Possibility analysis of thyroid imaging parameters for dose adjustment in 131I treatment of hyperthyroidism.

BACKGROUND: To determine the thyroid uptake rate by correcting the background and analyze its clinical significance. METHODS: The study included 161 patients with hyperthyroidism. The thyroid uptake rate was calculated by drawing a 100 pixels ROI (region of interest) background, above and below the thyroid and correcting the thyroid ROI for background counting. At the same time, the clinical baseline characteristic parameters such as age and thyroid volume etc. of patients with hyperthyroidism were collected. The consistency of 99mTcO4uptake rate before treatment and 131I-uptake rate after treatment, and the correlation between uptake rate of thyroid and baseline characteristic parameters were also analyzed. RESULTS: The uptake rate of 99mTcO4 was found positively correlated with 3 h-radioactive iodine uptake (RAIU), 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity free triiodothyronine (FT3) and free thyroxine (FT4), and showed negative correlation with age, effective half-life (P<0.05). The uptake rate of 131I was found positively correlated with 3 h-RAIU, 24 h-RAIU, 3 h/24 h conversion rate, thyroid volume, 131I activity, FT3, FT4 (P<0.05). In patients with positive thyrotrophin receptor antibody (TRAb), a significant positive correlation between uptake rate of 99mTcO4 and 131I (P<0.05) was observed. There was a high consistency between pretreatment uptake rate of 99mTcO4 and post-treatment uptake rate of 131I (P=0.009; W=0.7). CONCLUSIONS: The corrected thyroid uptake rate is remarkably correlated with clinical characteristic parameters of patients, which can be used to comprehensively evaluate the comprehensive condition of patients with hyperthyroidism.

A novel timesaving and semiquantitative method for radionuclide hepatobiliary scintigraphy for suspected biliary atresia.

BACKGROUND: To optimize the performance of the hepatobiliary scintigraphy (HS) for suspected biliary atresia (BA) using a timesaving and semiquantitative method without a loss in diagnostic accuracy. METHODS: A retrospective analysis of 185 patients with persistent jaundice who underwent surgery were included. According to the surgical evaluation and pathological diagnosis, patients were divided into a BA group (99 cases) and an infant hepatitis syndrome (IHS) group (86 cases). 99mTc-labeled diethylacetanilide-iminodiacetic acid (99mTc-EHIDA) HS was performed before surgery. The average intestinal radioactivity uptake value minus the background average of radioactivity uptake value at 6 h after label injection (abbreviated as 6-h I-B) was calculated and the difference in 6-h I-B between the two groups was evaluated. The difference in diagnostic efficacy between 6-h I-B and the conventional 24-h HS in BA was also evaluated. RESULTS: A significant difference in 6-h I-B between the two groups was found (t=-5.975, P<0.001) and a high level of efficacy of 6-h I-B in the diagnosis of BA was detected. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of 6-h I-B in the diagnosis of BA were 87.88%, 47.67%, 69.19%, 65.91%, and 77.36% respectively, while the corresponding parameters of the 24-h hepatobiliary imaging were 90.91%, 36.05%, 65.41%, 62.07%, and 77.50% respectively, with no significant difference between these values in the diagnosis of BA. CONCLUSIONS: HS plays an important role in the diagnosis of infantile jaundice due to conjugated hyperbilirubinemia. The timesaving and semiquantitative method of the 6-h hepatobiliary static imaging showed the same high sensitivity and NPV of the conventional 24-h HS in preventing unnecessary surgery. In the setting of suspected BA, imaging resource utilization could be improved via reducing the acquisition time and simplifying the examination process. The 24-h delay in imaging was considered unnecessary because it was not significantly superior.

Daidzin inhibits RANKL-induced osteoclastogenesis in vitro and prevents LPS-induced bone loss in vivo.

Osteoclasts are multinuclear giant cells responsible for bone resorption in bone loss diseases, including rheumatoid arthritis, periodontitis, and the aseptic loosening of orthopedic implants. Because of injurious side effects with currently available drugs, it is necessary to continue research novel bone-protective therapies. Daidzin, a naturally occurring isoflavone found in leguminous plants, has numerous beneficial pharmacologic effects, including anti-cancer, anti-cholesterol, and anti-angiocardiopathy, promoting osteoblasts differentiation, and even anti-osteoporosis. However, the effect of daidzin on the regulation of osteoclast activity has not yet been investigated. In this study, our study showed that daidzin significantly inhibited receptor activator of nuclear factor-kB ligand (RANKL)-induced osteoclast differentiation of bone marrow macrophages and the hydroxyapatite-resorbing activity of mature osteoclasts by inhibiting RANKL-induced NF-kB signaling pathway. In addition, daidzin could inhibit the expression of osteoclast marker genes, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene fos (c-Fos), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CTSK). Consistent with in vitro results, daidzin inhibited lipopolysaccharide-induced bone loss by suppressing the osteoclast differentiation. Together our data demonstrated that daidzin inhibits RANKL-induced osteoclastogenesis through suppressing NF-ĸB signaling pathway and that daidzin is a promising agent in the treatment of osteolytic diseases.

Arctigenin inhibits RANKL-induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle-induced bone loss in vivo.

Wear particle-induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle-induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle-induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti-inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle-induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle-induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow-derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast-related signaling pathways. The results showed that arctigenin inhibited RANKL-induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose-dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF-κB) ligand-induced NF-κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast-related osteolytic diseases caused by excessive osteoclast formation.

Cancer stem cell-like characteristics and telomerase activity of the nasopharyngeal carcinoma radioresistant cell line CNE-2R.

The radioresistance of nasopharyngeal carcinoma (NPC) may be related to cancer stem cells (CSCs), and the characteristics of CSCs may be maintained by telomerase activity. In this study, we explored the CSC-like characteristics and telomerase activity of the NPC radioresistant cell line CNE-2R. This work provides a foundation for future studies on stem cell-targeted therapies by targeting the radioresistance of NPC. The expression of stem cell-related genes/proteins and the hTERT gene/protein in CNE-2R and its parent radiosensitive cell line CNE-2 were detected using qPCR/Western Blot. Label-retaining cells (LRCs) were detected through immunocytochemistry, and telomerase activity was detected using a PCR-ELISA kit. CD133 expression was detected with flow cytometry. CNE-2R-CD133+ and CNE-2R-CD133- cells were separated with magnetic-activated cell sorting. The proliferation and tumorigenesis capacities of CNE-2R-CD133+, CNE-2R-CD133-, and CNE-2R cells were compared with a CCK-8 assay, sphere formation assay, and an in vivo experiment. Our results showed that the expression of stem cell-related genes and the hTERT gene in CNE-2R cells was higher than those in CNE-2 cells. Similarly, the expression of stem cell-related proteins and the hTERT protein in CNE-2R cells was markedly higher than those in CNE-2 cells. The proportion of LRCs in CNE-2R and CNE-2 cells was (3.10 ± 0.63%) vs (0.40 ± 0.35%; P < 0.001), respectively. Telomerase activity in CNE-2R cells was remarkably higher than that in CNE-2 cells. Flow cytometry suggested that the CD133 positive rates in CNE-2R and CNE-2 cells were (2.49 ± 0.56%) vs (0.76 ± 0.25%; P = 0.008), respectively. Meanwhile, the proliferation capacity, tumorigenesis capacity, and telomerase activity of CNE-2R-CD133+ cells were notably higher than those of CNE-2R-CD133- and CNE-2R cells. Collectively, CNE-2R displayed CSC-like characteristics; our results also showed that CNE-2R cells, especially the sorted CSCs, had high telomerase activity levels.

Silencing of c-jun decreases cell migration, invasion, and EMT in radioresistant human nasopharyngeal carcinoma cell line CNE-2R.

BACKGROUND: Previously, we found that c-jun was highly expressed in radiation-resistant human nasopharyngeal carcinoma cells (CNE-2R) compared with human nasopharyngeal carcinoma cells (CNE-2). MATERIALS AND METHODS: In this study, we first used the scratch assays and transwell assays to detect the migration and invasion of CNE-2R and CNE-2 cells and tested the epithelial mesenchymal transformation (EMT)-related proteins E-cadherin and N-cadherin by Western blot analysis. Subsequently, c-jun was knocked down to establish the effect of c-jun on EMT, migration, and invasion of CNE-2R cells both in vitro and in vivo. RESULTS: A high EMT level, CNE-2R cells were more capable of migration and invasion than CNE-2 cells. Moreover, silencing of c-jun has upregulated the expression of E-cadherin and downregulated N-cadherin in CNE-2R cells, and subsequently the migration and invasion capacity of the cells was decreased. Consistent with in vitro results, in vivo studies indicated that the c-jun silencing reduced pulmonary migration of CNE-2R cells. Immunohistochemistry of lung metastatic tumor tissue showed that E-cadherin was upregulated, and N-cadherin was downregulated. CONCLUSION: These findings suggest that silencing of c-jun in CNE-2R cells reduces cells migration, invasion, and EMT both in vitro and in vivo.

Cofilin-2 Acts as a Marker for Predicting Radiotherapy Response and Is a Potential Therapeutic Target in Nasopharyngeal Carcinoma.

BACKGROUND The purpose of this study was to determine whether cofilin-2 could serve as a protein marker for predicting radiotherapy response and as a potential therapeutic target in nasopharyngeal carcinoma (NPC). MATERIAL AND METHODS Cofilin-2 protein levels in serum and tissue samples from patients with NPC were assessed by sandwich ELISA and IHC. In vitro, cofilin-2 levels in CNE-2R cells were significantly higher than those of CNE-2 cells. Meanwhile, CNE-2R cells were silenced for cofilin-2 to obtain a stable cofilin-2-RNAi-LV3 cell line. Then, cell proliferation, radiosensitivity, invasion and migration abilities, cell cycle, and apoptosis were evaluated by Cell Counting Kit 8 assay (CCK-8), flow cytometry (FCM), clone formation assay, and in vitro. RESULTS The secreted levels of the cofilin-2 protein in radioresistant NPC patients were significantly higher than those of radiosensitive cases. After cofilin-2 knockdown in nasopharyngeal carcinoma CNE-2R cells, proliferation was decreased, while apoptosis and radiosensitivity were enhanced; cell cycle distribution was altered, and the transplanted tumors in nude mice grew significantly less. CONCLUSIONS Overall, our findings suggest that cofilin-2 acts as a marker for predicting radiotherapy response and is a potential therapeutic target in nasopharyngeal carcinoma.

Reduced QSOX1 enhances radioresistance in nasopharyngeal carcinoma.

Radioresistance is a major cause leads to treatment failure in nasopharyngeal carcinoma (NPC). In our previous study, we identified that QSOX1 is a differentially expressed protein in NPC cell lines with variable radiosensitivities. The present study aimed to investigate the biological behavior of QSOX1 in nasopharyngeal carcinoma (NPC) and its effect on radiosensitivity. The levels of QSOX1 detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in radioresistant NPC patient sera and tissue samples were markedly lower than those in radiosensitive samples. Small hairpin RNAs (shRNAs) were employed to knock down endogenous QSOX1 expression in CNE-2 cells, and then, radiosensitivity, apoptosis, migration and invasion were assessed using colony formation, Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays, respectively. Tumor growth and radioresistance were also evaluated using a xenograft model in nude mice. The shRNA-mediated knockdown of QSOX1 significantly increased cell survival under irradiation (IR) and weakened radiosensitivity, which was likely due to a reduction in the cell apoptosis rate after IR. Moreover, QSOX1 silencing led to the suppression of cellular migration and invasion. Similar results were obtained with the xenograft mouse model. Thus, targeting QSOX1 will provide a new avenue for increasing the sensitivity of NPC to radiotherapy.