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NADPH oxidases (NOXs) are comprised of different isoforms, NOX1 to 5 and Duox1 and 2, and they trigger diabetic nephropathy (DN) in the patients with diabetes mellitus. Recently, it was shown that, compared to the other isoforms, the expression of NOX5 was increased in the patients with DN and, NOX5 has been suggested to be important in the development of therapeutic agents. The effect of pan-NOX inhibition by APX-115 has also been investigated in type 2 diabetic mice. However, since NOX5 is absent in mice, we evaluated the effect of pan-NOX inhibition by APX-115 in Nox5 transgenic mouse. Wild type and renal podocyte specific NOX5 transgenic mice (NOX5 pod+) were fed with high-fat diet (60% kcal fat) and treated with APX-115 (60 mg/kg) by oral gavage for 14 weeks. APX-115 significantly improved pancreatic beta cell function by decreased fasting blood glucose levels and increased insulin levels. Further, the total serum cholesterol, triglycerides, and urinary albumin/creatinine levels were also significantly decreased by APX-115 treatment. Increased NOX5 mRNA expressions, increased desmin levels, and reduced podocin protein expressions in the kidney of NOX5 pod + mice were also significantly restored to normal levels by APX-115 treatment. Moreover, APX-115 inhibited the expression of inflammation-related proteins such as TRAF6. Collectively, these data suggest that APX-115 might be a promising therapeutic agent for the treatment of DN because of its pan-NOX inhibitory activity, including its NOX5 inhibitory activity, and also owing to its anti-inflammatory effect.

An ubiquinone derivative, pseudoalteromone A (1), has been isolated from two marine-derived Pseudoalteromonas spp., APmarine002 and ROA-050, and its anti-melanogenesis activity was investigated. The anti-melanogenic capacity of pseudoalteromone A was demonstrated by assessing the intracellular and extracellular melanin content and cellular tyrosinase activity in the B16 cell line, Melan-a mouse melanocyte cell line, and MNT-1 human malignant melanoma cell line. Treatment with pseudoalteromone A (40 μg/mL) for 72 h reduced α-melanocyte-stimulating hormone (α-MSH)-induced intracellular melanin production by up to 44.68% in B16 cells and 38.24% in MNT-1 cells. Notably, pseudoalteromone A induced a concentration-dependent reduction in cellular tyrosinase activity in B16 cell, and Western blot analyses showed that this inhibitory activity was associated with a significant decrease in protein levels of tyrosinase and tyrosinase-related protein 1 (Tyrp-1), suggesting that pseudoalteromone A exerts its anti-melanogenesis activity through effects on melanogenic genes. We further evaluated the skin-whitening effect of pseudoalteromone A in the three-dimensional (3D) pigmented-epidermis model, MelanoDerm, and visualized the 3D distribution of melanin by two-photon excited fluorescence imaging in this human skin equivalent. Collectively, our findings suggest that pseudoalteromone A inhibits tyrosinase activity and expression and that this accounts for its anti-melanogenic effects in melanocytes.

Ectopic fat accumulation in the kidneys causes oxidative stress, inflammation and cell death. Dehydrozingerone (DHZ) is a curcumin analog that exhibits antitumour, antioxidant and antidiabetic effects. However, the efficacy of DHZ in diabetic nephropathy (DN) is unknown. Here, we verified the efficacy of DHZ on DN. We divided the experimental animals into three groups: regular diet, 60% high‐fat diet (HFD) and HFD with DHZ for 12 weeks. We analysed levels of renal triglycerides and urinary albumin and albumin‐creatinine ratio, renal morphological changes and molecular changes via real‐time polymerase chain reaction and immunoblotting. Furthermore, high glucose (HG)‐ or palmitate (PA)‐stimulated mouse mesangial cells or mouse podocytes were treated with DHZ for 24 h. As a result, DHZ markedly reduced renal glycerol accumulation and albuminuria excretion through improvement of thickened glomerular basement membrane, podocyte loss and slit diaphragm reduction. In the renal cortex in the HFD group, phospho‐AMPK and nephrin expression reduced, whereas arginase 2 and CD68 expression increased; however, these changes were recovered after DHZ administration. Increased reactive oxygen species (ROS) stimulated by HG or PA in podocytes was inhibited by DHZ treatment. Collectively, these findings indicate that DHZ ameliorates DN via inhibits of lipotoxicity‐induced inflammation and ROS formation.

Curcumin, a compound found in Indian yellow curry, is known to possess various biological activities, including anti-oxidant, anti-inflammatory, and anti-cancer activities. Cur2004-8 is a synthetic curcumin derivative having symmetrical bis-alkynyl pyridines that shows a strong anti-angiogenic activity. In the present study, we examined the effect of dietary supplementation with Cur2004-8 on response to environmental stresses and aging using Caenorhabditis elegans as a model system. Dietary intervention with Cur2004-8 significantly increased resistance of C. elegans to oxidative stress. Its anti-oxidative-stress effect was greater than curcumin. However, response of C. elegans to heat stress or ultraviolet irradiation was not significantly affected by Cur2004-8. Next, we examined the effect of Cur2004-8 on aging. Cur2004-8 significantly extended both mean and maximum lifespan, accompanying a shift in time-course distribution of progeny production. Age-related decline in motility was also delayed by supplementation with Cur2004-8. In addition, Cur2004-8 prevented amyloid-beta-induced toxicity in Alzheimer's disease model animals which required a forkhead box (FOXO) transcription factor DAF-16. Dietary supplementation with Cur2004-8 also reversed the increase of mortality observed in worms treated with high-glucose-diet. These results suggest that Cur2004-8 has higher anti-oxidant and anti-aging activities than curcumin. It can be used for the development of novel anti-aging product.

Ginsenosides are active constituents of ginseng (Panax ginseng) that have possible anti-aging, physiological and pharmacological activities, such as anti-cancer and anti-inflammatory effects. Although the ginseng root is generally used more often than the aerial parts for medicinal purposes, the flowers also contain numerous ginsenosides, including Rb2, Rc, Rd, Re and Rg1. Therefore, an extract from the flowers of the P. ginseng could have the pharmacological efficacy of bioactive compounds including ginsenosides. The high hydrostatic pressure extraction (HHPE) is a method that is used for the efficient extraction of bioactive compounds from plant materials. In this study, we compared the yield of ginsenosides from ginseng flowers under different conditions of extraction pressure and time of HHPE. The results indicate that the total yield of the ginsenosides improved as the pressure increased from 0.1 to 80 MPa and treatment duration increased to 24 hours. In addition, the ginsenoside extracts from HHPE at 80 MPa, which possessed a higher total ginsenoside concentration, decreased the viability of the primary human epidermal keratinocytes (HEKs) significantly than the ginsenoside extracts from HHPE at 0.1 MPa. Collectively, we found that the method of HHPE that was performed for 24 hours at 80 MPa showed the highest yield of ginsenosides from the flowers of P. ginseng. In addition, our study provides a foundation for the efficient extraction of ginsenosides, which had a potent bioactivity, from flowers of P. ginseng through HHPE.

Background/Aims: Dehydroabietic acid (DAA) is a natural phytochemical found in red pine trees and herbal plants. While DAA and its derivatives are known for improving diabetes and hyperlipidemia, the antiaging effect and its underlying mechanisms of DAA on skin have not been fully examined. Here, we assessed the antiaging effects of DAA on human dermal fibroblasts and skin equivalents. Methods: We investigated the effect of DAA on the secretion of type I procollagen and matrix metalloproteinase-1 (MMP-1) in ultraviolet B (UVB)-irradiated neonatal normal human dermal fibroblasts (NHDFn). Using nonlinear optical imaging techniques, we visualized quantitative and qualitative changes of collagen fibers by DAA treatment in human skin equivalent models. Results: DAA induces increases in type I procollagen secretion when treated on UVB-irradiated NHDFn. DAA also downregulates secretion of MMP-1 through the inhibition of the JNK signaling pathway. In human skin equivalent models, we successfully visualized the spatial distribution of collagen fibers in the dermis and found that quantity, diameter, and arrangement of collagen fibers in the dermis were significantly improved by DAA treatment. Conclusion: Our results suggest that DAA could be a useful agent for improving skin photoaging through the protection and regeneration of collagen fibers in skin.

Precise measurement of particulate matter (PM) on skin is important for managing and preventing PM-related skin diseases. This study aims to directly visualize the deposition and penetration of PM into human skin using a multimodal nonlinear optical (MNLO) imaging system. We successfully obtained PM particle signals by merging two different sources, C–C vibrational frequency and autofluorescence, while simultaneously visualizing the anatomical features of the skin via keratin, collagen, and elastin. As a result, we found morphologically dependent PM deposition, as well as increased deposition following disruption of the skin barrier via tape-stripping. Furthermore, PM penetrated more and deeper into the skin with an increase in the number of tape-strippings, causing a significant increase in the secretion of pro-inflammatory cytokines. Our results suggest that MNLO imaging could be a useful technique for visualizing and quantifying the spatial distribution of PM in ex vivo human skin tissues.

The outer epidermal skin is a primary barrier that protects the body from extrinsic factors, such as ultraviolet (UV) radiation, chemicals and pollutants. The complete epithelialization of a wound by keratinocytes is essential for restoring the barrier function of the skin. However, age-related alterations predispose the elderly to impaired wound healing. Therefore, wound-healing efficacy could be also considered as a potent function of an anti-aging reagent. Here, we examine the epidermal wound-healing efficacy of the fourth-generation retinoid, seletinoid G, using HaCaT keratinocytes and skin tissues. We found that seletinoid G promoted the proliferation and migration of keratinocytes in scratch assays and time-lapse imaging. It also increased the gene expression levels of several keratinocyte proliferation-regulating factors. In human skin equivalents, seletinoid G accelerated epidermal wound closure, as assessed using optical coherence tomography (OCT) imaging. Moreover, second harmonic generation (SHG) imaging revealed that seletinoid G recovered the reduced dermal collagen deposition seen in ultraviolet B (UVB)-irradiated human skin equivalents. Taken together, these results indicate that seletinoid G protects the skin barrier by accelerating wound healing in the epidermis and by repairing collagen deficiency in the dermis. Thus, seletinoid G could be a potent anti-aging agent for protecting the skin barrier.

Meteorin‐like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium‐dependent AMPKα2 pathway in skeletal muscle cells and increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPKα2‐dependent manner. Phosphorylated HDAC5 interacts with 14‐3‐3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. An intraperitoneal injection of recombinant metrnl improved glucose tolerance in mice with high‐fat‐diet‐induced obesity or type 2 diabetes, but not in AMPK β1β2 muscle‐specific null mice. Metrnl improves glucose metabolism via AMPKα2 and is a promising therapeutic candidate for glucose‐related diseases such as type 2 diabetes., We found that metrnl, known as an adipomyokine, is secreted during muscle contractions. Metrnl increases glucose uptake via AMPKα in skeletal muscle cells and increases the phosphorylation of HDAC5 and TBC1D1 in AMPKα‐dependent manner. Recombinant metrnl improves glucose tolerance in mice with obesity or type 2 diabetes. These results suggest that metrnl is a promising therapeutic candidate for diabetes.

Hyperpigmentation is caused by excessive production of melanin in melanocytes. Mannosylerythritol lipids (MELs) are glycolipid biosurfactants that are abundantly produced by yeasts and used commercially in cosmetics. However, the potential depigmenting efficacy of MELs has not been evaluated. In this study, the depigmentary effect of MELs was tested in primary normal human melanocytes (NHMs), α-melanocyte-stimulating hormone (MSH)-stimulated B16 cells (murine melanoma cells) and a human skin equivalent (MelanoDerm) using photography, Fontana-Masson (F&M) staining and two-photon microscopy. Mannosylerythritol lipids significantly decreased the melanin contents in NHMs and α-MSH-stimulated B16 cells. Consistent with these findings, MELs treatment had a clear whitening effect in a human skin equivalent, brightening the tissue colour and reducing the melanin content. The molecular mechanism underlying the anti-melanogenic effect of MELs treatment was examined by real-time PCR and Western blotting. Mechanistically, MELs clearly suppressed the gene expression levels of representative melanogenic enzymes, including tyrosinase, Tyrp-1 and Tyrp-2, by inhibiting the ERK/CREB/MiTF signalling pathway in NHMs. This work demonstrates for the first time that MELs exert whitening effects on human melanocytes and skin equivalent. Thus, we suggest that MELs could be developed as a potent anti-melanogenic agent for effective whitening, beyond their use as a biosurfactant in cosmetics.

Objective Adipose tissue inflammation induced by macrophage infiltration through the C-C motif chemokine receptor (CCR) 2 or CCR5 pathway has a pivotal role in obesity-related disease and insulin resistance. Here, the effect of PF4178903, a dual CCR2/CCR5 antagonist, on obesity and insulin resistance was evaluated. Methods Forty male C57BL/6J mice were divided into four groups as follows: (1) regular diet (RD), (2) RD with PF4178903, (3) high-fat diet (HFD), and (4) HFD with PF4178903. All mice were sacrificed 12 weeks after the beginning of the experiment. Biochemical analyses and adipose tissue examinations were performed. Results After treatment with PF4178903, both body weight and adipocyte size in white adipose tissue were decreased in HFD-fed mice. Furthermore, PF4178903 treatment reduced adipose tissue macrophages (ATMs) and lowered serum proinflammatory cytokines in HFD-fed mice. PF4178903 treatment significantly improved HFD-induced insulin resistance and glucose intolerance. Fluorescence-activated cell sorter analysis revealed that PF4178903 treatment reduced the CD8 + T cell fraction in white adipose tissue of HFD-fed mice. PF4178903 treatment reduced M1-polarized macrophages while inducing an M2-dominant shift in macrophages within white adipose tissue in HFD-fed mice. Conclusions Dual CCR2/CCR5 antagonism ameliorates insulin resistance and inflammation in obesity by regulating ATM recruitment and polarization in white adipose tissue.

Background/Aims: Excessive melanogenesis often causes unaesthetic hyperpigmentation. In a previous report, our group introduced a newly synthesized depigmentary agent, Melasolv™ (3,4,5-trimethoxycinnamate thymol ester). In this study, we demonstrated the significant whitening efficacy of Melasolv using various melanocytes and human skin equivalents as in vitro experimental systems. Methods: The depigmentary effect of Melasolv was tested in melan-a cells (immortalized normal murine melanocytes), α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 murine melanoma cells, primary normal human melanocytes (NHMs), and human skin equivalent (MelanoDerm). The whitening efficacy of Melasolv was further demonstrated by photography, time-lapse microscopy, Fontana-Masson (F&M) staining, and 2-photon microscopy. Results: Melasolv significantly inhibited melanogenesis in the melan-a and α-MSH-stimulated B16 cells. In human systems, Melasolv also clearly showed a whitening effect in NHMs and human skin equivalent, reflecting a decrease in melanin content. F&M staining and 2-photon microscopy revealed that Melasolv suppressed melanin transfer into multiple epidermal layers from melanocytes as well as melanin synthesis in human skin equivalent. Conclusion: Our study showed that Melasolv clearly exerts a whitening effect on various melanocytes and human skin equivalent. These results suggest the possibility that Melasolv can be used as a depigmentary agent to treat pigmentary disorders as well as an active ingredient in cosmetics to increase whitening efficacy.

MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology. However, the mechanisms underlying MYH9-related glomerular diseases associated with proteinuria are poorly understood. Therefore, we investigated the role and mechanism of MYH9 in diabetic kidney injury. MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro. Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability. Ang II treatment increased NOX4 expression and ROS generation. The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability. Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins. Ang II-mediated TRPC6 activation reduced MYH9 expression. These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca2+ influx by NOX4-mediated ROS generation. These findings reveal a novel MYH9 function in maintaining urinary filtration barrier integrity. MYH9 may be a potential target for treating diabetic nephropathy.

The human skin is the outermost physical barrier and has its own circadian machinery that works either cooperatively with the central clock, or autonomously. Circadian rhythms have been observed in many functions related to epidermal homeostasis including hydration and inflammation, and this functional oscillation is disturbed by ultraviolet radiation (UVR), which is a strong environmental cue. Among the genes estimated to show circadian expression in the skin, metalloproteinase inhibitor 3 (TIMP3), has a rhythmic expression in synchronized human keratinocytes similar to that of the core clock gene PER1 and an epidermal circadian regulatory gene, aquaporin 3 (AQP3) but was antiphase to the core clock gene BMAL1. Tumor necrosis factor- (TNF-&alpha, ), the regulatory target of TIMP3 via a disintegrin and metalloproteinase domain 17 (ADAM17), was inversely regulated when TIMP3 expression was downregulated by ultraviolet B (UVB) treatment. When synthetic TIMP3 peptides were applied to the cells, the secretion of TNF- did not increase following the UVB treatment. Similar to TIMP3 peptides, Camellia sinensis leaf-derived extracts showed a distinguishing efficacy in recovering TIMP3 expression, downregulated by UVB treatment. Together, our results suggest that TIMP3 reversely mediates UVR-induced inflammation by being highly expressed during the daytime, therefore, recovering the circadian expression of TIMP3 using synthetic TIMP3 peptides or bioactive natural ingredients could at least in part inhibit the UVR-induced cellular phenomena.

Sugars are ubiquitous in organisms and well-known cosmetic ingredients for moisturizing skin with minimal side-effects. Glucose, a simple sugar used as an energy source by living cells, is often used in skin care products. Several reports have demonstrated that sugar and sugar-related compounds have anti-melanogenic effects on melanocytes. However, the underlying molecular mechanism by which glucose inhibits melanin synthesis is unknown, even though glucose is used as a whitening as well as moisturizing ingredient in cosmetics. Herein, we found that glucose significantly reduced the melanin content of &alpha, melanocyte-stimulating hormone (MSH)-stimulated B16 cells and darkly pigmented normal human melanocytes with no signs of cytotoxicity. Furthermore, topical treatment of glucose clearly demonstrated its whitening efficacy through photography, Fontana-Masson (F&amp, M) staining, and multi-photon microscopy in a pigmented 3D human skin model, MelanoDerm. However, glucose did not alter the gene expression or protein levels of major melanogenic proteins in melanocytes. While glucose potently decreased intracellular tyrosinase activity in melanocytes, it did not reduce mushroom tyrosinase activity in a cell-free experimental system. However, glucose was metabolized into lactic acid, which can powerfully suppress tyrosinase activity. Thus, we concluded that glucose indirectly inhibits tyrosinase activity through conversion into lactic acid, explaining its anti-melanogenic effects in melanocytes.

Dibenzoylmethane (DBM) is a beta-diketone analog of curcumin. Numerous studies have shown the beneficial effects of curcumin on diabetes, obesity and diabetic complications including diabetic nephropathy. Recently, we investigated the beneficial metabolic effects of DBM on high-fat diet-induced obesity. However, the effects and mechanisms of action of DBM in the kidney are currently unknown. To investigate the renoprotective effects of DBM in type 2 diabetes, we administered DBM (100 mg/kg) orally for 12 weeks to high-fat diet-induced diabetic model mice. We used mouse renal mesangial (MES13) and macrophage (RAW 264.7) cells to examine the mechanism of action of DBM (20 μM). After DBM treatment, the albumin-to-creatinine ratio was significantly decreased compared to that of the high-fat-diet group. Moreover, damaged renal ultra-structures and functions including increased glomerular volume, glomerular basement membrane thickness and inflammatory signals were ameliorated after DBM treatment. Stimulation of MES13 and RAW264.7 cells by palmitate or high-dose glucose with lipopolysaccharides increased inflammatory signals and macrophage migration. However, these changes were reversed by DBM treatment. In addition, DBM inhibited NADPH oxidase 2 and 4 expression and oxidative DNA damage. Collectively, these data suggested that DBM prevented diabetes-induced renal injury through its anti-inflammatory and antioxidant effects.

Meteorin-like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical-pulse-stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise-induced myokine. In addition, metrnl increases glucose uptake through the calcium-dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat-induced obesity or type 2 diabetes (db/db), but this is not seen in AMPK β1β2 muscle-specific null mice (AMPK β1β2 MKO). In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes.

Background Hyperglycemia-induced endoplasmic reticulum (ER) stress and oxidative stress could be causes of renal fibrosis in diabetes. Oleanolic acid (OA) naturally occurs in fruits and vegetables. It has anti-inflammatory, antihyperlipidemic and antioxidant effects. N-acetylcysteine (NAC) is a precursor of glutathione, which has a strong antioxidant effect in the body. In this study, we investigated the therapeutic effects of OA and NAC in diabetic nephropathy (DN). Methods Otsuka Long-Evans Tokushima Fatty rats were treated with OA (100 mg/kg/day) or NAC (300 mg/kg/day) for 20 weeks by oral gavage. Results The OA or NAC administration increased blood insulin secretion and superoxide dismutase levels, and decreased triglycerides and urinary albumin/creatinine levels. In the kidney, the damaged renal structure recovered with OA or NAC administration, through an increase in nephrin and endothelial selective adhesion molecules and a decrease in transforming growth factor-β/p-smad2/3 and ER stress. Reactive oxygen species and ER stress were increased by high glucose and ER stress inducers in cultured mesangial cells, and these levels recovered with OA (5.0 μM) or NAC (2.5 mM) treatment. Conclusion The findings in this study suggest that OA and NAC have therapeutic effects for DN through an antioxidant effect and ER stress reduction.

Objective Non-alcoholic fatty liver disease is characterized by high hepatic triacylglycerol contents, which is associated with endoplasmic reticulum (ER) stress and insulin resistance. Caffeic acid (CA) has antioxidant, immunomodulatory, and antiinflammatory effects. We investigated the effects of CA on hepatic steatosis and its mechanism of action. Methods We treated CA (50 µM) with AML12 cells. We categorized mice into three groups as follows: low-fat diet mice (LFD, n = 10), high-fat diet-induced obese mice (HFD, n = 10), and HFD fed with CA (50 mg/kg/d, n = 10) for 10 wk. Results CA did not cause any cytotoxic effect on AML12 cell line within the range of concentrations tested (0–200 µM). We found that CA (50 µM) treatment in palmitate-treated AML12 hepatocytes reduced lipid accumulation and lipogenesis markers, decreased ER stress, and increased autophagy markers. However, there was no significant difference in lipid droplets of palmitate-treated AML12 hepatocytes and CA-treated autophagy-related protein 7 deficiency AML12 hepatocytes with palmitate. Similarly, CA significantly lowered body and liver weights. Lipid accumulation in the liver decreased in the HFD + CA group compared with the HFD group. Glucose intolerance and insulin sensitivity also were markedly improved in the HFD + CA group. Moreover, the levels of ER stress markers were decreased in the livers of the HFD + CA group. Conclusion Autophagy markers were increased in the livers of the HFD + CA group. These results suggest that caffeic acid may ameliorate hepatic steatosis and decrease ER stress by increasing autophagy.

Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of an aldehyde to a carboxylic acid and are implicated in the etiology of numerous diseases. However, despite their importance, imaging ALDH activity in cells is challenging due to a lack of fluorescent imaging probes. In this report, we present a new family of fluorescent probes composed of an oligothiophene flanked by an aldehyde and an electron donor, termed thiophene-bridged aldehydes (TBAs), which can image ALDH activity in cells. The TBAs image ALDH activity via a fluorescence sensing mechanism based on the modulation of intramolecular charge transfer (ICT) and this enables the TBAs and their ALDH-mediated oxidized products, thiophene-bridged carboxylates (TBCs), to have distinguishable fluorescence spectra. Herein, we show that the TBAs can image ALDH activity in cells via fluorescence microscopy, flow cytometry, and in a plate reader. Using TBA we were able to develop a cell-based high throughput assay for ALDH inhibitors, for the first time, and screened a large, 1460-entry electrophile library against A549 cells. We identified α,β-substituted acrylamides as potent electrophile fragments that can inhibit ALDH activity in cells. These inhibitors sensitized drug-resistant glioblastoma cells to the FDA approved anti-cancer drug, temozolomide. The TBAs have the potential to make the analysis of ALDH activity in cells routinely possible given their ability to spectrally distinguish between an aldehyde and a carboxylic acid.

Long carbon fiber reinforced polypropylene (LCFP) composites were prepared at different fiber/resin input ratios and fiber lengths by extrusion and compression molding techniques. Fiber contents and fiber lengths were controlled by the carbon fiber/resin input ratio and screw extruder speed, respectively. The effects of the fiber content and fiber length on the mechanical properties of LCFP were investigated. The fiber length of the composites with the same fiber content decreased with an increase in screw speed. Further, the mechanical properties of the composites improved with an increase in the fiber content and mean fiber length. The fracture surfaces of the composites were investigated by scanning electron microscopy (SEM).

Microcrystalline cellulose (MCC) and polyamide 6 (PA6) fibers are used for the manufacture of thermoplastic nanocomposites. From the MCC (0.5 wt% of water), the cellulose nanofiber (CNF) with a mean fiber diameter below 30 nm is successfully obtained by a high pressure homogenizer with different processing conditions, such as various number of pass, nozzle size and operation pressure. As the operation pass number and pressure are increased, the specific surface area (SSA) of CNFs is increased due to the fibrillation during the homogenization process. The large surface area of CNF can improve the reinforcement effects for their nanocomposites. The composite papers, consisting of CNFs and PA6 fibers, are fabricated by a wet-laid sheet forming process. In this step, the pre-hydrolyzed silane coupling agent (0.1, 0.5, and 1.0 wt% in water) is added into the CNF slurry. The CNF/PA6 composites are pressed by a high pressure (3.4 and 4.8 MPa) calendering system. The tensile strengths of nanocomposites are increased by more than two times (max. 16.4 MPa) compared to PA6 100% sheets (6 MPa) due to the silane treatment, calendering process and reinforcement of CNFs. Open image in new window

The overexpression of vascular endothelial growth factor (VEGF) is known to be involved in the pathogenesis of diabetic nephropathy. In this study, the protective effects of taurine on diabetic nephropathy along with its underlying mechanism were investigated. Experimental animals were divided into three groups: LETO rats as normal group (n=10), OLETF rats as diabetic control group (n=10), and OLETF rats treated with taurine group (n=10). We treated taurine (200 mg/kg/day) for 20 weeks and treated high glucose (HG, 30 mM) with or without taurine (30 mM) in mouse cultured podocyte. After taurine treatment, blood glucose level was decreased and insulin secretion was increased. Taurine significantly reduced albuminuria and ACR. Also it decreased glomerular volume, GBM thickness and increased open slit pore density through decreased VEGF and increased nephrin mRNA expressions in renal cortex. The antioxidant effects of taurine were confirmed by the reduction of urine MDA in taurine treated diabetic group. Also reactive oxygen species (ROS) levels were decreased in HG condition with taurine treated podocytes compared to without taurine. These results indicate that taurine lowers glucose level via increased insulin secretion and ameliorates the progression of diabetic nephropathy through antifibrotic and antioxidant effects in type 2 diabetes rat model.

CCL2/CCR2 signaling is believed to play an important role in kidney diseases. Several studies have demonstrated that blocking of CCR2 has a therapeutic effect on kidney diseases. However, the effects of CCR2 knockout on obesity-induced kidney injury remain unclear. We investigated the therapeutic effects and the mechanism of CCL2/CCR2 signaling in obesity-induced kidney injury. We used C57BL/6-CCR2 wild type and C57BL/6-CCR2 knockout mice: Regular diet wild type (RD WT), RD CCR2 knockout (RD KO), High-fat diet WT (HFD WT), HFD CCR2 KO (HFD KO). Body weight of WT mice was significantly increased after HFD. However, the body weight of HFD KO mice was not decreased compared to HFD WT mice. Food intake and calorie showed no significant differences between HFD WT and HFD KO mice. Glucose, insulin, total cholesterol, and triglycerides levels increased in HFD WT mice were decreased in HFD KO mice. Insulin resistance, increased insulin secretion, and lipid accumulation showed in HFD WT mice were improved in HFD KO mice. Increased desmin expression, macrophage infiltration, and TNF-α in HFD mice were reduced in HFD KO mice. HFD-induced albuminuria, glomerular hypertrophy, glomerular basement membrane thickening, and podocyte effacement were restored by CCR2 depletion. HFD-induced elevated expressions of xBP1, Bip, and Nox4 at RNA and protein levels were significantly decreased in HFD KO. Therefore, blockade of CCL2/CCR2 signaling by CCR2 depletion might ameliorate obesity-induced albuminuria through blocking oxidative stress, ER stress, and lipid accumulation.

Mannosylerythritol lipids (MELs) are glycolipids and have several pharmacological efficacies. MELs also show skin-moisturizing efficacy through a yet-unknown underlying mechanism. Aquaporin-3 (AQP3) is a membrane protein that contributes to the water homeostasis of the epidermis, and decreased AQP3 expression following ultraviolet (UV)-irradiation of the skin is associated with reduced skin moisture. No previous study has examined whether the skin-moisturizing effect of MELs might act through the modulation of AQP3 expression. Here, we report for the first time that MELs ameliorate the UVA-induced downregulation of AQP3 in cultured human epidermal keratinocytes (HaCaT keratinocytes). Our results revealed that UVA irradiation decreases AQP3 expression at the protein and messenger RNA (mRNA) levels, but that MEL treatment significantly ameliorated these effects. Our mitogen-activated protein kinase inhibitor analysis revealed that phosphorylation of c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase or p38, mediates UVA-induced AQP3 downregulation, and that MEL treatment significantly suppressed the UVA-induced phosphorylation of JNK. To explore a possible mechanism, we tested whether MELs could regulate the expression of peroxidase proliferator-activated receptor gamma (PPAR-γ), which acts as a potent transcription factor for AQP3 expression. Interestingly, UVA irradiation significantly inhibited the mRNA expression of PPAR-γ in HaCaT keratinocytes, whereas a JNK inhibitor and MELs significantly rescued this effect. Taken together, these findings suggest that MELs ameliorate UVA-induced AQP3 downregulation in HaCaT keratinocytes by suppressing JNK activation to block the decrease of PPAR-γ. Collectively, our findings suggest that MELs can be used as a potential ingredient that modulates AQP3 expression to improve skin moisturization following UVA irradiation-induced damage.

Objective Changes in cholesterol ester (CE) content regulate the progression of atherosclerosis. However, the spatial dynamics of CE subsets and their quantitative changes during lesion progression are not well understood due to a lack of appropriate imaging techniques. In this study, we developed an imaging–based analysis method to map the distribution of CE subsets using time-of-flight secondary ion mass spectrometry (ToF-SIMS). Methods Serial sections of atherosclerotic aortic sinuses from apolipoprotein E knock-out mice ( n = 15) fed a 0.15% high-fat diet for 12–20 weeks were examined by ToF-SIMS. Results and conclusion We found that the ratio of cholesteryl palmitate (Ch-PA) to cholesteryl oleate (Ch-OA) increased by approximately 99% ( p = 0.02) as atherosclerosis progressed, whereas the ratios of cholesteryl linoleate ( p = 0.09) and cholesteryl stearate ( p = 0.22) to Ch-OA did not change significantly. In advanced atherosclerotic plaques, in situ and in-vitro cell death assays showed that local Ch-PA densities were highly correlated with an increase in the number of apoptotic cells. These results suggest that increased Ch-PA may contribute to the formation of a necrotic core by increasing cell death. Our results indicate that the regional ratio of CEs as measured by ToF-SIMS might be a valuable new marker of atherosclerotic progression.

Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.

We report the successful growth of quaternary Cu2ZnSnSe4 (CZTSe) thin films by pulsed laser deposition (PLD) using Nd:YAG laser. It was found that CZTSe films atomic ratios were close to target atomic ratios with a slight metal excess and selenium deficiency. Quaternary CZTSe films grew and crystallized as a stannite-type structure even at room temperature. All CZTSe films showed a p-type electrical conductivity with a high absorption coefficient of 104–105 cm–1, a bandgap of 1.5 eV and a carrier concentration of the order of 1017–1018 cm–3. These results show that pulsed laser deposition could be employed as a particularly effective deposition method for the preparation of quaternary compounds thin films. (© 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Cu 2 ZnSnSe 4 (CZTSe) thin films were grown in a single step procedure by RF magnetron sputtering from a compacted powder consisting of blended chalcogenides. Targets with various chalcogenide mole ratios were designed for the purpose of preparing stoichiometric as-grown films. The material concentrations of the films grown at room temperature were found to depend on the mole ratio of the chalcogenides in the targets. It was found that a significant deviation of material concentration of the films from ideal stoichiometry led to the formation of CuSe, ZnSe and SnSe secondary phases. CZTSe films with a stannite phase could be grown even at room temperature from the sputtering target containing Cu 2 Se with corresponding growth orientations of (101), (112), (220/204), (312/116) and (332/316). The p-type CZTSe film grown at a substrate temperature of 150 ∘ C showed a high absorption coefficient of 10 4 cm - 1 with an optical band gap of 1.56 eV, resistivity as low as 1.482 Ω cm and carrier concentration of 1 × 10 19 cm - 3 . These results suggested that the control of the target compositions was crucial to grow single phase and stoichiometric quaternary CZTSe films.

Polymer surfaces adsorb plasma proteins upon contact with blood. The nature of this adsorbed layer may determine the extent of platelet adhesion onto these surfaces. It is proposed in this study that incomplete terminal oligosaccharides, galactose, and N-acetyl-glucos-amine in adsorbed fibrinogen and γ-globulin are mainly responsible for the platelet adhesion, possibly via glycosyl transferase reactions. In order to verify these proposed mechanisms, platelet–protein interactions in the bulk state and platelet aggregation caused by the interactions were studied. The study was further extended into the reactions of platelets with adsorbed proteins. Data on protein adsorption from blood plasma onto model polymers (Teflon FEP, silastic rubber, Avcothane, and Biomer) provide supportive evidence for the proposed mechanism. The results discussed in this paper emphasize the important role of protein adsorption onto polymer surfaces and the possible involvement of specific reactions in platelet adhesion.

In this study, we attempted to use TRITON™ X (or octyl phenol ethoxylate (OPE) of different oxyethylene units (i.e., n = 2, 5, and 10))-based dispersants containing a carboxylic group in the oxyethylene chain end for the formulation of BAM phosphor paste. Thus, a three-component system employing OPE-COOH as a dispersant, terpineol as a solvent, and ethyl cellulose as a binder was compounded with BAM particles, and the rheological properties of the paste were investigated in detail. Among three acidic TRITON X-based compounds we tested (i.e., [OPE2-COOH], [OPE5-COOH], and [OPE10-COOH]), OPE10-COOH containing the highest number of oxyethylene units in the backbone was found to be the dispersant showing the lowest viscosity of BAM paste under identical conditions. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007

Dibenzoylmethane (DBM) has been shown to exert a variety of beneficial effects on human health. However, the mechanism of action is poorly understood. In this study, DBM increased phosphorylation of AMP-activated protein kinase (AMPK) and stimulated glucose uptake in a skeletal muscle cell line. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor blocked DBM-induced glucose uptake. DBM increased the concentration of intracellular calcium and glucose uptake due to DBM was abolished by STO-609 (a calcium/calmodulin-dependent protein kinase inhibitor). DBM stimulated phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which was blocked by pretreatment with compound C, an AMPK inhibitor. The expression of glucose transporter type 4 (GLUT4) was increased by DBM. The translocation of GLUT4 to the plasma membrane was also increased by DBM in AMPK dependently. In addition, DBM suppressed weight gain and prevented fat accumulation in the liver and abdomen in mice fed a high-fat diet. In pre-adipocyte cells, DBM decreased the activity of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid synthesis. Expression of the adipogenic gene, fatty acid synthase (FAS), was suppressed by DBM in an AMPK-dependent manner. These results showed that the beneficial metabolic effects of DBM might be due to regulation of glucose uptake via AMPK in skeletal muscle and inhibition of adipogenesis in pre-adipocytes.

Although lipid crystals (LCs) have received attention as a causative factor of plaque rupture, the mechanisms by which they increase plaque vulnerability are unknown. We examined whether solid-state LCs physically affect the adjacent extracellular matrix (ECM) using a combination of multimodal nonlinear optical (MNLO) imaging and finite element analysis (FEA).The changes of ECMs affected by lipids in atherosclerotic arteries in apolipoprotein E-deficient mice (n = 32) fed a high-fat diet for 20-30 weeks were micro-anatomically visualized by a 3D MNLO imaging platform including CARS for lipids, TPEF for elastin, and SHG for collagen.The TPEF signal of elastin was increased at the peripheral regions of LCs (10 μm) compared with foam cell regions. In order to confirm the increase of elastin, biochemical assay (western blot) was performed. The protein level of elastin was increased approximately 2.25-fold (p = 0.024) in LC-rich arteries. Under the hypothesis that the increase of elastin resulted from the mechanical stimulus from solid-state LCs, MNLO images were subjected to FEA to simulate the displacement according to the expanding magnitude of the vessel during cardiac cycles. We found that microscale focal stress was increased specifically around the LCs. These FEA results corresponded with the increase of elastin observed by TPEF. These data suggest that LCs mechanically stimulate the adjacent ECM to alter the composition of ECM and cause vessel remodeling. The combination of MNLO imaging and FEA has great potential to verify the mechanical predictions in cardiovascular diseases.

Oxidation and chemical modification of molybdenum micro tip surface have been investigated to understand the performance degradation mechanism of field emitter arrays(FEAs). Molybdenum FEAs could be easily oxidized due to their interaction with oxygen-containing species including O2, CO2 and H2O during cathode fabrication or thermal sealing processes of field emission displays(FEDs). During device operation, outgassing from phosphors due to electron-stimulated desorption and from other components inside a panel such as cathode, spacers, and sealant can lead to the chemical modification of the emitter surface. The oxidation and chemical modification of the emitter surface degrade the emission characteristics, resulting in the instability of an emission current, an increase of an electron extraction voltage for a given current, and lifetime reduction of the device. After the vacuum sealing and operation of the FED device, a micro tip is observed, and compared with an as-grown one by using scanning electron microscopy(SEM) and transmission electron microscopy(TEM). Chemical composition analyses of the degraded emitter surface by nano-probed Auger electron spectroscopy(AES) suggest that molybdenum micro tip is contaminated with S, In, C, and O after the device operation, where S and In seem to originate from the dissociation of phosphors by electron bombardment.

Morphologies of Spindt-type molybdenum microtips were modified by reactive ion etching following polyimide coating on field emitter arrays(FEAs). The modification produces nano-structured apexes on the microtips. The nano-structured geometry provides multiple emission sites to lower the driving gate bias by around 30V and to remarkably improve emission uniformity on 5.2″ FEAs. In addition, the double-gated FEAs, which are stable in a high voltage operation, were fabricated to achieve high brightness by taking advantage of the modification process.

Background Due to global marketing in the cosmetics industry, it is important to assess ethnic population susceptibility when evaluating the safety of cosmetic products or chemicals. Objectives To investigate ethnic variations in skin irritation response to positive irritants. Methods Clinical testing was performed in four countries on two ethnic groups – Asian and Caucasian. We performed patch tests on the subjects’ back with 0.5% aqueous sodium lauryl sulfate (SLS) and 0.15% retinol prepared in 1,3-butylene glycol. Stinging tests were performed using 5% aqueous lactic acid and 0.001% (w/v) capsaicin prepared in 10% ethanol solution separately. Results The incidence of self-perceived skin sensitivity was similar in the two ethnic groups. However, the incidence of adverse skin reaction to cosmetics appeared significantly higher in Asian (33.0%) than in Caucasian subjects (11.3%). For standard positive irritants such as 0.5% aqueous SLS solution, Asian subjects showed significantly higher scores than Caucasian subjects. The incidence of positive reaction to the 0.15% retinol patch test tended to be higher in Asian than in Caucasian subjects. Our data also showed that neurosensitivity to 5% lactic acid and 0.001% capsaicin was higher in Asian than in Caucasian subjects. Conclusion Although self-reported skin sensitivity does not appear to differ according to ethnicity, there are ethnic differences in objective and subjective skin irritation responses to several standard positive materials.

Background CCL2/C-C chemokine receptor 2 (CCR2) signalling is suggested to play a significant role in various kidney diseases including diabetic nephropathy. We investigated the renoprotective effect of a CCR2 antagonist, RS102895, on the development of diabetic nephropathy in a type 2 diabetic mouse model. Methods Six-week-old diabetic db/db and non-diabetic db/m mice were fed either normal chow or chow mixed with 2 mg/kg/day of RS102895 for 9 weeks. We investigated the effects of CCR2 antagonism on blood glucose, blood pressure, albuminuria and the structure and ultrastructure of the kidney. Results Diabetes-induced albuminuria was significantly improved after CCR2 antagonist treatment, and glucose intolerance was improved in the RS102895-treated diabetic mice. RS102895 did not affect blood pressure, body weight or kidney weight. Mesangial expansion, glomerular basement membrane thickening and increased desmin staining in the diabetic kidney were significantly improved after RS102895 treatment. The up-regulation of vascular endothelial growth factor mRNA expression and the down-regulation of nephrin mRNA expression were markedly improved in the kidneys of RS102895-treated diabetic mice. Increased renal CD68 and arginase II and urinary malondialdehyde in diabetes were effectively attenuated by RS102895 treatment. Conclusion Blockade of CCL2/CCR2 signalling by RS102895 ameliorates diabetic nephropathy not only by improving blood glucose levels but also by preventing CCL2/CCR2 signalling from altering renal nephrin and VEGF expressions through blocking macrophage infiltration, inflammation and oxidative stress in type 2 diabetic mice.

The lipid crystals are one of the important hallmarks of advanced atherosclerotic plaques. However, the detailed assessment of lipid crystals including their chemical compositions and morphological information at the tissue level are little known due to the lack of appropriate imaging techniques. Here, we developed a combinational method to characterize the morphology of lipid crystals precisely and concomitantly to identify their chemical compositions based on coherent anti-stokes raman scattering (CARS) spectroscopy and time-of-flight secondary-ion-mass-spectroscopy (ToF-SIMS). To accelerate the progression of atherosclerosis, partial ligation surgery of left carotid artery (LCA) in apolipoprotein E knock-out mice (n=26) was performed. The change of lipid crystals during the progression of atherosclerosis was studied by feeding high-fat diet for 1-8 weeks. We found the transition of chemical composition from oleate to the palmitate of atherosclerotic lipids at intermediate stage. Lipid crystals at advanced stage were dominantly observed at the inner side of internal elastic lamina and their distribution was clearly distinguished from other types of lipids. We also found that the lipid crystals showed distinct physical spectrum comparing to intra/extracellular lipid droplets by spectral CARS analysis. The same region of lipid crystals was subjected to investigation of chemical compositions using ToF-SIMS. We found that palmitate (m/z 255.2), a saturated fatty acid, was dominated in lipid crystal regions in advanced atherosclerotic stage. The developed technology based on the combination of CARS and ToF-SIMS could simultaneously provide the detailed lipid morphology with high resolution and chemical information correlating to their morphology. We expect that the results of lipid crystals with developed imaging platform could be further extended to better understanding for the mechanisms of plaque rupture.

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

Explosion phenomena of silver wires at reduced environmental air pressures have been investigated by applying oscillo-streak photographic technique, which has been designed for more exact temporal correlation between the oscilloscopic and streak records. Expanding speeds of metal cloud and shock wave increase at reduced pressure. However, for constant wire and discharging circuit parameters, traces of currents and voltages are not altered until the breakdown through metal cloud or air takes place. The critical pressure, below which the air surrounding metal cloud breaks down before the wire has been ruptured completely, has been found to be dependent on wire length and peak voltage induced during the rupture process in atmospheric condition. The empirical relationship between the ambient pressure, breakdown voltage, and wire length implies similarity between the breakdown of air ahead of the expanding metal cloud and the surface flash over of insulator at low pressure. Present results could support the concept that a metal wire bursts into nonconducting metal particles on the surface of the wire and the disintegration proceeds toward the wire axis.

On the basis of the universal cohesive energy model of Rose, Smith, Guinea and Ferrante (1981) it is shown that the temperature effects can be scaled so that the functional form of the pressure equation at finite temperatures is isomorphic to that of the cohesive pressure. Using the equation of state thus obtained, the authors calculate Hugoniot curves for some solids and compare the results with experimental data.

Background The human immunodeficiency virus type-1 (HIV-1) nucleocapsid protein (NC) is an essential and multifunctional protein involved in multiple stages of the viral life cycle such as reverse transcription, integration of proviral DNA, and especially genome RNA packaging. For this reason, it has been considered as an attractive target for the development of new anti-HIV drugs. Although a number of inhibitors of NC have been reported thus far, the search for NC-specific and functional inhibitor(s) with a good antiviral activity continues. Results In this study, we report the identification of A1752, a small molecule with inhibitory action against HIV-1 NC, which shows a strong antiviral efficacy and an IC50 around 1 μM. A1752 binds directly to HIV-1 NC, thereby inhibiting specific chaperone functions of NC including Psi RNA dimerization and complementary trans-activation response element (cTAR) DNA destabilization, and it also disrupts the proper Gag processing. Further analysis of the mechanisms of action of A1752 also showed that it generates noninfectious viral particles with defects in uncoating and reverse transcription in the infected cells. Conclusions These results demonstrate that A1752 is a specific and functional inhibitor of NC with a novel mode of action and good antiviral efficacy. Thus, this agent provides a new type of anti-HIV NC inhibitor candidate for further drug development. Electronic supplementary material The online version of this article (doi:10.1186/s12977-015-0218-9) contains supplementary material, which is available to authorized users.