Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i) inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK) pathway and activator protein 1 (AP-1) factor; (ii) suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB) pathway and cyclooxygenase 2 (COX-2) gene; (iii) apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS) / c-Jun NH(2)-terminal kinase (JNK)-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention

Enzymatic reactions in confined environments

Within each biological cell, surface- and volume-confined enzymes control a highly complex network of chemical reactions. These reactions are efficient, timely, and spatially defined. Efforts to transfer such appealing features to in vitro systems have led to several successful examples of chemical reactions catalysed by isolated and immobilized enzymes. In most cases, these enzymes are either bound or adsorbed to an insoluble support, physically trapped in a macromolecular network, or encapsulated within compartments. Advanced applications of enzymatic cascade reactions with immobilized enzymes include enzymatic fuel cells and enzymatic nanoreactors, both for in vitro and possible in vivo applications. In this Review, we discuss some of the general principles of enzymatic reactions confined on surfaces, at interfaces, and inside small volumes. We also highlight the similarities and differences between the in vivo and in vitro cases and attempt to critically evaluate some of the necessary future steps to improve our fundamental understanding of these systems

In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver conditions, and its treatment involves curing the patients without liver transplantation. Understanding the mechanism of NAFLD initiation and progression would enable the development of new diagnostic tools and drugs; however, until now, the underlying mechanisms of this condition remain largely unknown owing to the lack of experimental settings that can simplify the complicated NAFLD process in vitro. Microphysiological systems (MPSs) have long been used to recapture human pathophysiological conditions in vitro for applications in drug discovery. However, polydimethylsiloxane (PDMS) is used in most of these MPSs as the structural material; it absorbs hydrophobic molecules, such as free fatty acids (FFAs), which are the key components that initiate NAFLD. Therefore, the current PDMS-based MPSs cannot be directly applied to in vitro NAFLD modeling. In this work, we present an in vitro NAFLD model with an MPS made of cyclo-olefin polymer (COP), namely COP-MPS, to prevent absorption of FFAs. We demonstrated the induction of NAFLD-like phenotype in HepaRG hepatocyte-like cells cultured in the COP-MPS by treatment with FFAs. The FFAs induced lipid accumulation in the HepaRG cells, resulting in inactivation of the apoptotic cells. We believe that the proposed COP-MPS can contribute toward the investigation of NAFLD mechanisms and identification of new drugs to prevent the progression of liver disease and thus avoid liver transplantation

DESIGN AND DEVELOPMENT OF NANO-ARTIFICIAL-CELL MEMBRANE BASED NOVEL BIOSENSOR : APPLICATION FOR MONITORING OF AQUEOUS STRESSES

Joint Research on Environmental Science and Technology for the Eart

Dual optical channel three-dimensional neuroendoscopy: Clinical application as an assistive technique in endoscopic endonasal surgery

AbstractThree-dimensional (3D) high-definition endoscopy is an innovative technical advancement that helps surgeons gain precise depth perception and spatial recognition during endoscopic surgery. Here, we describe a new dual optical channel 3D neuroendoscopic technique and its clinical application. We performed endoscopic endonasal surgery on 88 patients using 3D and two-dimensional (2D) endoscopes in conjunction. We evaluated the usefulness of stereoscopic images acquired by dual optical channel 3D endoscopy during endoscopic surgery and compared the image resolution between dual optical channel 3D endoscopy and 2D endoscopy. Additionally, we compared the stereoscopic images acquired by dual optical channel and Visionsense 3D endoscopy in three cases. Combination surgery using 3D and 2D endoscopy was found to be safe. Stereoscopic images were useful in several surgical steps, especially in recognition of complex bony structures, bone drilling, and suprasellar manipulation. The magnitude of binocular disparity was greater in dual optical channel 3D endoscopy than in Visionsense 3D endoscopy. Stereoscopic images acquired by dual optical channel 3D neuroendoscopy were of adequate quality and were useful for endoscopic endonasal surgery. In consideration of its lower image resolution compared to that of 2D high-definition endoscopy, dual optical channel 3D neuroendoscopy can be applied as an assistive technique in endoscopic endonasal surgery. The magnitude of binocular disparity is one of the key factors to be considered for evaluation of the clinical significance of 3D endoscopy

Caffeoylquinic Acids Generated In Vitro in a High-Anthocyanin-Accumulating Sweet potato Cell Line

Accumulation of phenolic compounds has been monitored in a suspension culture of anthocyanin-accumulating sweet potato cell line grown under the conditions of modified Murashige and Skoog high-anthocyanin production medium (APM) over a period of 24 days. Tissue samples extracted with 15% acetic acid were analysed using HPLC at a detection wavelength of 326 nm. Among others, the following derivatives of caffeoylquinic acids were detected: 4,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and 3,4,5-tricaffeoylquinic acid. Their total amount reached a maximum of 110 mg/gFW between the 4th and the 15th day of culture growth on APM. The major compound of the phenolic mixture was 3,5-dicaffeoylquinic acid with maximum accumulation level of 80 mg/100 gFW. The potential effects of targeted phenolic compounds on the nutraceutical qualities of in vitro produced anthocyanin-rich extracts are discussed

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods

BACKGROUND: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded. We compared the maximal pressure during ablation and the total ablation time among the multi-step method, single-step method (a standard single-step full expansion with a LeVeen needle), and the method with a cool-tip electrode. Finally, we performed a preliminary comparison of the ablation times for these methods in HCC cases. RESULTS: A block of pig liver sealed in a rigid plastic case was used as a model of an HCC tumor with a capsule. The multi-step method with the LeVeen electrode resulted in the lowest pressure as compared with the single-step or cool-tip methods. There was no significant difference in the ablation time between the multi-step and cool-tip ablation methods, although the single-step methods had longer ablation times than the other ablation procedures. In HCC cases, the multi-step method had a significantly shorter ablation time than the single-step or cool-tip methods. CONCLUSION: We demonstrated that the multi-step method was useful to reduce the ablation time and to suppress the increase in pressure. The multi-step method using a LeVeen needle may be a clinically applicable procedure for RFA

The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina

Müller glial cells, which are the most predominant glial subtype in the retina, play multiple important roles, including the maintenance of structural integrity, homeostasis, and physiological functions of the retina. We have previously found that the Rax homeoprotein is expressed in postnatal and mature Müller glial cells in the mouse retina. However, the function of Rax in postnatal and mature Müller glial cells remains to be elucidated. In the current study, we first investigated Rax function in retinal development using retroviral lineage analysis and found that Rax controls the specification of late-born retinal cell types, including Müller glial cells in the postnatal retina. We next generated Rax tamoxifen–induced conditional KO (Rax iCKO) mice, where Rax can be depleted in mTFP-labeled Müller glial cells upon tamoxifen treatment, by crossing Raxflox/flox mice with Rlbp1-CreERT2 mice, which we have produced. Immunohistochemical analysis showed a characteristic of reactive gliosis and enhanced gliosis of Müller glial cells in Rax iCKO retinas under normal and stress conditions, respectively. We performed RNA-seq analysis on mTFP-positive cells purified from the Rax iCKO retina and found significantly reduced expression of suppressor of cytokine signaling-3 (Socs3). Reporter gene assays showed that Rax directly transactivates the Socs3 promoter. We observed decreased expression of Socs3 in Müller glial cells of Rax iCKO retinas by immunostaining. Taken together, the present results suggest that Rax suppresses inflammation in Müller glial cells by transactivating Socs3. This study sheds light on the transcriptional regulatory mechanisms underlying retinal Müller glial cell homeostasis.Yoshimoto T., Chaya T., Varner L.R., et al. The Rax homeoprotein in Müller glial cells is required for homeostasis maintenance of the postnatal mouse retina. Journal of Biological Chemistry 299, 105461 (2023); https://doi.org/10.1016/j.jbc.2023.105461