To Remove or Not to Remove? The Challenge of Extracting the Template to Make the Cavities Available in Molecularly Imprinted Polymers (MIPs)

Template removal is a critical step in the preparation of most molecularly imprinted polymers (MIPs). The polymer network itself and the affinity of the imprinted cavities for the template make its removal hard. If there are remaining template molecules in the MIPs, less cavities will be available for rebinding, which decreases efficiency. Furthermore, if template bleeding occurs during analytical applications, errors will arise. Despite the relevance to the MIPs performance, template removal has received scarce attention and is currently the least cost-effective step of the MIP development. Attempts to reach complete template removal may involve the use of too drastic conditions in conventional extraction techniques, resulting in the damage or the collapse of the imprinted cavities. Advances in the extraction techniques in the last decade may provide optimized tools. The aim of this review is to analyze the available data on the efficiency of diverse extraction techniques for template removal, paying attention not only to the removal yield but also to MIPs performance. Such an analysis is expected to be useful for opening a way to rational approaches for template removal (minimizing the costs of solvents and time) instead of the current trial-and-error methods.     

Scoping Review on Platelets and Tumor Angiogenesis: Do We Need More Evidence or Better Analysis?

Platelets are an active component of the tumor microenvironment (TME), involved in the regulation of multiple tumor processes, including angiogenesis. They are generated rich in angiogenic factors in their granules to actively participate in the hemostatic process by megakaryocytes and further enriched in angiogenic factors by all components of the tumor microenvironment to control the angiogenic process because of their preferential relationship with the endothelial component of vessels. In recent decades, the literature has reported a great deal of evidence on the role of platelets in tumor angiogenesis; however, it is unclear whether the number or mean volume of platelets and/or their content and localization in TME may have clinical relevance in the choice and management of therapy for the cancer patient. In this scoping review, we collected and critically reviewed the scientific evidence supporting a close relationship between platelets, cancer, and angiogenesis. The aim of this work was to define the landscape of platelet-activated angiogenesis in cancer progression and analyze what and how much evidence is present in the last 20 years in the literature at both the preclinical and clinical levels, to answer whether platelets could be a useful determinant for analyzing tumor angiogenesis. In conclusion, this scoping review indicates that there is much evidence, both preclinical and clinical, but in the preclinical context, studies demonstrate the direct involvement of platelets in tumor angiogenesis; in the clinical context the evidence is indirect, though strong, and the indication of how and to what extent platelet content contributes to tumor angiogenesis is lacking. So, do we need more evidence or better analysis? More molecular and quali-quantitative data is needed to translate the results obtained in preclinical studies into the clinical setting. This information about platelets, if correlated with tumor type and its biology, including tumor vasculature, type of angiogenesis, and patient characteristics (age, sex, comorbidities, drug treatments for chronic diseases) could be an important pa- rameter for correlating platelet biology to angiogenesis, for personalizing cancer therapy, and for clinical prognosis.     

Oral Corticosteroids Dependence and Biologic Drugs in Severe Asthma: Myths or Facts? A Systematic Review of Real-World Evidence

Airway inflammation represents an important characteristic in asthma, modulating airflow limitation and symptom control, and triggering the risk of asthma exacerbation. Thus, although corticosteroids represent the cornerstone for the treatment of asthma, severe patients may be dependent on oral corticosteroids (OCSs). Fortunately, the current humanised monoclonal antibodies (mAbs) benralizumab, dupilumab, mepolizumab, omalizumab, and reslizumab have been proven to induce an OCS-sparing effect in randomized controlled trials (RCTs), thus overcoming the problem of OCS dependence in severe asthma. Nevertheless, a large discrepancy has been recognized between selected patients enrolled in RCTs and non-selected asthmatic populations in real-world settings. It is not possible to exclude that the OCS-sparing effect of mAbs resulting from the RCTs could be different than the real effect resulting in clinical practice. Therefore, we performed a systematic review and correlation analysis to assess whether mAbs are effective in eliciting an OCS-sparing effect and overcoming the OCS dependence in severe asthmatic patients in real-world settings. Overall, real-world studies support the evidence that OCS dependence is a real condition that, however, can be found only in a small number of really severe asthmatic patients. In most patients, the dependence on OCS can be related to modifying factors that, when adequately modulated, may lead to a significant reduction or suspension of OCS maintenance. Conversely, in severe asthmatics in whom OCS resistance is proved by a high daily dose intake, mAbs allow reversion of the OCS dependence, leading to the suspension of OCS therapy in most patients or >50% reduction in the daily OCS dose.     

Gut Microbiota,Metabolic Disorders and Breast Cancer: Could Berberine Turn Out to Be a Transversal Nutraceutical Tool? A Narrative Analysis

Metabolic disorders, mainly characterized as the marked alteration of the lipid and carbohydrate profile, in addition to the clinical presence of the direct consequences of these alterations, are pathological conditions that have considerably increased in prevalence in recent years. They are directly linked to the onset of various pathologies, including cancer, particularly breast cancer, and are hormone-responsive. Alongside the known conditions responsible for this scenario, such as nutrition and lifestyle in general, the importance of both the colonic microbiota and the various organs and systems is becoming increasingly evident. In fact, it is now evident that microbial dysbiosis plays a fundamental role in the onset of these metabolic disorders, and therefore how these conditions are indirectly responsible for the onset and progression of neoplasms. Indirect mechanisms such as an altered Firmicutes/Bacteroidetes ratio; the formation of metabolites such as short-chain fatty acids (SCFAs), in particular, butyrate, which is capable of acting as a tumor suppressor; and the glucuronidase activity of estroboloma (bacteria responsible for estrogen metabolism) are just some of the most important mechanisms that contribute to the history of breast cancer. It is therefore understandable that in clinical terms, it is essential to associate the modulation of metabolic disorders and the microbial conditions that contribute to generating them with common therapies, preferably using compounds and solutions that are effective and acceptable for the patient without side effects. Nutraceuticals such as berberine (active both in metabolic scenarios and in the microbiota) and interventions modulating the microbial structure such as the use of probiotics and prebiotics seem to be ideal solutions for these preventive and no-longer-ignorable strategies in the light of numerous data now present in the literature.     

Antioxidant activity of burdock (Arctium lappa Linné): Its scavenging effect on free-radical and active oxygen

The antioxidant activity and free-radical and active oxygen-scavenging activity of burdock extracts were investigated. Of the solvents used for extraction, water yielded the greatest amount of extract that exhibited the strongest antioxidant activity. Water extracts of burdock (WEB) and hot water extracts of burdock (HWEB) exhibited comparable and marked activity on inhibition of linoleic acid peroxidation, indicating that heat treatment did not alter the antioxidant activity of WEB. WEB and HWEB produced significantly lower (P<0.05) malondialdehyde (MDA) in both linoleic acid and liposome model systems than did the control. Moreover, mixtures of tocopherol (Toc), WEB, and HWEB exhibited a remarkable synergistic antioxidant effect in a liposome system; WEB and HWEB thus potentiated the action of Toc. Furthermore, WEB and HWEB displayed a marked inhibitory effect on lipid peroxidation of rat liver homogenate in vitro. WEB and HWEB exhibited an 80% scavenging effect on α,α-diphenyl-β-picrylhydrazyl radical and marked reducing power, indicating that WEB and HWEB act as primary antioxidants. Both extracts at a dose of 1.0 mg exhibited a 60.4–65.0% scavenging effect on superoxide and an 80.5% scavenging effect on hydrogen peroxide. They also showed a marked scavenging effect on the hydroxyl radical. These results revealed that WEB and HWEB are also active as oxygen scavengers and as secondary antioxidants. Based on these results, termination of free-radical reactions and quenching of reactive oxygen species in burdock extracts are suggested to be, in part, responsible for the antioxidant activity of burdock extracts.     

Biodegradable poly(ester amide)s – A remarkable opportunity for the biomedical area: Review on the synthesis,characterization and applications

Poly(ester amide)s have emerged in the last years as an important family of biodegradable synthetic polymers. These polymers present both ester and amide linkages in their structure and they gather in the same entity the good degradability of polyesters with the good thermo-mechanical properties of polyamides. Particularly, poly(ester amide)s containing α-amino acids have risen as important materials in the biomedical field. The presence of the α-amino acid contributes to better cell–polymer interactions, allows the introduction of pendant reactive groups, and enhances the overall biodegradability of the polymers.     

Telomere Distribution in Human Sperm Heads and Its Relation to Sperm Nuclear Morphology: A New Marker for Male Factor Infertility?

Infertility is a problem affecting an increasing number of couples worldwide. Currently, marker tests for male factor infertility are complex, highly technical and relatively subjective. Up to 40% of cases of male factor infertility are currently diagnosed as idiopathic therefore, there is a clear need for further research into better ways of diagnosing it. Changes in sperm telomere length have been associated with infertility and closely linked to DNA damage and fragmentation, which are also known to be related to infertility. However, telomere distribution is a parameter thus far underexplored as an infertility marker. Here, we assessed morphological parameters of sperm nuclei in fertile control and male factor infertile cohorts. In addition, we used 2D and 3D fluorescence in situ hybridization (FISH) to compare telomere distribution between these two groups. Our findings indicate that the infertile cohort sperm nuclei were, on average, 2.9% larger in area and showed subtle differences in sperm head height and width. Telomeres were mainly distributed towards the periphery of the nuclei in the control cohort, with diminishing telomere signals towards the center of the nuclei. Sperm nuclei of infertile males, however, had more telomere signals towards the center of the nuclei, a finding supported by 3D imaging. We conclude that, with further development, both morphology and telomere distribution may prove useful investigative tools in the fertility clinic.     

Similarity of Cuticular Lipids Between a Caterpillar and Its Host Plant: A Way to Make Prey Undetectable for Predatory Ants?

Ithomiine butterflies (Nymphalidae) have long-lived, aposematic, chemically protected adults. However, little is known about the defense mechanisms in larvae and other juvenile stages. We showed that larvae Mechanitis polymnia are defended from ants by a chemical similarity between their cuticular lipids and those of the host plant, Solanum tabacifolium (Solanaceae). This is a novel defense mechanism in phytophagous insects. A field survey during one season showed that larval survivorship was up to 80%, which is high when compared with other juvenile stages. In a laboratory bioassay, live larvae on their host plant were not attacked by the predatory ant Camponotus crassus (Formicidae). Two experiments showed that the similarity between the cuticular lipids of M. polymnia and S. tabacifolium protected the larvae from C. crassus: (a) when the caterpillar was switched from a host plant to a non-host plant, the predation rate increased, and (b) when a palatable larva (Spodoptera frugiperda, Noctuidae) was coated with the cuticular lipids of M. polymnia and placed on S. tabacifolium leaves, it no longer experienced a high predation rate. This defensive mechanism can be defined as chemical camouflage, and may have a double adaptive advantage, namely, protection against predation and a reduction in the cost of sequestering toxic compounds from the host plant.     

TAS-120 Cancer Target Binding: Defining Reactivity and Revealing the First Fibroblast Growth Factor Receptor 1 (FGFR1) Irreversible Structure

1-[(3S)-3-[4-Amino-3-[2-(3,5-dimethoxyphenyl)ethynyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyrrolidinyl]-2-propen-1-one (TAS-120) is an irreversible inhibitor of the fibroblast growth factor receptor (FGFR) family, and is currently under phase I/II clinical trials in patients with confirmed advanced metastatic solid tumours harbouring FGFR aberrations. This inhibitor specifically targets the P-loop of the FGFR tyrosine kinase domain, forming a covalent adduct with a cysteine side chain of the protein. Our mass spectrometry experiments characterise an exceptionally fast chemical reaction in forming the covalent complex. The structural basis of this reactivity is revealed by a sequence of three X-ray crystal structures: a free ligand structure, a reversible FGFR1 structure, and the first reported irreversible FGFR1 adduct structure. We hypothesise that the most significant reactivity feature of TAS-120 is its inherent ability to undertake conformational sampling of the FGFR P-loop. In designing novel covalent FGFR inhibitors, such a phenomenon presents an attractive strategy requiring appropriate positioning of an acrylamide group similarly to that of TAS-120.     

Hybrid sol gel coating: A solution to prevent interactions between plasticized poly(vinyl chloride) and injectable drugs?

During the infusion of drugs with medical devices in plasticized poly(vinyl chloride) (PVC) release of plasticizers in the injectable solution and/or sorption of drugs on PVC may occur. Thus, patient safety and/or effectiveness of his therapy may be altered. In this study, we assessed the efficiency of a sol gel hybrid coating in preventing plasticizers' release (di‐(2‐ethylhexyl) phthalate (DEHP)) from PVC matrix and drug sorption into PVC. Remaining concentrations of drugs and plasticizer's concentration released after migration tests were assessed by liquid chromatography. Migration processes were followed by Fourier Transform Infrared – Attenuated Total Reflectance (FTIR‐ATR) spectroscopy and PVC surface changes were characterized by scanning electron microscopy (SEM). An evaluation of the mechanical properties of both uncoated and coated polymer was done. The hybrid coating protects PVC from plasticizers leaching. Sorption of drugs tested is also limited. However, the protection against plasticized PVC interactions isn't optimal, probably due to a degradation of the layer, as shown on SEM microphotographs. Furthermore improvements might provide an efficient barrier to advert risks impaired to PVC interactions, to provide patient care safety. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40145.     

Syngas to ethanol on MoCu(2 1 1) surface: Effect of promoter Mo on C—O bond breaking and C—C bond formation

The mechanism of syngas to ethanol on MoCu(2 1 1) surface has been researched by density functional theory (DFT) calculation, and the effects of Mo as a promoter on C—O bond breaking and C—C bond formation have been discussed. Calculations show that Cu-Mo atoms constitute the active sites on MoCu(2 1 1) surface after Mo atom being served as a promoter of Cu catalyst. Compared with Cu(2 1 1), MoCu(2 1 1) has two improvements. Firstly, CH₃ is the most advantageous monomer on the MoCu(2 1 1) surface, which provides abundant CH₃ intermediate for syngas to ethanol. Secondly, the C—C bond is formed mainly by inserting CHO into the abundant CH₃, and the generated CH₃CHO through multiple steps of hydrogenation to generate C₂H₅OH. The key of the promoter Mo on the MoCu(2 1 1) surface also has been verified by the analysis of its electronic properties. Differential charge density shows that the massive electron transfer from Mo to Cu, projected density of states (pDOS) shows that the electron transfer from Mo to Cu makes the d-band center of MoCu(2 1 1) nearer to the Fermi level, these indicate that the MoCu(2 1 1) catalytic capacity increased. The addition of Mo in the Cu-based catalyst not only can effectively solve the problem of C—O bond breaking, but also promote C—C bond formation. About the influence of Mo content on C—O bond breaking and C—C bond formation, compared with MoCu(2 1 1), the DFT results and the d-band center of Mo₂Cu(2 1 1) show that the increase of Mo content could not promote the synergistic effect of Cu/Mo on the generation of ethanol more effectively.     

What Molecular Recognition Systems Do Mesenchymal Stem Cells/Medicinal Signaling Cells (MSC) Use to Facilitate Cell-Cell and Cell Matrix Interactions? A Review of Evidence and Options

Mesenchymal stem cells, also called medicinal signaling cells (MSC), have been studied regarding their potential to facilitate tissue repair for >30 years. Such cells, derived from multiple tissues and species, are capable of differentiation to a number of lineages (chondrocytes, adipocytes, bone cells). However, MSC are believed to be quite heterogeneous with regard to several characteristics, and the large number of studies performed thus far have met with limited or restricted success. Thus, there is more to understand about these cells, including the molecular recognition systems that are used by these cells to perform their functions, to enhance the realization of their potential to effect tissue repair. This perspective article reviews what is known regarding the recognition systems available to MSC, the possible systems that could be looked for, and alternatives to enhance their localization to specific injury sites and increase their subsequent facilitation of tissue repair. MSC are reported to express recognition molecules of the integrin family. However, there are a number of other recognition molecules that also could be involved such as lectins, inducible lectins, or even a MSC-specific family of molecules unique to these cells. Finally, it may be possible to engineer expression of recognition molecules on the surface of MSC to enhance their function in vivo artificially. Thus, improved understanding of recognition molecules on MSC could further their success in fostering tissue repair.     

A Novel pH-Responsive p(AAm-co-METAC)/MMT Composite Hydrogel: Synthesis,Characterization and Its Absorption Performance on Heavy Metal İons

In this study, the preparation and characterization of the novel pH-sensitive poly(acrylamide-co-2-methacryloyloxy)ethyltrimethyl ammonium chloride)/montmorillonite (p(AAm-co-METAC)/MMT) composite superabsorbent hydrogels and their selective metal absorbtion properties were investigated. The adsorption of metal ions is highly dependent on the initial feed concentration, contact time, pH of the metal solution and adsorbent doses. The results were analyzed both by the Langmuir and Freundlich isotherms and the adsorption is found to follow pseudo-second-order kinetics. The adsorption capacity followed the order Zn²⁺ > Ni²⁺ > Cu²⁺ > Pb²⁺ and the maximum adsorption capacities of them were ～320, 285, 240 and 120 (mg g^?1), respectively.     

Effect of Co-catalyst (CuO,CoO or NiO) on Bi2O3–TiO2 Structures and Its Impact on the Photocatalytic Reduction of 4-nitrophenol

Topics in Catalysis - CoO, NiO or CuO oxides were employed as co-catalysts on Bi2O3–TiO2 (BT) structure in the photocatalytic reduction of 4-nitrophenol under UV light irradiation. The...     

MicroRNA-150 (miR-150) and Diabetic Retinopathy: Is miR-150 Only a Biomarker or Does It Contribute to Disease Progression?

Diabetic retinopathy (DR) is a chronic disease associated with diabetes mellitus and is a leading cause of visual impairment among the working population in the US. Clinically, DR has been diagnosed and treated as a vascular complication, but it adversely impacts both neural retina and retinal vasculature. Degeneration of retinal neurons and microvasculature manifests in the diabetic retina and early stages of DR. Retinal photoreceptors undergo apoptosis shortly after the onset of diabetes, which contributes to the retinal dysfunction and microvascular complications leading to vision impairment. Chronic inflammation is a hallmark of diabetes and a contributor to cell apoptosis, and retinal photoreceptors are a major source of intraocular inflammation that contributes to vascular abnormalities in diabetes. As the levels of microRNAs (miRs) are changed in the plasma and vitreous of diabetic patients, miRs have been suggested as biomarkers to determine the progression of diabetic ocular diseases, including DR. However, few miRs have been thoroughly investigated as contributors to the pathogenesis of DR. Among these miRs, miR-150 is downregulated in diabetic patients and is an endogenous suppressor of inflammation, apoptosis, and pathological angiogenesis. In this review, how miR-150 and its downstream targets contribute to diabetes-associated retinal degeneration and pathological angiogenesis in DR are discussed. Currently, there is no effective treatment to stop or reverse diabetes-caused neural and vascular degeneration in the retina. Understanding the molecular mechanism of the pathogenesis of DR may shed light for the future development of more effective treatments for DR and other diabetes-associated ocular diseases.     

Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α(1A)-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment

The α(1A)-adrenergic receptor (α(1A)-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α(1A)-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-oneout cross-validation correlation coefficients were q(2) (CoMFA) = 0.840 and q(2) (CoMSIA) = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r(2) (pred) (/CoMFA) = 0.694; r(2) (pred) (/CoMSIA) = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α(1A)-AR antagonists.     

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.     

Polymer blending or fiber blending: A comparative study using chitosan and poly(ε-caprolactone) electrospun fibers

Nonwoven membranes of poly(ε-caprolactone) (PCL) and chitosan (CS) were produced according to the two methods: by blending the polymers in solution followed by electrospinning – polymer blending method – and by simultaneous deposition of fibers electrospun from separate solutions – fiber blending (FB) method. The two production methods were compared by assessing fiber morphology, mass loss, swelling degree, water contact angle, and mechanical properties of the resulting electrospun membranes. Furthermore, the adhesion, proliferation, and morphology of human dermal fibroblasts on the eight types of scaffold produced were evaluated to assess if the blending method used would influence cell–scaffold interaction. Cell adhesion to the different scaffolds lied in the interval 40–60%, with the CS scaffold presenting the lowest value. Interestingly, cell proliferation was the same when comparing polymer blending and FB scaffolds having 3:1 or 1:3 PCL/CS ratios but very different when the ratio was 1:1 – the FB scaffold sustained a proliferation rate double that of the polymer blending scaffold. This work shows that, when blending polymers to improve the properties of a scaffold for tissue engineering or 3D cell culture, their spatial distribution may considerably affect scaffold's properties and should be considered as another parameter requiring optimization. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47191.