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This study aimed to investigate the effect of mixture of herbal extracts and supplementary formula (FNP-C) on hangovers and antioxidant enzymes in alcohol-induced liver damage in rats. HepG2 cells were used as the experimental cells and divided into five groups: non-treated control (normal), alcohol-induced control (control), mixture of herbal extracts (FNP-B), FNP-C, and a commercial treatment of liver diseases (Livers®); inhibition of detoxification and alcohol-induced damage was confirmed in vivo. Blood alcohol and acetaldehyde concentration after alcohol consumption were measured in a timely manner; alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), superoxide dismutase (SOD), glutathione (GSH), glutathione transferase (GST), and lactate dehydrogenase (LDH) levels were measured in the liver. FNP-C exhibited the highest effect. When FNP-C was administered to alcohol-induced animals, blood alcohol and acetaldehyde concentration decreased compared to FNP-B and Livers®. FNP-C reduced ADH levels and improved LDH, GSH, GST, and SOD levels. The FNP-C group was effective in preventing alcohol-induced hangovers and liver damage. Thus, FNP-C improves hangovers and increases antioxidant activity in an alcohol-induced model. Adding amino acids and vitamins to natural ingredients can potentially enhance the effect of improving hangovers.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder, which is characterized by cognitive deficit due to synaptic loss and neuronal death. Extracellular amyloid β plaques are one of the pathological hallmarks of AD. The autophagic lysosomal pathway is the essential mechanism to maintain cellular homeostasis by driving clearance of protein aggregates and is dysfunctional in AD. Here, we showed that inhibiting MEK/ERK signaling using a clinically available MEK1/2 inhibitor, trametinib (GSK1120212, SNR1611), induces the protection of neurons through autophagic lysosomal activation mediated by transcription factor EB (TFEB) in a model of AD. Orally administered trametinib recovered impaired neural structures, cognitive functions, and hippocampal long-term potentiation (LTP) in 5XFAD mice. Trametinib also reduced Aβ deposition via induction of autophagic lysosomal activation. RNA-sequencing analysis revealed upregulation of autophagic lysosomal genes by trametinib administration. In addition, trametinib inhibited TFEB phosphorylation at Ser142 and promoted its nuclear translocation, which in turn induced autophagic lysosomal related genes, indicating that trametinib activates the autophagic lysosomal process through TFEB activation. From these observations, we concluded that MEK inhibition provides neuronal protection from the Aβ burden by increasing autophagic lysosomal activity. Thus, MEK inhibition may be an effective therapeutic strategy for AD.

Poly(lactic acid) (PLA) has been highlighted for its excellent biodegradability and hydro-degradability. On the other hand, an estimation of the biodegradability of PLA generally requires lengthy measurements over several months because it is difficult for the terminal decomposer, a microorganism, to uptake and utilize the polymer material, making it difficult to analyze and compare the results quantitatively. In this study, it was hypothesized that the inclusion of mono lactic acid (LA) in a PLA blend improves the level of microbial attachment to the surface of the PLA blend, and increases the biodegradation rate. PLA blend films containing 1%, 2.5%, and 5% of LA were prepared, and their morphological changes to the surface and cross section of films were investigated. The biodegradation of a PLA/LA blend using digester sludge was estimated quantitatively from the specific gas production rate (SGPR) based on the surface area of the blend film. The physical and chemical properties before and after biodegradation were also compared. These results show that PLA/LA blends with a controlled degradation rate can be developed by incorporating readily degradable chemicals, and implemented as environmentally friendly plastics and polymers.

Biodegradable polymers and plastics have been investigated extensively and commercial applications of poly(lactic acid) (PLA) are being implemented. A feasible and rapid estimation of the biodegradability is urgently needed to satisfy environmental regulations and consumer’s desire considering the market situation. On the other hand, an estimation of the biodegradability of polymers normally requires a long time for measurement and there is less standardization, making it difficult to analyze and compare. This study examined the microbial degradation of PLA with anaerobic digester sludge. The gas production and by-product formation from PLA degradation were analyzed to assess the extent of biodegradation. The different specific surface areas of the PLA granules results in different gas production rates and degradation capacities, while an increase in surface area tends to increase the level of gas production. The specific CO2 and CH4 production rates were estimated based on the total surface area to quantify the biodegradability of PLA. The results showed that a rapid and feasible testing method of biodegradability is possible, and can be implemented to develop and optimize environmentally friendly plastics and polymers.

Ecological research often requires monitoring of a specific individual over an extended period of time. To enable non-invasive re-identification, consistent external marking is required. Treefrogs possess lateral lines for crypticity. While these patterns decrease predator detection, they also are individual specific patterns. In this study, we tested the use of lateral lines in captive and wild populations of Dryophytes japonicus as natural markers for individual identification. For the purpose of the study, the results of visual and software assisted identifications were compared. In normalized laboratory conditions, a visual individual identification method resulted in a 0.00 rate of false-negative identification (RFNI) and a 0.0068 rate of false-positive identification (RFPI), whereas Wild-ID resulted in RFNI = 0.25 and RFNI = 0.00. In the wild, female and male data sets were tested. For both data sets, visual identification resulted in RFNI and RFPI of 0.00, whereas the RFNI was 1.0 and RFPI was 0.00 with Wild-ID. Wild-ID did not perform as well as visual identification methods and had low scores for matching photographs. The matching scores were significantly correlated with the continuity of the type of camera used in the field. We provide clear methodological guidelines for photographic identification of D. japonicus using their lateral lines. We also recommend the use of Wild-ID as a supplemental tool rather the principal identification method when analyzing large datasets.

Background 3-Hydroxypropionic acid (3-HP) is an important platform chemical which can be produced biologically from glycerol. Klebsiella pneumoniae is an ideal biocatalyst for 3-HP because it can grow well on glycerol and naturally synthesize the essential coenzyme B12. On the other hand, if higher yields and titers of 3-HP are to be achieved, the sustained regeneration of NAD+ under anaerobic conditions, where coenzyme B12 is synthesized sustainably, is required. Results In this study, recombinant K. pneumoniae L17 overexpressing aldehyde dehydrogenase (AldH) was developed and cultured in a bioelectrochemical system (BES) with the application of an electrical potential to the anode using a chronoamperometric method (+0.5 V vs. Ag/AgCl). The BES operation resulted in 1.7-fold enhancement of 3-HP production compared to the control without the applied potential. The intracellular NADH/NAD+ ratio was significantly lower when the L17 cells were grown under an electric potential. The interaction between the electrode and overexpressed AldH was enhanced by electron shuttling mediated by HNQ (2-hydroxy-1,4-naphthoquinone). Conclusions Enhanced 3-HP production by the BES was achieved using recombinant K. pneumoniae L17. The quinone-based electron transference between the electrode and L17 was investigated by respiratory uncoupler experiments. This study provides a novel strategy to control the intracellular redox states to enhance the yield and titer of 3-HP production as well as other bioconversion processes.

The aim of this study was to screen for proteins that are susceptible to glycation under hyperglycemic conditions in patients with type 2 diabetic nephropathy. Serum proteins were analyzed by a proteomic approach using two-dimensional electrophoresis (2-DE) and ESI-Q-TOF MS/MS. Gels were stained with Pro-Q Emerald 488 to analyze the serum glycoproteome, followed by silver nitrate to examine the total serum proteome. Patient sera were divided into four groups according to their microalbuminuria index: type 2 diabetics with normoalbuminuria, microalbuminuria, and overt nephropathy, and healthy subjects. When the HbA1c levels of the diabetic groups were examined, groups with higher HbA1c exhibited higher fructosamine levels, suggesting that the loss of glycemic control affected the glycation of serum proteins. The proteins that became glycated under poor glycemic control were PEDF, apolipoprotein J precursor, hemopexin, immunoglobulin mu heavy chain, and immunoglobulin kappa chain. As albuminuria increased, a marker of kidney damage, the levels of glycated prekallikrein and complement factor C4B3 also increased. The glycated proteins identified in this study may provide the foundation for the development of novel markers of diabetes, hyperglycemia, and diabetic complications.

Wegener's granulomatosis (WG), Churg-Strauss syndrome, and microscopic polyangiitis (MPA) are closely related small vessel vasculitides characterized by anti-neutrophil cytoplasmic antibodies (ANCA). Although there were some reports of MPA presenting with claudication, there are very few reports on WG presenting with claudication of calf muscles. We report an unusual case of ANCA-associated vasculitis in a 75-year-old man who presented with bilateral calf claudication. Comprehensive evaluations, including electromyography, nerve conduction study, lower extremity magnetic resonance imaging, and Doppler scan, did not reveal any other cause of bilateral calf claudication. P-ANCA and anti-myeloperoxidase antibody was positive, but the anti-proteinase 3 antibody was negative. Chest computed tomography scan showed subpleural honeycombing and reticulation, predominantly in both basal lung areas. Biopsy of the calf muscle showed granulomatous vasculitis. Kidney biopsy was also performed which revealed focal necrotizing glomerulonephritis. Our patient does not exhibit typical clinical features for WG, but histopathologic findings of necrotizing granulomatous vasculitis in calf muscle biopsy is highly suggestive of WG.

Lysophospholipase D (lysoPLD) is known to convert lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA). In this study, we examined the inhibitory effect of fish egg extracts, containing lipids, on bovine lysoPLD activity. Fish eggs extracts were tested for the inhibition of lysoPLD activity, and the inhibitory action was expressed as 50% inhibitory concentration (IC50). Among fish egg extracts of 20 fish species, the most potent inhibition was expressed by Hairtail egg extract (IC50, 0.07 ± 0.01 mg egg weight/mL), followed by extract of Spanish mackerel egg extract (0.11 ± 0.02 mg egg weight/mL) and extract of Pacific saury egg (0.48 ± 0.03 mg egg weight/mL). In ESI/MS analysis, major lysoPLD-inhibitory lipid components in egg extracts were identified to be species of LPC, LPA and fatty acid. From these results, it is suggested that the strong inhibition of lysoPLD activity by fish egg extracts might be ascribed to the presence of lysophospholipids. In a separate study, enzymatic oxidation using lipoxygenase or non-enzymatic oxidations such as HOCl oxidation or Cu2+-catalyzed oxidation enhanced the inhibitory activity to some extent, suggesting that the oxidation of polyunsaturated lysophospholipids might contribute to the increase of lysoPLD-inhibitory action. Taken together, it is suggested that fish eggs may contain potent lipid inhibitors of lysoPLD, and that the inhibitory action of lipid inhibitors was enhanced by oxidative process.

Bone morphogenic protein 4 (BMP4), a member of the TGF-beta superfamily, induced neural differentiation of neural stem cells (NSCs) grown in a medium containing basic fibroblast growth factor (bFGF). The Ras protein level and the activities of the downstream ERKs were increased by transfection of BMP4 or treatment with recombinant BMP4. The effects of BMP4, including activation of the Ras-ERK pathway and induction of the neuron marker beta-tubulin type III (Tuj1), were blocked by co-treatment of the BMP4 antagonist, noggin. The roles of the Ras-ERK pathway in neuronal differentiation by BMP4 were revealed by measuring the effect of the ERK pathway inhibition by dominant negative Ras or PD98059, the MEK specific inhibitor. BMP4 is a transcriptional target of Wnt/beta-catenin signaling, and both the mRNA and protein levels of BMP4 were increased by treatment of valproic acid (VPA), a chemical inhibitor of glycogen synthase kinase 3beta (GSK3beta) activating the Wnt/beta-catenin pathway. The BMP4- mimicking effects of VPA, activation of the Ras-ERK pathway and induction of Tuj1, also were blocked by noggin. These results indicate the potential therapeutic usage of VPA as a replacement for BMP4.

Dried roots of the plants Acanthopanax senticosus, Angelica sinensis and Scutellaria baicalensis are used in traditional oriental medicine and reportedly possess anti-inflammatory properties. Using the murine air pouch model of inflammation, we investigated the efficacy and mode of action of an extract from these three plants in crystal-induced inflammation. Air pouches were raised on the backs of 8-week-old BALB/c mice. Mice were fed 100 mg/kg body weight of root extracts (A. senticosus:A. sinensis:S. baicalensis mixed in a ratio of 5:4:1 by weight) or vehicle only on days 3-6. Inflammation was elicited on day 6 by injecting 2 mg of monosodium urate (MSU) crystals into the pouch. Neutrophil density and IL-6 and TNF-alpha mRNA levels were determined in the pouch membrane, and the leukocyte count and IL-6, prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2) levels were determined in the pouch exudate. Treatment with the root extracts led to a reduction in all inflammatory parameters: the leukocyte count in the pouch exudate decreased by 82%; the neutrophil density in the pouch membrane decreased by 68%; IL-6 and TNF-alpha mRNA levels in the pouch membrane decreased by 100%; the IL-6 concentration in the pouch fluid decreased by 50%; and the PGE2 concentration in the pouch fluid decreased by 69%. Remarkably, the concentration of the potentially anti-inflammatory PGD2 rose 5.2-fold in the pouch exudate (p0.005), which led to a normalization of the PGD2:PGE2 ratio. A 3.7-fold rise in hematopoietic PGD synthase (h-PGDS) mRNA paralleled this rise in PGD2 (p = 0.01). Thus, the root extracts diminished MSU crystal-induced inflammation by reducing neutrophil recruitment and expression of pro-inflammatory factors and increasing the level of the potentially anti-inflammatory PGD2. These results support a need for further studies of the efficacy of these extracts in the treatment of inflammatory arthropathies and suggest elevation of PGD2 levels as a novel mechanism for an anti-inflammatory agent.