Improving the performance of inorganic perovskite solar cells via the perovskite quantum dot dynamically mediated film growth method.

Perovskite quantum dots (PQDs) are promising interface modification materials for perovskite solar cells (PSCs). However, due to the limitation of the preparation method, it is hard to use PQDs as substrates for the growth of perovskite films by the common solution process. In this work, by introducing the rare earth element Ce into PQDs with the vacuum freezing and drying technology, we have successfully improved the solvent stability of PQDs. Moreover, we propose a technology, PQD dynamically mediated growth of perovskite film (PDMG), to prepare high-quality perovskite films, which can avoid the formation of PQD charge-blocking layers. Thanks to the improvement of perovskite crystallinity and the charge transport ability, the PCE is improved from 10.44% to 12.14% for CsPbI2Br PSCs and from 14.43% to 16.38% for CsPbI3 PSCs. Our work opens an avenue for using PQDs as substrates in the fabrication of highly efficient PSCs.

Drug Exposure and Minimum Inhibitory Concentration Predict Pulmonary Tuberculosis Treatment Response.

BACKGROUND: Prospective studies correlating pharmacokinetic/pharmacodynamic (PK/PD) indices to clinical responses are urgently needed. This study aimed to find clinically relevant PK/PD thresholds that can be used for treatment optimization. METHODS: Pharmacokinetic sampling and minimum inhibitory concentration (MIC) measurements were performed for patients with culture-confirmed tuberculosis (TB). Classification and regression tree (CART) analysis was applied to obtain PK and/or PD thresholds for first-line drugs predictive of 2-week/month culture conversion, treatment outcome determined at 6-8 months, acute kidney injury (AKI), and drug-induced liver injury (DILI). Least absolute shrinkage and selection operator (LASSO) logistic regression was used for model development and validation. RESULTS: Finally, 168 and 52 patients with TB were included in development and validation cohorts for analysis, respectively. Area under the concentration-time curve (AUC)/MIC below CART-derived thresholds for pyrazinamide of 8.42, pyrazinamide of 2.79, or rifampicin of 435.45 were the predominant predictors of 2-week culture conversion, 2-month culture conversion, or treatment success, respectively. Isoniazid AUC >21.78 mg · h/L or rifampicin AUC >82.01 mg · h/L were predictive of DILI or AKI during TB treatment. The predictive performance of trained LASSO models in the validation cohort was evaluated by receiver operating characteristic curves and ranged from 0.625 to 0.978. CONCLUSIONS: PK/PD indices and drug exposure of TB drugs were associated with clinical outcome and adverse events. The effect of CART-derived thresholds for individualized dosing on treatment outcome should be studied in a randomized controlled trial.

Drug exposure of first-line anti-tuberculosis drugs in China: A prospective pharmacological cohort study.

AIM: Exploring the need for optimization of drug exposure to improve tuberculosis (TB) treatment outcome is of great importance. We aimed to describe drug exposure at steady state as well as the population pharmacokinetics (PK) of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) in Chinese TB patients. METHODS: A prospective multicentre PK study of RIF, INH and PZA was conducted in China between January 2015 and December 2017. Six blood samples were collected from each subject for drug concentration measurement. Nonlinear mixed effect analyses were used to develop population PK models. RESULTS: In total, 217 patients were included. Positive correlations between body weight, clearance and volume of distribution were identified for RIF and PZA, whereas body weight only influenced clearance for INH. In addition, males had higher RIF clearance and thus lower RIF exposure than women. Acetylator status was significantly associated with INH clearance as INH exposure in intermediate and fast acetylators was significantly lower than in slow acetylators, especially in low-weight bands. Simulations also showed significantly lower drug exposures in low-weight bands for all three drugs. Patients weighing <38 kg were respectively exposed to 30.4%, 45.9% and 18.0% lower area under the concentration-time curve of RIF, INH and PZA than those weighing ≥70 kg. Higher doses by addition of one fixed-dose combination tablet or 150 mg INH were simulated and found to be effective in improving INH drug exposures, especially in low-weight bands. CONCLUSION: PK variability of first-line anti-TB drugs is common in Chinese TB patients. The developed population PK models can be used to optimize drug exposures in Chinese patients. Moreover, standard dosing needs to be adjusted to increase target attainment.

Application of quantum dots in perovskite solar cells.

Perovskite solar cells (PSCs) are important candidates for next-generation thin-film photovoltaic technology due to their superior performance in energy harvesting. At present, their photoelectric conversion efficiencies (PCEs) are comparable to those of silicon-based solar cells. PSCs usually have a multi-layer structure. Therefore, they face the problem that the energy levels between adjacent layers often mismatch each other. Meanwhile, large numbers of defects are often introduced due to the solution preparation procedures. Furthermore, the perovskite is prone to degradation under ultraviolet (UV) irradiation. These problems could degrade the efficiency and stability of PSCs. In order to solve these problems, quantum dots (QDs), a kind of low-dimensional semiconductor material, have been recently introduced into PSCs as charge transport materials, interfacial modification materials, dopants and luminescent down-shifting materials. By these strategies, the energy alignment and interfacial conditions are improved, the defects are efficiently passivated, and the instability of perovskite under UV irradiation is suppressed. So the device efficiency and stability are both improved. In this paper, we overview the recent progress of QDs' utilizations in PSCs.

Interface modification of an electron transport layer using europium acetate for enhancing the performance of P3HT-based inorganic perovskite solar cells.

In recent years, although the power conversion efficiency (PCE) of thermally stable all-inorganic CsPbI3 perovskite solar cells (PSCs) had shown a great progress, the most reported CsPbI3 PSCs suffered from the large open-circuit voltage (Voc) loss, which is related to severe nonradiative recombination and a mismatch in energy level at the transport layer/perovskite interface. In this work, europium acetate (EuAc3) as a multifunction interface material is chosen to modify the TiO2/perovskite interface, the crystal quality of CsPbI3 perovskite films is improved, and both bulk and interfacial defects are reduced effectively. Meanwhile, the energy levels arrangement between TiO2 and CsPbI3 perovskites is also optimized, corresponding the raised built-in electric field afford a strength force to accelerate the transport and extraction of charge carriers from CsPbI3 perovskites to TiO2. As a result, the performance of CsPbI3 PSCs is largely enhanced with the PCE of 16.76%. When an Ag electrode was replaced by Au, the PCE further improves to 17.92%, which is the highest for CsPbI3 PSCs with P3HT as the HTL ever reported. Besides, the CsPbI3 PSC with the EuAc3 modification layer maintains 84% of the initial PCE under continuous UV irradiation for 250 h in a nitrogen filled glovebox, being obviously higher than the control devices with only 40% of the initial PCE after UV irradiation for 100 h in the same environment.

Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor.

Curcumin (Cur) is widely used as an anti-inflammation agent and has anti-depression potential. Neuroinflammation mediated by Ca2+ channel activation is closely associated with the progression of post-stroke depression (PSD). In the current study, the role of P2X7 receptor (P2X7R) in the anti-PSD function of Cur was explored. Rats were subjected to middle cerebral artery occlusion (MCAO) surgery and chronic mild stress administration to induce PSD symptoms and then treated with Cur. The behaviors of rats were assessed with sucrose preference and forced swim tests. The accumulation of Ca2+ and the systemic inflammatory response in rats were detected. To determine the role of P2X7R in the anti-PSD function of curcumin, the PSD mice were further administrated with P2X7R agonist and antagonist. The administration of Cur attenuated behavior disorders associated with PSD. Moreover, the Ca2+ accumulation and the inflammatory response associated with PSD were also blocked by Cur. Cur also inhibited the activation of Ca2+ channel. The induced activity of P2X7R blocked the function of Cur by maintaining the symptoms of PSD in Cur-treated rats. Collectively, the anti-PSD function of Cur was dependent on the inhibition of P2X7R, which then deactivated Ca2+ channel-mediated inflammatory response associated with PSD progression.

TP53 R249S mutation detected in circulating tumour DNA is associated with Prognosis of hepatocellular carcinoma patients with or without hepatectomy.

BACKGROUND AND AIMS: Somatic mutation R249S in TP53 is highly common in hepatocellular carcinoma (HCC). We aim to investigate the effects of R249S in ctDNA on the prognosis of HCC. METHODS: We analysed three cohorts including 895 HCC patients. TP53 mutation spectrum was examined by direct sequencing of genomic DNA from tissue specimens in HCC patients with hepatectomy (Cohort 1, N = 260). R249S and other recurrent missense mutations were assessed for their biological functions and associations with overall survival (OS) and progression-free survival (PFS) of HCC patients in Cohort 1. R249S within circulating tumour DNA (ctDNA) was detected through droplet digital polymerase chain reaction (ddPCR) and its association with OS and PRS was analysed in HCC patients with (Cohort 2, N = 275) or without (Cohort 3, N = 360) hepatectomy. RESULTS: In Cohort 1, R249S occupied 60.28% of all TP53 mutations. Overexpression of R249S induced more serious malignant phenotypes than those of the other three identified TP53 recurrent missense mutations. Additionally, R249S, but not other missense mutations, was significantly associated with worse OS (P = .006) and PFS (P = .01) of HCC patients. Consistent with the results in Cohort 1, HCC patients in Cohorts 2 and 3 with R249S had worse OS (P = 8.291 × 10-7 and 2.608 × 10-7 in Cohorts 2 and 3, respectively) and PFS (P = 5.115 × 10-7 and 5.900 × 10-13 in Cohorts 2 and 3, respectively) compared to those without this mutation. CONCLUSIONS: TP53 R249S mutation in ctDNA may serve as a promising prognosis biomarker for HCC patients with or without hepatectomy.

Genetic associations of docetaxel-based chemotherapy-induced myelosuppression in Chinese Han population.

WHAT IS KNOWN AND OBJECTIVE: Myelosuppression, an adverse drug reaction (ADR), often causes medical treatment termination in cancer patients. It has been known that genetic components, such as single-nucleotide polymorphisms (SNPs), influence the risk of myelosuppression at the individual-patient level. However, due to ethnic variation in frequency of genetic polymorphisms, results reported in Caucasian patients may not be generalizable to the Chinese Han population. Until now, few researches on myelosuppression included Chinese Han patients. In this study, we conducted a systematic study of potential biomarkers for docetaxel-induced myelosuppression in Han Chinese patients. METHODS: We examined 61 SNPs in 36 genes that code for drug transporters, metabolism enzymes, nuclear receptors and DNA repair pathway in 110 Chinese Han patients receiving docetaxel-based chemotherapy. Genotyping was conducted using the Sequenom MassARRAY system. Significant SNPs were identified by logistic regression, and gene-gene interactions were investigated by generalized multifactor dimensionality reduction (GMDR) analysis. RESULTS AND DISCUSSION: Our results revealed that 11 SNPs in nine genes (SLC15A1, SLCO1A2, CYP2D6, FMO3, UGT1A1, NAT2, SULT2A1, PXR and HNF4α) were associated with docetaxel-induced myelosuppression. GMDR analyses suggested that a 3-locus model: SLC15A1 rs2297322-PXR rs3732359-FMO3 rs2266782 was an appropriate predictive model of docetaxel-induced myelosuppression (P = .017, Testing Bal.Acc = 0.653, CV Consistency = 10/10). WHAT IS NEW AND CONCLUSION: Our findings suggest multiple novel predictive biomarkers of docetaxel-induced myelosuppression: SLC15A1 rs2297322, PXR rs3732359 and FMO3 rs2266782. These discoveries should help in advancing future personalized therapy of docetaxel-based chemotherapy specific to Chinese Han patients.

[Factors in first-time adrenocorticotropic hormone therapy and their influence on spasm control time in infantile spasms: a Cox proportional-hazards regression model analysis].

OBJECTIVE: To investigate the factors in first-time adrenocorticotropic hormone (ACTH) therapy and their influence on spasm control time in infants with infantile spasms. METHODS: A total of 72 infants with infantile spasms who were admitted from January 2008 to October 2013 were enrolled. Their clinical data were collected, and the exposure factors for infantile spasms were selected. A Cox proportional-hazards regression model analysis was performed for these factors to analyze their influence on spasm control time. RESULTS: Clarification of the etiology (known or unexplained etiology), frequency of spasms before treatment, and presence or absence of combination therapy (ACTH used alone or in combination with magnesium sulfate) had a significant influence on spasm control time in infants with infantile spasms. The infants with a known etiology had a significantly shorter spasm control time than those with unexplained etiology, and the infants with a low frequency of spasms before treatment and receiving ACTH combined with magnesium sulfate early had a significantly longer spasm control time than their counterparts (P<0.05). CONCLUSIONS: For infants with infantile spasms at initial diagnosis, etiology should be clarified, which may helpful for evaluating prognosis. A combination of ACTH and magnesium sulfate should be given as soon as possible, which may improve their prognosis.

Plasma soluble podoplanin is a novel marker for the diagnosis of tumor occurrence and metastasis.

Podoplanin (PDPN) is expressed on many tumors and is involved in tumor metastasis. The objective of the present study was to develop an ELISA for determining soluble PDPN (sPDPN) levels as a potential novel tumor marker in plasma of patients with cancers for detection of tumor occurrence and metastasis. Mouse monoclonal antibodies (mAb) against human PDPN were developed and characterized. Two anti-PDPN mAb, SZ-163 and SZ-168, were used in a sandwich ELISA to detect plasma sPDPN in patients with cancers and in normal individuals. The levels of sPDPN were detected in patients with adenocarcinoma (87 cases, 31.09 ± 5.48 ng/ml), squamous cell carcinoma (86 cases, 6.91 ± 0.59 ng/ml), lung cancer (45 cases, 26.10 ± 7.62 ng/ml), gastric cancer (38 cases, 23.71 ± 6.90 ng/ml) and rectal cancer (27 cases, 32.98 ± 9.88 ng/ml), which were significantly higher than those in normal individuals (99 cases, 1.31 ± 0.13 ng/ml) (P < .0001). Moreover, the sPDPN levels in patients with metastatic cancers were higher (192 cases, 30.35 ± 3.63 ng/ml) than those in non-metastatic cancer patients (92 cases, 6.28 ± 0.77 ng/ml) (P < .0001). The post-treatment sPDPN levels of cancer patients (n = 156) (4.47 ± 0.35 ng/ml) were significantly lower compared with those seen pre-treatment (n = 128) (43.74 ± 4.97 ng/ml) (P < .0001). These results showed that an ELISA method was successfully established for quantitation of plasma sPDPN and plasma sPDPN levels correlate significantly with tumor occurrence and metastasis.

Study on Surface and Crystallinity of TiO2 Microspheres as the Photoanode of Dye-Sensitized Solar Cells.

In this study, Titanium dioxide (TiO2) microspheres were synthesized by a hydrothermal method from the same precursor: titanium sulfate. Two different TiO2 microspheres with different surface and crystallinity were fabricated by adding different additives as the photoanode of dye-sensitized solar cells (DSSCs). The growth mechanisms of the TiO2 microspheres were discussed. The effect of surface status and the crystallinity of the TiO2 microspheres on the photovoltaic characteristic of DSSCs were investigated. It was found that when the TiO2 microsphere with loose construction and rough surfaces along with better crystallinity was applied on photoanode, the DSSC exhibited better photoelectric performance than the DSSC with dense TiO2 microsphere photoanode. TiO2 microsphere with loose construction and rough surface applied to photoanode, the DSSC showed photoelectric conversion performance of 3.83% which is 53.8% higher than DSSC with dense and smooth TiO2 microsphere photoanode, and it is also superior to the DSSC with P25 photoanode.

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells.

BACKGROUND: MiR-34a is identified as a tumor suppressor gene and involved in acute myeloid leukemia (AML) development. However, the regulatory mechanism of miR-34a in AML is unclear. METHODS: The expression of miR-34a and HMGB1 in HL-60, THP-1 and HS-5 cells were detected by qRT-PCR and western blot. Lipofectamine 2000 was used to transfect with miR-34a mimics, miR-34a inhibitor, si-HMGB1, pcDNA 3.1-HMGB1, and corresponding controls. The apoptosis and autophagy of transfected AML cells were assessed by flow cytometry and western blot, respectively. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-34a. The effects of miR-34a mimics or si-HMGB1 on chemotherapy-induced autophagy were further explored in HL-60 cells treated with all-trans retinoic acid (ATRA) along with lysosomal protease inhibitors E64d and pepstatin A. RESULTS: MiR-34a was lower expressed and HMGB1 mRNA and proteins were both higher expressed in HL-60 and THP-1 cells compared with that in HS-5 cells. Higher expression levels of MiR-34 and lower expression levels of HMGB1 both significantly promoted apoptosis and inhibited autophagy in HL-60 and THP-1 cells. Dual luciferase reporter system confirmed that HMGB1 was a potential target of miR-34a. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-34a. Higher expression level of miR-34a and lower expression level of HMGB1 both inhibited chemotherapy-induced autophagy by stimulating the LC3 conversion. CONCLUSION: MiR-34a promoted cell apoptosis and inhibited autophagy by targeting HMGB1. Therefore, miR-34a may be a potential promising molecular target for AML therapy.

Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.

UNLABELLED: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71) ≤ Pmeta ≤ 9.92 × 10(-7) ). CONCLUSION: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease.

Aberrant estrogen receptor alpha expression correlates with hepatocellular carcinoma metastasis and its mechanisms.

BACKGROUND/AIMS: Metastasis one of the obstacles before poor prognosis of hepatocellular carcinoma (HCC) is improved. Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of HCC. However, the molecular mechanism of ERalpha in mediating HCC metastasis is still unclear. The aim of the present study was to detect aberrant ERalpha expression in HCC and elucidate its possible mechanisms in HCC metastasis. METHODOLOGY: We detected expression of ERalpha, phospho-estrogen receptor alpha (p-ERalpha), nuclear factor kappa B (NF-kappaB) p65 and Matrix metalloproteinase-9 (MMP-9) between HCC tissues with portal vein tumor thrombus (PVTT) and those without PVTT by immunohistochemical method. Moreover, the expression of above parameters was also determined in HCC cells of different metastatic potential by using immunocytochemical and reverse transcriptase-polymerase chain reaction (RT-PCR) methods. RESULTS: The expression of ERalpha and p-ERalpha was lower in HCC with PVTT than those without PVTT. Meanwhile, the expression pattern of above parameters was also similar in HCC cells of different metastatic potential, whereas, the expression of NF-kappaB p65 and MMP-9 was higher in HCC with PVTT than those without PVTT. The expression of NF-kappaB p65 and MMP-9 in HCC cells was also analogous to the tissues. CONCLUSIONS: These results demonstrated that expression of ERalpha, p-ERalpha, NF-kappaB p65 and MMP-9 correlated with invasion and metastasis in HCC. The mechanism of HCC metastasis may mediate through cross-talk between the NF-KB and ER signaling pathways. Meanwhile, ERa regulated MMP-9 through NF-kappaB indirectly.

Overexpression of HOXA13 as a potential marker for diagnosis and poor prognosis of hepatocellular carcinoma.

HOXA13 is a member of homeobox genes that encode transcription factors regulating embryonic development and cell fate. Abnormal HOXA13 expression was reported in hepatocellular carcinoma (HCC), but its correlation with tumor angiogenesis and prognosis still remain unclear. This study was aimed to uncover the expression, diagnostic and prognostic significance of HOXA13 in HCC. Immunohistochemistry was performed to detect HOXA13 expression in HCC and corresponding paracarcinomatous tissues from 90 patients. Enzyme-linked immunosorbent assay was used to detect serum HOXA13 in 90 HCC patients and 20 healthy volunteers. Receiver operating characteristics was analyzed to calculate diagnostic accuracy of serum HOXA13, alpha-fetoprotein (AFP) and their combination. Immunoreactivity of HOXA13 was detected in 72.2% of HCC, and 12.2% of adjacent non-cancerous samples. HOXA13 expression was significantly associated with tumor size, microvascular invasion, pathological grade, tumor capsula status, AFP level, tumor-node-metastasis stage and positively correlated with VEGF (p < 0.001) and microvessel density (p < 0.001). The combination of serum HOXA13 and AFP had a markedly higher area under the curve than HOXA13 alone. HOXA13 expression was associated with unfavorable overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001). Multivariate analysis indicated that patients with HOXA13-expressing tumors had a significantly shorter OS (p = 0.030) and DFS (p = 0.005) than those with HOXA13-negative tumors. Thus, HOXA13 expression possibly plays an important role in tumor angiogenesis, progression and prognosis of HCC. Moreover, we demonstrate that serum HOXA13 may serve as a biomarker for early HCC diagnosing and predicting outcome.

Underlying the mechanism of vancomycin and human serum albumin interaction: a biophysical study.

In the present study, the binding mechanism of vancomycin with human serum albumin (HSA) was determined. Upon addition of vancomycin to HSA, the fluorescence emission was quenched and the binding constant of vancomycin with HSA was found to be 6.05 × 10(3) M(-1) at 295 K, which corresponds to -2.16 × 10(4) J·mol(-1) of free energy. The conformation of HSA was altered upon binding of vancomycin with a decrease in α helix and an increase in ß sheets and random coils, suggesting partial unfolding of the secondary structure. Molecular docking experiments found that vancomycin binds strongly with HSA at the hydrophobic pocket through hydrogen bonding and van der Waals interactions. An average binding distance of 4.71 nm has been determined on the basis of the Förster resonance energy theory. It was demonstrated that vancomycin binding to HSA causes protein structural changes.

Prognostic significance of osteopontin in hepatocellular carcinoma: a meta-analysis.

Osteopontin (OPN) has been implicated in tumor development and progression for several years. However, the prognostic value of OPN overexpression in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to assess the relationship between OPN overexpression and clinical outcome of HCC. A meta-analysis of seven studies (1,158 patients) was carried out to evaluate the association between OPN and overall survival (OS) and disease-free survival (DFS) in HCC patients. The correlation between OPN and tumor vascular invasion or other invasion-related parameters was also assessed. Data were synthesized with random effect model of DerSimonian and Laird, hazard ratio (HR) or odds ratio (OR) with its 95% confidence interval (CI) was used as the effect size estimate. Our analysis results indicated that high OPN expression predicted poor OS (HR: 1.37, 95% CI: 1.21-1.55) and DFS (HR: 1.62, 95% CI: 1.24-2.11) of HCC. OPN overexpression tended to be associated with the presence of tumor vascular invasion (OR: 1.93, 95% CI: 0.97-3.84) and advanced tumor grade (OR: 1.74, 95% CI: 0.95-3.18). By this study, we conclude that OPN overexpression indicates a poor prognosis for patients with HCC, it may also have predictive potential for HCC invasion and metastasis.

Activation of STAT3 signal pathway correlates with twist and E-cadherin expression in hepatocellular carcinoma and their clinical significance.

BACKGROUND: To examine the expression of signal transducer and activator of transcription 3 (STAT3) and its activated form (p-STAT3), Twist, and E-cadherin in hepatocellular carcinoma (HCC), and explore their correlations with HCC progression and prognosis. MATERIALS AND METHODS: The expression profiles of STAT3, p-STAT3, Twist, and E-cadherin were assessed on 100 clinical HCC samples and 10 normal liver tissues by using an immunohistochemical staining method, and their correlations with clinicopathologic parameters and survival of HCC patients were statistically analyzed. RESULTS: The results demonstrated that the positive rate of STAT3, p-STAT3, and Twist in HCC was significantly higher than that in normal liver tissues; furthermore, 52% of HCC lesions showed reduced E-cadherin expression. Correlation analysis indicated that p-STAT3 was positively correlated with Twist expression, whereas Twist was negatively correlated with E-cadherin expression; p-STAT3, Twist, or E-cadherin expression was significantly associated with HCC invasion and metastasis. Survival analysis showed that HCC patients with p-STAT3, Twist positive expression, or reduced E-cadherin expression had a significantly shorter survival duration than those with p-STAT3, Twist negative expression, or those with normal E-cadherin expression. Multivariate analysis identified p-STAT3, Twist, or E-cadherin expression as an independent prognostic factor for overall survival of HCC patients after surgery. CONCLUSIONS: By this study, we suggest that activated STAT3 signal may associate with Twist and E-cadherin expression and mediate HCC invasiveness and metastasis; abnormal p-STAT3/Twist/E-cadherin signal axis may predict poor prognosis of HCC patients.

Muscone improves hypoxia/reoxygenation (H/R)-induced neuronal injury by blocking HMGB1/TLR4/NF-κB pathway via modulating microRNA-142.

Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an in vitro model. The cerebral hypoxia injury cell model was produced by hypoxia/reoxygenation (H/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of GSE84216 retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H/R-exposed neurons. Subsequently, through analyzing GSE84216 from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4/NF-κB pathway, finally leading to the improvement of cell injury in H/R-exposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in in vitro experiments through blocking activation of the TLR4/NF-κB signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury.