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Hyaluronan (HA) is a central component of the extracellular matrix (ECM) in the brain and plays a pivotal role in neural development and plasticity. Brain HA exists in 2 distinct forms of the ECM: the diffuse ECM, which is soluble in saline and detergents, and the condensed ECM, which forms aggregates, such as perineuronal nets (PNNs). Although the physiological functions of HA significantly differ depending on its size, size differences in HA have not yet been examined in the 2 ECM types, which is partly because of the lack of methods to rapidly and accurately measure the molecular weight (MW) of HA. In this study, we established a simple method to simultaneously assess the MW of HA in multiple crude biological samples. HA was purified through single-step precipitation from tissue extracts using biotinylated HA-binding protein and streptavidin-coupled magnetic beads, followed by separation on gel electrophoresis. By applying this method to HA in the mouse brain, we revealed that the condensed ECM contained higher MW HA than the diffuse ECM. Higher MW HA and lower MW HA exhibited different spatial distributions: the former was confined to PNNs, whereas the latter was widely present throughout the brain. Furthermore, the limited degradation of HA showed that only higher MW HA was required to form an insoluble HA-aggrecan complex. The present study demonstrated that the MW of HA in the brain strongly correlates with the localization and solubility of the ECM it forms. [ABSTRACT FROM AUTHOR]

Background: Left‐ventricular systolic dysfunction (LVSD) comorbid with atrial fibrillation is reversible, but recovery is limited in a subset of patients. The Selvester QRS (S‐QRS) score is an electrocardiogram‐based assessment that reportedly reflects myocardial scar/damage. We evaluated the predictability of S‐QRS score for the recovery of left‐ventricular ejection fraction (LVEF) in persistent AF (PeAF) patients with LVSD undergoing catheter ablation (CA). Method: CA was performed in 51 PeAF patients with reduced LVEF (<40%); S‐QRS scores were measured after restoration of sinus rhythm. LVEF was re‐evaluated at one year after CA; LVEF recovery was related to the S‐QRS score. Results: The median [interquartile range] S‐QRS score was 1 point [0–2]. LVEF increased from 32% [28–37] at baseline to 56% [49–57] at 1 year after CA. Thirty‐seven patients achieved normalization of LVEF (≥50%, Group A); 14 patients did not (Group B). Group A had significantly lower S‐QRS scores than Group B (0 point [0–2] vs. 2 points [2–3], p <.05). In univariate/multivariate analyses, S‐QRS score was an independent predictor of LVEF normalization. In the receiver operating characteristic curve, the cut‐off value of S‐QRS score was 2 points for prediction of the LVEF normalization (AUC = 0.79). Patients with low S‐QRS score (<2 points) had greater LVEF improvement than those with high S‐QRS score (≥2 points, ΔLVEF: 23% [17–28] vs. 17% [12–24], p <.05). Conclusion: S‐QRS scoring noninvasively assesses the improvement of LVEF in PeAF patients with LVSD after CA. A high S‐QRS score may indicate underlying myocardial scar/damage associated with unknown etiologies for LVSD other than PeAF. [ABSTRACT FROM AUTHOR]

Investigates the strain effects on the enhancement of the luminescence capability of germanium/silicon (Ge/Si) disordered superlattices (d-SLs). Comparison of the photoluminescence properties of Ge/Si superlattices grown on Si substrate and on strain-free SiGe buffer layer; Observation of enhanced photoluminescence in the d-SLs grown on the SiGe buffer layer.

The properties of hydrolyzed feather keratin ( HFK) were compared to those of hydrolyzed wool keratin ( HWK) with the aim of developing better ways to utilize feather keratin waste. Amino acid analysis showed that HFK contained more hydrophobic amino acids did than HWK. Although gel permeation chromatography indicated that HFK and HWK had more low-molecular weight peptides than their intact sources, Fourier transform infrared spectroscopy indicated that both hydrolyzed keratins retained their original secondary structure. The physical properties of HFK were evaluated by treating HFK to human hair fibers. HFK treatment enhanced significantly the surface hydrophobicity and strength of fibers, and HFK was more permeable into hair fibers. These results suggest that HFK is suitable for industrial applications to improve fibers. In addition, HFK may be suitable for raw material of products requiring both flexibility and hydrophobicity, such as films and biodegradable plastics. [ABSTRACT FROM AUTHOR]

Mast cells are one of the major producers of prostaglandins (PGs). The final metabolite of PGs, 15-deoxy-delta-12,14-PGJ2 (15-deoxy-delta PGJ2) is the endogenous ligand of the peroxisome proliferator-activated receptor (PPAR) γ. PPARγ modulates adipocyte differentiation; therefore, we attempted to investigate whether PGs derived from mast cells influenced on adipogenesis. We found the increase of mast cell numbers in fat tissue of obese mice fed with a high fat diet, allowing us to speculate contributions of mast cells to adipogenesis. Mast cell-mediated induction of adipogenesis was evaluated by using 3T3 L1 cells. Supernatants obtained from mast cells stimulated with calcium ionophore or the high glucose condition contained 15-deoxy-delta PGJ2 and induced adipogenesis of 3T3 L1 cells. Agonistic activity of PGJ2 from the supernatants on PPARγ was confirmed by a reporter gene assay. Culture medium collected from calcium ionophore-stimulated BMCMC activated PPAR responsive element in NIH3T3 fibroblasts, and the specific inhibitor of PPARγ canceled the activation. Contribution of mast cells to obesity was evaluated by using mast cell-deficient mice fed with a western diet. Weight gain of mast cell-deficient mice during high-fat feeding was impaired as compared to their littermate wild type mice; on the other hand, transplantation of bone marrow-derived cultured mast cells to mast cell-deficient mice restored the weight gain by intake of a high-fat diet. In this study, we clearly demonstrated that mast cells produced PGs in response to the high glucose condition and induced adipocyte differentiation and possibly obesity. This is the first study that provides evidence for a novel role of mast cells in adipogenesis via PPARγ activation. [ABSTRACT FROM AUTHOR]

The article presents a study that evaluates the effects of control of collagen molecular assembly with anionic polysaccharides. It is undertaken through evaluating the effects of adding a polyanionic saccharide to a collagen solution on the reconstruction rate of collagen molecular assembly. Results show that the rate is reduced when alginic acid is added. The study also concludes that the use of a polyanionic saccharide makes it possible for reconstructed collagen fabrils to be endowed.

Decorin, the main proteoglycan in skin, has a small size with a core protein of &nvsim; 40kDa and one chondroitin sulfate/dermatan sulfate glycosaminoglycan (GAG) chain. The main function of decorin is to regulate the collagen matrix assembly. Decorin is distributed along collagen fibrils with the core protein and the decorin GAG chain controls the distance between the collagen fibrils. Reducing the length of the decorin GAG chain reduces the distance between the collagen fibrils. Age-related changes in decorin are apparent in the GAG chain in respect to the molecular size and sulfate position but not in the core protein. Structural changes in the decorin GAG chain may be involved in changes in collagen matrix assembly during the aging process. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The incidence of bovine spongiform encephalopathy has resulted in marine collagen hydrolysate (low-molecular-weight gelatin) being sold as supplements and cosmetics in Japan. Shark skin collagen is one of the important sources of marine collagen. We examined the effect of shark skin gelatin in an osteoporosis model animal. Methods: Shark skin gelatin was orally administered to ovariectomized rats with a low-protein diet. Bone mineral density of the right femur was measured. Collagen and glycosaminoglycan in the tibial end were extracted and analyzed by western blotting and cellulose acetate membrane electrophoresis, respectively. Results: Administering collagen to the ovariectomized rats resulted in the bone mineral density of the femur epiphysis being higher than that in the sham-operated rats. The contents of type I collagen and glycosaminoglycan in the epiphysis were increased by administering shark skin gelatin. Conclusions: These results indicated that shark skin gelatin would be useful as a dietary supplement for treating osteoporosis. [Copyright &y& Elsevier]

Studies renaturation properties of collagen type one from shark skin. Increase in optical rotation and viscosity of shark skin collagen; Renaturation of alpha one chains; Size exclusion chromatographic patterns; Denaturation of collagen to gelatin.

Introduction: Silent cerebral events (SCEs) are related to the potential thromboembolic risk in atrial fibrillation (AF) ablation. Periprocedural uninterrupted oral anticoagulation (OAC) reportedly reduced the risk of SCEs, but the incidence still remains. Methods and Results: AF patients undergoing catheter ablation were eligible. All patients took non–vitamin K antagonist oral anticoagulants (NOACs; n = 248) or vitamin K antagonist (VKA; n = 37) for periprocedural OAC (>4 weeks) without interruption during the procedure. Brain magnetic resonance imaging was performed within 2 days after the procedure to detect SCEs. Clinical characteristics and procedure‐related parameters were compared between patients with and without SCEs. SCEs were detected in 66 patients (23.1%; SCE[+]) but were not detected in 219 patients (SCE[−]). Age was higher in SCE[+] than in SCE[−] (66 ± 10 vs. 62 ± 12 years; p <.05). Persistent AF prevalence, CHADS2/CHA2DS2‐VASc scores, serum NT‐ProBNP levels, left atrial dimension (LAD), and spontaneous echo contrast prevalence in transesophageal echocardiography significantly increased in SCE[+] versus SCE[−]. SCE[+] had lower baseline activated clotting time (ACT) before heparin injection and longer time to reach optimal ACT (>300 s) than SCE[−] (146 ± 27 vs. 156 ± 29 s and 44 ± 30 vs. 35 ± 25 min; p <.05, respectively). In multivariate analysis, age, LAD, baseline ACT, and time to reach the optimal ACT were predictors for SCEs. The average values of the ACT parameters were significantly different among NOACs/VKA. Conclusion: Age, LAD, and intraprocedural ACT kinetics significantly affect SCEs during AF ablation. Different anticoagulants have different impacts on ACT during the procedure, which should be considered when estimating the risk of SCEs. [ABSTRACT FROM AUTHOR]

Persistent atrial fibrillation (PeAF) may develop arrhythmogenic substrates of rotors/multiple wavelets. However, the ways in which pulmonary vein isolation (PVI) affects the dynamics of rotor/multiple wavelets in PeAF patients remain elusive. Real-time phase-mapping (ExTRa mapping, EXT) in the whole left atrium (LA) was performed during PeAF before and after PVI (n = 111). The percentage of time in which rotor/multiple wavelets (phase singularities) was observed during each 5-s phase-mapping recording (non-passive activation ratio, %NP) was measured as an index of its burden. The mapping areas showing %NP ≥ 50% were defined as rotor/multiple-wavelet substrates (RSs). Before PVI, RSs were globally distributed in the LA. After PVI, %NP decreased (< 50%) in many RSs (PVI-modifiable RSs) but remained high (≥ 50%) in some RSs, especially localized in the anterior/septum/inferior regions (PVI-unmodifiable RSs, 2.3 ± 1.0 areas/patient). Before PVI, vagal response (VR) to high-frequency stimulation was observed in 23% of RSs, especially localized in the inferior region. VR disappearance after PVI was more frequently observed in PVI-modifiable RSs (79%) than in PVI-unmodifiable RSs (55%, p < 0.05), suggesting that PVI affects autonomic nerve activities and rotor/multiple wavelet dynamics. PVI-unmodifiable RSs were adjunctively ablated in 104 patients. The 1-year AT/AF-free survival rate was 70% in those with PVI alone (n = 115), and 86% in patients with the adjunctive ablation (log-rank test = 7.65, p < 0.01). PVI suppresses not only ectopic firing but also rotor/multiple wavelets partly via modification of autonomic nerve activities. The adjunctive ablation of PVI-unmodifiable RSs improved the outcome in PeAF patients and might be a novel ablation strategy beyond PVI. [ABSTRACT FROM AUTHOR]

We have investigated whether acidity can be used to control the physicochemical properties of chitin nanofibers (ChNFs). In this study, we define acidity as the molar ratio of dissociated protons from the acid to the amino groups in the raw chitin powder. The effect of acidity on the physicochemical properties of α- and β-ChNFs was compared. The transmittance and viscosity of the β - ChNFs drastically and continuously increased with increasing acidity, while those of the α - ChNFs were not affected by acidity. These differences are because of the higher ability for cationization based on the more flexible crystal structure of β-chitin than α-chitin. In addition, the effect of the acid species on the transmittance of β-ChNFs was investigated. The transmittance of β-ChNFs can be expressed by the acidity regardless of the acid species, such as hydrochloric acid, phosphoric acid, and acetic acid. These results indicate that the acidity defined in this work is an effective parameter to define and control the physicochemical properties of ChNFs. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs, miR) have been considered as biomarkers reflecting the underlying pathophysiology in atrial fibrillation (AF). Nevertheless, miRNA expression in the peripheral blood samples might not reflect a cardiac phenomenon since most miRNAs are expressed in numerous organs. This study aimed to identify the cardiac-specific circulating miRNAs as biomarkers for AF. Methods: Plasma samples were obtained from a luminal coronary sinus catheter (CS, cardiac-specific samples) and femoral venous sheath (FV, peripheral samples) in patients with AF and paroxysmal supraventricular tachycardia (control, CTL) undergoing catheter ablation. The circulating miRNA profiles were analyzed by small RNA sequencing. Differently expressed miRNAs between AF and CTL were identified in each sample of the CS and FV; miRNAs exhibiting similar expression patterns in the CS and FV samples were selected as candidates for cardiac-specific biomarkers. The selected miRNAs were related to the outcome of catheter ablation of AF. Results: Small RNA sequencing detected 849 miRNAs. Among the top 30 most differently expressed miRNAs between AF and CTL, circulating hsa-miR-20b-5p, hsa-miR-330-3p, and hsa-miR-204-5p had a similar pattern in the CS and FV samples. Another set of peripheral blood samples was obtained from AF patients undergoing catheter ablation (n = 141). The expression of the miR-20b-5p and miR-330-3p, but not the miR-204-5p, negatively correlated with the echocardiographic left-atrial dimension and was decreased in patients with AF recurrence as compared to those without AF recurrence during a 1-year follow-up. Conclusion: Circulating miR-20b-5p and miR-330-3p can be cardiac-specific biomarkers for atrial remodeling progression and arrhythmia recurrence after catheter ablation in AF patients. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in carbohydrate sulfotransferase 14 (CHST14) cause musculocontractural Ehlers–Danlos syndrome-CHST14 (mcEDS-CHST14), characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral and ocular system. The replacement of dermatan sulfate chains on decorin proteoglycan with chondroitin sulfate chains is proposed to lead to the disorganization of collagen networks in the skin. However, the pathogenic mechanisms of mcEDS-CHST14 are not fully understood, partly due to the lack of in vitro models of this disease. In the present study, we established in vitro models of fibroblast-mediated collagen network formation that recapacitate mcEDS-CHST14 pathology. Electron microscopy analysis of mcEDS-CHST14-mimicking collagen gels revealed an impaired fibrillar organization that resulted in weaker mechanical strength of the gels. The addition of decorin isolated from patients with mcEDS-CHST14 and Chst14−/− mice disturbed the assembly of collagen fibrils in vitro compared to control decorin. Our study may provide useful in vitro models of mcEDS-CHST14 to elucidate the pathomechanism of this disease. [ABSTRACT FROM AUTHOR]

Histidine-rich glycoprotein (HRG) is abundant plasma protein with various effects on angiogenesis, coagulation, and immune responses. Previously, we identified the base and amino acid sequences of equine HRG (eHRG) and revealed that eHRG regulates neutrophil functions. In this study, we first conducted a large-scale gene analysis with DNA samples extracted from 1700 Thoroughbred horses and identified unique insertion/deletion polymorphisms in the histidine-rich region (HRR) of eHRG. Here we report two types of polymorphisms (deletion type 1 [D1] and deletion type 2 [D2]) containing either a 45 bp or 90 bp deletion in the HRR of eHRG, and five genotypes of eHRG (insertion/insertion [II], ID1, ID2, D1D1, and D1D2) in Thoroughbred horses. Allele frequency of I, D1, and D2, was 0.483, 0.480, and 0.037 and the incidence of each genotype was II: 23.4%, ID1: 46.2%, ID2: 3.6%, D1D1: 23.1%, and D1D2: 3.7%, respectively. The molecular weights of each plasma eHRG protein collected from horses with each genotype was detected as bands of different molecular size, which corresponded to the estimated amino acid sequence. The nickel-binding affinity of the D1 or D2 deletion eHRG was reduced, indicating a loss of function at the site. eHRG proteins show a variety of biological and immunological activities in vivo, and HRR is its active center, suggesting that genetic polymorphisms in eHRG may be involved in the performance in athletic ability, productivity, and susceptibility to infectious diseases in Thoroughbred horses. [ABSTRACT FROM AUTHOR]

Collagen hydrolysate (CH) was orally administered to UVB-irradiated hairless mice at doses of 20, 200–2000 mg/kg BW/day. The low dose of CH increased the skin hydration and reduced the transepidermal water loss on damaged skin. These results suggested the optimal dose of collagen to improve the UV-damaged skin condition. [ABSTRACT FROM PUBLISHER]

Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. We examined the effects of AP on the progression of osteoarthritis (OA) AP was administered to surgically-induced OA model rats for 4 or 8 weeks. This treatment suppressed inflammation and oxidative stress in the synovium, resulting in a decrease in the OA severity score, and the expression of tumor necrosis factor (TNF)-α and matrix metalloproteinase (MMP)-13 in the synovium. It was suggested that long-term administration of AP may be effective for the treatment of OA. In addition, superoxide dismutase (SOD) activity was enhanced in serum samples by AP. AP or its constituent procyanidin B2 (PC) were added to HIG-82 synoviocytes. The results showed that AP enhanced cell proliferation and hyaluronan production. This indicates that AP may improve synovial conditions in OA and suppress OA progression. These effects may be attributed to the antioxidant and anti-inflammatory properties of AP. • Apple polyphenols (AP) have strong antioxidant and anti-inflammatory properties. • The effects of AP on the progression of osteoarthritis (OA) is studied. • AP suppresses inflammation and oxidative stress in the synovium. • Administration of AP may be effective to treat OA. • Superoxide dismutase (SOD) activity in serum was enhanced by AP. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate (CS) and heparan sulfate (HS) are sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide units composed of hexosamine and hexuronic acid. GAG chains exhibit diverse bioactivities in a structure-specific manner. Marine invertebrates are a rich source of highly sulfated and rare structures of GAG chains. Here, we isolated GAGs from the green-lipped mussel Perna canaliculus , an aquaculture species that is produced on a large scale. We separated GAGs based on the degree of negative charges and analyzed their disaccharide compositions. CS and HS both exhibited characteristic compositions of differently sulfated disaccharides. CS chains showed a higher degree of sulfation than HS chains and contained a high percentage of the E unit disaccharide GlcA-GalNAc(4,6- O -disulfate). Furthermore, CS chains rich in the E unit stimulated the neurite outgrowth of primary cultured neurons. The present results indicate the potential of P. canaliculus GAGs as biomaterials to study the structure-function relationships of GAGs. • Marine invertebrates are a rich source of rare structures of glycosaminoglycan chains. • Isolation of glycosaminoglycans from the green-lipped mussel Perna canaliculus. • The characteristic structure of chondroitin sulfate and heparan sulfate from P. canaliculus. • Chondroitin sulfate chains rich in the E unit stimulated the neurite outgrowth of neurons. • P. canaliculus is a promising source for preparing bioactive glycosaminoglycan chains. [ABSTRACT FROM AUTHOR]

Schematic summary of the anti-inflammatory effects induced by eugenol treatment in EAE-induced mice. Eugenol alleviated the progression of EAE, including hind-limb paralysis and demyelination resulting from neuroinflammation in the spinal cord, by suppressing microglial activation, proinflammatory mediators, and oxidation. [Display omitted] • Eugenol improved EAE-induced paralysis in mice. • Eugenol suppressed microglial activation and pro-inflammatory mediators in spinal cords with EAE. • Eugenol reduced the demyelination of spinal cords in EAE mice. • Eugenol alleviates neuroinflammation in the spinal cords in EAE mice, through an anti-inflammatory action. Eugenol is a principal compound in essential clove oil, known for its anti-inflammatory and antioxidant properties. While recent studies have demonstrated its neuroprotective effects on central nervous system (CNS) injuries, such as brain ischemia/reperfusion injuries, but its potential impact on multiple sclerosis (MS), an autoimmune disease of the CNS, has not yet been explored. We evaluated the therapeutic effects of eugenol on experimental autoimmune encephalomyelitis (EAE), an established animal model of MS. EAE was induced in C57BL/6 mice using the myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide. Clinical symptoms, including paralysis, were monitored daily, and levels of pro-inflammatory mediators were evaluated using real-time quantitative polymerase chain reaction, Western blot analyses, and immunohistochemistry. Daily oral administration of eugenol to MOG-induced EAE mice led to a notable decline in the severity of clinical symptoms. Eugenol inhibited EAE-related immune cell infiltration and the production of pro-inflammatory mediators. Histological examinations confirmed its ability to mitigate inflammation and demyelination in the spinal cord post-EAE induction. Eugenol alleviates neuroinflammation in the spinal cords of EAE-induced mice, primarily through anti-inflammatory action. [ABSTRACT FROM AUTHOR]

An algorithm to detect knock location was developed, utilizing differences in the arrival time of the pressure wave caused by knocking between 5 pressure sensors in the combustion chamber of a gasoline engine. In this algorithm, the time differences were derived from time-frequency analysis of the Fourier spectrum with an accuracy of several µs. Furthermore, calculation of knock location by the least square method correlated with the results of the experiment with minimum error. It was applied under certain conditions in a single cylinder engine, and knock locations were determined for both homogeneous and stratified combustion. [ABSTRACT FROM AUTHOR]

By immunohistochemistry, with or without chondroitinases, decorin was found to be distributed in the extracellular matrix of chorionic villi and amnia. The strength of staining intensified with increasing gestational age. Decorin was isolated from the placenta of 13- to 20-day-old pregnant rats and identified by Western blotting, using an antidecorin core protein antibody. The molecular weight of decorin is &nvsim;100 kDa, whereas the respective figures for the core protein treated with chondroitinase (chase) ABC and with chase B are &nvsim;40 kDa and 43 kDa. The difference in the molecular weight between the core protein with chase ABC and B suggests that the glycosaminoglycan (GAG)- base structure on the core protein was chondroitin sulfate (CS) without dermatan sulfate (DS). The decorin content and the proportion of CS to DS in GAG increased with age. We concluded that the age-related changes in the GAG chain may be related to specific functional properties and may have a crucial role in placental tissue organization. [ABSTRACT FROM AUTHOR]

Recently it has been reported that the molecular size of decorin dermatan sulfate (DS) was increased in healing skin after hapten application and that the elongated DS was distributed in enlarged interfibrillar space among thin collagen fibrils in situ. Here we show that such modulation of the length of decorin DS is temporary. Although the size of decorin DS was evidently increased on day 15, it decreased to almost normal size on day 35 when the altered disaccharide composition of DS was also recovered. Electron microscopic observation revealed that elongated decorin DS was localized among thin collagen fibrils packed loosely in hapten-treated skin on day 15. In contrast, decorin DS of normal size was distributed among thick collagen fibrils packed tightly on day 35. These results suggest that size control of decorin DS plays important roles in organization of collagen fibrils into bundles by regulating interfibrillar space in healing skin, particularly in maturation of collagen fibrils through shortening of decorin DS in later stages of healing. [Copyright &y& Elsevier]

Background: Ablation index (AI) linearly correlates with lesion depth and may yield better therapeutic performance in pulmonary vein isolation (PVI) when tailored to a patient's wall thickness (WT) in the left atrium (LA). Methods and results: First study: In paroxysmal atrial fibrillation patients (PAF; n = 20), the average LA WT (mm) in each anatomical segment for PVI was measured by intracardiac echocardiography (ICE) placed in the LA; the optimal AI for creating 1‐mm transmural lesion (AI/mm) was calculated. Second study: PAF (n = 80) patients were randomly assigned either to a force‐time integral protocol (FTI; 400 g·s, n = 40) or a tailored‐AI protocol (TAI; n = 40). In TAI, the LA WT in each segment was individually measured by ICE before starting ablation; a target AI was adjusted according to the individual WT in each segment (AI/mm × WT). The acute procedure outcomes and the 1‐year AF‐recurrence rate were compared between FTI and TAI. TAI had higher success rate of first‐pass isolation (88% vs. 65%) and had lower incidence of residual PV‐potentials/conduction‐gaps after a circular ablation than FTI (15% vs. 45%). The procedure time to complete PVI decreased in TAI compared to FTI (52 vs. 83 min), being attributed to the increased radiofrequency power and the decreased radiofrequency application time in each point in TAI. TAI had a lower 1‐year AF‐recurrence rate than FTI. Conclusion: TAI increased acute procedure success, decreased time for PVI, and reduced the 1‐year AF‐recurrence rate, compared to FTI. Understanding the precise ablation target and tailoring AI would improve the efficacy of PVI. [ABSTRACT FROM AUTHOR]

Loss-of-function variants in CHST14 cause a dermatan 4- O -sulfotransferase deficiency named musculocontractural Ehlers–Danlos syndrome- CHST14 (mcEDS- CHST14), resulting in complete depletion of the dermatan sulfate moiety of decorin glycosaminoglycan (GAG) chains, which is replaced by chondroitin sulfate. Recently, we uncovered structural alteration of GAG chains in the skin of patients with mcEDS- CHST14. Here, we conducted the first systematic investigation of Chst14 gene-deleted homozygote (Chst14 −/−) mice. We used skin samples of wild-type (Chst14 +/+) and Chst14 −/− mice. Mechanical fragility of the skin was measured with a tensile test. Pathology was observed using light microscopy, decorin immunohistochemistry and electron microscopy (EM) including cupromeronic blue (CB) staining. Quantification of chondroitin sulfate and dermatan sulfate was performed using enzymatic digestion followed by anion-exchange HPLC. In Chst14−/− mice, skin tensile strength was significantly decreased compared with that in Chst14 +/+ mice. EM showed that collagen fibrils were oriented in various directions to form disorganized collagen fibers in the reticular layer. Through EM-based CB staining, rod-shaped linear GAG chains were found to be attached at one end to collagen fibrils and protruded outside of the fibrils, in contrast to them being round and wrapping the collagen fibrils in Chst14 +/+ mice. A very low level of dermatan sulfate disaccharides was detected in the skin of Chst14 −/− mice by anion-exchange chromatography. Chst14−/− mice, exhibiting similar abnormalities in the GAG structure of decorin and collagen networks in the skin, could be a reasonable model for skin fragility of patients with mcEDS- CHST14 , shedding light on the role of dermatan sulfate in maintaining skin strength. [ABSTRACT FROM AUTHOR]

The article presents a study on the impacts of collagen peptide (CP) intake on skin damages caused by ultraviolet (UV) B irradiation. It mentions that fish scale-derived CP was administered to naked mice that was recurrently exposed to UV-B irradiation for examination in the study. Results show that CP inhibits UV-B induced skin hydration reduction, epidermis hyperlasia and decreases in soluble type I collagen. It concludes that CP is a good dietary supplement for UV-B induced skin damage.

Abstract Musculocontractural Ehlers-Danlos syndrome (mcEDS) due to CHST14/D4ST1 deficiency (mcEDS- CHST14) is a recently delineated type of EDS caused by biallelic loss-of-function mutations in CHST14 , which results in the depletion of dermatan sulfate (DS). Clinical characteristics of mcEDS- CHST14 consist of multiple malformations and progressive fragility-related manifestations, including skin hyperextensibility and fragility. Skin fragility is suspected to result from the impaired assembly of collagen fibrils caused by alteration of the glycosaminoglycan (GAG) chain of decorin-proteoglycan (PG) from DS to chondroitin sulfate (CS). This systematic investigation of the skin pathology of patients with mcEDS- CHST14 comprised both immunostaining of decorin and transmission electron microscopy-based cupromeronic blue staining to visualize GAG chains. Collagen fibrils were dispersed in the affected papillary to reticular dermis; in contrast, they were regularly and tightly assembled in controls. Moreover, the fibrils exhibited a perpendicular arrangement to the affected epidermis, whereas fibrils were parallel to control epidermis. Affected GAG chains were linear, stretching from the outer surface of collagen fibrils to adjacent fibrils; in contrast, those of controls were curved, maintaining close contact with attached collagen fibrils. This is the first observation of compositional alteration, from DS to CS, of GAG side chains, which caused structural alteration of GAG side chains and resulted in spatial disorganization of collagen networks; this presumably disrupted the ring-mesh structure of GAG side chains surrounding collagen fibrils. McEDS- CHST14 provides a critical example of the importance of DS in GAG side chains of decorin-PG during assembly of collagen fibrils in maintenance of connective tissues. Highlights • Skin pathological finding of musculocontractural Ehlers-Danlos syndrome were defined. • The shape of GAG chain changed due to difference in the composition of GAG chain. • Changes in the shape of GAG chain resulted in impaired assembly of collagen fibrils. [ABSTRACT FROM AUTHOR]

Collagen is one of the most important components of the extracellular matrix that is involved in the strength of tissues, cell adhesion and cell proliferation. Mutations in several collagen and posttranslational modification enzyme genes cause Ehlers-Danlos syndrome (EDS) characterized by joint and skin hyperextensibility as well as fragility of various organs. Carbohydrate sulfotransferase 14/dermatan 4-O-sulfotransferase-1 (CHST14/D4ST1) is a critical enzyme for biosynthesis of dermatan sulfate, a side chain of various proteoglycans including biglycan that regulates collagen fibrils through their interaction. Mutations in CHST14 were found to cause a new form of EDS, named musculocontractural type EDS (mcEDS-CHST14). Large subcutaneous hematomas are one of the most serious complications accompanied by decreased quality of life and potential lethality. In this study, Chst14 gene-deleted mice were expected to be an animal model of the vascular abnormalities of mcEDS-CHST14. However, only limited numbers of adult mice were generated because of perinatal lethality in most Chst14 gene-deleted homozygote (Chst14−/−) mice. Therefore, we investigated the placentas of these fetuses. The placentas of Chst14−/− fetuses showed a reduced weight, alterations in the vascular structure, and ischemic and/or necrotic-like changes. Electron microscopy demonstrated an abnormal structure of the basement membrane of capillaries in the placental villus. These findings suggest that Chst14 is essential for placental vascular development and perinatal survival of fetuses. Furthermore, placentas of Chst14−/− fetuses could be a useful model for vascular manifestations in mcEDS-CHST14, such as the large subcutaneous hematomas. [ABSTRACT FROM AUTHOR]

To investigate sexual dimorphism and postnatal changes in skin collagen expression, mRNA levels of collagens and their regulatory factors in male and female skin were examined during the first 120 days of age by quantitative realtime PCR. Levels of mRNAs encoding extracellular matrices did not show any differences between male and female mice until day 15. Col1a1 and Col1a2 mRNAs noticeably increased at day 30 and remained at high levels until day 120 in male mice, while those in female mice remained at low levels during the period. Consistent with the mRNA expression, pepsin-soluble type I collagen contents in skin was very high in mature male as compared to female. Col3a1 mRNA in male mice also showed significantly high level at day 120 as compared to female. On the other hand, expression of mRNAs encoding TGF-ßs and their receptors did not show apparent sexual dimorphism although small significant differences were observed at some points. Castration at 60 days of age resulted in a significant decrease in type I collagen mRNA expression within 3 days, and noticeably decreased expression of all fibril collagen mRNAs examined within 14 days, while administration of testosterone tube maintained the mRNA expression at high levels. Despite the in vivo effect of testosterone, administration of physiological concentrations of testosterone did not affect fibril collagen mRNA expression in either human or mouse skin fibroblasts in vitro, suggesting that testosterone does not directly affect collagen expression in fibroblasts. In summary, present study demonstrated dynamic postnatal changes in expression of collagens and their regulatory factors, and suggest that testosterone and its effects on collagen expression are responsible for the skin sexual dimorphism but the effects of testosterone is not due to direct action on dermal fibroblasts. [ABSTRACT FROM AUTHOR]

Hyaluronan (HA) has been utilized as a supplement. However, the absorption of orally administrated HA remains controversial. The degradation and absorption of HA in the intestine were investigated in this study. HA excretion into the feces, degradation in the intestinal tract, absorption through the large intestine, and translocation to the blood and skin were examined. HA administered orally was not detected in rat feces. HA was degraded by cecal content, but not by artificial gastric juice and intestinal juice. Oligosaccharide HA passed through excised large intestine sacs. Furthermore, disaccharides, tetrasaccharides, and polysaccharides HA were distributed to the skin of rats following oral administration of high molecular weight HA (300 kDa). The results of the study suggest that orally administered HA is degraded to oligosaccharides by intestinal bacteria, and oligosaccharide HA is absorbed in the large intestine and is subsequently distributed throughout the tissues, including the skin. [ABSTRACT FROM AUTHOR]

Hyaluronan is a component of the extracellular matrix that plays a role in water retention in tissues. In this study, we orally administered hyaluronans of varying molecular weights (300 k and less than 10 k) repeatedly to hairless mice exposed to ultraviolet (UV) irradiation and examined their effects on the skin of these mice. UV irradiation induces a marked increase in the epidermal thickness of the dorsal skin and a marked decrease in the skin moisture content; however, orally administered hyaluronan, particularly that with a molecular weight of less than 10 k, markedly reversed the increase and decrease in the epidermal thickness and skin moisture content, respectively. Furthermore, on analyzing the mice skin, orally administered hyaluronan with a molecular weight of less than 10 k increased the levels of the HAS2 gene expression in the skin. Based on these findings, it is assumed that orally administered hyaluronans, with molecular weight of 300 k and less than 10 k, reversed UV irradiation-induced skin disturbance. In particular, it was considered that the increase in the skin moisture content by orally administered hyaluronan, with a molecular weight of less than 10 k, was related to the effect on skin cells. [ABSTRACT FROM AUTHOR]

Objectives: Fish proteins are potential sources of natural medicines and food additives. There are many studies being performed to develop underutilized fish proteins. Therefore, the aim of this study was to determine how shark protein functions as a dietary supplement for bone health. Methods: Three groups of ovariectomized (OVX) rats were fed different diets containing 20% casein protein, 20% shark protein, or 20% cod protein for 4 wk. Bone mineral density of the right femur was measured by dual-energy x-ray absorptiometry and quantitative computed tomography. Furthermore, we prepared low-molecular-weight peptides from shark protein using protease for in vitro studies. Calcitriol was added to bone marrow cells and the receptor activator of the nuclear factor-κB ligand was added to RAW264 cells. After 7 d, the number of tartrate-resistant acid phosphatase-positive cells was counted. Results: In the shark protein-fed group, bone mineral density of the femur epiphysis was higher than that of the casein protein-fed group. In particular, the shark protein-fed group showed an increase in bone mineral density, represented mainly by trabecular bone. Shark protein hydrolysates inhibited osteoclast formation in bone marrow cells and RAW264 cells. Conclusions: These results suggest that shark protein might suppress the bone loss caused by estrogen deficiency through the suppression of osteoclast formation. [ABSTRACT FROM AUTHOR]

The article discusses the role of ascorbic acid (AA) in the epidermal atrophy and the effect of ultraviolet-b (UVB) radiation in senescence marker protein-30 (SMP30)/ gluconolactonase (GLN) knockout hairless mice. Ascorbic acid perform various functions in the body including as an electron donor to reduce reactive oxygen species protects keratinocytes and as a cofactor for hydroxylation of procollagen. SMP30/GNL knockout mice developed symptoms of scurvy when fed an AA-deficient diet.

The article focuses on the study that examines the effect of praline-hydroxyproline (pro-Hyp) in hyaluronic acid production using in vitro cultured synovium cells. It states that the study was performed in a guinea pig model of osteoarthritis, wherein various collagen hydrolysate suspensions were given to guinea pigs. It mentions that the administration of collagen hydrolysates results to the increase in proteoglycans in the epiphyses. It reveals that collagen hydrolysates can help treat OA.

Abstract: Senescence marker protein-30 (SMP30) is a gluconolactonase required for vitamin C (VC) synthesis. We examined effects of VC deficiency on the mouse skin using SMP30 knockout (KO) mice. SMP30 KO or wild type male mice were weaned around day 30 of age, and fed VC-deficient diet. They were given either VC water or control water. VC deficiency for 36days did not affect skin hydroxyproline contents, while VC deficiency for 60days decreased the hydroxyproline levels. Levels of some collagen mRNAs were different among the groups, but did not correlate with skin VC levels. The epidermis was morphologically abnormal in VC-deficient SMP30 KO mouse at 60days after the weaning. Interestingly, the hair cycle was not synchronized among the groups. These data suggest low susceptibility of the mouse skin to VC deficiency and involvement of VC in the regulation of keratinocyte function and hair cycle in vivo. [Copyright &y& Elsevier]

In this study we report the cloning and characterization of a novel human aminopeptidase, which we designate leukocyte-derived arginine aminopeptidase (LRAP). The sequence encodes a 960-amino acid protein with significant homology to placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase. The predicted L-RAP contains the HEXXH(X)[sub 18]E zinc-binding motif, which is characteristic of the MI family of zinc metallopeptidases. Phylogenetic analysis indicates that L-RAP forms a distinct subfamily with placental leucine aminopeptidase and adipocyte-derived leucine aminopeptidase in the MI family. Immunocytochemical analysis indicates that L-RAP is located in the lumenal side of the endoplasmic reticulum. Among various synthetic substrates tested, L-RAP revealed a preference for arginine, establishing that the enzyme is a novel arginine aminopeptidase with restricted substrate specificity. In addition to natural hormones such as angiotensin III and kallidin, L-RAP cleaved various N-terminal extended precursors to major histocompatibility complex class I-presented antigenic peptides. Like other proteins involved in antigen presentation, L-RAP is induced by interferon-γ. These results indicate that L-RAP is a novel aminopeptidase that can trim the N-terminal extended precursors to antigenic peptides in the endoplasmic reticulum. [ABSTRACT FROM AUTHOR]

The article focuses on an experiment conducted to show the effect of enhancement of tight junction functions. This enhancement occurred when the dietary glucosylceramide increased the expression of claudin - I in an ultraviolet B (UVB) radiation in epidermis of a mouse. This caused increase in electrical resistance of Sphingosine and phytosphingosine. This showed that increase in skin barrier resistance is due to enhancement of tight junction.