Detection and clearance in Alzheimer’s disease: leading with illusive chemical, structural and morphological features of the targets

Highly specific interactions between biomolecules,such as antigen-antibody,protein-ligand,or nucleic acid base pair complementary are on the basis of the organization of complex organisms.The same principles may be tentatively used in molecular medicine for diagnosis and therapeutics.A molecule can be designed to selectively bind a protease and thereby inhibit the production of a peptide that forms toxic aggregates in the brain or an antibody may be produced to bind specifically to that peptide for detection or clearance purposes.Unfortunately,interference in biological systems is not that simple.For a start there is the inhibition of the physiological role of the protease;moreover,several cleavage fragments may be produced,which may continue to diverge due to putative post-translational modification and self-assembly processes,hiding the toxic target in a“soup”of peptide species varying in size,structure and chemical composition.A perspective of the current status and challenges in targeting peptide species for diagnosis and treatment in the context of Alzheimer’s disease is given.

Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices

The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.

The left-right side-specific endocrine signaling:implications for neurological deficits in stroke and neurodevelopmental disorders

Brain injury-induced neurological deficits typically develop on the contralateral side of the body and include abnormal posture,motor weakness,and spasticity.It is believed that the interruption of descending neural pathways that convey supraspinal commands to the motoneurons in the spinal cord is the main cause of these deficits.

Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

The purpose of the current study was to evaluate the effect of a high-fat （HF） diet, energy restriction and exercise on the expression of vascular endothelial growth factor （VEGF）, angiopoietin （Ang） I and 2, and their receptors in rat corpus cavernosum （CC）. Male Wistar rats were fed adlibitum with an H F diet for 8 or 16 weeks. After 8 weeks of the H F diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays （VEGF, VEGF receptor （VEGFR） I and 2, Angl, Ang2 and Tie2） and semiquantification of VEGF, VEGFR 1, VEGFR2, Angl, Ang2, Tie2, endothelial nitric oxide synthase （eNOS） and Aktlphospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol （HDL-c） levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features.

Biomarkers of psoriasis severity and therapy monitoring

Psoriasis is a chronic, recurrent inflammatory cutaneous disease. Psoriasis patients alternate between periods of remission and periods of exacerbation of the disease. Usually, psoriasis severity is clinically evaluated using tools like Psoriasis Area and Severity Index that present some limitations and subjectivity. Clinicians select the therapy according to psoriasis severity, aiming that patients achieve longer remission periods and improve their quality of life. Biological markers for diagnosis and prognosis of psoriasis help to establish its severity and to monitor the therapeutic response; moreover, biomarkers of psoriasis assist clinicians in their therapeutic decision to treat psoriasis and to choose earlier and more adequate therapeutic strategies, avoiding or minimising worsening of psoriasis. With these markers, they would be able to monitor therapeutics, avoiding unnecessary therapeutic surcharge or changes to a more aggressive therapy. As any attempt to identify these biomarkers should be encouraged, in this review,we will debate published data concerning the proposal of biomarkers to evaluate severity and response to treatment of psoriasis vulgaris.

Expression and activity of heterologous hydroxyisocaproate dehydrogenases in Synechocystis sp.PCC 6803ΔhoxYH

Exploiting light to drive redox reactions is currently a hot topic since light is considered as an environmentally friendly source of energy.Consequently,cyanobacteria,which can use light e.g.,for generating NADPH,are in the focus of research.Previously,it has been shown that various heterologous redox enzymes could be expressed in these microorganisms.Here we demonstrated the successful inducer-free expression of𝛼-keto-acid dehydroge-nases(L-HicDH and D-HicDH)from Lactobacillus confusus DSM 20196 and Lactobacillus paracasei DSM 20008 in Synechocystis sp.PCC 6803ΔhoxYH mutant using replicative plasmids.While the L-HicDH showed poor activity limited by the amount of expressed enzyme,the D-HicDH was applied both in vivo and in vitro,transforming the selected𝛼-keto acids to the corresponding optically pure(R)-𝛼-hydroxy acids(ee>99%)in up to 53%and 90%conversion,respectively.

Assessment of the bioaccessibility and bioavailability prediction of omega 3 and conjugated fatty acids by in vitro standardized digestion model(INFOGEST)and cell model

Omega 3 EPA and DHA are polyunsaturated fatty acids with relevant health benefits.Conjugated linoleic and linolenic acids are known for their anti-carcinogenic effect,anti-inflammatory properties and body weight reduction.To achieve therapeutical doses,high amounts of these fatty acids’food sources must be consumed.Thus,the intake of enriched oils with a high concentration of these fatty acids is often used.But several factors influence their bioavailability.Here,by using the INFOGEST static in vitro protocol of gastrointestinal tract digestion it was studied the bioaccessibility of these fatty acids in different matrixes:Pomegranate and Fish oil and omega 3,CLA and CLNA soft-gel enriched capsules.After digestion,the Recovery Index for the major bioactive PUFAs are very low:Pomegranate oil is 2%,Fish oil 11-13%,CLNA 17%,CLA 6%and Omega 3 capsules 3%.Higher initial concentrations of these PUFAs seem to be related to higher degrees of oxidation.In Pomegranate oil,CLNA and Omega 3 capsules,the digestion process negatively influenced the antioxidant potential.The opposite was verified for the Fish oil and CLA capsules.Importantly,bioaccessibility studies of similar matrixes are very scarce and intestinal permeability is absent in most of the studies.Intestinal permeability studies were performed using a Caco-2/HT29-MTX co-culture:there is significative incorporation of the bioactive fatty acids into the intestinal cells,which may affect their permeability performance.Interestingly,most fatty acids remain in the non-bioaccessible fraction which may be relevant when designing oral routes of administration and in gut microbiota modulation.