New insights into bacterial cellulose materials: production and modification strategies

Komagataeibacter xylinus cultures produced high amount of bacterial cellulose (BC), which has a structure of nanoporous network of interlaced fibers. When the culture is performed under static experimental conditions, a membrane with characteristics of highly hydrated hydrogel and good mechanical properties is obtained with promissory applications in the biomedical field. Bacterial cellulose films can be used from dermal dressing and even as a controlled drug release system. Besides, stirred cultures of K. xylinus produced amorphous cellulose structures dispersed in the medium with physical and mechanical characteristics different from the membrane. In addition, new properties of BC can be obtained or added if the hydrogel is mixed with other compounds or modified post-purification using both organic and inorganic compounds.

Acute Activation of AMP-Activated Protein Kinase Prevents H2O2-Induced Premature Senescence in Primary Human Keratinocytes

We investigated the effects of AMPK on H2O2-induced premature senescence in primary human keratinocytes. Incubation with 50 µM H2O2 for 2 h resulted in premature senescence with characteristic increases in senescence-associated ß-galactosidase (SA-gal) staining 3 days later and no changes in AMPK or p38 MAPK activity. The increase in SA-gal staining was preceded by increases in both p53 phosphorylation (S15) (1 h) and transactivation (6 h) and the abundance of the cyclin inhibitor p21CIP1 (16 h). Incubation with AICAR or resveratrol, both of which activated AMPK, prevented the H2O2-induced increases in both SA-Gal staining and p21 abundance. In addition, AICAR diminished the increase in p53 transactivation. The decreases in SA-Gal expression induced by resveratrol and AICAR were prevented by the pharmacological AMPK inhibitor Compound C, expression of a DN-AMPK or AMPK knock-down with shRNA. Likewise, both knockdown of AMPK and expression of DN-AMPK were sufficient to induce senescence, even in the absence of exogenous H2O2. As reported by others, we found that AMPK activation by itself increased p53 phosphorylation at S15 in embryonic fibroblasts (MEF), whereas under the same conditions it decreased p53 phosphorylation in the keratinocytes, human aortic endothelial cells, and human HT1080 fibrosarcoma cells. In conclusion, the results indicate that H2O2 at low concentrations causes premature senescence in human keratinocytes by activating p53-p21CIP1 signaling and that these effects can be prevented by acute AMPK activation and enhanced by AMPK downregulation. They also suggest that this action of AMPK may be cell or context-specific

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enhance energy metabolism while it can repress inflammatory responses linked to chronic stress, e.g., in nutritional overload and during the aging process. AMPK can inhibit endoplasmic reticulum and oxidative stresses which are involved in metabolic disorders and the aging process. Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. The activation capacity of AMPK declines in metabolic stress and with aging which could augment the metabolic diseases and accelerate the aging process. We will review the AMPK pathways involved in the inhibition of NF-κB signaling and suppression of inflammation. We also emphasize that the capacity of AMPK to repress inflammatory responses can have a significant impact on both healthspan and lifespan

mRNA-Based Approaches to Treating Liver Diseases

Diseases that affect the liver account for approximately 2 million deaths worldwide each year. The increasing prevalence of these diseases and the limited efficacy of current treatments are expected to stimulate substantial growth in the global market for therapeutics that target the liver. Currently, liver transplantation is the only curative option available for many liver diseases. Gene therapy represents a valuable approach to treatment. The liver plays a central role in a myriad of essential metabolic functions, making it an attractive organ for gene therapy; hepatocytes comprise the most relevant target. To date, viral vectors constitute the preferred approach to targeting hepatocytes with genes of therapeutic interest. Alternatively, mRNA-based therapy offers a number of comparative advantages. Clinical and preclinical studies undertaken to treat inherited metabolic diseases affecting the liver, cirrhosis and fibrosis, hepatocellular carcinoma, hepatitis B, and cytomegalovirus using lipid nanoparticle-encapsulated mRNAs that encode the therapeutic or antigenic protein of interest are discussed

Distribution of insulin-like growth factor-I receptor mRNA in rat brain. Regulation of the hypothalamo-neurohypophysial system

The distribution and regulation of mRNA for the IGF-I receptor (IGF-I-R) in the adult rat brain were studied by in-situ hybridization with a 35S-labelled cRNA probe. The pituitary gland showed a strong hybridization signal in the pars tuberalis (the surface of the median eminence), pars distalis and pars intermedia. Within the brain, a strong hybridization signal was found in the circumventricular organs, olfactory bulb, hippocampus, cerebellum and hypothalamus. IGF-I-R mRNA was consistently found in cell bodies of the hypothalamo-neurophypophysial system. Six days of intermittent salt-loading resulted in an increase in IGF-I-R gene expression in the supraoptic nucleus. The increase in IGF-I-R mRNA was accompanied by a high expression of c-Fos immunoreactivity in the same cells. The presence and regulation of IGF-I-R mRNA in the hypothalamus suggest that IGF-I may affect the local plasticity or modulation of activated magnocellular neurones by an autocrine or paracrine action through specific receptors in the hypothalamo-neurohypophysial system.Peer Reviewe