Giant tunnel resistance effect in (SrTiO3)2/(BaTiO3)4/(CaTiO3)2 asymmetric superlattice with enhanced polarization.

In this work, we report the effectively enhanced tunneling electroresistance effect in Au/(SrTiO3)2/(BaTiO3)4/(CaTiO3)2/Nb:SrTiO3 superlattice ferroelectric tunnel junction (FTJ). The stable polarization switching and enhanced ferroelectricity were achieved in the nanoscale thickness high-quality epitaxial superlattice. A high ON/OFF current ratio of more than 105 was obtained at room temperature, which is an order of magnitude larger than the BaTiO3 FTJ with the same structure. Nonvolatile resistance switching controlled by nonvolatile polarization switching was observed in the superlattice FTJ. Driven by increased polarization and intrinsic asymmetric ferroelectricity, a highly asymmetric depolarization field is generated compared with the Au/BaTiO3/Nb:SrTiO3 FTJ, resulting in an enhanced tunneling electroresistance effect. These results provide a potential way to construct FTJ memory devices by constructing asymmetric three-component ferroelectric superlattices.

Supercritical antisolvent-fluidized bed for the preparation of dry powder inhaler for pulmonary delivery of nanomedicine.

The supercritical antisolvent-fluidized bed coating process (SAS-FB) shows great potential as a technique to manufacture dry powder inhaler (DPI) that incorporate nanodrugs onto micronized matrix particles, capitalizing on the merits of both nanoparticle and pulmonary delivery. In this study, naringin (NAR), a pharmacologically active flavonoid with low solubility and in vivo degradation issues, was utilized as a model active pharmaceutical ingredient to construct nanomedicine-based DPI through SAS-FB. It is showed that processed NAR exhibited a near-spherical shape and an amorphous structure with an average size of around 130 nm. Notably, SAS-FB products prepared with different fluidized matrices resulted in varying deposition patterns, particularly when mixed with a coarse lactose to enhance the fine particle fraction (FPF) of the formulations. The FPF was positively associated with specific surface area of the SAS-FB products, while the specific surface area was directly related to surface roughness and particle size. In vitro dissolution studies using simulated lung fluid revealed that the NAR nanoparticles coated on the products were released immediately upon contact with solution, with a cumulative dissolution exceeding 90% within the first minute. Importantly, compared to oral raw NAR, the optimized DPI formulation demonstrated superior in vivo plasmatic and pulmonary AUC0→∞ by 51.33-fold and 104.07-fold respectively in a Sprague-Dawley rat model. Overall, SAS- FB technology provides a practical approach to produce nanomedicine DPI product that combine the benefits of nanoparticles with the aerodynamics properties of inhaled microparticles.

Supercritical fluid coating of flavonoids on excipients enhances drug release and antioxidant activity.

Supercritical anti-solvent fluidized bed (SAS-FB) technology can be applied to reduce particle size, prevent particle aggregation, and improve the dissolution and bioavailability of poorly soluble drugs. In this work, drug-loaded microparticles of three similar structures, the flavonoids luteolin (LUT), naringenin (NGR), and dihydromyricetin (DMY) were prepared using SAS-FB technology, to explore its effect on the coating of flavonoid particles. Operating temperature, pressure, carrier, solvent, and concentration of drug solution were investigated for their effects on the yield and dissolution of flavonoid particles. The results showed that temperature, pressure, carrier, and drug solution concentration have a large effect on yield. Within the study range, low supercritical CO2 density at higher temperature and lower pressure, a larger surface area carrier, and moderate drug solution concentration led to a higher yield. The effect of the solvent on the yield of flavonoids is a result of multiple factors. Scanning electron microscopy (SEM) images showed that the drug-loaded particles prepared from different carriers and solvents have different precipitations pattern on the carrier surface, and their particle sizes were smaller than unprocessed particles and those prepared by the SAS process. Fluorescence microscopy (FM) results showed that the flavonoids were uniformly coated on the carrier. X-ray powder diffraction (XRPD) results showed that the crystalline morphology of SAS-FB particles remained unchanged after the SAS-FB process, although the diffraction peak intensity decreased. The cumulative dissolution of SAS-FB particles was more than four times faster in the first 5 min than that of the unprocessed flavonoids. The antioxidant activity of SAS-FB processed LUT, NGR and DMY was 1.89-3.78 times, 4.92-10.68 times and 0.99-2.57 times higher than that of the untreated flavonoids, respectively. The approach provides a reference for the application of SAS-FB technology in flavonoids.

The Impact of Late Follicular Phase Progesterone Elevation on Cumulative Live Birth Rate and Embryo Quality in 4072 Freeze-All Cycles.

Late follicular phase progesterone elevation during in vitro fertilization impedes embryo implantation. It is unclear whether late follicular phase progesterone elevation still has a negative effect on cumulative live births and embryo quality when a freeze-all strategy is adopted. Data from a total of 4072 patients were reviewed. All patients used the freeze-all strategy. Multivariate regression analyses were used to assess the association of progesterone levels with both cumulative live birth and embryo quality. There was no significant difference in the cumulative live birth rate between the groups with progesterone level <1.5 ng/mL and ≥1.5 ng/mL. The progesterone level was not associated with cumulative live birth and embryo quality.

Euploid blastocyst rates in patients from POSEIDON groups 3 and 4 using propensity score matching.

RESEARCH QUESTION: Do patients with low ovarian reserve, as defined by the patient-oriented strategies encompassing individualized oocyte number (POSEIDON) criteria, have low euploid blastocyst rates? DESIGN: Retrospective study of 548 IVF cycles of patients with unexplained recurrent miscarriage who underwent preimplantation genetic test for aneuploidy (PGT-A). Euploid blastocyst rates were analysed to compare patients from POSEIDON groups 3 and 4 (serum anti-Müllerian hormone [AMH] levels <1.2 ng/ml) with those who have normal ovarian reserve (AMH levels ≥1.2 ng/ml) before and after using propensity score matching to match selected variables, such as female age, body mass index, the number of clinical miscarriages, ovarian stimulation protocols and PGT-A analysis platforms. Cycles of patients from POSEIDON groups 3 and 4 were then divided into four groups according to median and quartiles of serum AMH levels: <0.668 ng/ml, 0.668-0.890 ng/ml, >0.890-1.070 ng/ml and >1.070-<1.20 ng/ml. The euploid blastocyst rates were compared across these four groups. RESULTS: After using propensity score matching, no difference was found in euploid blastocyst rates between patients from POSEIDON groups 3 and 4 and those with normal ovarian reserve. Among cycles of patients from POSEIDON groups 3 and 4, no difference was found in euploid blastocyst rates between the different AMH levels. CONCLUSIONS: The decline in ovarian reserve in patients from POSEIDON groups 3 and 4 was not related to low euploid blastocyst rates. Serum AMH levels do not seem to be a predictor of euploid blastocyst rates in such patients.

JPHYD Inhibits miR-21-5p/Smad7-Mediated Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells.

Background: Studies have shown that Jianpi Huayu Decoction (JPHYD) can inhibit the growth of hepatocellular carcinoma cells, but the mechanism of its effect was not clear at present. Methods: We assessed the effect of JPHYD using liver cancer cells as in vitro cell model and xenograft tumor as in vivo model. CCK8, EdU, wound-healing, and transwell assays were performed to assess the cell growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines HepG2 and MHCC97H. Western blot assay was performed to observe the protein level of E-cadherin, Smad7, N-cadherin, Snail, Smad3, Vimentin, and Zeb1. qRT-PCR assay was used to observe the expression of miR-21-5p in clinical liver cancer tissue samples and in HepG2 and MHCC97H cells. Animal tumorigenesis experiments and in vivo imaging experiments were performed to assess the results of in vitro experiments. Results: We found that JPHYD could inhibit the proliferation, invasion, and migration of hepatocellular carcinoma cells and JPHYD decreased the level of N-cadherin, Snail, Vimentin, Smad3, and Zeb1 and increased E-cadherin and Smad7 proteins. The expression of miR-21-5p was increased while that protein of Smad7 was decreased in HCC tissues. The vivo experiments also showed that miR-21-5p could promote the migration of HCC cells. JPHYD decreased miR-21-5p expression. The same results have been found in animal studies. Conclusion: Our results indicated that JPHYD inhibited epithelial-mesenchymal transition by increasing Smad7 expression and inhibiting miR-21-5p. Therefore, blocking the occurrence and development of EMT may be a new mechanism of JPHYD's anti-liver cancer effect.

Differential transcriptional profiles of human cumulus granulosa cells in patients with diminished ovarian reserve.

PURPOSE: This study compared the gene expression profiles of cumulus granulosa cells in patients with diminished ovarian reserve and those with normal ovarian reserves to identify genes that may be involved in the pathogenesis of diminished ovarian reserve. METHODS: After retrieval of the cumulus-oocyte complex, the cumulus granulosa cells that surrounded the oocytes of 25 patients with diminished ovarian reserve and 25 patients with normal ovarian reserves were removed by mechanical stripping. Extraction of RNA from the cumulus granulosa cells was for RNA sequencing and analysis. RT-PCR was used to confirm the candidate genes. Statistical analysis was performed using student's t test. RESULTS: A total of 294 upregulated genes and 336 downregulated genes were identified in the POSEIDON patients relative to the normal ovarian reserve group. Bioinformatic analysis showed that the downregulated genes were highly enriched in the Wnt signaling pathway, negative regulation of stress fiber assembly, and cell chemotaxis, while the upregulated genes were highly enriched in functions associated with the regulation of interleukin-5 production and regulation of immune system processes. According to the differential expression levels and their potential functions, IL1RL1, IL33, SFRP4, and S1PR1 were validated by quantitative RT-PCR. The results of RT-PCR were consistent with those of RNA sequencing. CONCLUSION: Expression of IL1RL1, IL33, SFRP4, and S1PR1 in the cumulus granulosa cells may be involved in the pathogenesis of diminished ovarian reserve.

Similar implantation competence in euploid blastocysts developed on day 5 or day 6 in young women: a retrospective cohort study.

The results from different studies are inconsistent regarding whether development potential correlated with embryo development speed after single euploid blastocyst transfer. The age-associated reproductive decline is not only because of the difference in aneuploidy rates but also because of metabolic and epigenetic changes of the embryos. Therefore, we aimed to assess the independent effect of embryo development speed on implantation potential in young women. A total of 326 young women who underwent preimplantation genetic testing for monogenic diseases with aneuploidy screening were analyzed. Day-5 and day-6 euploid blastocysts yielded similar implantation rates (65.20 vs. 61.22%). The odds ratio (OR) remained non-significant after adjusting for confounders (adjusted OR = 0.84, 95% confidence interval 0.52-1.36). There was a trend that day-6 euploid blastocysts had a higher miscarriage rate (13.33 vs. 9.20%). However, the live birth delivery rate of day-5 blastocysts was similar to that of day-6 blastocysts (59.20 vs. 53.06%). In the stratified analysis, live birth delivery rates were similar between day-5 and day-6 similarly graded euploid blastocysts (excellent and good, 62.04 vs. 64.71%; average, 58.73 vs. 53.70%; poor, 43.75 vs. 44.44%). Embryo development speed has no obvious impact on implantation competence in young women's vitrified/warmed euploid embryo transfer cycles.

Characterization of excipients to improve pharmaceutical properties of sirolimus in the supercritical anti-solvent fluidized process.

Enhanced drug release and bioavailability of poorly soluble active pharmaceutical ingredient (API) can be achieved via a fluidized bed coating integrated with supercritical anti-solvent (SAS-FB) - a process of precipitating drug particles onto carrier granules. However, in the absence of excipients, SAS-FB often results in crystalline of the API on the surface of carriers, limiting the improvement of pharmaceutical properties. Co-processing with excipients is considered an effective approach to improve drug release in the SAS-FB process. Our study used sirolimus, an immune suppressive agent, as the model API to characterize excipients for their effect on pharmaceutical properties in the SAS-FB process. We show that co-precipitation of excipients and sirolumus impacts on carrier specific surface area and drug yield. Among the tested excipients, formulation containing polyvinylpyrrolidone K30 achieved the highest drug yield. Importantly, compared with Rapamune® tablet, our optimized formulation displayed a superior in vivo oral bioavailability by 3.05-fold in Sprague-Dawley rats and 3.99-fold in beagle dogs. A series of characterization of the processed API was performed to understand the mechanism by which excipients contributed to drug dissolution properties. Our study provides a useful guidance for the use of excipients in the SAS-FB technology to improve pharmaceutical properties of sirolimus and other poorly soluble drugs.

Optimum synthesis of cactus-inspired SERS substrate with high roughness for paraquat detection.

Paraquat is a highly effective herbicide and widely used in agricultural production. However, paraquat residue is harmful for human health and can cause irreversible hazard. Thus, it is crucial for monitoring of paraquat residues. In this paper, an efficient SERS platform based on cactus-inspired nanoparticles is proposed for sensitive detection of paraquat. The cactus-liked nanoparticles obtained from one-pot stepwise reduction method possess multiple spiny structures and can produce abundant hot spots, resulting in remarkable SERS performance. SEM, TEM, UV-vis and Raman tests were conducted to characterize and optimize the morphology of cactus-liked nanoparticles under different preparation conditions. The synthesis mechanism and corresponding parameters influence mechanism of cactus-liked nanoparticles were explored in detail. Optimized substrate exhibited a high sensitivity with the detectable concentration of crystal violet (CV) down to 10-9 M and an excellent reproducibility proved by SERS mapping. Furthermore, it behaved good linear relationship with a correlation coefficient (R2) of 96.89% between Raman intensities and concentrations of paraquat, which indicates the SERS substrate prepared with cactus-liked nanoparticles could offer a great potential for identification of paraquat.

Optimum synthesis of Au@Ag nanoparticle as plasma amplifier to detect trace concentration of AFB1 via object-binder-metal SERS method.

The problem of aflatoxin contamination emerged gradually in the field of food safety. Surface-enhanced Raman spectroscopy (SERS) is an ultra-sensitive and non-destructive spectroscopy technology with extensive application prospects in the detection field. In this paper, with the detection of AFB1 as the target, Au@Ag NPs substrate with uniform morphology and strong SERS effect was prepared. Furthermore, the intermediates formed by hydrogen bonding between AFB1 and melamine facilitate the binding of toxin molecules to the substrate. Moreover, the AFB1-melamine-Au@Ag NPs detection system was established by optimizing the melamine dosage, and the limit of detection can reach 10-8 mol/L (M). In this method, AFB1 (concentration range of 10-4 M - 10-7 M) in tea oil, the Raman signal intensity of AFB1 shows an excellent linear, logarithmic relationship, and the correlation coefficient is 0.9685. Therefore, this work has achieved simple, sensitive, and stable AFB1 detection and has broad application potential in food safety detection.

Oocyte Degeneration After ICSI Is Not an Indicator of Live Birth in Young Women.

Introduction: Intracytoplasmic sperm injection (ICSI) was introduced in 1990s as one of the most dramatic breakthroughs in assisted reproductive technology. Even with advances in ICSI technology, this mechanical micromanipulation carries a 5 to 19% risk of oocyte degeneration. Whether the presence of oocyte degeneration reflects the sibling oocyte quality and predicts the sibling embryo development potential and clinical pregnancy outcomes remains controversial. There is no study showing the competence of the sibling embryos from the prospective of cumulative live birth rate. Whether oocyte degeneration is associated with poor quality of the remainder of the cohort remains further to be elucidated. Method: This retrospective observational study included a total of 488 OPU cycles underwent ICSI with fresh cleavage stage embryo transfer and successive frozen/thawed embryo transfer (FET) cycles from January 2018 to December 2019. All female patients were under the age of 35 years, and underwent ICSI with or without oocyte degeneration (OD). Cycles with at least one oocyte degenerated were defined as oocyte degeneration group (OD group), and cycles with no oocyte degenerated were defined as non-OD group. The OD group was further divided to three subgroups according to different oocyte degeneration rate (<10%, 10-20%, and >20%). Results: There were no significant differences with regards to implantation rate (38.5% vs 35.1%, P=0.302), clinical pregnancy rate (54.9% vs 50.3%, P=0.340), and LBR per OPU cycle (47.0% vs 42.9%, P=0.395) between OD and non-OD groups. Initial gonadotropin dosage, E2 level on hCG day and the number of matured oocytes appeared to be independent risk factors for OD. The adjusted odds ratio of live birth rate per OPU cycle were similar in different oocyte degeneration rate subgroups. The ongoing pregnancy/LBR per transfer in FET cycles was not significantly different between OD group and non-OD groups (38.8% vs 43.9%, P=0.439). The cumulative LBR per OPU cycle was also comparable between OD and non-OD group (63.4% vs 64.8%, P=0.760). Conclusion: The results provide cycle-based evidence that the presence of oocyte degeneration after ICSI is not an indicator for predicting the cumulative live birth rate per OPU cycle in young women.

Synergistic enhancement effect of MoO3@Ag hybrid nanostructures for boosting selective detection sensitivity.

An ex situ method was used to synthesize noble metals and metal oxide composite materials, due to the selective adsorption properties of metal oxides, the adsorption of different probe molecules by this composite structure had been studied. In the ex situ approach, we use (3-aminopropyl) diethoxy methylsilane (ATES) as a coupling agent which is easy for noble metal nanoparticles deposited on metallic oxide nanomaterials. The Raman scattering (SERS) substrate of 1D MoO3 nanowires (MoO3-NWs) @Ag nanoparticles (Ag-NPs) hybrid surface had been fabricated. Several parameters are presented in the following which influences the morphology of self-assembly and SERS activity: (i) coupling agent of ATES, (ii) ATES content (iii) Ag-NPs content. The finite difference time domain (FDTD) method is to explain the enhancement mechanism distribution of the hybrid substrate. Different probe molecules (R6G, Methylene Blue, Crystal Violet, and 4-ATP) have been adsorbed for SERS tests. Improved principle component analysis (PCA) is adopted to obtain the minimum detection limit of probe molecules. Through the DFT calculation, different absorption strengths between the target molecules and the MoO3(010) surface have been illustrated, which is also the main reason for the selective enhancement effect of MoO3@Ag hybrid nanostructures. This paper might propose a method to prepare such enhancement substrate based on the selective absorption properties of oxide semiconductors.

circ_0023642 promotes malignant biological behaviors of gastric cancer cells via regulating miR-508-3p/ERBB4 axis / 中国肿瘤生物治疗杂志

@#Objective: To explore the influence of circ_0023642 on the proliferation and metastasis of gastric cancer GMC-803 cells by modulating miR-508-3p/ERBB4 axis. Methods: Cancer tissues and corresponding para-cancer normal tissues from 31 gastric cancer patients, who underwent surgical resection at the Second People's Hospital of Nantong City from May 2015 to March 2018, were collected for this study; meanwhile, gastric cancer cell lines (MGC-803, MKN-45 and MKN-28) were also collected. qPCR was performed to determine the expression levels of circ_0023642 and miR-508-3p in above mentioned tissues and cell lines. WB was applied to measure the expressions of ERBB4, E-cadherin, N-cadherin and Vimentin in MGC-803 cells. CCK-8 assay and Transwell assay were used to evaluate the effects of circ_0023462 and miR-508-3p expression on proliferation, migration and invasion of MGC-803 cells. Dual-luciferase reporter gene was carried out to validate whether miR-508-3p could bind to the 3' UTR of circ_0023642 and ERBB4. Results: Compared with para-cancer tissues or normal gastric mucosal cells, the expression of circ_0023642 was significantly up-regulated in gastric cancer tissues and cells lines, and the expression was highest in MGC-803 cells (P<0.05 or P<0.01). Silencing circ_0023642 dramatically decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of MGC-803 cells (P<0.05 or P<0.01). Both circ_0023642 and ERBB4 could target the binding sites of miR-508-3p. Further experiments confirmed that circ_ 0023642 promoted the proliferation, migration, invasion and EMT of MGC-803 cells by sponging miR-508-3p (P<0.05 or P<0.01). Conclusion: circ_0023642, by competing ERBB4 to bind with miR-508-3p, promotes the proliferation and metastasis of gastric cancer MGC-803 cells, thus could be used as a marker for the clinical diagnosis of gastric cancer.

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis.

PURPOSE: This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection. METHODS: Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals. RESULTS: Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n = 1429; control group n = 1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group. CONCLUSION: The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

Overexpression of PCBP2 contributes to poor prognosis and enhanced cell growth in human hepatocellular carcinoma.

Poly(C)­binding protein 2 (PCBP2) is a member of the PCBP family, and plays an important role in post­transcriptional and translational regulation of various signaling molecules through direct binding to single­stranded poly(C) motifs. PCBP2 has been reported to play a critical role in the development of multiple human tumors. However, whether PCBP2 participates in hepatocellular carcinoma (HCC) development remains largely elusive. Herein, we showed that PCBP2 was upregulated in human HCC tissues and cell lines. Overexpression of PCBP2 predicted significantly worsened prognosis in HCC patients, suggesting that PCBP2 may serve as a prognostic marker of HCC. In addition, we found that depletion of PCBP2 inhibited HCC cell proliferation, accompanying the increase in the cyclin­dependent kinase inhibitor p27 level. Moreover, we found that high expression of PCBP2 may contribute to sorafenib resistance in HCC cells, involving dysregulated expression of Bax and Bcl­2 proteins. In conclusion, our results suggest that PCBP2 may serve as a prognostic marker and potential therapeutic target of HCC.

Silencing of CtBP1 suppresses the migration in human glioma cells.

Carboxyl-terminal binding protein 1 (CtBP1), up-regulated in various types of human cancers, has been functionally associated with proliferation, anti-apoptosis, and EMT in vitro studies. However, the functional significance of CtBP1 in the pathophysiology of glioma remains unknown. In the present study, we showed the expression of CtBP1 was markedly higher in glioma tissues compared with normal brain tissues by Western blot analysis. Immunohistochemical analysis revealed that CtBP1 mainly localized in the nucleus of glioma cells. Statistical analysis suggested the upregulation of CtBP1 was considerably correlated with the WHO grade (P < 0.05) and those patients with high CtBP1 levels exhibited shorter survival time (P < 0.01). Silencing CtBP1 by short hairpin RNAi caused an inhibition of cell migration. Moreover, knockdown of CtBP1 increases E-cadherin expression and decreases vimentin expression. These data uncovered that CtBP1 protein is a valuable marker of glioma pathogenic process and that CtBP1 can serve as a novel prognostic marker for glioma therapy.

The role of Alix in the proliferation of human glioma cells.

Apoptosis-linked-gene-2-interacting protein 1 (Alix) is involved in the endosome-lysosome system in the cytoplasm. The normal function of Alix may be altered by ALG-2 toward a destructive role during active cell death. Alix also may play a role in regulation of cell proliferation. However, the role of Alix in human glioma has not been elucidated yet. This study intended to clarify the relationship between Alix and glioma pathologic grades and its role in the proliferation of glioma cells. Our findings showed that Alix protein concentrations were significantly elevated in high-grade glioma tissue compared with low-grade glioma (P < .0001). Immunohistochemical study revealed that Alix was overexpressed in 75 resected glioma tissues and may forecast poor survival. Alix expression was increased in resting serum-stimulated glioma cells. Additionally, we reduced Alix expression in U251MG cells and then found that cell viability was decreased significantly when p21 expression increased. Colony formation assay and flow cytometry analysis demonstrated that reduced Alix expression may lead to growth inhibition and cell cycle arrest. In summary, our findings suggest that Alix plays an important role in the proliferation of glioma cells and may be a novel therapeutic target.

Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma.

p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.

Downregulated DYRK2 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular carcinoma.

We aimed to investigate the molecular mechanisms of DYRK2 and the HCC sensitivity to Oxaliplatin in DYRK2-depleted HCC cells. HCC tissue specimens were obtained from 86 HCC patients during hepatectomy. We used immunohistochemistry and western blot to analyze DYRK2 expression in HCC tissues and cell lines, and used siRNA transfection to decrease DYRK2 expression in HCC cells. Flow cytometry and CCK-8 assay were detected in cell cycle progression, cell proliferation and the efficacy of Oxaliplatin, DYRK2 was down-regulated in HCC tissues, compared with adjacent nontumor ones. The significant correlation between DYRK2 expression and clinicopathologic factors was apparently shown in the immunohistochemical and statistical analyses. The expression of DYRK2 was significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that DYRK2 was a significant predictor for overall survival of HCC patients. The depletion of DYRK2 promoted HCC cell proliferation, and increased resistance to Oxaliplatin. These data showed that the downregulated expression of DYRK2 in HCC tumor tissues could promote the proliferation of HCC cells. In addition, reducing DYRK2 expression was associated with poor prognosis and Oxaliplatin resistance in HCC.