Cryostructuring of Polymeric Systems: 67 Properties and Microstructure of Poly(Vinyl Alcohol) Cryogels Formed in the Presence of Phenol or Bis-Phenols Introduced into the Aqueous Polymeric Solutions Prior to Their Freeze-Thaw Processing.

Poly(vinyl alcohol) (PVA) physical cryogels that contained the additives of o-, m-, and p-bis-phenols or phenol were prepared, and their physico-chemical characteristics and macroporous morphology and the solute release dynamics were evaluated. These phenolic additives caused changes in the viscosity of initial PVA solutions before their freeze-thaw processing and facilitated the growth in the rigidity of the resultant cryogels, while their heat endurance decreased. The magnitude of the effects depended on the interposition of phenolic hydroxyls in the molecules of the used additives and was stipulated by their H-bonding with PVA OH-groups. Subsequent rinsing of such "primary" cryogels with pure water led to the lowering of their rigidity. The average size of macropores inside these heterophase gels also depended on the additive type. It was found also that the release of phenolic substances from the additive-containing cryogels occurred via virtually a free diffusion mechanism; therefore, drug delivery systems such as PVA cryogels loaded with either pyrocatechol, resorcinol, hydroquinone, or phenol, upon the in vitro agar diffusion tests, exhibited antibacterial activity typical of these phenols. The promising biomedical potential of the studied nanocomposite gel materials is supposed.

Cryostructuring of Polymeric Systems: 64. Preparation and Properties of Poly(vinyl alcohol)-Based Cryogels Loaded with Antimicrobial Drugs and Assessment of the Potential of Such Gel Materials to Perform as Gel Implants for the Treatment of Infected Wounds.

Physical macroporous poly(vinyl alcohol)-based cryogels formed by the freeze-thaw technique without the use of any foreign cross-linkers are of significant interests for biomedical applications. In the present study, such gel materials loaded with the antimicrobial substances were prepared and their physicochemical properties were evaluated followed by an assessment of their potential to serve as drug carriers that can be used as implants for the treatment of infected wounds. The antibiotic Ceftriaxone and the antimycotic Fluconazole were used as antimicrobial agents. It was shown that the Ceftriaxone additives caused the up-swelling effects with respect to the cryogel matrix and some decrease in its heat endurance but did not result in a substantial change in the gel strength. With that, the drug release from the cryogel vehicle occurred without any diffusion restrictions, which was demonstrated by both the spectrophotometric recording and the microbiological agar diffusion technique. In turn, the in vivo biotesting of such drug-loaded cryogels also showed that these materials were able to function as rather efficient antimicrobial implants injected in the artificially infected model wounds of laboratory rabbits. These results confirmed the promising biomedical potential of similar implants.

A Crosstalk between the Biorhythms and Gatekeepers of Longevity: Dual Role of Glycogen Synthase Kinase-3.

This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a "regulating valve" that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity.