Background This study attempted to provide the effects and mechanisms of two cannabinoids, O‐1602 and cannabidiol (CBD), on colonic motility of 2,4,6‐trinitro‐benzene sulfonic acid (TNBS) colitis. Methods TNBS was used to induce the model of motility disorder. G protein‐coupled receptor 55 (GPR55) expression was detected using real‐time PCR and immunohistochemistry in colon. Pro‐inflammatory cytokines and myeloperoxidase were also measured. The colonic motility was measured by upper GI transit in vivo and recorded using electrical stimulation organ bath technique in vitro. Freshly isolated smooth muscle from the rat colon were applied to determine the membrane potential and Ca2+‐ATPase activity, respectively. Key Results CBD or O‐1602 separately improved inflammatory conditions significantly in TNBS‐induced colitis rats. However, sole CBD pretreatment reduced GPR55 expression, which was up‐regulated in TNBS colitis. O‐1602 and CBD each lowered MPO and IL‐6 levels remarkably in TNBS colitis, while TNF‐α levels experienced no change. CBD rescued the downward colonic motility in TNBS colitis in vivo; however, it decreased the upward contraction of the smooth muscle strip under electrical stimulation in vitro. Pretreatment with CBD prevented against TNBS‐induced changes of Ca2+‐ATPase activity of smooth muscle cells. However, membrane potential of the smooth muscle cells decreased by TNBS experienced no change after O‐1602 or CBD import. Conclusions & Inferences The present study suggested that CBD participated in the regulation of colonic motility in rats, and the mechanisms may be involved in the regulation of inlammatory factors and Ca2+‐ATPase activity through GPR55.

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Aims Irisin is a newly discovered actin that has been shown to be effective against inflammation-related symptoms. The aim of this study was to investigate the influence of Irisin on LPS-induced inflammation in vitro and to investigate the role of the mitogen-activated protein kinase (MAPK) pathway in the protecting effect of Irisin in LPS-stimulated RAW 264.7 macrophages.Methods Cell viability was assessed using MTT assay and flow cytometry, cell morphology was measured by optical microscope, IL-12 and IL-23 were detected by Elisa, and the levels of related proteins were analyzed by western blot. Phagocytosis of zymosan and clearance of apoptotic cells were measured.Results MTT assay and flow cytometry results showed that LPS-induced cytotoxicity was reversed by Irisin(p<0.001), after coincubation with Irisin, the level of IL-12 and IL-23 decreased in LPS-stimulated RAW264.7 macrophages(p>0.05). Irisin pretreatment significantly inhibited the phosphorylation of ERK and AKT and increased the expression of PPAR α and PPAR γ(p<0.05). LPS-induced enhancement of phagocytosis(p<0.05) and cell clearance was reversed by Irisin pretreatment(p<0.001).Conclusions Irisin ameliorated LPS-induced inflammation by inhibiting cytotoxicity and apoptosis, and this protective effect may be mediated through the MAPK pathway.

BACKGROUND Immunoglobulin D (IgD) multiple myeloma (MM) is a rare subtype of MM and commonly occurs in younger subjects but at a later stage of the International Staging System (ISS) when admitted. As a special type of IgD myeloma, IgD-λ/λ biclonal MM is rarer. Its serum protein electrophoresis and serum immuno-fixation electrophoresis (IFE) might find no anomalies even if the bone marrow (BM) examination is performed. Thus, it is easy to miss the diagnosis. CASE SUMMARY A 62-year-old man diagnosed as IgD-λ/λ myeloma (ISS stage III) was admitted with fatigue and weight loss. The physical examination suggested an anemic face, a few moist rales at the left lung base, and mild concave edema in both lower extremities. Laboratory examinations showed the elevated creatinine levels, β2-microglobulin, lactic dehydrogenase, and erythrocyte sedimentation rate, while the decreased neutrophils, granulocytes, and hemoglobin. In the serum protein electrophoresis, there appeared two inconspicuous M-spikes. Serum IFE indicated an over-representation of lambda light chain and yielded two monoclonal bands in λ region, but only one corresponding heavy chain band in the antisera to IgD region. The BM histology and BM cytology both supported the diagnosis of IgD-λ/λ myeloma. CONCLUSION This case highlights the differential clinical manifestations and laboratory findings of IgD-λ/λ myeloma to help minimize the chance of misdiagnosis.