Icariin inhibits prostate cancer bone metastasis and destruction via suppressing TAM/CCL5-mediated osteoclastogenesis.

BACKGROUND: Bone metastasis occurs in nearly 70% of patients with metastatic prostate cancer (PCa), and represents the leading cause of death in patients with PCa. Emerging evidence has demonstrated the potential activities of icariin in modulating bone metabolism and remodelling the tumor microenvironment (TME). However, whether icariin could inhibit PCa bone metastasis and destruction by modulating the TME as well as the underlying mechanisms remains unclear. PURPOSE: This study investigated whether icariin could inhibit PCa bone metastasis and destruction by modulating the bone TME as well as the underlying mechanisms. METHODS: Osteoclasts were induced from mouse bone marrow-derived macrophages (BMMs) or Raw264.7 cells. PCa cells were cultured in the conditional medium (CM) of macrophages in vitro or co-injected with macrophages in vivo to simulate their coexistence in the TME. Multiple molecular biology experiments and the mouse RM1-Luc PCa bone metastasis model were used to explore the inhibitory activity and mechanism of icariin on PCa metastasis and bone destruction. RESULTS: Icariin treatment significantly suppressed PCa growth, bone metastasis and destruction as well as osteoclastogenesis in vivo. Furthermore, icariin remarkably inhibited osteoclast differentiation, even in the presence of the CM of tumor-associated macrophages (TAMs), while exhibiting no obvious effect on osteoblasts. Moreover, icariin suppressed the M2 phenotype polarization of Raw264.7-derived TAMs and transcriptionally attenuated their CC motif chemokine ligand 5 (CCL5) expression and secretion via inhibiting SPI1. Additionally, CCL5 induced the differentiation and chemotaxis of osteoclast precursor cells by binding with its receptor CCR5. The clinicopathological analysis further verified the positive correlation between the TAM/CCL5/CCR5 axis and osteoclastogenesis within the TME of PCa patients. More importantly, icariin remarkably suppressed PCa metastasis-induced bone destruction in vivo by inhibiting osteoclastogenesis via downregulating the TAM/CCL5 pathway. CONCLUSION: Altogether, these results not only implicate icariin as a promising candidate immunomodulator for PCa bone metastasis and destruction but also shed novel insight into targeting TAM/CCL5-mediated osteoclastogenesis as a potential treatment strategy for osteolytic bone metastasis. This study helps to advance the understanding of the crosstalk between bone TME and bone homeostasis.

Formation of pre-metastatic bone niche in prostate cancer and regulation of traditional chinese medicine.

Prostate cancer with bone metastasis has a high cancer-specific mortality. Thus, it is essential to delineate the mechanism of bone metastasis. Pre-metastatic niche (PMN) is a concept in tumor metastasis, which is characterized by tumor-secreted factors, reprogramming of stromal cells, and immunosuppression by myeloid-derived suppressor cells (MDSC), which is induced by bone marrow-derived cells (BMDC) in the target organ. However, PMN does not explain the predilection of prostate cancer towards bone metastasis. In this review, we discuss the initiation of bone metastasis of prostate cancer from the perspective of PMN and tumor microenvironment in a step-wise manner. Furthermore, we present a new concept called pre-metastatic bone niche, featuring inherent BMDC, to interpret bone metastasis. Moreover, we illustrate the regulation of traditional Chinese medicine on PMN.

Acupressure versus parecoxib sodium in acute renal colic: A prospective cohort study.

Background: Here provides a complementary treatment, acupressure at the Qiu acupoint, a novel acupoint, which potentially alleviates renal colic. Materials and methods: 90 patients were included in this study. Acupressure-group patients (n = 46) were administered acupressure at the Qiu acupoint following a preset protocol. Parecoxib sodium-group patients (n = 44) were administered parecoxib sodium (40 mg) (via the direct intravenous route). The visual analog scale (VAS) was used to evaluate pain intensity at baseline and at 1, 5, 10, 20, 30, and 120 min after initiating the intervention. Linear mixed effects model was performed to detect the rate of decrease of VAS per time and their covariant effect on the efficacy of acupressure. Results: No significant statistical differences in baseline data and VAS scores were observed. The acupressure group obtained lower VAS scores at the 1st, 5th, 10th, and 20th minute than the parecoxib sodium group after initiating the intervention (mean: 4.33 vs. 7.61, mean difference (MD): 3.29, 95% CI: 0.23, 2.84; mean: 2.65 vs. 7.61, MD: 4.96, 95% CI: 4.44, 5.49; mean: 1.63 vs. 6.59, MD: 4.96, 95% CI: 4.48, 5.44; mean: 1.26 vs. 3.64 MD: 2.38, 95% CI: 1.87, 2.88; P < 0.05). The markedly effective rate was similar between the two groups. The linear mixed effects model demonstrated that acupressure at the Qiu point was significantly faster than parecoxib sodium in decreasing VAS scores with an estimate of -2.05 (95% CI: -2.51, -1.59, p = 0.000), especially within 10 minutes with an estimate of 0.18 (95% CI: 0.12, 0.25, p = 0.000). Conclusion: Acupressure at the Qiu acupoint is significantly faster than parecoxib sodium in decreasing VAS scores within 10 minutes. Clinical trial registration: http://www.chictr.org.cn/, identifier 2100047168.

2-DE combined with two-layer feature selection accurately establishes the origin of oolong tea.

Taiwan is known for its high quality oolong tea. Because of high consumer demand, some tea manufactures mix lower quality leaves with genuine Taiwan oolong tea in order to increase profits. Robust scientific methods are, therefore, needed to verify the origin and quality of tea leaves. In this study, we investigated whether two-dimensional gel electrophoresis (2-DE) and nanoscale liquid chromatography/tandem mass spectroscopy (nano-LC/MS/MS) coupled with a two-layer feature selection mechanism comprising information gain attribute evaluation (IGAE) and support vector machine feature selection (SVM-FS) are useful in identifying characteristic proteins that can be used as markers of the original source of oolong tea. Samples in this study included oolong tea leaves from 23 different sources. We found that our method had an accuracy of 95.5% in correctly identifying the origin of the leaves. Overall, our method is a novel approach for determining the origin of oolong tea leaves.