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Highlights • Intra-articular comminuted fracture of MP joint was relatively rare. • MP joint of ring finger was injured. • Eventually range of motion of affected finger was fully recovered. • Ichi-Fixator System was useful for comminuted intraarticular fracture of MP joint., Introduction Comminuted fractures involving the articular surface of the base of the proximal phalanx are relatively rare. We treated a patient with this type of fracture by open reduction and internal fixation with a locked-wire-type external fixator (Ichi-Fixator System). Presentation of case A 45-year-old man was injured because his ring finger was kicked during a Futsal game. Radiographs and computed tomography revealed a comminuted intraarticular fracture of the proximal phalanx of this ring finger. We treated the fracture with open reduction and K-wires and external fixation. We removed the K-wire and external fixator 5 weeks postoperatively and initiated range of motion exercises. Five months postoperatively, his finger motion was fully recovered without restriction. Discussion Comminuted intraarticular fractures of the base of the proximal phalanx are usually treated with plating. Complications such as interference with excursion of the central slip and lateral bands, extensor tendon rupture, and plate prominence have been reported in these fractures. In our patient, the Ichi-Fixator System was useful as a distraction apparatus for metacarpophalangeal joint fixation. Conclusion A comminuted intra-articular fracture of the base of the proximal phalanx was treated successfully using the Ichi-Fixator system.

Summary Evidence regarding intraductal papillary neoplasm of the bile duct (IPNB) as a type of precancerous lesion of cholangiocarcinoma is limited. Moreover, a reproducible in vivo model is lacking, and IPNB pathogenesis remains unclear. Here, we use a doxycycline-inducible tetracycline (Tet)-on mice model to control fibroblast growth factor 10 (FGF10) expression, which regulates branching and tubule formation. FGF10-induced IPNB mimics the multifocal and divergent human IPNB phenotypes via the FGF10-FGF receptor 2 (FGFR2)-RAS-extracellular-signal-regulated kinase (ERK) signaling pathway. A paracrine/autocrine growth factor is sufficient to initiate and maintain IPNB originating from the peribiliary glands, including biliary stem/progenitor cells. With KrasG12D, p53, or p16 mutations or both, Fgf10-induced IPNB shows stepwise carcinogenesis, causing associated invasive carcinoma. Fgf10-induced papillary changes and progression are suppressed by the inhibition of the FGF10-FGFR2-RAS-ERK signaling pathway, demonstrating that the signal is a therapeutic target for IPNB and associated carcinoma.

Serrated lesions in the colon are classified as hyperplastic polyp (HP), sessile serrated adenoma/polyp (SSA/P), and traditional serrated adenoma by their histological features. Recently, the molecular features in the serrated lesions have been identified, and the serrated lesions are considered the precursors of colon carcinomas. In the classical adenoma-carcinoma sequence, which is closely associated with the Wnt/β-catenin signaling, the stem cell regulation in the normal crypts and carcinomas is an important therapeutic target. However, the serrated-carcinoma pathway is still poorly understood in terms of therapeutic strategies. Serrated lesions share several stem cell markers in the colon. Both serrated lesions and stem cells could collaborate to trigger endogenous drug resistance in colon cancer. We here mainly review the putative stem cell markers of the human serrated lesions and imply the possibility for the therapeutic strategies of serrated lesions and also drug resistance developed during cancer treatment.

Liver bipotential stem/progenitor cells can give rise to both hepatocytes and cholangiocytes. These cells might also be potential sources of liver cancers, such as hepatocellular carcionoma (HCC) and cholangiocarcinoma (CCA), and both are heterogeneous malignancies. Further, combined HCC-intrahepatic CCA, a form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation, has also been reported, supporting the existence of bipotent cancer stem cells in liver. HCC, CCA, and HCC-intrahepatic CCA are heterogeneous in the diagnosis by immunohistochemistry and include a subset of cells expressing various stem cell markers. In this chapter, we summarize the current knowledge of stem cells in normal liver and liver cancers and discuss the controversial points.

The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1⁺ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12⁺ endothelial cells and Cxcr4⁺ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche., National Institutes of Health (U.S.) (Grants 54CA126513, R01CA093405, R01CA120979, and R01DK052778)

The present study was performed to determine effects of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid, on acoustic injury. Albino guinea pigs were exposed to a 2 kHz pure tone of 120 or 125 dB sound pressure level for 10 min immediately after intravenous administration of DHEAS. Statistically significant improvement in the compound action potential threshold shifts and in amplitude reduction of distortion-product otoacoustic emissions was observed 1 week after the acoustic overexposure in the animals treated with DHEAS. The present results suggest that DHEAS has a protective effect against acoustic injury of the cochlea. Keywords:: dehydroepiandrosterone sulfate (DHEAS), acoustic injury, cochlea

High-density lipoprotein (HDL) is considered to be a major anti-atherogenic particle that inhibits conversion of low-density lipoprotein (LDL) into its oxidized form (oxLDL), reduction in the vasoregulatory function, and formation of foam cells. In in vitro experiments, the HDL particle is found to be more vulnerable to oxidative modification than LDL. In addition, recent attentive investigations of clinical specimens have shown that HDL from coronary artery disease and dyslipidemia subjects has a higher sensitivity to lipid oxidation, and that levels of plasma-oxidized HDL (oxHDL) in patients with atherosclerosis, diabetes mellitus, and renal failure are significantly higher, compared with those from healthy donors. Numerous studies using potential oxidants moreover suggest that the oxidative modification of HDL reduces its intrinsic beneficial properties, such as reverse cholesterol transport and antioxidant property, and progressively participates in the development of atherosclerosis through appearance of the pro-inflammatory and cytotoxic effects. By contrast, we recently found that 4-hydroxy-2-nonenal, which is generated during oxidation of HDL, induces cross-linking of apoproteins and upregulates antioxidant enzymes such as aldo-keto reductase (AKR) 1C1 and AKR1C3. In this chapter, we introduce the current literature on clinical relevance of oxHDL to vascular-related diseases, and the structural and functional alterations in HDL due to treating with oxidants. In addition, on the basis of the oxidation-elicited functional changes in HDL and cellular responses to the oxHDL treatment, we discuss whether oxHDL is a causal factor, like oxLDL, or a protective factor for the development of atherosclerosis.

Publisher Summary This chapter focuses on the functional change in the high density lipoprotein (HDL) particle by oxidative modification and its contribution to atherogenesis. HDL contains antioxidant molecules and enzymes in the particle, which oxidizes more rapidly than low density lipoprotein (LDL) during in vitro oxidation. This suggests a possibility that oxidized lipoproteins, including both HDL and LDL, are involved in the genesis of coronary artery diseases and reflect an oxidative stress state of the diseases. Myeloperoxidase, an enzyme in macrophages and neutrophils, may be one of the most potential enzymes concerning in vivo oxidant generation. This enzyme system generates reactive species including hypochlorous acid/hypochlorite, tyrosyl radicals, chloramines, and nitrogen dioxides. Lipoxygenase, which is produced by endothelial cells and macrophages, may also participate in the in vivo oxidation of lipoproteins, because treatment with the enzyme inhibitors prevents cell-mediated oxidation of LDL. The oxidative mechanism of lipoproteins by lipoxygenase is mediated by conversion of polyunsaturated fatty acids into lipid peroxides including 13S-hydroxy-9, 11-octadecadienoic acid, and the metabolites are detected in the early stage of atherosclerosis. Peroxynitrite can directly oxidize polyunsaturated fatty acids, tocopherols, carbohydrates, DNA, and proteins. Functional alterations in HDL by oxidation result in reverse cholesterol transport, reduction of cholesterol efflux, reduction of cholesterol esterification, disruption of cholesterol homeostasis, reduction of antioxidant activity, decrease in nitric oxide production and its function, induction of pro-inflammatory effect, increase in expression of plasminogen activator inhibitor, and induction of cytotoxic effect.