Objective:Breast cancer metastasis is a major cause of death. Lymphatic metastasis is one of the two main metastatic ways that is crucial to the metastasis process of breast cancer. To treat breast cancer metastasis, we prepared micelle-based drug carrier for lymphatic delivery. Methods:We used in vivo bioluminescence imaging for real-time dynamic monitoring of the inhibitory effect of polyethylene glycol phospholipid micelle encapsulating vinorelbine on breast cancer metastasis. Results: Compared with the free vinorelbine, vinorelbine-encapsulated micelles (NanoVin) showed a significantly enhanced anti-tumor activity both in primary and met-astatic tumors. Conclusion:Intravenous administration of NanoVin markedly prevented the metastasis of tumor cells through both he-matogenous and lymphatic systems. This study provides a new approach for treatment of metastatic tumors. Bioluminescence imaging is a powerful tool to dynamically monitor tumor metastasis and clinical therapeutic effect of anticancer drugs.

Metastasis is the main cause of death in cancer patients. To improve the outcomes of patients undergoing a surgery, new adjuvant therapies that can effectively inhibit metastases have to be developed. Studies have shown that flavonoid naringenin, a natural product that is mainly present in grapes and citrus, may contribute to cancer prevention. It has many advantages compared to traditional chemotherapeutic drugs, such as low toxicity. To determine whether naringenin can also inhibit metastases, a breast cancer resection model that mimics clinical situations was established. We found that orally administered naringenin significantly decreased the number of metastatic tumor cells in the lung and extended the life span of tumor resected mice. Flow cytometry analysis revealed that T cells displayed enhanced antitumor activity in naringenin treated mice, with an increased proportion of IFN-γ and IL-2 expressing T cells. In vitro studies further demonstrated that relief of immunosuppression caused by regulatory T cells might be the fundamental mechanism of metastasis inhibition by naringenin. These results indicate that orally administered naringenin can inhibit the outgrowth of metastases after surgery via regulating host immunity. Thus, naringenin can be an ideal surgical adjuvant therapy for breast cancer patients.
Animals ; Anticarcinogenic Agents ; administration & dosage ; therapeutic use ; Antigens, CD ; analysis ; Breast Neoplasms ; drug therapy ; immunology ; pathology ; surgery ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chemotherapy, Adjuvant ; Female ; Flavanones ; administration & dosage ; therapeutic use ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Interferon-gamma ; biosynthesis ; immunology ; Interleukin-2 ; biosynthesis ; immunology ; Lung Neoplasms ; drug therapy ; immunology ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; drug effects ; immunology ; metabolism

The differentiation of periodontal ligament (PDL) progenitor cells is important for maintaining the homeostasis of PDL tissue and alveolar bone. Vitamin C (VC), a water-soluble nutrient that cannot be biosynthesized by humans, is vital for mesenchymal stem cells differentiation and plays an important role in bone remodeling. Therefore, the objective of this study was to determine the function and mechanism of VC in PDL progenitor cells osteogenic differentiation at the molecular level. We demonstrated that VC could induce the osteogenic differentiation and maturation of PDL progenitor cell without other osteogenic agents. During the process, VC preferentially activated ERK1/2 but did not affect JNK or p38. Co-treatment with ERK inhibitor effectively decreased the Vitamin C-induced expression of Runx2. ERK inhibitor also abrogated Vitamin C-induced the minimized nodules formation. PELP1, a nuclear receptor co-regulator, was up-regulated under VC treatment. PELP1 knockdown inhibited ERK phosphorylation. The overexpression of PELP1 had a positive relationship with Runx2 expression. Taken together, we could make a conclude that VC induces the osteogenic differentiation of PDL progenitor cells via PELP1-ERK axis. Our finding implies that VC may have a potential in the regeneration medicine and application to periodontitis treatment.
Ascorbic Acid ; pharmacology ; Butadienes ; pharmacology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Co-Repressor Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Core Binding Factor Alpha 1 Subunit ; genetics ; metabolism ; Humans ; MAP Kinase Signaling System ; drug effects ; Mitogen-Activated Protein Kinase 1 ; antagonists & inhibitors ; metabolism ; Mitogen-Activated Protein Kinase 3 ; antagonists & inhibitors ; metabolism ; Nitriles ; pharmacology ; Periodontal Ligament ; cytology ; Phosphorylation ; drug effects ; RNA Interference ; RNA, Small Interfering ; metabolism ; Stem Cells ; cytology ; Transcription Factors ; antagonists & inhibitors ; genetics ; metabolism ; Up-Regulation ; drug effects

The effect of the anti-inflammatory flavonoid chrysin on osteogenesis was determined in preosteoblast MC3T3-E1 cells. Results demonstrated that chrysin could induce osteogenic differentiation in the absence of other osteogenic agents. Chrysin treatment promoted the expression of transcription factors (Runx2 and Osx) and bone formation marker genes (Col1A1, OCN, and OPN) as well as enhanced the formation of mineralized nodules. During osteogenic differentiation, chrysin preferentially activated ERK1/2, but not JNK nor the p38 MAPKs. Further experiments with inhibitors revealed the co-treatment of U0126, PD98059, or ICI182780 (a general ER antagonist) with chrysin effectively abrogated the chrysin-induced osteogenesis and ERK1/2 activation. Thus, the effect of chrysin on osteogenesis is ERK1/2-dependent and involves ER. Therefore, chrysin has the significant potential to enhance osteogenesis for osteoporosis prevention and treatment.
Animals ; Cell Differentiation ; drug effects ; Cell Line ; Enzyme Activation ; drug effects ; Flavonoids ; pharmacology ; therapeutic use ; Mice ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; Osteoblasts ; drug effects ; pathology ; Osteogenesis ; drug effects ; Osteoporosis ; drug therapy ; pathology ; Phosphorylation ; drug effects ; Receptors, Estrogen ; metabolism

Objective To evaluate the effect of united Organ Procurement Organization (OPO) on organ donation and procurement quality control indexes. Methods The differences in organ donation workload, work efficiency, organ donation quality control and management indexes in a united OPO-led hospital were retrospectively analyzed before (n=36) and after (n=33) the establishment of united OPO. Results After the establishment of united OPO, the organ donation workload and efficiency were enhanced. The annual donation cases, annual organ procurement cases, average organ procurement cases per day, organ donation rate of per million population (PMP), coordinator work efficiency index and other indexes were further improved. Before the establishment of united OPO, the donation conversion rate was 26.5%, and increased up to 29.0% after the establishment of united OPO. The average organ yield rate remained higher than 3.3 before and after the establishment of united OPO. No significant differences were noted in the utilization rate of procured organs, proportion of marginal donor organs, positive rate for pathogen culture in organ preservation solution, the incidence of primary nonfunction (PNF) and delayed graft function (DGF) before and after the establishment of united OPO (all P > 0.05). The biopsy rates of donated organs were 27.7% and 58.3%, and the organ outflow rates were 83.1% and 47.8% before and after the establishment of united OPO, and the differences were statistically significant (both P < 0.05). Conclusions The establishment of united OPO contributes to promoting efficient development of organ donation and procurement, lowering the cost of organ donation and procurement, and improving the effectiveness, quality control and management levels of organ donation and procurement.

【Objective】 To explore the effects of prucalopride (PRUC) on the intestinal function during the perioperative period of robot-assisted laparoscopic radical cystectomy (RARC) and urinary diversion. 【Methods】 A total of 75 patients undertaking RARC with urinary diversion (orthotopic neobladder or ileal bladder) in Nanjing Drum Hospital during Jan.and Dec.2021 were divided into PRUC group (n=28) and control group (n=47) according to whether they took PRUC or not.Postoperative intestinal ventilation time and defecation time, drainage tube retention time, tolerance time for first intake of semi-flow food, postoperative hospital stay, and incidence of complications were observed and recorded in the two groups.Postoperative C-reactive protein (CRP) and neutrophil/lymphocyte ratio (NLR) were compared. 【Results】 The PRUC group had shorter intestinal ventilation time and defecation time [(47.14±16.31) h vs.(74.04±35.33) h, P<0.01; (86.14±30.47) h vs.(123.57±79.12) h, P=0.02] , smaller change of ΔCRP and ΔNLR [(79.99±29.71) mg/L vs.(127.75±56.98) mg/L; (9.24±6.43) vs.(16.11±9.90), P<0.01] .All complications were minor, the incidence of intestinal obstruction in PRUC group tended to decrease within 90 days after operation (P=0.38), and there was no significant difference in other complications between the two groups (P>0.05). 【Conclusion】 The perioperative use of PRUC in RARC with urinary diversion is safe and effective, which can promote the recovery of intestinal function after operation.