An overview of 6-shogaol: new insights into its pharmacological properties and potential therapeutic activities.

Ginger (Zingiber officinale Roscoe) has traditionally been used as a cooking spice and herbal medicine for treating nausea and vomiting. More recently, ginger was found to effectively reduce the risk of diseases such as gastroenteritis, migraine, gonarthritis, etc., due to its various bioactive compounds. 6-Shogaol, the pungent phenolic substance in ginger, is the most pharmacologically active among such compounds. The aim of the present study was to review the pharmacological characteristic of 6-shogaol, including the properties of anti-inflammatory, antioxidant and antitumour, and its corresponding molecular mechanism. With its multiple mechanisms, 6-shogaol is considered a beneficial natural compound, and therefore, this review will shed some light on the therapeutic role of 6-shogaol and provide a theoretical basis for the development and clinical application of 6-shogaol.

Tongbi Huoluo Decoction alleviates cartilage degeneration in knee osteoarthritis by inhibiting degradation of extracellular matrix.

BACKGROUND: Knee osteoarthritis (KOA) is an age-related degenerative disease characterized by abrasion of articular cartilage. Tongbi Huoluo Decoction (TBHLD) has been transformed from the famous traditional Chinese medicine Duhuo Jisheng Decoction, which can effectively alleviate pain symptoms in KOA. However, the active components and mechanisms of TBHLD in treating KOA have not yet been elucidated. The purpose of the study was to demonstrate the molecular mechanism of TBHLD in treating KOA. METHODS: The components and targets of TBHLD and KOA were collected from multiple databases, and the protein to protein interaction (PPI) network was constructed. Next, we performed topological calculation and enrichment analysis. Besides, we performed virtual screening for molecular docking and molecular dynamics simulation (MDS). Furthermore, the vitro and vivo experiments were performed to evaluate the validity and mechanism of TBHLD. RESULTS: 206 active components and 187 potential targets were screened from Tongbi Huoluo Decoction. A total of 50 intersecting genes were identified between TBHLD and KOA, 20 core targets were calculated by network topology analysis. The core targets were enriched in the ECM interaction pathways. The results of virtual screening for molecular docking and MDS showed that the active components of TBHLD had steady binding conformations with core genes. Moreover, we identified 32 differential serum components in TBHLD-containing serum using LC-MS, including 22 upregulated and 10 downregulated serum components. TBHLD improved the proliferation activity of OA chondrocytes, decreased the expression of Col1a1, Col1a2, Mmp2, Mmp13 in OA chondrocytes, ameliorated the cartilage lesions and restored the cartilage abrasion. CONCLUSION: TBHLD inhibited degradation of cartilage ECM by regulating the expression of type I collagens and Mmps to ameliorate cartilage degeneration in KOA.

Myricitrin promotes osteogenesis and prevents ovariectomy bone mass loss via the PI3K/AKT signalling pathway.

This study aimed to explore the effect of myricitrin on osteoblast differentiation in mice immortalised bone marrow mesenchymal stem cells (imBMSCs). Additionally, ovariectomy (OVX) mice were employed to examine the effect of myricitrin on bone trabecular loss in vivo. The effect of myricitrin on the proliferation of imBMSCs was evaluated using a cell counting kit-8 assay. Alizarin red staining, alkaline phosphatase staining were performed to elucidate osteogenesis. Furthermore, qRT-PCR and western blot determined the expression of osteo-specific genes and proteins. To screen for candidate targets, mRNA transcriptome genes were sequenced using bioinformatics analyses. Western blot and molecular docking analysis were used to examine target signalling markers. Moreover, rescue experiments were used to confirm the effect of myricitrin on the osteogenic differentiation of imBMSCs. OVX mice were also used to estimate the delay capability of myricitrin on bone trabecular loss in vivo using western blot, micro-CT, tartaric acid phosphatase (Trap) staining, haematoxylin and eosin staining, Masson staining and immunochemistry. In vitro, myricitrin significantly enhanced osteo-specific genes and protein expression and calcium deposition. Moreover, mRNA transcriptome gene sequencing and molecular docking analysis revealed that this enhancement was accompanied by an upregulation of the PI3K/AKT signalling pathway. Furthermore, copanlisib, a PI3K inhibitor, partially reversed the osteogenesis promotion induced by myricitrin. In vivo, western blot, micro-CT, hematoxylin and eosin staining, Masson staining, Trap staining and immunochemistry revealed that bone trabecular loss rate was significantly alleviated in the myricitrin low- and high-dose groups, with an increased expression of osteopontin, osteoprotegerin, p-PI3K and p-AKT compared to the OVX group. Myricitrin enhances imBMSC osteoblast differentiation and attenuate bone mass loss partly through the upregulation of the PI3K/AKT signalling pathway. Thus, myricitrin has therapeutic potential as an antiosteoporosis drug.

A dual-nanozyme-loaded black phosphorus multifunctional therapeutic platform for combined photothermal/photodynamic/starvation cancer therapy.

The typical hypoxia of tumor microenvironments seriously affects the efficacy of starvation therapy (ST) and photodynamic therapy (PDT). Therefore, it is of great significance to prepare a multimodal combined therapy nanocomposite with the ability to relieve tumor hypoxia. It is an effective method to release oxygen into the tumor microenvironment using a nanoenzyme. In this work, two-dimensional black phosphorus nanosheets (BPNSs) were used as photothermal reagents and photosensitized agents due to the unique physical properties and also used as nano-carriers for the in situ reduction deposition of Au nanoparticles and fragmented MnO2 coatings. Finally, polyethylene glycol was introduced to obtain the nanocomposite BP@Au@MnO2-PEG (i.e., AMGP). In the tumor microenvironment, MnO2 can catalyze endogenous H2O2 to produce oxygen, improving the effect of ST and PDT. H2O2 generated via the catalytic oxidation of glucose by Au nanoparticles can continue to be used as the substrate catalyzed by MnO2. Meanwhile, black phosphorus nanosheets have excellent photothermal properties for photothermal treatment. The results of in vitro and in vivo experiments indicated that AMGP nanocomposites have good combined antitumor efficacies and biosafety.

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Fei Jin Sheng Formula in the Treatment of Lung Cancer.

BACKGROUND: Fei Jin Sheng Formula (FJSF) is widely used in clinical treatment of lung cancer. But the underlying active ingredients and mechanisms are unclear. OBJECTIVE: To investigate the active components and functional mechanisms of FJSF in treating lung cancer using a network pharmacology approach and molecular docking combined with vitro experiments Methods: Based on the TCMSP and related literature, the chemical components of related herbs in FJSF were collected. The active components of FJSF were screened by ADME parameters, and the targets were predicted by the Swiss Target Prediction database. The "drug-active ingredient-target" network was constructed by Cytoscape. Disease-related targets of lung cancer were acquired from GeneCards, OMIM, and TTD databases. Then drug-disease intersection target genes were obtained through the Venn tool. GO analysis and KEGG pathway enrichment analysis were performed via the Metascape database. Cytoscape was used to construct a PPI network and perform topological analysis. Kaplan-Meier Plotter was used to analyze the relationship between DVL2 and the prognosis of lung cancer patients. xCell method was used to estimate the relationship between DVL2 and immune cell infiltration in lung cancer. Molecular docking was performed by AutoDockTools-1.5.6. The results were verified by experiments in vitro. RESULTS: FJSF contained 272 active ingredients and 52 potential targets for lung cancer. GO enrichment analysis is mainly related to cell migration and movement, lipid metabolism, and protein kinase activity. KEGG pathway enrichment analysis mainly involves PI3K-Akt, TNF, HIF-1, and other pathways. Molecular docking shows that the compound Xambioona, quercetin and methyl palmitate in FJSF has a strong binding ability with NTRK1, APC, and DVL2. Analysis of the data in UCSC to analyze the expression of DVL2 in lung cancer shows that DVL2 was overexpressed in lung adenocarcinoma tissues. Kaplan-Meier analysis shows that the higher DVL2 expression in lung cancer patients was associated with poorer overall survival and poorer survival in stage I patients. It was negatively correlated with the infiltration of various immune cells in the lung cancer microenvironment. Vitro Experiment showed that Methyl Palmitate (MP) can inhibit the proliferation, migration, and invasion of lung cancer cells, and its mechanism of action may be to downregulate the expression of DVL2. CONCLUSION: FJSF may play a role in inhibiting the occurrence and development of lung cancer by downregulating the expression of DVL2 in A549 cells through its active ingredient Methyl Palmitate. These results provide scientific evidence for further investigations into the role of FJSF and Methyl Palmitate in the treatment of lung cancer.

Bioinformatics analysis combined with molecular dynamics simulation validation to elucidate the potential molecular mechanisms of Jianshen Decoction for treatment of osteoporotic fracture.

Osteoporotic fracture (OPF) is a prevalent skeletal disease in the middle-aged and elderly. In clinical practice, Jianshen Decoction (JSD) has been used to treat OPFs. However, the specific effective components and mechanisms of JSD on OPF have not been explored. Therefore, this study used bioinformatics analysis combined with molecular dynamics simulation validation to explore the molecular mechanism of JSD treatment of OPF. Public databases (TCMSP, Batman TCM) were used to find the effective active components and corresponding target proteins of JSD (screening conditions: OB ≥ 30%, drug-likeness ≥ 0.18, half-life ≥ 4). Differentially expressed genes (DEGs) related to OPF lesions were obtained based on the gene expression omnibus database (screening conditions: adjust P value < .01, | log2 FC | ≥ 1.0). The BisoGenet plug-in and the CytoNCA plug-in of Cytoscape were used to derive the potential core target proteins of JSD in the treatment of OPF. The JSD active ingredient target interaction network and the JSD-OPF target protein core network were constructed using the Cytoscape software. In addition, the R language Bioconductor package and clusterProfiler package were used to perform gene ontology (GO)/Kyoto Encylopedia Of Genes And Genome (KEGG) enrichment analysis on core genes to explain the biological functions and signal pathways of core proteins. Finally, molecular docking and molecular dynamics simulations were carried out through PyMOL, AutoDockTools 1.5.6, Vina, LeDock, Discovery Studio (DS) 2019, and other software to verify the binding ability of drug active ingredients and core target proteins. A total of 245 targets and 70 active components were identified. Through protein-protein interaction (PPI) network construction, 39 core targets were selected for further research. GO/KEGG enrichment analysis showed that the DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, MAPK signaling pathway, and ErbB signaling pathway were mainly involved. The results of molecular docking and molecular dynamics simulations supported the good interaction between MYC protein and Quercetin/Stigmasterol. In this study, bioinformatics, molecular docking, and molecular dynamics simulations were used for the first time to clarify the active components, molecular targets, and key biological pathways of JSD in the treatment of OPF, providing a theoretical basis for further research.

Quercetin protects against iron overload-induced osteoporosis through activating the Nrf2/HO-1 pathway.

AIMS: Eucommia is the tree bark of Eucommia japonica, family Eucommiaceae. In traditional Chinese medicine, Eucommia is often used to treat osteoporosis. Quercetin (QUE), a major flavonoid extract of Eucommia japonica, has been reported to have anti-osteoporosis effects. However, there are no studies reporting the mechanism of QUE in the treatment of iron overload-induced osteoporosis. This study set out to investigate the therapeutic effects of QUE against iron overload-induced bone loss and its potential molecular mechanisms. MATERIALS AND METHODS: In vitro, MC3T3-E1 cells were used to study the effects of QUE on osteogenic differentiation, anti-apoptosis and anti-oxidative stress damage in an iron overload environment (FAC 200 µM). In vivo, we constructed an iron overload mouse model by injecting iron dextrose intraperitoneally and assessed the osteoprotective effects of QUE by Micro-CT and histological analysis. KEY FINDINGS: In vitro, we found that QUE increased the ALP activity of MC3T3-E1 cells in iron overload environment, promoted the formation of bone mineralized nodules and upregulated the expression of Runx2 and Osterix. In addition, QUE was able to reduce FAC-induced apoptosis and ROS production, down-regulated the expression of Caspase3 and Bax, and up-regulated the expression of Bcl-2. In further studies, we found that QUE activated the Nrf2/HO-1 signaling pathway and attenuated FAC-induced oxidative stress damage. The results of the in vivo study showed that QUE was able to reduce iron deposition induced by iron dextrose and attenuate bone loss. SIGNIFICANCE: Our results suggested that QUE protects against iron overload-induced osteoporosis by activating the Nrf2/HO-1 signaling pathway.

Oxygen-deficient titanium dioxide-loaded black phosphorus nanosheets for synergistic photothermal and sonodynamic cancer therapy.

Malignant tumors, particularly those located in deep tissues, have always been a grievous threat to human health. Sonodynamic therapy (SDT) has recently attracted great attention due to deep tissue penetration. However, the lack of effective sonosensitizers and the poor therapeutic efficacy severely limit their wider use. Herein, dual-functionalized black phosphorus nanosheets (BP@PEI-PEG, i.e., PPBP) integrating black oxygen-deficient titanium dioxide particles (B-TiO2) were successfully constructed (PPBP-B-TiO2) for synergistic photothermal (PTT)/sonodynamic therapy. In these nanocomposites, black titanium dioxide can enhance the separation of electrons (e-) and holes (h+) due to the oxygen-deficient structure and significantly improves the production of reactive oxygen species (ROS) for SDT, while the BP nanosheets endow the nanocomposites with a higher photothermal conversion capability for photothermal therapy (η = 44.1%) which can prolong the blood circulation and improve the O2 supply. In vivo experiments prove that PPBP-B-TiO2 nanocomposites exhibited outstanding tumor inhibition efficacy and excellent biocompatibility. This work provides a prospective platform for combined photothermal/sonodynamic cancer therapy.

Hemin-loaded black phosphorus-based nanosystem for enhanced photodynamic therapy and a synergistic photothermally/photodynamically activated inflammatory immune response.

The biocompatible nanosystem integrating hemin into black phosphorus nanosheets was ingeniously constructed through the easy modified strategy. Taking advantage of the enhanced permeability and retention (EPR) effect, the designed nanosystem could accumulate into the tumor location, leading to attractive cytotoxicity through the enhanced photodynamic therapy (PDT) ascribing to the catalytic oxygen supply and GSH depletion of hemin. Simultaneously, combining PDT and photothermal therapy (PTT) showed an apparent promotion in anti-tumor effect. Moreover, inflammatory response and immune activation amplified anti-tumor effect, which could compensate limitations of exogenous therapy (i.e., limited tissue depth and intensity-dependent curation effect) and potentiate the efficiency of the endogenous immune-activating behavior. Especially, the designed nanosystem degraded followed by being metabolized in the blood circulation. By and large, this constructed nanosystem provides the new insight into designing biocompatible nanomaterials and paves the ideal way for anti-tumor therapy. STATEMENT OF SIGNIFICANCE: Biocompatible nanomaterials-based synergistic tumor therapy offers the potential application prospect. Taking advantage of degradable black phosphorus, the nanosystem integrating hemin into black phosphorus for the enhanced photodynamic therapy and synergistic photothermal-photodynamic activating inflammation-immune response was developed and the results demonstrate that tumor growth was inhibited followed by activating inflammatory factors and leading to satisfactory immune response.

Study on the Mechanism of Sancao Tiaowei Decoction in the Treatment of MNNG-Induced Precancerous Lesions of Gastric Carcinoma Through Hedgehog Signaling Pathway.

Sancao Tiaowei Decoction (SCTWD), a traditional Chinese medicine created by Professor Chen Weijian, has been used in the prevention and treatment of precancerous lesions of gastric carcinoma (PLGC). However, its mechanism has not been made clear. This study aimed to evaluate the therapeutic effect of SCTWD on 1-methyl-3-nitro-1-nitrosoguanidine-induced PLGC in rats and the mechanism of this effect. We found that SCTWD effectively repaired gastric mucosal injury, reversed the process of PLGC, and inhibited the occurrence of gastric cancer to some extent. In the results of hematoxylin-eosin (HE) staining, the number and arrangement of mucosal glands and the number of mononuclear cells in the lamina propria were improved in varying degrees; the enzyme-linked immunosorbent assay (ELISA) showed that the PG I and PGR of the medication treatment group were significantly higher; a Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test showed that SCTWD could significantly upregulate the expression levels of Shh, Ptch, and Gli-1 in the gastric tissue of rats. The immunohistochemical method showed that SCTWD could significantly upregulate the protein expressions of Shh, Gli-1, Smo, cyclin D1, CDKN2A/p16INK4a, and NF-κBP65 and could reduce the expression of Ptch at the same time. Through the preliminary analysis of 75 compounds screened by UPLC-Q-TOF-MS, the main components, such as organic acids, esters and anhydrides, flavonoids, phenols, tanshinones, and so on, have anti-inflammatory and anti-tumor pharmacological effects. The results of KEGG enrichment analysis showed that 5 signaling pathways related to this project were found, and 33 differential genes were presented to construct the interaction network. These results suggested that SCTWD had a good regulatory effect on PLGC and thus may have a multi-targeted effect; SCTWD can not only significantly improve the pathological changes of gastric mucosa in rats with PLGC but also exert a strong effect of the regulation of the hedgehog signaling pathway.

Bioinformatics analysis combined with experimental validation to explore the mechanism of XianLing GuBao capsule against osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: XianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear. AIM OF THE STUDY: This study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB. MATERIALS AND METHODS: Disease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism. RESULTS: A total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1ß, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats. CONCLUSIONS: XLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.

Emerging two-dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers.

In recent years, more and more research enthusiasm has been devoted to the development of emerging two-dimensional (2D) monoelement materials (Xenes) and explored potential applications in various fields, especially biomedicine and bioimaging. The inspiring results attribute to their excellent physicochemical properties, including adjustable band gap, surface electronic layout characteristics, and so on, making it easier for surface modification in order to meet designated needs. As a popular interdisciplinary research frontier, a variety of methods for fabricating 2D Xenes have recently been adopted for pre-preparing future practical bioimaging applications, which implies that these materials will have broad clinical application prospects in the future. In this review, we will concentrate on the family of 2D Xenes and summarize their fabrication and modification methods firstly. Then, their applications in bioimaging as nanocarriers will be described according to the Periodic Table of Elements. In addition, current challenges and prospects for further clinical applications will be under discussion and use black phosphorus as a typical example. At last, general conclusion will be made that it is worth expecting that 2D Xenes will play a key role in the next generation of oncologic bioimaging in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Biodegradable L-lysine-modified amino black phosphorus/poly(l-lactide-coε-caprolactone) nanofibers with enhancements in hydrophilicity, shape recovery and osteodifferentiation properties.

Biodegradable poly-(lactide-coε-caprolactone) (PLCL) scaffolds have opened new perspectives for tissue engineering due to their nontoxic and fascinating functionality. Herein, a black phosphorus-based biodegradable material with a combination of promising enhanced hydrophilicity, shape recovery and osteodifferentiation properties was proposed. First, amino black phosphorous (BP-NH2) was prepared by a simple ball milling method. Then, L-lysine-modified black phosphorous (L-NH-BP) was formed by hydrogen bonding between L-lysine and amino BP and integrated into PLCL to form PLCL/L-NH-BP composite fibers. The scaffolds had excellent shape recovery and shape fixity properties. Moreover, based on gene expression and protein level assessment, the scaffolds could enhance the expression of alkaline phosphatase (ALP) and bone morphogenetic protein 2 (BMP2), simultaneously improving the mineralization ability of bone mesenchymal stem cells. Specifically, this new composite material was experimentally verified to be degradable under mild conditions. This strategy provided new insight into the design of multifunctional materials for diverse applications.

Electroacupuncture as an Adjuvant Approach to Rehabilitation during Postacute Phase after Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Increasing attention has been paid to electroacupuncture (EA) for promoting postoperative rehabilitation, but the effectiveness of EA for rehabilitation after total knee arthroplasty (TKA) remains obscure. OBJECTIVE: To examine the effect of EA on rehabilitation after TKA. METHODS: Database searches on PubMed, CINAHL, Embase, and China National Knowledge Infrastructure (CNKI) were carried out to obtain articles, from inception to 15 October 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was conducted to assess the effects of acupuncture on pain, range of knee motion, and postoperative vomiting after TKA. RESULTS: In the current study, a total of ten randomized clinical trials were included according to the inclusion and exclusion criteria. Compared to basic treatment, EA combined with basic treatment showed a significantly greater pain reduction on 3, 7, and 14 days postoperatively after TKA. However, we found that EA had no significant improvement in enhancing the range of knee motion and decreasing the percentage of vomiting. Subgroup analysis suggested that a combination of EA and rehabilitation training was superior to rehabilitation training in pain relief, while EA combined with celecoxib capsules showed no significant difference in improving pain compared to celecoxib capsules alone. CONCLUSIONS: In the postacute phase after TKA, EA, as a supplementary treatment, could reduce postoperative pain, but no evidence supported the benefits of EA for improving ROM of knee and decreasing the ratio of vomiting. Additional high-quality and large-scale RCTs are warranted.

The Efficacy of Backward Walking on Static Stability, Proprioception, Pain, and Physical Function of Patients with Knee Osteoarthritis: A Randomized Controlled Trial.

OBJECTIVE: Impaired static stability and proprioception have been observed in individuals with knee osteoarthritis (KOA), which serves as a major factor increasing risk of fall. This study aimed to investigate the effects of backward walking (BW) on static stability, proprioception, pain, and physical function in KOA patients. METHODS: Thirty-two subjects with knee osteoarthritis were randomly assigned to either an BW group (BG, n = 16) or a control group (CG, n = 16). The participants in the BG received combination treatment of a 4-week BW training and conventional treatments, while those in the CG was treated with conventional treatments alone. All the participants were tested for the assessment of static stability [center of pressure (COP) sway, including sway length (SL, mm) and sway area (SA, mm2)] and proprioception [average trajectory error (ATE, %) and completion time (CT, second)]. Additionally, pain and knee function scores were measured by the numerical rating scale (NRS) and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index, respectively. The assessments were conducted before and after intervention. RESULTS: The COP sway (SA and SL), ATE, NRS, and WOMAC showed a significant decline at week 4 in the two groups in contrast to their baseline (P < 0.05). Moreover, after 4-week intervention, the SA [(610.50 ± 464.26) mm2 vs. (538.69 ± 420.52) mm2], NRS [(1.56 ± 0.63) vs. (2.25 ± 0.86)], and WOMAC [(11.69 ± 2.50) vs. (16.19 ± 3.94)] showed a significantly greater decrease in the BG compared to the CG (P < 0.05, respectively). However, the proprioception (ATE and CT) was closely similar between both groups at week 4 (P > 0.05). CONCLUSION: BW is an effective adjunct to conventional treatment in reducing pain, improving physical function and static stability for KOA patients. It should be taken into consideration when developing rehabilitation programs for people with KOA.

Highly Expressed CYBRD1 Associated with Glioma Recurrence Regulates the Immune Response of Glioma Cells to Interferon.

Invasiveness, resistance to treatment, and recurrence of gliomas are significant hurdles to successful treatment regimens. Data sets from Gene Expression Omnibus (GEO), CGGA-RNAseq, and The Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) were analyzed, and an increased expression of Cytochrome B Reductase 1 (CYBRD1) was identified and could be associated with aggravated clinical outcomes. Gene ontology (GO) enrichment analysis indicated that CYBRD1 co-expressed genes are enriched during an immune response. CYBRD1 overexpression in glioma cell lines is enhanced, whereas CYBRD1 silencing attenuated the aggressiveness of glioma cells. In IFN-α-treated glioma cells, IFN-α suppressed the viability and migratory ability and invasive ability of glioma cells, whereas CYBRD1 overexpression attenuated the antitumor effects of IFN-α. CYBRD1 could potentially serve as a biomarker for glioma recurrence. CYBRD1 overexpression enhances glioma cell aggressiveness and attenuates glioma cell response to IFN-α.

Study on the potential active components and molecular mechanism of Xiao Huoluo Pills in the treatment of cartilage degeneration of knee osteoarthritis based on bioinformatics analysis and molecular docking technology.

BACKGROUND: Knee osteoarthritis is a common joint degenerative disease. Xiao Huoluo Pills (XHLP) has been used to treat degenerative diseases such as osteoarthritis and hyperosteogeny. However, XHLP's specific effective ingredients and mechanism of action against osteoarthritis have not been explored. Therefore, bioinformatics technology and molecular docking technology are employed in this study to explore the molecular basis and mechanism of XHLP in the treatment of knee osteoarthritis. METHODS: Public databases (TCMSP, Batman-TCM, HERB, DrugBank, and UniProt) are used to find the effective active components and corresponding target proteins of XHLP (screening conditions: OB > 30%, DL ≥ 0.18). Differentially expressed genes related to cartilage lesions of knee osteoarthritis are obtained based on the GEO database (screening conditions: adjust P value < 0.01, |log2 FC|≥1.0). The Venn package in R language and the BisoGenet plug-in in Cytoscape are adopted to predict the potential molecules of XHLP in the treatment of knee osteoarthritis. The XHLP-active component-target interaction network and the XHLP-knee osteoarthritis-target protein core network are constructed using Cytoscape software. Besides, GO/KEGG enrichment analysis on core genes is performed using the Bioconductor package and clusterProfiler package in the R language to explain the biological functions and signal pathways of the core proteins. Finally, molecular docking is performed through software such as Vina, LeDock, Discovery Studio 2016, PyMOL, AutoDockTools 1.5.6, so as to verify the binding ability between the active components of the drug and the core target protein. RESULTS: XHLP has been screened out of 71 potentially effective active compounds for the treatment of OA, mainly including quercetin, Stigmasterol, beta-sitosterol, Izoteolin, and ellagic acid. Knee osteoarthritis cartilage lesion sequencing data (GSE114007) was screened out of 1672 differentially expressed genes, including 913 upregulated genes and 759 downregulated genes, displayed as heat maps and volcano maps. Besides, 33 core target proteins are calculated by Venn data package in R and BisoGenet plug-in in Cytoscape. The enrichment analysis on these target genes revealed that the core target genes are mainly involved in biological processes such as response to oxygen levels, mechanical stimulus, vitamin, drug, and regulation of smooth muscle cell proliferation. These core target genes are involved in signaling pathways related to cartilage degeneration of knee osteoarthritis such as TNF signaling pathway and PI3K-Akt signaling pathway. Finally, the molecular docking verification demonstrates that some active components of the drug have good molecular docking and binding ability with the core target protein, further confirming that XHLP has the effect of inhibiting cartilage degeneration in knee osteoarthritis. CONCLUSIONS: In this study, based on the research foundation of bioinformatics and molecular docking technology, the active components and core target molecules of XHLP for the treatment of cartilage degeneration of knee osteoarthritis are screened out, and the potential mechanism of XHLP inhibiting cartilage degeneration of knee osteoarthritis is deeply explored. The results provide theoretical basis and new treatment plan for XHLP in the treatment of knee osteoarthritis.

Ultrasmall MoS2 nanodots-wrapped perfluorohexane nanodroplets for dual-modal imaging and enhanced photothermal therapy.

Development of a multifunctional nanotherapeutic agent with high contrast-enhanced dual-modal imaging and photothermal therapy (PTT) efficacy is of great interest. Combination of ultrasound (US) and computed tomography (CT) imaging offers high spatial resolution images, showing great potential in medical imaging. Herein, the semiconducting perfluorohexane (PFH) nanodroplets, MoS2-PFH-PLLAs, are developed by stabilizing PFH droplets with the coating shell of poly (lactic-co-glycolic acid) (PLLA) and encapsulating the droplets with photoabsorbers of ultrasmall molybdenum disulfide (MoS2) nanodots. Upon near-infrared (NIR) irradiation, the MoS2-PFH-PLLAs can absorb the NIR light and convert it into heat, which not only promotes liquid-to-gas phase transition of PFH but also triggers photothermal heating, resulting in contrast-enhanced US/CT imaging and photothermal killing effect in vitro. Furthermore, the production of microbubbles can serve as the blasting agents to collaboratively enhance PTT efficacy after NIR irradiation. When intravenously injected into tumor-bearing mice, the MoS2-PFH-PLLAs exhibit a dual-modal US/CT imaging-guided synergistically therapeutic efficacy under NIR irradiation, resulting in tumor ablation. These nanotherapeutic agents demonstrate good biocompatibility, highly contrast-enhanced US/CT imaging, and combinational enhanced PTT efficacy.

Relationship between hip joint medial space ratio and collapse of femoral head in non-traumatic osteonecrosis: a retrospective study.

To retrospectively analyze the medial space ratio (MSR) of the hip joint to evaluate its efficacy in predicting osteonecrosis of femoral head (ONFH)-induced collapse and its impacts on the mechanical environment of necrotic femoral head. In this retrospective analysis of traditional Chinese medicine, non-traumatic ONFH (NONFH) patients from January 2008 to December 2013 were selected. The patients were divided into collapse group and non-collapse group based on whether the femoral head collapsed. The anatomical parameters including center-edge (CE) angle, sharp angle, acetabular depth ratio and MSR were evaluated. Receiver operating characteristic curves were estimated to evaluate the sensitivity and specificity of MSR and CE angle in collapse prediction. The results showed that 135 patients (151 hips) were included in this study. The differences in CE angle and MSR between collapse group and non-collapse group were statistically significant. The mean survival time of the hips of patients with MSR <20.35 was greater (P < 0.001) than that of patients with MSR >20.35. The ONFH patients with MSR >20.35 were prone to stress concentration. We could conclude that the hip joint MSR and CE angle strongly correlated with the collapse of NONFH. The specificity of MSR is higher than that of CE angle. When MSR is >20.35, the collapse rate of ONFH will increase significantly.

Acupuncture for Rehabilitation After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: There is an increasing interest in acupuncture for promoting post-operative rehabilitation, but the effectiveness of acupuncture for rehabilitation after total knee arthroplasty (TKA) remains controversial. Objective: This study aims to investigate the effect of acupuncture on rehabilitation after TKA. Methods: Database searches of PubMed, EMBASE, CINAHL, and China National Knowledge Infrastructure (CNKI) were conducted to obtain articles published until August 2020. All identified articles were screened, and data from each included study were extracted independently by two investigators. Meta-analysis was performed to examine the effects of acupuncture on pain, range of knee motion, function, and nausea/vomiting after TKA. Results: A total of nine randomized clinical trials were included according to the inclusion and exclusion criteria in this review. Compared with routine treatment, acupuncture combined with routine treatment showed a significantly greater pain reduction at 8, 12, 24, and 48 h post-operatively after TKA. Meanwhile, we found that the acupuncture groups showed a significant function improvement and a lower percentage of nausea/vomiting in comparison with the control groups after operation. However, acupuncture groups demonstrated no statistically significant improvement in post-operative pain at 4 h, 7 days, 14 days, and more than 21 days, and no significant difference in range of knee motion was observed between the acupuncture groups and control groups after surgery. Conclusions: Acupuncture, as a supplementary treatment after TKA, could improve function and reduce nausea/vomiting. However, the effect of acupuncture on pain relief may be mainly achieved within post-operative 48 h, and it had no efficacy in improving range of knee motion. More large-scale and high-quality studies are warranted.