Multiorgan-on-a-chip for realization of gut-skin axis.

The concept of physiological link between the gut and the skin, known as the gut-skin axis, has been gaining more evidence recently. Although experimental data from animal and human studies support the existence of the gut-skin axis, in vitro model platforms that can test the hypothesis are lacking. Organ-on-a-chip offers the possibility of connecting different tissues and recapitulating interactions between them. In this study, we report a multiorgan chip that can capture the basic interorgan communication between the gut and the skin. Its modular design enables separate culture and differentiation of the gut and skin tissues, and after assembly the two organs are connected via microfluidic channels than enables perfusion and mass transfer. We showed that the impairment of the gut barrier function exacerbated the adverse effect of fatty acids on skin cells, with decreased viability, increased level of cytokine secretion and human beta defensin-2 (hBD-2), an inflammatory dermal disease marker. Based on these results, we believe that our multiorgan chip can be a novel in vitro platform for recapitulating complex mechanisms underlying the gut-skin axis.

Relationships of viscosity with contact hardness and modulus of bone matrix measured by nanoindentation.

Creep is an active form of time-dependent viscoelastic deformation that occurs in bone tissue during daily life. Recent findings indicate bone mineralization, which is involved in determining the elastic and plastic properties of bone matrix, can also contribute in controlling its viscoelastic property. Nanoindentation viscosity was used as a direct measure for the capacity of a material to resist viscous-like flow under loading. The objectives of this study were to examine (1) whether the nanoindentation viscosity obtained using the traditional viscoelastic Voigt model can describe creep response of bone matrix and (2) how the nanoindentation viscosity is related to contact hardness and elastic modulus. The Voigt model accurately described the creep behavior of bone matrix (r(2)>0.96, p<0.001). The nanoindentation viscosity had strong relationships with nanoindentation contact hardness (r(2)=0.94, p<0.001) and modulus (r(2)=0.83, p<0.001) independent of tissue ages of osteonal bone matrix. The strong positive relationships of nanoindentation viscosity with contact hardness and modulus can be interpreted as increases in the mineral portion of bone matrix may limit the interfibril motion of collagen while enhancing the mechanical stability of bone. We suggest that previous nanoindentation results can be reanalyzed to characterize the viscoelastic creep using the Voigt model.

Biodegradation of bisphenol A and its halogenated analogues by Cunninghamella elegans ATCC36112.

Bisphenol A and its halogenated analogues are commonly used industrial chemicals with strong toxicological effects over many organisms. In this study, metabolic fate of bisphenol A and its halogenated analogues were evaluated with Cunninghamella elegans ATCC36112. Bisphenol A and related analogues were rapidly transformed into several metabolites by C. elegans within 2-4 days. Detailed analysis of metabolites reveals that both phase I and II metabolism occurred in C. elegans. Cytochrome P450-dependent hydroxylation was observed in BPA. However, major reaction with bisphenol A and analogues with 1-2 halogen atoms were the formation of glucose-conjugate, not being inhibited by cytochrome P450 inhibitor. Overall metabolic rates decreased with increasing number of substitution at 2- and 6-position of BPA structures, which may be consequences of limited bioavailability or steric hindrance to conjugate-forming reaction. Information from the current study will provide detailed insights over the fungal metabolism of BPA and analogues.

Using Light Quality for Growth Control of Cucumber Seedlings in Closed-Type Plant Production System.

During seedling production, growth control of seedlings is an important problem because the overgrowth of seedlings causes a decrease of seedling quality and has disadvantages after transplanting. In this study, we aim to evaluate the possibility of replacing chemical plant growth regulators using light quality in a closed-type plant production system (CPPS) for cucumber seedling production. We used various light treatments, such as monochromatic or combined red (R) and blue (B), and combined R and B with UV-A or Far-red (Fr) light, to compare with a chemical plant growth regulator conventionally using in nursery farms. The combined R and B treatment decreased stem elongation and increased dry matter and compactness. UV-A treatment increased compactness but did not significantly affect the stem elongation or dry matter. Fr increased stem elongation and stem diameter and decreased compactness and dry matter. In leaf growth, combined R and B treatments and UV-A treatments increased leaf area, specific leaf weight, and SPAD value, and decreased leaf shape index. Fr treatments increased leaf area and leaf shape index and decreased specific leaf weight (SLW) and SPAD values. Cucumber seedlings have many different morphological changes, and R5B5 light quality was more effective in growth control due to higher compactness than chemical plant growth regulators. Also, R5B5 light quality has increased seedling quality, such as dry matter and SLW compared with fluorescent lamps. Thus, the use of light quality is a possible alternative to a chemical plant growth regulator.

Growth and Bioactive Compound Content of Glehnia littoralis Fr. Schmidt ex Miquel Grown under Different CO2 Concentrations and Light Intensities.

This study aims to determine the effect of different CO2 concentrations and light intensities on the growth, photosynthetic rate, and bioactive compound content of Glehnia littoralis Fr. Schmidt ex Miquel in a closed-type plant production system (CPPS). The plants were transplanted into a deep floating technique system with recycling nutrient solution (EC 1.0 dS·m-1 and pH 6.5) and cultured for 96 days under a temperature of 20 ± 1 °C, a photoperiod of 12/12 h (light/dark), and RGB LEDs (red:green:blue = 7:1:2) in a CPPS. The experimental treatments were set to 500 or 1500 µmol∙mol-1 CO2 concentrations in combination with one of the three light intensities: 100, 200, or 300 µmol∙m-2∙s-1 photosynthetic photon flux density (PPFD). The petiole length of G. littoralis was the longest in the 500 µmol∙mol-1 CO2 concentration with the 100 µmol∙m-2∙s-1 PPFD. The fresh weight (FW) and dry weight (DW) of shoots and roots were the heaviest in the 300 µmol∙m-2∙s-1 PPFD regardless of the CO2 concentration. Higher CO2 concentrations and light intensities produced the greatest photosynthetic rates. However, the SPAD value was not significantly different between the treatments. Higher light intensities produced greater content per biomass of chlorogenic acid and total saponin, although the concentration per DW or FW was not significantly different between treatments. The first and second harvest yields were the greatest in the 300 µmol∙m-2∙s-1 PPFD, regardless of the CO2 concentration. These results show that the 300 µmol∙m-2∙s-1 PPFD enhanced the growth, photosynthetic rate, and bioactive compound accumulation of G. littoralis, regardless of the CO2 concentration in a CPPS.

Cholera outbreaks caused by an altered Vibrio cholerae O1 El Tor biotype strain producing classical cholera toxin B in Vietnam in 2007 to 2008.

Vibrio cholerae O1 isolates collected during cholera outbreaks occurring from late 2007 to early 2008 in northern Vietnam were revealed to represent an altered strain containing the RS1 element followed by a CTX prophage harboring El Tor type rstR and classical ctxB on the large chromosome.

Growth Characteristics of Adenophora triphylla var. japonica Hara Seedlings as Affected by Growing Medium.

Adenophora triphylla var. japonica Hara is a highly valued medicinal plant that is used to treat or prevent bronchitis, cough, cancer, and obesity. However, there has been no study on the production of Adenophora triphylla var. japonica Hara seedlings in a closed-type plant production system (CPPS). This study was conducted to examine the growth characteristics of Adenophora triphylla var. japonica Hara seedlings as affected by different growing media. The seeds were sown on a 128-cell plug tray filled with urethane sponges (US), LC grow foam (LC), rockwool (RW), or terra-plugs (TP). The seedlings were cultured for a duration of 54 days under temperature 25 ± 1°C, a photoperiod of 12/12 h (light/dark), and light intensity of 180 µmol·m-2·s-1 photosynthetic photon flux density provided by RB LEDs (red:blue = 8:2) in a closed-type plant production system (CPPS). The germination rate of Adenophora triphylla var. japonica Hara was significantly highest in the TP. Also, seedling shoot growth indicators of plant height, leaf length, leaf width, number of leaves, fresh weight (FW), and dry weight (DW) of the shoot, and leaf area were markedly the greatest in the TP and the lowest in the US. The SPAD (soil-plant analysis development) value was higher in the TP and US than in the LC or RW. In addition, the seedling root growth characteristics of total root length, root surface area, root volume, and number of root tips were significantly greatest in the TP. Moreover, the maximum root diameter, FW and DW of roots were the greatest in the TP. In conclusion, the results suggest that TP are viable for the growth development of Adenophora triphylla var. japonica Hara seedlings.

Characteristics of a pandemic clone of O3 : K6 and O4 : K68 Vibrio parahaemolyticus isolated in Beira, Mozambique.

The genetic characteristics of Vibrio parahaemolyticus strains isolated in 2004 and 2005 in Mozambique were assessed in this study to determine whether the pandemic clone of V. parahaemolyticus O3 : K6 and O4 : K68 serotypes has spread to Mozambique. Fifty-eight V. parahaemolyticus strains isolated from hospitalized diarrhoea patients in Beira, Mozambique, were serotyped for O : K antigens and genotyped for toxR, tdh and trh genes. A group-specific PCR, a PCR that detects the presence of ORF8 of the filamentous phage f237, arbitrarily primed PCR, PFGE and multilocus sequence typing were performed to determine the pandemic status of the strains and their ancestry. All strains of serovars O3 : K6 (n=38) and O4 : K68 (n=4) were identified as a pandemic clonal group by these analyses. These strains are closely related to the pandemic reference strains of O3 : K6 and O4 : K68, which emerged in Asia in 1996 and were later found globally. The pandemic serotypes O3 : K6 and O4 : K68 including reference strains grouped into a single cluster indicating emergence from a common ancestor. The O3 : K58 (n=8), O4 : K13 (n=6), O3 : KUT (n=1) and O8 : K41 (n=1) strains showed unique characteristics different from the pandemic clone.

Prednisolone-loaded coatable polyvinyl alcohol/alginate hydrogel for the treatment of atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting pruritic, erythema, edema, excoriation, and thickening of the skin, and thus leads to significant impairment in the patient's life. The objective of this study is to develop a steroid drug [prednisolone (PS)]-loaded coatable hydrogel for the treatment of AD. PS-loaded hydrogel was composed of PVA entrapped in mildly crosslinked alginate (PS-loaded PVA/ALG hydrogel). The PS concentration to be loaded in the hydrogel that takes AD efficacy without cell necrosis was determined from the cytotoxicity test using human dermal fibroblasts. The in vivo therapeutic effects for AD of the PS-loaded PVA/ALG hydrogel were evaluated using 2, 4-dinitrochlorobenzene (DNCB)-induced AD Balb/c mouse model. The PS-loaded hydrogel has an appropriate viscosity for easy application and provides moisturizing effect on the skin, as well as anti-inflammatory effect by the sustained drug release for effective AD treatment. From the animal study, the PS-loaded PVA/ALG hydrogel showed effective suppressions of various AD symptoms such as ear edema, pruritus, high IgE levels, epidermal swelling, and mast cell infiltration. Our findings suggest that the PS-loaded coatable PVA/ALG hydrogel may be a promising therapeutic system for the treatment of AD.

Phospholipid End-Capped Acid-Degradable Polyurethane Micelles for Intracellular Delivery of Cancer Therapeutics.

Nanoscale drug carriers fabricated by phospholipid end-capped polyurethane bearing acetal backbones that degrade in acidic conditions are fabricated. These micelles effectively allow drugs to enter the blood circulation, and then disintegrate in acidic endosomes and lysosomes for intelligent delivery of payloads.

Polymer Nanocomposite Electrode Consisting of Polyaniline and Modified Multi-Walled Carbon Nanotube for Rechargeable Battery.

In this study, PANI nanocomposite with modified multi-walled carbon nanotube (mMWCNT) was prepared. Herein MWCNT was modified by Friedel-Crafts acylation reaction. The dc conductivity of PANI nanocomposite according to the content of mMWCNT was measured by four-point probe. The highest conductivity of 9.49 S/cm was obtained in case of PANI nanocomposite with 3 wt% of mMWCNT. And it could be known that MWCNT was less damaged by the modification of Friedel-Crafts acylation reaction (mMWCNT) than strong acid treatment (aMWCNT), so the thermal stability of PANI nanocomposite was higher than that of pure PANI. And the morphology and crystallinity of the PANI nanocomposite were investigated by field emission scanning electron microscope (FE-SEM), transmission electron microscope (TEM) and X-ray diffraction. Also the electrochemical property of PANI nanocomposite was intensively investigated by cyclic voltammetry (CV) and charge-discharge capacity. From the CV data, it could be known that the charge-discharge capacity of PANI nanocomposite electrode was improved compared to pure PANI and PANI + aMWCNT electrodes.

Efficient, Solvent-Free, Multicomponent Method for Organic-Base-Catalyzed Synthesis of ß-Phosphonomalonates.

An efficient, one-pot, di-n-butylamine-catalyzed, three-component synthesis of ß-phosphonomalonates has been developed. A wide range of substrates, including aromatic and fused aromatic aldehydes, were condensed with enolizable C-H activated compounds and dialkylphosphites to give the desired products in excellent yields. This method provides an eco-friendly alternative approach to rapid construction of a diversity-oriented library of ß-phosphonomalonates.

Poly(PEGA)-b-poly(L-lysine)-b-poly(L-histidine) Hybrid Vesicles for Tumoral pH-Triggered Intracellular Delivery of Doxorubicin Hydrochloride.

A series of poly(ethylene glycol) methyl ether acrylate-block-poly(L-lysine)-block-poly(L-histidine) [p(PEGA)30-b-p(Lys)25-b-p(His)n] (n = 25, 50, 75, 100) triblock copolypeptides were designed and synthesized for tumoral pH-responsive intracellular release of anticancer drug doxorubicin hydrochloride (Dox). The tumoral acidic pH-responsive hybrid vesicles fabricated were stable at physiological pH 7.4 and could gradually destabilize in acidic pH as a result of pH-induced swelling of the p(His) block. The blank vesicles were nontoxic over a wide concentration range (0.01-100 µg/mL) in normal cell lines. The tumor acidic pH responsiveness of these vesicles was exploited for intracellular delivery of Dox. Vesicles efficiently encapsulated Dox, and pH-induced destabilization resulted in the controlled and sustained release of Dox in CT26 murine cancer cells, and dose-dependent cytotoxicity. The tumor-specific controlled release Dox from vesicles demonstrates this system represents a promising theranostic agent for tumor-targeted delivery.

Effect of estrogen deficiency on regional variation of a viscoelastic tissue property of bone.

Estrogen deficiency changes the regional distribution of tissue mineral density leading to alteration of the mechanical properties of bone at the tissue level. Direct measurement of the regional variation of elastic modulus and viscosity, which is the capacity to resist time-dependent viscoelastic deformation, will aid in our understanding of how estrogen deficiency alters bone quality. It was observed that, compared to bone from other anatomical sites, the jaw bone is less sensitive to estrogen deficiency. Thus, the objective of this study was to examine the effect of estrogen deficiency on (1) the regional variations of tissue modulus and viscosity of bone using nanoindentation, and (2) the modulus-viscosity relationships in jaw and vertebral bones for comparison between different anatomical sites. Mandibular and vertebral bone specimens of sham surgery and ovariectomized (OVX) rat groups were subject to nanoindentation in hydration. Indentation modulus and viscosity were measured at relatively new (less mineralized) tissue regions and at the corresponding pre-existing old (more mineralized) tissue regions of mandibular and vertebral bones. In the mandibular bones, significant regional variations of indentation modulus and viscosity were observed (p<0.039) and OVX increased the indentation viscosity. While significant positive correlations were found between indentation modulus and viscosity (p<0.001), the correlation slopes for the mandibular and vertebral bones were significant different (p<0.001). The current results indicated that changes in viscoelastic property and its regional variation should be examined to obtain a better understanding of estrogen deficiency-dependent alteration of bone quality.

Increased variability of bone tissue mineral density resulting from estrogen deficiency influences creep behavior in a rat vertebral body.

Progressive vertebral deformation increases the fracture risk of a vertebral body in the postmenopausal patient. Many studies have observed that bone can demonstrate creep behavior, defined as continued time-dependent deformation even when mechanical loading is held constant. Creep is a characteristic of viscoelastic behavior, which is common in biological materials. We hypothesized that estrogen deficiency-dependent alteration of the mineral distribution of bone at the tissue level could influence the progressive postmenopausal vertebral deformity that is observed as the creep response at the organ level. The objective of this study was thus to examine whether the creep behavior of vertebral bone is changed by estrogen deficiency, and to determine which bone property parameters are responsible for the creep response of vertebral bone at physiological loading levels using an ovariectomized (OVX) rat model. Correlations of creep parameters with bone mineral density (BMD), tissue mineral density (TMD) and architectural parameters of both OVX and sham surgery vertebral bone were tested. As the vertebral creep was not fully recovered during the post-creep unloading period, there was substantial residual displacement for both the sham and OVX groups. A strong positive correlation between loading creep and residual displacement was found (r=0.868, p<0.001). Of the various parameters studied, TMD variability was the parameter that best predicted the creep behavior of the OVX group (p<0.038). The current results indicated that creep caused progressive, permanent reduction in vertebral height for both the sham and OVX groups. In addition, estrogen deficiency-induced active bone remodeling increased variability of trabecular TMD in the OVX group. Taken together, these results suggest that increased variability of trabecular TMD resulting from high bone turnover influences creep behavior of the OVX vertebrae.

Effects of pesticides on the bacterial production of pyrrolnitrin.

Pyrrolnitrin is a halogenated bacterial metabolite with antifungal and antibacterial activities which served as a lead structure of synthetic fungicides. Several pyrrolnitrin-producing bacteria are considered to be promising biopesticides. However, the application of these microorganisms is not straightforward since many synthetic pesticides usually coexist in agricultural fields and inevitably affect the efficacy of biocontrol agents. In this regard, effects of 25 xenobiotics, including 18 pesticides, were investigated for pyrrolnitrin biosynthesis by Burkholderia sp. O33 and Pseudomonas fluorescens Pf-5. Strong inhibition of pyrrolnitrin synthesis was observed in 9 chemicals, including 6 pesticides, while glyphosate and validamycin enhance biosynthesis. Fenpiclonil and fludioxonil strongly inhibit the oxidative transformation of aminopyrrolnitrin to pyrrolnitrin. Halogenation reaction to aminopyrrolnitrin was reduced by methimazole, a well-known flavin-dependent monooxygenase inhibitor. Most pesticides gave moderate growth inhibitory effects. The results suggested that synthetic chemicals can modulate the efficacy of pyrrolnitrin producing bacteria, through the inhibition of cell growth or pyrrolnitrin biosynthesis. Pathway specific inhibition by fenpiclonil, fludioxonil, and methimazole will give structural insights of corresponding enzymes.