Regulation of Adipogenesis Through Differential Modulation of ROS and Kinase Signaling Pathways by 3,4'-Dihydroxyflavone Treatment.

Studies on adipogenesis may be important for regulating human and/or animal obesity, which causes several complications such as, type II diabetes, hypertension, and cardiovascular disease, thus giving rise to increased economic burden in many countries. Previous reports revealed that various flavonoids have anti-apoptotic, antioxidant, and cell differentiation-regulating activities with a number of physiological benefits, including protection from cardiovascular disease, cancers, and oxidative stress. As we found that the hydroxylation patterns of the flavonoid B ring are known to play a critical role in their function, we screened several flavonoids containing different numbers and positions of OH substitutions in B ring for their modulatory property on adipogenesis. In this study, we revealed the anti-adipogenic activity of the naturally derived flavonoid, 3,4'-dihydroxyflavone (3,4'-DHF) in murine 3T3-L1 pre-adipocytes and equine adipose-derived stromal cells (eADSCs). We found that treatment with 3,4'-dihydroxyflavone (3,4'-DHF) led to decreased expression of adipogenic markers and lipid deposition with differential modulation of ROS and kinase signaling pathways. Regulation of ROS generation through the differential modulation of ROS-regulating gene expression was revealed to have an important role in the suppression of adipogenesis and increase of osteogenesis in eADSCs following 3,4'-DHF treatment. These results suggest that the flavonoid 3,4'-DHF can be used to regulate adipogenesis in ADSCs, which has potential therapeutic application in regenerative medicine or health care for humans and many sport or companion animals. J. Cell. Biochem. 118: 1065-1077, 2017. © 2016 Wiley Periodicals, Inc.

Correlation between Oxidative Stress, Nutrition, and Cancer Initiation.

Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30-35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regulate ROS downstream mechanisms, which could have potential implications in anticancer research. Cancer initiation may be modulated by the nutrition-mediated elevation in ROS levels, which can stimulate cancer initiation by triggering DNA mutations, damage, and pro-oncogenic signaling. Therefore, in this review, we have provided an overview of the relationship between nutrition, oxidative stress, and cancer initiation, and evaluated the impact of nutrient-mediated regulation of antioxidant capability against cancer therapy.

The immobilization of fibronectin- and fibroblast growth factor 2-derived peptides on a culture plate supports the attachment and proliferation of human pluripotent stem cells.

Pluripotent stem cells (PSCs) offer a promising tool for regenerative medicine. The clinical application of PSCs inevitably requires a large-scale culture in a highly defined environment. The present study aimed to devise defined coating materials for the efficient adhesion and proliferation of human PSCs (hPSCs). We tested the activity of seven fibronectin-derived peptides and three laminin-derived peptides for the attachment and proliferation of hPSCs through their immobilization on the bottom of culture dishes by creating a fusion protein with the mussel adhesion protein. Among the extracellular matrix (ECM) mimetics tested, one fibronectin-derived peptide, PHSRN-GRGDSP, significantly promoted adhesion, enhanced alkaline phosphatase activity, and increased pluripotency-related gene expression in hPSCs compared to Matrigel. Furthermore, co-immobilization of a particular canofin peptide derived from fibroblast growth factor 2 increased pluripotency marker expression, which may offer the possibility of culture without growth factor supplementation. Our findings afford a novel defined condition for the efficient culture of hPSCs and may be utilized in future clinical applications.

Accessory gallbladder in an intrahepatic location mimicking a cystic tumor of the liver: A case report.

BACKGROUND: Double gallbladder (GB) is a rare congenital anomaly of the biliary system characterized by the presence of an accessory GB. CLINICAL FINDINGS: A 38-year-old female presented with a history of right upper quadrant (RUQ) pain. Computed tomography (CT) showed a lobulated cystic mass involving the center portion of liver. Magnetic resonance imaging (MRI) additionally revealed a tubular structure of T2 bright signal intensity (SI), which connected the cystic lesion of the liver to the bile duct. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) confirmed the connection between the intrahepatic cystic lesion and the left main hepatic duct. We regarded as a cystic mass with biliary communication, such as a cystic intraductal papillary neoplasm of the bile duct (IPNB) or localized Caroli disease. The patient underwent partial hepatectomy for the cystic mass of the liver and a final diagnosis of chronic inflammation of an intrahepatically located accessory GB was made. CONCLUSION: We report a case of an accessory GB in an intrahepatic location mimicking a cystic mass such as cystic IPNB or localized Caroli disease of the liver showing a cystic mass with biliary communication.

Primary Pleural Synovial Sarcoma with Metastatic Cardiac Involvement: A Case Report.

Primary pleuropulmonary synovial sarcomas are rare soft tissue malignancies; combined metastatic involvement of the heart is extremely rare. In this case report, a 17-year-old female presented with a history of chest pain. Chest radiographs revealed a round mass in the left upper hemithorax, and computed tomography (CT) showed a well-defined heterogeneous enhancing mass abutting the pleura. A core needle biopsy revealed malignant spindle cells. Surgical resection was performed, and a final diagnosis of primary pleural synovial sarcoma, monophasic fibrous type, was made. The patient underwent radical irradiation and chemotherapy and remained stable for 28 months until a follow-up chest CT showed a poorly enhancing nodule in the left pericardial region that enlarged after 5 months. Surgical resection was performed. Histological examination confirmed metastatic cardiac involvement from a primary pleural synovial sarcoma. We report this unusual case of a primary pleural synovial sarcoma metastasis to the heart.

Efficient mRNA delivery with graphene oxide-polyethylenimine for generation of footprint-free human induced pluripotent stem cells.

Clinical applications of induced pluripotent stem cells (iPSCs) require development of technologies for the production of "footprint-free" (gene integration-free) iPSCs, which avoid the potential risk of insertional mutagenesis in humans. Previously, several studies have shown that mRNA transfer can generate "footprint-free" iPSCs, but these studies did not use a delivery vehicle and thus repetitive daily transfection was required because of mRNA degradation. Here, we report an mRNA delivery system employing graphene oxide (GO)-polyethylenimine (PEI) complexes for the efficient generation of "footprint-free" iPSCs. GO-PEI complexes were found to be very effective for loading mRNA of reprogramming transcription factors and protection from mRNA degradation by RNase. Dynamic suspension cultures of GO-PEI/RNA complexes-treated cells dramatically increased the reprogramming efficiency and successfully generated rat and human iPSCs from adult adipose tissue-derived fibroblasts without repetitive daily transfection. The iPSCs showed all the hallmarks of pluripotent stem cells including expression of pluripotency genes, epigenetic reprogramming, and differentiation into the three germ layers. These results demonstrate that mRNA delivery using GO-PEI-RNA complexes can efficiently generate "footprint-free" iPSCs, which may advance the translation of iPSC technology into the clinical settings.

Highly flexible, proton-conductive silicate glass electrolytes for medium-temperature/low-humidity proton exchange membrane fuel cells.

We demonstrate highly flexible, proton-conductive silicate glass electrolytes integrated with polyimide (PI) nonwoven fabrics (referred to as "b-SS glass electrolytes") for potential use in medium-temperature/low-humidity proton exchange membrane fuel cells (PEMFCs). The b-SS glass electrolytes are fabricated via in situ sol-gel synthesis of 3-trihydroxysilyl-1-propanesulfonic acid (THPSA)/3-glycidyloxypropyl trimethoxysilane (GPTMS) mixtures inside PI nonwoven substrates that serve as a porous reinforcing framework. Owing to this structural uniqueness, the b-SS glass electrolytes provide noticeable improvements in mechanical bendability and membrane thickness, in comparison to typical bulk silicate glass electrolytes that are thick and easily fragile. Another salient feature of the b-SS glass electrolytes is the excellent proton conductivity at harsh measurement conditions of medium temperature/low humidity, which is highly important for PEMFC-powered electric vehicle applications. This beneficial performance is attributed to the presence of a highly interconnected, proton-conductive (THPSA/GPTMS-based) silicate glass matrix in the PI reinforcing framework. Notably, the b-SS glass electrolyte synthesized from THPSA/GPTMS = 9/1 (mol/mol) exhibits a higher proton conductivity than water-swollen sulfonated polymer electrolyte membranes (here, sulfonated poly(arylene ether sulfone) and Nafion are chosen as control samples). This intriguing behavior in the proton conductivity of the b-SS glass electrolytes is discussed in great detail by considering its structural novelty and Grotthuss mechanism-driven proton migration that is strongly affected by ion exchange capacity (IEC) values and also state of water.

Hydrophilicity/porous structure-tuned, SiO2/polyetherimide-coated polyimide nonwoven porous substrates for reinforced composite proton exchange membranes.

Porous substrate-reinforced composite proton exchange membranes have drawn considerable attention due to their promising application to polymer electrolyte membrane fuel cells (PEMFCs). In the present study, we develop silica (SiO(2)) nanoparticles/polyetherimide (PEI) binders-coated polyimide (PI) nonwoven porous substrates (referred to as "S-PI substrates") for reinforced composite membranes. The properties of S-PI substrates, which crucially affect the performance of resulting reinforced composite membranes, are significantly improved by controlling the hygroscopic SiO(2) particle size. The 40 nm S-PI substrate (herein, 40 nm SiO(2) particles are employed) shows the stronger hydrophilicity and highly porous structure than the 530 nm S-PI substrate due to the larger specific surface area of 40 nm SiO(2) particles. Based on the comprehensive understanding of the S-PI substrates, the structures and performances of the S-PI substrates-reinforced composite membranes are elucidated. In comparison with the 530 nm S-PI substrate, the hydrophilicity/porous structure-tuned 40 nm S-PI substrate enables the impregnation of a large amount of a perfluorosulfonic acid ionomer (Nafion), which thus contributes to the improved proton conductivity of the reinforced Nafion composite membrane. Meanwhile, the reinforced Nafion composite membranes effectively mitigate the steep decline of proton conductivity with time at low humidity conditions, as compared to the pristine Nafion membrane. This intriguing finding is further discussed by considering the unusual features of the S-PI substrates and the state of water in the reinforced Nafion composite membranes.