The efficacy of extracorporeal shock wave therapy for knee osteoarthritis : an umbrella review.

BACKGROUND: An umbrella review was conducted to compare the effectiveness of extracorporeal shock wave therapy (ESWT) versus non-ESWT in the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: Three databases including PubMed, Embase and Web of science were searched up to September 2023. Literature screening, quality evaluation, and data extraction were performed according to inclusion and exclusion criteria. Meta-analysis of outcome indicators was performed using Revman 5.4 software. RESULTS: A total of eight meta-analysis were included in this umbrella review. All meta-analysis were graded against a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) and scored between 8 and 11. Compared to the sham group, the ESWT group showed better results in WOMAC (Western Ontario and McMaster Universities Arthritis Index) [mean difference (MD)=-2.94, 95% CI: -5.52, -0.37, P=0.03, I²=60%], Visual Analog Scale (VAS) (MD=-2.0, 95% CI: -2.5, -1.5, P<0.01, I²=0%), range of motion (ROM) (MD=17.55, 95% CI: 13.49, 21.61, P<0.00001, I²=0%), and Lequesne index (MD=-2.85, 95% CI: -3.64, -2.07, P<0.00001, I²=48%). CONCLUSION: Based on the results of our analysis, ESWT is now an effective therapy for improving pain and function in patients with KOA.

Extraction-free, immuno-RPA-CRISPR/Cas13a-based one-pot detection of glypican-3 directly from extracellular vesicles.

BACKGROUND: Glypican-3 (GPC3) is a heparan sulfate proteoglycan (HSPG) that binds to the cell membrane via glycosylphosphatidylinositol (GPI). It is not found in healthy adult liver but is overexpressed in human hepatocellular carcinoma (HCC). The protein marker GPC3 on extracellular vesicles (GPC3+ EVs) is also useful for HCC detection. Nevertheless, the absence of practical and dependable quantitative techniques to evaluate EVs proteins prevents their clinical implementation. RESULTS: Here, using an immuno-recombinase polymerase amplification (immuno-RPA) process and dual amplification of clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a, we firstly create an extraction-free one-pot immuno-RPA-CRISPR (opiCRISPR) for the direct and extremely sensitive detection of EVs proteins. The EVs protein-targeted detection probe is amplified by RPA to generate a long repetitive sequence containing multiple CRISPR RNA (crRNA) targeting barcodes, and the signal is further amplified by the CRISPR-Cas13a side-chain cleavage activity to generate a fluorescent signal. The results show that circulating extracellular vesicle GPC3 (eGPC3) levels are a reliable marker for GPC3 expression in tumor, opening up new avenues for tumor diagnosis. SIGNIFICANCE AND NOVELTY: We created an eGPC3 assay based on the CRISPR-Cas13a system, and successfully study the significance of extracellular vesicle GPC3 markers in hepatocellular carcinoma.

Current status and influencing factors of self-management in knee joint discomfort among middle-aged and elderly people: a cross-sectional study.

BACKGROUND: This study aims to identify the current status and factors influencing self-management of knee discomfort in middle-aged and elderly people in China. METHODS: A stratified multistage cluster sampling method was used to select participants from communities in China from January 15 to May 31, 2020. A cross-sectional survey was conducted using the general information questionnaire and the Knee Joint Discomfort Self-management Scale. Univariate analysis and a generalized linear model were used to analyze the factors influencing self-management. RESULTS: The prevalence of knee discomfort was 77%. Moderate to severe discomfort accounted for 30.5%. The average item score of self-management in 9640 participants was 1.98 ± 0.76. The highest and lowest levels were: 'daily life management' and 'information management'. Gender, ethnicity, education level, economic source, chronic disease, knee pain in the past month, and the degree of self-reported knee discomfort were significant predictors of self-management. CONCLUSION: The self-management of knee discomfort in middle-aged and elderly people is poor, and the degree of discomfort is a significant predictor. Healthcare providers should consider socioeconomic demographic and clinical characteristics to help these individuals improve their self-management skills. Attention should also be given to improving their ability to access health information and making them aware of disease risks.

DNA Methylation and Histone Modification in Dental-derived Mesenchymal Stem Cells.

Epigenetic regulation, mainly involving DNA methylation, histone modification, and noncoding RNAs (ncRNAs), is essential for the regulation of multiple cellular processes. Dental-derived mesenchymal stem cells (DMSCs), a kind of multipotent cells derived from dental tissues, are impactful in regenerative medicine. Recent studies have shown that epigenetic regulation plays a major role in DMSCs. Therefore, exploring how epigenetic regulation is involved in DMSCs may be of guiding significance for tissue repair and regeneration or for exploring more effective treatments. A number of research of ncRNAs in DMSCs have been reported. However, little is known about the roles of DNA methylation and histone modifications in DMSCs. In this review, we summarize the important roles of DNA methylation and histone modifications of the fate of DMSCs.

Progress in the Study of Non-Coding RNAs in Multidifferentiation Potential of Dental-Derived Mesenchymal Stem Cells.

For decades, the desire for tissue regeneration has never been quenched. Dental-derived mesenchymal stem cells (DMSCs), with the potential of self-renewal and multi-directional differentiation, have attracted much attention in this topic. Growing evidence suggests that non-coding RNAs (ncRNAs) can activate various regulatory processes. Even with a slight decrease or increase in expression, ncRNAs can weaken or even subvert cellular fate. Therefore, a systematic interpretation of ncRNAs that guide the differentiation of DMSCs into cells of other tissue types is urgently needed. In this review, we introduce the roles of ncRNAs in the differentiation of DMSCs, such as osteogenic differentiation, odontogenic differentiation, neurogenic differentiation, angiogenic differentiation and myogenic differentiation. Additionally, we illustrate the regulatory mechanisms of ncRNAs in the differentiation of DMSCs, such as epigenetic regulation, transcriptional regulation, mRNA modulation, miRNA sponges and signalling. Finally, we summarize the types and mechanisms of ncRNAs in the differentiation of DMSCs, such as let-7 family, miR-17∼92 family, miR-21, lncRNA H19, lncRNA ANCR, lncRNA MEG3, circRNA CDR1as and CircRNA SIPA1L1. If revealing the intricate relationship between ncRNAs and pluripotency of DMSCs 1 day, the application of DMSCs in regenerative medicine and tissue engineering will be improved. Our work could be an important stepping stone towards this future.

Relationship between knee joint discomfort, self-management behavior, and quality of life in the middle-aged and elderly people in China: A cross-sectional study.

Background: The aim of this study was to describe the knee joint discomfort, self-management behavior, and quality of life (QoL) in the middle-aged and elderly people in China and to clarify the relationship between the knee joint discomfort, self-management behavior, and QoL. Methods: It is a cross-sectional study and in this study, a stratified multistage random sampling method was used to collect data on the three factors such as knee joint discomfort, self-management behavior, and QoL among the middle-aged and elderly people in the Hunan Province. Spearman's correlation analysis was used to test the relationship between the knee joint discomfort, self-management behavior, and QoL. Results: The results of the present study showed that among them, the prevalence of knee pain was the highest (52.1%), followed by knee weakness (42.5%), numbness (41.8%), cold feeling (40.0%), tenderness (38.3%), and distension feeling (37.5%). Average score of self-management of knee joint discomfort in the middle-aged and elderly people was 2.14 ± 0.67. The level of self-management in each dimension ranged from high to low as emotional management, daily management, symptoms management, and information management. The average scores of physical component summary (PCS) and mental component summary (MCS) were 42.85 ± 5.34 and 43.62 ± 8.43, respectively. The occurrence, frequency, and severity of discomfort symptoms were positively correlated with the symptoms management, daily management, information management, and self-management behaviors, and negatively correlated with the emotional management, PCS and MSC, except for the occurrence of discomfort symptoms (P < 0.05). Conclusion: Knee joint discomfort was prevalent in the middle-aged and elderly people. In addition, they displayed a low level of self-management behavior and poor QoL. The middle-aged and elderly people faced knee discomfort symptoms, the more frequent and severe symptoms, the higher level of symptom management, daily management, and information management, and the lower level of emotional management and QoL.

MicroRNA-183 attenuates osteoarthritic pain by inhibiting the TGFα-mediated CCL2/CCR2 signalling axis.

AIMS: MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. METHODS: Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1ß, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. RESULTS: miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1ß, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. CONCLUSION: Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548-557.

Inhibition of microRNA-27b-3p relieves osteoarthritis pain via regulation of KDM4B-dependent DLX5.

Osteoarthritis (OA) represents a progressive degenerative disorder that predominantly affects the synovial membranes of joints. Recent studies have highlighted the significant role played by microRNAs (miRNAs) in OA development. The current study aimed to elucidate the underlying modulatory role of miR-27b-3p in the development of OA. The expression of miR-27b-3p in the OA patients and rat models post anterior cruciate ligament transection operation was measured using reverse transcription quantitative polymerase chain reaction, through which overexpressed miR-27b-3p was found in both of the samples. To further explore the miR-27b-3p functions in OA, western blot analysis, enzyme-linked immunosorbent assay, and ß-galactosidase activity assay were conducted with the results showing that knockdown of miR-27b-3p promoted expression of the osteogenic differentiation markers while inhibiting expression of the adipogenic differentiation markers, inflammatory factors, and cellular senescence of bone marrow mesenchymal stem cells (BMSCs). After that, the interactions between miR-27b-3p, lysine Demethylase 4B (KDM4B), and Distal-Less Homeobox 5 (DLX5) identified using dual-luciferase reporter gene assay and ChIP assay revealed that miR-27b-3p inhibited KDM4B and further reduced expression of DLX5. Finally, the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were assessed in rat models, and increased PWT and PWL were detected after miR-27b-3p silencing. In conclusion, suppression of miR-27b-3p could enhance KDM4B and DLX5 to alleviate OA pain, shedding light on a new potential therapeutic target for OA.

Autophagy participates in isoliquiritigenin-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.

Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes. Since autophagy has been reported to be related to melanin degradation, we also examined the activation of autophagy by ISL treatment in keratinocytes by measurement of autophagy-related proteins, ATG7, LC3 and p62. Moreover, si-ATG7-induced ATG7 knockdown and autophagy inhibitor 3-MA decreased LC3 II protein levels and increased PMEL17, p62 and melanin levels in HaCaT cells, which could be partially reversed by ISL treatment, indicating that autophagy participated in melanin degradation. The decreased p-AKT and p-mTOR proteins upon ISL treatment indicated the involvement of PI3K/AKT/mTOR signaling in ISL-induced melanin degradation. Taken together, we demonstrated that autophagy participates in ISL-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.

[Efficacy of health education on patients with hip replacement based on the Internet].

OBJECTIVE: To evaluate the efficacy of health education on patients with hip replacement based on the Internet, and to establish a new health education model through modern technology. METHODS: A total of 300 patients with hip replacement from March to August, 2015 were enrolled in this study. The participants were divided into a control group and an experimental group according to months surgeries performed. Traditional education was applied in the control group while the multimedia source material plus the Internet platform of Joint Registration System were applied in the experimental group. Levels of anxiety, degree of satisfaction, and postoperative complications were analyzed. RESULTS: The levels of knowledge, attitude and behavior compliance in the patients of the experimental group were significantly improved, while the levels of postoperative anxiety were decreased compared with those in the control group (P<0.05). CONCLUSION: Education based on the Internet platform of Joint Registration System and the computer video could improve patients' knowledge, attitude, and behavior, which is worthy of clinical spread.

Mixed system of Eudragit s-100 with a designed amphipathic peptide: control of interfacial elasticity by solution composition.

We report an interfacially active system based on an informational peptide surfactant mixed with an oppositely charged polyelectrolyte. The 21-residue cationic peptide, AM1, has previously been shown to respond reversibly to pH and metal ions at fluid interfaces, forming elastic films that can be rapidly switched to collapse foams or emulsions on demand. Here we report the reversible association of AM1 with the methacrylate-based anionic polymer Eudragit S-100. The strength of the association, in bulk aqueous solution, is modulated by added metal ions and by ionic strength. Addition of zinc ions to the peptide-polymer system promotes complex formation and phase separation, while addition of a chelating agent reverses the association. The addition of salt weakens peptide-polymer interactions in the presence or absence of zinc. At the air-water interface, Eudragit S-100 forms an elastic mixed film with AM1 in the absence of metal, under conditions where the peptide alone does not show interfacial elasticity. When zinc is present, the elasticity of the mixed film is increased, but the rate of interfacial adsorption slows due to formation of peptide-polymer complexes in bulk solution. An understanding of these interactions can be used to identify favorable foam-forming conditions in the mixed system.