Sinomenine regulates circTRPM7-related pathway to inhibit gastric cancer cell growth and metastasis.

Sinomenine has been found to have antitumor effects in a variety of cancers, including gastric cancer. Circular RNA (circRNA) is an important regulator of gastric cancer progression. However, it is not known whether Sinomenine mediates gastric cancer processes by regulating circRNA-related pathways. Quantitative real-time PCR was used to measure the expression of circTRPM7, microRNA-145-5p (miR-145-5p), and pre-B-cell leukemia homeobox 3 (PBX3). MTT assay, colony formation assay, EdU assay, transwell assay, wound-healing assay, and flow cytometry were used to detect cell proliferation, migration, invasion, and apoptosis. The expression of related proteins was detected by Western blot. Mechanically, the interaction of miR-145-5p with circTRPM7/PBX3 was validated by dual-luciferase reporter assay and RIP assay. Our study showed that circTRPM7 expression was reduced in Sinomenine-treated gastric cancer cells. Moreover, overexpression of circTRPM7 upregulated the growth and metastasis of Sinomenine-treated gastric cancer cells. CircTRPM7 could sponge miR-145-5p, and miR-145-5p reversed the effect of circTRPM7 on the growth and metastasis of Sinomenine-treated gastric cancer cells. PBX3 was the target of miR-145-5p, and knockdown of PBX3 could restore the in-miR-145-5p promotion effect on the malignant behavior of Sinomenine-treated gastric cancer cells. To sum up, our data indicated that Sinomenine played an antitumor role in gastric cancer cells via circTRPM7/miR-145-5p/PBX3 axis.

Progress in the chemotherapeutic treatment of osteosarcoma.

Osteosarcoma (OS) is the most common type of primary bone tumor in children and adolescents and has been associated with a high degree of malignancy, early metastasis, rapid progression and poor prognosis. However, the use of adjuvant chemotherapy improves the prognosis of patients with OS. OS chemotherapy is based primarily on the use of adriamycin, cisplatin (DDP), methotrexate (MTX), ifosfamide (IFO), epirubicin (EPI) and other drugs. Previous studies have revealed that the survival rate for patients with OS appears to have plateaued: 5-year survival rates remain close to 60%, even with the use of combined chemotherapy. The most limiting factors include complications and fatal toxicity associated with chemotherapy agents, particularly high-dose MTX (HD-MTX), for which high toxicity and great individual variation in responses have been observed. Docetaxel (TXT) is a representative member of the relatively recently developed taxane class of drugs, which function to inhibit OS cell proliferation and induce apoptosis. Recently, more clinical studies have reported that TXT combined with gemcitabine (GEM) is effective in the treatment of OS (relapse/refractory and progressive), providing evidence in support of potential novel treatment strategies for this patient population. However, there is still no global consensus on this type of chemotherapy approach. The present review summarizes current studies surrounding progress in the chemotherapeutic treatment of OS and discusses the advantages and potential feasibility of TXT+GEM in the treatment of OS.

Expression of long non­coding RNA and mRNA in the hippocampus of mice with type 2 diabetes.

Long non­coding RNAs (lncRNAs) serve key roles in cell growth, development and various diseases associated with the central nervous system. However, differential expression profiles of lncRNAs in type 2 diabetes have not been reported. The present study aimed to analyze the expression pattern of lncRNA­mRNA in a type 2 diabetic mouse model using microarray analysis. The mouse model of type 2 diabetes was established and the total RNAs were extracted from the hippocampus of the mice used in the present study. The total RNAs were then examined by the GeeDom human lncRNA + mRNA V4.0 expression profile and analyzed through comparing Gene Ontology (GO) enrichment analysis and signal pathway analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. There were statistically significant differences between the expression of IncRNAs and mRNA in the healthy mice and that of the diabetic mice. In the diabetic mice, 130 different lncRNAs were expressed with 126  significantly upregulated and 4 significantly downregulated and 49 different mRNAs were detected with 45 significantly upregulated and 4 downregulated. GO analysis indicated that the mRNAs that are affected are involved in transport, cell adhesion, ion transport and metabolic processes. KEGG and Reactome enrichment analysis indicated that mRNAs impact on cholinergic synapses, nuclear factor­kB pathway, Toll like receptor 4 cascade and zinc transporter are correlated with cognitive dysfunction in type 2 diabetes. A dynamic lncRNA­mRNA network was constructed containing 123 lncRNAs and 48 mRNAs, which can elucidate the interaction between lncRNA and mRNA. Overall, this is the first study to indicate that lncRNAs are differentially expressed in the type 2 diabetic mice.

Does intensified chemotherapy increase survival outcomes of osteosarcoma patients? A meta-analysis.

STUDY DESIGN: Meta-analysis. BACKGROUND: Although some new insights have been offered for clinical and scientific relevance, minor progress has been made in osteosarcoma treatment after a dramatic survival improvement in the late 1980s with the addition of chemotherapy to surgery. Intensified chemotherapy strategies have been suggested to increase the survival rate of patients with osteosarcoma. We performed this study to access whether intensified chemotherapy strategiesincreased survival outcomes of osteosarcoma patients compared with conventional chemotherapy strategies. METHODS: MEDLINE/PubMed, EMBASE, BIOSIS Previews, and Cochrane Library were searched from database set up to October2016. Randomized controlled trials (RCTs) and comparative clinical trials (CCTs) on intensified versus conventional chemotherapy strategies for osteosarcoma patients met the inclusion criteria, and the methodological quality standard were retrieved and reviewed. Data on participant characteristics, interventions, follow-up period, and outcomes were extracted from the included studies and analyzed by Review Manager 5.3. RESULTS: 12 studies (8 RCTs and 4CCT) involving 4112 patients were selected. There were no significant differences between intensified and conventional chemotherapy strategies group in 3-year event-free survival (OR, 1.01; 95% CI, [0.74-1.37]; P = 0.97), 5-year event-free survival (OR, 1.00; 95% CI, [0.86-1.17]; P = 0.97), and 5-year overall survival (OR, 1.04; 95% CI, [0.87-1.26]; P = 0.64), and good histologic response to preoperative chemotherapy (OR, 1.12; 95% CI, [0.78-1.60]; P = 0.55). Pooled analysis of local recurrence rate showed that local recurrence rate was significantly decreased in the intensified group compared with that in the conventional group (OR, 0.60; 95% CI, [0.42-0.85]; P = 0.004). CONCLUSIONS: Intensified chemotherapy might not be a preferred treatment for all of the osteosarcoma patients.

Effects of short-term warming and nitrogen addition on the quantity and quality of dissolved organic matter in a subtropical Cunninghamia lanceolata plantation.

Increasing temperature and nitrogen (N) deposition are two large-scale changes projected to occur over the coming decades. The effects of these changes on dissolved organic matter (DOM) are largely unknown. This study aimed to assess the effects of warming and N addition on the quantity and quality of DOM from a subtropical Cunninghamia lanceolata plantation. Between 2014 and 2016, soil solutions were collected from 0-15, 15-30, and 30-60 cm depths by using a negative pressure sampling method. The quantity and quality of DOM were measured under six different treatments. The spectra showed that the DOM of the forest soil solution mainly consisted of aromatic protein-like components, microbial degradation products, and negligible amounts of humic-like substances. Warming, N addition, and warming + N addition significantly inhibited the concentration of dissolved organic carbon (DOC) in the surface (0-15 cm) soil solution. Our results suggested that warming reduced the amount of DOM originating from microbes. The decrease in protein and carboxylic acid contents was mostly attributed to the reduction of DOC following N addition. The warming + N addition treatment showed an interactive effect rather than an additive effect. Thus, short-term warming and warming + N addition decreased the quantity of DOM and facilitated the migration of nutrients to deeper soils. Further, N addition increased the complexity of the DOM structure. Hence, the loss of soil nutrients and the rational application of N need to be considered in order to prevent the accumulation of N compounds in soil.

Serve the people: understanding ideology and professional ethics of medicine in China.

The article explores the communist ideology that has guided the formation of professional ethics of medicine in China. It first explores the constitutions of the People's Republic of China and the Chinese Communist Party and codes of practice for medicine enforced since 1949, showing that the core of the ideology in relation to health provision and doctor-patient relationship has always been 'serving the people wholeheartedly'. The ideological undertaking, however, has never been successfully exercised. In the pre-reform era, the bureaucratisation of health professionals led to the emergence of 'bureaucratic medicine' featuring negligence of patients' interests. In the reform era, the prevailing commercialisation of health care is in fundamental conflict with the ideological commitment to serving the people. As a result, the socialist professional ethics of medicine has not been satisfactorily practiced in reality.

Cell density and serum exposure modify the function of the glucocorticoid receptor C/EBP complex.

The glucocorticoid receptor (GR) is a major control factor for proliferation, differentiation, and inflammation. Our knowledge about the GR is focused on its function as a transcription regulator. However, cells do not always respond to steroids in the same way or develop resistance. The mechanism underlying such a modified steroid response is not well understood, and may depend on the microenvironment of the cells or on the stage of their differentiation. Therefore, we studied the effect of cell density and inflammatory conditions on the expression, compartmentalization, activation, and the anti-proliferative function of the GR in primary human lung fibroblast cultures. In subconfluent cells the GR was located perinuclear, while in confluent cells it was ubiquitously expressed. Serum stimulation up-regulated the level of GR mRNA and protein under all conditions. In subconfluent cells dexamethasone activated the nuclear accumulation and DNA binding of the GR persistently, while in confluent cells its activity declined after 6 hours. In subconfluent cells, but not in confluent cells, the GR interacted with a 42-kD, but not the 30-kD C/EBP-alpha isoprotein, which resulted in an up-regulation of p21((Waf1/Cip1)) expression and suppression of proliferation. In confluent cells, glucocorticoids induced p27((Kip1)) expression via p38 mitogen-activated protein kinase and a 52-kD C/EBP-beta isoprotein. However, p27((Kip1)) did not mediate the antiproliferative effect of glucocorticoids, but simultaneous inhibition of p21((Waf1/Cip1)) and p27((Kip1)) unlocked contact inhibition in confluent cells. Our results indicate that cell density and serum exposure alter the localization and function of the GR.

Mesenchymal Stem Cells Derived from Human Bone Marrow Support Hematopoiesis in Vitro.

Bone marrow mesenchymal stem cells (MSCs) are multipotential progenitors of connective tissues and bone marrow stroma as well, which implies the modulatory function of MSCs in hematopoiesis. To clarify the contributions of MSCs to hematopoiesis, the methods for isolation and expansion of MSCs were established and long-term bone marrow cultures were performed using irradiated MSCs as the feeder layer. The results here showed that CD34(+) cells from cord blood formed hematopoietic foci adherent to the monolayer. Furthermore, colony-forming cells remained in the coculture of 5 weeks, indicating the maintenance of long-term culture-initiating cells (LTC-IC). Flow cytometry analysis showed that about 1% of the hematopoietic cells in the culture were positive for CD34 and around 15% were CD41a-positive. It is clear that MSCs maintain LTC-IC in vitro and promote differentiation of hematopoietic progenitors especially into megakaryocytic lineage. The preliminary results here demonstrate that MSCs residing in the bone marrow might be a crucial cellular component in the hematopoietic microenvironment.