Roles of Keratins in Intestine

Keratins make up a major portion of epithelial intermediate filament proteins. The widely diverse keratins are found in both the small and large intestines. The human intestine mainly expresses keratins 8, 18, 19, and 20. Many of the common roles of keratins are for the integrity and stability of the epithelial cells. The keratins also protect the cells and tissue from stress and are biomarkers for some diseases in the organs. Although an increasing number of studies have been performed regarding keratins, the roles of keratin in the intestine have not yet been fully understood. This review focuses on discussing the roles of keratins in the intestine. Diverse studies utilizing mouse models and samples from patients with intestinal diseases in the search for the association of keratin in intestinal diseases have been summarized.     

Pinostrobin Suppresses the α-Melanocyte-Stimulating Hormone-Induced Melanogenic Signaling Pathway

Pinostrobin is a dietary flavonoid found in several plants that possesses pharmacological properties, such as anti-cancer, anti-virus, antioxidant, anti-ulcer, and anti-aromatase effects. However, it is unclear if pinostrobin exerts anti-melanogenic properties and, if so, what the underlying molecular mechanisms comprise. Therefore, we, in this study, investigated whether pinostrobin inhibits melanin biosynthesis in vitro and in vivo, as well as the potential associated mechanism. Pinostrobin reduced mushroom tyrosinase activity in vitro in a concentration-dependent manner, with an IC₅₀ of 700 μM. Molecular docking simulations further revealed that pinostrobin forms a hydrogen bond, as well as other non-covalent interactions, between the C-type lectin-like fold and polyphenol oxidase chain, rather than the previously known copper-containing catalytic center. Additionally, pinostrobin significantly decreased α-melanocyte-stimulating hormone (α-MSH)-induced extracellular and intracellular melanin production, as well as tyrosinase activity, in B16F10 melanoma cells. More specifically, pinostrobin inhibited the α-MSH-induced melanin biosynthesis signaling pathway by suppressing the cAMP–CREB–MITF axis. In fact, pinostrobin also attenuated pigmentation in α-MSH-stimulated zebrafish larvae without causing cardiotoxicity. The findings suggest that pinostrobin effectively inhibits melanogenesis in vitro and in vivo via regulation of the cAMP–CREB–MITF axis.     

Two methods for the calculation of the degree of an approximate greatest common divisor of two inexact polynomials

The calculation of the degree d of an approximate greatest common divisor of two inexact polynomials f(y) and g(y) reduces to the determination of the rank loss of a resultant matrix, the entries of which are functions of the coefficients of f(y) and g(y). This paper considers this issue by describing two methods to calculate d, such that knowledge of the noise level imposed on the coefficients of f(y) and g(y) is not assumed. One method uses the residual of a linear algebraic equation whose coefficient matrix and right hand side vector are derived from the Sylvester resultant matrix S(f,g), and the other method uses the first principal angle between a line and a hyperplane, the equations of which are calculated from S(f,g). Computational results on inexact polynomials whose exact forms have multiple roots of high degree are shown and very good results are obtained. These results are compared with the rank loss of S(f,g) for the calculation of d, and it is shown that this method yields incorrect results for these examples.     

CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer

There is an urgent need for identification of new prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC). In this study, we evaluated immune cells markers in 100 NSCLC specimens. Immunohistochemical analysis revealed no prognostic value for the markers studied, except CD163 and CD206. At the same time, macrophage markers iNOS and CHID1 were found to be expressed in tumor cells and associated with prognosis. We showed that high iNOS expression is a marker of favorable prognosis for squamous cell lung carcinoma (SCC), and NSCLC in general. Similarly, high CHID1 expression is a marker of good prognosis in adenocarcinoma and in NSCLC in general. Analysis of prognostic significance of a high CHID1/iNOS expression combination showed favorable prognosis with 20 months overall survival of patients from the low CHID1/iNOS expression group. For the first time, we demonstrated that CHID1 can be expressed by NSCLC cells and its high expression is a marker of good prognosis for adenocarcinoma and NSCLC in general. At the same time, high expression of iNOS in tumor cells is a marker of good prognosis in SCC. When used in combination, CHID1 and iNOS show a very good prognostic capacity for NSCLC. We suggest that in the case of lung cancer, tumor-associated macrophages are likely ineffective as a therapeutic target. At the same time, macrophage markers expressed by tumor cells may be considered as targets for anti-tumor therapy or, as in the case of CHID1, as potential anti-tumor agents.     

Activation of Nrf2/HO-1 by Peptide YD1 Attenuates Inflammatory Symptoms through Suppression of TLR4/MYyD88/NF-κB Signaling Cascade

In this study, we investigate the immunomodulatory effects of a novel antimicrobial peptide, YD1, isolated from Kimchi, in both in vitro and in vivo models. We establish that YD1 exerts its anti-inflammatory effects via up-regulation of the Nrf2 pathway, resulting in the production of HO-1, which suppresses activation of the NF-κB pathway, including the subsequent proinflammatory cytokines IL-1β, IL-6, and TNF-α. We also found that YD1 robustly suppresses nitric oxide (NO) and prostaglandin E2 (PGE₂) production by down-regulating the expression of the upstream genes, iNOS and COX-2, acting as a strong antioxidant. Collectively, YD1 exhibits vigorous anti-inflammatory and antioxidant activity, presenting it as an interesting potential therapeutic agent.     

Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminus

The two-pore domain K⁺ (K_2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the γ-aminobutyric acid (GABA) receptors (GABA_AR and GABA_BR) reduces cellular excitability through Cl^- influx and K⁺ efflux in neurons. Relatively little is known about the link between GABA_AR and the K⁺ channel. The present study was performed to identify the effect of GABAR agonists on K_2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABA_AR and GABA_BR agonists. In particular, muscimol, a GABA_AR agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABA_AR antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl^- influx in GABAergic neurons.     

Encapsulation by spray drying of bioactive components, physicochemical and morphological properties from purple sweet potato

Purple-fleshed sweet potato flour could be used to enhance the colour, flavour and nutrients in food products. Thus, the investigation was to produce encapsulated flours from purple-fleshed sweet potato by spray drying using combinations of various levels of ascorbic acid (5 g kg⁻¹ and 10 g kg⁻¹) and maltodextrin (30 g kg⁻¹ and 100 g kg⁻¹) and to evaluate their effects on bioactive components, physicochemical and morphological properties. Encapsulated flours had higher total phenolic content, antioxidant capacity and water solubility index than non-encapsulated flour. There were no significant differences in anthocyanin content between encapsulated and non-encapsulated flours. However, water absorption index and flavonoids content of encapsulated flours depended on concentrations of ascorbic acid and maltodextrin. In addition, the high concentrations of ascorbic acid and maltodextrin encapsulated flours had higher glass transition temperature as compared to that of lower concentrations. In respect to morphology, the particles of encapsulated flours with high concentration of ascorbic acid and maltodextrin were more aggregated than those encapsulated with lower concentrations. Therefore, flours encapsulated with 10 g kg⁻¹ ascorbic acid and 30 g kg⁻¹ maltodextrin could be used to enhance the antioxidant activities of functional food ingredients.     

Modeling for multilevel switching in oxide-based bipolar resistive memory

We report a physical model for multilevel switching in oxide-based bipolar resistive memory (ReRAM). To confirm the validity of the model, we conduct experiments with tantalum-oxide-based ReRAM of which multi-resistance levels are obtained by reset voltage modifications. It is also noticeable that, in addition to multilevel switching capability, the ReRAM exhibits extremely different switching timescales, i.e. of the order of 10(-7)?s to 10(0)?s, with regard to reset voltages of only a few volts difference which can be well explained by our model. It is demonstrated that with this simple model, multilevel switching behavior in oxide bipolar ReRAM can be described not only qualitatively but also quantitatively.     

Integrated microfluidic drug delivery devices: a component view

Research on drug delivery devices is progressing rapidly with the main objective being the delivery of precise quantity of drugs into the target area of the body. A drug delivery device (DDD) needs to accurately control the flow rate of drug delivery and protects the body from undesired additional doses. An integrated microfluidic drug delivery device (IMDDD) is a miniature device that can regulate and monitor the delivery of the right amount of drug using micro-scale components. IMDDDs offer several advantages including ease of use, electro-chemical controllability, low power consumption, simplicity, fast fabrication, and good bio-compatibility. Various IMDDDs have been developed for treatment of cancer, cardiovascular disorder, eye and brain diseases, stress, and diabetes. This paper presents a generic architecture for IMDDDs, discusses the existing drug delivery methods, summarizes the specifications of the components, and identifies a number of performance evaluation parameters. The operation of IMDDDs is presented through fourteen potential internal components. In addition, recommendations on how enhance the design and fabrication process of IMDDDs are given.     

Synthesis of highly concentrated suspension of chemically converted graphene in organic solvents: Effect of temperature on the extent of reduction and dispersibility

We report the effect of temperature on the extent of graphene oxide reduction by hydrazine and the dispersibility of the resulting chemically converted graphene (CCG) in polar organic solvents. The extent of graphene oxide reduction at high temperatures was only slightly higher than at low temperatures (30–50 °C), while the dispersibility of the resulting CCG in organic solvents decreased markedly with increasing temperature. The low dispersibility of CCGs prepared at high temperatures was greatly affected by reduction and influenced by the formation of an irreversible agglomerate of CCG at high temperatures. The reduction of graphene oxide at low temperatures is necessary to prepare highly dispersible CCG in organic solvents. CCG prepared at 30 °C is dispersible in N-methyl-2-pyrrolidone concentrations as high as 0.71 mg/mL. The free-standing paper made of this CCG possessed an electrical conductivity of more than 22,000 S/m, one of the highest values ever reported.