Cognitive Impairment in the Post-Acute Phases of COVID-19 and Mechanisms: An Introduction and Narrative Review.

Cognitive impairment is a primary manifestation of neurological symptoms associated with COVID-19 and may occur after disease resolution. Although cognitive impairment has been extensively reported in the literature, its duration and rate of remission remain controversial. This study discusses the various factors that influence cognitive impairment, including demographic characteristics, genetics, as well as disease course and severity. Furthermore, imaging and laboratory data have suggested various associations with cognitive impairment, most notably changes in EEG patterns, PET imaging, and serum markers. Some findings suggest similarities and potential links between COVID-related cognitive impairment and Alzheimer's disease. Moreover, this study reviews the various mechanisms proposed to explain the development of cognitive impairment in COVID-19, including cytokine storm, damage to the blood-brain barrier, compromise of small vessel integrity, hypoxic conditions, and immune dysregulation.

Convenient and Controllable Synthesis of Poly(2-oxazoline)-Conjugated Doxorubicin for Regulating Anti-Tumor Selectivity.

Polyethylene glycol (PEG)-doxorubicin (DOX) conjugation is an important strategy to improve toxicity and enhance clinically therapeutic efficacy. However, with the frequent use of PEG-modified drugs, the accumulation of anti-PEG antibodies has become a tough issue, which limits the application of PEG-drug conjugation. As an alternative solution, poly(2-oxazoline) (POX)-DOX conjugation has shown great potential in the anti-tumor field, but the reported conjugation process of POX with DOX has drawbacks such as complex synthetic steps and purification. Herein, we propose a convenient and controllable strategy for the synthesis of POX-DOX conjugation with different chain lengths and narrow dispersity by N-boc-2-bromoacetohydrazide-initiated 2-ethyl-oxazoline polymerization and the subsequent deprotection of the N-Boc group and direct reaction with DOX. The DOX-PEtOx conjugates were firstly purified, and the successful conjugations were confirmed through various characterization methods. The synthetic DOX-PEtOxn conjugates reduce the toxicity of DOX and increase the selectivity to tumor cells, reflecting the promising application of this POX-DOX conjugation strategy in drug modification and development.

Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria.

Extensive use of antibiotics accelerates the emergence of drug-resistant bacteria and related infections. Host defense peptides (HDPs) have been studied as promising and potential therapeutic candidates. However, their clinical applications of HDPs are limited due to their high cost of synthesis and low stability upon proteolysis. Therefore, HDP mimics have become a new approach to address the challenge of bacterial resistance. In this work, we design the amphiphilic peptoid polymers by mimicking the positively charged and hydrophobic structures of HDPs and synthesize a series of cyclic peptoid polymers efficiently via the polymerization on α-amino acid N-substituted glycine N-carboxyanhydrides (α-NNCAs) using 1,8-diazabicycloundec-7-ene (DBU) as the initiator. The optimal cyclic peptoid polymer, poly(Naeg0.7Npfbg0.3)20, displays strong antibacterial activities against drug-resistant bacteria, but low hemolysis and cytotoxicity. In addition, the mode-of-action study indicates that the antibacterial mechanism is associated with bacterial membrane interaction. Our study implies that HDP mimicking cyclic peptoid polymers have potential application in treating drug-resistant bacterial infections.

Host Defense Peptide-Mimicking Amphiphilic ß-Peptide Polymer (Bu:DM) Exhibiting Anti-Biofilm, Immunomodulatory, and in Vivo Anti-Infective Activity.

Therapeutic options to treat multidrug resistant bacteria, especially when present in biofilms, are limited due to their high levels of antibiotic resistance. Here, we report the anti-biofilm and immunomodulatory activities of the host defense peptide (HDP)-mimicking ß-peptide polymer (20:80 Bu:DM) and investigated its activity in vivo. The polymer outperformed antibiotics in the removal and reduction of the viability of established biofilms, achieving a maximum activity of around 80% reduction in viability. Interestingly the polymer also exhibited HDP-like immunomodulation in inducing chemokines and anti-inflammatory cytokines and suppressing lipopolysaccharide-induced proinflammatory cytokines. When tested in a murine, high-density skin infection model using P. aeruginosa LESB58, the polymer was effective in diminishing abscess size and reducing bacterial load. This study demonstrates the dual functionality of HDP-mimicking ß-peptide polymers in inhibiting biofilms and modulating innate immunity, as well as reducing tissue dermonecrosis.

An alpha/beta chimeric peptide molecular brush for eradicating MRSA biofilms and persister cells to mitigate antimicrobial resistance.

Infections involving methicillin-resistant Staphylococcus aureus present great challenges, especially when biofilms and persister cells are involved. In this work, an α/ß chimeric polypeptide molecular brush (α/ß CPMB) is reported to show excellent performance in inhibiting the formation of biofilms and eradicating established biofilms. Additionally, the polymer brush efficiently killed metabolically inactive persister cells that are antibiotic-insensitive. Antimicrobial mechanism studies showed that α/ß CPMB causes membrane disturbance and a substantial increase in reactive oxygen species (ROS) levels to kill bacteria, and mesosome-like structure formation was also observed. Furthermore, the polymer brush was able to kill clinically isolated multidrug resistant Gram-positive bacteria with no risk of antimicrobial resistance. The α/ß CPMB has demonstrated great potential in addressing the great challenge of eradicating multidrug resistant Gram-positive bacterial infections.