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.

Methyl protodioscin reduces c-Myc to ameliorate diabetes mellitus erectile dysfunction via downregulation of AKAP12.

BACKGROUND: Diabetes mellitus erectile dysfunction (DMED) is one of common complications of diabetes. We aimed to investigate the potential efficacy of methyl protodioscin (MPD) in DMED and explored the underlying mechanism. METHODS: Diabetic mice were induced by streptozotocin, while vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) were stimulated with high glucose. MPD was administrated in vitro and in vivo to verify its efficacy on DMED. The interaction of c-Myc and AKAP12 was determined by luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS: c-Myc and AKAP12 were upregulated in penile tissues in DMED mice. In high glucose-stimulated VSMCs or VECs, MPD intervention enhanced cell viability, inhibited apoptosis, decreased c-Myc and AKAP12, as well as elevated p-eNOS Ser1177. MPD-induced apoptosis inhibition, AKAP12 reduction and p-eNOSSer1177 elevation were reversed by AKAP12 overexpression. c-Myc functioned as a positive regulator of AKAP12. Overexpression of c-Myc reversed the effects induced by MPD in vitro, which was neutralized by AKAP12 silencing. MPD ameliorated erectile function in diabetic mice via inhibiting AKAP12. CONCLUSIONS: MPD improved erectile dysfunction in streptozotocin-caused diabetic mice by regulating c-Myc/AKAP12 pathway, indicating that MPD could be developed as a promising natural agent for the treatment of DMED.

Preparation of a 3D printable high-performance GelMA hydrogel loading with magnetic cobalt ferrite nanoparticles.

Osteosarcoma remains a worldwide concern due to the poor effectiveness of available therapies in the clinic. Therefore, it is necessary to find a safe and effective therapy to realize the complete resection of osteosarcoma and reconstruction of the bone defect. Magnetic hyperthermia based on magnetic nanoparticles can kill tumor cells by raising the temperature without causing the side effects of conventional cancer treatments. This research aims to design a high-performance magnetic hydrogel composed of gelatin methacrylate and highly magnetic cobalt ferrite (CFO) nanoparticles for osteosarcoma treatment. Specifically, CFO is surface functionalized with methacrylate groups (MeCFO). The surface modified CFO has good biocompatibility and stable solution dispersion ability. Afterward, MeCFO nanoparticles are incorporated into GelMA to fabricate a three-dimensional (3D) printable MeCFO/GelMA magnetic hydrogel and then photocross-linked by UV radiation. MeCFO/GelMA hydrogel has high porosity and swelling ability, indicating that the hydrogel possesses more space and good hydrophily for cell survival. The rheological results showed that the hydrogel has shear thinning property, which is suitable as a bioprinting ink to produce desired structures by a 3D printer. Furthermore, 50 µg/mL MeCFO not only decreases the cell activity of osteosarcoma cells but also promotes the osteogenic differentiation of mBMSCs. The results of the CCK-8 assay and live/dead staining showed that MeCFO/GelMA hydrogel had good cytocompatibility. These results indicated that MeCFO/GelMA hydrogel with potential antitumor and bone reconstruction functions is a promising therapeutic strategy after osteosarcoma resection.

A review focusing on the benefits of plant-derived polysaccharides for osteoarthritis.

Osteoarthritis (OA) is a chronic joint disease characterized by progressive cartilage degeneration, which imposes a heavy physical and financial burden on the middle-aged and elderly population. As the pathogenesis of OA has not been fully elucidated, it is of great importance to develop targeted therapeutic or preventive medications. Traditional therapeutic drugs, such as non-steroidal anti-inflammatory drugs, steroids and opioids, have significant side effects, making the exploration for safe and effective alternative therapeutic drugs urgent. In recent years, many studies have reported the role of plant-derived polysaccharides in anti-inflammation, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection, and have demonstrated their great potential in the treatment of OA. Therefore, by focusing on studies related to the intervention of plant-derived polysaccharides in OA, including in vivo and in vitro experiments, this review aimed to classify and summarize the existing research findings according to different mechanisms of action. In addition, reports on plant-derived polysaccharides as nanoparticles were also explored. Then, candidate monomers and theoretical bases were provided for the further development and application of novel drugs in the treatment of OA.

Chemical Structures and Pharmacological Properties of Typical Bioflavonoids in Polygonati Rhizoma (PGR).

Most medicines are coming with toxic and detrimental side effects. In addition, microbials are resisting the medicine. Therefore, alternative drugs with low toxic and side effects and low microbial resistance are needed. Plants offer good potential candidates due to a broad range of chemicals they contain. These chemicals have been studied, and research is still going on to probe chemical properties of plant chemicals. In China, traditional Chinese medicine is practised, whereby plant extracts are obtained, and then sold in packages for reasons like memory enhancement, cancer treatment, boosting immune system, and so on. Among the herbs cultivated in China is Polygonati rhizoma (PGR). This plant contains various bioflavonoids such as diosgenin, kaempferol, catechin, daidzein, and 3'-methoxydaidzein. In this review, we discussed the pharmacological effects of these chemicals, including luteolin antimicrobial activity in a manner that it circumvents antibiotic resistance; rutin antivenom property; kaempferol as an agent that mitigates neuropathic pain; genistein anticancer property; isorhamnetin's ability to alleviate chronic obstructive pulmonary diseases (COPD); proanthocyanidins' ability to deal with diabetic neuropathy and analgesic property of catechin.

A chitosan and hyaluronic acid-modified layer-by-layer lubrication coating for cardiovascular catheter.

Despite the fact that transcatheter cardiovascular interventions are increasingly prevalent nowadays, friction damage caused by mechanical interaction between blood vessel and cardiovascular catheter limit their therapeutic utility. Based on dopamine-modified hyaluronic (HA-DN) acid and chitosan (CHI), a layer-by-layer lubricating coating for cardiovascular catheters was designed and assessed in this work. Results showed that the CHI/HA-DN composite coatings became more hydrophilic as the deposition layers were increased. The (CHI/HA-DN)8 assembly effectively reduced the coefficient of friction (COF) and related frictional energy dissipation. Besides, the fluorescent intensity, number of nucleus, SEM morphology and histological slices after friction experiment demonstrated that the (CHI/HA-DN)8 coating can protect the aorta from mechanical injury related to the control group. In conclusion, the CHI/HA-DN assembly can provide an alternative selection for low-damage lubricating cardiovascular catheter.

Catechol-modified chitosan hydrogel containing PLGA microspheres loaded with triclosan and chlorhexidine: a sustained-release antibacterial system for urinary catheters.

Blockage and infection are common in hospitals, especially with long-term indwelling catheters, due to bacterial adhesion, colonization, and other reasons. A drug-sustained-release antibacterial coating for urinary catheters was described in this paper. Chlorhexidine (CHX) and triclosan (TCS) were encapsulated in poly(lactic-co-glycolic acid) microspheres and mixed with a modified chitosan hydrogel deposited on the surface of silicone rubber. The results showed that drugs can be released continuously more than 35 days. Catechol-modified chitosan (Chi-C) hydrogel was successful synthesized according to FT-IR and UV spectrophotometry, as well as 1H NMR. Furthermore, the coating with CHX and TCS presented stable antibacterial ability compared to the other groups. The results of CCK-8 revealed that the coating was cytotoxic-free and had a wide range of applications. The findings could provide a new drug sustained-release system and hydrogel-microsphere assembly for urinary catheters. HighlightsThe microspheres presented a sustained release more than 40 days with a remarkable initial burst release.The microspheres/catechol-modified chitosan (Chi-C)/silicon rubber system emerged stable binding ability in liquid environment more than 14 days.The Chi-C/chlorhexidine (CHX)+triclosan (TCS) microspheres system presented better antimicrobial property for entire experiment period.The coated samples showed no significant difference for relative growth rate (RGR) compared to different groups.

Low Cost Three-Dimensional Programmed Mini-Pump Used in PCR.

Programmed mini-pumps play a significant role in various fields, such as chemistry, biology, and medicine, to transport a measured volume of liquid, especially in the current detection of COVID-19 with PCR. In view of the cost of the current automatic pipetting pump being higher, which is difficult to use in a regular lab, this paper designed and assembled a three-dimensional programmed mini-pump with the common parts and components, such as PLC controller, motor, microinjector, etc. With the weighting calibration before and after pipetting operation, the error of the pipette in 10 µL (0.2%), 2 µL (1.8%), and 1 µL (5.6%) can be obtained. Besides, the contrast test between three-dimensional programmed mini-pump and manual pipette was conducted with the ORF1ab and pGEM-3Zf (+) genes in qPCR. The results proved that the custom-made three-dimensional programmed mini-pump has a stronger reproducibility compared with manual pipette (ORF1ab: 24.06 ± 0.33 vs. 23.50 ± 0.58, p = 0.1014; pGEM-3Zf (+): 11.83.06 ± 0.24 vs. 11.50 ± 0.34, p = 0.8779). These results can lay the foundation for the functional, fast, and low-cost programmed mini-pump in PCR or other applications for trace measurements.

Developing a novel calcium magnesium silicate/graphene oxide incorporated silk fibroin porous scaffold with enhanced osteogenesis, angiogenesis and inhibited osteoclastogenesis.

Recently, biofunctional ions (Mg2+, Si4+, etc) and graphene derivatives are proved to be promising in stimulating bone formation. In this study, a novel inorganic/organic composite porous scaffold based on silk fibroin (SF), graphene oxide (GO), and calcium magnesium silicate (CMS) was developed for bone repair. The porous scaffolds obtained by lyophilization showed a little difference in pore structure while GO and CMS displayed a good interaction with SF matrix. The addition of CMS with good mineralization potential and sustainedly release ability of biofunctional ions (Ca2+, Mg2+and Si4+) increased the strength of SF scaffolds a little and facilitated the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by upregulating bone formation-related genes (ALP, COL1, OC and Runx2). The further incorporation of GO in SF scaffolds enhanced the compressive strength and water retention, and also remarkably promoted the osteogenic differentiation of BMSCs. Besides, the angiogenesis of human umbilical vein endothelial cells was significantly promoted by CMS/GO/SF scaffold extract through the upregulation of angiogenesis genes (eNOs and bFGF). Moreover, the osteoclastic formation ability of RAW264.7 cells was suppressed by the released ions from CMS/GO/SF scaffold through the down-regulation of CAK, MMP9 and TRAP. The promoted osteogenesis, angiogenesis and inhibited osteoclastogenesis functions of CMS/GO/SF composite scaffold may enable it as a novel therapy for bone repair and regeneration.

Advances in Filament Structure of 3D Bioprinted Biodegradable Bone Repair Scaffolds.

Conventional bone repair scaffolds can no longer meet the high standards and requirements of clinical applications in terms of preparation process and service performance. Studies have shown that the diversity of filament structures of implantable scaffolds is closely related to their overall properties (mechanical properties, degradation properties, and biological properties). To better elucidate the characteristics and advantages of different filament structures, this paper retrieves and summarizes the state of the art in the filament structure of the three-dimensional (3D) bioprinted biodegradable bone repair scaffolds, mainly including single-layer structure, double-layer structure, hollow structure, core-shell structure and bionic structures. The eximious performance of the novel scaffolds was discussed from different aspects (material composition, ink configuration, printing parameters, etc.). Besides, the additional functions of the current bone repair scaffold, such as chondrogenesis, angiogenesis, anti-bacteria, and anti-tumor, were also concluded. Finally, the paper prospects the future material selection, structural design, functional development, and performance optimization of bone repair scaffolds.

Patient-specific finite element analysis of frictional behavior in different esophageal regions during endoscopy.

PURPOSE: Endoscopy is a common and effective method to treat digestive system diseases. Not only can it detect the physiological state of the digestive tract, but also can conduct clinical operations. As a result, it's of great significance to make clear the relationship between the clinical operation and the complications. METHODS: Considering the difficulty in measuring the contact force and determining the stress distribution in real time during endoscopy, a specific-patient finite element model for the frictional behavior at the endoscope-esophagus interface was built in current study. By collecting the CT data of the patient, a 3D esophagus model was built and divided into three characteristic regions (narrow region, thoracic region and abdominal region) according to the physiological structure. RESULTS: Results showed that the radius of the narrowest position was the dominant factor for the maximum von Mises stress when the endoscope passed through the narrow region. For abdominal region and thoracic region, with the increasing coefficient of friction (COF) and amplitude, the total force duo to frictional force (CFSM), frictional dissipation (FD), strain energy (SE) and maximum von Mises stress (Max) all increased correspondingly. Meanwhile, the region of stress concentration gradually approached the initial contact stage. CONCLUSIONS: The results can provide theoretical basis and technical support for clinical application and offer some suggestions for medical workers during endoscopy as well.

Role of endothelial glycocalyx in sliding friction at the catheter-blood vessel interface.

Catheterization is a common medical operation to diagnose and treat cardiovascular diseases. The blood vessel lumen is coated with endothelial glycocalyx layer (EGL), which is important for the permeability and diffusion through the blood vessels wall, blood hemodynamics and mechanotransduction. However EGL's role in catheter-blood vessel friction is not explored. We use a porcine aorta to mimic the blood vessel and a catheter loop was made to rub in reciprocating sliding mode against it to understand the role of catheter loop curvature, stiffness, normal load, sliding speed and EGL on the friction properties. Trypsin treatment was used to cause a degradation of the EGL. Decrease in catheter loop stiffness and EGL degradation were the strongest factors which dramatically increased the coefficient of friction (COF) and frictional energy dissipation at the aorta-catheter interface. Increasing sliding speed caused an increase but increase in normal load first caused a decrease and then an increase in the COF and frictional energy. These results provide the basic data for safety of operation and damage control during catheterization in patients with degraded EGL.

Nanostructured Coating for Biomaterial Lubrication through Biomacromolecular Recruitment.

Biomaterials employed in the articular joint cavity, such as polycarbonate urethane (PCU) for meniscus replacement, lack of lubrication ability, leading to pain and tissue degradation. We present a nanostructured adhesive coating based on dopamine-modified hyaluronan (HADN) and poly-lysine (PLL), which can reestablish boundary lubrication between the cartilage and biomaterial. Lubrication restoration takes place without the need of exogenous lubricious molecules but through a novel strategy of recruitment of native lubricious molecules present in the surrounding milieu. The biomimetic adhesive coating PLL-HADN (78 nm thickness) shows a high adhesive strength (0.51 MPa) to PCU and a high synovial fluid responsiveness. The quartz crystal microbalance with dissipation monitoring shows the formation of a thick and softer layer when these coatings are brought in contact with the synovial fluid. X-ray photoelectron spectroscopy and ConA-Alexa staining show clear signs of lubricious protein (PRG4) recruitment on the PLL-HADN surface. Effective recruitment of a lubricious protein by PLL-HADN caused it to dissipate only one-third of the frictional energy as compared to bare PCU when rubbed against the cartilage. Histology shows that this reduction makes the PLL-HADN highly chondroprotective, whereas PLL-HA coatings still show signs of cartilage wear. Shear forces in the range of 0.07-0.1 N were able to remove ∼80% of the PRG4 from the PCU-PLL-HA but only 27% from the PCU-PLL-HADN. Thus, in this study, we have shown that surface recruitment and strong adsorption of biomacromolecules from the surrounding milieu is an effective biomaterial lubrication strategy. This opens up new possibilities for lubrication system reconstruction for medical devices.