Monocyte chemoattractant protein-1, transforming growth factor-β1, nerve growth factor, resistin and hyaluronic acid as serum markers：comparison between recurrent acute and chronic pancreatitis

BACKGROUND： Diagnostic parameters that can predict the presence of chronic pancreatitis（CP） in patients with recurrent pain due to pancreatitis would help to direct appropriate therapy. This study aimed to compare the serum levels of monocyte chemoattractant protein-1（MCP-1）, transforming growth factor-β1（TGF-β1）, nerve growth factor（NGF）, resistin and hyaluronic acid（HA） in patients with recurrent acute pancreatitis（RAP） and CP to assess their ability to differentiate the two conditions.METHODS： Levels of serum markers assessed by enzymelinked immunosorbent assay（ELISA） were prospectively compared in consecutive patients with RAP, CP and in controls and stepwise discriminant analysis was performed to identify the markers differentiating RAP from CP.RESULTS： One hundred and thirteen consecutive patients（RAP=32, CP=81） and 78 healthy controls were prospectively enrolled. The mean（SD） age of the patients was 32.0（14.0）years; 89（78.8%） were male. All markers were significantly higher in CP patients than in the controls（P〈0.001）; MCP-1NGF and HA were significantly higher in RAP patients than in the controls（P〈0.001）. Stepwise discriminant analysis showed significant difference（P=0.002） between RAP and CP for resistin with an accuracy of 61.9%, discriminant scores of ≤-0.479 and ≥0.189 indicating RAP and CP, respectively. The other markers had no differential value between RAP and CP.CONCLUSION： Serum resistin is a promising marker to differentiate between RAP and CP and needs validation in future studies, especially in those with early CP.

The HMGB1 signaling pathway activates the inflammatory response in Schwann cells

Schwann cells are not only myelinating cells, but also function as immune cells and express numerous innate pattern recognition receptors, including the Toll-like receptors. Injury to peripheral nerves activates an inflammatory response in Schwann cells. However, it is unclear whether specific endogenous damage-associated molecular pattern molecules are involved in the inflammatory response following nerve injury. In the present study, we demonstrate that a key damage-associated molecular pattern molecule, high mobility group box 1（HMGB1）, is upregulated following rat sciatic nerve axotomy, and we show colocalization of the protein with Schwann cells. HMGB1 alone could not enhance expression of Toll-like receptors or the receptor for advanced glycation end products（RAGE）, but was able to facilitate migration of Schwann cells. When Schwann cells were treated with HMGB1 together with lipopolysaccharide, the expression levels of Toll-like receptors and RAGE, as well as inflammatory cytokines were upregulated. Our novel findings demonstrate that the HMGB1 pathway activates the inflammatory response in Schwann cells following peripheral nerve injury.

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

This study investigated whether bone marrow mesenchymal stem cell（BMSC） transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs（h BMSCs） were injected into the tail vein. Fourteen days later, we found that h BMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor（s EPOR） was injected into the lateral ventricle, and on the next 13 consecutive days. s EPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the h BMSCs ＋ s EPOR group than in the h BMSCs ＋ heat-denatured s EPOR group. The adhesive-removal test result and the modified Neurological Severity Scores（m NSS） were lower in the h BMSCs ＋ s EPOR group than in the heat-denatured s EPOR group. The adhesive-removal test result and m NSS were similar between the h BMSCs ＋ heat-denatured s EPOR group and the h BMSCs ＋ s EPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.