Synthesis,characterization, and antimicrobial activity of chitosan hydrazide derivative

A series of modified chitosan derivatives 1–4 has been synthesized. Modification process of chitosan was achieved through a sequence of four reactions starting by protection of its amino group with benzaldehyde (derivative 1), followed by reaction with epichlorohydrine (derivative 2), then reaction with benzhydrazide (derivative 3), and finally restoring the free amino groups on the chitosan by removing of benzaldehyde molecules (derivative 4). These four derivatives were characterized by elemental analyses, FTIR, and X-ray. The four chitosan derivatives showed better antibacterial and antifungal activities than that of chitosan. Derivative 4 exhibited the highest antimicrobial activity relative to the other derivatives.     

Ecosystem matters: fish consumption, mercury intake and exposure among fluvial lake fish-eaters

Many studies use the number of fish meals as an estimate of Hg intake, although fish Hg concentrations, even within the same species, can greatly vary. Furthermore, most freshwater advisories only refer to local catch, while market fish advisories only focus on market fish, although both can contribute to Hg body burden. The present study, carried out in lakeside communities from 2 ecosystems in Quebec, Canada, sought to (i) estimate Hg intake from local freshwater sources, hunted waterfowl and market fish and seafood, and (ii) examine the relations between fish consumption, estimated Hg intake and biomarkers of exposure. A total of 238 adults (18-74 years), who had consumed local catch within the past three months, responded to an extensive interview-administered fish and waterfowl frequency questionnaire. Anthropometric measures were taken and a self-administered questionnaire was used to obtain socio-demographic information. Hg intake was estimated as µg Hg/kg body weight/day. Blood and hair samples were analyzed for Hg content. Results showed that persons from one ecosystem ate significantly more fish compared to those from the other (median: 52.1 g/day vs 38.9 g/day), but presented significantly lower concentrations of hair Hg (median: 448.0 ng/g vs 730.5 ng/g), blood organic Hg (median: 1.1 µg/L vs 3.4 µg/L) and inorganic Hg (median: 0.4 µg/L vs 0.8 µg/L). Median daily total Hg intake was 0.080 µg/kg bw/day for the former community and 0.141 µg/kg bw/day for the latter. Overall, 59.5% from the first ecosystem and 41.0% from the other, exceeded the US EPA RfD (0.1 µg/kg bw/day), while 13.2% and 6.0%, respectively, exceeded the Canadian tolerable daily intake (0.47 µg/kg bw/day) for adults. For the two groups, freshwater fish consumption frequency, but not total fish, was positively associated with bioindicators of Hg while estimated Hg intake from freshwater catch as well as from total fish consumption were positively related to Hg biomarkers. There was a positive relation between consumption and estimated Hg intake from freshwater fish and blood inorganic Hg. These findings indicate that the number of fish can be a poor surrogate for Hg exposure. The differences observed here for Hg intake and exposure reflect ecosystem disparities in fish diversity and Hg bioaccumulation. Studies and advisories need to consider Hg fish concentrations and fish-eating patterns in different ecosystems, as well as the contribution of market fish. The relation between fish consumption and inorganic Hg exposure, reported as well in other studies, needs to be further investigated.     

Insight into Factors Influencing Wound Healing Using Phosphorylated Cellulose-Filled-Chitosan Nanocomposite Films

Marine polysaccharides are believed to be promising wound-dressing nanomaterials because of their biocompatibility, antibacterial and hemostatic activity, and ability to easily shape into transparent films, hydrogels, and porous foams that can provide a moist micro-environment and adsorb exudates. Current efforts are firmly focused on the preparation of novel polysaccharide-derived nanomaterials functionalized with chemical objects to meet the mechanical and biological requirements of ideal wound healing systems. In this contribution, we investigated the characteristics of six different cellulose-filled chitosan transparent films as potential factors that could help to accelerate wound healing. Both microcrystalline and nano-sized cellulose, as well as native and phosphorylated cellulose, were used as fillers to simultaneously elucidate the roles of size and functionalization. The assessment of their influences on hemostatic properties indicated that the tested nanocomposites shorten clotting times by affecting both the extrinsic and intrinsic pathways of the blood coagulation system. We also showed that all biocomposites have antioxidant capacity. Moreover, the cytotoxicity and genotoxicity of the materials against two cell lines, human BJ fibroblasts and human KERTr keratinocytes, was investigated. The nature of the cellulose used as a filler was found to influence their cytotoxicity at a relatively low level. Potential mechanisms of cytotoxicity were also investigated; only one (phosphorylated microcellulose-filled chitosan films) of the compounds tested produced reactive oxygen species (ROS) to a small extent, and some films reduced the level of ROS, probably due to their antioxidant properties. The transmembrane mitochondrial potential was very slightly lowered. These biocompatible films showed no genotoxicity, and very importantly for wound healing, most of them significantly accelerated migration of both fibroblasts and keratinocytes.     

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.