To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

Introduction: Acquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for compounds to improve the effect of classic steroids. We sought to unravel how a plant-original compound, ginsenoside Rh1, potentiates dexmethasone (DEX)’s potential anti-inflammation properties. Methods: Ginsenoside Rh1 combined with DEX was applied in a short-term and long-term treatment protocol for inflammation. Its potential mechanism on anti-inflammation was explored. In addition, the effect of Rh1 on the side-effect induced by DEX was studied. Furthermore, the in vivo anti-inflammatory effects of Rh1 combined with DEX were evaluated in a collagen-induced arthritis (CIA) mice model. Results: Ginsenoside Rh1 potentiates DEX’s anti-inflammatory effects even after prolonged DEX treatment. Rh1 could improve the glucocorticoid receptor (GR)’s transrepression on nuclear factor kappa B (NF-κB) and transactivation on dual specificity protein phosphatase 1 (DUSP1), which is responsible for DEX’s anti-inflammatory effects. Parallel Western blot assay and radioligand binding analysis revealed that Rh1 could increase the expression and binding of GR. This is in sharp contrast to DEX alone, showing a direct link among prolonged treatment, decreasing GR and the abolishment of anti-inflammation. Interestingly, Rh1 does not enhance the transactivation of glucocorticoid-responsive elements (GRE) driven genes - gluconeogenic enzyme glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinasee phosphatase (PEPCK) in primary mouse hepatocytes, a mechanism partly held accountable for the metabolic side-effects. Similar results were found in CIA mice. Conclusion: Rh1 could potentiate DEX’s anti-inflammatory effects and does not cause a hyperglycemic side effect. Ginsenoside Rh1 combined with DEX may be a promising candidate treatment option for chronic inflammatory diseases in need of long-term immunosuppression therapies.

Background: Bufalin is a major active compound of cinobufacini, which comes from dried toad venom and has been used for treatments of various cancers in China for many years. A number of studies have demonstrated that bufalin can induce apoptosis in some cancers. However, effects and mechanism of bufalin on prostate cancer cells remain unknown. Methods: Apoptosis assay was measured by the annexin-V/PI flow cytometric assay. Western blot was used to measure Caspase-3 and Bcl-2. qRT-PCR was used to measure the relative expression of miR-181a. Results: Bufalin was found to induce the expression of miR-181a, a small non-coding RNA believed to induce apoptosis by repressing its target gene, BCL-2. In prostate cancer PC-3cell line, bufalin-induced apoptosis can be largely attenuated by a miR-181a inhibitor, which blocked bufalin-induced Bcl-2 reduction and caspase-3 activation. Conclusions: Our dataindicatedthat miR-181a mediates bufalin-induced apoptosis in PC-3 cells. Thus, we presented here a new pharmacological mechanism for bufalin in anti-tumor therapy.

Individuals with acute neurological or limb-related disorders may be temporarily bedridden and unable to go to the physical therapy departments. The rehabilitation training of these patients in the ward can only be performed manually by therapists because the space in inpatient wards is limited. This paper proposes a bedside cable-driven lower-limb rehabilitation robot based on the sling exercise therapy theory. The robot can actively drive the hip and knee motions at the bedside using flexible cables linking the knee and ankle joints. A human–cable coupling controller was designed to improve the stability of the human–machine coupling system. The controller dynamically adjusts the impedance coefficient of the cable driving force based on the impedance identification of the human lower-limb joints, thus realizing the stable motion of the human body. The experiments with five participants showed that the cable-driven rehabilitation robot effectively improved the maximum flexion of the hip and knee joints, reaching 85° and 90°, respectively. The mean annulus width of the knee joint trajectory was reduced by 63.84%, and the mean oscillation of the ankle joint was decreased by 56.47%, which demonstrated that human joint impedance identification for cable-driven control can effectively stabilize the motion of the human–cable coupling system.

Introduction: Music interventions have been proposed in recent years as a treatment for chronic pain. However, the mechanisms by which music relieves pain are unclear, and the effects of music intervention on physiological indicators in patients with chronic pain remain to be explored. This study aimed to explore whether a music intervention would have effects on subjective pain ratings, heart rate variability, and functional connectivity of the cerebral cortex in patients with chronic pain.Methods: A randomized controlled study was conducted on 37 pain patients aged 18–65 years, with the control group receiving usual care, and the intervention group receiving music intervention (8–150 Hz, 50–70 dB) for 30 min before bedtime for 7 days on top of usual care. Pain visual analog scale and heart rate variability were used as subjective and objective physiological indices before and after the music intervention, respectively. Changes in oxyhemoglobin and deoxyhemoglobin concentrations in the cerebral cortex were measured by functional near-infrared spectroscopy, and whole-brain correlation analysis was used to quantify the connectivity of prefrontal brain regions associated with the pain response.Results: Results showed that patients with chronic pain in the intervention group had significantly lower visual assessment scale scores, as well as significantly lower overall voluntary mobility during pain episodes, resulting in relatively higher vagal innervation compared to the control group. In addition, connections between the bilateral dorsolateral prefrontal cortex (BA9, BA46) and frontal areas (BA10) were significantly higher in the intervention group.Discussion: This study demonstrates the effectiveness of the combined application of music interventions with usual care in reducing pain levels in patients with chronic pain and provides insight into the pathological mechanisms of music interventions for analgesia, providing direction for new baseline indicators for quantitative clinical assessment of pain. The study was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100052993).Clinical trial registration: [https://www.chictr.org.cn/showproj.aspx?proj=136268], identifier [ChiCTR2100052993].