Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose's action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski's rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.

Inactivation and photoreactivation of blaNDM-1-carrying super-resistant bacteria by UV, chlorination and UV/chlorination.

The excessive dissemination of New Delhi metallo-ß-lactamase-1 (NDM-1), which mediates resistance to a majority of clinical ß-lactam antibiotics, has created a major public health problem worldwide. Herein, a blaNDM-1-carrying (plasmid encoded) super-resistant bacterium, Acinetobacter sp. CS-2, was selected to reveal its mechanisms of inactivation and photoreactivation during UV, chlorination and UV/chlorination disinfection. The inactivated CS-2 underwent a certain photoreactivation after UV and chlorination. The logistic model precisely fitted the data obtained in the photoreactivation experiments by UV treatment, with the estimated kinetic parameters Sm (0.530%-12.071%) and k2 (0.0009-0.0471). The photoreactivation of Acinetobacter sp. CS-2 was observed when treated by chlorination at a dosage of 0.5 mg/L with a survival ratio of 34.04%. UV/chlorination not only resulted in the high-efficiency reduction of CS-2 but also effectively controlled its photoreactivation with a survival ratio of 0%- 0.87%. UV/chlorination showed great advantages in causing the irreversible destruction of bacterial surface structures by making the cell membranes wrinkled and incomplete compared with UV disinfection. The singlet oxygen (1O2) generated during UV/chlorination treatment played a vital role in blaNDM-1 removal. This study proposed new insights into the mechanism of inactivation and the characteristics of photoreactivation for the super-resistant bacteria by UV, chlorination and UV/chlorination.

99Tc-Methylene Diphosphonate Treatment is Safe and Efficacious for Osteoporosis in Postmenopausal Differentiated Thyroid Cancer Patients Undergoing TSH Suppression: A Three-Center Non-Randomized Clinical Study.

Objective: To investigate the effects of 99Tc-methylene diphosphonate (99Tc-MDP) on osteoporosis (OS) in postmenopausal patients with differentiated thyroid cancer (DTC) under thyroid stimulating hormone (TSH) suppression. Patients and Methods: Patients (n = 142) were divided into two groups: (1) 99Tc-MDP (n = 70) and (2) alendronate (n = 72) treatments (NCT02304757). Bone mineral density (BMD) in the lumbar spine and hip was evaluated by DXA, along with bone turnover markers, safety, and quality of life (QOL) using SF-36 at three time points: before treatment and at 6 and/or 12 months after treatment. Results: The percentage change of BMD in total lumbar spine or hip showed no significant difference throughout the study (P > 0.025). 99Tc-MDP and alendronate treatment alone significantly increased BMD in the lumbar spine, but alendronate treatment also significantly increased BMD in total hip at 6 and 12 months, as compared with the baseline. There were no significant differences in the results of the SF-36 scores between the two treatment groups at any time during the whole study period. 99Tc-MDP significantly increased bone formation markers of osteocalcin at 6 and 12 months (P all < 0.05), PINP at 12 months (P = 0.001), and bone resorption markers of ß-CTX at 6 and 12 months (p < 0.05) as compared with the alendronate treated group. No adverse event was observed in the 99Tc-MDP treatment group compared with alendronate (P = 0.014). Conclusion: 99Tc-MDP was as efficacious as alendronate in the improvement of lumbar BMD for DTC patients with OS under TSH stimulation. 99Tc-MDP was shown to be safe and improved patients' QOL.

miR­367­3p downregulates Rab23 expression and inhibits Hedgehog signaling resulting in the inhibition of the proliferation, migration, and invasion of prostate cancer cells.

MicroRNAs play an important role in tumor cell proliferation, invasion, and Rab23 is a member of the Ras­related small GTPase family and plays a critical role in the progression of may types of tumors. The present study was designed to investigate the inhibitory effect of microRNA (miR)­367­3p on the proliferation, invasion, and metastasis of prostate cancer cells. qRT­PCR was used to detect the expression of miR­367­3p in prostate cancer and adjacent tissues. Cell proliferation, scratch, and Transwell assays were performed to verify the inhibitory effect of miR­367­3p overexpression or Ras­related protein Rab 23 (Rab23) knockdown on prostate cancer. Double luciferase reporter assay was utilized to verify whether miR­367­3p could target the Rab23 3'­untranslated region (UTR). The expression levels of Rab23, Gli1, and Gli2 in prostate cancer cells transfected with the miR­367­3p mimic were detected via qRT­PCR analysis. miR­367­3p expression in the prostate cancer tissues was downregulated compared with that in the para­cancer control tissues. miR­367­3p expression in DU145 and PC3 cells was also downregulated compared with that in the human prostate epithelial cell line RWPE­1. The overexpression of miR­367­3p or the knockdown of Rab23 inhibited the proliferation, invasion, and metastasis of prostate cancer cells. The results of the luciferase reporter assay confirmed that Rab23 was a target gene that was regulated by miR­367­3p. miR­367­3p specifically bound to the 3'­UTR of Rab23 mRNA. The overexpression of miR­367­3p inhibited Rab23 expression and the Hedgehog pathway. Cell function experiments confirmed that the overexpression of Rab23 reversed the anticancer effect of miR­367­3p. miR­367­3p was able to inhibit the Hedgehog pathway by targeting the expression of the Rab23 gene, thus inhibiting the proliferation, invasion, and metastasis of prostate cancer cells.

99mTc-Methylene Diphosphonate Uptake in Soft Tissue Tumors on Bone Scintigraphy Differs Between Pediatric and Adult Patients and Is Correlated with Tumor Differentiation.

OBJECTIVE: To analyze the difference in 99mTc-methylene diphosphonate (MDP) uptake on bone scintigraphy in extraosseous soft tissue tumors between children and adults and the correlation between tracer uptake and tumor differentiation and histopathology. METHODS: Patients with neoplasms with MDP uptake were retrospectively identified. Based on histopathology, tumors were categorized as epithelial malignant tumors, mesenchymal tumors, blastomas and germ cell tumors. The degree of radioactivity accumulation in lesions relative to the uptake in ribs and sternum or spine was classified as "+", "++" and "+++". The results were compared between children and adults. The correlations between MDP uptake in soft tumors and tumor differentiation and pathology were investigated. RESULTS: Extraosseous soft tissue tumors that accumulated MDP were found in 33 children and 31 adults. In children, neuroblastoma was the most common extraosseous soft tissue tumor that accumulated MDP; in adults, MDP uptake was mostly found in lung cancer. MDP uptake in pediatric soft tissue tumors was higher than that in adults. MDP uptake in extraosseous soft tissue tumors with different histopathologic classifications was significantly different among 64 patients. In 41 patients with available tumor differentiation data from histopathology, MDP uptake in low or poorly differentiated soft tumors was higher than that in the moderately or well-differentiated lesions. Necrosis and/or calcifications were showed in most of pediatric and adult neoplasms. CONCLUSION: Significant elevations in MDP uptake in extraosseous soft tissue tumors are associated with poorly differentiated tumors in both children and adults. The mechanism of bone tracer uptake in pediatric and adult neoplasms was mostly related to necrosis and/or necrosis and calcification. The extraosseous soft tissue tumors with MDP uptake in pediatric patients were different from those in adults. In addition, consistent with the inherent degree of tumor malignancy, MDP uptake in children was higher than that in adults.

Fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography findings in a pediatric mucoepidermoid carcinoma and differential diagnosis.

An 11 years old boy was referred to our hospital. He complained for the last three months for intermittent cough and shortness of breath after exercise which worsened recently. Airways computed tomography (CT) showed an abnormal endobronchial tumor, obstructing the right main bronchus and also atelectasis in the upper lobe of the right lung. Bronchoscopy showed a wet on its surface mass obstructing the right main bronchus. Biopsy showed a mucoepidermoid carcinoma (MEC). The fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan showed in the same area a mass with slightly increased 18F-FDG uptake (maximum standardized uptake value, SUVmax: 3.8), without mediastinal lymph nodes involvement. The boy had thoracoscopic resection of the right upper lobe, right main bronchus and right inferior lobe bronchial sleeve anastomosis. Histological examination confirmed the diagnosis of a low to intermediate grade malignant MEC without lymph nodes metastases. The patient has been well and free from recurrence for 2 years postoperatively.