Protection of gut microbiome from antibiotics: development of a vancomycin-specific adsorbent with high adsorption capacity.

The fraction of administered antibiotics that reach the cecum and colon causes dysbiosis of the gut microbiome, resulting in various diseases. Protection of the gut microbiome from antibiotics using antibiotic adsorbents in the cecum and colon is a promising method to overcome this issue. Previously, activated charcoal (AC) has been reported to protect the gut microbiome of host animals. AC is an adsorbent that is widely used to capture toxic compounds and overdosed drugs in the gastrointestinal tract. The specificity of adsorbents for antibiotics is critical to avoid the risk of unexpected side effects caused by nonspecific adsorption of biological compounds in the intestinal fluid, such as bile acids and essential micronutrients. Here, we have developed specific adsorbents for vancomycin (VCM), which is known to cause gut dysbiosis. The adsorbents were composed of polyethyleneglycol-based microparticles (MPs) in which a specific ligand for VCM, D-Ala-D-Ala-OH, was attached via dendrons of D-lysine to raise the content of the ligand in the MPs. The MPs successfully protected Staphylococcus lentus from VCM in vitro because of the adsorption of VCM in the culture media. Pre-administration of MPs to mice reduced the amount of free VCM in the feces to an undetectable level. This treatment minimized the effect of VCM on gut microbiota and provided protection against Clostridioides difficile infection after oral challenge with spores.

Synthesis of peptide conjugates with vitamins for induction of antigen-specific immunotolerance.

In this report, we designed conjugates of an antigen peptide with the immunosuppressive vitamins all-trans retinoic acid (ATRA) and vitamin D3 for efficient induction of antigen-specific immunotolerance. We established a synthetic scheme for the preparation of the peptide-vitamin conjugates, which the chemically unstable vitamins tolerated. Among the obtained conjugates, the ATRA conjugate successfully suppressed inflammatory effects in macrophages and dendritic cells and induced antigen presentation in dendritic cells. This synthetic method of conjugate is conceivably applicable to other antigen peptides for induction of antigen-specific immunotolerance.

Nutritional status and dietary diversity of school-age children living with HIV: a cross-sectional study in Phnom Penh, Cambodia.

BACKGROUND: HIV/AIDS continues to be a major public health concern for children. Each day, worldwide, approximately 440 children became newly infected with HIV, and 270 children died from AIDS-related causes in 2018. Poor nutrition has been associated with accelerated disease progression, and sufficient dietary diversity is considered a key to improve children's nutritional status. Therefore, this study aims to 1) examine nutritional status of school-age children living with HIV in Phnom Penh, Cambodia, and 2) identify factors associated with their nutritional status, especially taking their dietary diversity into consideration. METHODS: This cross-sectional study was conducted in May 2018 within the catchment area of the National Pediatric Hospital, Cambodia. Data from 298 children and their caregivers were included in the analyses. Using semi-structured questionnaires, face-to-face interviews were conducted to collect data regarding sociodemographic characteristics, quality of life, and dietary diversity. To assess children's nutritional status, body weight and height were measured. Viral load and duration of antiretroviral therapy (ART) were collected from clinical records. Multiple logistic regression analyses were performed to identify factors associated with stunting and wasting. RESULTS: Of 298 children, nearly half (46.6%) were stunted, and 13.1% were wasted. The mean number of food groups consumed by the children in the past 24 h was 4.6 out of 7 groups. Factors associated with children's stunting were age (adjusted odds ratio [AOR] 2.166, 95% confidence interval [CI]: 1.151, 4.077), household wealth (AOR 0.543, 95%CI: 0.299, 0.986), duration of receiving ART (AOR 0.510, 95%CI: 0.267, 0.974), and having disease symptoms during the past 1 year (AOR 1.871, 95%CI: 1.005, 3.480). The only factor associated with wasting was being male (AOR 5.304, 95%CI: 2.210, 12.728). CONCLUSIONS: Prevalence of stunting was more than double that of non-infected school-age children living in urban areas in Cambodia. This highlights the importance of conducting nutritional intervention programs, especially tailored for children living with HIV in the country. Although dietary diversity was not significantly associated with children's nutritional status in this study, the findings will contribute to implementing future nutritional interventions more efficiently by indicating children who are most in need of such interventions in Cambodia.

Preparation of Complexes between Ovalbumin Nanoparticles and Retinoic Acid for Efficient Induction of Tolerogenic Dendritic Cells.

The induction of antigen-specific immunotolerance has been gathering attention concerning the therapy of allergy and autoimmune diseases. Tolerogenic dendritic cells (tDCs) play crucial roles in immunotolerance therapy because they induce anergic responses for auto-reactive helper T cells, and also enhance differentiation to regulatory T cells to maintain tolerance against auto-antigens. All-trans retinoic acid (ATRA) is one of the representative molecules used to induce tDCs. We have proposed a simple formulation of ovalbumin nanoparticles complexed with ATRA (OVA/RA NPs). OVA/RA NPs were taken up by DCs and successfully induced phenotypes of tDCs.

Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer-lipid hybrid nanoparticles.

Inflammatory activation of macrophages is a key factor in chronic inflammatory diseases such as ulcerative colitis. The excessive production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) by macrophages causes oxidative stress during the inflammatory response and exaggerates inflammatory lesions in ulcerative colitis. Inhibition of the inflammatory activation of macrophages is a promising treatment for chronic inflammatory diseases. Here, we prepared self-filling polymer-lipid hybrid nanoparticles (PST-PLNPs) consisting of poly dl-lactic acid as a hydrophobic biodegradable polymer core encapsulating α-tocopherol (T) and phosphatidylserine (PS) both on the surface and interior of the particle. We confirmed the anti-inflammatory response of these hybrid nanoparticles in activated murine macrophages. PS has anti-inflammatory effects on macrophages by modulating the macrophage phenotype, while α-tocopherol is an antioxidant that neutralizes ROS. We found that PS-containing (PS-PLNPs) and PS plus α-tocopherol-containing (PST-PLNPs) polymer-lipid hybrid nanoparticles significantly increased the viability of lipopolysaccharide (LPS)-treated macrophages compared with phosphatidylcholine-containing PLNPs. PST-PLNPs had a better effect than PS-PLNPs, which was attributed to the synergy between PS and α-tocopherol. This synergic action of PST-PLNPs reduced NO and pro-inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine (TGF-ß1) production when incubated with activated macrophages. Thus, these self-filling biodegradable polymer-lipid hybrid nanoparticles (PST-PLNPs) containing anti-oxidant and anti-inflammatory molecules might be potential alternative drug carriers to liposomes and polymeric nanoparticles for the treatment of chronic inflammatory diseases such as ulcerative colitis.