Abstract Combination cancer therapy has emerged as crucial approach for achieving superior anti-cancer efficacy. In this study, we developed a strategy by localized co-delivery of ...PLK1shRNA/polylysine-modified polyethylenimine (PEI-Lys) complexes and doxorubicin (DOX) using biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for treatment of osteosarcoma. When incubated with osteosarcoma Saos-2 and MG-63 cells, the hydrogel containing PLK1shRNA/PEI-Lys and DOX displayed significant synergistic effects in promoting the apoptosis of osteosarcoma cells in vitro . After subcutaneous injection of the hydrogel containing PLK1shRNA/PEI-Lys and DOX beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts, the hydrogels exhibited superior antitumor efficacy in vivo compared to the hydrogels loaded with PLK1shRNA/PEI-Lys or DOX alone. It is noteworthy that the combination treatment in vivo led to almost complete suppression of tumor growth up to 16 days, significantly enhanced PLK1 silencing, higher apoptosis of tumor masses, as well as increased cell cycle regulation. Additionally, ex vivo histological analysis of major organs of the mice indicated that the localized treatments showed no obvious damage to the organs, suggesting lower systemic toxicity of the treatments. Therefore, the strategy of localized, sustained co-delivery of PLK1shRNA and DOX by using the biodegradable, injectable hydrogel may have potential for efficient clinical treatment of osteosarcoma.
The replacing and surpassing of some functions of traditional metal-based photocatalysts by low-cost and high-efficiency non-metal semiconductor materials have become a research hotspot in functional ...materials. In this paper, the ultra-thin nanoporous g-C
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nanosheets were successfully embedded with highly dispersed S quantum dots (S QDs) by ultrasonic-assisted in-situ growth method, which originates from the disproportionation reaction of sodium thiosulfate. The formation of the composite was proved by XRD, XPS, AFM, TEM and HRTEM and proved that S QDs with a size of 1–3.5 nm were uniformly embedded in the surface of ultra-thin nanoporous g-C
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, in which a tight and uniform 0D/2D heterojunction structure was designed and built. Meanwhile, the photocatalytic mechanism was investigated. It showed that the tight Z-Scheme heterojunction structure formed between S QDs and g-C
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improved the redox activity as well as the transfer ability of photogenerated electron holes. The system exhibited excellent photocatalytic efficiency that the complete degradation of RhB was achieved within 90 min under visible-light irradiation and revealed high stability. We believe that this research is important for the development of low-cost and efficient non-metal photocatalysts.
Graphical abstract
Osteoporosis is a common metabolic skeletal disease and usually lacks obvious symptoms. Many individuals are not diagnosed until osteoporotic fractures occur. Bone mineral density (BMD) measured by ...dual-energy X-ray absorptiometry (DXA) is the gold standard for osteoporosis detection. However, only a limited percentage of people with osteoporosis risks undergo the DXA test. As a result, it is vital to develop methods to identify individuals at-risk based on methods other than DXA.
We proposed a hierarchical model with three layers to detect osteoporosis using clinical data (including demographic characteristics and routine laboratory tests data) and CT images covering lumbar vertebral bodies rather than DXA data via machine learning. 2210 individuals over age 40 were collected retrospectively, among which 246 individuals' clinical data and CT images are both available. Irrelevant and redundant features were removed via statistical analysis. Consequently, 28 features, including 16 clinical data and 12 texture features demonstrated statistically significant differences (p < 0.05) between osteoporosis and normal groups. Six machine learning algorithms including logistic regression (LR), support vector machine with radial-basis function kernel, artificial neural network, random forests, eXtreme Gradient Boosting and Stacking that combined the above five classifiers were employed as classifiers to assess the performances of the model. Furthermore, to diminish the influence of data partitioning, the dataset was randomly split into training and test set with stratified sampling repeated five times. The results demonstrated that the hierarchical model based on LR showed better performances with an area under the receiver operating characteristic curve of 0.818, 0.838, and 0.962 for three layers, respectively in distinguishing individuals with osteoporosis and normal BMD.
The proposed model showed great potential in opportunistic screening for osteoporosis without additional expense. It is hoped that this model could serve to detect osteoporosis as early as possible and thereby prevent serious complications of osteoporosis, such as osteoporosis fractures.
This paper presents a new method of delivering shRNA with biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for gene treatment of osteoarthritis （OA）. OA is a chronic debilitating disease. ...Without the proper treatment and prognosis, it may result in the loss of joint function in aged people. Currently, gene therapy targeted on WISP-1 has emerged as an alternative method for OA treatment. In order to constantly release shRNA at 37.0 ℃, we synthetized the hydrogels via ring-opening copolymerization of lactide （LA） and glycolide （GA） using Polyethylene glycol （PEG Mn = 1000） and stannous octoate （Sn（Oct）2, 95%） as the macroinitiator and catalyst. First, the PLGA-PEG-PLGA copolymer was mixed with WISP- 1 shRNA and PEI-Lys in distilled water at 4.0 ℃. Then, the WISP-lshRNA/PEI-Lys loaded hydrogel was formed after incubation of the mixed solution at 37.0 ℃. During tests, the plasmid was released from this hydrogel complex constantly, and enhanced the transfection efficiency of WISP-1 shRNA. In addition, silencing WISP-1 results to lower expression of MMP-3 and ADAMTS, and the accumulation of HBP 1 in synoviocytes. Therefore, the hydrogel containing WISP-1 shRNA is demonstrated an efficient way for the treatment of OA.
Localized cancer treatments with combination drugs have recently emerged as crucial approaches for effective inhibition of tumor growth and reoccurrence. In this study, we present a new strategy for ...the osteosarcoma treatment by localized co-delivery of multiple drugs, including doxorubicin (DOX), cisplatin (CDDP) and methotraxate (MTX), using thermosensitive PLGA-PEG-PLGA hydrogels. The release profiles of the drugs from the hydrogels were investigated in vitro. It was found that the multidrug coloaded hydrogels exhibited synergistic effects on cytotoxicity against osteosarcoma Saos-2 and MG-63 cells in vitro. After a single peritumoral injection of the drug-loaded hydrogels into nude mice bearing human osteosarcoma Saos-2 xenografts, the hydrogels coloaded with DOX, CDDP, and MTX displayed the highest tumor suppression efficacy in vivo for up to 16 days, as well as led to enhanced tumor apoptosis and increased regulation of the expressions of apoptosis-related genes. Moreover, the monitoring on the mice body change and the ex vivo histological analysis of the key organs indicated that the localized treatments caused less systemic toxicity and no obvious damage to the normal organs. Therefore, the approach of localized co-delivery of DOX, CDDP, and MTX by the thermosensitive hydrogels may be a promising approach for enhanced osteosarcoma treatment.
Photocatalytic performance is significantly influenced by the efficiency of photogenerated electron-hole pairs separation and transfer. In this paper, rational designed Z-scheme Bi/Black Phosphorus ...Nanosheets/P-doped BiOCl (Bi/BPNs/P–BiOCl) nanoflower photocatalyst was synthesized by a facile in-situ reduction process. The interfacial P–P bond between Black phosphorus nanosheets (BPNs) and P-doped BiOCl (P–BiOCl) was investigated by the XPS spectrum. The Bi/BPNs/P–BiOCl photocatalysts exhibited enhanced photocatalytic performance for H2O2 production and RhB degradation. The optimally modified photocatalyst (Bi/BPNs/P–BiOCl-20) showed an excellent photocatalytic H2O2 generation rate of 4.92 mM/h and RhB degradation rate of 0.1169 min−1 under simulated sunlight irradiation, which was 1.79 times and 1.25 times greater than the P–P bond free Bi/BPNs/BiOCl-20. The mechanism was investigated through charge transfer route, radical capture experiments, and band gap structure analysis, indicating that the formation of Z-scheme heterojunctions and interfacial P–P bond not only enhances the redox potential of the photocatalyst but also facilitates the separation and migration of photogenerated electrons-holes. This work might provide a promising strategy for constructing Z-scheme 2D composite photocatalysts combining interfacial heterojunction and elemental doping engineering for efficient photocatalytic H2O2 production and organic dye pollutant degradation.
A flower-like Z-scheme Bi/BPNs/P–BiOCl with interfacial P–P bond between BP nanosheets and P–BiOCl has been fabricated via in-situ reduction method which possess high photocatalytic H2O2 production and RhB degradation activity. Display omitted
•Flower-like Bi/BPNs/P–BiOCl photocatalyst with interfacial P–P bond was fabricated.•The Bi/BPNs/P–BiOCl-20 achieves excellent photocatalytic activity using solar light.•Interfacial P–P bond facilitates the migration of photogenerated charge carriers.•Metallic Bi nanoparticles could enhance the light absorption of Bi/BPNs/P–BiOCl.•A reasonable mechanism was discussed for RhB photodegradation in Bi/BPNs/P–BiOCl.
Interleukin-17 (IL-17) is the production of T helper type 17 (Th17) cells and has been reported to play a pro-inflammatory role in the immunopathogenesis of intervertebral disc degeneration. ...Peroxisome proliferator-activated receptor γ (PPAR-γ) activators display anti-inflammatory and anti-degeneration roles in osteoarthritis and rheumatoid arthritis. However, the expression level of PPAR-γ and related regulatory mechanisms in the nucleus pulposus tissues are not clear. Herein we report that PPAR-γ was down-regulated both in the nucleus pulposus tissue of intervertebral disc degeneration patient and in the cultured nucleus pulposus cells stimulated with IL-17. This study was undertaken to investigate the potential therapeutic effect of pioglitazone, as a PPAR-γ ligand, and its underlying molecular mechanism in IL-17-induced human intervertebral disc degeneration model in vitro. Our results indicate that pioglitazone administration suppressed the production of pro-inflammatory cytokines and down-regulated the mRNA expression levels of inflammatory mediators in the cultured human nucleus pulposus cells and tissue. Consistently, pioglitazone decreased the levels of metalloproteinase and maintained the expression of critical matrix components, such as aggrecan and type II collagen. Moreover, the activation of NF-κB signaling in the nucleus pulposus tissue during the intervertebral disc degeneration development was antagonized by pioglitazone administration. In conclusion, our current findings provide scientific evidence for the assessment of pioglitazone as a potential therapeutic approach to treat the intervertebral disc degeneration.
•IL-17 promotes the progression of the lumbar disc degeneration.•The PPAR-γ level was decreased in nucleus pulposus tissue of lumbar disc degeneration patients.•IL-17 combine with TNF-α significantly down-regulated the expression of PPAR-γ in the nucleus pulposus culture model.•Pioglitazone decreased IL-17 induced nucleus pulposus degeneration via inhibiting NF-κB signaling in vitro.
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