Modulatory Effects of NBF1, an Algal Fiber-Rich Bioformula, on Adiponectin and C-Reactive Protein Levels, and Its Therapeutic Prospects for Metabolic Syndrome and Type-2 Diabetes Patients.

An unhealthy diet can lead to the development of metabolic disorders. C-reactive protein (CRP) has been reported to be an inflammatory component of metabolic disorders. Additionally, reduced adiponectin (APN) levels is known as a predictor of metabolic disorders. We report on the beneficial effects of NBF1, an algal fiber-rich formula, on CRP, APN, and diabetes markers. Additionally, associations between dietary nutrients, CRP, and APN were investigated. A dietary survey that used a brief self-administered diet history questionnaire, a validated 58-item fixed-portion-type questionnaire, and a 4-week placebo-controlled dietary intervention were carried out. The latter consisted of a twice daily intake of 3 g of sujiaonori alga-based powder as a supplement (NBF1, n = 16), whereas the placebo group received the same amount of corn starch powder (n = 15). CRP and APN levels were assayed by ELISA. Clinical cases comprising three subjects with metabolic disorders treated with NBF1, including two type 2 diabetes mellitus patients and one subject with hypercholesterolemia, are also reported. They received 2.1g NBF1 once daily for 12 weeks. Intakes of algal fiber and n-3 PUFA were positively associated with the increase of APN, and n-3PUFA intake was inversely associated with CRP. All cases had improved metabolic health profile.

Clinical Characteristics of Lower-Limb Ischemia in Japanese Patients with Type 2 Diabetes and Usefulness of the Great Toe Blood Flow as a Predictive Indicator of Leg Arterial Obstruction.

Nurses are required to make quantitative, evidence-based observations when implementing diabetic foot care. This study aimed to clarify the characteristics of lower-limb ischemia in patients with type 2 diabetes using subjective and objective symptoms and physiological indicators and whether the physiological characteristics are established as predictive indicators of arterial obstruction. Fifty Japanese patients with type 2 diabetes (100 limbs) were classified into three groups using the ankle-brachial index (ABI). Patients with an ABI of ≤0.69 had subjective and objective symptoms of blood flow disturbance, such as pain at rest, cold sensation, pale skin, and imperceptibility to the dorsalis pedis artery. Blood flow in the first toe was the lowest. Binary logistic regression analysis established hallux perfusion as a predictive model for lower-limb arterial occlusion (odds ratio = 0.979, 95% confidence interval 0.900-0.999). Thus, when nurses perform diabetic foot care, it is necessary to evaluate not only subjective and objective symptoms, but also blood flow at the microcirculatory level of the great toe.

Dynamic change of fecal microbiota and metabolomics in a polymicrobial murine sepsis model.

Aim: Sepsis causes a systemic inflammatory reaction by destroying intestinal flora, which leads to a poor prognosis. In this study, we sought to clarify the characteristics of fecal flora and metabolites in a mouse model of sepsis by comprehensive metagenomic and metabolomic analysis. Methods: We performed a cecal ligation and puncture model procedure to create a mild sepsis model. We collected fecal samples on day 0 (healthy condition) and days 1 and 7 after the cecal ligation and puncture to determine the microbiome and metabolites. We analyzed fecal flora using 16S rRNA gene sequencing and metabolites using capillary electrophoresis mass spectrometry with time-of-flight analysis. Results: The abundance of bacteria belonging to the family Enterobacteriaceae significantly increased, but that of order Clostridiales such as the families Lachnospiraceae and Ruminococcaceae decreased on day 1 after the cecal ligation and puncture compared with those before the cecal ligation and puncture. The family Enterobacteriaceae significantly decreased, but that of order Clostridiales such as the families Lachnospiraceae and Ruminococcaceae increased on day 7 compared with those on day 1 after the cecal ligation and puncture. In the fecal metabolome, 313 metabolites were identified. Particularly, essential amino acids such as valine and non-essential amino acids such as glycine increased remarkably following injury. Betaine and trimethylamine also increased. In contrast, short-chain fatty acids such as isovaleric acid, butyric acid, and propionic acid decreased. Conclusion: The fecal microbiota following injury showed that Enterobacteriaceae increased in acute phase, and Lachnospiraceae and Ruminococcaceae increased in subacute phase. The metabolites revealed an increase in essential amino acids and choline metabolites and a decrease in short-chain fatty acids.

Relationship between Pressure Ulcers in Elderly People and Physiological Indices of the Skin.

This study examined the relationship between skin physiological indices and pressure ulcers in elderly people. The subjects were 55 bedridden elderly Japanese patients with a median age of 85 years. The following parame-ters were measured using non-invasive devices: skin surface temperature, moisture content in the stratum corneum, moisture content in the dermis, transepidermal water loss as an index of skin barrier function, skin erythema and skin elasticity. The sacral and 2 heel areas were observed as sites predisposed to pressure ulcers. Within one month after measuring the skin physiological indices, we confirmed pressure ulcers of National Pressure Ulcer Advisory Panel classification Stage II or worse based on medical records. Among the 55 patients, 4 (7.3%) prospectively developed a total of 5 pressure ulcers within 16 days. Only the skin erythema score was significantly higher with than without pressure ulcers (p < 0.001). We performed a binary logistic regression analysis and confirmed a significant relationship between pressure-ulcer development and the level of erythema (odds ratio = 1.026; 95% confidence interval: 1.011-1.042). Skin erythema increased before the development of pressure ulcers. Taken together, our results show that the high skin erythema score can be a predictive indicator of pressure ulcers.

Malaria rapid diagnostic test (HRP2/pLDH) positivity, incidence, care accessibility and impact of community WASH Action programme in DR Congo: mixed method study involving 625 households.

BACKGROUND: Malaria is one of the most prevalent and deadliest illnesses in sub-Saharan Africa. Despite recent gains made towards its control, many African countries still have endemic malaria transmission. This study aimed to assess malaria burden at household level in Kongo central province, Democratic Republic of Congo (DRC), and the impact of community participatory Water, Sanitation and Hygiene (WASH) Action programme. METHODS: Mixed method research was conducted in two semi-rural towns, Mbanza-Ngungu (a WASH action site) and Kasangulu (a WASH control site) in DRC between 1 January 2017 through March 2018, involving 625 households (3,712 household members). Baseline and post-intervention malaria surveys were conducted with the use of World Bank/WHO Malaria Indicator Questionnaire. An action research consisting of a six-month study was carried out which comprised two interventions: a community participatory WASH action programme aiming at eliminating mosquito breeding areas in the residential environment and a community anti-malaria education campaign. The latter was implemented at both study sites. In addition, baseline and post-intervention malaria rapid diagnostic test (RDT) was performed among the respondents. Furthermore, a six-month hospital-based epidemiological study was conducted at selected referral hospitals at each site from 1 January through June 2017 to determine malaria trend. RESULTS: Long-lasting insecticide-treated net (LLIN) was the most commonly used preventive measure (55%); 24% of households did not use any measures. Baseline malaria survey showed that 96% of respondents (heads of households) reported at least one episode occurring in the previous six months; of them only 66.5% received malaria care at a health setting. In the Action Research, mean incident household malaria cases decreased significantly at WASH action site (2.3 ± 2.2 cases vs. 1.2 ± 0.7 cases, respectively; p < 0.05), whereas it remained unchanged at the Control site. Similar findings were observed with RDT results. Data collected from referral hospitals showed high malaria incidence rate, 67.4%. Low household income (ORa = 2.37; 95%CI: 1.05-3.12; p < 0.05), proximity to high risk area for malaria (ORa = 5.13; 95%CI: 2-29-8.07; p < 0.001), poor WASH (ORa = 4.10; 95%CI: 2.11-7.08; p < 0.001) were predictors of household malaria. CONCLUSION: This research showed high prevalence of positive malaria RDT among the responders and high household malaria incidence, which were reduced by a 6-month WASH intervention. DRC government should scale up malaria control strategy by integrating efficient indoor and outdoor preventive measures and improve malaria care accessibility.

Interstitial cells of Cajal are diminished in critically ill patients: Autopsy cases.

OBJECTIVE: Gastrointestinal dysmotility in critically ill patients is important as enteral nutrition is crucial. However, normal gut motility is impaired under conditions of critical illness subsequent to severe insult. Interstitial cells of Cajal (ICC) form an extensive network associated with the myenteric plexus in the enteric nervous system. There are few reports about ICC distribution in critically ill patients. The aim of this study was to evaluate ICC in critically ill patients. METHODS: Postmortem colon harvest was obtained from critically ill patients. Control specimens were obtained from patients without bowel movement problems who underwent hemicolectomy. The tissues were stained with c-Kit for ICC. The number of ICC was identified by counting from 10 high-power fields (HPFs). RESULTS: Specimens from six patients were analyzed and compared with those from six control patients. All patients had abnormalities of crypt architecture and inflammatory cell infiltrations. Mucosal thickness tended to be lower in the critically ill patients than in the controls (147 ± 47 versus 231 ± 127 µm; P = 0.15). Muscle layer thickness tended to be higher in the critically ill patients than in the controls (494 ± 163 versus 394 ± 258 µm; P = 0.44). ICC in the critically ill patients were almost depleted in the colon compared with those in the controls. Significantly fewer ICC were present in the critically ill patients than in the controls (0.45 versus 7.25 cells/HPF; P < 0.05). CONCLUSIONS: Critical illness is associated with diminished numbers of ICC in the colon. This finding could have implications for dysmotility in critically ill patients.

Environmental and sociodemographic factors associated with household malaria burden in the Congo.

BACKGROUND: Malaria is one of the most severe public health issues that result in massive morbidity and mortality in most countries of the sub-Saharan Africa (SSA). This study aimed to determine the scope of household, accessibility to malaria care and factors associated with household malaria in the Democratic Republic of Congo (DRC). METHODS: This was a community-based cross-sectional study conducted in an urban and a rural sites in which 152 households participated, including 82 urban and 70 rural households (1029 members in total). The 'malaria indicator questionnaire' (MIQ) was anonymously answered by household heads (respondents), reporting on malaria status of household members in the last 12 months. RESULTS: There were 67.8% of households using insecticide-treated bed nets (ITN) only, 14.0% used indoor residual spraying (IRS) only, 7.3% used ordinary bed nets (without insecticide treatment), 1.4% used mosquito repelling cream, 2.2% combined ITN and IRS, whereas 7.3% of households did not employ any preventive measure; p < 0.01). In addition, 96.7% of households were affected by malaria (at least one malaria case), and malaria frequency per household was relatively high (mean: 4.5 ± 3.1 cases reported) in the last 12 months. The mean individual malaria care expenditure was relatively high (101.6 ± 10.6 USD) in the previous 12 months; however, the majority of households (74.5%) earned less than 50 USD monthly. In addition, of the responders who suffered from malaria, 24.1% did not have access to malaria care at a health setting. Furthermore, a multivariate analysis with adjustment for age, education level and occupation showed that household size (OR = 1.43 ± 0.13; 95% CI 1.18-1.73; p < 0.001), inappropriate water source (OR = 2.41 ± 0.18; 95% CI 1.17-2.96; p < 0.05) absence of periodic water, sanitation and hygiene (WASH) intervention in residential area (OR = 1.63 ± 1.15; 95% CI 1.10-2.54; p < 0.05), and rural residence (OR = 4.52 ± 2.47; 95% CI 1.54-13.21; p < 0.01) were associated with household malaria. CONCLUSION: This study showed that household size, income, WASH status and rural site were malaria-associated factors. Scaling up malaria prevention through improving WASH status in the residential environment may contribute to reducing the disease burden.

Colonic ischemia possibly due to resuscitative endovascular balloon occlusion of the aorta (REBOA) used to manage amniotic fluid embolism: a case report.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) can control massive postpartum hemorrhage. CASE PRESENTATION: A 41-year-old woman transferred to hospital following cesarean section presented in refractory hemorrhagic shock. REBOA was blindly performed in the emergency department. She immediately underwent hysterectomy and damage control surgery in the operating room. The aortic balloon, whose position was confirmed at zone II by postoperative X-ray, provided intermittent occlusion for 40 min during surgery. Hemodynamics were stabilized with these interventions, with massive transfusion required for severe coagulopathy perioperatively. She gradually recovered with intensive care but suffered ascending colon ischemia with perforation on day 16. She received a colostomy and was discharged without sequelae after 130 days. Amniotic fluid embolism was diagnosed according to clinical criteria and supplemental serum markers. CONCLUSIONS: This patient suffered colonic ischemia possibly due to REBOA used to manage amniotic fluid embolism. REBOA requires careful consideration to avoid complications.

The clinical importance of a cytokine network in the acute phase of sepsis.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1ß, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Synbiotics modulate gut microbiota and reduce enteritis and ventilator-associated pneumonia in patients with sepsis: a randomized controlled trial.

BACKGROUND: Commensal microbiota deteriorate in critically ill patients. The preventive effects of probiotic/synbiotic therapy on microbiota and septic complications have not been thoroughly clarified in patients with sepsis. The objective of this study was to evaluate whether synbiotics have effects on gut microbiota and reduce complications in mechanically ventilated patients with sepsis. METHODS: Sepsis patients who were mechanically ventilated in the intensive care unit (ICU) were included in this randomized controlled study. Patients receiving daily synbiotics (Bifidobacterium breve strain Yakult, Lactobacillus casei strain Shirota, and galactooligosaccharides) initiated within 3 days after admission (the Synbiotics group) were compared with patients who did not receive synbiotics (the No-Synbiotics group). The primary outcome was infectious complications including enteritis, ventilator-associated pneumonia (VAP), and bacteremia within 4 weeks from admission. The secondary outcomes included mortality within 4 weeks, fecal bacterial counts, and organic acid concentration. Enteritis was defined as the acute onset of continuous liquid stools for more than 12 h. RESULTS: Seventy-two patients completed this trial; 35 patients received synbiotics and 37 patients did not receive synbiotics. The incidence of enteritis was significantly lower in the Synbiotics than the No-Synbiotics group (6.3% vs. 27.0%; p < 0.05). The incidence of VAP was also significantly lower in the Synbiotics than the No-Synbiotics group (14.3% vs. 48.6%; p < 0.05). The incidence of bacteremia and mortality did not differ significantly between the two groups. In the analysis of fecal bacteria, the number of Bifidobacterium and Lactobacillus in the Synbiotics group was significantly higher than that in the No-Synbiotics group. In the analysis of fecal organic acids, total organic acid concentration, especially the amounts of acetate, were significantly greater in the Synbiotics group than in the No-Synbiotics group at the first week (p < 0.05). CONCLUSIONS: Prophylactic synbiotics could modulate the gut microbiota and environment and may have preventive effects on the incidence of enteritis and VAP in patients with sepsis. TRIAL REGISTRATION: UMIN, R000007633 . Registered on 29 September 2011.

Association of prophylactic synbiotics with reduction in diarrhea and pneumonia in mechanically ventilated critically ill patients: A propensity score analysis.

INTRODUCTION: The preventive association of synbiotics therapy has not been thoroughly clarified in mechanically ventilated patients. The purpose of this study was to evaluate whether synbiotics therapy has preventive association against septic complications in ventilated critically ill patients. METHODS: Critically ill patients who were mechanically ventilated were included in this retrospective observational study. Patients who received synbiotics (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides) within 3 days after admission (denoted as synbiotics group) were compared with patients who did not receive synbiotics. The incidences of enteritis, pneumonia, and bacteremia were evaluated as clinical outcome. Enteritis was defined as an acute onset of diarrhea consisting of continuous liquid watery stools for more than 12 h. The confounding factors include APACHE II on admission, gender, the cause of admission and antibiotics. RESULTS: We included 179 patients in this study: 57 patients received synbiotics and 122 patients did not receive synbiotics. The incidences of enteritis were significantly lower in the synbiotics group compared with the control group (3.5% vs. 15.6%; p < 0.05). The odds ratios for diarrhea-free days during the first 28 days for the synbiotics group as compared with the controls were 4.354 (95% confidence interval (CI), 2.407 to 7.877; p < 0.001) in an ordinal logistic regression model with propensity scores. The odds ratios for pneumonia-free days during the first 28 days for the synbiotics group were 2.529 (95% CI, 1.715 to 3.731; p < 0.001). The incidences of bacteremia did not have significant differences. CONCLUSION: Prophylactic synbiotics appeared to have preventive association on enteritis and pneumonia in mechanically ventilated critically ill patients.

Hydrogen-Rich Saline Regulates Intestinal Barrier Dysfunction, Dysbiosis, and Bacterial Translocation in a Murine Model of Sepsis.

Bacterial translocation is a major cause of multiple organ dysfunction syndrome in critical illness, and its management is an important therapeutic strategy. In this study, we focused on the key factors responsible for bacterial translocation including the intestinal microbiome and investigated the impact of molecular hydrogen therapy as a countermeasure against bacterial translocation in a murine model of sepsis. The experimental protocols were divided into the sham, saline treatment (control), and hydrogen treatment (H2) groups. In the H2 group, 15 mL/kg of hydrogen-rich saline (7 ppm) was gavaged daily for 7 days following cecal ligation and puncture (CLP). In the control group, normal saline was gavaged in the same way. In the results, the 7-day survival rate was significantly improved in the H2 group versus the control group (69% vs. 31%, P < 0.05). The incidence of bacterial translocation at 24 h after CLP as assessed by cultivation of mesenteric lymph nodes and blood was significantly decreased in the H2 group versus the control group. Administration of hydrogen-rich saline also prevented the expansion of facultative anaerobic Enterobacteriaceae and ameliorated intestinal hyperpermeability at 24 h after CLP. Intestinal tissue levels of inflammatory mediators such as inducible nitric oxide synthases, tumor necrosis factor α, interleukin (IL)-1ß, IL-6, and oxidative stress marker malondialdehyde at 6 h after CLP were down-regulated in the H2 group. These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.

Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis.

PURPOSE: One of the pathophysiological processes in sepsis is endothelial dysfunction, which leads to disseminated intravascular coagulation (DIC). Syndecan-1 is a major structural component of the endothelium and plays a key role in endothelial function. The purpose of this study was to assess the value of syndecan-1 as a predictive marker for DIC in sepsis. METHODS: We performed a prospective observational study of patients with sepsis from February 2014 to July 2015. Serial change of hemostatic markers, anticoagulant and fibrinolytic markers (antithrombin, PAI-1), endothelial markers (syndecan-1, VCAM-1, E-selectin), and inflammatory markers (IL-1ß, IL-6, IL-8, HMGB-1, histone-H3) were analyzed. Clinical data including APACHE II, SOFA, and DIC scores and 28-day mortality were also evaluated. RESULTS: During the study, 39 septic patients and 15 healthy controls were included. Syndecan-1 levels were significantly increased in the septic patients compared with the healthy controls. Of the septic patients, non-survivors had higher syndecan-1 levels than did the survivors on days 1, 2, and 4. Significant correlations on day 1 were found between syndecan-1 levels and APACHE II, SOFA, and DIC scores, hemostatic markers, IL-1ß, IL-8, and PAI-1. Syndecan-1 levels on day 1 were also significantly higher in patients with than without DIC and had strong discriminative power for the prediction of both DIC development and subsequent mortality, with AUCs of 0.79 and 0.85, respectively. CONCLUSION: Syndecan-1 levels were associated with not only the severity of illness and mortality but also DIC development in sepsis, suggesting that syndecan-1 could be a predictive marker of DIC.

Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

Sujiaonori-Derived Algal Biomaterials Inhibit Allergic Reaction in Allergen-Sensitized RBL-2H3 Cell Line and Improve Skin Health in Humans.

Sujiaonori, a river alga growing in the Kochi prefecture, Japan, contains several bioactive compounds such as sulfated polysaccharides (ulvans), ω-3 fatty acids, and vitamins. Dietary intake of this alga-based supplement has been reported to increase circulatory adiponectin, a salutary hormone that is reported to be associated with healthy longevity and prevents a number of cardiovascular and metabolic disorders. This report highlights the anti-allergic and skin health enhancing effects of Sujiaonori-derived ulvan (Tosalvan) and supplement, respectively. RBL-2H3 cell line was used to investigate the anti-allergic effect of algal SP through the evaluation of ß-hexosaminidase activity. Algal sulfated polysaccharides or SP (Tosalvan, Yoshino SP) were extracted from powders of dried alga samples provided by local food manufacturers. Report on the effect of daily dietary intake of Sujiaonori-based supplement on skin health is part of a four-week clinical investigation that, in comparison with a supplement made of 70% corn starch powder and 30% spinach powder mixture (twice 3 g daily), explore the beneficial effects of Sujiaonori algal biomaterial (SBM; 3 g taken twice daily) on cardiovascular, gastrointestinal and skin health in a sample of Japanese women. Transepidermal water loss (TEWL) was the skin health marker used in this study and was measured with the use of a corneometer. Significant reduction of ß-hexosaminidase activity was observed in Tosalvan and Yoshino SP-treated cells (vs. control; p < 0.05), whereas dietary intake of SBM markedly reduced TEWL level after four weeks of supplementation, as compared to baseline TEWL (p < 0.001). Additionally, SBM improved TEWL better than the control product (p < 0.001). Findings contained in this report suggest that Sujiaonori-derived Tosalvan and Yoshino SP have anti-allergic potential and that the dietary intake of SBM has a beneficial effect on skin health.

Laxative Effects of Dietary Supplementation with Sujiaonori Algal Biomaterial in Japanese Adult Women with Functional Constipation: A Case Study.

Constipation is a gastrointestinal motility disorder that represents a major health problem in Japan. Approximately 26% of young Japanese adult women are reported to have this complaint. We report on the health effects of daily intake of Sujiaonori algal biomaterial (SBM) on constipation on 12 Japanese adult women. Data are from a four-week dietary intervention study on the health effects of daily Sujiaonori supplementation on cardiovascular, skin, and gastrointestinal health in which 32 adult Japanese volunteers (age range: 20-54 years) participated. They underwent clinical and laboratory investigations, and completed two study questionnaires (the brief diet history questionnaire (BDHQ) and the current health questionnaire) before and after dietary intervention. Of the 12 women volunteers with functional constipation, there were six SBM-supplemented subjects who received 3 g of Sujiaonori powder twice daily during meal, whereas the six others (controls) were from the group of those who took 3 g of a power made of 70% corn starch and 30% Japanese spinach mixture. The analysis of data on daily nutrient intake showed no significant dietary changes for nutrients (minerals, proteins, fiber, fat) and calorie intake (except alcohol intake that was reduced) in both groups. In SBM group, a significant reduction of the proportion of women with constipation was observed (p < 0.001), whereas no significant change was noted within the control group (p > 0.05). When both groups were compared, SBM was more effective than the control product; 66.7% (4/6) of SBM-supplemented women had their constipation relieved, whereas only one control (16.7%) controls benefited from dietary intervention (p < 0.001). In addition, no adverse effect was reported in the SBM group, whereas two controls reported nausea at post-survey. These results suggest that Sujiaonori contains compounds that can improve gastrointestinal function and relieve constipation.

Anti-allergic and Profilaggrin (ProFLG)-mRNA expression modulatory effects of sacran.

Atopic dermatitis (AD) is a skin disorder characterized by filaggrin (FLG) defect. We evaluated sacran's effects on dust-mite extracts (DME)-induced AD-like disease and also its effect on profilaggrin (proFLG) in a murine model of 2,4-dinitroflurobenze (DNFB)-induced contact hypersensitivity. In the murine AD-like disease model, allergic NC/Nga mice (N=60) were randomly divided into five treatment groups of 12 animals each: 0.2% and 1%sacran; 0.1% Tacrolimus; Vaseline and buffer-treated controls. Blood samples were drawn and serum levels of representative Th-1, Th-2 and also Th-17 (IL-17A) cytokines were assayed by Cytometric Bead Array (CBA). In the contact hypersensitivity model, diseased NC/Nga mice (N=20) were divided into four groups of five mice each [0.05%sacran, 0.05% chondroitin sulfate (CS), 0.5% prednisolone (PD), non-treated control group] and were treated for 14days. Skin biopsies were performed for the measurement of proFLG-mRNA by real-time PCR. Sacran solutions and 0.1%Tacrolimus reduced disease severity, suppressed histological changes and decreased the serum Th-1 (IFN-γ, TNF-α, IL-2) and Th-2 (IL-4, IL-6, IL-10) cytokines in allergic mice (vs. controls). Additionally, a marked increase of proFLG-mRNA expression was observed in 0.05%sacran group (vs. control 0.05% CS and 0.5% PD groups). Thus, Sacran might be useful as a natural skin barrier enhancer and anti-allergic agent.

Critical involvement of ZEB2 in collagen fibrillogenesis: the molecular similarity between Mowat-Wilson syndrome and Ehlers-Danlos syndrome.

Mowat-Wilson syndrome (MOWS) is a congenital disease caused by de novo heterozygous loss of function mutations or deletions of the ZEB2 gene. MOWS patients show multiple anomalies including intellectual disability, a distinctive facial appearance, microcephaly, congenital heart defects and Hirschsprung disease. However, the skin manifestation(s) of patients with MOWS has not been documented in detail. Here, we recognized that MOWS patients exhibit many Ehlers-Danlos syndrome (EDS)-like symptoms, such as skin hyperextensibility, atrophic scars and joint hypermobility. MOWS patients showed a thinner dermal thickness and electron microscopy revealed miniaturized collagen fibrils. Notably, mice with a mesoderm-specific deletion of the Zeb2 gene (Zeb2-cKO) demonstrated redundant skin, dermal hypoplasia and miniaturized collagen fibrils similar to those of MOWS patients. Dermal fibroblasts derived from Zeb2-cKO mice showed a decreased expression of extracellular matrix (ECM) molecules, such as collagens, whereas molecules involved in degradation of the ECM, such as matrix metalloproteinases (MMPs), were up-regulated. Furthermore, bleomycin-induced skin fibrosis was attenuated in Zeb2-cKO mice. We conclude that MOWS patients exhibit an EDS-like skin phenotype through alterations of collagen fibrillogenesis due to ZEB2 mutations or deletions.

Uncovering Adiponectin Replenishing Property of Sujiaonori Algal Biomaterial in Humans.

The replenishment of adiponectin-an adipocyte-derived hormone with salutary health effects-has recently been proposed as a new approach to treat hypertension, also ameliorate cardiovascular and metabolic risks. We conducted a prospective placebo-controlled, non-randomized and investigator-blinded dietary intervention study to evaluate the health effects of dietary intake of Sujiaonori (Ulva/Enteromorpha prolifera Müller) algal biomaterial (SBM), especially on adiponectin production, blood pressure (BP), and body mass index (BMI) in human subjects. Participants (N = 32) were divided into two equally sized groups (n = 16 for each group): SBM group (subjects supplemented with 3 g SBM powder twice a day during meal) and the control group (subjects who took 3 g of a supplement made of 70% corn starch powder and 30% spinach twice a day) for four weeks. Two health survey questionnaires (dietary and current health questionnaires) were completed anonymously, saliva sampling was done for adiponectin measurement by ELISA, and blood pressure (BP) and anthropometric parameters were measured at baseline and four weeks later. Student paired t-test was performed to compare baseline and post-intervention data on outcome variables between the two study groups. Results showed a 2.24-fold increase in adiponectin level in SBM group (2.81 and 6.26 ng/mL at baseline and at the end of study, respectively) (p < 0.01); whereas no significant change was observed in controls (3.58 and 3.51 ng/mL, respectively) (p > 0.05). In SBM subjects, an improvement of BP profile was noted with a significant decrease in systolic BP (p < 0.01). A positive correlation was found between SBM supplementation and adiponectin level, whereas an inverse correlation was noted between SBM supplementation and blood pressure, and also BMI. These findings suggest that SBM-increased adiponectin level and improved BP in a sample of Japanese young adults, and has the potential to improve blood pressure in humans.