria and memory deterioration. Brain magnetic resonance imaging(MRI) showed mass focal lesion in white matter of left parietal lobes. The biopsy showed numerous infiltrating macrophages and lymphocytes within the perivascular. The patient responded clinically to corticosteroid and intravenous immunoglobulin(IVIG) therapy. According to the results of the biopsy and the MRI , a diagnosis of inflammatory pseudotumor of the central nervous system was made. The vascular dysfunction may act in the pathogenesis of inflammatory pseudotumor of the central nervous system.

[The clinical and pathological characteristics of a patient with glycogen storage disease IV].

OBJECTIVE: To report the clinical and pathological characteristics of one patient with glycogen storage disease IV (Anderson disease). METHODS: The patient was received detailed clinical examinations, ultrasound, electromyography, head MRI and muscle biopsy. RESULTS: The onset of the 22 years old male patient was 7 yrs. The main symptoms were intolerance and fatigue in proximal limbs muscular movement, cardiopalmus by chance. Abdominal ultrasound examinations showed cirrhosis, portal hypertension, splenomegaly. Echocardiogram showed left ventricular myohypertrophia, mild mitral and tricuspid valve insufficiency. Electrophysiology study revealed widespread myogenic changes. Cranial MRI, MRA and MRS were normal. Muscle biopsy showed basophilic intracytoplasmic material in a lot of fibers deposits, which was intensively PAS-positive material and partially resistant to diastase digestion. In the electron microscope, the storage material consisted of filamentous and finely granular material. CONCLUSIONS: There was the first case of glycogen storage disease IV reported in our country, mainly involved skeletal muscle, liver, spleen and cardiac muscle.

[Rheumatoid leptomeningitis: a case report and literature review].

To report the clinical, radiological and neuropathological findings of a patient with rheumatoid meningitis. The patient was a 71-year-old Chinese man with a two-year history of rheumatoid arthritis and no other significant medical history, who presented to our hospital recurrent weakness of his left extremities, dysarthria and a continuous bilateral hand tremor. Cerebrospinal fluid (CSF) and serum examinations were normal apart from a mildly raised serum perinuclear antineutrophil cytoplasmic autoantibody (p-ANCA). Brain magnetic resonance imaging (MRI) showed leptomeningeal enhancement in both frontal and parietal lobes, in addition to several old white matter infarcts. Meningeal biopsy showed numerous infiltrating macrophages and lymphocytes within the leptomeninges. The patient responded clinically and radiologically to corticosteroid and cyclophosphamide therapy. The patient subsequently developed herpes zoster over his left chest as a complication of his immunosuppressive treatment. His cyclophosphamide was ceased and intravenous immunoglobulin (IVIG) therapy was commenced, with good clinical response to both the herpes zoster and meningitis. According to the result of the biopsy, aseptic meningitis was considered the MRI results and the patient's clinical history were given, and a diagnosis of rheumatoid meningitis was made. The patient was p-ANCA positive. Although there was no evidence for cerebral vasculitis on biopsy, it remains a possibility that the patient's recurrent minor cerebral infarcts visible on MRI were vasculitic in nature.