Gunnegholm2429

The present study evaluated whether the oxidative stress caused by antimicrobial photodynamic therapy (aPDT) affects the expression of C. albicans genes related to adhesion and biofilm formation (ALS1 and HPW1) and oxidative stress response (CAP1, CAT1, and SOD1). The aPDT was mediated by two photosensitizing agents (PSs) Photodithazine® (PDZ at 100 and 200 mg/L) or Curcumin (CUR at 40 and 80 µM)-and LED (37.5 J/cm2 or 50 J/cm2). Need to state what kind of samples were evaluated. The quantification of the expression was performed by Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR) using specific primers for the target genes. The data were analyzed by Analysis of Variance (α = 0.05), followed by Tukey's post-test. It was observed reduction in the expression of ALS1, HWP1, CAP1, CAT1, and SOD1 when aPDT was performed using 200 mg/L PDZ and 80 µM CUR associated to LED (37.7 and 50 J/cm2, respectively) and using 100 mg/L PDZ and 40 µM CUR with LED of 50 J/cm2 (versus control). Also, the expression of CAP1 and SOD1 genes was reduced after aPDT using 100 mg/L PDZ and LED of 37.5 J/cm2. There was a significant reduction in the expression of genes HWP1, CAP1, and SOD1 after aPDT using 40 µM CUR and 37.5 J/cm2 (versus the control group). The application of LED only at 37.5 and 50 J/cm2 promoted down-regulation of ALS1, CAP1, CAT1, and SOD1 genes (versus the control group). Therefore, aPDT mediated by LED -associated PSs PDZ and CUR promoted a reduction in the expression of the five C. albicans genes evaluated.Metabolic addiction, an organism that is metabolically addicted with a compound to maintain its growth fitness, is an underexplored area in metabolic engineering. Microbes with heavily engineered pathways or genetic circuits tend to experience metabolic burden leading to degenerated or abortive production phenotype during long-term cultivation or scale-up. A promising solution to combat metabolic instability is to tie up the end-product with an intermediary metabolite that is essential to the growth of the producing host. Here we present a simple strategy to improve both metabolic stability and pathway yield by coupling chemical addiction with negative autoregulatory genetic circuits. Naringenin and lipids compete for the same precursor malonyl-CoA with inversed pathway yield in oleaginous yeast. Negative autoregulation of the lipogenic pathways, enabled by CRISPRi and fatty acid-inducible promoters, repartitions malonyl-CoA to favor flavonoid synthesis and increased naringenin production by 74.8%. With flavonoid-sensing transcriptional activator FdeR and yeast hybrid promoters to control leucine synthesis and cell grwoth fitness, this amino acid feedforward metabolic circuit confers a flavonoid addiction phenotype that selectively enrich the naringenin-producing pupulation in the leucine auxotrophic yeast. The engineered yeast persisted 90.9% of naringenin titer up to 324 generations. TH-Z816 Cells without flavonoid addiction regained growth fitness but lost 94.5% of the naringenin titer after cell passage beyond 300 generations. Metabolic addiction and negative autoregulation may be generalized as basic tools to eliminate metabolic heterogeneity, improve strain stability and pathway yield in long-term and large-scale bioproduction.Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease (PD) with the dysregulation of microglial activity being tightly linked to dopaminergic degeneration. Fractalkine (CX3CL1), a chemokine mainly expressed by neurons, can modulate microglial activity through binding to its sole G-protein-coupled receptor (CX3CR1), expressed by microglia. Fractalkine/CX3CR1 signaling is one of the most important mediators of the communication between neurons and microglia, and its emerging role in neurodegenerative disorders including PD has been increasingly recognized. Pre-clinical evidence has revealed that fractalkine signaling axis exerts dual effects on PD-related inflammation and degeneration, which greatly depend on the isoform type (soluble or membrane-bound), animal model (mice or rats, toxin- or proteinopathy-induced), route of toxin administration, time course and specific brain region (striatum, substantia nigra). Furthermore, although existing clinical evidence is scant, it has been indicated that fractalkine may be possibly associated with PD progression, paving the way for future studies investigating its biomarker potential. In this review, we discuss recent evidence on the role of fractalkine/CX3CR1 signaling axis in PD pathogenesis, aiming to shed more light on the molecular mechanisms underlying the neuroinflammation commonly associated with the disease, as well as potential clinical and therapeutic implications.Inflammation is an obligatory marker of arterial disease, both stemming from the inflammatory activity of cholesterol itself and from well-established molecular mechanisms. Raised progenitor cell recruitment after major events and clonal hematopoiesis related mechanisms have provided an improved understanding of factors regulating inflammatory phenomena. Trials with inflammation antagonists have led to an extensive evaluation of biomarkers such as the high sensitivity C reactive protein (hsCRP), not exerting a causative role, but frequently indicative of the individual cardiovascular (CV) risk. Aim of this review is to provide indication on the anti-inflammatory profile of agents of general use in CV prevention, i.e. affecting lipids, blood pressure, diabetes as well nutraceuticals such as n-3 fatty acids. A crucial issue in the evaluation of the benefit of the anti-inflammatory activity is the frequent discordance between a beneficial activity on a major risk factor and associated changes of hsCRP, as in the case of statins vs PCSK9 antagonists. In hypertension, angiotensin converting enzyme inhibitors exert an optimal anti-inflammatory activity, vs the case of sartans. The remarkable preventive activity of SLGT-2 inhibitors in heart failure is not associated with a clear anti-inflammatory mechanism. Finally, icosapent ethyl has been shown to reduce the CV risk in hypertriglyceridemia, with a 27% reduction of hsCRP. The inflammation-based approach to arterial disease has considerably gained from an improved understanding of the clinical diagnostic strategy and from a better knowledge on the mode of action of numerous agents, including nutraceuticals.