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Rice bran residues are known as low economic-value and contain high protein nutritional value. This notion has caught interest of scientists to study the proteins and their hydrolysates from this bioresource. However, reports on the biological activities of rice bran residue proteins and their hydrolysates are still limited. Hench, this study aimed to fractionate 4 rice bran protein fractions including albumin (ABM), globulin (GBL), prolamin (PLM), and glutelin (GTL) from Riceberry and to investigate the chemical properties and bio-protective potentials of these proteins and their hydrolysates. Riceberry GTL presented the highest yield. Phenolic compounds including anthocyanin were higher in Riceberry bran proteins. Notably, GTL hydrolysate from the Riceberry showed the strongest antioxidant activity and the best antimutagenicity. Four promising dipeptides identified in the GTL hydrolysate were pGlu-Val, pGlu-Asp, pGlu-Asn, and pGlu-Glu. This study suggested that GTL hydrolysate from Riceberry bran proteins could be further developed as functional foods for chemoprevention.

Exercise activates the metabolic system in skeletal muscles, which is modulated by antioxidant supplementation. Some antioxidants such as glutathione accelerate metabolic adaptation induced by exercise training, whereas other antioxidants such as vitamin C suppress it. Thus, the present study aimed to elucidate the effects of oral administration of glutathione and vitamin C on metabolic and redox responses after acute exercise in mice. ICR mice were randomly divided into sedentary, exercise, exercise with glutathione, and exercise with vitamin C groups. In the exercise groups, mice were subjected to treadmill running at 30 m/min for 30 min. Immediately after exercise, glutathione (2% w/v, 5uL/g body weight) or vitamin C (10% w/v, 5uL/g body weight) were administered. Gastrocnemius muscle and plasma samples were collected at 3 h post-exercise. We found that plasma creatine kinase levels were only elevated in the exercise group. Malondialdehyde levels in skeletal muscle were elevated after exercise, but this elevation was suppressed by glutathione administration. PGC-1α expression was increased in both the exercise and glutathione groups compared with the sedentary group; however, the expressions of its downstream proteins were only increased in the glutathione group. Reduced glutathione form was notably increased in the mitochondria, whereas oxidized glutathione was significantly increased in the cytosol of the glutathione administration group compared with the exercise group. Thioredoxin reductase activity was also higher in the glutathione group than in the sedentary and exercise groups. Thus, this study demonstrates that post-exercise glutathione administration accelerates the exercise-induced responses of mitochondrial factors in skeletal muscle, which may be mediated by the modulation of the redox system.

Introduction: A stoma prolapse is easy to diagnose by visual examination, and it rarely incarcerates. Therefore, manual reduction is usually performed as soon as the diagnosis is made. In this report, we describe a case of stoma prolapse that could not be reduced manually and ruptured because an incarcerated parastomal hernia occurred in the stoma, mimicking stoma prolapse. Case Presentation: A 66-year-old woman underwent total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, resection of dissemination, and low anterior resection with formation of a sigmoid end colostomy for endometrial cancer with infiltration of the rectum. Fourteen months after the initial operation, she presented with stoma prolapse and multiple episodes of vomiting. The prolapsed stoma was 20 cm in length, appeared swollen and edematous, and was somewhat firm. Although it looked viable, some of the mucosa was darkish red, indicating congestion. Therefore, the diagnosis was sigmoid end colostomy prolapse with an ischemic component. An attempt at manual reduction resulted in rupture, so an emergency laparotomy was performed. Intraoperatively, we found that the ileum was incarcerated in the aperture created where the colostomy had been formed. When the incarcerated ileum was released, the stoma prolapse could be reduced easily. The end colostomy was refashioned in the left upper quadrant of the abdomen. Conclusion: An incarcerated parastomal hernia can mimic stoma prolapse. If the findings differ from those of typical stoma prolapse, imaging should be performed to confirm whether another clinical entity is involved in the stoma prolapse.

Objective: Uncoupling protein 2 (UCP2) is an ion/anion transporter in the mitochondrial inner membrane that plays a crucial role in immune response, regulation of oxidative stress, and cellular metabolism. UCP2 polymorphisms are linked to chronic inflammation, obesity, diabetes, heart disease, exercise efficiency, and longevity. Daily step count and number of teeth are modifiable factors that reduce mortality risk, although the role of UCP2 in this mechanism is unknown. This study aimed to assess the possible effects of UCP2 polymorphisms on the association between daily step count and number of teeth with all-cause mortality. Methods: This study was conducted as a cohort project involving adult Japanese outpatients at Sado General Hospital (PROST). The final number of participants was 875 (mean age: 69 y). All-cause mortality during thirteen years (from June 2008 to August 2021) was recorded. The functional UCP2 genotypes rs659366 and rs660339 were identified using the Japonica Array®. Survival analyses were performed using multivariate Cox proportional hazard models. Results: There were 161 deaths (mean observation period: 113 months). Age, sex, daily step count, and the number of teeth were significantly associated with mortality. In females, UCP2 polymorphisms were associated with mortality independent of other factors (rs659366 GA compared to GG + AA; HR = 2.033, p = 0.019, rs660339 C T compared to CC + TT; HR = 1.911, p = 0.029). Multivariate models, with and without UCP2 genotypes, yielded similar results. The interaction terms between UCP2 genotype and daily step count or number of teeth were not significantly associated with mortality. Conclusion: The effects of UCP2 polymorphisms on the association between daily step count or the number of teeth and all-cause mortality were not statistically significant. In females, UCP2 polymorphisms were significantly associated with all-cause mortality. Our findings confirmed the importance of physical activity and oral health and suggested a role of UCP2 in mortality risk independently with those factors.

Myostatin (MSTN) is a negative regulator of skeletal muscle growth and a popular target for enhancing the productivity of farmed fish. We previously developed an mstn-knockout breed of the aquaculture fish red sea bream (Pagrus major) using genome editing technology. However, little is known about the effects of mstn disruption on the fillet quality of red sea bream and other fish species. In this study, we used fillets of mstn-deficient red sea bream to evaluate their compositional and textural changes during refrigeration. Compared to the wild type, the mutant fillets exhibited an increase in moisture content and a decrease in drippings, indicating an enhanced water-holding capacity. Furthermore, the mutant fillets showed increased water retention and marginally lower collagen content, resulting in lower breaking force, an index of texture. In conclusion, we demonstrated that mstn disruption alters the compositional and textural properties of red sea bream fillets.

Vital signs are crucial for assessing the condition of a patient and detecting early symptom deterioration. Noncontact sensor technology has been developed to take vital measurements with minimal burden. This study evaluated the accuracy of a mat-type noncontact sensor in measuring respiratory and pulse rates in patients with cardiovascular diseases compared to conventional methods. Forty-eight hospitalized patients were included; a mat-type sensor was used to measure their respiratory and pulse rates during bed rest. Differences between mat-type sensors and conventional methods were assessed using the Bland–Altman analysis. The mean difference in respiratory rate was 1.9 breaths/min (limits of agreement (LOA): −4.5 to 8.3 breaths/min), and proportional bias existed with significance (r = 0.63, p < 0.05). For pulse rate, the mean difference was −2.0 beats/min (LOA: −23.0 to 19.0 beats/min) when compared to blood pressure devices and 0.01 beats/min (LOA: −11.4 to 11.4 beats/min) when compared to 24-h Holter electrocardiography. The proportional bias was significant for both comparisons (r = 0.49, p < 0.05; r = 0.52, p < 0.05). These were considered clinically acceptable because there was no tendency to misjudge abnormal values as normal. The mat-type noncontact sensor demonstrated sufficient accuracy to serve as an alternative to conventional assessments, providing long-term monitoring of vital signs in clinical settings.

Background: Recent studies have investigated the effects of exercise on the functional capacity of older adults; training with a balance exercise assist robot (BEAR) effectively improves posture. This study compared the clinical safety and efficacy of training using BEAR video games to conventional resistance training in older adults with cardiovascular disease (CVD). Methods: Ninety patients (mean age: 78 years) hospitalized due to worsening CVD were randomized to cardiac rehabilitation (CR) Group R (conventional resistance training) or Group B (training using BEAR). After appropriate therapy, patients underwent laboratory testing and functional evaluation using the timed up-and-go test (TUG), short physical performance battery (SPPB), and functional independence measure (FIM) just before discharge and 4 months after CR. The rates of CVD readmission, cardiac death, and fall-related fractures were monitored. Results: BEAR had no adverse effects during exercise. At 4 months, TUG and SPPB improved significantly in both groups, with no significant difference between them. FIM motor and the Geriatric Nutritional Risk Index were significantly improved in Group B versus Group R. There was no significant difference in cardiac events and fall-related fractures between the two groups. Conclusion: CR with BEAR is safe and comparable to conventional resistance training for improving balance in older adults with CVD.

Several reports have demonstrated the effectiveness of neurorehabilitation, such as mirror therapy or virtual reality, in treating phantom limb pain (PLP). This case study describes the effect of virtual reality training (VRT) on severe, long-term PLP and upper limb activity on the amputated side in a patient who underwent digit amputation 9 years prior. A woman in her 40 s underwent amputation of 2–5 fingers 9 years prior due to a workplace accident. She experienced persistent pain in the palms of her hand near the amputation sites. A single case design (ABA’B’) was applied. Periods A and A’ were set as periods without VRT intervention, and Periods B and B’ were set as periods with VRT intervention. Periods A, B, A’, and B’ lasted 4, 10, 8, and 10 weeks, respectively. VRT was a task during which visual stimulation and upper limb movements were linked. The task consisted of catching a rolling ball in the display with a virtual hand, operated with both hands using a controller. VRT was performed once every 2–4 weeks for 30 min. Pain intensity was assessed using the short-form McGill Pain Questionnaire-2. Bilateral upper limb activity was measured continuously for 24 h using a triaxial accelerometer attached to the right and left wrist joints. The pain intensity was 147/220 points during Period A, 128 points during Period B, 93 points during Period A’, and 100 points during Period B’, showing a gradual decrease. Upper limb activity occurred mainly on the intact side during Periods A and B, whereas the activity on the amputated side increased 2-fold after Period A’, and both upper extremities were used equally. Virtual reality training resulted in reduced pain intensity and increased activity in the upper limb. VRT may have induced reintegration of the sensory-motor loop, leading to a decrease in the PLP intensity. The upper limb activity on the amputated side may have also increased with the pain reduction. These results suggest that VRT may be valuable in reducing severe, long-term PLP.

The replacement of LiOH with KOH for pH control in the primary water of pressurized water reactors (PWRs) is being considered due to the growing cost of enriched 7Li. This study aims to investigate the susceptibility of the primary water stress corrosion cracking (PWSCC) initiation in simulated primary water with KOH. Firstly, the susceptibilities in KOH and LiOH chemistries were compared by conducting uniaxial constant load tests on Alloy X-750 at 360°C. The results showed no significant difference in the time to initiation between the two chemistries. Secondly, the effect of dissolved hydrogen (DH) concentration in the KOH chemistry was examined. The DH concentration of the test water was varied at 5, 30 or 45 ml/kg-H2O. The results showed that the time to initiation of PWSCC was significantly extended under the low DH condition (5 ml/kg-H2O). This observed effect of DH concentration in the KOH environment agrees with the previously reported effect observed in the conventional LiOH environment. To investigate the mechanisms underlying the PWSCC tests, the oxide films on the test specimens were characterized using electron microscopes. The oxide films formed in the KOH and LiOH chemistries did not show significant differences. Additionally, under the low DH condition, the occurrence of selective internal oxidation under the inner oxide film was relatively minor. The results suggest that the use of KOH would not have an adverse effect on PWSCC initiation, and PWSCC initiation can be mitigated with a low concentration of DH in the KOH environment as well as in the LiOH environment.

Abstract Background The introduction of nursing care-support devices using robotic technology is expected to reduce the task burden in long-term care facilities. Objective To investigate the use of the rise-assisting robot, Resyone, in extending and improving the life space of nursing home residents with severe care needs. Methods We performed a feasibility study in which Resyone was used to facilitate visits to additional sites in and around the nursing home as part of the care package of three residents. Two weeks before and four weeks after implementation of the new arrangements, the 30 caregivers involved were asked to record transfer times and destinations, while also checking the residents’ facial expressions. Results Before implementation, participants had limited life spaces, but afterwards they regularly visited additional destinations including the garden, home entrance and corridors, which previously they had not visited frequently. The residents' facial expressions became more positive and less negative. This study demonstrates that Resyone can enrich care activities in severely disabled individuals. Conclusion These findings suggest that the sustainable use of Resyone would improve the quality of care at care facilities. Moreover, the extension of otherwise limited life space has the potential to improve care receivers’ quality of life. Trial registration UMIN Clinical Trials Registry No. UMIN000039204 (20/01/2020); retrospectively registered; interventional study; parallel, non-randomized, single blinded. URL of trial registry records: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000044709 .

Comparing the distribution of school districts in Shizuoka Prefecture with a Voronoi diagram generated for school locations, the application of Voronoi diagrams to the field of urban planning is pursued. The original statistics have been released by the government in the form of GIS data. Data processing and analysis are carried out utilizing open-source libraries.

The objective of this study is to incorporate varied geospatial data into CAD/BIM systems, which are now essential design tools for architects. Those geospatial data include digital information of topography, water features, roads and streets, existing buildings, and so on. Those data have been released by the government as public information, and their full utilization in actual design projects would be highly beneficial.

Influenza remains a worldwide health concern. Antiviral drugs are considered as one of the useful options for its prevention as a complementary measure to vaccination. Baloxavir acid selectively inhibits the cap-dependent endonuclease of influenza viruses and exhibits marked viral titre reduction in patients. Here, we describe the prophylactic potency of baloxavir acid against lethal infection with influenza A and B viruses in mice. BALB/c mice were subcutaneously administered once with baloxavir acid suspension, or orally administered once daily for 10 days with oseltamivir phosphate solution at human relevant doses. Next, the mice were intranasally inoculated with A/PR/8/34 (H1N1) or B/Hong Kong/5/72 strain at 24 to 96 h after the initial dosing. Prophylactic treatment with the antiviral drugs significantly reduced the lung viral titres and prolonged survival time. In particular, baloxavir acid showed a greater suppressive effect on lung viral titres compared to oseltamivir phosphate. In this model, baloxavir acid maintained significant prophylactic effects against influenza A and B virus infections when the plasma concentration at the time of infection was at least 0.88 and 3.58 ng/mL, respectively. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of baloxavir marboxil for prophylaxis against influenza in humans.

Drivers occasionally need to resume vehicle control when an automated driving system (ADS) cannot handle a situation. However, a lack of driver readiness can prevent a smooth transition. For example, in an obstacle avoidance situation, a method to transfer the vehicle control based on the driver’s input of the steering angle can be adopted where rapid steering operation by the driver is required immediately after resuming control. It was observed from the previous studies based on a fixed-based driving simulator that the discontinuity in control due to a sudden disengagement of the control torque of the ADS resulted in steering instability. In addition, the previous studies had proposed a shared mode, in which haptic shared control (HSC) was placed between the automated and manual driving. It was demonstrated that steering stability could be improved through the shared mode. However, in the previous studies, the observation of steering instability and verification of HSC effectiveness of the shared mode were limited to fixed-based driving simulator experiments, in which there was no vehicle motion. In addition, for practical applications, a method using a torque sensor in the previous method is expected to be replaced by a more robust method, because it may introduce noise and the use of a lowpass filter leads to some time lag. Therefore, in this study, we developed a new control transition method that uses only the steering angle. We conducted experiments using a real car, in which the participants were instructed to resume steering control from the automated driving mode. The results demonstrate that the discontinuity in control during the control transition deteriorates the steering stability and vehicle motion, and the shared mode can improve them.

Abstract Collagens act as cellular scaffolds in extracellular matrixes, and their breakdown products may also have important biological functions. We hypothesize that collagen dipeptide Pro-Hyp induces favorable healing activities and examined the effects of Pro-Hyp administered via different routes on wound healing using our novel murine model, in which an advanced fibrosis-prone scar lesion was developed in the abdominal muscle wall under the skin. After excising a part of the abdominal wall, a free-drinking experiment was performed using solutions with casein (CS), high molecular weight collagen peptides (HP), and low molecular weight collagen peptides including Pro-Hyp and Hyp-Gly (LP), in addition to water (HO). On day 21 of the study, when compared to the HO and CS groups, muscle regeneration in the LP group was significantly advanced in the granulation tissue, which was associated with a decrease in fibrosis. To clarify the effects of Pro-Hyp, daily intraperitoneal administration of pure Pro-Hyp was performed. Pro-Hyp administration induced many myogenically differentiated cells, including myogenin-positive myoblasts and myoglobin-positive myocytes, to migrate in the granulation tissue, while scar tissue decreased. These results indicated that Pro-Hyp administration accelerates muscle regenerative healing accompanied by less scarring after wounding on the abdominal wall.

Purpose External rectal prolapse (ERP) is frequently associated with other pelvic disorders, such as enterocele, rectocele, and perineal descent. Evacuation proctography makes it possible to visualize the development of such anatomical abnormalities. The aim of this study was to identify the variables that would predict associated abnormalities in patients with ERP. Methods Between February 2010 and August 2019, 124 female patients with ERP, who were evaluated using proctography were included in this study. Enterocele was diagnosed when the extension of the loop of the small bowel was located between the vagina and rectum. A significant rectocele was defined as >20 mm in diameter. Multivariate analysis was used to establish which morphological parameters best predicted the presence of enterocele or rectocele. Results Sixty-five patients had ERP alone, while 59 patients (47.6%) had additional findings on proctography. The most frequently associated abnormality was enterocele with 48 of the patients (38.7%) having this condition. Rectocele was detected in 17 of the 124 patients (13.7%). The median length of the ERP was 30 mm (range, 7 to 147 mm). The results of the stepwise multiple regression analysis showed that a history of hysterectomy and the length of the ERP were significantly associated with the presence of enterocele. The analysis showed that the longer the prolapse, the higher the incidence of enterocele. A history of hysterectomy was also significantly associated with the presence of rectocele. Conclusion Patients with ERP often have associated anatomical abnormalities and should be investigated thoroughly before planning surgical treatment.

Abstract This study examined the effects of oral administration of water extract of chlorella (WEC) (100 mg/kg bodyweight) and phenethylamine (10 μg/kg bodyweight) on high-fat diet (HFD)-induced liver damage in mice. Phenethylamine significantly mitigated HFD-induced lipid oxidation (generation of malondialdehyde) and liver damage without markedly decreasing hepatic lipid accumulation. WEC exerted similar effects although with decreased efficacy. In addition, WEC and phenethylamine decreased the methylglyoxal levels and increased the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) protein levels in the liver. Methylglyoxal is generated from substrates of GAPDH, dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. These facts indicate that methylglyoxal triggers oxidation of accumulated lipid, which generates malondialdehyde and consequently induces liver damage. Suppression of generation of toxic aldehydes by WEC and phenethylamine was also confirmed by maintaining hepatic cysteine, highly reactive to aldehydes. Thus, trace amounts of phenethylamine alleviate HFD-induced liver damage by regulating methylglyoxal via increase of GAPDH.

[Purpose]: We used a near-infrared ray catheter (NIRC) in a child with cloacal exstrophy presenting with hematometra and assessed whether the NIRC could help with complicated adhesiolysis during hemi-hysterectomy in children. [Method]: A 6-French pig tail-type NIRC was inserted into the left ureter with guidance from a cystoscope. Laparoscopic hemi-hysterectomy with fluorescence observation was performed using the VISERA ELITE 2 system. [Result]: NIRC insertion into the left ureter was not as difficult as expected despite the eccentric position of the left ureter orifice. When we found an enlarged left uterus and fallopian tube, adhesion was extremely severe around them due to chronic inflammation caused by hematometra. When near-infrared rays were applied, a fluorescent ureteral catheter that emitted bright green excitation light was observed on the dorsal side of the enlarged left uterus and fallopian tube. Under ureteral navigation with an NIRC, dissection of the adhesions was performed safely and smoothly. Hemi-hysterectomy and adnexectomy were performed successfully. The patient was doing well 2 years postoperatively without any complications. [Conclusion]: An NIRC can provide useful real-time visualization of the ureter course and reduce the risk of ureteral damage in children with advanced adhesions.

Abstract Purpose The objective is to clarify the practical problem of the preimplantation genetic testing (PGT) for myotonic dystrophy type 1 (DM1) in Japanese subjects. Methods For the 32 couples who consented to participate in PGT for DM1, CTG repeats number on the unaffected alleles was analyzed. Based on the allele combination, they were classified into 3 groups by the number of diagnostic allelic pattern; “full informative,” “semi informative,” and “noninformative.” According to the Japan Society of Obstetrics and Gynecology (JSOG) principle, PGT was performed using the direct diagnosis to the 288 embryos from the 17 couples who received the ethical approval from both our institution and JSOG. Results In the 32 couples, the frequency of CTG repeats on the unaffected alleles showed bimodal distribution. The “full informative,” “semi informative,” and “noninformative” couples accounted for 46.9% (15/32 couples), 46.9% (15/32 couples) and 6.2% (2/32 couples), respectively. The transferable embryos accounted for 28.9% (33/114 embryos) in the “full informative” couples, although it was limited to 12.6% (22/174 embryos) in the “semi informative” couples. Conclusion The loss of unaffected embryos which cannot be diagnosed as transferable was a clinically major problem and implied an increase in oocyte retrieval, especially for “semi informative” couples.

Life-space activities are a measure of daily activity level. Here, we examined the association between life-space activities and prognosis in 129 cardiovascular diseases (CVD) patients 65 years of age or older (average age, 79.2 ± 7.6 years; mean left ventricular ejection fraction, 56.7 ± 13.2%) who had been admitted to our hospital for worsening CVD. Subjects were followed, and the primary endpoints were cardiovascular hospitalization and cardiovascular death. Receiver operating characteristic analysis produced a cutoff value for life-space assessment (LSA) score for increased risk of cardiovascular hospitalization for two years of 53.0 points (sensitivity, 55.9%; specificity, 82.1%). Kaplan–Meier analysis using this cutoff value revealed that the rates of cardiovascular hospitalization and cardiovascular death were significantly higher in subjects with an LSA score below the cutoff than in those with a score above the cutoff (both p < 0.001). Cox proportional analysis revealed that low LSA score was independently associated with cardiovascular hospitalization (HR, 2.540; 95% CI, 1.135–5.680; p = 0.023) and cardiovascular death (HR, 15.223; 95% CI, 1.689–137.180; p = 0.015), even after adjusting for age, sex, left ventricular ejection fraction, and log-transformed brain natriuretic peptide level. Thus, life-space activities are associated with prognosis in older adults with CVD.

We examined whether adding robot-supported balance exercises to cardiac rehabilitation improves the ability to balance in older adults with cardiovascular disease (CVD). We conducted a prospective study in 52 older adults who had been hospitalized for worsening CVD. Once weekly for four months, for a total of sixteen sessions as outpatients, the subjects used a Balance Exercise Assist Robot (BEAR) to perform balance exercises and an ergometer for aerobic exercises. Participants’ mean age was 76.9 ± 6.8 years (range, 65–95 years), and their mean brain natriuretic protein level was 164.0 ± 190.0 pg/mL. After the intervention, participants showed significant improvements in gait speed (before, 1.06 ± 0.33 m/s; after, 1.23 ± 0.30 m/s; p < 0.001), Short Physical Performance Battery score (before, 10.02 ± 2.25; after, 10.88 ± 1.79; p ˂ 0.001), timed up-and-go (before, 11.11 ± 5.07 s; after, 9.45 ± 3.45 s; p ˂ 0.001), and knee extension (before, 26.97 ± 11.78 kgf; after, 30.13 ± 13.04 kgf; p = 0.001). Cardiac rehabilitation including exercises using BEAR improved physical functioning and the ability to balance in older adults with CVD. Frail and prefrail patients improved, whereas robust ones did not change.

Abstract Background Remifentanil decreases blood loss during spinal surgery, rhinoplasty, and endoscopic sinus surgery. However, there are no reports regarding its effect on intraoperative blood loss during endoscopic body surface surgery. The present study aimed to investigate the effect of intraoperative remifentanil on blood loss during endoscopic subcutaneous mastectomy. Methods In this single-center, retrospective observational study conducted from August 2005 to June 2010, 443 patients who underwent either endoscopic subcutaneous partial mastectomy or quadrantectomy were included (n = 231 and 212, respectively). Patients were categorized into the remifentanil and non-remifentanil groups (n = 154 and 289, respectively) based on intraoperative use of remifentanil. We compared the amount of blood loss between the remifentanil and non-remifentanil groups. Results Blood loss was significantly smaller in the remifentanil group than in the non-remifentanil group in patients undergoing partial mastectomy (median [25%, 75%], 60 [30, 94] vs. 90 [50, 165] ml, P

The present study was conducted to identify anti-fatigue peptides in porcine liver hydrolysate (LH) and to evaluate their effects. Peptides in LH were fractionated into hydrophilic and hydrophobic fractions and further into peptides with amino groups (Pep-NH2) and pyroglutamyl peptide fractions (pE). Low dose of hydrophobic Pep-NH2 fraction reversed the decrease in locomotor activity after forced walking in a mouse model upon intraperitoneal (i.p.) administration. The anti-fatigue effects of i.p. injection of Asp-Val, Asp-Leu, and Asp-Phe with α and β peptide bonds and D- and L- asparatyl residue, which appeared in blood after oral administration of LH, were examined. In particular, Asp-Leu (Lβ), Asp-Phe (Dα), and Asp-Phe (Lα) exerted anti-fatigue effects at a low concentration (0.03 mg/kg). We found that Asp-Phe (Lα), but not other dipeptides, activated adenosine monophosphate-activated protein kinase (AMPK) in the liver, indicating that Asp-Phe (Lα) could induce recovery from fatigue via AMPK activation.

Many cells and soluble factors are involved in the wound healing process, which can be divided into inflammatory, proliferative, and remodeling phases. Fibroblasts play a crucial role in wound healing, especially during the proliferative phase, and show heterogeneity depending on lineage, tissue distribution, and extent of differentiation. Fibroblasts from tissue stem cells rather than from healthy tissues infiltrate wounds and proliferate. Some fibroblasts in the wound healing site express the mesenchymal stem cell marker, p75NTR. In the cell culture system, fibroblasts attached to collagen fibrils stop growing, even in the presence of protein growth factors, thus mimicking the quiescent nature of fibroblasts in healthy tissues. Fibroblasts in wound healing sites proliferate and are surrounded by collagen fibrils. These facts indicate presence of new growth-initiating factor for fibroblasts attached to collagen fibrils at the wound healing site, where the collagen-derived peptide, prolyl-hydroxyproline (Pro-Hyp), is generated. Pro-Hyp triggers the growth of p75NTR-positive fibroblasts cultured on collagen gel but not p75NTR-negative fibroblasts. Thus, Pro-Hyp is a low molecular weight growth-initiating factor for specific fibroblasts that is involved in the wound healing process. Pro-Hyp is also supplied to tissues by oral administration of gelatin or collagen hydrolysate. Thus, supplementation of gelatin or collagen hydrolysate has therapeutic potential for chronic wounds. Animal studies and human clinical trials have demonstrated that the ingestion of gelatin or collagen hydrolysate enhances the healing of pressure ulcers in animals and humans and improves delayed wound healing in diabetic animals. Therefore, the low molecular weight fibroblast growth-initiating factor, Pro-Hyp, plays a significant role in wound healing and has therapeutic potential for chronic wounds.

Background: Previous studies have reported associations between nonalcoholic fatty liver disease, periodontitis, and obesity. Serum immunoglobulin G (IgG) antibody titer against Porphyromonas gingivalis, a major pathogen of periodontitis, is an established indicator of periodontal infection. However, the relationship between the antibody titer and liver enzyme levels has not been clarified yet. A study in the elderly was needed to evaluate the effect of long-term persistent bacterial infection on liver function. The objective of this study was to investigate the association between liver function and infection by P. gingivalis, and the effect of obesity on the association. Methods: A cross-sectional study was conducted in adult outpatients visiting Sado General Hospital, in Niigata Prefecture, Japan, from 2008 to 2010. The final participants included 192 men and 196 women (mean age 68.1 years). Multivariable logistic regression analyses were performed to assess the association between the serum IgG antibody titer and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamine transferase (GGT) levels. Results: In women, serum IgG antibody titers against P. gingivalis was associated with elevated ALT, but not with AST or GGT, independent of covariates (p = 0.015). No significant association was found between the antibody titer and the elevated liver enzymes in men. The effect of obesity on the relationship between antibody titer and liver enzyme levels was not statistically significant. Conclusions: A cross-sectional analysis of adult outpatients suggested an association between P. gingivalis infection and ALT levels in women. The effect of obesity on this association was not statistically significant.

Synovial sarcoma (SS) is an aggressive soft-tissue cancer with a poor prognosis and a propensity for local recurrence and distant metastasis. In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Next, we identified that genetic depletion of Skp2 reduced mesenchymal and stemness markers, and inhibited the invasive and proliferative capacities of SS cell lines. Furthermore, Skp2 depletion markedly suppressed the growth of SS xenografts tumors. Treatment of SS cell lines with the skp2 inhibitor flavokawain A (FKA) reduced Skp2 expression in a dose-dependent manner and resulted in cell cycle arrest and apoptosis. FKA also suppressed the invasion and tumor-initiating properties in SS, similar to the effects of Skp2 knockdown. In addition, a combination of FKA and conventional chemotherapy showed a synergistic therapeutic efficacy. Taken together, our results suggest that Skp2 plays an essential role in the biology of SS by promoting the mesenchymal state and cancer stemness. Given that chemotherapy resistance is often associated with cancer stemness, strategies of combining Skp2 inhibitors with conventional chemotherapy in SS may be desirable.

Influenza viruses cause seasonal outbreaks and pose a continuous pandemic threat. Although vaccines are available for influenza control, their efficacy varies each season and a vaccine for a novel pandemic virus manufactured using current technology will not be available fast enough to mitigate the effect of the first pandemic wave. Antivirals can be effective against many different influenza viruses but have not thus far been used extensively for outbreak control. Baloxavir, a recently licensed antiviral drug that targets the influenza virus endonuclease, has been shown to reduce virus shedding more effectively than oseltamivir, a widely used neuraminidase inhibitor drug. Thus it is possible that treatment with baloxavir might also interrupt onward virus transmission. To test this, we utilized the ferret model, which is the most commonly used animal model to study influenza virus transmission. We established a subcutaneous baloxavir administration method in ferrets which achieved similar pharmacokinetics to the approved human oral dose. Transmission studies were then conducted in two different locations with different experimental setups to compare the onward transmission of A(H1N1)pdm09 virus from infected ferrets treated with baloxavir, oseltamivir or placebo to naïve sentinel ferrets exposed either indirectly in adjacent cages or directly by co-housing. We found that baloxavir treatment reduced infectious viral shedding in the upper respiratory tract of ferrets compared to placebo, and reduced the frequency of transmission amongst sentinels in both experimental setups, even when treatment was delayed until 2 days post-infection. In contrast, oseltamivir treatment did not substantially affect viral shedding or transmission compared to placebo. We did not detect the emergence of baloxavir-resistant variants in treated animals or in untreated sentinels. Our results support the concept that antivirals which decrease viral shedding could also reduce influenza transmission in the community.

Prolyl-hydroxyproline (Pro-Hyp) levels increase in human blood on ingesting collagen hydrolysate and trigger proliferation of primary cultured fibroblasts attached on collagen. Such proliferative effects have been associated with the beneficial effects of collagen hydrolysate ingestion including enhancement of wound healing. However, some fibroblast cell lines do not respond to Pro-Hyp. In this study, we focused on the mesenchymal stem cell marker p75 neurotrophin receptor (p75NTR), because p75NTR-positive cells are increased at wound healing sites. Most fibroblasts that had migrated from the dissected mouse skin for 1–4 days expressed p75NTR. After prolonged cultivation, however, the ratio of p75NTR-positive fibroblasts dropped. The p75NTR-positive fibroblasts specifically incorporated fluorescein isothiocyanate (FITC)-labeled Pro-Hyp and Pro-Hyp significantly increased the number of p75NTR-positive fibroblasts grown on collagen gel. These results suggest that Pro-Hyp could enhance wound healing by stimulating p75NTR-positive fibroblasts at wound healing sites, while it has little effect on p75NTR-negative resident fibroblasts in normal tissues.

During treatment with protein therapeutics, such as monoclonal antibodies, the development of anti-drug antibodies is a serious side-effect of modern pharmacology. Anti-drug antibodies are produced as the number and exposure to therapeutic proteins increase. In this context, less immunogenic responses could diminish these noxious effects. Biophysical characterization of antigens, that is size, chemical composition, physical form, and degrability, are known to influence the outcome of immune responses. Here, using chemical modification, we have prepared oligomers of hen egg lysozyme (HEL), 3- to 5-mer, as a typical antigen in immunology and evaluated the efficacy as a tolerogen in HEL-specific antibody responses. Our results clearly demonstrated that pre-exposed the HEL-oligomers into mice effectively suppressed HEL-specific IgG responses regardless of the cross-linking mode. Therefore, the oligomerization is a method to induce tolerogenicity of proteins and may emerge as a promising strategy to control the production of undesirable anti-protein drug antibodies. Keywords: Anti-drug antibodies, Hen egg white lysozyme, Immune tolerance, Oligomerization

Abstract Background Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. Methods We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. Results Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p

Background: The fruit of Katsura-uri, traditionally used in the preparation of pickles in Japan, is facing an extinction crisis. In addition to the traditional dishes prepared from Katsura-uri, alternative dishes using the fruit should be devised to increase consumer demands for the protection of the heirloom vegetable. We attempted designing new Katsura-uri contemporary dishes and assessed the application of Katsura-uri juice as a functional drink without raising blood glucose levels. Methods: Cooking experiments were conducted with Katsura-uri in its ripening stages, based on the advice from a licensed chef and a registered dietitian in Japan. In the questionnaire-based sensory evaluation, consumer acceptability of Katsura-uri juice was assessed. The blood glucose levels were measured after healthy volunteers consumed the juice. Results: We demonstrated six new Katsura-uri dishes. In the questionnaire-based sensory evaluation of Katsura-uri juice, the assessment values for taste and fragrance were high. In human trials, the levels of incremental area under the curve and glucose spike were significantly lower after consumption of Katsura-uri juice, as compared to those after consumption of muskmelon juice. Conclusion: Katsura-uri-containing contemporary dishes and juice would help continue the consumption of the vegetable. Based on the results of the questionnaire, we also concluded that the use of Katsura-uri as a functional drink without raising blood glucose levels is superior to its use as contemporary dishes. These findings provide useful strategies to protect Katsura-uri from extinction. Keywords: Blood glucose, Diabetes, Functional food, Heirloom vegetable, Traditional customs

Different proteases can be applied to produce certain bioactive peptides. This study focused on the effects of some commercial proteases and drying processes on the physical, chemical, and biological properties of chicken breast hydrolysates (CBH). Chicken breast hydrolyzed with Alcalase® presented a higher degree of hydrolysis (DH) than papain. Moreover, the treatment with Alcalase®, followed by papain (A-P), was more proficient in producing antioxidant activities than a single enzyme treatment. Conditions comprising 0.63% Alcalase® (w/w) at pH 8.0 and 52.5 °C for 3 h, followed by 0.13% papain (w/w) at pH 6.0 and 37 °C for 3 h, resulted in the highest yields of DH and peptide contents. The spray-dried microencapsulated powder improved the physicochemical properties including moisture content, color measurement, solubility, and particle morphology. In summary, the dual enzyme application involving the hydrolysis of Alcalase® and papain, coupled with the spray-drying process, could be used to produced antioxidant CBH.

The sense of agency (SoA) is part of psychophysiological modules related to the self. Disturbed SoA is found in several clinical conditions, hence understanding the neural correlates of the SoA is useful for the diagnosis and determining the proper treatment strategies. Although there are several neuroimaging studies on SoA, it is desirable to translate the knowledge to more accessible and inexpensive EEG-based biomarkers for the sake of applicability. However, SoA has not been widely investigated using EEG. To address this issue, we designed an EEG experiment on healthy adults (n = 15) to determine the sensitivity of EEG on the SoA paradigm using hand movement with parametrically delayed visual feedback. We calculated the power spectral density over the traditional EEG frequency bands for ten delay conditions relative to no delay condition. Independent component analysis and equivalent current dipole modeling were applied to address artifact rejection, volume conduction, and source localization to determine the effect of interest. The results revealed that the alpha and low-beta EEG power increased in the parieto-occipital regions in proportion to the reduced SoA reported by the subjects. We conclude that the parieto-occipital alpha and low-beta EEG power reflect the sense of agency.

A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans. GLE treatment ameliorated H2O2-induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson’s syndrome.

Abstract Background Glutathione plays crucial roles in the detoxification and antioxidant systems of cells and has been used to treat acute poisoning and chronic liver diseases by intravenous injection. This is a first study examining the therapeutic effects of oral administration of glutathione in patients with nonalcoholic fatty liver disease (NAFLD). Methods The study was an open label, single arm, multicenter, pilot trial. Thirty-four NAFLD patients diagnosed using ultrasonography were prospectively evaluated. All patients first underwent intervention to improve their lifestyle habits (diet and exercise) for 3 months, followed by treatment with glutathione (300 mg/day) for 4 months. We evaluated their clinical parameters before and after glutathione treatment. We also quantified liver fat and fibrosis using vibration-controlled transient elastography. The primary outcome of the study was the change in alanine aminotransferase (ALT) levels. Results Twenty-nine patients finished the protocol. ALT levels significantly decreased following treatment with glutathione for 4 months. In addition, triglycerides, non-esterified fatty acids, and ferritin levels also decreased with glutathione treatment. Following dichotomization of ALT responders based on a median 12.9% decrease from baseline, we found that ALT responders were younger in age and did not have severe diabetes compared with ALT non-responders. The controlled attenuation parameter also decreased in ALT responders. Conclusions This pilot study demonstrates the potential therapeutic effects of oral administration of glutathione in practical dose for patients with NAFLD. Large-scale clinical trials are needed to verify its efficacy. Trial registration UMIN000011118 (date of registration: July 4, 2013).

Background: Katsura-uri (Cucumis melo var. conomon), an heirloom vegetable cultivated in Kyoto, Japan is at the risk of extinction. Japanese food culture has traditionally used immature and midripened fruit in the preparation of pickles, the consumer demand of which has markedly decreased. A new strategy was adopted for Katsura-uri, aimed at increasing its inclusion in the present diet habit (e.g., Katsura-uri juice as a functional drink to prevent obesity and diabetes). Methods: Chemical analysis was performed to determine sugar profiles of fully ripened Katsura-uri fruits that uniquely possess muskmelon-like fragrance. In the questionnaire-based sensory evaluation, palatability was compared among the fruit juices without sweeteners and those with sugar or zero-calorie sweetener. Results: Chemical analysis results showed that the fully ripened Katsura-uri fruit had significantly lower levels of fructose, glucose, and sucrose (low-calories and lack of sweetness) than muskmelon fruits. In the questionnaire-based sensory evaluation, zero-calorie sweetener dramatically improved the palatability of the unprocessed fruit juice without altering its low-calorie properties and muskmelon-like fragrance. Conclusion: This demonstrated a new strategy to protect this heirloom vegetable from extinction by adding a new function that could increase its demand as a low-calorie fruit in the present diet habit for human health.

Two pyroglutamyl peptides with anti-colitic activity were identified in Japanese rice wine, sake, by oral administration of a small dose (0.1–1.0 mg/kg body weight) and in vivo activity-guided fractionation. Compounds in sake were fractionated by preparative isoelectric focusing followed by preparative reversed phase-liquid chromatography. Anti-colitic activity was evaluated using a dextran sulphate sodium (DSS)-induced colitis mouse model. The final active fraction contained three pyroglutamyl peptides: pyroglutamyl-tyrosine (pyroGlu-Tyr), pyroglutamyl-asparaginyl-isoleucine (pyroGlu-Asn-Ile) and pyroglutamyl-asparaginyl-isoleucyl-asparagyl-asparaginyl-proline (pyroGlu-Asn-Ile-Asp-Asn-Pro). Orally administrating artificially synthesized pyroGlu-Tyr (1.0 mg/kg body weight) and pyroGlu-Asn-Ile (0.1 and 1.0 mg/kg body weight) exhibited a significant protective effect against colitis in mice, whereas pyroGlu-Asn-Ile-Asp-Pro showed no significant effect. Additionally, administrating pyroGlu-Asn-Ile normalized colitis-induced colonic dysbiosis, whereas pyroGlu-Tyr did not. These results suggest that identified pyroglutamyl peptides exhibited an anti-colitic activity via different mechanisms.

Ureteral involvement is rare, with an estimated frequency of 10â14% in cases of deep infiltrating endometriosis. An important complication of ureteral involvement is asymptomatic loss of renal function. We reported that a 49-year-old woman presented with chronic pelvic pain due to severe dysmenorrhea and without any urological symptoms. Magnetic resonance imaging (MRI) identified a 7Â cm endometrioma compressing and infiltrating the rectal wall, and chronic left hydronephrosis. Isotope renogram decreased 14% function in the left kidney. We performed adhesiolysis, freeing of the uterus and appendages, hysterectomy, bilateral oophorectomy. However, we performed only to resect a part of left deep infiltrating endometriosis with ureteral involvement to avoid ureteral injury. After surgery, hydronephrosis was improved and those endometriosis left was not enlarged after 1 years of follow-up. We have to consider bilateral oophorectomy since endometriosis develops by the estrogen-dependent and it may decrease reproductive hormone derived from ovary. Keywords: Deep infiltrating endometriosis, Hydronephrosis, Laparoscopy, Peri-menopausal women

Comprehensive serum glycopeptide spectra analysis (CSGSA) evaluates >10,000 serum glycopeptides and identifies unique glycopeptide peaks and patterns via supervised orthogonal partial least-squares discriminant modeling. CSGSA was more accurate than cancer antigen 125 (CA125) or human epididymis protein 4 (HE4) for detecting early stage epithelial ovarian cancer. Combined CSGSA, CA125, and HE4 had improved diagnostic performance. Thus, CSGSA may be a useful screening tool for detecting early stage epithelial ovarian cancer.

Ovarian cancer is a leading cause of deaths among gynecological cancers, and a method to detect early-stage epithelial ovarian cancer (EOC) is urgently needed. We aimed to develop an artificial intelligence (AI)-based comprehensive serum glycopeptide spectra analysis (CSGSA-AI) method in combination with convolutional neural network (CNN) to detect aberrant glycans in serum samples of patients with EOC. We converted serum glycopeptide expression patterns into two-dimensional (2D) barcodes to let CNN learn and distinguish between EOC and non-EOC. CNN was trained using 60% samples and validated using 40% samples. We observed that principal component analysis-based alignment of glycopeptides to generate 2D barcodes significantly increased the diagnostic accuracy (88%) of the method. When CNN was trained with 2D barcodes colored on the basis of serum levels of CA125 and HE4, a diagnostic accuracy of 95% was achieved. We believe that this simple and low-cost method will increase the detection of EOC.

Prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp-Gly) appear in human blood after ingestion of collagen hydrolysate and trigger growth of fibroblasts attached on collagen gel, which has been associated with beneficial effects upon ingestion of collagen hydrolysate, such as improvement of skin and joint conditions. In the present study, inconsistent results were obtained by using different lots of fetal bovine serum (FBS). Fibroblasts proliferated in collagen gel without adding Pro-Hyp and Hyp-Gly and did not respond to addition of Pro-Hyp and Hyp-Gly, which raises doubts about conclusions from prior research. Unexpectedly high levels of hydroxyprolyl peptides, including Pro-Hyp, however, were present in the FBS (approximately 100 µM), and also in other commercially available forms of FBS (70−80 µM). After removal of low molecular weight (LMW, < 6000 Da) compounds from the FBS by size exclusion chromatography, Pro-Hyp and Hyp-Gly again triggered growth of fibroblasts attached on collagen and increased the number of fibroblasts migrated from mouse skin. These results indicate the presence of bioactive hydroxyprolyl peptides in commercially available FBS, which can mask effects of Pro-Hyp and Hyp-Gly supplementation; our work confirms that Pro-Hyp and Hyp-Gly do play crucial roles in proliferation of fibroblasts.

The n-hexane extract from spearmint (Mentha spicata) leaves was purified via a bioassay-guided fractionation scheme, which was based on the induction of differentiation in a RCM-1 human colon cancer cell line. One of the criteria of a differentiation marker is the formation of ducts determined visually using phase contrast microscopy, the most potent fraction contained piperitenone oxide, based on EI-MS, 1H-NMR and 13C-NMR spectra. Previously, the role of piperitenone oxide was considered as an odor producing compound in spearmint cultivars, but this study indicates the potential medical benefits of this compound. The effective dose of piperitenone oxide was lower than that of any differentiation-inducers found in the bioassay. Piperitenone oxide was categorized into monoterpene such as carvone and menthol, which are also familiar ingredients in Mentha genus plants. However, carvone and menthol did not possess the differentiation-inducing effect.

A shark cartilage proteolytic digest was fractionated by selective extraction with 75% ethanol. Peptides in the digest were recovered in the 75% ethanol-soluble fraction. The ethanol-soluble fraction showed lower viscosity and higher solubility in water than the crude digest. Oxonate-induced hyperuricemia in rat was suppressed by the oral administration of the ethanol-soluble fraction of the digest (1 g/kg body weight/day) for 28 days. Single administration of the ethanol-soluble fraction also reduced blood uric acid level in a dose-dependent manner. Administration of the ethanol-soluble fraction of the digest (1 g/kg body weight/day) significantly increased serum inhibitory activity against xanthine oxidase, whereas the ethanol-soluble fraction had no in vitro xanthine oxidase inhibitory activity. These facts suggest that peptides in the ethanol-soluble fraction might be converted into smaller peptides with xanthine oxidase inhibitory activity during digestion, absorption, and metabolism.

Direct addition of a food additive-grade Aspergillus niger phytase preparation to 30% brown rice flour-added bread ingredients reduced the bread myo-inositol hexaphosphate (IP6) content. The phytase preparation had protease and amylase activities. Addition of the crude phytase preparation induced bread crust collapse. Protease-free high- and low-amylase phytase fractions were prepared using preparative ampholyte-free isoelectric focusing (autofocusing). Addition of the protease-free low-amylase phytase fraction did not significantly affect loaf volume and did not collapse the crust. Addition of the protease-free high-amylase phytase fraction significantly increased loaf volume approximately 1.5× in the presence of amylase at 193–1029 U. However, addition of 1029 and 2058 U of amylase induced partial and whole bread crust collapse, respectively. Therefore, removal of protease and control of amylase activities in the phytase preparation are crucial in the preparation of brown rice flour-added bread with a low myo-inositol phosphate (IP6) and good swelling property.

Levels of short linear hydroxyproline (Hyp)-containing peptides, such as prolyl-hydroxyproline (Pro-Hyp), increase in human blood after the ingestion of collagen hydrolysate, which has been associated with beneficial effects for human skin and joints. The present study demonstrates the presence of a novel food-derived collagen peptide, cyclic Pro-Hyp, in human blood after the ingestion of collagen hydrolysate. The cyclic Pro-Hyp levels in plasma samples were estimated by liquid chromatography mass spectrometry (LC-MS). Cyclic Pro-Hyp levels significantly increased in the plasma after ingestion of collagen hydrolysate, reaching a maximum level after 2 h and then decreasing. The maximum level of cyclic Pro-Hyp in plasma ranged from 0.1413 to 0.3443 nmol/mL, representing approximately 5% of linear Pro-Hyp in plasma after ingestion of collagen hydrolysate. Addition of cyclic Pro-Hyp in medium at 7 nmol/mL significantly enhanced the growth rate of mouse skin fibroblasts on collagen gel more extensively compared to linear Pro-Hyp.

[This corrects the article DOI: 10.1371/journal.pone.0112408.].

TNF-α plays a crucial role in psoriasis; therefore, TNF inhibition has become a gold standard for the treatment of psoriasis. TNF-α is processed from a membrane-bound form by TNF-α converting enzyme (TACE) to soluble form, which exerts a number of biological activities. EGF receptor (EGFR) ligands, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and transforming growth factor (TGF)-α are also TACE substrates and are psoriasis-associated growth factors. Vascular endothelial growth factor (VEGF), one of the downstream molecules of EGFR and TNF signaling, plays a key role in angiogenesis for developing psoriasis. In the present study, to assess the possible role of TACE in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA-induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model of psoriasis. In this mouse model, TNF-α, amphiregulin, HB-EGF and TGF-α were significantly up-regulated in the skin lesions, similar to human psoriasis. Treatment of K5.Stat3C mice with TNF-α or EGFR inhibitors attenuated the skin lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble TNF-α. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte proliferation and VEGF production in vitro, suggesting that TACE was involved in both epidermal hyperplasia and angiogenesis during psoriasis development. These results strongly suggest that TACE contributes to the development of psoriatic lesions through releasing two kinds of psoriasis mediators, TNF-α and EGFR ligands. Therefore, TACE could be a potential therapeutic target for the treatment of psoriasis.