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Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B‐cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis‐HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin‐resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin‐resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly. It is characterized by the progressive decline of joint cartilage and alterations in the underlying bone. Several probiotic strains have exhibited immunomodulatory and anti‐inflammatory properties. Here, we examined the functions of live and dead Clostridium butyricum GKB7 (GKB7‐L and GKB7‐D) in a preclinical anterior cruciate ligament transection (ACLT)‐enhanced OA procedure. Oral administration of GKB7‐L and GKB7‐D ameliorated ACLT‐induced bone pain as assessed by weight‐bearing behavioral testing but did not affect body weight. Micro‐computed tomography (CT) results showed that GKB7‐L and GKB7‐D diminished ACLT‐induced bone destruction and loss. GKB7‐L and GKB7‐D‐enriched therapies also reduced ACLT‐induced production of the pro‐inflammatory cytokines interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α, as well as the chondrolytic factor matrix metalloproteinase (MMP)‐3, leading to inhibition of aggrecan and collagen type II degradation and thereby blocking cartilage breakdown. We therefore suggest that oral supplementation with GKB7‐L or GKB7‐D can be beneficial in the prevention and treatment of OA. [ABSTRACT FROM AUTHOR]

Metastatic lung cancer is a highly prevalent cancer with a very low chance of long‐term survival. Metastasis at secondary sites requires that cancer cells develop anoikis resistance to survive during circulation. High levels of bone sialoprotein (BSP), a member of the small integrin‐binding ligand N‐linked glycoproteins (SIBLINGs), have been shown to promote the spread of lung cancer cells; however, the effects of BSP in anoikis resistance are largely unknown. In this study, we determined that BSP promotes anoikis resistance in lung cancer cells. BSP was also shown to promote the expression of E‐cadherin and vimentin (epithelial‐to‐mesenchymal transition markers, which have been utilized as indicators of anoikis resistance). It appears that BSP facilitates MMP‐14‐dependent anoikis resistance by inhibiting the synthesis of miR‐150‐5p and activating the ERK signalling pathway. Knockdown of BSP expression was shown to block lung cancer metastasis by lowering anoikis resistance in vivo. These results indicate that BSP is a promising target to deal with anoikis resistance and metastasis in human lung cancers. [ABSTRACT FROM AUTHOR]

Bone metastasis is the primary cause of death among patients with advanced prostate cancer (PCa). PCa tends to spread to bones and acquire the bone‐like phenotype, causing osteoblastic bone metastasis. Unfortunately, there is no effective treatment for this condition. However, melatonin, which regulates our circadian rhythm, has been found to have anti‐tumor properties. It has yet to be established whether it is effective in treating osteoblastic PCa metastasis. Our findings show that melatonin inhibits the production of endothelin‐1 (ET‐1) in osteoblastic PCa cells, suppressing osteoblast differentiation. Clinical results indicate that bone metastatic PCa patients have higher levels of ET‐1 compared to nonmetastatic PCa patients. Furthermore, melatonin‐induced miR‐let‐7f‐5p inhibits ET‐1‐promoted osteoblast differentiation in osteoblastic PCa. Melatonin also suppresses the property of osteomimicry in osteoblastic PCa cells. Importantly, in the intratibia injection PCa metastasis model, melatonin decreased osteoblastic PCa tumor growth, inhibiting ET‐1 production and osteoblast differentiation in vivo. Taken together, melatonin inhibits osteoblastic PCa‐regulated osteoblastogenesis by reducing ET‐1 production through upregulation of miR‐let‐7f‐5p, while suppressing the property of osteomimicry in osteoblastic PCa. Melatonin therapy could be a promising approach to treating bone metastasis in osteoblastic PCa. [ABSTRACT FROM AUTHOR]

Melatonin has been reported to regulate circadian rhythms and have anti‐inflammatory characteristics in various inflammatory autoimmune diseases, but its effects in diseases‐associated muscle atrophy remain controversial. This study is aimed to determine the evidence of melatonin in rheumatoid arthritis (RA)‐related pathological muscle atrophy. We used initially bioinformatics results to show that melatonin regulated significantly the correlation between pro‐inflammation and myogenesis in RA synovial fibroblasts (RASF) and myoblasts. The conditioned medium (CM) from melatonin‐treated RASF was incubated in myoblasts with growth medium and differentiated medium to investigate the markers of pro‐inflammation, atrophy, and myogenesis. We found that melatonin regulated RASF CM‐induced pathological muscle pro‐inflammation and atrophy in myoblasts and differentiated myocytes through NF‐κB signaling pathways. We also showed for the first time that miR‐30c‐1‐3p is negatively regulated by three inflammatory cytokines in human RASF, which is associated with murine‐differentiated myocytes. Importantly, oral administration with melatonin in a collagen‐induced arthritis (CIA) mouse model also significantly improved arthritic swelling, hind limb grip strength as well as pathological muscle atrophy. In conclusion, our study is the first to demonstrate not only the underlying mechanism whereby melatonin decreases pro‐inflammation in RA‐induced pathological muscle atrophy but also increases myogenesis in myoblasts and differentiated myocytes. [ABSTRACT FROM AUTHOR]

Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX‐dependent cell migration and invasion in chondrosarcoma by suppressing miR‐26b‐5p generation through the c‐Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT‐facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma. [ABSTRACT FROM AUTHOR]

Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Extracellular vesicles called exosomes are primarily used as mediators of intercellular signal transmission to control tumor metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with exosome generation in chondrosarcoma motility remains undetermined. Our results found that overexpressing visfatin augments the production of exosomes from chondrosarcoma cells. Visfatin‐treated chondrosarcoma exosomes educate macrophage polarization towards the M2 but not M1 phenotype. Interestingly, M2 macrophages polarized by exosomes return to chondrosarcoma cells to facilitate cell motility. According to these findings, chondrosarcoma cells emit more exosomes when treated with visfatin. The stimulation of exosome generation by visfatin polarizes M2 macrophages and enhances the motility of chondrosarcoma. [ABSTRACT FROM AUTHOR]

Background: Fu's subcutaneous needling (FSN) is a novel acupuncture technique for pain treatment. This study investigated the effects of postsurgical FSN on postoperative pain in patients receiving surgery for degenerative spinal disorders. Methods: This single-center, single-blind, randomized-controlled study involved patients undergoing surgery for degenerative spinal disorders. Participants were randomized into either an FSN group or a control group that received sham FSN. The primary outcomes were scores on the Brief Pain Inventory Taiwan version (BPI-T) and Oswestry Disability Index before and at 1, 24, and 48 hours after surgery. Secondary outcomes were muscle hardness, pethidine use, and inflammatory biomarker presence. Results: Initially, 51 patients met the inclusion criteria and were allocated (26 in the FSN group and 25 in the control group). Two patients were lost to follow-up, and finally, 49 patients (25 in the FSN group and 24 in the control group) who completed the study were analyzed. The FSN group had significantly lower pain intensity measured on the BPI-T compared with the control group at 1, 24, 48, and 72 hours after surgical treatment (all p < 0.001). Additionally, pain interference as measured on the BPI-T was lower in the FSN group than in the control group 1 hour (p = 0.001), 24 hours (p = 0.018), 48 hours (p = 0.001), and 72 hours (p = 0.017) after surgical treatment. Finally, the FSN group exhibited less muscle hardness in the latissimus dorsi and gluteus maximus 24, 48, and 72 hours (all p < 0.05) after surgery compared with the control group; patients in the FSN group also exhibited less muscle hardness in the L3 paraspinal muscle 48 hours (p = 0.001) and 72 hours (p < 0.001) after surgery compared with the control group. There were no significant differences in serum CRP, IL-1β, IL-2, IL-6, and TNF-α levels between the FSN and control groups at 24 hours, 72 hours, and 1-month post-surgery (all p > 0.05). Conclusion: FSN treatment can reduce postoperative pain in patients receiving surgery for degenerative spinal disorders. However, larger sample sizes and multicenter clinical trials are required to verify these findings. [ABSTRACT FROM AUTHOR]