Polygonatum sibiricum polysaccharides protect against knee osteoarthritis by inhibiting the TLR2/NF-κB signaling pathway in vivo and in vitro.

Polygonatum sibiricum polysaccharides (PSP), the primary constituent of Polygonatum sibiricum, have been shown to exhibit a wide range of pharmacological effects, but their impact on osteoarthritis (OA) remains unclear. The objective of this study was to investigate the protective effects of PSP against OA and to elucidate its underlying molecular mechanism. In our in vitro experiments, PSP not only inhibited the IL-1ß-induced inflammatory responses and the nuclear factor kappa-B (NF-κB) signaling pathway in chondrocytes but also regulated the cartilage matrix metabolism. In addition, we detected 394 significantly differentially expressed genes through RNA-seq analysis on PSP-intervened chondrocytes, and the toll-like receptor 2 (TLR2) was identified as the most important feature by functional network analysis and qRT-PCR. It was also revealed that PSP treatment significantly reversed the IL-1-induced up-regulation of TLR2 expression in chondrocytes, while TLR2 overexpression partially inhibited the regulatory effects of PSP on inflammation, NF-κB signaling pathway and matrix metabolism. In our in vivo experiments, PSP treatment alleviated the development of destabilization of medial meniscus (DMM)-induced OA in mouse knee joints, inhibited the DMM-induced activation of the TLR2/NF-κB signaling pathway in mouse knee joint cartilage, and reduced the serum levels of inflammatory cytokines. In conclusion, PSP exerts its anti-inflammatory, matrix synthesis-promoting and matrix catabolism-suppressing effects in knee OA by inhibiting the TLR2/NF-κB signaling pathway, suggesting that PSP may be potentially targeted as a novel all-natural, low-toxicity drug for OA prevention and treatment.

A review focusing on the role of pyroptosis in prostate cancer.

As one of the types of programmed cell death, pyroptosis has become a focus of research in recent years. Numerous studies have shown that pyroptosis plays a regulatory role in tumor cell invasiveness, differentiation, proliferation, and metastasis. It has been demonstrated that pyroptosis is involved in the regulation of signaling pathways implicated in the pathogenesis of prostate cancer (PCa). Furthermore, the loss of expression of pyroptosis-related genes in PCa has been reported, and pyroptosis-related genes have demonstrated a considerable ability in predicting the prognosis of PCa. Therefore, the potential role of pyroptosis in regulating the development of PCa warrants further investigation and attention. In this review, we summarize the basics of the role of pyroptosis and also discuss research into the mechanisms of action associated with pyroptosis in PCa. It is hoped that by exploring the potential of the pyroptosis pathway in intervening in PCa, it will provide a viable direction for the diversification of PCa treatment.

Multifunctional 3D sponge-like macroporous cryogel-modified long carbon fiber reinforced polyetheretherketone implants with enhanced vascularization and osseointegration.

Long carbon fiber reinforced polyetheretherketone (LCFRPEEK), a newly developed high-performance composite material, is being investigated as a possible orthopedic implant. However, its inability of angiogenesis and osseointegration after implantation makes it difficult for use as a long-term osteogenic fixation implant, which limits its scope of clinical application. Therefore, we design and construct a multifunctional 3D sponge-like macroporous cryogel to modify sulfonated LCFRPEEK using a cryogelation method based on free radical photopolymerization. The cryogel is mainly composed of graphene oxide-hydroxyapatite (GO-HAP) nanocomposites and gelatin methacrylate/polyethylene glycol diacrylate (GelMA/PEGDA). The results reveal that the multifunctional LCFRPEEK implant shows excellent biocompatibility and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) due to the incorporation of HAP nanoparticles into GO-HAP nanocomposites. Systematic in vivo animal studies further confirm that the multifunctional surface improves the bone remodeling and osseointegration of the LCFRPEEK implant. Additionally, the characteristic 3D sponge-like macroporous structures of cryogels promote the ingrowth and migration of human umbilical vein endothelial cells (HUVECs) and GO in the GO-HAP also boosts HUVEC migration and tube formation showing that they are beneficial for vascularization during osteogenesis. Therefore, the developed 3D sponge-like macroporous GelMA/PEGDA/GO-HAP cryogel fabricated on sulfonated LCFRPEEK implants with enhanced angiogenesis and osseointegration capabilities has great potential for clinical use as an orthopedic implant material.

An injectable adhesive antibacterial hydrogel wound dressing for infected skin wounds.

It's an exigent need for the improvement of novel antibacterial wound dressings with the increasing threats of drug resistance caused by excessive use of the antibiotics. In this work, an injectable, adhesive, hemostatic, biocompatible and bactericidal hydrogel wound dressing was fabricated. An injectable hydrogel can fill the irregular wound due to the characteristic of reversible sol-gel transition, whereas conventional dressings don't possess this ability. Oxidized alginate (ADA) and catechol-modified gelatin (Gel-Cat) were selected as the polymer backbones and they can crosslink in situ through double dynamic bonds, which were Schiff base and catechol-Fe coordinate bond; polydopamine decorated silver nanoparticles (PDA@Ag NPs) were also introduced into the hydrogel network. The double dynamic bonds endowed the hydrogel with injectable ability, shorter gelation time and enhanced mechanical property. And the aldehyde and catechol groups on the chains of ADA and Gel-Cat gave the hydrogel excellent adhesiveness. In addition, the PDA@Ag NPs in this system play two roles: one is bactericidal agent which can release from the hydrogel to kill the bacteria; the other is photothermal agent to convert 808 nm near-infrared light into heat to realize sterilization. In vitro study, the hydrogel displayed bactericidal ability against S. aureus and E. coli whether in photothermal antimicrobial test or agar diffusion test. In vivo test also testified that the hydrogel had a prominent therapeutic effect on infected wound through reducing inflammatory response and accelerating angiogenesis. Thus, we anticipate that our double dynamic bonds crosslinked hydrogel with PDA@Ag NPs as the antimicrobial agent can be a novel therapeutic way for infected wounds.

Nanosecond tunable laser for the all-optical switching network.

The optically switched network can offset the increasing gap between datacenter traffic growth and electrical switch capacity due to the slowdown of Moore's law. Ultra-high-speed wavelength tunable lasers are especially vital for the high integration and performance improvement of the all-optical switching system. In this paper, a fast tunable laser based on a laser array is realized. The 2×8 matrix structure of the laser array is fabricated by the reconstruction-equivalent-chirp (REC) technique. Aiming at the 2×8 array, a drive control system is designed to provide stable and fast switching, to achieve high-speed switching of the laser wavelength, and to keep the wavelength stable after switching. The simulation and experimental results show that the switching time between any two wavelength channels of the laser is less than 10 ns. The switching time of any two channels of the laser can be reduced by 2-3 ns after the pre-emphasis processing of the electrical signal.

The surface modification of long carbon fiber reinforced polyether ether ketone with bioactive composite hydrogel for effective osteogenicity.

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.

A bi-layered scaffold of a poly(lactic-co-glycolic acid) nanofiber mat and an alginate-gelatin hydrogel for wound healing.

A resveratrol-loaded bi-layered scaffold (RBS) that consists of a resveratrol-loaded poly(lactic-co-glycolic acid) (Res-PLGA) electrospinning nanofiber mat (upper layer) and an alginate di-aldehyde (ADA)-gelatin (GEL) crosslinking hydrogel (ADA-GEL) (lower layer) was fabricated as a wound dressing material. It was made through mimicking the epidermis and dermis of the skin. The RBS exhibited good hemostatic ability and proper swelling ability. Furthermore, HaCaT cells and human embryonic skin fibroblasts (ESFs) were also cultured in the nanofiber layer and hydrogel layer of RBS, and the results indicated that both HaCaT and ESFs could grow well in the materials. The in vivo experiment using a Sprague-Dawley (SD) rat skin wound as a model showed that the RBS could accelerate the wound healing rate compared with the Res-PLGA group and ADA4-GEL6 group. These results indicated that this resveratrol-loaded bi-layered scaffold can be a potential candidate in promoting wound healing.

Three-Dimensional Coating of SF/PLGA Coaxial Nanofiber Membranes on Surfaces of Calcium Phosphate Cement for Enhanced Bone Regeneration.

Calcium phosphate cements (CPCs) have been widely used for the study of bone regeneration because of their excellent physical and chemical properties, but poor biocompatibility and lack of osteoinductivity limit potential clinical applications. To overcome these limitations, and based on our previous research, CPC scaffolds were prepared with CPC as the principal material and polyethylene glycol (PEG) as a porogen to introduce interconnected macropores. Using a bespoke electrospinning auxiliary receiver, silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) coaxial nanofibers containing dexamethasone (DXM) and recombinant human bone morphogenetic protein-2 (rhBMP2) were fabricated which were coated on the surface of the CPC. By comparing the surface morphology by SEM, hydrophilicity, results of FTIR spectroscopy, and mechanical properties of the composite materials fabricated using different electrospinning times (20, 40, 60 min), the CPC surface constructed by electrospinning for 40 min was found to exhibit the most appropriate physical and chemical properties. Therefore, composite materials were built for further study by electrospinning for 40 min. The osteogenic capacity of the SF/PLGA/CPC, SF-DXM/PLGA/CPC, and SF-DXM/PLGA-rhBMP2/CPC scaffolds was evaluated by in vitro cell culture with rat bone marrow mesenchymal stem cells (BMSCs) and using a rat cranial defect repair model. ALP activity, calcium deposition levels, upregulation of osteogenic genes, and bone regeneration in skull defects in rats with SF-DXM/PLGA-rhBMP2/CPC implants were significantly higher than in rats implanted with the other scaffolds. These results suggest that drug-loaded coaxial nanofiber coatings prepared on a CPC surface can continuously and effectively release bioactive drugs and further stimulate osteogenesis. Therefore, the SF-DXM/PLGA-rhBMP2/CPC scaffolds prepared in this study demonstrated the most significant potential for the treatment of bone defects.

Inhibition of prostate cancer RM1 cell growth in vitro by hydroxyapatite nanoparticle­delivered short hairpin RNAs against Stat3.

The present study investigated the effect of signal transducer and activator of transcription 3 (Stat3) interference on RM1 prostate cancer cell viability in vitro, using plasmid­based Stat3 specific short hairpin RNA (sh­Stat3) delivered by hydroxyapatite nanoparticles (HAP). HAP carrying sh­Stat3 plasmids were transfected into tumor cells. MTT assays were used to measure RM1 cell viability 24 and 48 h following transfection, and the apoptosis rate and cell cycle phase distribution were determined by flow cytometry. Stat3 mRNA expression levels were measured by reverse transcription­quantitative polymerase chain reaction and Stat3, Cyclin D1, B cell lymphoma 2 apoptosis regulator (Bcl­2), vascular endothelial growth factor (VEGF), Bcl­2 associated X apoptosis regulator (Bax) and cleaved­caspase­3 protein expression levels were detected using western blot analysis. The results demonstrated that HAP­delivered sh­Stat3 significantly decreased RM1 cell viability through the promotion of cell cycle arrest and apoptosis. Stat3 mRNA and protein expression levels were significantly downregulated in RM1 cells. Bcl­2, VEGF and Cyclin D1 were also significantly downregulated, but cleaved­caspase­3 and Bax mRNA and protein expression levels were significantly upregulated. HAP­delivered sh­Stat3 decreased RM1 cell viability in vitro, and HAP assisted plasmid­based delivery of shRNA into tumor cells. The present results suggest that HAP may be a useful method for successful shRNA delivery into tumors.

Plasmid-Based Stat3 siRNA Delivered by Functional Graphene Oxide Suppresses Mouse Malignant Melanoma Cell Growth.

RNA interference (RNAi) has been used for cancer gene therapy in recent years. However, the application of RNAi is hindered in the absence of safe and efficient gene delivery. In this article, a novel vehicle of graphene oxide functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) was successfully synthetized and then used to deliver plasmid-based Stat3 siRNA. The carrier can readily bind plasmid with high transfection efficiency. Moreover, molecular biology studies reveal that Stat3-related gene and protein expressions were significantly inhibited, suggesting that the formation of GO-PEI-PEG complexes could be utilized as a promising gene delivery in cancer therapy.

Stat3-siRNA inhibits the growth of gastric cancer in vitro and in vivo.

Gastric cancer remains one of the most prevalent and lethal malignancies in the world. Despite new advances in treatment and diagnosis, patients with advanced gastric cancer are still difficult to cure resulting in a high mortality rate and poor prognosis. Signal transducer and activator of transcription 3 (Stat3) is observed aberrant in multiple tumours, including gastric cancer. Stat3 overexpression was confirmed performing a vital role in tumorigenesis. In the present study, we constructed a pSi-Stat3 plasmid to silence Stat3 and investigated the effect of pSi-Stat3 on cell proliferation, apoptosis and cell cycle progression in gastric cancer cell line SGC-7901 and mice xenograft model. Downstream proteins of Stat3, including Cyclin-D1, Survivin and Bcl-2, were detected as well for the underlying mechanism exploration. It showed that pSi-Stat3 can effectively silence the expression of Stat3 and inhibits the growth of gastric tumour both in vitro and in vivo significantly via cell apoptosis and cell cycle shift induction. The findings suggest that Stat3 signal pathway might be a promising therapeutic target for tumour treatment, including gastric cancer.