Nanofibrous ε-Polycaprolactone Matrices Containing Nano-Hydroxyapatite and Humulus lupulus L. Extract: Physicochemical and Biological Characterization for Oral Applications.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study, poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their potential for drug delivery and bone regeneration. The fabricated matrices were analyzed using scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FTIR assay, and in vitro hydrolytic degradation. The antimicrobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved using the MTT assay. SEM analysis established the nanostructured matrices present in the three-dimensional interconnected network. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and have the potential to be used in oral applications.

Target Genes of c-MYC and MYCN with Prognostic Power in Neuroblastoma Exhibit Different Expressions during Sympathoadrenal Development.

Deregulation of the MYC family of transcription factors c-MYC (encoded by MYC), MYCN, and MYCL is prevalent in most human cancers, with an impact on tumor initiation and progression, as well as response to therapy. In neuroblastoma (NB), amplification of the MYCN oncogene and over-expression of MYC characterize approximately 40% and 10% of all high-risk NB cases, respectively. However, the mechanism and stage of neural crest development in which MYCN and c-MYC contribute to the onset and/or progression of NB are not yet fully understood. Here, we hypothesized that subtle differences in the expression of MYCN and/or c-MYC targets could more accurately stratify NB patients in different risk groups rather than using the expression of either MYC gene alone. We employed an integrative approach using the transcriptome of 498 NB patients from the SEQC cohort and previously defined c-MYC and MYCN target genes to model a multigene transcriptional risk score. Our findings demonstrate that defined sets of c-MYC and MYCN targets with significant prognostic value, effectively stratify NB patients into different groups with varying overall survival probabilities. In particular, patients exhibiting a high-risk signature score present unfavorable clinical parameters, including increased clinical risk, higher INSS stage, MYCN amplification, and disease progression. Notably, target genes with prognostic value differ between c-MYC and MYCN, exhibiting distinct expression patterns in the developing sympathoadrenal system. Genes associated with poor outcomes are mainly found in sympathoblasts rather than in chromaffin cells during the sympathoadrenal development.

An origami-based technique for simple, effective and inexpensive fabrication of highly aligned far-field electrospun fibers.

Fabrication of highly aligned fibers by far-field electrospinning is a challenging task to accomplish. Multiple studies present advances in the alignment of electrospun fibers which involve modification of the conventional electrospinning setup with complex additions, multi-phased fabrication, and expensive components. This study presents a new collector design with an origami structure to produce highly-aligned far-field electrospun fibers. The origami collector mounts on the rotating drum and can be easily attached and removed for each round of fiber fabrication. This simple, effective, and inexpensive technique yields high-quality ultra-aligned fibers while the setup remains intact for other fabrication types. The electrospun poly(ɛ-caprolactone) (PCL) fibers were assessed by scanning electron microscope (SEM), fiber diameter distribution, water contact angle (WCA), Fast Fourier Transform analysis (FFT), surface plot profile, and pixel intensity plots. We thoroughly explored the impact of influential parameters, including polymer concentration, injection rate, collector rotation speed, distance from the collector to the tip, and needle gauge number on fibers' quality and alignment. Moreover, we employed machine learning algorithms to predict the outcomes and classify the high-quality fibers instead of low-quality productions.

Drug-Eluting, Bioresorbable Cardiovascular Stents─Challenges and Perspectives.

Globally, the leading causes of natural death are attributed to coronary heart disease and type 1 and type 2 diabetes. High blood pressure levels, high cholesterol levels, smoking, and poor eating habits lead to the agglomeration of plaque in the arteries, reducing the blood flow. The implantation of devices used to unclog vessels, known as stents, sometimes results in a lack of irrigation due to the excessive proliferation of endothelial tissue within the blood vessels and is known as restenosis. The use of drug-eluting stents (DESs) to deliver antiproliferative drugs has led to the development of different encapsulation techniques. However, due to the potency of the drugs used in the initial stent designs, a chronic inflammatory reaction of the arterial wall known as thrombosis can cause a myocardial infarction (MI). One of the most promising drugs to reduce this risk is everolimus, which can be encapsulated in lipid systems for controlled release directly into the artery. This review aims to discuss the current status of stent design, fabrication, and functionalization. Variables such as the mechanical properties, metals and their alloys, drug encapsulation and controlled elution, and stent degradation are also addressed. Additionally, this review covers the use of polymeric surface coatings on stents and the recent advances in layer-by-layer coating and drug delivery. The advances in nanoencapsulation techniques such as liposomes and micro- and nanoemulsions and their functionalization in bioresorbable, drug-eluting stents are also highlighted.

The evolution of nutrition intervention during the COVID-19 pandemic / A evolução da intervenção nutricional durante a pandemia de COVID-19

Abstract COVID-19 has challenged health professionals in widely divergent areas, including innovation of practice, communication, multidisciplinary activities, broader use of technology, and adaptability. The role of the dietitian and other health professionals in dealing with the evolving crisis might be considered essential in treating patients. Given the limited access to various food options, nutrition screening and assessment deserves a high priority to complete a comprehensive nutrition evaluation, identify nutrition risks, prioritize care, and provide early nutrition intervention and support to all patients with or who have had, COVID-19 and are experiencing ongoing symptoms. Such an intervention would benefit the patients and the health system by reducing the length of hospital stay, ameliorating further complications, limiting hospital readmission, enhancing recovery, and assisting in the management of comorbidities and their metabolic alterations. This brief overview outlines the essential role of nutrition intervention and support as part of an integrated, multidisciplinary treatment program for the care of COVID-19 patients during the pandemic. Restrictive movements have changed consultative approaches, and the importance of Telenutrition for the effective communication of health status and recommendations.

Resumo A COVID-19 desafiou profissionais de saúde em diversas áreas, incluindo inovação da prática, comunicação, atividades multidisciplinares, uso amplo de tecnologia e adaptabilidade. O papel do nutricionista e de outros profissionais de saúde para lidar com a crise em expansão pode ser considerado essencial no tratamento de pacientes. Devido ao acesso limitado a várias opções de alimentos, a triagem e a avaliação nutricional devem ser priorizadas para a obtenção de uma avaliação nutricional abrangente, a fim de identificar riscos nutricionais, priorizar atendimento e possibilitar a intervenção nutricional precoce e o apoio a todos os pacientes com, ou que tiveram, COVID-19 e apresentem sintomas contínuos. Tal intervenção traria grande benefício aos pacientes e ao sistema de saúde, ao reduzir o tempo de internação, amenizar complicações posteriores, limitar a readmissão hospitalar, potencializar a recuperação e auxiliar no manejo das comorbidades e suas alterações metabólicas. Esta breve descrição elucida o papel essencial da intervenção nutricional e do apoio como parte de um programa de tratamento multidisciplinar para o cuidado de pacientes com COVID-19 durante a pandemia. Movimentos restritivos mudaram as abordagens consultivas e a importância da telenutrição para a comunicação eficaz do estado de saúde e das recomendações.

COVID-19: the impact on oral health care / COVID-19: o impacto na saúde bucal

Abstract The COVID-19 pandemic has highlighted the economic, social, and oral care health inequities in societies, especially in the developing world. Severe restrictions have been imposed on dental practices, limiting prophylactic and routine oral care health, allowing treatment only for emergencies. Since dental care includes procedures that generate aerosols, the risk of infection for dental personnel has increased significantly. In this review, a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the impacts it is having on oral health care is presented. The ongoing repercussions in dental practice and in dental education, including the opportunities for practice innovation that are evolving, are also indicated. Also, a discussion of the psychosocial factors that affect health and the quality of life of an individual, such as stress, depression, and anxiety, is provided. This pandemic may be an opportunity to promote the inclusion of well-established prevention measures, together with the use of teledentistry in academic dental curricula, encourage the implementation of new perspectives for the effective instruction and interactions with students, and foster the transition toward e-learning strategies in dental education.

Resumo A pandemia COVID-19 destacou as desigualdades econômicas, sociais e de saúde bucal, especialmente no mundo em desenvolvimento. Severas restrições têm sido impostas para a prática odontológica, limitando a rotina de saúde bucal, permitindo o tratamento apenas em emergências. Como o atendimento odontológico inclui procedimentos que geram aerossóis, o risco de infecção para a equipe odontológica aumentou significativamente. Nesta revisão, é abordada uma fonte abrangente e atualizada de informações sobre o SARS-CoV-2/COVID-19 e os impactos que têm nos cuidados de saúde bucal. As repercussões contínuas na profissão odontológica e na educação odontológica, incluindo as oportunidades de inovação da prática. Além disso, é fornecido o efeito de fatores psicossociais que afetam a saúde e a qualidade de vida, como estresse, depressão e ansiedade. Esta pandemia pode ser uma oportunidade para promover a inclusão de medidas de prevenção bem estabelecidas, juntamente com o uso da teledontologia nos currículos acadêmicos de odontologia, trazendo novas perspectivas sobre a forma de ensinar e interagir com os alunos, com a transição para estratégias de e-learning na educação odontológica.

Expression and activation of nuclear hormone receptors result in neuronal differentiation and favorable prognosis in neuroblastoma.

BACKGROUND: Neuroblastoma (NB), a childhood tumor derived from the sympathetic nervous system, presents with heterogeneous clinical behavior. While some tumors regress spontaneously without medical intervention, others are resistant to therapy, associated with an aggressive phenotype. MYCN-amplification, frequently occurring in high-risk NB, is correlated with an undifferentiated phenotype and poor prognosis. Differentiation induction has been proposed as a therapeutic approach for high-risk NB. We have previously shown that MYCN maintains an undifferentiated state via regulation of the miR-17 ~ 92 microRNA cluster, repressing the nuclear hormone receptors (NHRs) estrogen receptor alpha (ERα) and the glucocorticoid receptor (GR). METHODS: Cell viability was determined by WST-1. Expression of differentiation markers was analyzed by Western blot, RT-qPCR, and immunofluorescence analysis. Metabolic phenotypes were studied using Agilent Extracellular Flux Analyzer, and accumulation of lipid droplets by Nile Red staining. Expression of angiogenesis, proliferation, and neuronal differentiation markers, and tumor sections were assessed by immunohistochemistry. Gene expression from NB patient as well as adrenal gland cohorts were analyzed using GraphPad Prism software (v.8) and GSEA (v4.0.3), while pseudo-time progression on post-natal adrenal gland cells from single-nuclei transcriptome data was computed using scVelo. RESULTS: Here, we show that simultaneous activation of GR and ERα potentiated induction of neuronal differentiation, reduced NB cell viability in vitro, and decreased tumor burden in vivo. This was accompanied by a metabolic reprogramming manifested by changes in the glycolytic and mitochondrial functions and in lipid droplet accumulation. Activation of the retinoic acid receptor alpha (RARα) with all-trans retinoic acid (ATRA) further enhanced the differentiated phenotype as well as the metabolic switch. Single-cell nuclei transcriptome analysis of human adrenal glands indicated a sequential expression of ERα, GR, and RARα during development from progenitor to differentiated chromaffin cells. Further, in silico analysis revealed that patients with higher combined expression of GR, ERα, and RARα mRNA levels had elevated expression of neuronal differentiation markers and a favorable outcome. CONCLUSION: Together, our findings suggest that combination therapy involving activation of several NHRs could be a promising pharmacological approach for differentiation treatment of NB patients.

COVID-19: the impact on oral health care.

The COVID-19 pandemic has highlighted the economic, social, and oral care health inequities in societies, especially in the developing world. Severe restrictions have been imposed on dental practices, limiting prophylactic and routine oral care health, allowing treatment only for emergencies. Since dental care includes procedures that generate aerosols, the risk of infection for dental personnel has increased significantly. In this review, a comprehensive and updated source of information about SARS-CoV-2/COVID-19 and the impacts it is having on oral health care is presented. The ongoing repercussions in dental practice and in dental education, including the opportunities for practice innovation that are evolving, are also indicated. Also, a discussion of the psychosocial factors that affect health and the quality of life of an individual, such as stress, depression, and anxiety, is provided. This pandemic may be an opportunity to promote the inclusion of well-established prevention measures, together with the use of teledentistry in academic dental curricula, encourage the implementation of new perspectives for the effective instruction and interactions with students, and foster the transition toward e-learning strategies in dental education.

The evolution of nutrition intervention during the COVID-19 pandemic.

COVID-19 has challenged health professionals in widely divergent areas, including innovation of practice, communication, multidisciplinary activities, broader use of technology, and adaptability. The role of the dietitian and other health professionals in dealing with the evolving crisis might be considered essential in treating patients. Given the limited access to various food options, nutrition screening and assessment deserves a high priority to complete a comprehensive nutrition evaluation, identify nutrition risks, prioritize care, and provide early nutrition intervention and support to all patients with or who have had, COVID-19 and are experiencing ongoing symptoms. Such an intervention would benefit the patients and the health system by reducing the length of hospital stay, ameliorating further complications, limiting hospital readmission, enhancing recovery, and assisting in the management of comorbidities and their metabolic alterations. This brief overview outlines the essential role of nutrition intervention and support as part of an integrated, multidisciplinary treatment program for the care of COVID-19 patients during the pandemic. Restrictive movements have changed consultative approaches, and the importance of Telenutrition for the effective communication of health status and recommendations.

Dental Applications of Carbon Nanotubes.

Glass ionomer cements and resin-based composites are promising materials in restorative dentistry. However, their limited mechanical properties and the risk of bulk/marginal fracture compromise their lifespan. Intensive research has been conducted to understand and develop new materials that can mimic the functional behavior of the oral cavity. Nanotechnological approaches have emerged to treat oral infections and become a part of scaffolds for tissue regeneration. Carbon nanotubes are promising materials to create multifunctional platforms for dental applications. This review provides a comprehensive survey of and information on the status of this state-of-the-art technology and describes the development of glass ionomers reinforced with carbon nanotubes possessing improved mechanical properties. The applications of carbon nanotubes in drug delivery and tissue engineering for healing infections and lesions of the oral cavity are also described. The review concludes with a summary of the current status and presents a vision of future applications of carbon nanotubes in the practice of dentistry.

Longitudinal In-Vivo X-Ray Fluorescence Computed Tomography With Molybdenum Nanoparticles.

X-ray fluorescence computed tomography (XFCT) with nanoparticles (NPs) as contrast agents shows potential for molecular biomedical imaging with higher spatial resolution than present methods. To date the technique has been demonstrated on phantoms and mice, however, parameters such as radiation dose, exposure times and sensitivity have not yet allowed for high-spatial-resolution in vivo longitudinal imaging, i.e., imaging of the same animal at different time points. Here we show in vivo XFCT with spatial resolution in the 200- [Formula: see text] range in a proof-of-principle longitudinal study where mice are imaged five times each during an eight-week period following tail-vein injection of NPs. We rely on a 24 keV x-ray pencil-beam-based excitation of in-house-synthesized molybdenum oxide NPs (MoO2) to provide the high signal-to-background x-ray fluorescence detection necessary for XFCT imaging with low radiation dose and short exposure times. We quantify the uptake and clearance of NPs in vivo through imaging, and monitor animal well-being over the course of the study with support from histology and DNA stability analysis to assess the impact of x-ray exposure and NPs on animal welfare. We conclude that the presented imaging arrangement has potential for in vivo longitudinal studies, putting emphasis on designing biocompatible NPs as the future focus for active-targeting preclinical XFCT.

Influence of Controlled Cooling on Crystallinity of Poly (L-Lactic Acid) Scaffolds after Hydrolytic Degradation.

The use of hybrid manufacturing to produce bimodal scaffolds has represented a great advancement in tissue engineering. These scaffolds provide a favorable environment in which cells can adhere and produce new tissue. However, there are several areas of opportunity to manufacture structures that provide enough strength and rigidity, while also improving chemical integrity. As an advancement in the manufacturing process of scaffolds, a cooling system was introduced in a fused deposition modeling (FDM) machine to vary the temperature on the printing bed. Two groups of polylactic acid (PLA) scaffolds were then printed at two different bed temperatures. The rate of degradation was evaluated during eight weeks in Hank's Balanced Salt Solution (HBSS) in a controlled environment (37 °C-120 rpm) to assess crystallinity. Results showed the influence of the cooling system on the degradation rate of printed scaffolds after the immersion period. This phenomenon was attributable to the mechanism associated with alkaline hydrolysis, where a higher degree of crystallinity obtained in one group induced greater rates of mass loss. The overall crystallinity was observed, through differential scanning calorimetry (DSC), thermo gravimetric analysis (TGA), and Fourier transformed infrared spectroscopy (FTIR) analysis, to increase with time because of the erosion of some amorphous parts after immersion.

Latest Updates in Dengue Fever Therapeutics: Natural, Marine and Synthetic Drugs.

In this paper, we review the history of Dengue, the mechanism of infection, the molecular characteristics and components of Dengue, the mechanism of entry to the target cells, cyclization of the genome and replication process, as well as translation of the proteins for virus assembly. The major emphasis of this work is on natural products and plant extracts, which were used for as palliative or adjuvant treatment of Dengue. This review article also summarizes the latest findings in regards to the marine products as effective drugs to target different symptoms of Dengue. Furthermore, an update on synthetic drugs for treating Dengue is provided in this review. As a novel alternative, we describe monoclonal antibody therapy for Dengue management and treatment.

Dengue Fever: A Worldwide Threat An Overview of the Infection Process, Environmental Factors for a Global Outbreak, Diagnostic Platforms and Vaccine Developments.

Current review article focuses on dengue, which is one of the most fatal infectious illnesses and is considered to be a worldwide threat. The paper covers essential topics including an overview on neglected tropical diseases with specific emphasis on Dengue fever, mosquito's cycle of life and mechanism of infection, adaptive response, and different stages in dengue immunopathogenesis. The current work is also dedicated to the thorough study of dengue outbreak across the globe with a narrowed study to tropical and subtropical regions. Moreover, this review article demonstrates the correlation between climate factors and dengue incidence. Furthermore, we present an overview of the detection strategies of dengue including the latest developments in commercial and non-commercial platforms. Several attempts in developing an effective vaccine to protect individuals from dengue infection and the stage of clinical trials are gathered in the present work as well. Future directions including bio-control are also discussed in this review article. In an overall view, effective management of Dengue is a multidisciplinary task that requires international involvement from different backgrounds and expertise to address this global concern. This review article briefly portrays some of these connecting areas across the disciplines while many other perspectives remain uncovered.

GLUT1 protects prostate cancer cells from glucose deprivation-induced oxidative stress.

Glucose, chief metabolic support for cancer cell survival and growth, is mainly imported into cells by facilitated glucose transporters (GLUTs). The increase in glucose uptake along with tumor progression is due to an increment of facilitative glucose transporters as GLUT1. GLUT1 prevents cell death of cancer cells caused by growth factors deprivation, but there is scarce information about its role on the damage caused by glucose deprivation, which usually occurs within the core of a growing tumor. In prostate cancer (PCa), GLUT1 is found in the most aggressive tumors, and it is regulated by androgens. To study the response of androgen-sensitive and insensitive PCa cells to glucose deprivation and the role of GLUT1 on survival mechanisms, androgen-sensitive LNCaP and castration-resistant LNCaP-R cells were employed. Results demonstrated that glucose deprivation induced a necrotic type of cell death which is prevented by antioxidants. Androgen-sensitive cells show a higher resistance to cell death triggered by glucose deprivation than castration-resistant cells. Glucose removal causes an increment of H2O2, an activation of androgen receptor (AR) and a stimulation of AMP-activated protein kinase activity. In addition, glucose removal increases GLUT1 production in androgen sensitive PCa cells. GLUT1 ectopic overexpression makes PCa cells more resistant to glucose deprivation and oxidative stress-induced cell death. Under glucose deprivation, GLUT1 overexpressing PCa cells sustains mitochondrial SOD2 activity, compromised after glucose removal, and significantly increases reduced glutathione (GSH). In conclusion, androgen-sensitive PCa cells are more resistant to glucose deprivation-induced cell death by a GLUT1 upregulation through an enhancement of reduced glutathione levels.

MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling.

Neuroblastoma (NB) is a remarkably heterogenic childhood tumor of the sympathetic nervous system with clinical behavior ranging from spontaneous regression to poorly differentiated tumors and metastasis. MYCN is amplified in 20% of cases and correlates with an undifferentiated, aggressive phenotype and poor prognosis. Estrogen receptor alpha (ERα) and the nerve growth factor (NGF) receptors TrkA and p75NTR are involved in neuronal differentiation and survival. We have previously shown that MYCN, via miR-18a, targets ERα in NB cells. Here, we demonstrate that interference with miR-18a or overexpression of ERα is sufficient to induce NGF signaling and to modulate both basal and NGF-induced neuronal differentiation in MYCN-amplified NB cells. Proteomic analysis confirmed an increase of neuronal features and showed that processes linked to tumor initiation and progression were inhibited upon ERα overexpression. Indeed, ectopic ERα expression was sufficient to inhibit metabolic activity and tumorigenic processes, including glycolysis, oxidative phosphorylation, cell viability, migration, and anchorage independent growth. Importantly, ERα overexpression reduced tumor burden in NB mouse models and high ERα levels were linked to improved survival in patients. In addition to ERα, several other nuclear hormone receptors (NHRs), including the glucocorticoid and the retinoic acid receptors, correlated with clinical markers for favorable and low-stage NB disease. Our data suggest that MYCN targets ERα and thereby NGF signaling to maintain an undifferentiated and aggressive phenotype. Notably, we identified the estrogen-NGF crosstalk, as well as a set of other NHRs, as potential prognostic markers and targets for therapeutic strategies against NB.

Polymethacrylate Coated Electrospun PHB Fibers as a Functionalized Platform for Bio-Diagnostics: Confirmation Analysis on the Presence of Immobilized IgG Antibodies against Dengue Virus.

In this article, a combination of far field electrospinning (FFES) and free-radical polymerization has been used to create a unique platform for protein immobilization via the physical attachment of biomolecules to the surface of the fiber mats. The large specific surface area of the fibers with its tailored chemistry provides a desirable platform for effective analyte-surface interaction. The detailed analysis of protein immobilization on a newly developed bio-receptive surface plays a vital role to gauge its advantages in bio-diagnostic applications. We relied on scanning electron microscopy (SEM), diameter range analysis, and X-ray photoelectron spectroscopy (XPS), along with thermal gravimetric analysis (TGA), water-in-air contact angle analysis (WCA), Fourier transform infrared spectroscopy (FTIR), and atomic force microscopy (AFM) to study our developed platforms and to provide valuable information regarding the presence of biomolecular entities on the surface. Detailed analyses of the fiber mats before and after antibody immobilization have shown obvious changes on the surface of the bioreceptive surface including: (i) an additional peak corresponding to the presence of an antibody in TGA analysis; (ii) extra FTIR peaks corresponding to the presence of antibodies on the coated fiber platforms; and (iii) a clear alteration in surface roughness recorded by AFM analysis. Confirmation analyses on protein immobilization are of great importance as they underlay substantial grounds for various biosensing applications.

Influence of Controlled Cooling in Bimodal Scaffold Fabrication Using Polymers with Different Melting Temperatures.

The combination of different materials and capabilities to manufacture at several scales open new possibilities in scaffold design for bone regeneration. This work is focused on bimodal scaffolds that combine polylactic acid (PLA) melt extruded strands with polycaprolactone (PCL) electrospun fibers. This type of bimodal scaffold offers better mechanical properties, compared to the use of PCL for the extruded strands, and provides potential a means for controlled drug and/or growth factor delivery through the electrospun fibers. The technologies of fused deposition modeling (FDM) and electrospinning were combined to create 3D bimodal constructs. The system uses a controlled cooling system allowing the combination of polymers with different melting temperatures to generate integrated scaffold architecture. The thermoplastic polymers used in the FDM process enhance the mechanical properties of the bimodal scaffold and control the pore structure. Integrated layers of electrospun microfibers induce an increase of the surface area for cell culture purposes, as well as potential in situ controlled drug and/or growth factor delivery. The proposed bimodal scaffolds (PLA extruded strands and PCL electrospun fibers) show appropriate morphology and better mechanical properties when compared to the use of PCL extruded strands. On average, bimodal scaffolds with overall dimensions of 30 × 30 × 2.4 mm³ (strand diameter of 0.5 mm, strand stepover of 2.5 mm, pore size of 2 mm, and layer height of 0.3 mm) showed scaffold stiffness of 23.73 MPa and compression strength of 3.85 MPa. A cytotoxicity assay based human fibroblasts showed viability of the scaffold materials.

Anticancer potential of Thevetia peruviana fruit methanolic extract.

BACKGROUND: Thevetia peruviana (Pers.) K. Schum or Cascabela peruviana (L.) Lippold (commonly known as ayoyote, codo de fraile, lucky nut, or yellow oleander), native to Mexico and Central America, is a medicinal plant used traditionally to cure diseases like ulcers, scabies, hemorrhoids and dissolve tumors. The purpose of this study was to evaluate the cytotoxic, antiproliferative and apoptotic activity of methanolic extract of T. peruviana fruits on human cancer cell lines. METHODS: The cytotoxic activity of T. peruviana methanolic extract was carried out on human breast, colorectal, prostate and lung cancer cell lines and non-tumorigenic control cells (fibroblast and Vero), using the MTT assay. For proliferation and motility, clonogenic and wound-healing assays were performed. Morphological alterations were monitored by trypan blue exclusion, as well as DNA fragmentation and AO/EB double staining was performed to evaluate apoptosis. The extract was separated using flash chromatography, and the resulting fractions were evaluated on colorectal cancer cells for their cytotoxic activity. The active fractions were further analyzed through mass spectrometry. RESULTS: The T. peruviana methanolic extract exhibited cytotoxic activity on four human cancer cell lines: prostate, breast, colorectal and lung, with values of IC50 1.91 ± 0.76, 5.78 ± 2.12, 6.30 ± 4.45 and 12.04 ± 3.43 µg/mL, respectively. The extract caused a significant reduction of cell motility and colony formation on all evaluated cancer cell lines. In addition, morphological examination displayed cell size reduction, membrane blebbing and detachment of cells, compared to non-treated cancer cell lines. The T. peruviana extract induced apoptotic cell death, which was confirmed by DNA fragmentation and AO/EB double staining. Fractions 4 and 5 showed the most effective cytotoxic activity and their MS analysis revealed the presence of the secondary metabolites: thevetiaflavone and cardiac glycosides. CONCLUSION: T. peruviana extract has potential as natural anti-cancer product with critical effects in the proliferation, motility, and adhesion of human breast and colorectal cancer cells, and apoptosis induction in human prostate and lung cancer cell lines, with minimal effects on non-tumorigenic cell lines.

Thioredoxin 1 modulates apoptosis induced by bioactive compounds in prostate cancer cells.

Accumulating evidence suggests that natural bioactive compounds, alone or in combination with traditional chemotherapeutic agents, could be used as potential therapies to fight cancer. In this study, we employed four natural bioactive compounds (curcumin, resveratrol, melatonin, and silibinin) and studied their role in redox control and ability to promote apoptosis in androgen sensitive and insensitive prostate cancer cells. Here is shown that curcumin and resveratrol promote ROS production and induce apoptosis in LNCaP and PC-3. An increase in reactive species is a trigger event in curcumin-induced apoptosis and a consequence of resveratrol effects on other pathways within these cells. Moreover, here we demonstrated that these four compounds affect differently one of the main intracellular redox regulator, the thioredoxin system. Exposure to curcumin and resveratrol promoted TRX1 oxidation and altered its subcellular location. Furthermore, resveratrol diminished TRX1 levels in PC-3 cells and increased the expression of its inhibitor TXNIP. Conversly, melatonin and silibinin only worked as cytostatic agents, reducing ROS levels and showing preventive effects against TRX oxidation. All together, this work explores the effect of compounds currently tested as chemo-preventive agents in prostate cancer therapy, on the TRX1 redox state and function. Our work shows the importance that the TRX system might have within the differences found in their mechanisms of action. These bioactive compounds trigger different responses and affect ROS production and redox systems in prostate cancer cells, suggesting the key role that redox-related pathways might play in processes like differentiation or survival in prostate cancer.