Combustion synthesis and spark plasma sintering of apatite-tricalcium phosphate nanocomposites

A processing route consisting of Spark Plasma Sintering (SPS) of precursor powders prepared by Solution Combustion Synthesis (SCS) is proposed for the first time for the fabrication of bulk nanostructured biphasic calcium phosphates. The apatite phase content in the product obtained by SCS was maximized using a fuel to oxidizer ratio of 1.1. After a post-synthesis air-annealing step conducted a 700 °C/3 h, powders consisted of 83 wt.% of carbonated apatite, with average crystallite size less than 70 nm, and β- and α-TCP (tricalcium phosphate), as secondary phases. Detailed structural analyses evidenced that the original nanostructure was retained after sintering at 900 °C, with the obtainment of nearly 91% dense, apatite-rich, biphasic bioceramics, with grains size of about 100 nm. The developed nanostructured biphasic material is expected to possess a higher resorption rate than standard microcrystalline hydroxyapatite, which makes it preferable for bone tissue regeneration

Mycobacterial PIMs Inhibit Host Inflammatory Responses through CD14-Dependent and CD14-Independent Mechanisms

Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM1 isomer and PIM2 mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM1 and PIM2 analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM1 and PIM2 analogues. CD14 was dispensable for PIM1 and PIM2 analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM1 and PIM2 analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway

The Rts1 Regulatory Subunit of Protein Phosphatase 2A Is Required for Control of G1 Cyclin Transcription and Nutrient Modulation of Cell Size

The key molecular event that marks entry into the cell cycle is transcription of G1 cyclins, which bind and activate cyclin-dependent kinases. In yeast cells, initiation of G1 cyclin transcription is linked to achievement of a critical cell size, which contributes to cell-size homeostasis. The critical cell size is modulated by nutrients, such that cells growing in poor nutrients are smaller than cells growing in rich nutrients. Nutrient modulation of cell size does not work through known critical regulators of G1 cyclin transcription and is therefore thought to work through a distinct pathway. Here, we report that Rts1, a highly conserved regulatory subunit of protein phosphatase 2A (PP2A), is required for normal control of G1 cyclin transcription. Loss of Rts1 caused delayed initiation of bud growth and delayed and reduced accumulation of G1 cyclins. Expression of the G1 cyclin CLN2 from an inducible promoter rescued the delayed bud growth in rts1Δ cells, indicating that Rts1 acts at the level of transcription. Moreover, loss of Rts1 caused altered regulation of Swi6, a key component of the SBF transcription factor that controls G1 cyclin transcription. Epistasis analysis revealed that Rts1 does not work solely through several known critical upstream regulators of G1 cyclin transcription. Cells lacking Rts1 failed to undergo nutrient modulation of cell size. Together, these observations demonstrate that Rts1 is a key player in pathways that link nutrient availability, cell size, and G1 cyclin transcription. Since Rts1 is highly conserved, it may function in similar pathways in vertebrates

Current trends in the pharmacotherapy of uterine myoma, associated with heavy menstrual bleeding and anemia: a literature review

Aim: to summarize up-to-date world data on current opportunities of drug therapy in treatment of symptomatic myoma accompanied with heavy menstrual bleeding and anemia.Materials and Methods. A search of publications was carried out in the main international databases published in Russian and English: PubMed/MEDLINE, The Cochrane Library, Embase, and eLibrary. The analysis included studies published over the last 10 years examining the clinical efficacy and safety of various groups of pharmacological agents used for treatment of uterine myoma combined with heavy menstrual bleeding in women of reproductive age.Results. Currently, treatment of uterine fibroids consists of the three major approaches: surgical, minimally invasive organpreserving methods, and pharmacotherapy. Until now, surgical intervention remains the main method of treatment, unfortunately being often performed in a foem of hysterectomy. However, today it is important to apply a personalized approach to the management of a female patient with symptomatic uterine myoma, taking into account her wish to preserve reproductive function. Advances in drug therapy greatly contributed to optimizing management of such patients.Conclusion. Treatment of symptomatic uterine fibroids globally tends to lowering the number of radical interventions, as well as develop and improve new therapeutic approaches for. Currently, pharmacotherapy of leiomyoma can substantially improve the quality of patients' life, lower number of radical surgical interventions, optimize surgical treatment, and even fully negate, in some cases, a need for surgery