Angiosuppression and chemotherapy: strategies aimed at their integration in cancer patients

A number of antiangiogenic agents have been developed as pharmaceuticals and are currently being tested in clinical studies. Potential strategies to enhance the activity of angiogenesis inhibitors could be to combine them, or better still, to administer them either sequentially or concurrently with cytotoxic drugs. Chemotherapy would be a more appropriate initial choice for patients with advanced disease since cytostatic agents can induce a fast regression of the tumor and cancer-related symptoms. Antiangiogenic treatment could be used after chemotherapy in patients who achieve disease remission to prolong the time to progression, the symptom-free interval and the overall survival. Antiangiogenic treatment is likely to attain an important role in the adjuvant setting. In fact, it could be used for prolonged periods after radical surgery to maintain dormancy of residual tumor cells. In spite of these promising preclinical data, several points need to be clarified before the initiation of clinical trials. In fact, certain misconceptions may interfere with their optimum design and result analysis.     

Antifouling activity of enzyme‐functionalized silica nanobeads

The amelioration of biofouling in industrial processing equipment is critical for performance and reliability. While conventional biocides are effective in biofouling control, they are potentially hazardous to the environment and in some cases corrosive to materials. Enzymatic approaches have been shown to be effective and can overcome the disadvantages of traditional biocides, however they are typically uneconomic for routine biofouling control. The aim of this study was to design a robust and reusable enzyme‐functionalized nano‐bead system having biofilm dispersion properties. This work describes the biochemical covalent functionalization of silica‐based nanobeads (hereafter referred to as Si‐NanoB) with Proteinase K (PK). Results showed that PK‐functionalized Si‐NanoB are effective in dispersing both protein‐based model biofilms and structurally altering Pseudomonas fluorescens biofilms, with significant decreases in surface coverage and thickness of 30.1% and 38.85%, respectively, while increasing surface roughness by 19 % following 24 h treatments on bacterial biofilms. This study shows that enzyme‐functionalized nanobeads may potentially be an environmentally friendly and cost effective alternative to pure enzyme and chemical treatments. Biotechnol. Bioeng. 2016;113: 501–512. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.     

Metabolism of fluoroorganic compounds in microorganisms: impacts for the environment and the production of fine chemicals

Incorporation of fluorine into an organic compound can favourably alter its physicochemical properties with respect to biological activity, stability and lipophilicity. Accordingly, this element is found in many pharmaceutical and industrial chemicals. Organofluorine compounds are accepted as substrates by many enzymes, and the interactions of microorganisms with these compounds are of relevance to the environment and the fine chemicals industry. On the one hand, the microbial transformation of organofluorines can lead to the generation of toxic compounds that are of environmental concern, yet similar biotransformations can yield difficult-to-synthesise products and intermediates, in particular derivatives of biologically active secondary metabolites. In this paper, we review the historical and recent developments of organofluorine biotransformation in microorganisms and highlight the possibility of using microbes as models of fluorinated drug metabolism in mammals.     

Endoscopic Endonasal Approach in the Management of Rathke’s Cleft Cysts

Objective

Rathke’s cleft cysts (RCCs) are quite uncommon sellar lesions that can extend or even arise in the suprasellar area. The purpose of this study is to evaluate the effectiveness of both standard and extended endoscopic endonasal approaches in the management of different located RCCs.

Methods

We retrospectively analyzed a series of 29 patients (9 males, 20 females) complaining of a RCC, who underwent a standard or an extended endoscopic transsphenoidal approach at the Division of Neurosurgery, Department of Neurosciences and Reproductive and Odontostomatological Sciences, of the Università degli Studi di Napoli "Federico II”. Data regarding patients’ demographics, clinical evaluation, cyst characteristics, surgical treatments, complications and outcomes were extracted from our electronic database (Filemaker Pro 11, File Maker Inc., Santa Clara, California, USA).

Results

A standard transsphenoidal approach was used in 19 cases, while the extended variation of the approach in 10 cases (5 purely suprasellar and 5 intra-suprasellar RCC). Cysts contents was fully drained in all the 29 cases, whilst a gross total removal, that accounts on the complete cyst wall removal, was achieved in an overall 55,1% of patients (16/29), specifically 36,8% (7/19) that received standard approach and 90% (9/10) of those that underwent to extended approach. We reported a 56.2% of recovery from headache, 38.5% of complete recovery and 53.8% of improvement from visual field defect and an overall 46.7% of improvement of the endocrine functions. Postoperative permanent DI rate was 10.3%, overall post-operative CSF leak rate 6.9%; recurrence/regrowth occurred in 4 patients (4/29, 13.8%), but only one required a second surgery.

Conclusion

The endoscopic transsphenoidal approach for the removal of a symptomatic RCC offers several advantages in terms of visualization of the surgical field during both the exposure and removal of the lesion. The “extended” variation of the endoscopic approach provides a direct access to the supradiaphragmatic space, allowing adequate view and room for the safe removal of selected supradiaphragmatic RCCs, regardless of the sellar size (even a not enlarged sella), and provides a higher likelihood of preserving normal pituitary tissue and functions.     

Theory of Mind and Emotional Functioning in Fibromyalgia Syndrome: An Investigation of the Relationship between Social Cognition and Executive Function

Background

Fibromyalgia (FM) is a syndrome primarily characterised by chronic, widespread musculoskeletal pain. In the aetiology of this syndrome a crucial role is played by complex interactions among biological, genetic, psychological, and socio-cultural factors. Recently, researchers have started to explore emotional functioning in FM, with their attention focused on alexithymia, a personality construct that affects the regulation of a person’s own emotions. On the other hand, the detection and experience of emotional signals from other people have only been sparsely investigated in FM syndrome and no studies have investigated the ability to represent other people’s mental states (i.e. Theory of Mind, ToM) in these patients. Here we present the first study investigating a large set of social-cognitive abilities, and the possible relationships between these abilities and the performance on executive-function tasks, in a homogenous sample of patients with FM.

Methodology

Forty women with FM and forty-one healthy women matched for education and age were involved in the study. Social cognition was assessed with a set of validated experimental tasks. Measures of executive function were used to test the correlations between this dimension and the social-cognitive profile of patients with FM. Relationships between social-cognitive abilities and demographic, clinical and psychological variables were also investigated.

Principal Findings

Patients with FM have impairments both in the regulation of their own affect and in the recognition of other’s emotions, as well as in representing other people’s mental states. No significant correlations were found between social cognition tasks and the subcomponents of the executive function that were analysed.

Conclusions

The results show the presence of several impairments in social cognition skills in patients with FM, which are largely independent of both executive function deficits and symptoms of psychological distress. The impairments reported highlight the importance of adequately assessing ToM and emotional functioning in clinical practice.     

<Emphasis Type="Italic">CAPN1</Emphasis> markers in three Argentinean cattle breeds: report of a new InDel polymorphism within intron 17

In this study, the genotype distribution and allelic frequencies of CAPN1 (Calcium activated neutral protease) single nucleotide polymorphisms (SNPs) were analyzed taking advantage of the different genetic backgrounds provided by Hereford, Brahman and Braford cattle. We report a new insertion/deletion (InDel) polymorphism, consisting of a change of seven nucleotides for only one nucleotide (TCTGGGT → C) within intron 17 of the CAPN1 gene. The segregation pattern of this polymorphism was analyzed together with the markers CAPN316, CAPN530 and CAPN4751 already described. The allele distribution of CAPN1 markers in the Braford crossbreed (3/8 Brahman 5/8 Hereford) is described for the first time. Four assays of allelic discrimination were designed: the tetra primer ARMS-PCR technique for genotyping the new InDel and the CAPN4751 marker, and a PCR-RFLP method for genotyping the markers CAPN316 and CAPN530. The genotypic and minor allele frequencies (MAFs) obtained showed that the InDel polymorphism does not provide redundant information to that already provided by the other CAPN1 markers and segregates differently between breeds, being a common SNP (MAF ≥ 0.05) in the herds with a high percentage of Bos indicus background. The high percentage of heterozygous individuals found in the Braford crossbreed for the markers assessed reveals enough genetic variation that could help to solve the tenderness problem of tropical-adapted cattle.     

Compressive properties of cd-HA-gelatin modified intrasynovial tendon allograft in canine model in vivo

Although we sometimes use the intrasynovial tendon allograft as a donor, the gliding ability of allograft prepared by lyophilization is significantly decreased. The gliding ability of the grafted tendon after tendon reconstruction is very important because the high gliding resistance causes more adhesion and leads to poor clinical results. We recently revealed that tendon surface treatment with a carbodiimide derivatized HA (cd-HA)-gelatin mixture for intrasynovial tendon allograft significantly improved its gliding ability. The purpose of this study was to investigate whether this cd-HA-gelatin treatment affects the tendon mechanical property or not. A total of 40 flexor digitorum profundus (FDP) tendons from canines were evaluated for compressive property by using indentation test. Indentation stiffness was measured for normal tendon, rehydrated tendon after lyophilization, rehydrated tendon after lyophilization that was implanted 6 weeks in vivo, and cd-HA treated rehydrated tendon after lyophilization that was implanted 6 weeks in vivo. The results for all groups showed no significant difference in the tendon compressive properties. The findings of these results demonstrate that cd-HA treatment for intrasynovial tendon allograft is an excellent method to improve the tendon gliding ability after lyophilization without changing the compressive property of donor tendon.     

Synthesis, crystal structure, solution behavior and catalytic activity of a palladium(II)-allyl complex containing a 2-pyridyl-1,2,3-triazole bidentate ligand

The synthesis and characterization of the cationic complex [Pd(η³-C₃H₅)(2-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)pyridine)](BF₄) (2) are reported. The solid-state structure of 2 has been unambiguously confirmed by single-crystal X-ray diffraction analysis. ¹H NMR spectroscopy reveals that in solution complex 2 is dynamic and that syn-syn, anti-anti exchange of the allyl protons occurs. Complex 2 exhibits good activity in the Suzuki-Miyaura coupling of aryl bromides with phenyl boronic acid.     

Characterization of the Endocannabinoid System in Human Neuronal Cells and Proteomic Analysis of Anandamide-induced Apoptosis

Anandamide (AEA) is an endogenous agonist of type 1 cannabinoid receptors (CB1R) that, along with metabolic enzymes of AEA and congeners, compose the “endocannabinoid system.” Here we report the biochemical, morphological, and functional characterization of the endocannabinoid system in human neuroblastoma SH-SY5Y cells that are an experimental model for neuronal cell damage and death, as well as for major human neurodegenerative disorders. We also show that AEA dose-dependently induced apoptosis of SH-SY5Y cells. Through proteomic analysis, we further demonstrate that AEA-induced apoptosis was paralleled by an ∼3 to ∼5-fold up-regulation or down-regulation of five genes; IgG heavy chain-binding protein, stress-induced phosphoprotein-1, and triose-phosphate isomerase-1, which were up-regulated, are known to act as anti-apoptotic agents; actin-related protein 2/3 complex subunit 5 and peptidylprolyl isomerase-like protein 3 isoform PPIL3b were down-regulated, and the first is required for actin network formation whereas the second is still function-orphan. Interestingly, only the effect of AEA on BiP was reversed by the CB1R antagonist SR141716, in SH-SY5Y cells as well as in human neuroblastoma LAN-5 cells (that express a functional CB1R) but not in SK-NBE cells (which do not express CB1R). Silencing or overexpression of BiP increased or reduced, respectively, AEA-induced apoptosis of SH-SY5Y cells. In addition, the expression of BiP and of the BiP-related apoptotic markers p53 and PUMA was increased by AEA through a CB1R-dependent pathway that engages p38 and p42/44 mitogen-activated protein kinases. Consistently, this effect of AEA was minimized by SR141716. In conclusion, we identified BiP as a key protein in neuronal apoptosis induced by AEA.Endocannabinoids bind to and activate both type 1 (CB1R)⁴ and type 2 (CB2R) cannabinoid receptors and are widely recognized as important regulators of central and peripheral functions (1–3). The most studied endocannabinoids are anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) (1, 3). AEA, unlike 2-AG, binds to and activates also transient receptor potential vanilloid 1 (TRPV1), thus being considered a true “endovanilloid” (4).The “endocannabinoid system (ECS)” includes the receptors, their ligands AEA and 2-AG, and the enzymes that synthesize (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL)) or degrade (fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)) AEA and 2-AG, respectively (1–3). On the other hand, there is still controversy about the identity and even the existence of purported “endocannabinoid transporters” that have not yet been cloned, isolated, or characterized (5). A growing interest is concerned with the ability of AEA to induce apoptosis in neuronal and non-neuronal cells (for comprehensive reviews see Refs. 6–9). Such a pro-apoptotic activity of AEA appears to be mediated by divergent pathways, each potentiated, reduced, or unaffected by cannabinoid or TRPV1 receptors (6–9). They can also be dependent on membrane cholesterol content (10, 11), generation of reactive oxygen species (12, 13), or even release of ethanolamine from AEA catalyzed by FAAH (14). In this context, it should be stressed that data on ECS and AEA-induced apoptosis in human neuronal cells are still very scant. Furthermore, a proteomic analysis of AEA-induced apoptosis has never been performed, leaving open the question of which proteins (if any) might be modulated at the level of expression upon induction of programmed cell death by this endocannabinoid. On this basis, we sought to characterize through functional and immunochemical assays and confocal microscopy the ECS components in human neuroblastoma SH-SY5Y cells. In addition, we performed a proteomic analysis of AEA-induced apoptosis in these cells that identified five proteins whose expression was modified. Among these proteins, one (BiP/GRP78) was shown to be modulated by AEA in a CB1R-dependent manner, in parallel with apoptosis. Through silencing and overexpression experiments, it was found to be a key player in the death program.     

Brain evolution and uniqueness in the human genome

Despite an ever-expanding database of sequenced mammalian genomes to be mined for clues, the emergence of the unique human brain remains an evolutionary enigma. In their new study, trawl the human genome and those of other mammals in search of short conserved DNA elements that show extremely rapid evolution only in humans. As they report in a recent issue of Nature, their scan yielded a gene for a novel noncoding RNA that adopts a human-specific structure and may regulate neurodevelopment.