Role of PACAP and VIP Signalling in Regulation of Chondrogenesis and Osteogenesis

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are multifunctional proteins that can regulate diverse physiological processes. These are also regarded as neurotrophic and anti-inflammatory substances in the CNS, and PACAP is reported to prevent harmful effects of oxidative stress. In the last decade more and more data accumulated on the similar function of PACAP in various tissues, but its cartilage- and bone-related presence and functions have not been widely investigated yet. In this summary we plan to verify the presence and function of PACAP and VIP signalling tool kit during cartilage differentiation and bone formation. We give evidence about the protective function of PACAP in cartilage regeneration with oxidative or mechanically stress and also with the modulation of PACAP signalling in vitro in osteogenic cells. Our observations imply the therapeutic perspective that PACAP might be applicable as a natural agent exerting protecting effect during joint inflammation and/or may promote cartilage regeneration during degenerative diseases of articular cartilage

14-3-3 zeta is a molecular target in guggulsterone induced apoptosis in Head and Neck cancer cells

<p>Abstract</p> <p>Background</p> <p>The five-year survival rates for head and neck squamous cell carcinoma (HNSCC) patients are less than 50%, and the prognosis has not improved, despite advancements in standard multi-modality therapies. Hence major emphasis is being laid on identification of novel molecular targets and development of multi-targeted therapies. 14-3-3 zeta, a multifunctional phospho-serine/phospho-threonine binding protein, is emerging as an effector of pro-survival signaling by binding to several proteins involved in apoptosis (Bad, FKHRL1 and ASK1) and may serve as an appropriate target for head and neck cancer therapy. Herein, we determined effect of guggulsterone (GS), a farnesoid X receptor antagonist, on 14-3-3 zeta associated molecular pathways for abrogation of apoptosis in head and neck cancer cells.</p> <p>Methods</p> <p>Head and neck cancer cells were treated with guggulsterone (GS). Effect of GS-treatment was evaluated using cell viability (MTT) assay and apoptosis was verified by annexin V, DNA fragmentation and M30 CytoDeath antibody assay. Mechanism of GS-induced apoptosis was determined by western blotting and co-IP assays using specific antibodies.</p> <p>Results</p> <p>Using in vitro models of head and neck cancer, we showed 14-3-3 zeta as a key player regulating apoptosis in GS treated SCC4 cells. Treatment with GS releases BAD from the inhibitory action of 14-3-3 zeta in proliferating HNSCC cells by activating protein phosphatase 2A (PP2A). These events initiate the intrinsic mitochondrial pathway of apoptosis, as revealed by increased levels of cytochrome c in cytoplasmic extracts of GS-treated SCC4 cells. In addition, GS treatment significantly reduced the expression of anti-apoptotic proteins, Bcl-2, xIAP, Mcl1, survivin, cyclin D1 and c-myc, thus committing cells to apoptosis. These events were followed by activation of caspase 9, caspase 8 and caspase 3 leading to cleavage of its downstream target, poly-ADP-ribose phosphate (PARP).</p> <p>Conclusion</p> <p>GS targets 14-3-3 zeta associated cellular pathways for reducing proliferation and inducing apoptosis in head and neck cancer cells, warranting its investigation for use in treatment of head and neck cancer.</p

Nucleation and crystallization in bio-based immiscible polyester blends

Bio-based thermoplastic polyesters are highly promising materials as they combine interesting thermal and physical properties and in many cases biodegradability. However, sometimes the best property balance can only be achieved by blending in order to improve barrier properties, biodegradability or mechanical properties. Nucleation, crystallization and morphology are key factors that can dominate all these properties in crystallizable biobased polyesters. Therefore, their understanding, prediction and tailoring is essential. In this work, after a brief introduction about immiscible polymer blends, we summarize the crystallization behavior of the most important bio-based (and immiscible) polyester blends, considering examples of double-crystalline components. Even though in some specific blends (e.g., polylactide/polycaprolactone) many efforts have been made to understand the influence of blending on the nucleation, crystallization and morphology of the parent components, there are still many points that have yet to be understood. In the case of other immiscible polyester blends systems, the literature is scarce, opening up opportunities in this environmentally important research topic.The authors would like to acknowledge funding by the BIODEST project ((RISE) H2020-MSCA-RISE-2017-778092

Social and biological determinants of iron deficiency anemia

This cross-sectional study aimed to identify the social and biological determinants of anemia in children enrolled in the Brazilian Income Transfer Program (PBF). The study evaluated 446 children (69.1% of the total enrolled) ranging from 6 to 84 months of age, of whom 262 were receiving the income transfer (60.2% of the beneficiaries) and 184 were not (87.6% of the non-beneficiaries). Testing for anemia was performed with the Hemocue portable hemoglobinometer, and the cutoff points were set at 11.0 and 11.5g/dL, according to age bracket. The data were analyzed using Poisson hierarchical regression with robust variance for multivariate analysis. There was no difference in the anemia prevalence rates between the beneficiary and non-beneficiary groups. Risk factors for anemia were low paternal schooling, cesarean birth, consumption of untreated water, stunting, and age less than 24 months. Prevalence of anemia in the group of non-beneficiary children under two years of age was significantly higher than in the beneficiary group in the same age bracket, suggesting the importance of the PBF income transfer for preventing anemia in children.Neste estudo transversal, objetivou-se conhecer a determinação social e biológica da anemia em crianças cadastradas no Programa Bolsa Família (PBF). Foram avaliadas 446 crianças (69,1% do total cadastrado) com idade entre 6 e 84 meses, sendo que 262 (60,2%) recebiam o benefício, e 184 (87,6%) não recebiam. O teste de anemia foi realizado com o hemoglobinômetro portátil Hemocue, e os pontos de corte adotados foram 11,0 e 11,5g/dL, segundo a faixa etária. Utilizou-se regressão de Poisson hierarquizada com variância robusta para análise multivariada. Não houve diferença entre as prevalências de anemia entre os grupos beneficiários e não-beneficiários. Os fatores de risco para essa carência foram baixa escolaridade paterna, parto cesariano, consumo de água sem tratamento, baixa estatura e idade inferior a 24 meses. A prevalência de anemia no grupo de crianças menores de dois anos não-beneficiárias foi significantemente maior do que no grupo beneficiário de mesma idade, o que sugere a importância do benefício do PBF no combate à anemia em crianças

Backbending, seniority, and Pauli blocking of pairing correlations at high rotational frequencies in rapidly rotating nuclei

Garrett et al. systematically investigated band-crossing frequencies resulting from the rotational alignment of the first pair of i13/2 neutrons (AB) in rare-earth nuclei. In that study, evidence was found for an odd-even neutron number dependence attributed to changes in the strength of neutron pairing correlations. The present paper carries out a similar investigation at higher rotational frequencies for the second pair of aligning i13/2 neutrons (BC). Again, a systematic difference in band-crossing frequencies is observed between odd-N and even-N Er, Yb, Hf, and W nuclei, but in the BC case, it is opposite to the AB neutron-number dependence. These results are discussed in terms of a reduction of neutron pairing correlations at high rotational frequencies and of the effects of Pauli blocking on the pairing field by higher-seniority configurations. Also playing a significant role are the changes in deformation with proton and neutron numbers, the changes in location of single-particle orbitals as a function of quadrupole deformation, and the position of the Fermi surface with regard to the various ω components of the neutron i13/2 shell

Bark Extract of Bathysa cuspidata in the Treatment of Liver Injury Induced by Carbon Tetrachloride in Rats

The aim of this study was to investigate the effect of bark extract Bathysa cuspidata (BCE) in the reconstitution of hepatic parenchyma and stroma after dysfunction induced by the CCl4. Liver lesions were induced by intraperitoneal administration of CCl4 (1 mL/kg) every 48 h for 12 days. The animals were treated with B. cuspidata extract (BCE) administered by gavage for another 12 days. Forty-nine rats were randomized into seven treatment groups with seven animals receiving CCl4, BCE (200, or 400 mg/kg) and the vehicle DMSO alone, or in different combinations. The extract alone showed no evidence of hepatic toxicity. In general, rats acutely exposed to CCl4 without the treatment with BCE presented high ALT and AST serum levels and high tissue content of lipid hydroperoxides, malondialdehyde, and lipid droplets. BCE administration, especially at 400 mg/kg attenuated significantly all these parameters. Furthermore, the antioxidant activities of the enzymes superoxide dismutase and catalase were significantly increased in the groups receiving this extract. These results showed that the extract of B. cuspidata stem bark stimulated the antioxidant defense system and reduced the morphological and functional liver damage in Wistar rats previously exposed to CCl4