Types Of Bioactive Molecules Research Articles

Terminus-Selective Covalent Immobilization of Heparin on a Thermoresponsive Surface Using Click Chemistry for Efficient Binding of Basic Fibroblast Growth Factor.

Cell therapy using endothelial cells (ECs) has great potential for the treatment of congenital disorders, such as hemophilia A. Cell sheet technology utilizing a thermoresponsive culture dish is a promising approach to efficiently transplant donor cells. In this study, a new method to prepare terminus-selective heparin-immobilized thermoresponsive culture surfaces is developed to facilitate the preparation of EC sheets. Alkynes are introduced to the reducing terminus of heparin via reductive amination. Cu-catalyzed azide-alkyne cycloaddition (CuAAC) facilitates efficient immobilization of the terminus of heparin on a thermoresponsive surface, resulting in a higher amount of immobilized heparin while preserving its function. Heparin-immobilized thermoresponsive surfaces prepared using CuAAC exhibit good adhesion to human endothelial colony-forming cells (ECFCs). In addition, upon further binding to basic fibroblast growth factor (bFGF) on heparin-immobilized surfaces, increased proliferation of ECFCs on the surface is observed. The confluent ECFC monolayer cultured on bFGF-bound heparin-immobilized thermoresponsive surfaces exhibits relatively high fibronectin accumulation and cell number and detaches at 22°C while maintaining the sheet-like structure. Because heparin has an affinity for several types of bioactive molecules, the proposed method can be applied to facilitate efficient cultures and sheet formations of various cell types.

Plant hairy roots for the production of extracellular vesicles with antitumor bioactivity

Plant extracellular vesicles (EVs) concentrate and deliver different types of bioactive molecules in human cells and are excellent candidates for a next-generation drug delivery system. However, the lack of standard protocols for plant EV production and the natural variations of their biomolecular cargo pose serious limitation to their use as therapeutics. To overcome these issues, we set up a versatile and standardized procedure to purify plant EVs from hairy root (HR) cultures, a versatile biotechnological system, already successfully employed as source of bioactive molecules with pharmaceutical and nutraceutical relevance. Herewith, we report that HR of Salvia dominica represent an excellent platform for the production of plant EVs. In particular, EVs derived from S. dominica HRs are small round-shaped vesicles carrying typical EV-associated proteins such as cytoskeletal components, chaperon proteins and integral membrane proteins including the tetraspanin TET-7. Interestingly, the HR-derived EVs showed selective and strong pro-apoptotic activity in pancreatic and mammary cancer cells. These results reveal that plant hairy roots may be considered a new promising tool in plant biotechnology for the production of extracellular vesicles for human health.

Discovery of Channa StriataExtracts as Regenerative Medicine in Promoting Wound Healing and Scarless Skin Regeneration

Channa striata (also known as Channa striatus) is an air-breathing freshwater snakehead fish that is well known in the Asian region for its medicinal properties, particularly in wound healing. It is recognised as a traditional medicine (TM), which can be served as alternative treatment method. With the advancement of technology, researchers have made a lot of progress in characterising the biomolecules of this fish. Various types of bioactive molecules have been identified in the fish, and their therapeutic effects are being studied. The C. striata have exhibited antibacterial, antinociceptive and effective wound recovery property through various pharmacology assays. It has been regarded as a source of traditional medicine that could complement modern medicine in promoting human health. The applications of C. striata extracts by practitioners in treating different illnesses are discussed. Besides, the approaches towards scarless wound in future applications involving the snakehead fish are also highlighted. Challenges and solutions to develop an aquatic-derived drug were also covered. The Channa striata extract as a natural product has shown great prospects for wound healing enhancement. Many biomolecules associated with antibacterial and antinociceptive properties, which are crucial for healthy wound recovery were identified in the species. Significant advances and researches in the region have successfully led to a better understanding of the species, which provide a promising future for drug development.

Investigation of human adipose-derived stem-cell behavior using a cell-instructive polydopamine-coated gelatin-alginate hydrogel.

Hydrogels can be fabricated and designed to exert direct control over stem cells' adhesion and differentiation. In this study, we have investigated the use of polydopamine (pDA)-treatment as a binding platform for bioactive compounds to create a versatile gelatin-alginate (Gel-Alg) hydrogel for tissue engineering applications. Precisely, pDA was used to modify the surface properties of the hydrogel and better control the adhesion and osteogenic differentiation of human adipose-derived stem cells (hASCs). pDA enabled the adsorption of different types of bioactive molecules, including a model osteoinductive drug (dexamethasone) as well as a model pro-angiogenic peptide (QK). The pDA treatment efficiently retained the drug and the peptide compared to the untreated hydrogel and proved to be effective in controlling the morphology, cell area, and osteogenic differentiation of hASCs. Overall, the findings of this study confirm the efficacy of pDA treatment as a valuable strategy to modulate the biological properties of biocompatible Gel-Alg hydrogels and further extend their value in regenerative medicine.

A rational in silico approach to identify inhibitors of Batroxrhagin from Bothrops atrox

Bothrops atrox venom comprises several types of bioactive molecules, enzymatic and non-enzymatic, among those, Batroxrhagin is the most predominant SVMP P-III enzyme, which are responsible for induction of local and systemic hemorrhage and muscle fibers damage, impairing regeneration. Due to great difficulties in establishing an antibothropic drug, new strategies must be addressed to achieve a more effective and efficient treatment. There are no studies of specific catalytic inhibitors of Batroxrhagin. However, there are in vitro studies that have described similar metalloprotease inhibitors. The inhibitor batimastat was used as a leading compound for the search and selection of similar candidates. This molecule is widely cited as a metalloprotease inhibitor and as an antimetastatic. In addition to batimastat-like molecules, four other reported metalloprotease inhibitors were included to compose the study's positive control group. Hence, 580 molecules were tested. The three-dimensional structure of B. atrox Batroxrhagin was predicted based on homologous structures using Modeller 9.20. Molecular docking calculation was performed using Autodock 4.2 and molecular surfaces and interactions were analyzed using Biovia/Discovery Studio 2017. Among 576 molecules, 42 similar to batismast resulted in a better energy of interaction than all positive controls, including batimastat itself. The batimastat-like molecules with lowest energy and positive controls were subjected to molecular dynamics for 30 ns in Gromacs 2019.4. This batimastat-like molecule produced better stability among all the Batroxrhagin-ligand complexes analyzed. Overall, the proposed compounds present justifiable evidence for future in vitro tests aiming to inhibit Batroxrhagin. Communicated by Ramaswamy H. Sarma

An effective dual-factor modified 3D-printed PCL scaffold for bone defect repair.

Numerous bioactive molecules produced in cells are involved in the process of bone formation. We consider that appropriate, simultaneous application of two types of bioactive molecules would accelerate the regeneration of tissues and organs. Therefore, we combined aspirin-loaded liposomes (Asp@Lipo) and bone forming peptide-1 (BFP-1) on three dimensional-printed polycaprolactone (PCL) scaffold and determined whether this system improved bone regeneration outcomes. in vitro experiments indicated that Asp@Lipo/BFP-1at a 3:7 ratio was the best option for enhancing the osteogenic efficiency of human mesenchymal stem cells (hMSCs). This was confirmed in an in vivo cranial defect animal model. In addition, RNA-Seq was applied for preliminarily exploration of the mechanism of action of this composite scaffold system, and the results suggested that it mainly improved bone regeneration via the PI3K/AKT signaling pathway. This approach will have potential for application in bone tissue engineering and regenerative medicine.

Aqueous Two-Phase Droplet-Templated Colloidosomes Composed of Self-Formed Particles via Spatial Confined Biomineralization.

A facile and green approach is developed for fabricating colloidosomes with well-controlled size and structure from the microfluidic-generated aqueous two-phase system (ATPS) emulsion droplet. Unlike other methods that rely on self-assembly of externally added colloidal particles at the emulsion interface, urease-mediated biomineralization induced by "drainage" is introduced to form CaCO3 particles at the alginate emulsion interface for preparing Ca-alg@CaCO3 colloidosomes. Two types of bioactive molecules (bovine serum albumin and catalase) can be encapsulated with high efficiency (>85%) because of the partitioning effect of the ATPS and high viscosity of alginate solution. The encapsulated bioactive molecules can be controllably released by regulating the compactness of colloidosomes. Moreover, after being freeze-dried or dried at 37 °C, the activity of catalase in colloidosomes is obviously higher than that in alginate hydrogels, which confirms that the Ca-alg@CaCO3 structure has strong protection for inclusions. We believe that the biocompatible and controllable Ca-alg@CaCO3 colloidosomes possess great potential applications in bioencapsulation for foods, daily chemicals, and synthetic protocell formation.

DNA nanostructure-based universal microarray platform for high-efficiency multiplex bioanalysis in biofluids.

Microarrays of biomolecules have greatly promoted the development of the fields of genomics, proteomics, and clinical assays because of their remarkably parallel and high-throughput assay capability. Immobilization strategies for biomolecules on a solid support surface play a crucial role in the fabrication of high-performance biological microarrays. In this study, rationally designed DNA tetrahedra carrying three amino groups and one single-stranded DNA extension were synthesized by the self-assembly of four oligonucleotides, followed by high-performance liquid chromatography purification. We fabricated DNA tetrahedron-based microarrays by covalently coupling the DNA tetrahedron onto glass substrates. After their biorecognition capability was evaluated, DNA tetrahedron microarrays were utilized for the analysis of different types of bioactive molecules. The gap hybridization strategy, the sandwich configuration, and the engineering aptamer strategy were employed for the assay of miRNA biomarkers, protein cancer biomarkers, and small molecules, respectively. The arrays showed good capability to anchor capture biomolecules for improving biorecognition. Addressable and high-throughput analysis with improved sensitivity and specificity had been achieved. The limit of detection for let-7a miRNA, prostate specific antigen, and cocaine were 10 fM, 40 pg/mL, and 100 nM, respectively. More importantly, we demonstrated that the microarray platform worked well with clinical serum samples and showed good relativity with conventional chemical luminescent immunoassay. We have developed a novel approach for the fabrication of DNA tetrahedron-based microarrays and a universal DNA tetrahedron-based microarray platform for the detection of different types of bioactive molecules. The microarray platform shows great potential for clinical diagnosis.

Gold nanostructures encoded by non-fluorescent small molecules in polyA-mediated nanogaps as universal SERS nanotags for recognizing various bioactive molecules

Surface-enhanced Raman scattering (SERS) has recently been used to design novel nanoprobes called “SERS tags” which hold great promise for the fields of biosensing and nanomedicine. More recent advances have shed new light on the synthesis of uniform nanostructures with interior nanogaps for stable SERS enhancement. However, producing interior nanogap-based SERS nanotags directly and controllably with strong and stable multiplex SERS signals as well as developing a multiplex analytical platform to recognize different types of bioactive molecules still remain highly challenging. To address this challenge, we herein develop a novel approach for the direct synthesis of nanogap-based universal SERS nanotags by mediating poly-adenine (polyA) and encoding non-fluorescent small molecules. The universal nanotags were then functionalized by different types of biological probes and used as SERS nanoprobes to recognize various bioactive molecules. To the best of our knowledge, this is the first example of using SERS nanotags to develop a simultaneous multianalysis platform for all of the major types of bioactive analytes, including nucleic acids, proteins and small molecules. Furthermore, the nanotags show great promise for fluorescence-SERS bimodal bioanalysis and bioimaging.

Synthesis of new 4-methyl-3-piperidones via an iron-catalyzed intramolecular tandem isomerization–aldolisation process

A new versatile synthesis of 3-piperidones is described, starting from amino acids. It uses, as a key step, an iron carbonyl-mediated intramolecular tandem isomerization–aldolisation reaction. These new heterocycles appear as useful scaffolds for the total synthesis of various types of bioactive molecules.

Abstract 1487: Tumor-derived microvesicles induce proangiogenic phenotype in endothelial cells via endocytosis

Abstract Background: Increasing evidence indicates that tumor endothelial cells (TEC) differ from normal endothelial cells (NEC). Our previous reports also showed that TEC were different from NEC. For example, TEC have chromosomal abnormality and proangiogenic properties such as high motility and proliferative activity. However, the mechanism by which TEC acquire a specific character remains unclear. To investigate this mechanism, we focused on tumor-derived microvesicles (TMV). Recent studies have shown that TMV contain numerous types of bioactive molecules and affect normal stromal cells in the tumor microenvironment. However, most of the functional mechanisms of TMV remain unclear. Methodology/Principal Findings: Here we showed that TMV isolated from tumor cells were taken up by NEC through endocytosis. In addition, we found that TMV promoted random motility and tube formation through the activation of the phosphoinositide 3-kinase/Akt pathway in NEC. Moreover, the effects induced by TMV were inhibited by the endocytosis inhibitor dynasore. Our results indicate that TMV could confer proangiogenic properties to NEC partly via endocytosis. Conclusion: We for the first time showed that endocytosis of TMV contributes to tumor angiogenesis. These findings offer new insights into cancer therapies and the crosstalk between tumor and endothelial cells mediated by TMV in the tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1487. doi:1538-7445.AM2012-1487

Controlled heparin conjugation on electrospun poly(ε-caprolactone)/gelatin fibers for morphology-dependent protein delivery and enhanced cellular affinity

Electrospun fibrous scaffolds have now been shown to possess great potential for tissue engineering applications, owing to their unique mimicry of natural extracellular matrix structure. In this study, poly(ε-caprolactone) and gelatin were electrospun to fabricate tissue-engineered scaffolds with three different fiber morphologies (1.0μm, 3.0μm and co-electrospun containing both 1.0 and 3.0μm diameter fibers). Subsequently, these scaffolds were conjugated with heparin to immobilize a bioactive molecule by electrostatic interactions. This study determined the quantity of heparin conjugation on the scaffolds and that the crosslinking time and the fiber morphologies govern the extent of heparin conjugation on the fibers. In order to evaluate the release capacity of the heparin-conjugated scaffolds, lysozyme was used as a model protein for conjugation. The heparin-conjugated scaffolds provided high loading efficiency and cumulative release of lysozyme with a relatively linear relationship. In addition, the release kinetics was significantly dependent on heparin conjugation and fiber morphology. This fundamental investigation into how fiber morphology and crosslinking protocols can affect the heparin binding ability of electrospun fibers is crucial for predicting the delivery of many different types of bioactive molecules from an electrospun scaffold for tissue engineering applications.

Antibacterial activity of rare Streptomyces species against clinical resistant bacteria

In the search for new antibiotics from Steptomyces, investigating extremes habitats enhances the probability of isolating novel producers. In this context, the antibacterial activity of four Streptomyces strains isolated from Ezzmoul saltpans was studied. Two of them showed antibacterial activity against antibiotic's resistant bacteria (Bacillus cereus: β-lactamines and sulfamides resistant, Streptococcus faecalis: penicillin, tetracycline and cotrimoxazole resistant, and Staphylococcus aureus Mu 50: vancomycine resistant). The most active Streptomyces strain produces one type of polar bioactive molecules that resists to temperature variation and light exposition. Its activity appears in the first culture day and reaches its maximal value in the fourth day. The second strain presents themoresistant activity that reaches its maximal value in the first culture day. It produces two types of bioactive molecules, one is polar and the second is non polar (according to thin layer chromatography technique results).