MicroRNA-18 facilitates the stemness of gastric cancer by downregulating HMGB3 though targeting Meis2.

The recurrence and metastasis of gastric cancer are related to the stemness of gastric cancer cells. Researches have shown that miR-18 level is negatively correlated to the occurrence and development of certain cancer types. However, the effects of miR-18 on the stemness of gastric cancer remain uncertain. In this research, gastric cancer cell lines with stable overexpression of miR-18 were constructed through lentivirus infection. CCK-8 assay, RT-qPCR, Western blot, flow cytometry, and in vivo tumorigenesis assays were performed to evaluate the effects of miR-18 on the stemness of gastric cancer cells. Moreover, luciferase reporter assays found that Meis2 was the target of miR-18. Furthermore, we also found that the low-expressed oncogene HMGB3 is involved in this miR-18/Meis2 axis to further promote the stemness of gastric cancer cells. These findings suggest that the miR-18/Meis2/HMGB3 axis may be potential prognostic indicators for patients with gastric cancer.

Current Strategies for Cancer Cell-Derived Extracellular Vesicles for Cancer Therapy.

Cancer cell-derived extracellular vesicles (CEVs), a novel type of therapeutic agent in cancer treatment, can be prepared from the autocrine secretion of various cancer cells, the direct extraction of cancer cells and the combination of cancer cell-derived membranes with advanced materials. With various bioactive molecules, exosomes are produced by cells for intercellular communication. Although cancer cell-derived exosomes are known to inhibit tumor apoptosis and promote the progression of cancer, researchers have developed various innovative strategies to prepare anti-tumor vesicles from cancer cells. With current strategies for anti-tumor vesicles, four different kinds of CEVs are classified including irradiated CEVs, advanced materials combined CEVs, chemotherapeutic drugs loaded CEVs and genetically engineered CEVs. In this way, CEVs can not only be the carriers for anti-tumor drugs to the target tumor area but also act as immune-active agents. Problems raised in the strategies mainly concerned with the preparation, efficacy and application. In this review, we classified and summarized the current strategies for utilizing the anti-tumor potential of CEVs. Additionally, the challenges and the prospects of this novel agent have been discussed.

The effect of highly inhomogeneous biphasic properties on mechanical behaviour of articular cartilage.

BACKGROUND AND OBJECTIVE: Investigating the biomechanics of cartilage could help to understand the unique load-bearing property of the cartilage and optimize the scaffold design in tissue-engineering. It is important to model the cartilage as a highly inhomogeneous fibril-reinforced biphasic material to represent its complex composition and structure. The depth-dependent and strain-dependent properties of the cartilage would also play an important role in its mechanical behaviour. However, the differences in representing the cartilage as a highly inhomogeneous model or as simplified models still remain unclear. Hence, in this study, a highly inhomogeneous fibril-reinforced biphasic cartilage model considering both the depth-dependent and strain-dependent properties was constructed; the effect of highly inhomogeneous properties on the mechanical behaviour of articular cartilage was investigated. METHODS: A finite element model of the cartilage was developed based on a flat-ended indentation test. Compressive forces were applied to four various inhomogeneous layered models through a porous indenter (Model 1: nine layers with strain-dependent permeability; Model 2: three layers with strain-dependent permeability; Model 3: single layer with strain-dependent permeability; Model 4: nine layers with constant permeability). RESULTS: Models 1 and 2 provided similar results with less than 3% difference in the peak effective stress, contact pressure, fluid pressure as well as fluid support ratio. However, Model 1 to Model 3 differed in stress and strain distribution patterns along depth over prolonged loads, which may provide an important insight into the highly inhomogeneous depth-dependent properties of cartilage. In addition, Model 1 with strain-dependent permeability demonstrated an enhanced capability on fluid pressurisation as compared with Model 4 which had constant permeability. CONCLUSIONS: A highly inhomogeneous fibril-reinforced biphasic model considering both depth-dependent and strain-dependent properties was developed in this study, in order to illustrate the effect of highly inhomogeneous properties on the mechanical behaviour of the articular cartilage. The number of layers in the models with depth-dependent properties should be selected according to the research questions and clinical demands. The model with strain-dependent permeability offers an enhanced capability on fluid pressurisation. In future studies, the proposed model could be adopted in cell-models to provide more in-depth information or in tissue-engineering to optimize the depth-dependent scaffold structure.

Current strategies of virotherapy in clinical trials for cancer treatment.

As a novel immune-active agent for cancer treatment, viruses have the ability of infecting and replicating in tumor cells. The safety and efficacy of viruses has been tested and confirmed in preclinical and clinical trials. In the last decade, virotherapy has been adopted as a monotherapy or combined therapy with immunotherapy, chemotherapy, or radiotherapy, showing promising outcomes against cancer. In this review, the current strategies of viruses used in clinical trials are classified and described. Besides this, the challenge and future prospects of virotherapy in the management for cancer patients are discussed in this review.

Long noncoding RNA MRAK009713 is a novel regulator of neuropathic pain in rats.

Long noncoding RNAs have been implicated in neuropathy. Here, we identify and validate a long noncoding RNA, MRAK009713, as the primary regulator of neuropathic pain in chronic constriction injury (CCI) rats. MRAK009713 expression was markedly increased in CCI rats associated with enhanced pain behaviors, and small interfering RNA against MRAK009713 significantly reduced both mechanical and thermal hyperalgesia in the CCI rats. MRAK009713 is predicted to interact with the nociceptive P2X3 receptor by CatRAPID, a bioinformatics technology. Overexpression of MRAK009713 markedly increased expression of P2X3 in the dorsal root ganglia of the control rats, and MRAK009713 small interfering RNA significantly inhibited the P2X3 expression in the dorsal root ganglia of the CCI rats. MRAK009713 directly interacted with the P2X3 protein heterologously expressed in the human embryonic kidney (HEK) 293 cells and potentiated P2X3 receptor function. Thus, MRAK009713 is a novel positive regulator of neuropathic pain in rats through regulating the expression and function of the P2X3 receptor.

Switching from Negative to Positive Photoconductivity toward Intrinsic Photoelectric Response in InAs Nanowire.

Negative photoconductivity (NPC) and positive photoconductivity (PPC) are observed in the same individual InAs nanowires grown by metal-organic chemical vapor deposition. NPC displays under weak light illumination due to photoexcitation scattering centers charged with hot carrier in the native oxide layer. PPC is observed under high light intensity. Through removing the native oxide layer and passivating the nanowire with HfO2, we eliminate the NPC effect and realize intrinsic photoelectric response in InAs nanowire.

Study of baicalin on sympathoexcitation induced by myocardial ischemia via P2X3 receptor in superior cervical ganglia.

After the myocardial ischemia, injured myocardial tissues released large quantity of ATP, which activated P2X3 receptor in superior cervical ganglia and made the SCG postganglionic neurons excited. Excitatory of sympathetic postganglionic efferent neurons increased the blood pressure and heart rates, which aggravated the myocardial ischemic injury. Baicalin has anti-inflammatory and anti-oxidant properties. Our study showed that baicalin reduced the incremental concentration of serum CK-MB, cTn-T, epinephrine and ATP, decreased the up-regulated expression levels of P2X3 mRNA and protein in SCG after MI, and then inhibited the sympathetic excitatory activity triggered by MI injury. These results indicated that baicalin acted on P2X3 receptor was involved in the transmission of sympathetic excitation after the myocardial ischemic injury. Baicalin might decrease sympathetic activity via inhibiting P2X3 receptor in rat SCG to protect the myocardium.

P2X7 receptor of rat dorsal root ganglia is involved in the effect of moxibustion on visceral hyperalgesia.

Irritable bowel syndrome (IBS) and inflammatory bowel disease often display visceral hypersensitivity. Visceral nociceptors after inflammatory stimulation generate afferent nerve impulses through dorsal root ganglia (DRG) transmitting to the central nervous system. ATP and its activated-purinergic 2X7 (P2X7) receptor play an important role in the transmission of nociceptive signal. Purinergic signaling is involved in the sensory transmission of visceral pain. Moxibustion is a therapy applying ignited mugwort directly or indirectly at acupuncture points or other specific parts of the body to treat diseases. Heat-sensitive acupoints are the corresponding points extremely sensitive to moxa heat in disease conditions. In this study, we aimed to investigate the relationship between the analgesic effect of moxibustion on a heat-sensitive acupoint "Dachangshu" and the expression levels of P2X7 receptor in rat DRG after chronic inflammatory stimulation of colorectal distension. Heat-sensitive moxibustion at Dachangshu acupoint inhibited the nociceptive signal transmission by decreasing the upregulated expression levels of P2X7 mRNA and protein in DRG induced by visceral pain, and reversed the abnormal expression of glial fibrillary acidic protein (GFAP, a marker of satellite glial cells) in DRG. Consequently, abdominal withdrawal reflex (AWR) score in a visceral pain model was reduced, and the pain threshold was elevated. Therefore, heat-sensitive moxibustion at Dachangshu acupoint can produce a therapeutic effect on IBS via inhibiting the nociceptive transmission mediated by upregulated P2X7 receptor.

[Transumbilical single-port access laparoscopic surgery for colorectal cancer].

OBJECTIVE: To evaluate the surgical outcomes after transumbilical single-port access laparoscopic surgery for colorectal cancer. METHODS: Patients undergoing transumbilical single-port access laparoscopic radical resection for colorectal cancer at the Zhongshan Hospital of Xiamen University were included. RESULTS: Three patients underwent transumbilical single-port access laparoscopic radical resection for sigmoid colon cancer and 1 for rectal cancer between August 2010 and September 2010. There were no intraoperative or postoperative complications. No conversion was required. The mean operative time was 206 min and the mean estimated blood loss was 75 ml. The mean number of harvested lymph nodes was 21. Patients were ambulatory in the same day of surgery or postoperative day 1. Length of hospital stay ranged from 7 to 10 days. CONCLUSIONS: Transumbilical single-port access laparoscopic surgery is safe for colorectal cancer. Long-term outcomes warrant further investigation.