ß-Mangostin inhibits the metastatic power of cervical cancer cells attributing to suppression of JNK2/AP-1/Snail cascade.

ß-Mangostin is a natural mangostin with potent anticancer activity against various cancers. In this study, we further explored the anticancer activity of ß-mangostin on cervical cancer cells. ß-Mangostin did not affect cell viability and cell cycle distribution in HeLa and SiHa cells; however, it dose-dependently inhibited the migration and invasion of both the human cervical cancer cell lines. In addition, we observed that ß-mangostin suppressed the expression of integrin αV and ß3 and the downstream focal adhesion kinase/Src signaling. We also found that Snail was involved in the ß-mangostin inhibited cell migration and invasion of HeLa cell. Then, our findings showed that ß-mangostin reduced both nuclear translocation and messenger RNA expression of AP-1 and demonstrated that AP-1 could target to the Snail promoter and induce Snail expression. Kinase cascade analysis and reporter assay showed that JNK2 was involved in the inhibition of AP-1/Snail axis by ß-mangostin in HeLa cells. These results indicate that ß-mangostin can inhibit the mobility and invasiveness of cervical cancer cells, which may attribute to the suppression of both integrin/Src signaling and JNK2-mediated AP-1/Snail axis. This suggests that ß-mangostin has potential antimetastatic potential against cervical cancer cells.

Impact of COVID-19 Preventative Measures on Otolaryngology in Taiwan: A Nationwide Study.

BACKGROUND: Taiwan always had low case rates of COVID-19 compared with other countries due to its immediate control and preventive measures. However, the effects of its policies that started on 2020 for otolaryngology patients were unknown; therefore, the aim of this study was to analyze the nationwide database to know the impact of COVID-19 preventative measures on the diseases and cases of otolaryngology in 2020. METHOD: A case-compared, retrospective, cohort database study using the nationwide database was collected from 2018 to 2020. All of the information from outpatients and unexpected inpatients with diagnoses, odds ratios, and correlation matrix was analyzed. RESULTS: The number of outpatients decreased in 2020 compared to in 2018 and 2019. Thyroid disease and lacrimal system disorder increased in 2020 compared to 2019. There was no difference in carcinoma in situ, malignant neoplasm, cranial nerve disease, trauma, fracture, and burn/corrosion/frostbite within three years. There was a highly positive correlation between upper and lower airway infections. CONCLUSIONS: COVID-19 preventative measures can change the numbers of otolaryngology cases and the distributions of the disease. Efficient redistribution of medical resources should be developed to ensure a more equitable response for the future.

Comparative outcomes between all-inside arthroscopic suture anchor technique versus arthroscopic transosseous suture technique in patients with triangular fibrocartilage complex tear: a retrospective comparative study.

BACKGROUND: Triangular fibrocartilage complex (TFCC) has become an interest over the last few decades, discovering its understanding in anatomy, pathomechanism, biomechanics, and management in treatments. Currently, TFCC does not have a golden standard procedure, and not one surgical procedure is superior to the other. This study is to evaluate the comparative outcomes in TFCC patients that underwent either in all-inside arthroscopic suture anchors or the arthroscopic transosseous suture technique. METHOD: From 2017 to 2019, 30 patients were analyzed. Eight patients were in an arthroscopic transosseous group and 22 patients were in an all-inside arthroscopic group. Comparison between patients' flexion and extension range of motion (ROM), grip strength, and visual analog pain scale (VAS) preoperative and six-month follow-up were analyzed. RESULT: There were significant increases in flexion ROM, extension ROM, and VAS between preoperative and postoperative in all-inside arthroscopic and arthroscopic transosseous. Only the all-inside arthroscopic group had a significant increase in grip strength. Postoperative flexion ROM had a significant difference between all-inside arthroscopic and arthroscopic transosseous. CONCLUSION: Both the all-inside arthroscopic suture anchor technique and the arthroscopic transosseous suture technique are appropriate treatments to treat patients with TFCC. Both procedures have achieved the ultimate goal of improved longevity and optimal function. LEVEL OF EVIDENCE: Level III; retrospective comparative cohort study.

Adenine Inhibits the Invasive Potential of DLD-1 Human Colorectal Cancer Cell via the AMPK/FAK Axis.

Tumor metastasis is a major cause of death of patients with colorectal cancer (CRC). Our previous findings show that adenine has antiproliferation activity against tumor cells. However, whether adenine reduces the invasiveness of DLD-1 and SW480 CRC cells has not been thoroughly explored. In this study, we aimed to explore the effects of adenine on the invasion potential of DLD-1 cells. Our findings showed that adenine at concentrations of ≤200 µM did not influence the cell viability of DLD-1 and SW480 CRC cells. By contrast, adenine reduced the migratory potential of the CRC cells. Moreover, it decreased the invasion capacity of the CRC cells in a dose-dependent manner. We further observed that adenine downregulated the protein levels of tissue plasminogen activator, matrix metalloproteinase-9, Snail, TWIST, and vimentin, but upregulated the tissue inhibitor of metalloproteinase-1 expression in DLD-1 cells. Adenine decreased the integrin αV level and reduced the activation of integrin-associated signaling components, including focal adhesion kinase (FAK), paxillin, and Src in DLD-1 cells. Further observations showed that adenine induced AMP-activated protein kinase (AMPK) activation and inhibited mTOR phosphorylation in DLD-1 cells. The knockdown of AMPK restored the reduced integrin αV level and FAK/paxillin/Src signaling inhibited by adenine in DLD-1 cells. Collectively, these findings reveal that adenine reduces the invasion potential of DLD-1 cells through the AMPK/integrin/FAK axis, suggesting that adenine may have anti-metastatic potential in CRC cells.

Laser acupuncture for refractory coccydynia after traumatic coccyx fracture: A case report.

RATIONALE: Coccyx fracture is an injury usually caused by trauma. In most cases, the fractures recover after conservative therapy. For refractory cases that exhibit coccydynia after more than 2 months of conservative treatment, coccygectomy is indicated. However, limited information about the efficacy of this procedure is available, and it is known to have a high complication rate. As such, other therapeutic approaches are needed. Here, we report our experience using another conservative treatment option, low-level laser therapy, to successfully reduce refractory coccydynia in a patient with coccyx fracture. PATIENT CONCERNS: A 23-year-old woman had refractory coccydynia and increased pain after a traffic accident-induced coccyx fracture. DIAGNOSES: Initially, the patient reported transient improvement after conservative treatment with non-steroidal anti-inflammatory drugs. However, the pain increased in severity (numerical rating scale score of 8) soon after she resumed work in her office, and progressed in the following 2 months. Surgical intervention was suggested owing to the prolonged coccydynia following the failure of conservative treatment and difficulties in performing daily life activities. However, she sought other conservative therapy options, because she was concerned about the risks associated with the coccygectomy surgery. INTERVENTIONS: The patient received low-level laser therapy once a week, for 24 weeks. OUTCOMES: After 11 weeks of treatment, the patient reported significant improvements in her symptoms; her pain was reduced to a numerical rating scale score of 2 and bone healing was noted on radiographs. The patient could eventually perform her daily activities satisfactorily, without coccydynia, after 24 weeks of treatment. LESSONS: Laser acupuncture produced analgesic effects in this patient with refractory coccydynia after traumatic coccyx fracture. This is the first case report to apply laser acupuncture for refractory coccydynia after traumatic coccyx fracture. Our findings imply that laser acupuncture may be a good conservative therapy option for coccyx fracture.

Aluminum Parts Fabricated by Laser-Foil-Printing Additive Manufacturing: Processing, Microstructure, and Mechanical Properties.

Fabrication of dense aluminum (Al-1100) parts (>99.3% of relative density) by our recently developed laser-foil-printing (LFP) additive manufacturing method was investigated as described in this paper. This was achieved by using a laser energy density of 7.0 MW/cm2 to stabilize the melt pool formation and create sufficient penetration depth with 300 µm thickness foil. The highest yield strength (YS) and ultimate tensile strength (UTS) in the LFP-fabricated samples reached 111 ± 8 MPa and 128 ± 3 MPa, respectively, along the laser scanning direction. These samples exhibited greater tensile strength but less ductility compared to annealed Al-1100 samples. Fractographic analysis showed elongated gas pores in the tensile test samples. Strong crystallographic texturing along the solidification direction and dense subgrain boundaries in the LFP-fabricated samples were observed by using the electron backscattered diffraction (EBSD) technique.

Dietary delphinidin inhibits human colorectal cancer metastasis associating with upregulation of miR-204-3p and suppression of the integrin/FAK axis.

Delphinidin is a flavonoid belonging to dietary anthocyanidin family that has been reported to possess diverse anti-tumoral activities. However, the effects of delphinidin on colorectal cancer (CRC) cells and the underlying mechanisms are not fully understood. Thus, we aimed to investigate the anti-cancer activity of delphinidin in CRC cells and the underlying molecular mechanisms. The effects of delphinidin on the viability, metastatic characteristics, signaling, and microRNA (miR) profile of human CRC cell lines used were analyzed. In vivo metastasis was also evaluated using xenograft animal models. Our findings showed that delphinidin (<100 µM) inhibited the colony formation of DLD-1, SW480, and SW620 cells, but non-significantly affected cell viability. Delphinidin also suppressed the migratory ability and invasiveness of the tested CRC cell lines, downregulated integrin αV/ß3 expression, inhibited focal adhesion kinase (FAK)/Src/paxillin signaling, and interfered with cytoskeletal construction. Analysis of the miR expression profile revealed a number of miRs, particularly miR-204-3p, that were significantly upregulated and downregulated by delphinidin. Abolishing the expression of one upregulated miR, miR-204-3p, with an antagomir restored delphinidin-mediated inhibition of cell migration and invasiveness in DLD-1 cells as well as the αV/ß3-integrin/FAK/Src axis. Delphinidin also inhibited the lung metastasis of DLD-1 cells in the xenograft animal model. Collectively, these results indicate that the migration and invasion of CRC cells are inhibited by delphinidin, and the mechanism may involve the upregulation of miR-204-3p and consequent suppression of the αV/ß3-integrin/FAK axis. These findings suggest that delphinidin exerts anti-metastatic effects in CRC cells by inhibiting integrin/FAK signaling and indicate that miR-204-3p may play an important role in CRC metastasis.

Loss of endothelial cell-specific molecule 1 promotes the tumorigenicity and metastasis of prostate cancer cells through regulation of the TIMP-1/MMP-9 expression.

The Endothelial cell specific molecule-1 (ESM1) protein has been involved in proliferation and metastatic progression in multiple tumors. However, there are no studies regarding the mechanism of ESM1 in prostate cancer. We found that ESM1 knockdown in prostate cancer cells resulted in increased cell proliferation and colony formation ability response evidenced by decreased expression of p21 and increased expression of cyclin D1 in prostate cancer cells. Moreover, we revealed that knockdown ESM1 also induced the epithelial-mesenchymal transition (EMT), motility and invasiveness in accordance with the upregulated the MMP-9 expression, while downregulated the TIMP-1 expression. Recombinant human (Rh) TIMP-1 significantly attenuated ESM1-mediated cell migration and invasion. Additionally, ESM1 knockdown increased in vivo tumorigenicity and metastasis of prostate cancer cells. These findings provide the first evidence that the imbalance of MMP-9/TIMP-1, is one of the regulation mechanisms by which ESM1 promotes tumorigenicity and metastasis of prostate cancer cells.

Solanum nigrum Suppress Angiogenesis-Mediated Tumor Growth Through Inhibition of the AKT/mTOR Pathway.

Solanum nigrum L., an edible plant and local dish, has been assigned anticancer activities. However, the anticancer mechanisms of S. nigrum are poorly understood. Here, we investigated whether the water or polyphenol extracts of S. nigrum (SNWE or SNPE) could inhibit angiogenesis-mediated tumor growth. In nude mice bearing tumor xenografts, SNWE or SNPE significantly reduced the volume and weight of the tumors, and decreased the expression of CD31, a marker for angiogenesis. SNWE or SNPE was found to inhibit the VEGF-induced capillary structure formation of endothelial cells. The chicken egg chorioallantoic membrane (CAM) and matrigel plug assays showed further that SNWE or SNPE inhibited tumor angiogenesis. In human umbilical vascular endothelial cells (HUVECs), SNWE or SNPE suppressed the VEGF-induced activation of AKT and mTOR. Moreover, SNWE or SNPE inhibited the viability of human hepatoma HepG2 cells, and these effects were correlated with the extent of inhibition of the AKT/mTOR pathway. Taken together, our data imply that SNWE or SNPE downregulated the AKT/mTOR pathway in HUVECs and HepG2 cells, which lead to reduced tumor growth and angiogenesis.

Polyphenolic extract from Hibiscus sabdariffa reduces body fat by inhibiting hepatic lipogenesis and preadipocyte adipogenesis.

Diets high in fat lead to excess lipid accumulation in adipose tissue, which is a crucial factor in the development of obesity, hepatitis, and hyperlipidemia. In this study, we investigated the anti-obesity effect of Hibiscus sabdariffa extract (HSE) in vivo. Hamsters fed a high-fat diet (HFD) develop symptoms of obesity, which were determined based on body weight changes and changes in plasma and serum triglycerides, free fatty acid concentrations, total cholesterol levels, LDL-C levels, HDL-C levels, and adipocyte tissue weight. HFD-fed hamsters were used to investigate the effects of HSE on symptoms of obesity such as adipogenesis and fatty liver, loss of blood glucose regulation, and serum ion imbalance. Interestingly, HSE treatment effectively reduced the effects of the HFD in hamsters in a dose-dependent manner. Further, after inducing maturation of preadipocytes, Hibiscus sabdariffa polyphenolic extract (HPE) was shown to suppress the adipogenesis of adipocytes. However, HPE does not affect the viability of preadipocytes. Therefore, both HSE and HPE are effective and viable treatment strategies for preventing the development and treating the symptoms of obesity.