Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.

Brevibacillus thermoruber 423 is a Gram-positive, motile, red-pigmented, spore-forming, aerobic, and thermophilic bacterium that is known to produce high levels of exopolysaccharide (EPS) with many potential uses in food, feed, cosmetics, and pharmaceutical and chemical industries. This bacterium not only is among the limited number of reported thermophilic EPS producers but also exceeds other thermophilic producers in light of the high level of polymer synthesis. By a systems-based approach, whole-genome analysis of this bacterium was performed to gain more insight about the biological mechanisms and whole-genome organization of thermophilic EPS producers and hence to develop rational strategies for the genetic and metabolic optimization of EPS production. Also with this study, the first genome analysis was performed on a thermophilic Brevibacillus species. Essential genes associated with EPS biosynthesis were detected by genome annotation, and together with experimental evidences, a hypothetical mechanism for EPS biosynthesis was generated. B. thermoruber 423 was found to have many potential applications in biotechnology and industry because of its capacity to utilize xylose and to produce EPS, isoprenoids, ethanol/butanol, lipases, proteases, cellulase, and glucoamylase enzymes as well as its resistance to arsenic.

Unusual composition of an exopolymer (EP) from an obligate halophilic bacterium Chromohalobacter canadensis 28 has triggered an interest in development of an effective bioreactor process for its production. Its synthesis was investigated in 2‐L bioreactor at agitation speeds at interval 600‐1000 rpm, at a constant air flow rate of 0.5 vvm; aeration rates of 0.5, 1.0, and 1.5 vvm were tested at constant agitation rate of 900 rpm. EP production was affected by both, agitation and aeration. As a result twofold increase of EP yield was observed and additionally increased up to 3.08 mg/mL in a presence of surfactants. For effective scale‐up of bioreactors mass transfer parameters were estimated and lowest values of KLa obtained for the highest productivity fermentation was established. Emulsification activity of EP exceeded that of trade hydrocolloids xanthan, guar gum, and cellulose. A good synergism between EP and commercial cellulose proved its potential exploration as an enhancer of emulsifying properties of trade emulsions. A pronounced lipophilic effect of EP was established toward olive oil and liquid paraffin. Cultivation of human keratinocyte cells (HaCaT) with crude EP and purified γ‐polyglutamic acid (PGA) showed higher viability than control group.

Aims: This study aims to identify a high level exopolysaccharide (EPS) producer thermophile that in turn could be used as a model organism to study the biological mechanisms and whole genome organization of EPS-producing thermophilic bacteria. Methods and Results: Thermophilic isolates were screened, and then growth and EPS production of the best producer Brevibacillus thermoruber strain 423 were investigated under different carbon and nitrogen sources, temperature, pH and agitation rates. Rheological characterization revealed that the EPS behaved like a typical Newtonian fluid and viscosity of the EPS solution increased with increasing Ca 2+ ion concentration. Chemical characterization by TLC, GC-MS, FT-IR and NMR suggested a heteropolymer structure with glucose as major monomer unit. High biocompatibility of pure EPS fractions suggested their potential use in biomedical applications. Conclusions: This study reports on the comprehensive description of microbial production conditions as well as chemical, rheological and biological characterization of the EPS produced by B. thermoruber strain 423. The bioreactor cultures were found to reach two times higher yields and three times higher productivities when compared with literature. Significance and Impact of the Study: Brevibacillus thermoruber strain 423 combined the advantages of its nonpathogenicity with the advantages of fast productivity and hence proved to be a very promising model organism and cell factory for microbial EPS production.

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