Fisetin, a natural flavonoid, is known to have anticarcinogenic effects against several cancers, but its role in mediating renal cell carcinoma (RCC) progression has not been delineated. Cell viability, cytotoxicity, and cell cycle distribution were measured using the 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and propidium iodide staining with flow cytometry. The in vitro migration and invasion assay was used to examine in vivo cell migration and invasion. Human protease antibody array analysis was conducted with cell migration/invasion-related proteins. Western blotting and quantitative reverse transcription polymerase chain reaction were used for assessing protein expression related to the cell cycle, cell invasion, and mitogen-activated protein kinase (MAPK) signaling pathway. We found that fisetin significantly inhibited cell viability through cell cycle arrest in the G2/M phase, in addition to downregulating cyclin D1 and upregulating p21/p27. Fisetin inhibited the migration and invasion of human RCC cells through the downregulation of CTSS and a disintegrin and metalloproteinase 9 (ADAM9). Fisetin also upregulated ERK phosphorylation in 786-O and Caki-1 cells. Furthermore, treatment with a MEK inhibitor (UO126) reduced the inhibitory effects of fisetin on the metastasis of RCC cells through the ERK/CTSS/ADAM9 pathway. Fisetin inhibits proliferation and metastasis of RCC cells by downregulating CTSS and ADAM9 through the MEK/ERK signaling pathway. These findings indicate that fisetin is a promising antitumor agent against RCC.

Osteosarcoma, which is the most prevalent malignant bone tumor, is responsible for the great majority of bone cancer-associated deaths because of its highly metastatic potential. Although tomatidine is suggested to serve as a chemosensitizer in multidrug-resistant tumors, the anti-metastatic effect of tomatidine in osteosarcoma is still unknown. Here, we tested the hypothesis that tomatidine suppresses migration and invasion, features that are associated with metastatic process in human osteosarcoma cells and also investigate its underlying pathway. Tomatidine, up to 100 μM, without cytotoxicity, inhibited the invasion and migration capabilities of human osteosarcoma U2OS and HOS cells and repressed presenilin 1 (PS-1) expression of U2OS cells. After the knockdown of PS-1, U2OS and HOS cells’ biological behaviors of cellular invasion and migratory potential were significantly reduced. While tomatidine significantly decreased the phosphorylation of c-Raf, mitogen/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated protein kinase (ERK)1/2 in U2OS cells, no obvious influences on p-Jun N-terminal kinase, p38, and Akt, including their phosphorylation, were observed. In ERK 1 silencing U2 OS cells, tomatidine further enhanced the decrease of their migratory potential and invasive activities. We conclude that both PS-1 derived from U2OS and HOS cells and the c-Raf–MEK–ERK pathway contribute to cellular invasion and migration and tomatidine could inhibit the phenomenons. These findings indicate that tomatidine might be a potential candidate for anti-metastasis treatment of human osteosarcoma.

Background and Objectives: Research on the impact of leucine on older sarcopenic patients is scarce, and investigations on this subject have led to contradictory findings in the literature. Our goal was to compile data from the available studies in the literature to explore the effect of leucine supplementation on parameters associated with sarcopenia in elderly individuals. Methods: The meta-analysis included older persons over 65 years of age who were recruited on the basis of the European Working Group on Sarcopenia in Older People sarcopenia criteria. Studies that were included were those in which at least one sarcopenia criterion was measured, including grip strength, appendicular skeletal muscle mass/height², gait speed, and the short physical performance battery index. Results: The meta-analysis included ten randomized controlled trials and one prospective study. The leucine group included 566 participants, whereas the placebo group included 567 patients. Patients receiving leucine and patients receiving a placebo had significantly different handgrip (p = 0.03), appendicular skeletal muscle mass/height² (p = 0.0.2), and gait speed (p = 0.008). Patients received a high dosage of leucine, and there was a significant difference in the appendicular skeletal muscle mass/height² (p = 0.02) and gait speed (p = 0.01) between the high dosage of the leucine group and the control group. When vitamin D was combined with leucine, the appendicular skeletal muscle mass/height² (p = 0.03) significantly differed between the leucine group receiving vitamin D and the control group. Conclusions: Low-quality evidence was found that older sarcopenic patients receiving leucine may show trends toward improved skeletal muscle strength, skeletal muscle quality, and physical performance. The capacity of leucine supplementation to have a beneficial therapeutic impact in older sarcopenic individuals is restricted when it is used alone without concurrent additional therapy.

Study Design: This study employed a retrospective study design. Objective: This retrospective cohort study aimed to compare the outcomes of anterior cervical discectomy and fusion (ACDF), and those of conservative treatment for patients with cervical angina. Summary of Background Data: Cervical angina is typically characterized by intolerable and paroxysmal angina-like precordial pain, which is caused by cervical disk degeneration in patients without definitive cardiovascular abnormalities. Diagnosis is either delayed or neglected because of its various clinical manifestations. Whether conservative or surgical treatment is appropriate remains controversial because of the lack of comparative studies. Materials and Methods: From 2009 to 2016, 163 patients with cervical angina with advanced chest pain, tightness, or palpitation were retrospectively studied. Twenty-three patients underwent ACDF, and the other 140 patients were treated nonsurgically by medication, physical therapy, collar immobilization, or stellate ganglion block. Japanese Orthopedic Association (JOA) score and 20-point autonomic nervous system (ANS) score were assessed pretreatment and posttreatment. Patients’ satisfaction was assessed using the Odom criteria. Results: The average age of the patients was 50 years, and most of them were females. The average follow-up was 25.5 months. The pretreatment JOA and 20-point ANS scores in the conservative and ACDF groups were 13.3 versus 11.7 (P=0.110) and 13.0 versus 13.3 (P=0.928), respectively. Generalized estimating equation analysis showed that posttreatment JOA and ANS scores at each observation interval improved significantly in the ACDF group (P<0.001). Angina-like symptoms also improved significantly in the ACDF group (P<0.001). During an average 2-year follow-up, good or excellent results were obtained in 78.2% of surgical patients and 35% of nonsurgical patients. Conclusions: Compared with conservative therapy, surgical treatment with ACDF for cervical angina provided better and more consistent relief from angina-like symptoms and overall sympathetic symptoms. Level of Evidence: Level III.