GSH-activable heterotrimeric nano-prodrug for precise synergistic therapy of TNBC.

Combination chemotherapy is an effective approach for triple-negative breast cancer (TNBC) therapy, especially when drugs are administered at specific optimal ratios. However, at present, strategies involving precise and controllable ratios based on effective loading and release of drugs are unavailable. Herein, we designed and synthesized a glutathione (GSH)--responsive heterotrimeric prodrug and formulated it with an amphiphilic polymer to obtain nanoparticles (DSSC2 NPs) for precise synergistic chemotherapy of TNBC. The heterotrimeric prodrug was prepared using docetaxel (DTX) and curcumin (CUR) at the optimal synergistic ratio of 1: 2. DTX and CUR were covalently conjugated by disulfide linkers. Compared with control NPs, DSSC2 NPs had quantitative/ratiometric drug loading, high drug co-loading capacity, better colloidal stability, and less premature drug leakage. After systemic administration, DSSC2 NPs selectively accumulated in tumor tissues and released the encapsulated drugs triggered by high levels of GSH in cancer cells. In vitro and in vivo experiments validated that DSSC2 NPs released DTX and CUR at the predefined ratio and had a highly synergistic therapeutic effect on tumor suppression in TNBC, which can be attributed to ratiometric drug delivery and synchronous drug activation. Altogether, the heterotrimeric prodrug delivery system developed in this study represents an effective and novel approach for combination chemotherapy.

[Development and Clinical Application of Multifunctional Inflation-Free Lumpectomy Aid].

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases. The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared. The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group, while the postoperative satisfaction was higher in the endoscopic group than in the open group. This set of instruments has advantage of novel design, scientific structure, safe application. It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures, which can promote the development and popularization of laparoscopic technology.

Clinical analysis of a new multifunctional instrument set for gasless endoscopic thyroidectomy with two different approaches.

BACKGROUND: Following the rapid development of endoscopic thyroidectomy techniques, various surgical procedures have been developed (e.g., transoral, submandibular, areolar, axillary, retroauricular, and combined procedures), and each of these procedures has its own advantages. In recent years, gasless endoscopic thyroidectomy has emerged as a feasible procedure, and it has replaced traditional CO2 insufflation approaches because of advantages such as stable cavity construction, pollution reduction, resource saving, and risk reduction. However, each gasless procedure requires special instruments for cavity construction, and this results in enormous wastage of medical resources. In the present study, we introduced a set of instruments developed by our team. This set of instruments is designed to be compatible with the current gasless endoscopic thyroidectomy approaches, including transoral, submandibular, transareolar, transaxillary, retroauricular, combined, and lateral cervical lymph node dissection. Here, we introduced this set of instruments for two gasless endoscopic thyroidectomy procedures (transaxillary and transareolar). Following the incorporation of this set of instruments in regular clinical practice, it could be used for more gasless endoscopic thyroidectomy procedures in the future. OBJECTIVE: To investigate the feasibility, safety, and efficacy of the self-developed instruments for gasless endoscopic thyroidectomy in two different approaches. METHODS: A total of 180 patients diagnosed to have papillary thyroid carcinoma (PTC) between January 2020 and April 2022 were retrospectively investigated. The patients were assigned to a gasless transaxillary group (group A) and a gasless transareolar group (group B). The same gasless endoscopic-assisted instruments were used for both groups. The clinical characteristics, treatment results, and complications were compared between the two groups. RESULTS: All 180 patients were successfully operated. The extent of surgical resection in all patients was the same: "unilateral glandular lobectomy + isthmus combined with ipsilateral central zone lymph node dissection." There were 130 and 50 patients in group A and group B, respectively; one patient in the former group was converted to open surgery due to intraoperative bleeding. No significant difference was observed between the two groups in terms of gender, age, body mass index (BMI), education level, and proportion of concomitant Hashimoto's thyroiditis (P > 0.05). The establishment of cavity time was significantly longer in group A than in group B (35.62 ± 5.07 min vs. 17.46 ± 2.55 min, P < 0.01). The number of lymph nodes cleared was slightly less in group A than in group B (4.06 ± 2.93 vs. 4.52 ± 2.38, P = 0.07). Moreover, the two groups showed no significant differences (P > 0.05) in the total operative time (145.54 ± 45.11 min vs. 143.06 ± 46.70 min), tumor size (0.68 ± 0.46 cm vs. 0.71 ± 0.49 cm), postoperative hospital stay (4.08 ± 1.48 days vs. 3.72 ± 1.07 days), vocal cord paralysis [4 (3.1%) vs. 2 (4%)], postoperative swallowing discomfort [24 (18.5%) vs. 5 (10%)], and postoperative recurrence and satisfaction scores (3.27 ± 1.52 vs. 3.28 ± 1.53). CONCLUSION: Although the two approaches of gasless endoscopic surgery have different operative paths and different time periods for cavity construction, both approaches are similar in terms of the principle of cavity construction, safe and reliable postoperative efficacy, and good cosmetic effect. Therefore, the same set of instruments can be used to complete the surgery in both approaches, thus saving medical resources and facilitating the popularization of this technology.

Characterization, mechanical properties, corrosion behavior and bone-like apatite formation ability of fluorine substituted hydroxyapatite coating.

Hydroxyapatite (HA) is a non-bioceramic commonly used in human implants in the form of coatings, which are limited in their application by mechanical and wear resistance properties, as well as biodegradability. In this study, fluorine substituted hydroxyapatite (FHA) coatings were prepared on Ti-6Al-4V surfaces by plasma spraying method using a mixture of calcium fluoride and hydroxyapatite powders. The prepared coatings were characterized by X-ray diffraction and fourier transform infrared (FTIR) spectroscopy at different levels of calcium fluoride (3 wt%, 6 wt%, 9 wt%, and 12 wt%). The biocompatibility of the coatings was evaluated by in vitro mineralization experiments. Experimental results showed that at 9 wt% of calcium fluoride, the prepared FHA coatings had better mechanical properties, with improved bond strength (28.2 MPa). The X-ray diffraction patterns of the coatings reflect the fluorine substitution during the spraying process and the 9FHA has the highest crystallinity according to the XRD analysis, which is closely related to the biological activity of the coating. In addition, Potentiodynamic polarisation showed that the sample coated with the 9FHA coating had the highest Ecorr and lowest Icorr, indicating the best corrosion resistance. The FHA coating exhibits faster apatite deposition in simulated body fluid, and the efficiency of apatite deposition increases with the increase of CaF2.

LncRNA MIR31HG promotes cell proliferation and invasive properties of the MCF-7 cell line by regulation of receptor-interacting serine-threonine kinase 4.

LncRNA MIR31HG is involved in many types of cancers, while its roles in breast cancer are still unknown. The current study aimed to explore the function of lncRNA MIR31HG in breast cancer and the underlying mechanisms. Stable expression cell lines were constructed by using lentivirus particles. MTT assay was used to determine cell viability. Wound healing and Transwell assay were used to determine cell migration and invasion, respectively. The changes in biomarkers were determined by using qPR-PCT and Western blotting, respectively. BALB/c nude mice were used to generate a xenograft mouse model. MIR31HG regulated cell proliferation, migration and invasion in MCF7 cells. Besides, MIR31HG regulated N-Cadherin, Vimentin, and E-Cadherin. MIR31HG positively regulated receptor-interacting serine-threonine kinase 4 (RIPK4), as supported by the fact that knockdown of MIR31HG suppressed RIPK4, and the knockdown of RIPK4 did not affect MIR31HG. Additionally, we found that RIPK4 regulated cell proliferation, migration and invasion in MCF7 cells. The changes in RIPK4 regulated N-Cadherin, Vimentin, and E-Cadherin. Consistently, in vivo studies showed that the knockdown of MIR31HG or RIPK4 reduced tumor size in xenograft animal models. The roles of lncRNA MIR31HG in breast cancer were associated with its regulatory effects against RIPK4.

Rhinacanthin C Ameliorates Insulin Resistance and Lipid Accumulation in NAFLD Mice via the AMPK/SIRT1 and SREBP-1c/FAS/ACC Signaling Pathways.

Rhinacanthin C (RC) is a naphthoquinone ester with an anti-inflammatory activity extracted from Rhinacanthus nasutus (L.) Kurz (Rn). It has been proven to improve hyperglycemia and hyperlipidemia, but the prevention and mechanism of RC in nonalcoholic fatty liver disease (NAFLD) are not clear. In the current study, we first extracted RC from Rn using ethyl acetate and identified it by HPLC, MS, and NMR. At the same time, molecular docking analysis of RC with AMPK and SREBP-1c was performed using AutoDock software. In addition, the mouse model of NAFLD was induced by a high-fat diet in vivo, and low, medium, and high concentrations of RC were used for intervention. The results showed that RC significantly reduced the body mass and liver body coefficient of NAFLD mice, inhibited liver inflammation and fat accumulation, and improved insulin resistance. Further studies showed that RC significantly reduced the levels of serum leptin and resistin, upregulated the expression levels of adiponectin and adiponectin receptor in the liver, and inhibited the expression levels of MCP-1, TNF-α, and IL-6. In terms of mechanism, RC upregulates the expression of p-AMPK and SIRT1 and downregulates the expression of p-p65, SREBP-1c, Fas, Acc-α, PPAR-γ, and SCD1. These studies suggest that RC improves insulin resistance and lipid accumulation in NAFLD by activating the AMPK/SIRT1 and SREBP-1c/Fas/ACC pathways, respectively.

Comparison of surgical smoke between two approaches for endoscopic thyroidectomy and open thyroidectomy.

BACKGROUND: Surgical smoke has been recognized as a potential health risk by an increasing number of researchers. Moreover, the counts of surgical smoke produced during different surgical approaches are different. This study aimed to measure and compare the particulate matter (PM) of surgical smoke generated during open thyroidectomy and two endoscopic approaches for thyroidectomy to provide guidance for safe clinical practices. METHODS: Forty-eight patients with thyroid cancer admitted to our hospital from June 2020 to December 2021 and treated with different surgical approaches were enrolled in this study. The total and peak counts of PM, dynamic changes, and other characteristics of surgical smoke produced during surgery were recorded. PM was classified as PM2.5 (size ≤ 2.5 µm) and PM10 (size ≤ 10 µm). RESULTS: In a single cut, both the peak and total counts of PM2.5 and PM10 of surgical smoke in the open thyroidectomy group (n = 15) were significantly higher than those in the breast approach endoscopic thyroidectomy with CO2 insufflation group (n = 15) and the gasless transaxillary endoscopic thyroidectomy group (n = 18) (p < 0.001). Moreover, the latter two groups showed no significant differences in the peak and total counts of PM2.5 and PM10 (p > 0.05). CONCLUSION: In thyroid surgery, more surgical smoke is produced during open thyroidectomy than during endoscopic thyroidectomy, while different endoscopic approaches showed no significant difference in surgical smoke production. Thus, endoscopic approaches outperform the open thyroidectomy approach with regard to surgical smoke production.

Dynamic Modeling and Attitude Decoupling Control for a 3-DOF Flexible Piezoelectric Nano-Positioning Stage Based on ADRC.

The paper proposes a three-degrees-of-freedom flexible nano-positioning stage constructed from compliant flexures and piezoelectric thin-sheet actuators, featuring a compact size and fast dynamic responses, which can be extensively applied to the typical micro/nano-positioning applications. Meanwhile, the dynamic model of the flexible PZT nano-positioning with distributed parameter characteristics is established to distinctly reflect the piezoelectric-mechanical coupling relationship between the four flexible PZT actuators and the three outputs of such a system. Furthermore, the attitude decoupling control for the 3-DOF flexible piezoelectric nano-positioning stage is achieved by the Active Disturbance Rejection Control (ADRC) method to compensate for the positioning errors in the actual positioning process. After this, a real-time experimental apparatus with two Position-Sensitive Detectors (PSDs) is also proposed and fabricated to test the three outputs of the flexible piezoelectric thin-sheet (PZT-5A) nano-positioning stage and validate the effectiveness of the dynamic modeling method and attitude decoupling control in the piezoelectric nano-positioning stage ranges.

[Corrigendum] 3­Bromopyruvate sensitizes human breast cancer cells to TRAIL­induced apoptosis via the phosphorylated AMPK­mediated upregulation of DR5.

Following the publication of this article, an interested reader drew to the authors' attention that the western blotting data shown in Fig. 3 on. p. 2439 contained apparent anomalies; first, the protein bands shown to represent the CHOP and p­AMPK experiments in Fig. 3A were strikingly similar. Secondly, the same data bands were inadvertently included in the figure to represent the GRP78 and Bax experiments for the MCF­7 group. The authors have re­examined their original data and realized that this figure was assembled incorrectly (the CHOP and GRP78 data were inadvertently duplicated in the figure). The corrected version of Fig. 3, showing the correct data for the p­AMPK and Bax experiments for the MCF­7 group in Fig. 3A, is shown on the next page. The authors sincerely apologize for the error that was introduced during the preparation of this figure, thank the Editor of Oncology Reports for granting them the opportunity to publish a Corrigendum, and are grateful to the reader for alerting them to this issue. The authors also regret any inconvenience that this mistake may have caused. [the original article was published in Oncology Reports 40: 2435­2444, 2018; DOI: 10.3892/or.2018.6644].

Surface Integrity and Friction Performance of Brass H62 Textured by One-Dimensional Ultrasonic Vibration-Assisted Turning.

The processing method, one-dimensional ultrasonic vibration-assisted turning (1D UVAT), is a potential and efficient way for fabricating a micro-textured surface. This paper aims at exploring the surface integrity and friction performance of brass H62 textured by the 1D UVAT. Four micro-textured surfaces with a specific distribution, size, and shape of dimples were fabricated by optimizing processing parameters, and the corresponding surface topography, subsurface microstructure, and surface roughness were observed and analyzed. A series of friction tests were carried out under oil-lubricating conditions to research the friction performance of micro-textured surfaces. The results show that the reason for the deviation between theoretical and experimental values of dimple depth was further revealed by observing the corresponding subsurface microstructure. The surface roughness of the micro-textured surfaces prepared is related to the number of micro-dimples per unit area and dimple size, which is greater than the surface generated by conventional turning. Compared with the polished surface and micro-grooved surface, the micro-textured surfaces have better friction performance with a lower frictional coefficient (COF) and wear degree. For the micro-textured surface fabricated by 1D UVAT, the number of micro-dimples per unit area has a great effect on the friction performance, and choosing a larger number is more conducive to improving the friction performance under the oil-lubricating condition. Consequently, this study proves that the proposed 1D UVAT can be a feasible candidate for preparing a micro-textured surface with better tribological property.

MiR-98-5p/IGF2 Axis Influence Herceptin Sensitivity through IGF1R/HER2 Heterodimer Formation and AKT/mTOR Signal Pathway in HER2 Positive Breast Cancer.

BACKGROUND AND AIM: IGF1R and HER2 are both members of the growth factor receptor family which is known to play a different role in breast cancer. However, correlation between IGF1R and HER2 has created a controversial situation that need to be fully delineated in development of Herceptin resistance. The aim of this study was to investigate the mechanism of Herceptin resistance through the IGF1R pathway in HER2 positive breast cancer. MATERIALS AND METHODS: Clinical data were obtained from TCGA database and archived documents from The First Affiliated Hospital of Bengbu Medical College. Western blot and immunohistochemistry were used to detect proteins and their phosphorylation. Cell transfection were constructed using shRNA lentivirus vectors. RNAs were analyzed by RT-qPCR. Proteins in serum were analyzed by ELISA assay. Cell proliferation was analyzed by MTS method. Luciferase report experiment was conducted to verify RNA's inter-reaction. RESULTS: Western blot showed IGF2 protein was significantly increased in Herceptin resistant SKBR3-R cells (P<0.01), and IGF1R/HER2 heterodimer level was significantly increased (P<0.01). Luciferase reporter assay verified miR-98-5p could bind to 3 'UTR of IGF2 mRNA. When miR-98-5p was upregulated, the expression level of IGF2 was decreased(P<0.01), the cell invasive ability was reduced(P<0.01), and ultimately, Herceptin resistant cells regained their sensitivity to Herceptin. In clinical research, we found that decreased miR-98-5p level or increased IGF2 level significantly associated with poor treatment response and poor overall survival (OS), poor recurrence free survival (RFS) and poor distant metastasis-free survival (DMFS) in HER2-positive breast cancer. CONCLUSION: MiR-98-5p and IGF2 might potential candidates for predicting Herceptin sensitivity and provides a new way to overcome Herceptin resistance in clinic.

Lobetyolin inhibits the proliferation of breast cancer cells via ASCT2 down-regulation-induced apoptosis.

This study aimed to investigate the anti-cancer effect of lobetyolin on breast cancer cells. Lobetyolin was incubated with MDA-MB-231 and MDA-MB-468 breast cancer cells for 24 h. Glucose uptake and the mRNA expression of GLUT4 (SLC2A4), HK2 and PKM2 were detected to assess the effect of lobetyolin on glucose metabolism. Glutamine uptake and the mRNA expression of ASCT2 (SLC1A5), GLS1, GDH and GLUL were measured to assess the effect of lobetyolin on glutamine metabolism. Annexin V/PI double staining and Hoechst 33342 staining were used to investigate the effect of lobetyolin on cell apoptosis. Immunoblot was employed to estimate the effect of lobetyolin on the expression of proliferation-related markers and apoptosis-related markers. SLC1A5 knockdown with specific siRNA was performed to study the role of ASCT2 played in the anti-cancer effect of lobetyolin on MDA-MB-231 and MDA-MB-468 breast cancer cells. C-MYC knockdown with specific siRNA was performed to study the role of c-Myc played in lobetyolin-induced ASCT2 down-regulation. Myr-AKT overexpression was performed to investigate the role of AKT/GSK3ß signaling played in lobetyolin-induced down-regulation of c-Myc and ASCT2. The results showed that lobetyolin inhibited the proliferation of both MDA-MB-231 and MDA-MB-468 breast cancer cells. Lobetyolin disrupted glutamine uptake via down-regulating ASCT2. SLC1A5 knockdown attenuated the anti-cancer effect of lobetyolin. C-MYC knockdown attenuated lobetyolin-caused down-regulation of ASCT2 and Myr-AKT overexpression reversed lobetyolin-caused down-regulation of both c-Myc and ASCT2. In conclusion, the present work suggested that lobetyolin exerted anti-cancer effect via ASCT2 down-regulation-induced apoptosis in breast cancer cells.

The knockdown of the sepiapterin reductase gene suppresses the proliferation of breast cancer by inducing ROS-mediated apoptosis.

BACKGROUND: Sepiapterin reductase (SPR) is an important regulator of the biosynthesis of tetrahydrobiopterin (BH4), which has been shown to be a promoter of different kinds of tumors. This study aims to investigate the role of SPR in breast cancer and to explore its molecular mechanism. METHODS: SPR expressions in breast cancer tissues with different pathological stages were compared with the corresponding pericarcinomatous tissues and were analyzed using immunohistochemical staining and western blot. SPR knockdown was performed in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer cells using specific siRNAs. Quantitative real-time PCR and western blot were used to determine the efficiency of the SPR knockdown. The intracellular BH4 levels were measured using HPLC, and the intracellular ROS levels were measured using an ROS detection kit. Clone formation and cell proliferation assays were used to study the effect of the SPR knockdown on cell proliferation. Annexin V/PI double staining, cell mitochondria isolation, and western blot were performed to study the effect of the SPR knockdown on cell apoptosis. ROS scavenger NAC was used to inhibit increased ROS caused by the SPR knockdown. RESULTS: SPR is highly expressed in breast cancer tissues compared with the pericarcinomatous tissues and positively correlated with the pathological stages. The knockdown of SPR causes decreased intracellular BH4 and increased intracellular ROS and inhibits the proliferation of MDA-MB-231 and MDA-MB-468 cells. The knockdown of SPR also induces mitochondrial pathway-mediated apoptosis. NAC suppresses the SPR knockdown-caused cell apoptosis and cell death. CONCLUSIONS: SPR promotes the proliferation of breast cancer cells. The knockdown of SPR suppresses the proliferation of breast cancer cells by inducing ROS-mediated apoptosis.

Simultaneous Determination of 5 Components in the Leaves of Dimocarpus longan by Quantitative Analysis of Multicomponents by Single Marker (QAMS) Based on UPLC and HPLC.

The pharmacodynamic effect of longan leaves was attributed to various components, especially the flavonoids. In this paper, a new strategy of quantitative analysis of multicomponents by a single marker (QAMS) method was first established to synchronously determine 5 components (ethyl gallate (C1), astragalin (C2), quercetin (C3), luteolin (C4), and kaempferol (C5)) in Dimocarpus longan by ultra-performance liquid chromatography (UPLC) and high-performance liquid chromatography (HPLC). Quercetin (C3) was chosen as the internal reference. Relative correction factors (RCFs, ƒs/i) of the other 4 components were calculated by two correction methods (multipoint correction and slope correction) to effectuate QAMS. At the same time, the difference between the results measured by the QAMS and external standard methods was compared to verify the accuracy of QAMS. Within the linear range, the results showed that all ƒs/i values were obtained with good durability under diverse chromatographic conditions (RSD < 2.28%). The quantitative results of 5 components in the leaves of Dimocarpus longan collected from 10 producing areas by different chromatographic systems and quantitative methods were significantly correlated (Pearson's r > 97.0%). The applicability and feasibility of the QAMS method established in this study were evaluated to be favorable for quality control of the leaves of Dimocarpus longan. As a new model of quality control, it can provide one more choice of multicomponent quality-control method in the absence of standard substances or instruments.

miR-338-3p regulates osteoclastogenesis via targeting IKKß gene.

This study determined the effects of miR-338-3p on osteoclast (OC) differentiation and activation. The change levels of miR-338-3p in differentiated OCs were investigated by microRNA microarray assay and quantitative real-time PCR analysis. The effects of miR-338-3p on the differentiation and activation of OCs were determined by tartrate-resistant acid phosphatase staining resorption activity assay and Western blot. Target genes of miR-338-3p were identified by target gene prediction and dual-luciferase reporter gene detection assay as well as Western blot. Results showed that miR-338-3p was markedly downregulated in differentiated OCs. miR-338-3p could inhibit the formation and absorption activity of OCs. Western blot showed that miR-338-3p could influence the change levels of OC differentiation-related proteins. Dual-luciferase reporter gene detection assay and Western blot both showed that miR-338-3p directly targeted IKKß gene. In conclusion, miR-338-3p may affect the formation and activity of OCs by targeting the IKKß gene.

3-(4-methoxyl)-1-(2-(4-coumarin)prop)-2-en-1-one inhibits the differentiation of Gaoyou duck embryonic osteoclasts in vitro.

This study determined the influence of 3-(4-methoxyl)-1-(2-(4-coumarin)prop)-2-en-1-one (MCPEO) on the differentiation of Gaoyou duck embryo osteoclasts cultured in vitro. Bone marrow mononuclear cells (BM-MNCs) were harvested from 23-day-old Gaoyou duck embryos and induced by receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in the presence of MCPEO at different concentrations (i.e., 1, 5, 10, 20, and 40 µM). Cell viability measurement, tartrate-resistant acid phosphatase (TRAP) staining, resorption activity assay, and co-staining with Tetramethylrhodamine (TRITC)-conjugated phalloidin and Hoechst 33,258 were conducted. Results indicated that MCPEO influenced the cell viability of the M-CSF + RANKL-induced BM-MNCs in a concentration-dependent manner, reduced the formation of positive multinucleated cells, and restrained the resorption capability of osteoclasts. Microfilament and nuclear staining indicated that MCPEO restricted the differentiation of BM-MNCs into large multinucleated osteoclasts. In short, MCPEO can inhibit the differentiation of BM-MNCs into mature osteoclasts in duck embryos. Therefore, MCPEO is a promising agent for the treatment of poultry osteoporosis.

3­Bromopyruvate sensitizes human breast cancer cells to TRAIL­induced apoptosis via the phosphorylated AMPK­mediated upregulation of DR5.

Previous studies have indicated that the sensitivity of breast cancer cells to tumor necrosis factor­related apoptosis­inducing ligand (TRAIL)­induced apoptosis is associated with the expression of death receptors on the cell membrane. However, drug resistance limits the use of TRAIL in cancer therapy. Numerous studies have indicated that death receptors, which induce apoptosis, are upregulated by the endoplasmic reticulum (ER) stress response. 3­Bromopyruvate (3­BP), an anticancer agent, inhibits cell growth and induces apoptosis through interfering with glycolysis. In the present study, it was demonstrated that 3­BP synergistically sensitized breast cancer cells to TRAIL­induced apoptosis via the upregulation of death receptor 5 (DR5). Furthermore, we found that the protein levels of glucose­related protein 78 (GRP78) and CCAAT­enhancer­binding protein homologous protein (CHOP) increased following treatment with 3­BP. The expression of Bax (in MCF­7 cells) and caspase­3 (in MDA­MB­231 cells) increased following co­treatment with 3­BP and TRAIL, whereas the expression of the anti­apoptotic protein Bcl­2 decreased. In order to investigate the molecular mechanism regulating this effect, the expression of adenosine monophosphate­activated protein kinase (AMPK), activated by 3­BP, was determined. It was demonstrated that phosphorylated­AMPK was upregulated following treatment with 3­BP. Notably, Compound C, an AMPK inhibitor, reversed the effects of 3­BP. Finally, a synergistic antitumor effect of 3­BP and TRAIL was observed in MCF­7 cell xenografts in nude mice. In conclusion, these results indicated that 3­BP sensitized breast cancer cells to TRAIL via the AMPK­mediated upregulation of DR5.

Volatiles released by Chinese liquorice roots mediate host location behaviour by neonate Porphyrophora sophorae (Hemiptera: Margarodidae).

BACKGROUND: The cochineal scale, Porphyrophora sophorae (Hemiptera: Coccoidea, Margarodidae), is one of the most serious arthropod pests of Chinese liquorice, Glycyrrhiza uralensis (Fabaceae), an important medicinal herb. The adult females tend to deposit the ovisacs in soil relatively far away from liquorice plants. After hatching, neonates move out of the soil and may use chemical cues to search for new hosts. RESULTS: We collected and analysed the volatiles from soils with and without liquorice roots, and chromatographic profiles revealed hexanal, ß-pinene and hexanol as potential host-finding cues for P. sphorae. The attractiveness of these compounds to neonates was studied in the laboratory using four-arm olfactometer bioassays. The larvae showed a clear preference for ß-pinene over hexanal and hexanol, as well as all possible combinations of the three compounds. In addition, a field experiment confirmed that ß-pinene was significantly more attractive than hexanal and hexanol. CONCLUSION: Newly eclosed larvae of P. sphorae exploit root volatiles as chemical cues to locate their host plant. ß-Pinene proved to be the major chemical cue used by P. sphorae neonates searching for roots of their host plant. © 2016 Society of Chemical Industry.

Smac mimetic­induced caspase­independent necroptosis requires RIP1 in breast cancer.

There is an urgent requirement for the development of novel targeted therapies to treat breast cancer, which is the most comment type of malignancy among women. The evasion of apoptosis is a hallmark of cancer, and is often due to the upregulation of inhibitor of apoptosis proteins (IAPs) in tumor cells. Second mitochondrial­derived activator of caspase/direct IAP­binding protein with low PI is a natural IAP antagonist, which is found in the mitochondrion; this protein has a motif, which binds to a surface groove on the baculovirus IAP repeat domains of the IAPs. In the present study, the effects of the LCL161 Smac mimetic, a small molecule IAP antagonist, on breast cell lines was examined. The results from MTT and colony formation assays demonstrated that LCL161 markedly inhibited the proliferation and induced the apoptosis of MDA­MB­231 and MCF­7 cell lines. As determined by western blotting, cIAP1 was degraded in the breast cancer cells, which occurred in an LCL161­dependent manner. Upon caspase activation, LCL161 treatment induced necroptosis, another form of programmed cell death. The downregulation of receptor­interacting protein kinase­1 via small interfering RNA protected the cells from LCL161­induced necroptosis. Taken together, the results of the present study showed that LCL161 can induce multiple forms of programmed cell death in breast cancer cells, and may thus offer promise as an anticancer agent in diverse genotypic backgrounds.

MiR-423-3p enhances cell growth through inhibition of p21Cip1/Waf1 in colorectal cancer.

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths globally, with many oncogenes and tumor suppressors involved. The miRNAs are small non-coding RNAs known to play a vital role in the pathogenesis of CRC. The miR-423-3p was reported to act as an oncogene; however, its role in CRC growth remains unknown. METHODS: qPCR assay was used to detect miR-423-3p expression in CRC specimens. Cell proliferation assay and transwell assay were conducted to evaluate CRC cell proliferation and migration. Luciferase reporter assay was to identify the target gene of miR-423-3p. And tumorigenesis model was established to test the role of miR-423-3p in CRC development in vivo. RESULTS: Here, we showed that miR-423-3p was significantly up regulated in CRC tissues and cells compared with normal tissues and cells. Overexpression of miR-423-3p promoted CRC cell proliferation via enhancing the G1/S transition phase of the cell cycle, while inhibition of miR-423-3p repressed cell growth. Further studies showed that p21Cip1/Waf1 mediated the function of miR-423-3p, and overexpression of p21Cip1/Waf1 reversed the augmented effect of miR-423-3p on cell proliferation. Importantly, all these data were validated in the tumorigenesis assay in vivo. CONCLUSIONS: In conclusion, our findings demonstrated a critical impact of miR-423-3p on CRC growth.