Mass-forming immunoglobulin G4-related disease shows indolent clinical course after surgical resection, clinicopathological analysis of a series of 15 cases.

The purpose of this study is to characterize the clinicopathological features of mass-forming immunoglobulin G4-related disease (IgG4-RD). A retrospective search for cases of mass-forming IgG4-RD diagnosed at Singapore General Hospital between 2008 and 2019 was performed. A total of 15 cases of mass-forming IgG4-RD were identified. The male-to-female ratio was 2.5:1, and the median age was 61 years old. The majority of cases showed a solitary lesion (12/15) with a mean size of 35 mm. IgG4-RD was considered as a clinical differential diagnosis only in one case (1/15) prior to the surgical resection. Diagnostic histopathological features, such as dense lymphoplasmacytic infiltrate positive for IgG4 plasma cells (15/15), storiform fibrosis (15/15), and obliterative phlebitis (9/15), were observed in most cases. These findings were distributed heterogeneously within the lesions. Cases with single organ involvement showed a low relapse rate (2/10) and normal serum IgG4 level after surgical resection. Mass-forming IgG4-RD has a male predilection and involves various organ systems. It may be initially misdiagnosed as malignancy and undergo surgical resection. The diagnostic histological features of IgG4-RD are readily identified in different organs. However, they may be distributed heterogeneously within a single lesion. Cases of single organ involvement show an indolent clinical course and normal serum IgG4 level after surgical resection.

Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy.

Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.

Spontaneous partial regression of a microcystic jejunal mesenteric lymphangioma and a proposed management algorithm.

Mesenteric lymphangiomas are relatively rare, with clinical symptoms ranging from an asymptomatic presentation to an acute abdomen. The natural history and biological behaviour of this entity can range from slow indolent lesions to aggressive tumours with a risk of malignant transformation. Spontaneous regression of a mesenteric lymphangioma is rare. We herein report a case of a jejunal mesenteric lymphangioma that was initially detected incidentally in an asymptomatic patient with a subsequent sudden increase in size with resulting surrounding mass effect after 9 months and a spontaneous partial regression at surgical resection. Our case is the first reported case which outlines a period in the natural history and evolution of microcystic mesenteric lymphangioma, illustrating the sudden enlargement likely attributable to spontaneous and self-limiting haemorrhage and subsequent partial regression at surgical resection. We thenceforth propose a possible management algorithm for adult patients with mesenteric lymphangiomas.

Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance.

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has been shown to have anti-inflammatory, anti-cancer, anti-steatotic effects on the liver. Autophagy also mediates similar effects; however, it is not currently known whether EGCG can regulate hepatic autophagy. Here, we show that EGCG increases hepatic autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in hepatic cells and in vivo. EGCG also increases phosphorylation of AMPK, one of the major regulators of autophagy. Importantly, siRNA knockdown of AMPK abrogated autophagy induced by EGCG. Interestingly, we observed lipid droplet within autophagosomes and autolysosomes and increased lipid clearance by EGCG, suggesting it promotes lipid metabolism by increasing autophagy. In mice fed with high-fat/western style diet (HFW; 60% energy as fat, reduced levels of calcium, vitamin D3, choline, folate, and fiber), EGCG treatment reduces hepatosteatosis and concomitantly increases autophagy. In summary, we have used genetic and pharmacological approaches to demonstrate EGCG induction of hepatic autophagy, and this may contribute to its beneficial effects in reducing hepatosteatosis and potentially some other pathological liver conditions.