Strontium and simvastatin dual loaded hydroxyapatite microsphere reinforced poly(ε-caprolactone) scaffolds promote vascularized bone regeneration.

The promotion of vascular network formation in the early stages of implantation is considered a prerequisite for successful functional bone regeneration. In this study, we successfully constructed 3D printed scaffolds with strong mechanical strength and a controllable pore structure that can sustainably release strontium (Sr) ions and simvastatin (SIM) for up to 28 days by incorporation of Sr2+ and SIM-loaded hydroxyapatite microspheres (MHA) into a poly(ε-caprolactone) (PCL) matrix. In vitro cell experiments showed that Sr-doped scaffolds were beneficial to the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs), an appropriate dose of SIM was beneficial to cell proliferation and angiogenesis, and a high dose of SIM was cytotoxic. The Sr- and SIM-dual-loaded scaffolds with an appropriate dose significantly induced osteogenic differentiation of BMSCs and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and promoted vascular network and functional bone formation in vivo. Ribose nucleic acid (RNA) sequencing analysis suggested that the mechanism of promotion of vascularized bone regeneration by fabricated scaffolds is that dual-loaded Sr2+ and SIM can upregulate osteogenic and vasculogenic-related genes and downregulate osteoclast-related genes, which is beneficial for vascular and new bone regeneration. The 3D printed composite scaffolds loaded with high-stability and low-cost inorganic Sr2+ ions and SIM small-molecule drugs hold great promise in the field of promoting vascularized bone regeneration.

Recent advances in the development of bitter gourd seed oil: from chemical composition to potential applications.

Non-conventional seed oils are being considered novelty foods due to the unique properties of their chemical constituents. Numerous such seed oils serve as nutritional and functional supplements, making them a point of interest for scholars. Bitter gourd (Momordica charantia L.) seed oil (BGSO) has been widely used in folk medicine worldwide for the treatment of different pathologies, such as diabetes, cancer, and several inflammatory diseases. Therefore, its nutritional and medicinal value has been extensively studied. Considering the potential use of BGSO, it is imperative to have a comprehensive understanding of this product to develop and use its biologically active ingredients in innovative food and pharmaceutical products. An extensive understanding of BGSO would also help improve the economic feasibility of the bitter gourd seed processing industry and help prevent environmental pollution associated with the raw waste produced during the processing of bitter gourd seeds. This review addresses the potential uses of BGSO in terms of food and pharmaceuticals industry perspectives and comprehensively summarizes the oil extraction process, chemical composition, biological activity, and the application prospects of BGSO in clinical medicine.

Therapeutic Targeting of GSK3ß-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis.

Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. Salvia miltiorrhiza and its major active component Salvianolic acid A (Sal A) have demonstrated a beneficial effect in myriad diseases. However, their effect on peritoneal fibrosis is unknown. In murine models of peritoneal dialysis, daily Sal A treatment substantially improved the peritoneal dialysis fluid (PDF) elicited peritoneal fibrosis, marked by thickening of the submesothelial compact zone, accumulation of extracellular matrix and increased expression of vimentin and PAI-1, concomitant with attenuation of GSK3ß hyperactivity. This coincided with diminished nitrotyrosine in peritoneal tissues and increased Nrf2 nuclear translocation, entailing a lessened oxidative injury and reinforced Nrf2 antioxidant response. Meanwhile, inflammatory infiltration and maladaptive angiogenesis in peritoneal tissues provoked by PDF injury were also mitigated by Sal A, associated with a suppressed NFκB activation. Mechanistically, ectopic expression of the constitutively active GSK3ß blunted the NFκB-suppressing and Nrf2-activating efficacy of Sal A in peritoneal mesothelial cells exposed to hypertonic dextrose, suggesting that GSK3ß inhibition mediates the protective effect of Sal A. Collectively, our findings may open the avenue for developing a novel therapy based on Sal A for preventing peritoneal fibrosis in peritoneal dialysis.

Protein-Bound Anthocyanin Compounds of Purple Sweet Potato Ameliorate Hyperglycemia by Regulating Hepatic Glucose Metabolism in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.

Purple sweet potato is known as a rich source of protein and anthocyanins. Anthocyanins can form complexes with protein present in food products through non-covalent forces or covalent bonds during processing, transportation, and storage as their protein affinity. We evaluated the hypoglycemic effects of protein-bound anthocyanin compounds of purple sweet potato (p-BAC-PSP) and free anthocyanin compounds of purple sweet potato (FAC-PSP) in high-fat diet/streptozotocin-induced diabetic mice. The results showed that administration of both p-BAC-PSP and FAC-PSP improved diabetic condition, as evidenced by the improvement of glucose tolerance and lipid metabolism, and the decrease of oxidative stress and liver damage. For the mechanism study, we have found that p-BAC-PSP and FAC-PSP induced the expression of AMP-activated protein kinase in liver. With p-BAC-PSP or FAC-PSP treatment, glucose transporter type 2, the protein levels of glucokinase, and insulin receptor α were found to be improved significantly (p < 0.05). Glycolysis key genes, phosphofructokinase and pyruvate kinase, were upregulated in two treatment groups, while gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, were downregulated. Our findings suggested that p-BAC-PSP has great potential as a dietary supplement with hypoglycemic activity for general, pre-diabetic, and diabetic population.

Remediation of oil-based drill cuttings using low-temperature thermal desorption: Performance and kinetics modeling.

A bench-scale apparatus was used for the low-temperature thermal desorption (LTTD) treatment of oil-based drill cuttings (OBDCs). The effects of treatment temperature, treatment duration, sand/OBDCs mixing ratio, and initial oil content on the LTTD treatment performance were investigated. It was found that the petroleum hydrocarbons (PHCs) were barely left in the high-oil-content drill cuttings after LTTD (at 300 °C for 20 min), and thus the overall soil health was improved. The desorption kinetics models of PHCs under various conditions were established, and it was found that the LTTD of OBDCs followed nonlinear least-squares exponential kinetics (adjusted R2 > 0.9). The energy consumption models of LTTD treatment under different temperatures were also developed. The modeling results are of practical guiding significance and useful for designing effective LTTD treatment systems of OBDCs.

Nanoscale Hybrid Coating Enables Multifunctional Tissue Scaffold for Potential Multimodal Therapeutic Applications.

Through a nature-inspired layer-by-layer assembly process, we developed a unique multifunctional tissue scaffold that consists of porous polyurethane substrate and nanoscale chitosan/graphene oxide hybrid coating. Alternative layers of drug-laden chitosan and graphene oxide nanosheets were held together through strong electrostatic interaction, giving rise to a robust multilayer architecture with control over structural element orientation and chemical composition at nanoscale. Combined pH-controlled co-delivery of multiple therapeutic agents and photothermal therapy has been achieved by our scaffold system. The new platform technology can be generalized to produce other tissue scaffold systems and may enable potential multimodal therapeutic applications such as bone cancer managements.

Chitosan-based asymmetric topological membranes with cell-like features for healthcare applications.

Chitosan-based guided tissue regeneration (GTR) membranes are extensively used in orthopedic/stomatological regenerative medicine since chitosan shares many chemical and structural similarities with glycosaminoglycans (GAGs) in the extracellular matrix. However, the available chitosan-based GTR membranes mostly lack topological features of natural tissues, resulting in unsatisfactory biocompatibility. To address this limitation, we developed a novel biologically-inspired asymmetric topological chitosan (ATCS) membrane supported by a nanoporous anodic aluminum oxide (AAO) template. We, thereafter, investigated the mechanical properties, degradation, and cytocompatibility of the ATCS membranes and compared them with those of the symmetric chitosan (SyCS) membranes, produced with a smooth Al template. The asymmetric topological structure significantly increased the tensile strength but decreased the extent of degradation of the ATCS membranes compared to those of SyCS. In the in vitro studies, the ATCS membranes outperformed the SyCS membranes in cytocompatibility due to their cell-like features. In addition to the ATCS membranes, the ethylene vinyl acetate (EVA) membranes with a similar cell-like structure were successfully fabricated using the AAO template to verify the universality of the AAO template-assisted technique. Accordingly, the AAO template-assisted strategy, defined in this study, is an innovative, universal, and facile way to fabricate polymeric asymmetric membranes with cell-like features. The bioengineered ATCS membranes with tunable degradability, prominent mechanical properties and biocompatibility are promising candidates for orthopedic healthcare applications.

Investigation of waste biomass co-pyrolysis with petroleum sludge using a response surface methodology.

The treatment of waste biomass (sawdust) through co-pyrolysis with refinery oily sludge was carried out in a fixed-bed reactor. Response surface method was applied to evaluate the main and interaction effects of three experimental factors (sawdust percentage in feedstock, temperature, and heating rate) on pyrolysis oil and char yields. It was found that the oil and char yields increased with sawdust percentage in feedstock. The interaction between heating rate and sawdust percentage as well as between heating rate and temperature was significant on the pyrolysis oil yield. The higher heating value of oil originated from sawdust during co-pyrolysis at a sawdust/oily sludge ratio of 3:1 increased by 5 MJ/kg as compared to that during sawdust pyrolysis alone, indicating a synergistic effect of co-pyrolysis. As a result, petroleum sludge can be used as an effective additive in the pyrolysis of waste biomass for improving its energy recovery.

Heavy metals and nutrients (carbon, nitrogen, and phosphorus) in sediments: relationships to land uses, environmental risks, and management.

Management of sediments in polluted rivers requires an inventory of sediment quantities as well as their nutrient and metal contents and the chemical forms of pollutants. We investigated the influence of three major land uses (i.e., orange plantation-OP, OP + residential + industrial-OPRI, and residential + industrial-RI) on the quality of surface sediments (0-20 cm below water/sediment interface) at the Sanyang Wetland (China). The total contents of metals (As, Cd, Cr, Cu, Ni, Pb, and Zn) and nutrients (C, N, and P) as well as metal speciation in sediments were examined. GIS technology was used to estimate the volume of sediments needed to calculate the amounts of stored nutrients and metals in sediments. The surface sediments in the 3.2-km2 study area contain more than 2800 Mg C, 200 Mg N, and 100 Mg P. OPRI and RI land uses contribute more total C, N, P, Zn, and Cd to sediments than OP land use. High contents of C, N, and P may provide options to recycle the sediments as fertilizer but must be used with caution due to high levels of metals. Total Cd in sediments is at an order of magnitude (up to 59 mg kg-1) higher than the Level III criterion in the Chinese Environmental Quality Standards for Soil. Sediments in all land uses have very high risks due to >50% exchangeable + carbonate-bound Zn, Ni, and Cd. It is suggested that toxicity tests be conducted to better assess the environmental risks associated with any potential use of sediments.

Oil recovery from petroleum sludge through ultrasonic assisted solvent extraction.

The effect of ultrasonic assisted extraction (UAE) process on oil recovery from refinery oily sludge was examined in this study. Two types of UAE treatment including UAE probe (UAEP) system and UAE bath (UAEB) system were investigated. Their oil recovery efficiencies were compared to that of mechanical shaking extraction (MSE). Three solvents including cyclohexane (CHX), ethyl acetate (EA), and methyl ethyl ketone (MEK) were examined as the extraction solvents. The influence of experimental factors on oil and solvent recovery was investigated using an orthogonal experimental design. Results indicated that solvent type, solvent-to-sludge (S/S) ratio, and treatment duration could have significant effects on oil recovery in UAE treatment. Under the optimum conditions, UAEP treatment can obtain an oil recovery of 68.8% within 20 s, which was higher than that (i.e., 62.0%) by MSE treatment after 60 min' extraction. UAEB treatment can also obtain a promising oil recovery within shorter extraction duration (i.e., 15 min) than MSE. UAE was thus illustrated as an effective and improved approach for oily sludge recycling.

Hierarchical Structure and Mechanical Improvement of an n-HA/GCO-PU Composite Scaffold for Bone Regeneration.

To improve the mechanical properties of bone tissue and achieve the desired bone tissue regeneration for orthopedic surgery, newly designed hydroxyapatite/polyurethane (HA/PU) porous scaffolds were developed via in situ polymerization. The results showed that the molecular modification of PU soft segments by glyceride of castor oil (GCO) can increase the scaffold compressive strength by 48% and the elastic modulus by 96%. When nano-HA (n-HA) particles were incorporated into the GCO-PU matrix, the compressive strength and elastic modulus further increased by 49 and 74%, from 2.91 to 4.34 MPa and from 95 to 165.36 MPa, respectively. The n-HA particles with fine dispersity not only improved the interface bonding with the GCO-PU matrix but also provided effective bioactivity for bonding with bone tissue. The hierarchical structure and mechanical quality of the n-HA/GCO-PU composite scaffold were determined to be appropriate for the growth of cells and the regeneration of bony tissues, demonstrating promising prospects for bone repair and regeneration.

Preparation and characterization of vanillin-crosslinked chitosan therapeutic bioactive microcarriers.

Chitosan microspheres with diameter of 14.3-48.5 µm were prepared by emulsion method and using natural vanillin as cross-linking agent. The surface morphology and microstructure of the microspheres were characterized by scanning electron microscopy, X-ray diffraction and Fourier-transform infrared spectroscopy, etc. The hollow microspheres showed a well-defined spherical shape with median diameter of 30.3 µm and possessed a uniform surface with micro-wrinkles, which is in favor of the drug release. Interpenetrating network cross-linking mechanism might result from the Schiff base reaction and the acetalization of hydroxyl and carbonyl between chitosan and vanillin. Berberine, as a model drug, was loaded in the microspheres and released in a sustainable manner. The drug loading ratio could change from 9.16% to 29.70% corresponding to the entrapment efficiency of 91.61% to 74.25%. In vitro cell culture study using MG63 cells and in vivo implantation clearly showed that the microspheres could provide favorable cell attachment and biocompatibility. The results confirm that the drug-loaded vanillin-crosslinked chitosan microspheres could be a worthy candidate either as carriers of drugs and cells, or as therapeutic matrix for bone repair and regeneration.

Enhancement of bone formation by BMP-7 transduced MSCs on biomimetic nano-hydroxyapatite/polyamide composite scaffolds in repair of mandibular defects.

This study was to evaluate enhanced bone formation by bone morphogenetic protein-7 (BMP-7) transduced MSCs on nano-hydroxyapatite/polyamide (n-HA/PA) composite scaffolds for bone tissue engineering in repair of mandibular defect. n-HA/PA scaffolds were prepared and rabbit MSCs were separated and expanded; and then infected with adenoviral-mediated BMP-7 in vitro. The MSCs-BMP-7 and MSCs were seeded on the porous scaffolds. Scaffold/MSCs-BMP-7 constructs and scaffold/MSCs constructs were implanted in the defects of rabbits' mandible as the experimental groups A (n = 18) and groups B (n = 18), respectively, the pure scaffolds were implanted as controls (group C, n = 18). Six animals were sacrificed at 4-, 8-, and 16-week postimplantation, respectively. Their mandibles were removed and processed for radiographic, biomechanical tests, histological, and histomorphometric analysis. Group A animals showed greater bone formation and earlier mineralization than group B at 4- and 8-week postimplantation and similarly group B more than group C. However, no difference was found among three groups at 16-week postimplantation. The results of this study suggest that BMP-7 transduced MSCs-n-HA/PA composite could significantly accelerate bone formation in the implant at early stage. BMP-7 mediated ex vivo gene transfer based on MSCs as seed cells, combined with porous n-HA/PA as scaffolds for bone tissue engineering might be an alternative or supplemental approach to repair the mandibular defects.