Serotonin enhances the production of type IV collagen by human mesangial cells

BACKGROUND: The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells. METHODS: Human mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-beta (TGF-beta) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-beta mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively. RESULTS: 5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF-beta. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-beta antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF-beta. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-beta, but did not inhibit exogenous TGF-beta-induced increase in type IV collagen secretion. CONCLUSIONS: Our results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF-beta activity.     

Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone

Granisetron (G) is an effective antiemetic drug that is used to prevent cisplatin-induced emesis, although it is less effective for delayed emesis. To enhance the antiemetic effects of granisetron, corticosteroid analogues such as methylprednisolone (M) and dexamethasone (D) were employed in a study of patients treated with cisplatin (CDDP). We investigated the clinical response and urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of serotonin, in 31 patients with ovarian cancer or uterine endometrial cancer who received CAP therapy (CDDP 75 mg/m2) in a 3-day cross-over trial comparing G + M and G + D treated patients. Both regimens were and delayed emesis than G + D. We conclude that G + D is a more efficacious combination than G + D in protecting patients from CDDP-induced acute and delayed emesis.     

Comparison of Macro and Microtribological Property of Molybdenum Disulfide Film Exposed to LEO Space Environment

Macro- and microtribological properties of the MoS₂ film exposed to atomic oxygen, ultraviolet rays and radiation both in low earth orbit (LEO) and in ground-based facility were evaluated relevance to micro/nano satellites. MoS₂ samples are exposed to LEO space environment by the space environment exposure device experiment on international space station. Laser-detonation atomic oxygen beam source was used for atomic oxygen simulation on the ground. X-ray photoelectron spectroscopy and energy dispersive spectroscopy measurements suggested that electron beam and ultraviolet exposure did not affect chemical structure of MoS₂ surfaces. However, atomic oxygen-exposed and flight samples showed surface oxidation. It was found that the macroscopic friction coefficient of the flight sample was similar to that of the control sample. In contrast, remarkable increase in friction coefficient in microscopic properties was observed.     

Is the Efficiency of RNA Silencing Evolutionarily Regulated?

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) regulate gene expression in a sequence-specific manner. Genes with partial complementarity to siRNA/miRNA sequences in their 3′-untranslated regions (UTRs) are suppressed by a mechanism referred to as the siRNA off-target effect or miRNA-mediated RNA silencing. However, the determinants of such RNA silencing efficiency are poorly understood. Previously, I and co-workers reported that the efficiency of RNA silencing is strongly correlated with the thermodynamic stability of base pairing in the duplex formed within an siRNA/miRNA and between the seed region and its target mRNA. In this review, I first summarize our previous studies that identified the thermodynamic parameter to estimate the silencing efficiency using the calculated base pairing stability: siRNAs downregulate the expression of off-target genes depending on the stability of binding between the siRNA seed region (nucleotides 2–8) and off-target mRNAs, and miRNAs downregulate target mRNA expression depending on the stability of the duplex formed between the 5′ terminus of the miRNA and its target mRNA. I further discuss the possibility that such thermodynamic features of silencing efficiency may have arisen during evolution with increasing body temperature in various organisms.     

Long‐term changes in Japanese women's facial skin color

It has been suggested that skin color changes not only with advancing age but also with the times. The purpose of this study was to investigate changes in Japanese women's facial skin color over 25 years, as well as the changes in skin pigmentation that affect skin color. First, skin color changes in terms of Munsell color values were investigated. A total of 3181 Japanese women residing in the greater Tokyo area were enrolled, and datasets were collected using spectrophotometers, designated as the 1991, 2001, 2005, and 2015 data. The mean Munsell hue, value, and chroma were calculated for each measurement year. Next, the concentrations of melanin and hemoglobin were calculated from spectral data, to investigate changes in skin pigmentations. Finally, Monte Carlo simulations were performed to verify that the suggested changes in skin pigmentations brought about skin color changes. As a result, skin color significantly changed toward high lightness, low saturation, and high yellowness from the 1991 data to the 2001 data. From the 2005 to 2015 data, the skin color distribution shifted toward lower saturation and increased redness. In addition, the concentration of hemoglobin decreased significantly from the 1991 data to the 2001 data, while the melanin concentration decreased significantly from the 2005 data to the 2015 data.     

Titanium Fiber Plates for Bone Tissue Repair

Titanium plates are widely used in clinical settings because of their high bone affinity. However, owing to their high elastic modulus, these plates are not suitable for bone repair since their proximity to the bone surface for prolonged periods can cause stress shielding, leading to bone embrittlement. In contrast, titanium fiber plates prepared by molding titanium fibers into plates by simultaneously applying compression and shear stress at normal room temperature can have an elastic modulus similar to that of bone cortex, and stress shielding will not occur even when the plate lies flush against the bone's surface. Titanium fibers can form a porous structure suitable for cell adhesion and as a bone repair scaffold. A titanium fiber plate is combined with osteoblasts and shown that the titanium fiber plate is better able to facilitate bone tissue repair than the conventional titanium plate when implanted in rat bone defects. Capable of being used in close contact with bone for a long time, and even capable of promoting bone repair, titanium fiber plates have a wide range of applications, and are expected to make great contributions to clinical management of increasing bone diseases, including bone fracture repair and bone regenerative medicine.     

Influences of Soaking Temperature and Storage Conditions on Hardening of Soybeans (Glycine max) and Red Kidney Beans (Phaseolus vulgaris)

The influences of soaking treatment and storage conditions on the softening of cooked beans, namely, soybeans and red kidney beans, were investigated. It was revealed that the softening of fresh soybeans and fresh red kidney beans was suppressed during subsequent boiling after soaking treatment at 50 and 60 °C. Furthermore, in treated aged soybeans and red kidney beans that were subjected to storage at 30 °C/75% relative humidity for 6 mo and soaking treatment at 50 to 60 °C, the hardness during cooking was further amplified. This suggested that the mechanism of softening suppression differs depending on the influences of soaking and storage. Analysis of the pectin fraction in alcohol insoluble solid showed insolubilization of metal ions upon storage at high temperature and high humidity in both soybeans and red kidney beans, which suggests interaction between Ca ions and hemicellulose or cellulose as cell wall polysaccharides. The results of differential scanning calorimetry (DSC) showed that aged soybeans exhibited a shift in the thermal transition temperature of glycinin‐based protein to a higher temperature compared with fresh soybeans. From the results of DSC and scanning electron microscopy for aged red kidney beans, damaged starch is not conspicuous in the raw state after storage but is abundant upon soaking treatment. As for the influence of soaking at 60 °C, it can be suggested that its influence on cell wall crosslinking was large in soybeans and red kidney beans in both a fresh state and an aged state.     

Fiber of poly(vinyl alcohol) derived from vinyl trifluroacetate. III. Production and properties of fibers

The direct wet-spinning of syndiotacticity-rich poly(vinyl alcohol) from ammonolysis solutions of poly(vinyl trifluoroacetate) was carried out. The high draft in spinning could not be accomplished at lower and higher polymer concentration, but it was accomplished at a certain middle polymer concentration. The drawn fibers with high draft have not always high strength. The fibers with high strength were obtained from fibers wound at moderate draft in spinning and then drawn at higher times without solvent. The strength was independent on the degree of polymerization (in a range from DP = 1870 to DP = 5580), but it became higher in the case of thinner fibers obtained from the solutions of lower polymer concentration. Here, the highest Young's modulus and strength at break were 13.8 GPa and 12 gr/denier, respectively.     

Oral sustained delivery of paracetamol from in situ gelling xyloglucan formulations

The purpose of this study was to evaluate the potential of a xyloglucan formulation with in situ gelling properties for the oral sustained delivery of paracetamol. Gelation of dilute aqueous solutions of the polysaccharide xyloglucan occurred in rabbit and rat stomachs as the orally administered chilled solutions attained body temperature. In vitro studies demonstrated diffusion-controlled release of paracetamol from the gels over a period of 6 hr. The bioavailabilities of paracetamol from the xyloglucan gels formed in situ in the stomachs of rabbits after oral administration of the liquid formulations were similar to that of a commercially available suspension containing an identical dose of paracetamol.