Glioma apoptosis induced by macrophages involves both death receptor-dependent and independent pathways

Apoptosis of glioma may represent a promising intervention for tumor treatment. Macrophages are able to induce apoptosis in a number of tumor cells, including glioma. It is known that apoptosis of cells is executed on either a death receptor-dependent or independent pathway. Whether and how apoptosis of glioma cells induced by activated macrophages is involved in these two pathways simultaneously are not known. Using in vitro and in vivo experimental models, we investigated Bcl-2 system and Fas/FasL channel, representing the death receptor-dependent and independent pathways, respectively, in glioma cells treated with the supernatant from the activated macrophages, which was rich in tumor necrosis factor-alpha and interferon-gamma. We found that levels of Fas and FasL were up-regulated both in vitro and in vivo, accompanying an increase in the expression of caspase-8. The number of apoptotic cells was also increased significantly, although the percentage of death cells exceeded the number of tumor cells positive for Fas or FasL. It was also evident that the expression of Bax was increased, whereas the level of Bcl-2 was decreased, in glioma cells treated with the supernatant from the activated macrophages. The alteration of molecules related to both death pathways led to apoptosis of glioma and the inhibition of xenograft glioma growth in mice. Apoptosis of glioma induced by the activated macrophage is executed by way of both death receptor-dependent and independent pathways, and such an apoptosis-induced approach can effectively inhibit the growth of glioma in vivo.     

Magnetic suspension of the rotor of a ventricular assist device of mixed flow type

Abstract:  This work presents results of preliminary studies concerning application of magnetic bearing in a ventricular assist device (VAD) being developed by Dante Pazzanese Institute of Cardiology—IDPC (São Paulo, Brazil). The VAD-IDPC has a novel architecture that distinguishes from other known VADs. In this, the rotor has a conical geometry with spiral impellers, showing characteristics that are intermediate between a centrifugal VAD and an axial VAD. The effectiveness of this new type of blood pumping principle was showed by tests and by using it in heart surgery for external blood circulation. However, the developed VAD uses a combination of ball bearings and mechanical seals, limiting the life for some 10 h, making impossible its long-term use or its use as an implantable VAD. As a part of development of an implantable VAD, this work aims at the replacement of ball bearings by a magnetic bearing. The most important magnetic bearing principles are studied and the magnetic bearing developed by Escola Politécnica of São Paulo University (EPUSP-MB) is elected because of its very simple architecture. Besides presenting the principle of the EPUSP-MB, this work presents one possible alternative for applying the EPUSP-MB in the IDPC-VAD.     

Results From Extrapleural Clipping of a Patent Ductus Arteriosus in Seriously Ill Preterm Infants

Minithoracotomy for extrapleural closure of the patent ductus arteriosus (PDA) in seriously ill patients offers a fast and less invasive alternative to conventional transpleural ductal closure. This study reports the immediate postoperative clinical outcomes for 24 extrapleurally clipped premature infants presenting with congestive heart failure in high-risk comorbidity status between March 2007 and November 2010. The demographics, preoperative clinical characteristics, and postoperative outcomes of the patients, including echocardiographic assessments, were evaluated. No surgery-related mortalities occurred. Four mortalities occurred after surgery due to sepsis and bleeding diathesis. All 20 surviving patients exhibited normal left ventricular dimensions and systolic function in the immediate follow-up period. The study shows that extrapleural clip closure in seriously ill premature infants has an acceptable overall short-term mortality and complication rate with a high rate of ductal closure.     

Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.     

Protein kinase C-alpha-mediated regulation of low-density lipoprotein receptor related protein and urokinase increases astrocytoma invasion

Aggressive and infiltrative invasion is one of the hallmarks of glioblastoma. Low-density lipoprotein receptor-related protein (LRP) is expressed by glioblastoma, but the role of this receptor in astrocytic tumor invasion remains poorly understood. We show that activation of protein kinase C-alpha (PKC-alpha) phosphorylated and down-regulated LRP expression. Pretreatment of tumor cells with PKC inhibitors, phosphoinositide 3-kinase (PI3K) inhibitor, PKC-alpha small interfering RNA (siRNA), and short hairpin RNA abrogated phorbol 12-myristate 13-acetate-induced down-regulation of LRP and inhibited astrocytic tumor invasion in vitro. In xenograft glioblastoma mouse model and in vitro transmembrane invasion assay, LRP-deficient cells, which secreted high levels of urokinase-type plasminogen activator (uPA), invaded extensively the surrounding normal brain tissue, whereas the LRP-overexpressing and uPA-deficient cells did not invade into the surrounding normal brain. siRNA, targeted against uPA in LRP-deficient clones, attenuated their invasive potential. Taken together, our results strongly suggest the involvement of PKC-alpha/PI3K signaling pathways in the regulation of LRP-mediated astrocytoma invasion. Thus, a strategy of combining small molecule inhibitors of PKC-alpha and PI3K could provide a new treatment paradigm for glioblastomas.     

Determinants of consumer adoption of halal cosmetics: A systematic literature review

Background

The global halal cosmetics market is projected to grow during the forecast period. However, the factors that influenced consumers in the world to opt for halal cosmetics remain ambiguous.

Objectives

The objective of this study was to understand the universal concept of halal cosmetics and a framework of critical points that influence consumers in purchasing halal cosmetic products.

Method

The method used was Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement by using Web of Science and Scopus databases. This study extends the systematic literature review covering all variables in purchasing halal cosmetics as halal cosmetic is not simply a religious issue, but it is also an opportunity to increase sales and acquire a competitive advantage.

Results

This study found 14 articles that mainly discussed the critical points related to religiosity and product factors, that is, ingredient, halal logo, and halal certification as the highest driver in influencing consumers to purchase halal cosmetics. Other related factors in this study are price, promotion, place, social factors, and characteristics of consumers. These factors should be taken into consideration as they provide a plus point and an extra edge to local or international manufacturers to tap the global markets for halal cosmetic products that cater to both Muslims and non-Muslims communities.

Practical Implications

Cosmetic manufacturers and marketers must ensure that their products suit the expectation of consumers as todays halalan and tayyiban products are being searched rather than branded products due to their cleanliness, safety, and hygienic.

Originality/Value

This study is among the earliest study examining the factors of purchase intention in halal cosmetics using a systematic literature review method that integrates marketing stimulus (product, price, promotion, and place) and other stimuli (social, religious, and characteristics).     

Myoclonus in patients with COVID-19: Findings of autoantibodies against brain structures in cerebrospinal fluid

Background and purpose

COVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed.

Metods

Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry.

Results

Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus.

Conclusion

Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.     

Oral lichen planus and the p53 family: what do we know?

J Oral Pathol Med (2011) 40 : 281–285 Oral lichen planus (OLP) is a relatively common chronic disease of the oral mucosa for which the aetiopathogenesis is not fully understood. It mainly affects middle aged and elderly. The finding of autoantibodies against p63, a member of the p53 family, is a strong indication of autoimmunity as a causative or contributing factor. The WHO classified OLP as a potentially malignant disorder, but still there is an ongoing debate in the literature on this subject. The TP53 gene encodes a tumour suppressor protein that is involved in induction of cell‐cycle arrest or apoptosis of DNA‐damaged cells. The p63 gene encodes six different proteins that are crucial for formation of the oral mucosa and skin. The coordinated stabilization of p53 and decreased expression of p63 seen in OLP cause induction of apoptosis enabling removal of DNA‐damaged cells. In view of the complexity of cancerogenesis, no firm statement can at present be made about the relevance of the observed relationship between p53 and p63 and the possible malignant transformation of OLP.