Efficacy of virtual reality exercise in knee osteoarthritis rehabilitation: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to investigate the effects of virtual reality (VR) exercise compared to traditional rehabilitation on pain, function, and muscle strength in patients with knee osteoarthritis (KOA). Additionally, the study explores the mechanisms by which VR exercise contributes to the rehabilitation of KOA patients. Methods: We systematically searched PubMed, the Cochrane Library, Embase, Web of Science, Scopus, and PEDro according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Our search spanned from the library construction to 24 May 2024, focusing on randomized controlled trials Primary outcomes included pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and muscle strength. Meta-analysis was conducted using RevMan (version 5.4) and Stata (version 14.0). The bias risk of included studies was assessed using the Cochrane RoB 2.0 tool, while the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: This meta-analysis and systematic review included nine studies involving 456 KOA patients. The results indicated that VR exercise significantly improved pain scores (SMD, -1.53; 95% CI: -2.50 to -0.55; p = 0.002), WOMAC total score (MD, -14.79; 95% CI: -28.26 to -1.33; p = 0.03), WOMAC pain score (MD, -0.93; 95% CI: -1.52 to -0.34; p = 0.002), knee extensor strength (SMD, 0.51; 95% CI: 0.14 to 0.87; p = 0.006), and knee flexor strength (SMD, 0.65; 95% CI: 0.28 to 1.01; p = 0.0005), but not significantly for WOMAC stiffness (MD, -0.01; 95% CI: -1.21 to 1.19; p = 0.99) and physical function (MD, -0.35; 95% CI: -0.79 to -0.09; p = 0.12). Conclusion: VR exercise significantly alleviates pain, enhances muscle strength and WOMAC total score in KOA patients, but improvements in joint stiffness and physical function are not significant. However, the current number of studies is limited, necessitating further research to expand on the present findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024540061, identifier CRD42024540061.

Protective effects of butyrate on cerebral ischaemic injury in animal models: a systematic review and meta-analysis.

Introduction: Cerebral ischaemic stroke is a common disease that poses a serious threat to human health. Butyrate is an important metabolite of intestinal microorganisms. Recent studies have shown that butyrate has a significant protective effect in animal models of cerebral ischaemic injury. Objective: The aim of this study was to evaluate the protective effect of butyrate on cerebral ischaemic stroke by meta-analysis, aiming to provide a scientific basis for the clinical application of butyrate in patients with cerebral ischaemia. Materials and methods: A systematic search was conducted for all relevant studies published before 23 January 2024, in PubMed, Web of Science, Cochrane Library, and Embase. Methodological quality was assessed using Syrcle's risk of bias tool for animal studies. Data were analysed using Rev Man 5.3 software. Results: A total of nine studies were included, and compared with controls, butyrate significantly increased BDNF levels in the brain (SMD = 2.33, 95%CI = [1.20, 3.47], p < 0.005) and P-Akt expression (SMD = 3.53, 95% CI = [0.97, 6.10], p < 0.05). Butyrate also decreased IL-ß levels in the brain (SMD = -2.02, 95% CI = [-3.22, -0.81], p < 0.005), TNF-α levels (SMD = -0.86, 95% CI = [-1.60, -0.12], p < 0.05), and peripheral vascular IL-1ß levels (SMD = -2.10, 95%CI = [-3.59, -0.61], p < 0.05). In addition, butyrate reduced cerebral infarct volume (MD = -11.29, 95%CI = [-17.03, -5.54], p < 0.05), mNSS score (MD = -2.86, 95%CI = [-4.12, -1.60], p < 0.005), foot fault score (MD = -7.59, 95%CI = [-9.83, -5, 35], p < 0.005), and Morris water maze time (SMD = -2.49, 95%CI = [-4.42, -0.55], p < 0.05). Conclusion: The results of this study indicate that butyrate has a protective effect on cerebral ischaemic stroke in animal models, and the mechanism is related to reducing inflammation and inhibiting apoptosis. It provides an evidence-based basis for the future clinical development of butyrate in the treatment of ischaemic stroke. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42023482844.

Photobiomodulation improves depression symptoms: a systematic review and meta-analysis of randomized controlled trials.

Background: Depression is a common mental illness that is widely recognized by its lack of pleasure, fatigue, low mood, and, in severe cases, even suicidal tendencies. Photobiomodulation (PBM) is a non-invasive neuromodulation technique that could treat patients with mood disorders such as depression. Methods: A systematic search of ten databases, including randomized controlled trials (RCTs) for depression, was conducted from the time of library construction to September 25, 2023. The primary outcome was depression. The secondary outcome was sleep. Meta-analysis was performed using RevMan (version 5.4) and Stata (version 14.0). Subgroup analyses were performed to identify sources of heterogeneity. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Three thousand two hundred and sixty-five studies were retrieved from the database and screened for inclusion in eleven trials. The forest plot results demonstrated that PBM alleviated depression (SMD = -0.55, 95% CI [-0.75, -0.35], I2 = 46%). But it is not statistically significant for patients' sleep outcomes (SMD = -0.82, 95% CI [-2.41, 0.77], I2 = 0%, p > 0.05). Subgroup analysis showed that s-PBM was superior to t-PBM in relieving symptoms of depression. The best improvement for t-PBM was achieved using a wavelength of 823 nm, fluence of 10-100 J/cm2, irradiance of 50-100 mW/cm2, irradiance time of 30 min, treatment frequency < 3/week, and number of treatments >15 times. The best improvement for s-PBM was achieved using a wavelength of 808 nm, fluence ≤1 J/cm2, irradiance of 50-100 mW/cm2, irradiance time ≤ 5 min, treatment frequency ≥ 3/week, number of treatments >15 times. All results had evidence quality that was either moderate or very low, and there was no bias in publication. Conclusion: We conclude that PBM is effective in reducing depression symptoms in patients. However, the current number of studies is small, and further studies are needed to extend the current analysis results. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42023444677.

Correction: Adsorption of polycyclic aromatic hydrocarbons over CuZnFeAl-LDH modified by sodium dodecyl sulfate.

[This corrects the article DOI: 10.1039/D2RA03968K.].

Adsorption of polycyclic aromatic hydrocarbons over CuZnFeAl-LDH modified by sodium dodecyl sulfate.

Polycyclic aromatic hydrocarbons (PAHs) have received extensive attention due to being highly toxic, mutagenic, and carcinogenic organic pollutants. As a result, a series of adsorbents have been designed and developed to solve the problem. In this paper, CuZnFeAl-S has been explored as a highly efficient adsorbent for PAHs. First, CuZnFeAl-LDH was prepared using a coprecipitation method and then calcined at 500 °C to obtain CuZnFeAlO. Finally, CuZnFeAl-S was prepared by modifying CuZnFeAlO with sodium dodecyl sulfate (SDS). The physical and chemical properties of the adsorbents were characterized by XRD, N2 adsorption-desorption, SEM, ICP, FT-IR, TG-DSC, and IGC; subsequently their adsorption performance was investigated. The results show that the surface properties of CuZnFeAl-S changed from hydrophilic to hydrophobic after SDS modification, which enhanced the adsorption of PAHs obviously. The removal of naphthalene and phenanthrene on CuZnFeAl-S reached 97.3% and 90.3%, respectively. And the adsorption process of naphthalene and phenanthrene conforms to Langmuir adsorption and Freundlich adsorption, respectively. Besides, the adsorption thermodynamics indicate that the adsorption of PAHs was a spontaneous exothermic reaction. The highly efficient PAH adsorption performance of CuZnFeAl-S is the synergistic result of various molecule interactions, such as hydrogen bonding, π-π interactions, and electrostatic attraction.

Carnosol inhibits osteoclastogenesis in vivo and in vitro by blocking the RANKL­induced NF­κB signaling pathway.

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast­mediated bone formation. Disruption of bone homeostasis due to excessive osteoclastogenesis or reduced osteogenesis results in various disorders, such as postmenopausal osteoporosis. Receptor activator of NF­κB ligand (RANKL) stimulation of the NF­κB signaling pathway is essential in osteoclastogenesis. The aim of the present study was to investigate the novel effects of carnosol, an active compound found in Rosmarinus officinalis, on RANKL­induced osteoclastogenesis both in vitro and in vivo. TRAP staining showed that carnosol significantly inhibited osteoclasts differentiation of bone marrow monocytes and RAW264.7 cells. Western blot results showed that the protein expression levels of osteoclastogenesis­associated genes, including cathepsin K, tartrate­resistant acid phosphatase and MMP­9, were markedly inhibited by carnosol, which may have suppressed osteoclast function. Furthermore, western blot and immunofluorescent staining results revealed that carnosol markedly suppressed the phosphorylation of p65 induced by RANKL and blocked its nuclear translocation, indicating the suppression of NF­κB signaling pathway. H&E staining and micro­CT results showed that in vivo treatment with carnosol significantly attenuated ovariectomy­induced bone loss in mice. In conclusion, the present study indicated that carnosol may suppress osteoclastogenesis both in vivo and in vitro by inhibiting the activation of the NF­κB signaling pathway. Carnosol may therefore be a potential novel therapeutic candidate for the clinical treatment of osteoclast­related disorders.

Down-regulation of protease-activated receptor 2 ameliorated osteoarthritis in rats through regulation of MAPK/NF-κB signaling pathway in vivo and in vitro.

Recently, protease-activated receptor 2 (PAR2) has been proved to be involved in the inflammatory response including osteoarthritis (OA). In the present study, we found that PAR2 antagonist could remarkably improve the pathological condition of OA rats in vivo. In addition, we also found that PAR2 antagonist could suppress the production of inflammatory factors (TNF-α and Cox-2), decrease the levels of MMP-1 and MMP-13, and restrain the levels of P62 proteins and aggravate the expression of LC3-II both in vivo and in vitro. Besides, in vitro, PAR2 antagonist could increase the proliferation and colony formation of chondrocytes induced with IL-1ß. Moreover, PAR2 antagonist could decrease the expression of expressions of p-p38, p-IκBα and p-NF-κB in vitro. However, PAR2 agonist exhibited the opposite effects. Furthermore, SB203580, a p38 MAPK inhibitor, could remarkably promote the proliferation of chondrocytes induced with IL-1ß, could alleviate the production of TNF-α and Cox-2, could down-regulate the protein expressions of MMP-1 and MMP-13, and could decrease the expression of P62 and increase the expressions of LC3-II of chondrocytes induced with IL-1ß. Importantly, SB203580 could reverse the effects of PAR2 agonist on the functions of chondrocytes induced with IL-1ß. Taken together, the present data suggest that down-regulation of PAR2 can ameliorate OA through inducing autophagy via regulation of MAPK/NF-κB signaling pathway in vivo and in vitro, and PAR2 can be considered as a potential candidate to treat OA.

High-coordinate CoII and FeII compounds constructed from an asymmetric tetradentate ligand show slow magnetic relaxation behavior.

Using an asymmetric tetradentate ligand N-((6-(1H-pyrazol-1-yl)pyridin-2-yl)methylene)benzohydrazide (pypzbeyz), two high-coordinate 3d transition metal compounds [CoII(pypzbeyz)(NO3)2] (1) and [FeII(pypzbeyz)2](BF4)2(CH3CN) (2) have been synthesized and characterized by structural and magnetic measurements. X-ray crystallographic analyses revealed that compound 1 is seven-coordinate with a distorted pentagonal bipyramidal geometry (pseudo-D5h) and compound 2 is eight-coordinate with a triangular dodecahedral geometry (pseudo-D2d). Direct current (dc) magnetic susceptibilities revealed that compound 1 shows easy-plane magnetic anisotropy (D = +29.9 cm-1, E = 0.31 cm-1) and 2 shows easy-axis magnetic anisotropy (D = -6.6 cm-1, E = 0.02 cm-1). Alternating current (ac) magnetic measurements indicate that both compounds exhibit field-induced slow magnetic relaxation behavior. Furthermore, ab initio calculations also demonstrate that compound 1 presents a strong easy-plane magnetic anisotropy and 2 presents an easy-axis magnetic anisotropy, which are further identified by the calculated orientations of the local magnetic axes. These results demonstrate an effective way to achieve the targeted synthesis of high-coordinate 3d SIMs.

S100B suppresses the differentiation of C3H/10T1/2 murine embryonic mesenchymal cells into osteoblasts.

S100 calcium-binding protein B (S100B) is expressed and released by adipocytes, and is positively correlated with body mass index, however, the direct effects of S100B on adipocytes remain unclear. Bone marrow­derived mesenchymal stem cells have the capacity to differentiate into osteoblasts and adipocytes, which is important for bone metabolism. The current study aimed to determine the effect of S100B on adipogenesis and osteogenesis. The mouse embryo cell line C3H/10T1/2 was used to build cell models with varying levels of S100B protein expression. Western blot analysis was performed to assess the expression of various marker proteins. Oil red O staining and alizarin red S staining were used to detect adipogenesis and osteogenesis, respectively. S100B overexpression was associated with a significant increase in oil red O staining and a significant reduction in alizarin red S staining. Runt­related transcription factor­2 and bone morphogenetic protein 2 expression levels were significantly increased in the S100B underexpression group, however not in the S100B overexpression group. By contrast, the expression levels of the adipogenesis markers peroxisome proliferator­activated receptor Î³ and CCAAT­enhancer­binding protein α was significantly increased in the S100B overexpression group, however not in the S100B underexpression group. Osteogenesis stimulation increased extracellular signal­regulated kinase (ERK) phosphorylation, and adipogenesis stimulation increased c­Jun N­terminal kinase (JNK) phosphorylation. The results suggest that S100B inhibits osteogenesis, however stimulates adipogenesis. The ERK pathway is involved in the regulation of osteogenesis, whereas the JNK pathway is involved in the regulation of adipogenesis.

Perifosine induces cell apoptosis in human osteosarcoma cells: new implication for osteosarcoma therapy?

Despite the advances of adjuvant chemotherapy and significant improvement of survival, the prognosis for patients with osteosarcoma is generally poor. The search for more effective anti-osteosarcoma agents is necessary and urgent. Here we report that perifosine induces cell apoptosis and growth inhibition in cultured human osteosarcoma cells. Perifosine blocks Akt/mTOR complex 1 (mTORC1) signaling, while promoting caspase-3, c-Jun N-terminal kinases (JNK), and p53 activation. Further, perifosine inhibits survivin expression probably by disrupting its association with heat shock protein-90 (HSP-90). These signaling changes together were responsible for a marked increase of osteosarcoma cell apoptosis and growth inhibition. Finally, we found that a low dose of perifosine enhanced etoposide- or doxorubicin-induced anti-OS cells activity. The results together suggest that perifosine might be used as a novel and effective anti-osteosarcoma agent.

Co-administration phenoxodiol with doxorubicin synergistically inhibit the activity of sphingosine kinase-1 (SphK1), a potential oncogene of osteosarcoma, to suppress osteosarcoma cell growth both in vivo and in vitro.

Elucidation of the mechanisms of chemo-resistance and implementation of strategies to overcome it will be pivotal to improve the survival for osteosarcoma (OS) patients. We here suggest that sphingosine kinase-1 (SphK1) might be the key factor contributing to chemo-resistance in OS. Our Western-blots and immunohistochemistry results showed that SphK1 is over-expressed in multiple clinical OS tissues. Over-expression of SphK1 in OS cell line U2OS promoted its growth and endorsed its resistance against doxorubicin, while knocking-down of SphK1 by shRNA inhibited U2OS cell growth and increased its sensitivity to doxorubicin. Co-administration phenoxodiol with doxorubicin synergistically inhibited SphK1 activity to trigger cellular ceramide accumulation, and achieved synergistic anti-OS growth effect, accompanied with a significant increased of apoptosis and cytotoxicity. Increased cellular level of ceramide by the co-administration induced the association between Akt and Protein Phosphatase 1 (PP1) to dephosphorylate Akt, and to introduce a constitutively active Akt (CA-Akt) restored Akt activation and diminished cell growth inhibition. Further, phenoxodiol and doxorubicin synergistically activated apoptosis signal-regulating kinase 1(ASK1)/c-jun-NH2-kinase (JNK) signaling, which also contributed to cell growth inhibition. Significantly, the role of SphK1 in OS cell growth and the synergistic anti-OS effect of phenoxodiol and doxorubicin were also seen in a mice OS xenograft model. In conclusion, our data suggest that SphK1 might be a critical oncogene of OS and co-administration phenoxodiol with doxorubicin synergistically inhibited the activity of SphK1 to suppress osteosarcoma cell growth both in vivo and in vitro.