With the increased prevalence of antibiotic-resistant infections, there is an urgent need for innovative antimicrobial treatments. One such area being actively explored is the use of self-assembling cationic polymers. This relatively new class of materials was inspired by biologically pervasive cationic host defense peptides. The antimicrobial action of both the synthetic polymers and naturally occurring peptides is believed to be complemented by their three-dimensional structure. In an effort to evaluate shape effects on antimicrobial materials, triblock polymers were polymerized from an assembly directing terephthalamide-bisurea core. Simple changes to this core, such as the addition of a methylene spacer, served to direct self-assembly into distinct morphologies-spheres and rods. Computational modeling also demonstrated how subtle core changes could directly alter urea stacking motifs manifesting in unique multidirectional hydrogen-bond networks despite the vast majority of material consisting of poly(lactide) (interior block) and cationic polycarbonates (exterior block). Upon testing the spherical and rod-like morphologies for antimicrobial properties, it was found that both possessed broad-spectrum activity (Gram-negative and Gram-positive bacteria as well as fungi) with minimal hemolysis, although only the rod-like assemblies were effective against Candida albicans.
Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1β were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-β were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.
The
discovery of antibiotics was one of the crowning achievements
of the 20th century, revolutionizing the treatment of infectious disease.
However, widespread improper use of antibiotics has led to the development
of antibiotic-resistant bacteria, resulting in a healthcare crisis
and the urgent need to develop new effective antibiotics. Moreover,
current antibiotic therapies are inefficient in treating biofilm-protected
and intracellular organisms such as Mycobacterium tuberculosis (Mtb) and non-tuberculous mycobacteria. Herein,
we present a strategy for the construction of macromolecular antimicrobial
compounds using a catalyst-free, polyaddition polymerization process
of monomers derived from poly(ethylene terephthalate) (PET) refuse.
The initial depolymerization of PET refuse via aminolysis is highly
amenable and scalable process to access a broad array of functional
tertiary amine-containing terephthalamide polymer-grade monomers.
This new monomer platform was subsequently used to construct antimicrobial
cationic polyionenes via a polyaddition polymerization. The composition
and structure of the antimicrobial polyionenes were varied to study
their antimicrobial activity against a broad spectrum of pathogenic
microbes including Mtb. Polymers with optimized compositions
have potent antimicrobial activity with low minimum inhibitory concentrations
of 3.9–15.8 μg/mL against microbes including Mtb and high selectivity for microbes over mammalian cells.
Similarly, activity against Mtb ranged from 2 to
16 μg/mL, while values for Mycobacterium avium and Mycobacterium abscessus were
higher. In addition, antimicrobial polyionenes were able to target
and kill M. avium residing inside
human macrophages. Overall, PET refuse was successfully used as a
feedstock to generate new functional terephthalamide monomers for
new macromolecular antimicrobial polyionenes. These polyionenes are
promising candidate agents to treat difficult-to-treat bacterial and
mycobacterial infections that are currently resistant to existing
antibiotics.
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