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1.
ISME Commun ; 3(1): 28, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37002405

ABSTRACT

Compost is used worldwide as a soil conditioner for crops, but its functions have still been explored. Here, the omics profiles of carrots were investigated, as a root vegetable plant model, in a field amended with compost fermented with thermophilic Bacillaceae for growth and quality indices. Exposure to compost significantly increased the productivity, antioxidant activity, color, and taste of the carrot root and altered the soil bacterial composition with the levels of characteristic metabolites of the leaf, root, and soil. Based on the data, structural equation modeling (SEM) estimated that amino acids, antioxidant activity, flavonoids and/or carotenoids in plants were optimally linked by exposure to compost. The SEM of the soil estimated that the genus Paenibacillus and nitrogen compounds were optimally involved during exposure. These estimates did not show a contradiction between the whole genomic analysis of compost-derived Paenibacillus isolates and the bioactivity data, inferring the presence of a complex cascade of plant growth-promoting effects and modulation of the nitrogen cycle by the compost itself. These observations have provided information on the qualitative indicators of compost in complex soil-plant interactions and offer a new perspective for chemically independent sustainable agriculture through the efficient use of natural nitrogen.

2.
Front Microbiol ; 13: 991819, 2022.
Article in English | MEDLINE | ID: mdl-36386693

ABSTRACT

Aquaculture is attracting attention as a sustainable protein source. Salmoniformes, which are generally called salmon, are consumed in large quantities worldwide and are popularly used for aquaculture. In this study, the relationship between muscle metabolites, intestinal microbiota, and nonnumerical information about the ecology of salmoniformes was investigated to improve the efficiency of aquaculture using nuclear magnetic resonance and next-generation sequencing with bioinformatics approach. It was revealed that salmoniformes are rich in anserine and creatine, which are useful for human health care, along with collagen and lipids. The important factors in increasing these useful substances and manage the environment of salmoniformes aquaculture should be noted.

3.
J Biosci Bioeng ; 134(2): 105-115, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35718655

ABSTRACT

Weizmannia coagulans SANK70258 is a spore-forming thermostable lactic acid bacterium and an effective probiotic for the growth of livestock animals, but its growth-promoting mechanism remains unclear. Here, the composition of fecal metabolites in broilers continuously administered with W. coagulans SANK70258 was assessed under a regular program with antibiotics, which was transiently given for 6 days after birth. Oral administration of W. coagulans to broiler chicks tended to increase the average daily gain of body weights thereafter. The composition of fecal metabolites in the early chick stage (day 10 after birth) was dramatically altered by the continuous exposure. The levels of short-chain fatty acids (SCFAs) propionate and butyrate markedly increased, while those of acetate, one of the SCFAs, and lactate were reduced. Simultaneously, arabitol, fructose, mannitol, and erythritol, which are carbohydrates as substrates for gut microbes to produce SCFAs, also increased along with altered correlation. Correlation network analyses classified the modularity clusters (|r| > 0.7) among carbohydrates, SCFAs, lactate, amino acids, and the other metabolites under the two conditions. The characteristic diversities by the exposure were visualized beyond the perspective associated with differences in metabolite concentrations. Further, enrichment pathway analyses showed that metabolic composition related to biosynthesis and/or metabolism for SCFAs, amino acids, and energy were activated. Thus, these observations suggest that W. coagulans SANK70258 dramatically modulates the gut metabolism of the broiler chicks, and the metabolomics profiles during the early chick stages may be associated with growth promotion.


Subject(s)
Lactobacillales , Probiotics , Amino Acids , Animals , Carbohydrates , Chickens/metabolism , Fatty Acids, Volatile/metabolism , Lactates , Lactobacillales/metabolism
4.
Sci Total Environ ; 836: 155520, 2022 Aug 25.
Article in English | MEDLINE | ID: mdl-35508250

ABSTRACT

Effective biological utilization of wood biomass is necessary worldwide. Since several insect larvae can use wood biomass as a nutrient source, studies on their digestive microbial structures are expected to reveal a novel rule underlying wood biomass processing. Here, structural inferences for inhabitant bacteria involved in carbon and nitrogen metabolism for beetle larvae, an insect model, were performed to explore the potential rules. Bacterial analysis of larval feces showed enrichment of the phyla Chroloflexi, Gemmatimonadetes, and Planctomycetes, and the genera Bradyrhizobium, Chonella, Corallococcus, Gemmata, Hyphomicrobium, Lutibacterium, Paenibacillus, and Rhodoplanes, as bacteria potential involved in plant growth promotion, nitrogen cycle modulation, and/or environmental protection. The fecal abundances of these bacteria were not necessarily positively correlated with their abundances in the habitat, indicating that they were selectively enriched in the feces of the larvae. Correlation and association analyses predicted that common fecal bacteria might affect carbon and nitrogen metabolism. Based on these hypotheses, structural equation modeling (SEM) statistically estimated that inhabitant bacterial groups involved in carbon and nitrogen metabolism were composed of the phylum Gemmatimonadetes and Planctomycetes, and the genera Bradyrhizobium, Corallococcus, Gemmata, and Paenibacillus, which were among the fecal-enriched bacteria. Nevertheless, the selected common bacteria, i.e., the phyla Acidobacteria, Armatimonadetes, and Bacteroidetes and the genera Candidatus Solibacter, Devosia, Fimbriimonas, Gemmatimonas Opitutus, Sphingobium, and Methanobacterium, were necessary to obtain good fit indices in the SEM. In addition, the composition of the bacterial groups differed depending upon metabolic targets, carbon and nitrogen, and their stable isotopes, δ13C and δ15N, respectively. Thus, the statistically derived causal structural models highlighted that the larval fecal-enriched bacteria and common symbiotic bacteria might selectively play a role in wood biomass carbon and nitrogen metabolism. This information could confer a new perspective that helps us use wood biomass more efficiently and might stimulate innovation in environmental industries in the future.


Subject(s)
Carbon , Coleoptera , Acidobacteria/metabolism , Animals , Bacteria/metabolism , Carbon/metabolism , Coleoptera/metabolism , Larva/metabolism , Nitrogen/metabolism , Wood/metabolism
6.
Sci Rep ; 8(1): 17322, 2018 11 23.
Article in English | MEDLINE | ID: mdl-30470792

ABSTRACT

CD80, which regulates T cell activation, may provide a differential diagnostic marker between minimal change disease (MCD) and other renal diseases, including focal segmental glomerular sclerosis (FSGS). However, recent reports show contrasting results. Therefore, we evaluated the utility of urinary CD80 as a diagnostic biomarker. We collected 65 urine samples from 55 patients with MCD (n = 31), FSGS (n = 4), inherited nephrotic syndrome (n = 4), Alport syndrome (n = 5) and other glomerular diseases (n = 11), and control samples (n = 30). We measured urinary CD80 levels by ELISA. Urinary CD80 (ng/gCr) (median, interquartile range) levels were significantly higher in patients with MCD in relapse (91.5, 31.1-356.0), FSGS (376.2, 62.7-1916.0), and inherited nephrotic syndrome (220.1, 62.9-865.3), than in patients with MCD in remission (29.5, 21.7-52.8) (p < 0.05). Elevation of urinary CD80 was observed, even in patients with inherited nephrotic syndrome unrelated to T cell activation. Additionally, urinary CD80 was positively correlated with urinary protein levels. Our results suggest that urinary CD80 is unreliable as a differential diagnostic marker between MCD in relapse and FSGS or inherited kidney diseases. Increased urinary CD80 excretion was present in all patients with active kidney disease.


Subject(s)
B7-1 Antigen/urine , Biomarkers/urine , Kidney Diseases/classification , Kidney Diseases/diagnosis , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Female , Glomerulosclerosis, Focal Segmental/diagnosis , Glomerulosclerosis, Focal Segmental/urine , Humans , Infant , Kidney Diseases/urine , Male , Nephrosis, Lipoid/diagnosis , Nephrosis, Lipoid/urine , Nephrotic Syndrome/diagnosis , Nephrotic Syndrome/urine , ROC Curve , Recurrence , Retrospective Studies , Urinalysis , Young Adult
7.
Nutrients ; 9(12)2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29194366

ABSTRACT

Prebiotics and probiotics strongly impact the gut ecosystem by changing the composition and/or metabolism of the microbiota to improve the health of the host. However, the composition of the microbiota constantly changes due to the intake of daily diet. This shift in the microbiota composition has a considerable impact; however, non-pre/probiotic foods that have a low impact are ignored because of the lack of a highly sensitive evaluation method. We performed comprehensive acquisition of data using existing measurements (nuclear magnetic resonance, next-generation DNA sequencing, and inductively coupled plasma-optical emission spectroscopy) and analyses based on a combination of machine learning and network visualization, which extracted important factors by the Random Forest approach, and applied these factors to a network module. We used two pteridophytes, Pteridium aquilinum and Matteuccia struthiopteris, for the representative daily diet. This novel analytical method could detect the impact of a small but significant shift associated with Matteuccia struthiopteris but not Pteridium aquilinum intake, using the functional network module. In this study, we proposed a novel method that is useful to explore a new valuable food to improve the health of the host as pre/probiotics.


Subject(s)
Ferns/chemistry , Food , Gastrointestinal Tract/physiology , Machine Learning , Models, Biological , Humans , Male , Microbiota , Prebiotics , Probiotics
8.
Int Immunol ; 29(10): 471-478, 2017 12 18.
Article in English | MEDLINE | ID: mdl-29186424

ABSTRACT

Nasopharynx-associated lymphoid tissue (NALT) is one of the major constituents of the mucosa-associated lymphoid tissue (MALT), and has the ability to induce antigen-specific immune responses. However, the molecular mechanisms responsible for antigen uptake from the nasal cavity into the NALT remain largely unknown. Immunohistochemical analysis showed that CCL9 and CCL20 were co-localized with glycoprotein 2 (GP2) in the epithelium covering NALT, suggesting the existence of M cells in NALT. In analogy with the reduced number of Peyer's patch M cells in CCR6-deficient mice, the number of NALT M cells was drastically decreased in CCR6-deficient mice compared with the wild-type mice. Translocation of nasally administered Salmonella enterica serovar Typhimurium into NALT via NALT M cells was impaired in CCR6-deficient mice, whereas S. Typhimurium demonstrated consistent co-localization with NALT M cells in wild-type mice. When wild-type mice were nasally administered with an attenuated vaccine strain of S. Typhimurium, the mice were protected from a subsequent challenge with wild-type S. Typhimurium. Antigen-specific fecal and nasal IgA was detected after nasal immunization with the attenuated vaccine strain of S. Typhimurium only in wild-type mice but not in CCR6-deficient mice. Taken together, these observations demonstrate that NALT M cells are important as a first line of defense against infection by enabling activation of the common mucosal immune system (CMIS).


Subject(s)
Epithelial Cells/immunology , Immunity, Mucosal/immunology , Lymphoid Tissue/immunology , Nasopharynx/immunology , Animals , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
9.
Sci Rep ; 7(1): 4382, 2017 06 29.
Article in English | MEDLINE | ID: mdl-28663544

ABSTRACT

Cognitive impairment is more prevalent in those with decreased kidney function. We tested a hypothesis that an increased homocysteine and/or cerebral small vessel diseases (SVDs) mediate the link between kidney and cognitive functions in a cross-sectional study in 143 type 2 diabetes patients without diagnosis of dementia or prior stroke. The exposure and outcome variables were estimated glomerular filtration rate (eGFR) and cognitive performance evaluated with Modified Mini-Mental State (3 MS) examination, respectively. The candidate mediators were plasma homocysteine concentration, and SVDs including silent cerebral infarction, cerebral microbleed, periventricular hyperintensity, and deep and subcortical white matter hyperintensity by magnetic resonance imaging. In multiple regression models adjusted for 12 potential confounders, eGFR was positively associated with 3 MS score, inversely with homocysteine, but not significantly with the presence of any type of SVD. The association of eGFR with 3 MS remained significant when each of the SVDs was added to the model, whereas it disappeared when homocysteine was included in place of SVD. Mediation analysis indicated nearly significant mediation of homocysteine (P = 0.062) but no meaningful mediations of SVDs (P = 0.842-0.930). Thus, homocysteine, not SVDs, was shown to be the possible mediator between kidney and cognitive functions in patients with type 2 diabetes mellitus.


Subject(s)
Cerebral Small Vessel Diseases/etiology , Cerebral Small Vessel Diseases/psychology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Homocysteine/blood , Kidney Diseases/etiology , Kidney Diseases/physiopathology , Aged , Aged, 80 and over , Biomarkers , Cerebral Small Vessel Diseases/diagnosis , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/psychology , Female , Glomerular Filtration Rate , Humans , Kidney Diseases/diagnosis , Kidney Function Tests , Male , Middle Aged , Odds Ratio , Prognosis
10.
Nephron ; 135(2): 129-136, 2017.
Article in English | MEDLINE | ID: mdl-27974720

ABSTRACT

BACKGROUND/AIMS: The renal prognosis of post-renal acute kidney injury (PoR-AKI) has not been verified so far. The objective of this study was to assess the association of baseline anemia with long-term renal prognosis in patients with PoR-AKI. METHODS: We performed a multicenter retrospective cohort study. Consecutive adult patients from December 2006 to February 2010, who met the requirements as mentioned in the definition of PoR-AKI, were included. Patients without data on baseline renal function and at 6 months after PoR-AKI were excluded. We set baseline hemoglobin (Hb) level (g/dl) as the main exposure to be tested. The main outcome measure was long-term renal prognosis as determined by the difference between proximate estimated glomerular filtration rate (eGFR) at 6 months after diagnosis of PoR-AKI and baseline eGFR prior to the occurrence of the present PoR-AKI (ΔeGFR after 6 months) using the general linear model. RESULTS: We included 136 patients with PoR-AKI. The most frequent cause of PoR-AKI was malignancy, accounting for 39.0% (n = 53) of cases. Multivariate analysis adjusted for possible confounders showed that ΔeGFR after 6 months significantly changed by -4.28 ml/min/1.73 m2 for every 1 g/dl lower Hb at diagnosis (95% CI 1.86-6.69, p < 0.01). An additional multivariate analysis that was stratified by the presence or absence of malignancy as the cause of PoR-AKI yielded the same significant result only in the stratum of the nonmalignant cause of PoR-AKI. CONCLUSION: Patients with a nonmalignant cause of PoR-AKI who have baseline anemia may have poor long-term renal prognosis. In these cases, close observation of renal function after renal recovery may be required.


Subject(s)
Acute Kidney Injury/complications , Anemia/etiology , Acute Kidney Injury/etiology , Acute Kidney Injury/physiopathology , Aged , Anemia/blood , Cohort Studies , Female , Glomerular Filtration Rate , Hemoglobins/metabolism , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Risk Factors
11.
Clin J Am Soc Nephrol ; 11(9): 1557-1565, 2016 09 07.
Article in English | MEDLINE | ID: mdl-27354659

ABSTRACT

BACKGROUND AND OBJECTIVES: In the general population, the presence of cerebral microbleeds on T2*-weighted magnetic resonance imaging has been reported to be a predictor of future stroke. Patients with CKD have a high prevalence of microbleeds and are at higher risk of ESRD as well as cardiovascular disease, including stroke. Because endothelial dysfunction is the common pathophysiology among microbleeds, CKD, and cardiovascular disease, we hypothesized that the presence of microbleeds would be an important predictor of composite outcome, including both cardiovascular disease and renal events, in those with CKD. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: This was a prospective cohort study of 404 patients with CKD who underwent T2*-weighted magnetic resonance imaging for this study between January of 2008 and January of 2011. The primary outcome was composite of cardiovascular and renal outcomes. Cardiovascular outcomes included cardiovascular death, the new onset of myocardial infarction, coronary revascularization, stroke, and amputation/revascularization because of peripheral artery disease. Renal outcomes included doubling of the serum creatinine level and development of ESRD requiring dialysis or transplantation. RESULTS: At baseline, microbleeds were present in 83 (20.5%) patients. During the follow-up median period of 2.3 years, 124 of the 404 patients experienced the composite outcome. The presence of microbleeds was associated with higher risk for the composite outcome in an unadjusted Cox model, and it remained significant after adjustment for age, sex, diabetes, and systolic BP (hazard ratio [HR], 2.58; 95% confidence interval [95% CI], 1.68 to 3.46 for composite outcome; hazard ratio, 2.41; 95% CI, 1.55 to 3.77 for renal outcome; hazard ratio, 3.46; 95% CI, 1.62 to 7.43 for cardiovascular disease outcome). CONCLUSIONS: In patients with CKD, the presence of microbleeds is a novel and independent predictor of both renal and cardiovascular disease end points.


Subject(s)
Cerebral Hemorrhage/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Adult , Aged , Cerebral Hemorrhage/diagnostic imaging , Coronary Artery Disease/surgery , Creatinine/blood , Female , Follow-Up Studies , Humans , Japan/epidemiology , Kidney Transplantation , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged , Myocardial Infarction/epidemiology , Neuroimaging , Peripheral Arterial Disease/surgery , Prospective Studies , Renal Dialysis , Renal Insufficiency, Chronic/blood , Stroke/epidemiology
12.
J Antibiot (Tokyo) ; 69(4): 319-26, 2016 04.
Article in English | MEDLINE | ID: mdl-26419414

ABSTRACT

The 14-membered macrolide erythromycin A expresses three distinct biological properties, including antibacterial activity, gastrointestinal motor-stimulating activity and anti-inflammatory and/or immunomodulatory effects. Although low-dose, long-term therapy using 14- and 15-membered macrolides displaying anti-inflammatory and/or immunomodulatory activity effectively treats diffuse panbronchiolitis and chronic sinusitis, bacterial resistance may emerge. To address this issue, we developed the 12-membered non-antibiotic macrolide (8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900) that promotes monocyte to macrophage differentiation, a marker for anti-inflammatory and/or immunomodulatory effects, without possessing antibacterial activity. In this article, we report that the new macrolide derivative (8R,9S) -de(3'-N-methyl)-3'-N-(p-chlorobenzyl)-de(3-O-cladinosyl)-3-dehydro-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A 12,13-carbonate (EM939) exhibited stronger promotive activity for monocyte to macrophage differentiation than that of the parent compound EM900 in addition to reduced cytotoxicity toward THP-1 cells and antibacterial inactivity. In a cigarette-smoking model used to simulate chronic obstructive pulmonary disease (COPD), the EM900 derivatives significantly attenuated lung and alveolar inflations, functionally and histologically, via oral administration. Because of these marked therapeutic effects, non-antibiotic EM900 derivatives may become central to the treatment of chronic inflammatory diseases such as COPD.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Macrolides/pharmacology , Pulmonary Disease, Chronic Obstructive/drug therapy , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/therapeutic use , Cell Differentiation/drug effects , Cell Line , Disease Models, Animal , Erythromycin/analogs & derivatives , Erythromycin/chemistry , Erythromycin/pharmacology , Erythromycin/therapeutic use , Guinea Pigs , Lung/pathology , Macrolides/chemical synthesis , Macrolides/therapeutic use , Macrophages/drug effects , Macrophages/pathology , Microbial Sensitivity Tests , Monocytes/drug effects , Monocytes/pathology , Pulmonary Disease, Chronic Obstructive/etiology , Smoking/adverse effects
13.
CEN Case Rep ; 4(2): 185-189, 2015 Nov.
Article in English | MEDLINE | ID: mdl-28509099

ABSTRACT

A 71-year-old man who developed renal failure was admitted to our hospital. Computed tomography without contrast enhancement showed bilateral hydronephrosis together with a soft tissue mass around the abdominal aorta, leading to the diagnosis of retroperitoneal fibrosis. Serum levels of immunoglobulin G4 were within the normal range. The patient was then evaluated for the presence of undiagnosed malignancy as a possible cause of secondary retroperitoneal fibrosis. Upper gastrointestinal tract endoscopy demonstrated esophageal cancer. Histology of the esophageal lesion and the retroperitoneal mass showed squamous cell carcinoma (SCC). Therefore, the retroperitoneal fibrosis was considered to be due to the invasion of SCC of the esophagus, and chemotherapy was chosen as the treatment. This is the first case report of postrenal failure due to secondary retroperitoneal fibrosis caused by the direct invasion of esophageal SCC. Physicians should be aware of occult malignancy as the cause of unexplained retroperitoneal fibrosis, even clinically silent, to avoid inappropriate management or delay in the treatment of potentially life-threatening co-morbidities.

15.
Ther Apher Dial ; 18 Suppl 2: 13-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24975890

ABSTRACT

In 2012, bixalomer was launched as new non-calcium (Ca) containing phosphorus (P) binder, increasing the choices available for the treatment of hyperphosphatemia. In this study, among the maintenance dialysis patients at our hospital, we newly administered bixalomer to 21 patients who were not receiving any P binders, and switched to bixalomer for 13 patients who had been receiving sevelamer hydrochloride and 23 patients who had been receiving lanthanum carbonate. The initial dosage of bixalomer was set as 1500 mg/day for new administration patients and dosage equivalent to that of the previously-used P binder for patients who were switched to bixalomer. The dosage of bixalomer was increased if the effects were insufficient. The serum P, Ca and intact parathyroid hormone concentrations as well as serum pH, HCO3 concentration and base excess were evaluated prior to administering bixalomer, 3 months and 6 months after administering bixalomer. For the group who were newly administered bixalomer, significant reductions in serum P concentrations were seen (P<0.01) and no significant changes were seen in clinical test items that serve as indices for acidosis. For the group who were switched from sevelamer hydrochloride to bixalomer, significant reductions in serum P concentrations were seen (P<0.01) together with significant improvements in acidosis (P<0.01). For the group who were switched from lanthanum carbonate to bixalomer, by increasing the dosage of bixalomer to approximately three times the dosage of lanthanum carbonate, it was possible to maintain post-switch serum P concentrations at almost the same levels as before the switch. Furthermore, there were minor, yet significant improvements in acidosis (P<0.01). From these results, it was shown that bixalomer can be useful treatment alternative in dialysis patients for whom it is necessary to change the P binder due to insufficient management of serum P concentrations or development of acidosis.


Subject(s)
Hyperphosphatemia/drug therapy , Polyamines/blood , Polyamines/therapeutic use , Renal Dialysis/adverse effects , Aged , Calcium/blood , Chelating Agents/therapeutic use , Female , Follow-Up Studies , Humans , Hydrogen-Ion Concentration/drug effects , Hyperphosphatemia/blood , Hyperphosphatemia/etiology , Japan , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Middle Aged , Parathyroid Hormone/blood , Phosphorus/blood , Prospective Studies , Sevelamer
16.
Int Immunol ; 26(11): 619-25, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24908678

ABSTRACT

Mucosal vaccines can induce mucosal immunity, including antigen-specific secretory IgA production, to protect from invasion by pathogens and to neutralize toxins at mucosal surfaces. We established an effective antigen-delivering fusion protein, anti-GP2-SA, as a mucosal vaccine. The anti-GP2-SA consists of streptavidin (SA) fused to the antigen-binding fragment region from a mAb against glycoprotein 2 (GP2), an antigen-uptake receptor specifically expressed on M cells. Anti-GP2-SA targets antigen-sampling M cells in the follicle-associated epithelium covering Peyer's patches. Immunofluorescence showed that anti-GP2-SA specifically bound to M cells. Orally administered biotinylated ovalbumin peptide (bOVA) conjugated with anti-GP2-SA more efficiently induced OVA-specific fecal IgA secretion compared with bOVA alone or bOVA conjugated with SA. Furthermore, mice immunized by oral administration of the biotinylated Salmonella enterica serovar Typhimurium (S. Typhimurium) lysate conjugated with anti-GP2-SA were significantly better protected from subsequent infection by virulent S. Typhimurium than mice treated with the bacterial lysate alone or conjugated with SA. These results suggest that anti-GP2-SA-based M-cell-targeting vaccines are a novel strategy for inducing efficient mucosal immunity.


Subject(s)
Antigens/immunology , Immunity, Mucosal , Immunoglobulin A/immunology , Mucous Membrane/immunology , Peyer's Patches/immunology , Vaccines/immunology , Animals , Antibody Specificity/immunology , Antigens, Bacterial/immunology , GPI-Linked Proteins/genetics , GPI-Linked Proteins/immunology , Immunoglobulin A, Secretory/immunology , Male , Mice , Mice, Knockout , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Salmonella Infections/prevention & control , Salmonella typhimurium/immunology , Vaccines/administration & dosage
17.
J Atheroscler Thromb ; 21(4): 346-54, 2014.
Article in English | MEDLINE | ID: mdl-24335047

ABSTRACT

AIM: Remnant lipoproteins are atherogenic and increased in patients with type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD) and other conditions. Thus far, information is limited regarding the synthesis and absorption of cholesterol in CKD patients and a possible link to the remnant levels. We examined possible alterations in serum markers of cholesterol synthesis and absorption and their potential associations with remnant lipoproteins in patients with CKD. METHODS: The subjects included 146 consecutive patients with T2DM in various stages of CKD. We measured the levels of remnant lipoprotein cholesterol (RemL-C), lathosterol (a cholesterol synthesis marker) and campesterol (a cholesterol absorption marker). The urinary albumin to creatinine ratio (U-ACR) and estimated glomerular filtration rate (eGFR) were used to describe the degree of CKD. RESULTS: The median (interquartile range) levels of RemL-C, lathosterol and campesterol were 14.5 (11.5-23.4) mg/dL, 2.1 (1.7-2.9) µg/mL and 2.3 (1.7-3.0) µg/mL, respectively. The RemL-C level was positively correlated with the U-ACR and inversely correlated with the eGFR. The RemL-C level was positively correlated with both the lathosterol and campesterol levels. The lathosterol level was not significantly correlated with the U-ACR, although it was positively correlated with the eGFR. In contrast, the campesterol level was positively correlated with the ACR and inversely with the eGFR. In the multiple regression analysis, both lathosterol and campesterol were positively associated with the RemL-C level, independent of the U-ACR, eGFR and other variables. CONCLUSIONS: The serum campesterol concentrations are higher in patients with a greater degree of albuminuria and a lower renal funtion. In this study, the markers of cholesterol absorption and synthesis were independent determinants of the RemL-C level. Increased intestinal cholesterol absorption may be an additional mechanism for remnant accumulation in T2DM patients with CKD.


Subject(s)
Cholesterol/metabolism , Diabetes Complications/blood , Kidney/physiology , Lipoproteins/metabolism , Aged , Cholesterol/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Female , Glomerular Filtration Rate , Humans , Kidney/metabolism , Male , Middle Aged , Regression Analysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/metabolism
18.
Nephrology (Carlton) ; 18(10): 676-81, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23782310

ABSTRACT

AIM: Cerebral white matter hyperintensities (WMHs), comprised of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH), have been presumed to be predictors for future stroke, cognitive impairment and dementia in the general population. However, no longitudinal studies have been performed to determine the clinical significance of WMHs in haemodialysis (HD) patients. In the present study, we investigated the influence of WMHs as a predictor of future cardiovascular disease in HD patients. METHODS: Cranial magnetic resonance imaging was performed on 179 HD patients with no past history of stroke from April 2006 to October 2009, and the prevalence of WMHs was investigated. The patients were followed prospectively until March 2012 or death or renal transplantation. The influence of WMHs on cardiovascular events was investigated using the Kaplan-Meier method and Cox proportional hazards analysis. RESULTS: The patients with advanced PVH and DSWMH had a significantly higher incidence of cardiovascular morbidity than those without advanced PVH and DSWMH by Kaplan-Meier analysis. By multivariate Cox proportional hazards analysis, the presence of advanced PVH and DSWMH increased the risk of cardiovascular events, independent of other cardiovascular risk factors. In addition, the present study revealed that of the subtypes of WMHs, PVH was a stronger predictor of cardiovascular events compared to DSWMH. CONCLUSIONS: The present study indicates that the presence of WMHs is a novel predictor of cardiovascular events in HD patients, and that PVH is more closely associated with incident cardiovascular disease.


Subject(s)
Brain/pathology , Cardiovascular Diseases/epidemiology , Kidney Diseases/therapy , Leukoencephalopathies/epidemiology , Renal Dialysis/adverse effects , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/mortality , Chi-Square Distribution , Female , Humans , Incidence , Japan/epidemiology , Kaplan-Meier Estimate , Kidney Diseases/epidemiology , Kidney Diseases/mortality , Kidney Transplantation , Leukoencephalopathies/mortality , Leukoencephalopathies/pathology , Magnetic Resonance Imaging , Male , Middle Aged , Multivariate Analysis , Predictive Value of Tests , Prevalence , Prognosis , Proportional Hazards Models , Prospective Studies , Renal Dialysis/mortality , Risk Factors , Time Factors , Young Adult
19.
Am J Kidney Dis ; 62(3): 568-76, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23602192

ABSTRACT

BACKGROUND: Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk. STUDY DESIGN: An observational study including cross-sectional and longitudinal analyses. SETTING & PARTICIPANTS: Single-center study of 517 maintenance hemodialysis patients in an urban area in Japan. PREDICTORS: Serum EPA, DHA, and AA concentrations and EPA:AA, DHA:AA, and (EPA+DHA):AA ratios. OUTCOMES: CVD events, including ischemic heart disease, stroke, peripheral artery disease, pulmonary edema, and valve disease. RESULTS: Hemodialysis patients showed lower (EPA+DHA):AA, EPA:AA, and DHA:AA ratios than 122 controls similar in age and sex. During follow-up, 190 CVD events were recorded. (EPA+DHA):AA ratio was not associated significantly with CVD in unadjusted analysis, but was associated significantly and inversely with CVD in Cox models adjusted for age and other confounding variables, with HRs in the range of 1.71-1.99 in the lowest versus highest quartile of (EPA+DHA):AA ratios. Similarly, EPA:AA and DHA:AA ratios showed inverse associations with CVD, whereas serum EPA, DHA, and AA concentrations were not predictive of CVD. LIMITATIONS: No information for dietary intake, use of dietary supplements, or cell membrane PUFA content. CONCLUSIONS: In hemodialysis patients, serum PUFA profile is unfavorably altered, and the low n-3-PUFA:AA ratios are independent predictors of CVD.


Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/blood , Renal Dialysis/adverse effects , Aged , Biomarkers/blood , Cohort Studies , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests
20.
Kidney Blood Press Res ; 38(2-3): 196-204, 2013.
Article in English | MEDLINE | ID: mdl-24732137

ABSTRACT

BACKGROUND/AIM: The aim of the present study was to quantitatively examine factors associated with aortic calcification in non-dialysis CKD patients. METHODS: We quantitatively investigated aortic calcification from the renal artery to the bifurcation in 149 non-dialysis CKD patients (58±16 years; 96 males and 53 females, 48 diabetics; eGFR 40.3 ± 29.3 ml/min), and measured Agatston scores using multi-slice computed tomography. RESULT: Of 149 patients, aortic calcification was present in 117. In patients with aortic calcification, age (p<0.001), C-reactive protein (p<0.001), and intact-PTH (p < 0.001) were significantly higher, estimated glomerular filtration rate (eGFR) was significantly lower (p<0.001), and diabetes was observed more often (p<0.05). In regards to the degree of aortic calcification, the Agatston scores correlated significantly and positively with age (ρ=0.438, p<0.001) and serum phosphate (ρ=0.208, p=0.024), and correlated significantly but negatively with e-GFR (ρ=-0.353, p<0.001). In multiple regression analysis, eGFR was associated significantly and independently with the log [Agatston score] (ß=-0.346, p<0.01), after adjustment for several confounders including serum phosphate and the presence of diabetes. CONCLUSIONS: Hyperphospatemia, chronic inflammation, diabetes, and decreased GFR are associated significantly with the presence of aortic calcification in non-dialysis CKD patients. Decreased eGFR was associated significantly and independently with the quantitative degree of aortic calcification.


Subject(s)
Aorta, Abdominal/diagnostic imaging , Calcinosis/diagnostic imaging , Renal Insufficiency, Chronic/diagnostic imaging , Adult , Aged , Calcinosis/etiology , Diabetic Nephropathies/diagnostic imaging , Disease Progression , Female , Glomerular Filtration Rate , Humans , Hypertension, Renal/complications , Male , Middle Aged , Renal Dialysis , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/physiopathology , Tomography, X-Ray Computed
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