Effect of multidisciplinary cooperative continuous nursing and psychological nursing on multiple myeloma with a peripherally inserted central catheter.

Objective: This study was conducted to analyze the effectiveness of multidisciplinary cooperative continuous nursing combined with psychological nursing intervention in multiple myeloma (MM) patients undergoing peripherally inserted central catheter (PICC). Methods: The Numerical Pain Rating Scale (NPRS), Anxiety Self-Assessment Scale (SAS), Depression Self-Assessment Scale (SDS) and Revised Piper Fatigue Scale (PFS-R), Self-Care Ability Scale (ESCA), Quality of Life Core Questionnaire (QLQ-C30), incidence of unplanned extubation of PICC, total incidence of catheter-related complications and satisfaction with nursing were compared between the two groups of patients in a prospective study. Results: Patients in the observation group had reduced NPRS, SAS, SDS and PFS-R scores, total incidence of unplanned extubation of PICC and the total incidence of catheter-related complications, and a higher nursing satisfaction rate in comparison to those in the control group. Conclusion: Multidisciplinary cooperative continuous nursing combined with psychological nursing interventions can relieve pain in MM patients.

Inhibition of FSTL3 abates the proliferation and metastasis of renal cell carcinoma via the GSK-3ß/ß-catenin signaling pathway.

Renal cell carcinoma (RCC) is a lethal malignancy of the genitourinary system. Follistatin-like 3 (FSTL3), which mediates cell differentiation and growth, acts as a biomarker of tumors and participates in cancer development and progression. Presently, the FSTL3's functions in RCC were investigated. Quantitative reverse transcription PCR (qRT-PCR), Western Blot, and enzyme linked immunosorbent assay (ELISA) were conducted to verify FSTL3 expression in RCC tissues and cell lines. BrdU assay and CCK8 experiment were made to monitor cell proliferation. Transwell was implemented to examine the invasion of the cells. Flow cytometry analyzed cell apoptosis, and Western Blot evaluated the protein levels of E-cadherin, Twist, and Slug. In the meantime, the protein profiles of the GSK-3ß, ß-catenin, and TGF-ß signaling pathways were ascertained. Moreover, the Xenograft tumor model was constructed in nude mice for measuring tumor growth in vivo. The statistics showed that FSTL3 presented an overexpression in RCC, and patients with a lower expression of FSTL3 manifested a better prognosis. Down-regulated FSTL3 hampered the proliferation, invasion, EMT, and tumor growth of RCC cells and caused cell apoptosis. On the contrary, FSTL3 overexpression enhanced the malignant behaviors of RCC cells. Furthermore, FSTL3 knockdown bolstered GSK-3ß, suppressed ß-catenin, and reduced BMP1-SMAD pathway activation. Inhibited ß-catenin substantially mitigated FSTL3-mediated promoting functions in RCC. In short, FSTL3 functions as an oncogene in RCC by modulating the GSK-3ß/ß-catenin signaling pathway.

FAST1 Predicts Poor Survival of Renal Carcinoma and Promotes Its Progression Through the TGF-ß/Smad Pathway.

PURPOSE: Renal carcinoma (RC) originates in the renal tubular epithelial system, among which renal cell carcinoma (RCC) is the most frequent one. The forkhead activin signal transducer 1 (FAST1) has been shown to interfere with tumor progression as an oncogene, while its role in RC is limited. Therefore, this paper explored the prognostic significance, specific effects, and related mechanisms of FAST1 on RC. PATIENTS AND METHODS: Cell colony formation assay, cell counting kit-8 (CCK8) assay, flow cytometry and Transwell assay were used to test cell proliferation, viability, apoptosis, migration and invasion, respectively. Western blot (WB) was employed to determine the protein level of FAST1. RESULTS: Our study confirmed that FAST1 was up-regulated in RC tissues and cell lines, and its overexpression often represented a poor prognosis of RC patients. Meanwhile, the in vitro experiments showed that overexpressing FAST1 facilitated RC cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT), and repressed cell apoptosis. In addition, the in vivo experiments illustrated that the up-regulation of FAST1 strengthened tumor growth. On the contrary, knocking down FAST1 had the opposite effects. Mechanistically, The TGF-ß/Smad pathway contributed to RC evolvement and was activated by FAST1 both in vitro and in vivo. CONCLUSION: This article suggests that FAST1 exerts a carcinogenic role in RC by regulating the TGF-ß/Smad signaling.

Rapamycin inhibited the function of lung CSCs via SOX2.

The presence of cancer stem cells (CSCs) is the source of occurrence, aggravation, and recurrence of lung cancer. Accordingly, targeting killing the lung CSCs has been suggested to be an effective approach for lung cancer treatment. In this study, we showed that rapamycin inhibited the mammalian target of rapamycin (mTOR) signal transduction in A549 cells and improved the sensitivity to cisplatin (DDP). The mechanisms involve inhibition of the SOX2 expression, cell proliferation, epithelial-mesenchymal transition (EMT) phenotype, and sphere formation. Interestingly, knocked down SOX2 was a similar effect with rapamycin in A549 sphere. Furthermore, we showed that ectopic expression of Sox2 in A549 cells was sufficient to render them more resistant to rapamycin treatment in vitro. These data suggested that rapamycin inhibited the function of lung CSCs via SOX2. It will be of great interest to further explore the therapeutic strategies of lung cancer.

Enhanced expression of stem cell markers and drug resistance in sphere-forming non-small cell lung cancer cells.

There is growing evidence suggesting that cancer stem cells (CSCs) are playing critical roles in tumor progression, metastasis and drug resistance. However, the role of CSCs in non-small cell lung cancer (NSCLC) remains elusive. In this study, we enriched for stem-like cells from tumor spheres derived from NSCLC cell line A549 cultured in serum-free medium. Our results showed that sphere-derived cells expressed various stem cell markers such as CD44, CD133, Sox2 and Oct4. Compared with the corresponding cells in monolayer cultures, sphere-derived cells showed marked morphologic changes and increased expression of the stem cell markers CD133. Furthermore, we found that sphere-derived cells exhibited increased proliferation, cell-cycle progression as well as drug-resistant properties as compared to A549 adherent cells. Consistently, expression of several drug resistance proteins, including lung resistance-related protein (LRP), glutathion-S-transferase-π (GST-π) and multidrug resistance proteins-1 (MRP1) were all significantly enhanced in sphere-derived cells. These results indicate the enrichment of CSCs in sphere cultures and support their role in regulating drug resistance in NSCLC.

Biopharmaceutical and pharmacokinetic characterization of asiatic acid in Centella asiatica as determined by a sensitive and robust HPLC-MS method.

ETHNOPHARMACOLOGICAL RELEVANCE: Asiatic acid is one of the main components in the herb Centella asiatica, which is a well-known herbal medicine for its excellent pharmacological effects. To enhance the development potentials of asiatic acid as a chemopreventative agent, there is a great need to further understand its biopharmaceutical and pharmacokinetic properties. The aim of this research is to clarify the mechanisms of absorption and metabolism of asiatic acid, and explore its biopharmaceutical and pharmacokinetic properties in rats by using a sensitive and robust HPLC-MS method. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to 2 groups and administered with asiatic acid by oral and intravenous administration. Plasma concentrations of asiatic acid were determined at designated points and main pharmacokinetic parameters were estimated. The absorption of asiatic acid was investigated by using Caco-2 cell line absorption model in vitro and rat intestinal perfusion model in situ. The metabolic rate of asiatic acid was investigated by incubating it in rat liver microsome system in vitro. In addition, the solubility of asiatic acid in aqueous solution was also determined by using HPLC-MS method. RESULTS: The absolute oral bioavailability of asiatic acid is 16.25%. It was found that the permeability of asiatic acid is more than 10(-5) in the Caco-2 cell monolayer and rat intestinal perfusion model, and its main absorption region is the jejunum in rats. The metabolic rate of asiatic acid in rat liver microsomes, t1/2, is 9.493min, which shows that asiatic acid can be metabolized rapidly. The solubility of aisiatic acid was 0.1583mgmL(-1), and its poor solubility will result in low bioavailability. CONCLUSIONS: The asiatic acid in a variety of matrixes was analyzed by using a sensitive and specific HPLC-MS method, and its absolute oral bioavailability in rats was very low. Asiatic acid can be metabolized rapidly in rat liver microsomes, and has good permeability across Caco-2 monolayer cell and rat intestine perfusion. It can be deduced that the low bioavailability of asiatic acid results from poor solubility and rapid metabolism.

Comparative pharmacokinetics of hypaconitine after oral administration of pure hypaconitine, Aconitum carmichaelii extract and Sini Decoction to rats.

Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction (SND), composed of Aconitum carmichaelii, Glycyrrhiza uralensis and Zingiber officinale, is a traditional Chinese multi-herbal formula for recuperating the depleted yang. The aim of this study was to compare the pharmacokinetics of HC in rat plasma after oral administration of HC, AC extract and SND, and investigate the effect of other two herbal ingredients on absorption, metabolism and elimination of HC. A sensitive and specific LC-MS/MS method was developed to determine HC in rat plasma. Eighteen male Sprague-Dawley rats were randomly assigned to three groups: HC, AC and SND group. Plasma concentrations of HC were determined at designated points after oral administration, and main pharmacokinetic parameters were estimated. It was found that there was obvious difference (p < 0.05) on the pharmacokinetic parameters among three groups. Compared with AC group, Tmax, Cmax, k, AUC(0-24) and AUC(0-∞) decreased in SND group, while t1/2 and MRT had been lengthened, which indicated that the ingredients in other two herbs could influence the pharmacokinetic behavior of HC.

Intestinal transport of sophocarpine across the Caco-2 cell monolayer model and quantification by LC/MS.

Sophocarpine is a biologically active component obtained from the foxtail-like sophora herb and seed that is often orally administered for the treatment of cancer and chronic bronchial asthma. The aim of this study was to develop a rapid and specific LC/MS method for the determination of sophocarpine and to explore its transcellular transport mechanism across the Caco-2 (the human colon adenocarcia cell lines) monolayer cell transwell model. Caco-2 cells were seeded on permeable polycarbonate membranes and incubated for 21 days. Before the experiment, the trans-epithelial electric resistance, integrity and alkaline phosphatase activity of the Caco-2 monolayers were verified and used in subsequent experiments. In the Caco-2 model constructed, many influencing factors were investigated, including time, concentration, pH and different protein inhibitors. The results suggested that sophocarpine was transported mainly by passive diffusion. The flux of sophocarpine was time- and concentration-dependent, and the pH also had an effect on its transportation. The PappBA was higher than PappAB , indicating that a polarized transport might exist for sophocarpine. MK-571 and reserpine, inhibitors of the multidrug resistance associated protein 2 and the breast cancer resistance protein, decreased the efflux of sophocarpine, while verapamil had no effect on its transport. These results revealed that sophocarpine is absorbed mainly by passive diffusion, and that a carrier-mediated mechanism is also involved in the transport of sophocarpine.