Three new metabolites from the endophyte Fusarium proliferatum T2-10.

One new cyclopeptide, cyclo-(L-Trp-L-Phe-L-Phe) (1), one new 2-pyridone derivative, fusarone A (3), and one new natural indole derivative, ethyl 3-indoleacetate (4), along with six known compounds were isolated from the endophytic fungus Fusarium proliferatum T2-10. The planar structures of three new compounds were identified by spectral methods including 1D and 2D NMR techniques, and the absolute configuration of compound 1 was elucidated by Marfey-MS method. In addition, all compounds were evaluated for their cytotoxic and antibacterial activities in vitro. Compound 2 showed remarkable cytotoxic activities against two human hepatoma cell lines SMMC7721 and HepG2 with IC50 values of 5.89 ± 0.74 and 6.16 ± 0.52 µM, and showed moderate antibacterial activities against Staphylococcus aureus and Enterococcus faecalis with MIC values of 7.81 and 15.62 µg/mL, respectively.

Relationship between plasma circulating cell-free DNA concentration and treatment outcomes including prognosis in patients with advanced non-small cell lung cancer.

BACKGROUND: Some research found that elevated plasma cell-free DNA (cfDNA) concentrations and poor prognosis are associated in non-small cell lung cancer (NSCLC). However, more studies need to be carried out to verify this conclusion. Therefore, this study investigated the relationship between cfDNA concentration and treatment outcomes including prognosis in patients with advanced NSCLC. METHODS: We retrospectively collected medical records and cfDNA data from 160 patients with advanced NSCLC. Progression-free survival (PFS) were calculated using the Kaplan-Meier method and were compared between groups using the log rank test. Cox regression analysis was used for estimating the independent predictors of PFS. And we used logistic regression to evaluate the relationship between baseline biomarkers and efficacy. In our study, BT1 cfDNA, BT2 cfDNA, and BT3 cfDNA were defined as cfDNA concentration before the first treatment (baseline cfDNA concentration), cfDNA concentration before the second treatment, and cfDNA concentration before the third treatment, respectively. RESULTS: Patients with low cfDNA (BT1 cfDNA < 15 (ng/mL)) were reported a significantly prolonged median progression-free survival (mPFS) compared with patients with patients with high cfDNA (BT1 cfDNA ≥ 15(ng/mL)) (mPFS: 14.6 vs. 8.3 months, P = 0.002), as well as patients with neutrophil/lymphocyte ratio (NLR)<2.98 (mPFS: 13.1 vs. 7.9 months, P = 0.023). In addition, Cox proportional hazards regression analysis identified independent indicators associated with PFS including BT1 cfDNA ≥ 15 (ng/mL), NLR ≥ 2.98 and extrapulmonary metastasis. The best cut-off value for BT3 cfDNA for predicting disease progression is 41.46 (ng/mL) (Area Under the Curve (AUC): 0.652, 95%CI: 0.516-0.788), achieving 90.7% sensitivity and 37.5% specificity for the prediction of disease progression. BT3 cfDNA (OR = 6.08, 95% CI: 1.94-19.57, P = 0.002) was an independent factor for disease progression in patients with advanced NSCLC. CONCLUSIONS: BT1 cfDNA may be a biomarker to assess the prognosis of advanced NSCLC. Patients with advanced NSCLC with lower cfDNA and NLR before treatment had a better prognosis. Increased BT3 cfDNA concentration was an independent factor of disease progression in advanced NSCLC patients. These findings may assist in identifying high-risk patients and guiding treatment strategies.

Two new chromone derivatives from the rhizosphere soil fungus Ilyonectria robusta.

Two new chromone derivatives (1 and 2), and two known compounds (3 and 4) were isolated from the rhizosphere soil fungus Ilyonectria robusta. Their planar structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Additionally, all the isolated compounds were evaluated for their antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli, but no obvious activity was observed at a concentration of 128 µg/mL.

Pseudocercones A-C, three new polyketide derivatives from the endophytic fungus Pseudocercospora sp. TSS-1.

Chemical investigation of an EtOAc extract of the endophytic fungus Pseudocercospora sp. TSS-1 led to the isolation of three new polyketide derivatives, including one benzophenon derivative (1), two spirocyclic polyketides (4 and 5), along with four known compounds (2, 3, 6 and 7). Their structures and the absolute configurations were characterized by means of NMR, HRESIMS, 13C NMR and theoretical electronic circular dichroism calculations. Furthermore, all compounds were evaluated for their antibacterial activity against four microbial pathogens (Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Escherichia coli), and compounds 1, 2, 3 and 5 displayed significant selective antibacterial activity against S. aureus with MIC values ranging from 3.9 to 7.8 µg/mL.

ß-catenin correlates with the progression of colon cancers and berberine inhibits the proliferation of colon cancer cells by regulating the ß-catenin signaling pathway.

INTRODUCTION: Berberine was one of the active components in Chinese herb and exerted tumor suppressive role in cancer progression, but the exact antitumor mechanism is still not clearly clarified. In the present study, bioinformatics analysis was performed on COAD patients from TCGA, HPA database, UALCAN and GEPIA 2 platform. We also explored the role of berberine on progression of human colon cancers in vitro and in vivo and clarified weather the antitumor effects of berberine was mediated by Wnt/beta-catenin pathway. METHODS: Cell viability was determined by MTT assay. The protein levels were tested by western blotting and the distribution of ß-catenin was observed by confocal microscope. RESULTS: The results showed the levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. The diagnostic value of CTNNB1 was AUC = 0.882 (CI:0.854-0.911) with sensitivity of 1.000 and specificity of 0.777. The promoter methylation level of CTNNB1 in COAD patients was significantly decreased. Moreover, univariate analysis and multivariate analysis results showed the expression of CTNNB1 in COAD patients was associated with T stage (p = 0.010), pathological stage (p = 0.025) and perineural invasion (p = 0.025). Furthermore, the in vitro assay results showed ß-catenin signaling was highly activated in human colon cancer cells and berberine inhibited the cell viability of colon cancer cells in vitro and in vivo in a dose-and time-dependent manner. Moreover, berberine induced the translocation of ß-catenin to cytoplasm from nucleus. CONCLUSION: The levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. Berberine inhibited the proliferation of colon cancer cells by regulating the beta-catenin signaling pathway.

[Effect of recombinant connective tissue growth factor on proliferation and odontogenic differentiation of dental pulp cells].

PURPOSE: To analyze the effect of recombinant connective tissue growth factor(rCTGF) on proliferation and differentiation of human dental pulp cells(hDPCs). METHODS: Human dental pulp cells were cultured in vitro and treated with rCTGF at different concentrations (0, 1, 10, 100 ng/mL). The proliferation of dental pulp cells was detected by CCK8 assay. The formation of mineralized nodules was determined by alizarin red staining and half-quantitative alizarin Red S assay. qRT-PCR was utilized to detect the expression of odontogenic differentiation related genes DMP-1, DSPP and OC, and the phosphorylation level of ERK1/2 signaling pathway was detected by Western blot. The data were analyzed with SAS 9.3 software package. RESULTS: High concentration of rCTGF(100 ng/mL) could promote proliferation of dental pulp cells. After mineralization induction, 10 g/mL rCTGF had the best effect on promoting the formation of mineralized nodules in dental pulp cells, and calcium ion deposition was the most obvious(P<0.05). The expression of odontogenic differentiation related genes DMP-1 and DSPP was significantly up-regulated(P<0.05). Western blot results showed that hDPCs stimulated by 10 ng/mL rCTGF could increase the expression of p-ERK1/2. CONCLUSIONS: rCTGF may promote the proliferation and differentiation of human dental pulp cells through activating ERK1/2 signaling pathway.

[Effect of serum starvation and culture to confluence on cell cycle synchronization and mineralization of human dental pulp cells].

PURPOSE: To compare the effect of serum starvation and culture to confluence on cell cycle synchronization and mineralization of human dental pulp cells (hDPCs). METHODS: HDPCs were cultured to 80% and 100% confluence respectively, and then cultured for 24, 48 and 72 hours by culture medium containing 0.5% fetal bovine serum(FBS). Cell cycle of hDPCs were identified by flow cytometry. Then hDPCs cultured by serum starvation for 48h after culturing to 100% confluence were used as the experimental group, and hDPCs cultured to 80% confluence were used as the control group. The expression of alkaline phosphatase(ALP), collagen type Ⅰ(COL-Ⅰ) and osteocalcin(OCN) was detected at gene level; activity of ALPase was detected at protein level. SPSS 13.0 software was used for statistical analysis. RESULTS: When hDPCs were cultured by serum starvation for 48h after culturing to 100% confluence, cells at G0/G1 stage were more than culture to 100% confluence and serum starvation group (P＜0.05). At the genetic level, the expression of COL-Ⅰand OC in the experimental group was not statistically different from that of the control group, but can promote the expression of ALP(P＜0.05), and stimulate the secretion of hDPCs at protein level at the same time (P＜0.05). CONCLUSIONS: Culture to confluence combined serum starvation can synchronize more hDPCs at G0/G1 stage and promote mineralization of hDPCs.

[Mechanisms and applications of transcutaneous electrical nerve stimulation in analgesia].

Transcutaneous electrical nerve stimulation (TENS), as a non-pharmacological and non-invasive analgesic therapy with low-cost, has been widely used to relieve pain in various clinical applications, by delivering current pulses to the skin area to activate the peripheral nerve fibers. Nevertheless, analgesia induced by TENS varied in the clinical practice, which could be caused by the fact that TENS with different stimulus parameters has different biological mechanisms in relieving pain. Therefore, to advance our understanding of TENS in various basic and clinical studies, we discussed (1) neurophysiological and biochemical mechanisms of TENS-induced analgesia; (2) relevant factors that may influence analgesic effects of TENS from the perspectives of stimulus parameters, including stimulated position, pulse parameters (current intensity, frequency, and pulse width), stimulus duration and used times in each day; and (3) applications of TENS in relieving clinical pain, including post-operative pain, chronic low back pain and labor pain. Finally, we propose that TENS may involve multiple and complex psychological neurophysiological mechanisms, and suggest that different analgesic effects of TENS with different stimulus parameters should be taken into consideration in clinical applications. In addition, to optimize analgesic effect, we recommend that individual-based TENS stimulation parameters should be designed by considering individual differences among patients, e.g., adaptively adjusting the stimulation parameters based on the dynamic ratings of patients' pain.

Room-temperature soft mode and ferroelectric like polarization in SrTiO3 ultrathin films: Infrared and ab initio study.

Due to the remarkable possibilities of epitaxially growing strontium titanate (SrTiO3 or STO) on silicon, this oxide is widely used as a buffer layer for integrating other perovskite oxides which allows for the development of various functional electronic devices on silicon. Moreover, STO is known to be an incipient ferroelectric in bulk but may become ferroelectric when in the form of strained ultrathin films. Given the importance of the potential applications for electronics if this property is demonstrated, we performed a spectroscopic study of STO on Si(001) templates coupling experimental and ab initio investigations. We selected six samples of ultrathin films: three strained samples (of thickness 4, 9 and 48 nm) and three relaxed samples (of equivalent thickness). Their infrared spectra show that both the mechanical stress and the thickness play major roles: higher energy modes evolve as soft modes in thinner strained films. In order to support these observations, the dynamical ab initio calculations allowed deriving the conditions for STO films to become ferroelectric at room temperature as shown by the development of a soft mode and the divergence of the in-plane dielectric constant.

[The Research Advances of the Pathomechanism of Phantom Limb Pain (PLP)].

Phantom limb pain (PLP) is a hallucination that the patient feels the existence off the limb after its loss and experiences somewhat pain of the missing limb. Such a pain normally appears in the distal end of the missing limb. Currently, the pathomechanism of PLP is still unclear, and the clinical research of PLP mainly relies on the subjective report of the patients and the psychophysical measurements. In this paper, we discuss extensively the pathomechanism of PLP, and summarize comprehensively the advanced methods for studying the pathomechanism of PLP. In short, the paper could deepen our understanding of the pathomechanism of PLP, and could serve as an effective instruction basis for researchers and doctors to diagnose and treat the PLP.

[Study of Terahertz Amplitude Imaging Based on the Mean Absorption].

A new method of terahertz (THz) imaging based on the mean absorption is proposed. Terahertz radiation is an electromagnetic radiation in the range between millimeter waves and far infrared. THz pulse imaging emerges as a novel tool in many fields because of its low energy and non-ionizing character, such as material, chemical, biological medicine and food safety. A character of THz imaging technique is it can get large amount of information. How to extract the useful parameter from the large amount of information and reconstruct sample's image is a key technology in THz imaging. Some efforts have been done for advanced visualization methods to extract the information of interest from the raw data. Both time domain and frequency domain visualization methods can be applied to extract information on the physical properties of samples from THz imaging raw data. The process of extracting useful parameter from raw data of the new method based on the mean absorption was given in this article. This method relates to the sample absorption and thickness, it delivers good signal to noise ratio in the images, and the dispersion effects are cancelled. A paper with a "THz" shape hole was taken as the sample to do the experiment. Traditional THz amplitude imaging methods in time domain and frequency domain are used to achieve the sample's image, such as relative reduction of pulse maximum imaging method, relative power loss imaging method, and relative power loss at specific frequency imaging method. The sample's information that reflected by these methods and the characteristics of these methods are discussed. The method base on the mean absorption within a certain frequency is also used to reconstruct sample's image. The experimental results show that this new method can well reflect the true information of the sample. And it can achieve a clearer image than the other traditional THz amplitude imaging methods. All the experimental results and theoretical analyses indicate that the method base on the mean absorption within a certain frequency can reflects sample absorb and thickness information, it can achieve good signal to noise ratio in the images. Because the absorption is mean absorption within in a certain frequency, so the method proposed in this article is especially suitable for samples with simple structure. And this new method can be a useful added tool for the other traditional THz amplitude imaging methods.

Effects of deferoxamine on the repair ability of dental pulp cells in vitro.

INTRODUCTION: In previous studies, we found that hypoxia promoted the mineralization of dental pulp cells (DPCs). However, the clinical application of hypoxia as a therapy is questionable or unfeasible. Deferoxamine (DFO), a medication for iron overload, has also been shown to induce hypoxia. The purpose of this study was to investigate the effects of DFO on the repair ability of DPCs. METHODS: DPCs were obtained by using a tissue explant technique in vitro and were treated with different concentrations of DFO or hypoxia culture for 2 days. The viability, proliferation, migration, and odontogenic differentiation of DPCs were assayed and analyzed. The expression of hypoxia-inducible factor 1-alpha (HIF-1α) was assessed through Western blotting. RESULTS: Ten micromolars of DFO enhanced the expression of HIF-1α similarly to hypoxia and did not affect the viability of DPCs for 2 days. Furthermore, the proliferation, migration, and odontogenic differentiation of DPCs were promoted by DFO. CONCLUSIONS: These results suggest that DFO might improve the repair ability of DPCs by HIF-1α.

Isolation and identification of CXCR4-positive cells from human dental pulp cells.

INTRODUCTION: In previous studies, we found expression of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) in human dental pulp and the SDF-1α-CXCR4 axis might play a role in the recruitment of CXCR4-positive dental pulp cells (CXCR4(+) DPCs) toward the damaged sites. However, the specific function of CXCR4(+) DPCs in the injured dental pulp was still unknown. The purpose of this study was to isolate CXCR4(+) DPCs from dental pulp cells in vitro to pave the way for further study of their characteristics. METHODS: CXCR4(+) DPCs were isolated with magnetic-activated cell sorting (MACS). Freshly isolated CXCR4(+) DPCs were identified by immunohistochemistry with light microscopy or confocal microscopy. Then the phenotypes CXCR4, stromal cell surface marker-1 (STRO-1), CD146, and CD34 in 3 groups (ie, CXCR4(+) DPCs, CXCR4(-) DPCs, or non-sorted DPCs) were analyzed by flow cytometry after they were cultured and expanded in vitro. RESULTS: The results indicated the isolated subpopulation of DPCs was enriched with CXCR4(+) DPCs, and the positive rates of STRO-1 and CD146 in CXCR4(+) DPCs group were higher than CXCR4(-) DPCs or non-sorted DPCs groups (P < .05). There was no expression of CD34 in each group. CONCLUSIONS: We can isolate CXCR4(+) DPCs from DPCs with MACS and identify them by immunohistochemistry and flow cytometry.

Proliferation and multilineage potential of CXCR4-positive human dental pulp cells in vitro.

INTRODUCTION: Although the results of our previous studies showed that the stromal cell-derived factor (SDF)-1α-CXC chemokine receptor 4 (CXCR4) axis may play a role in the recruitment of CXCR4-positive dental pulp cells (CXCR4(+) DPCs) toward the damaged sites, the specific function of CXCR4(+) DPCs in the injured dental pulp was still unknown. The purpose of this study was to verify whether CXCR4(+) DPCs possessed stem cells properties so that we can understand their role in area of injury. METHODS: CXCR4(+) DPCs were isolated from normal DPCs with magnetic-activated cell sorting. The characteristics of the cells from the 3 groups of cells (ie, CXCR4(+) DPCs, CXCR4(-) DPCs, or nonsorted DPCs) were analyzed in colony formation, proliferation, and multilineage differentiation including odontogenic and adipogenic lineages. RESULTS: The results showed that CXCR4(+) DPCs were the most dominant population in colony formation, proliferation, alkaline phosphatase activity, calcium content, and adipogenic differentiation among the 3 groups. CONCLUSIONS: CXCR4(+) DPCs may contain more stem cells than nonsorted DPCs.

Gastrostomy tube placement by radiological versus endoscopic methods in an acute care setting: a retrospective review of frequency, indications, complications and outcomes.

OBJECTIVES: To describe the current practice of placing gastrostomy tubes (endoscopic and radiological), patient characteristics, indications for enteral support, complications and outcomes over a 13-month period, and explore factors that influenced complications and outcomes. Second, to provide Canadian data regarding feeding tube placement because no current literature reflecting these practices for Canadian hospitals is available. METHODS: Retrospective chart reviews were conducted. Patients who had initial percutaneous endoscopic gastrostomy (PEG) or percutaneous radiological gastrostomy (PRG) tubes inserted for nutritional purposes were included in the study. RESULTS: A total of 136 charts which included 30 PEG and 44 PRG procedures were reviewed. The PRG group was older than the PEG group (mean [+/-SD+/-5D; age 68+/-19 years versus 55+/-21 years, respectively; P=0.008). Patients in PEG group had longer lengths of hospital stay and more intensive care unit admissions than the PRG group (P=0.029). The main reason for tube insertion was dysphagia/aspiration (PEG [60%] and PRG [77%]). Minor complications were comparable between the two groups (P=0.678). There were three cases of major complications overall. More subjects in the PRG group died (18%) while in hospital than in the PEG group (3%) (P=0.055). No procedure-related deaths occurred in either group. CONCLUSIONS: Both methods of tube insertion provided a safe route for nutrition delivery despite a significant cost differential with PEGs costing 44% more than PRGs. Characteristics such as age, presence of ascites and severity of disease influenced the method of insertion despite the lack of current guidelines. Overall, the present study provides new descriptive data in a Canadian context.