Annexin A1 Mimetic Peptide AC2-26 Inhibits Sepsis-induced Cardiomyocyte Apoptosis through LXA4/PI3K/AKT Signaling Pathway

The aim of the present study was to explore the effects of annexin A1(ANXA1) mimetic peptide AC2-26 on sepsis-induced cardiomyocyte apoptosis in vivo and in vitro and the underlying mechanisms.In the in vivo study,a rat septic model was established by the cecal ligation and puncture (CLP).The rats were divided into control group,sepsis group and AC2-26 group.The rats in the AC2-26 group were intraperitoneally injected with AC2-26(1mg/kg)2h before CLP,and those in the control group and sepsis group were injected with the same volume of normal saline.The myocardial tissue was examined by hematoxylin and eosin (HE)staining and transmission electron microscopy (TEM).Furthermore,myocardial apoptosis was measured by terminal dUTP nick end-labeling (TUNEL)assay.In the in vitro study,H9C2cells were cultured and divided into three groups:control group,in which cells were only given the basic culture medium;LPS group,in which cells were treated with 10μg/mL LPS;AC2-26 group,in which cells were treated with 0.5μmol/L AC2-262h before 10μg/mL LPS was given.The apoptosis of H9C2 cells was detected by flow cytometry.The levels of lipoxin A4 receptor (LXA4),phosphoinositide3-kinase (PI3K)and protein kinase B (PKB or AKT)protein were measured by Western blotting, the activity of NF-KB and the level of TNF-α by ELISA and the activities of caspase-3/8by using the caspase activity kits.The in vivo study showed that the myocardial pathological damage and myocardial ultrastructural damage were significantly alleviated and the myocardial apoptosis significantly decreased in the AC2-26 group as compared with the sepsis group (P<0.05 for all). The in vivo study revealed that the apoptosis of H9C2 cells was profoundly ameliorated in the AC2-26 group relative to the sepsis group (P<0.05).The protein expression levels of LXA4 were significantly up-regulated,and those of PI3K and AKT prominently down-regulated in the AC2-26 group when compared with those in the LPS group (P<0.05 for all).The activity of NF-κB was greatly inhibited and the level of TNF-α markedly decreased in the AC2-26 group as compared with those in the LPS group (P<0.05 for all).AC2-26 treatment also significantly suppressed the activities of caspase-3/8 in H9C2 cells.In conclusion,these findings suggest that AC2-26 may alleviate the sepsis-induced cardiomyocyte apoptosis in vivo and in vivo through the LXA4/PI3K/ AKT signaling pathway.

Primary mucosa-associated lymphoid tissue lymphoma in the midbrain:A case report

BACKGROUND Primary non-dural central nervous system mucosa-associated lymphoid tissue(MALT)lymphoma is a rare indolent B-cell lymphoma,with only a few reported cases worldwide.CASE SUMMARY A 33-year-old man presented with a 5-mo history of left blepharoptosis and a 4-mo history of right limb numbness and weakness.Magnetic resonance imaging showed a significantly enhanced mass in the left midbrain.Subsequent positron emission tomography revealed that the lesion had increased glucose uptake.A stereotactic robotic biopsy supported a diagnosis of MALT lymphoma.Then he was treated with radiation therapy(30Gy/15F),which resulted in complete remission.We also review the literature on brain parenchymal-based MALT lymphoma,including the clinical presentation,treatment options,and outcomes.CONCLUSION Although there is no consensus on the optimal treatment for this rare disease,patients can respond well when treated with radiotherapy alone.

Disseminated intravascular coagulation as an unusual feature of hypereosinophilic syndrome

To the Editor:A 66-year-old man complaining abdominal pain and bloating for 1 month was admitted to the Department of General Surgery of Xuanwu Hospital,Beijing,China.The patient had a normal body temperature and did not have symptoms such as nausea,diarrhea,or bone/joint pain.He had no history of allergies,no particular past medical or family history.He had taken no medications that could cause eosinophilia.No parasites were found in the stool.Abdominal computerized tomography(CT)scan showed thickening of the stomach wall and peristaltic stiffness with the swelling of the surrounding lymph nodes,indicating possibility of gastric cancer[Figure 1A].Biopsy from gastroscopy showed a massive eosinophil infiltration of the stomach wall[Figure 1B].Meanwhile,blood test showed white blood cell(WBC)count was elevated to 11.09×10^9/L,eosinophils were elevated to 2.53×10^9/L,hemoglobin 160 g/L,and platelet 269×10^9/L.A bone marrow biopsy showed normal cellularity with increased eosinophils.breakpoint cluster region/c-abl oncogene 1,non-receptor tyrosine kinase and Fip1-like1 and platelet-derived growth factor receptor alpha fusion genes were not detected.He was diagnosed as hypereosinophilic syndrome(HES)and treated with corticosteroids(prednisone 20 mg,oral,twice per day).The patient’s abdominal pain and bloating symptoms gradually reduced,and the total number of eosinophils was back to normal in 2 weeks.The follow-up gastroscopy performed at 3 and 6 months after treatment showed normal stomach wall[Figure 1C and Figure 1D].The corticosteroid was tapered and stopped after 8 months treatment.