Myeloid cells expressing VEGF and arginase-1 following uptake of damaged retinal pigment epithelium suggests potential mechanism that drives the onset of choroidal angiogenesis in mice

Whilst data recognise both myeloid cell accumulation during choroidal neovascularisation (CNV) as well as complement activation, none of the data has presented a clear explanation for the angiogenic drive that promotes pathological angiogenesis. One possibility that is a pre-eminent drive is a specific and early conditioning and activation of the myeloid cell infiltrate. Using a laser-induced CNV murine model, we have identified that disruption of retinal pigment epithelium (RPE) and Bruch's membrane resulted in an early recruitment of macrophages derived from monocytes and microglia, prior to angiogenesis and contemporaneous with lesional complement activation. Early recruited CD11b(+) cells expressed a definitive gene signature of selective inflammatory mediators particularly a pronounced Arg-1 expression. Accumulating macrophages from retina and peripheral blood were activated at the site of injury, displaying enhanced VEGF expression, and notably prior to exaggerated VEGF expression from RPE, or earliest stages of angiogenesis. All of these initial events, including distinct VEGF (+) Arg-1(+) myeloid cells, subsided when CNV was established and at the time RPE-VEGF expression was maximal. Depletion of inflammatory CCR2-positive monocytes confirmed origin of infiltrating monocyte Arg-1 expression, as following depletion Arg-1 signal was lost and CNV suppressed. Furthermore, our in vitro data supported a myeloid cell uptake of damaged RPE or its derivatives as a mechanism generating VEGF (+) Arg-1(+) phenotype in vivo. Our results reveal a potential early driver initiating angiogenesis via myeloid-derived VEGF drive following uptake of damaged RPE and deliver an explanation of why CNV develops during any of the stages of macular degeneration and can be explored further for therapeutic gain

Xiaoke Pill (消渴丸) and anti-diabetic drugs: A review on clinical evidence of possible herb-drug interactions

Objective: To critically analyze the clinically-based evidence of herb-drug interaction on Xiaoke Pill (消渴丸) and its concomitant use with anti-diabetic drugs. Methods: MEDLINE, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), International Pharmaceutical Abstracts (IPA), Chinese BioMedical Literature Database (CBM), Traditional Chinese Medical Database System (TCMDS), China National Knowledge Infrastructure Database (CNKI) and Wangfang Databases were searched. Levels of Evidence and Severity Level of Interaction were used to evaluate the quality of the included studies. Results: A total of 27 studies published in Chinese, including 2 randomized controlled trials, 3 case series and 22 case reports, were included. Eighteen herbdrug interactions were reported involving Xiaoke Pill as monotherapy, while 6 herb-drug interactions occurred associated with Xiaoke Pill in combination with anti-diabetic drugs. The clinical results of herb-drug interaction of Xiaoke Pill were reported as additive blood glucose-lowering effects with anti-diabetic drugs, including benefifi cial and adverse hypoglycemic effects, anaphylactic shock and severe hair loss. Of these interactions 82.8% were reported to be associated with potential deterioration of the patients’ conditions including hypoglycemic coma, stroke, mental disorder and even death. Conclusions: This review helped establish the clinically-based evidence about herb-drug interaction of Xiaoke Pill and its concomitant use with anti-diabetic drugs. The fifi ndings would help arouse the awareness of both health professionals and the general public to avoid the adverse herb-drug interactions of Xiaoke Pill in healthcare and community settings