Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration

SmartBone^® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.     

Expression of Opioid Receptors in Cells of the Immune System

The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.     

4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene,a Major Active Metabolite of Bisphenol A,Triggers Pancreatic β-Cell Death via a JNK/AMPKα Activation-Regulated Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway

4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), a major active metabolite of bisphenol A (BPA), is generated in the mammalian liver. Some studies have suggested that MBP exerts greater toxicity than BPA. However, the mechanism underlying MBP-induced pancreatic β-cell cytotoxicity remains largely unclear. This study demonstrated the cytotoxicity of MBP in pancreatic β-cells and elucidated the cellular mechanism involved in MBP-induced β-cell death. Our results showed that MBP exposure significantly reduced cell viability, caused insulin secretion dysfunction, and induced apoptotic events including increased caspase-3 activity and the expression of active forms of caspase-3/-7/-9 and PARP protein. In addition, MBP triggered endoplasmic reticulum (ER) stress, as indicated by the upregulation of GRP 78, CHOP, and cleaved caspase-12 proteins. Pretreatment with 4-phenylbutyric acid (4-PBA; a pharmacological inhibitor of ER stress) markedly reversed MBP-induced ER stress and apoptosis-related signals. Furthermore, exposure to MBP significantly induced the protein phosphorylation of JNK and AMP-activated protein kinase (AMPK)α. Pretreatment of β-cells with pharmacological inhibitors for JNK (SP600125) and AMPK (compound C), respectively, effectively abrogated the MBP-induced apoptosis-related signals. Both JNK and AMPK inhibitors also suppressed the MBP-induced activation of JNK and AMPKα and of each other. In conclusion, these findings suggest that MBP exposure exerts cytotoxicity on β-cells via the interdependent activation of JNK and AMPKα, which regulates the downstream apoptotic signaling pathway.     

Mesenchymal and Proneural Subtypes of Glioblastoma Disclose Branching Based on GSC Associated Signature

Glioblastomas (GBM)—the most common, therapy-resistant, and lethal tumors driven by populations of glioma stem cells (GSCs) are still on the list of the most complicated pathologies. Thus, deeper understanding and characterization of GSCs is indispensable to find suitable targets and develop more effective therapies. In the present study, we applied native glioblastoma cells and GSCs sequencing, screened for GSC-specific targets and checked if the signature is related to GBM patient pathological, clinical data as well as molecular subtypes applying TCGA cohort. Data analysis revealed that tumors of proneural and mesenchymal subtypes are branching in separate clusters based on screened gene expression. Samples of the same subtype revealed significantly different patient survival prognosis as well as recurrence chance between the clusters. Recently, different subpopulations of mesenchymal GSC demonstrating different properties were shown, which indicates possible internal heterogeneity of GBM subtypes as well. Current findings also revealed branching of molecular GBM subtypes that were significantly linked to patient outcome and that might be decided by distinct GSC subpopulations.     

From Stem Cells to Bone-Forming Cells

Bone formation starts near the end of the embryonic stage of development and continues throughout life during bone modeling and growth, remodeling, and when needed, regeneration. Bone-forming cells, traditionally termed osteoblasts, produce, assemble, and control the mineralization of the type I collagen-enriched bone matrix while participating in the regulation of other cell processes, such as osteoclastogenesis, and metabolic activities, such as phosphate homeostasis. Osteoblasts are generated by different cohorts of skeletal stem cells that arise from different embryonic specifications, which operate in the pre-natal and/or adult skeleton under the control of multiple regulators. In this review, we briefly define the cellular identity and function of osteoblasts and discuss the main populations of osteoprogenitor cells identified to date. We also provide examples of long-known and recently recognized regulatory pathways and mechanisms involved in the specification of the osteogenic lineage, as assessed by studies on mice models and human genetic skeletal diseases.     

Configurational Isomers Induced Significant Difference in All-Polymer Solar Cells

The design of polymer acceptors plays an essential role in the performance of all-polymer solar cells. Recently, the strategy of polymerized small molecules has achieved great success, but most polymers are synthesized from the mixed monomers, which seriously affects batch-to-batch reproducibility. Here, a method to separate γ-Br-IC or δ-Br-IC in gram scale and apply the strategy of monomer configurational control in which two isomeric polymeric acceptors (PBTIC-γ-2F2T and PBTIC-δ-2F2T) are produced is reported. As a comparison, PBTIC-m-2F2T from the mixed monomers is also synthesized. The γ-position based polymer (PBTIC-γ-2F2T) shows good solubility and achieves the best power conversion efficiency of 14.34% with a high open-circuit voltage of 0.95 V when blended with PM6, which is among the highest values recorded to date, while the δ-position based isomer (PBTIC-δ-2F2T) is insoluble and cannot be processed after parallel polymerization. The mixed-isomers based polymer, PBTIC-m-2F2T, shows better processing capability but has a low efficiency of 3.26%. Further investigation shows that precise control of configuration helps to improve the regularity of the polymer chain and reduce the π–π stacking distance. These results demonstrate that the configurational control affords a promising strategy to achieve high-performance polymer acceptors.     

Stable Light-Emitting Electrochemical Cells Using Hyperbranched Polymer Electrolyte

The choice of an adequate electrolyte is a fundamental aspect in polymer light-emitting electrochemical cells (PLECs) as it provides the in situ electrochemical doping and influences the performance of these devices. In this study, a hyperbranched polymer (Hybrane DEO750 8500) blended with a Li salt is used as a novel electrolyte in state-of-the-art Super Yellow (a polyphenylenevinylene) based LECs. Due to the desirable properties of the hyperbranched polymer and the homogeneous and smooth films that it forms with the emitting polymer, PLEC with excellent electroluminescent properties are obtained using a pulsed current bias scheme. The devices are very stable, with lifetimes in excess of 2000 h with initial luminance values above 450 cd m⁻², a peak efficiency of 12.6 lm W⁻¹, and sub-minute turn-on times. The stability of the devices is also studied by measuring the photoluminescence (PL) of the semiconductor during electroluminescent operation. The findings suggest that it is possible to observe the quenching of the PL in vertically stacked devices due to the advancement of the doped fronts in the film and an immediate PL recovery when the bias is removed.     

Dithizone,carminic acid and pyrocatechol violet dyes sensitized metal (Ho,Ba& Cd) doped TiO2/CdS nanocomposite as a photoanode in hybrid heterojunction solar cell

Considering the great importance of nanocomposite based photo-active nanomaterials for a variety of electronics, photonics and photovoltaics application, it is always worth considering to synthesize new hetreostructure. This paper describes the sol-gel and hydrothermal synthesis of metal (holmium, barium, and cadmium) doped TiO₂/CdS nanocomposites for photoanode applications. Various characterization techniques, including XRD, FTIR, UV–VIS, EDX, and SEM were used to examine the synthesized heterostructures. The band gap of pure TiO₂ NPs is 3.10 eV, which was effectively decreased to 2.16 eV by doping and coupling with CdS. The nanomaterial's crystallinity, crystallite size, morphology and elemental composition were determined by XRD, SEM and EDX, respectively. As sensitizers, the organic dyes dithizone, carminic acid, and pyrocatechol violet were used. FTIR was used to analyze the effective dye grafting on the surface of nanomaterials. In the presence of hole conducting P3HT polymer as solid state electrolyte, the sensitized materials were evaluated for solid state dye-sensitized solar cells. Compared to the reference device, Cd–TiO₂/CdS photosensitized using Pyrocatechol violet dye demonstrated the highest efficiency of 2.68% (0.82%). Other parameters of this device, including open circuit voltage (Voc) and short circuit current (Jsc), were determined to be 16.97 mA cm² and 0.41V, respectively.