AIM: To identify whether Aspergillus fumigatus(A.fumigatus) hyphae antigens induced the release of interleukin-8(IL-8) in anti-fungal innate immunity of cultured human corneal epithelial cells(HCECs) ...and determine the involvement of intracellular signalling pathways. METHODS: HCECs were treated with A. fumigatus hyphae antigens with different concentrations and time.The cytoplasmic calcium of HCECs were assessed by fluorescence imaging. Western blot was used to detect the expression of Ca2 +-dependent protein kinase C(PKC). The IL-8 levels were determined by specific human IL-8 enzyme-linked immunosorbent assay(ELISA) and reverse transcriptase polymerase chain reaction(RT-PCR). Using a series of pharmacological inhibitors, we examined the upstream signalling pathway responsible for IL-8 expression in response to A.fumigatus hyphae antigens. RESULTS: Cells exposed to A. fumigatus hyphae antigens showed higher level of IL-8 m RNA expression and protein production. We demonstrated here that stimulation of HCECs with A. fumigatus hyphae triggers an intracellular Ca2 +flux and results in the activation of Ca2 +-dependent PKC(α, βⅠ and βⅡ) which can be attenuated by pre-treatment of cells with laminarin,suggesting that Dectin-1 signals pathway induced cytoplasmic calcium and influence the activation of PKC in HCECs. Inhibitors of Ca2 +-dependent PKC(Ro-31-8220 and Go6976) significantly abolished hyphae-induced expression of IL-8.CONCLUSION: Our findings suggest that A. fumigatushyphae-induced IL-8 expression was regulated by the activation of Dectin-1-mediated Ca2 +-dependent PKC in HCECs.
•sPD-L1 level was significantly elevated in patients with poor HCC outcomes after TACE.•High sPD-L1 was an independent predictive indicator for HCC prognosis after TACE.•High sPD-L1 correlated with ...high sIL-2R, IL-10 and HBV-loads, which indicated immunosuppressive status.•High sPD-L1 levels correlated with increased numbers of Treg cells, Macrophage cells, and M2-Macrophage cells.
The present study aimed to determine the prognostic significance of soluble Programmed Death-ligand 1 (sPD-L1) in hepatocellular carcinoma (HCC) patients undergoing transcatheter arterial chemoembolization (TACE).
We treated 114 HCC patients with TACE from 2012 to 2013 and determined their sPD-L1 levels by enzyme-linked immunosorbent assay. We evaluated prognosis according to mRESIST criteria and analyzed prognostic values by Cox regression and Kaplan-Meier analysis. We further evaluated correlations between sPD-L1 level and inflammatory status, as well as immunosuppressive environment.
sPD-L1 levels were significantly increased in patients who developed HCC progression (P = 0.002) and death (P < 0.001). Patients with higher pre-treatment sPD-L1 levels had a significantly shorter time to progression (10.50 vs. 18.25 months, P = 0.001) and decreased overall survival (16.50 vs. 28.50 months, P = 0.003). Importantly, sPD-L1 levels positively correlated with SII (r = 0.284, P = 0.002), sIL-2R (r = 0.239, P = 0.010), IL-10 (r = 0.283, P = 0.002), HBV-DNA loads (r = 0.229, P = 0.014), and CRP (r = 0.237, P = 0.011). Moreover, high sPD-L1 levels had increased numbers of Treg cells (FOXP3+; P = 0.026), Macrophage cells (CD68+; P = 0.014), and M2-Macrophage cells (CD163+; P = 0.026)
sPD-L1 level is a prognostic indicator of poor outcomes after TACE. High sPD-L1 might reflect increased immune activation in an immunosuppressive environment that hindered anti-tumor response activity.
Background
High rates of postoperative tumor recurrence contribute to poor outcome in hepatocellular carcinoma (HCC). Here, we investigated whether circulating tumor cells (CTCs) status can predict ...the benefit of adjuvant transcatheter arterial chemoembolization (TACE) in patients with HCC.
Methods
The retrospective study enrolled 344 HCC patients with preoperative CTCs analysis. Clinical outcomes including recurrence and survival were compared between those who received and who did not receive adjuvant TACE. Similar comparisons were made for patients stratified according to CTC status (CTC‐negative CTC = 0, n = 123; CTC‐positive CTC ≥ 1, n = 221). Propensity score matching (PSM) strategy was adopted to offset differences between two groups.
Results
In the study cohort as a whole or in CTC‐negative cohort, there were no observable differences in overall survival (OS) or time to recurrence (TTR) between TACE and control group (P > .05). In CTC‐positive patients, PSM generated 64 patient pairs, and patients with adjuvant TACE had significantly better clinical outcomes (OS: not reached vs 36.4 months, P < .001; TTR: 45.8 vs 9.8 months, P < .001). Adjuvant TACE significantly reduced early recurrence (≤2 years) (64.1% vs 31.7%, P < .001) in CTC‐positive patients. Notably, adjuvant TACE influenced TTR and OS even in subgroups of CTC‐positive patients with low risk of recurrence according to traditional evaluation.
Conclusions
Preoperative CTC status could serve as an indicator for the administration of adjuvant TACE in HCC patients. Adjuvant TACE benefits CTC‐positive HCC patients mainly by reducing early recurrence.
No uniform criteria had been established for the administration of adjuvant transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients after surgery. Results from this large‐sample, retrospective study showed that adjuvant TACE can significantly reduce tumor recurrence for circulating tumor cell‐positive patients. TACE can reduce tumor early recurrence and improve clinical outcomes for selected HCC patients.
AIM： To investigate the intratumoral expression of metastasis-associated in colon cancer 1 （MACC1） and c-Met and determine their clinical values associated with hepatitis B virus （HBV）-related ...hepatocellular carcinoma （HCC）. METHODS： A retrospective study admitted three hundred fifty-four patients with HBV-related HCC. The expression and distribution of MACC1 and c-Met were assessed by quantitative real-time polymerase chain reaction and immunohistochemistry staining. Prognostic factors influencing survival, metastasis and recurrence were assessed. RESULTS： Intratumoral MACC1 level was found to be associated with HCC disease progression. Both median tumor-free survival （TFS） and overall survival （OS） were significantly shorter in the postoperative HCC patients with high intratumoral MACC1 expression, as compared to those with low intratumoral MACC1 levels （TFS： 34 mo vs 48.0 mo, P 〈 0.001; OS： 40 mo vs 48 mo, P 〈 0.01）. Multivariable analysis indicated that high MACC1 expression or co-expression with c-Met were independent predictors for HCC clinic outcome （P 〈 0.001）. CONCLUSION： High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.
The aim of the present study was to investigate the effects of glucose fluctuation on neointimal proliferation after stent implantation by optical coherence tomography (OCT) in a ...diabetic/hypercholesterolemic (DM/HC) swine model.A total of 24 everolimus-eluting stents (EES) were implanted in the right coronary artery (RCA) of the animals using a 20% overstretch ratio. The 24 swines were divided into a DM-high glucose fluctuation (HGF) group (n = 8), DMlow glucose fluctuation (LGF) group (n = 8), and a control group (n = 8). Percent diameter stenosis (%DS), late loss (LL), percent area stenosis (%AS), and neointimal thickness (NIT) were analyzed. The differences in neointimal characteristics and circulating oxidative stress and inflammation biomarkers were assessed and measured.At 28 days, the highest values of %DS, LL, %AS, and NIT were achieved in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). The highest frequency of the heterogeneous pattern was in the HGF group followed by the LGF group (P < 0.05) and the control group (P < 0.05). This was also the case for the oxidative stress and inflammation biomarkers.DM might have a deleterious impact on neointimal proliferation after EES implantation in this DM/HC swine model. The extent of glucose fluctuation may be related to the degree of neointimal proliferation and this needs to be further confirmed by long-term follow-up and histology.
Uneven zinc (Zn) deposition typically leads to uncontrollable dendrite growth, which renders an unsatisfactory cycling stability and Coulombic efficiency (CE) of aqueous zinc ion batteries (ZIBs), ...restricting their practical application. In this work, a lightweight and flexible three-dimensional (3D) carbon nanofiber architecture with uniform Zn seeds (CNF-Zn) is prepared from bacterial cellulose (BC), a kind of biomass with low cost, environmental friendliness, and abundance, as a host for highly reversible Zn plating/stripping and construction of high-performance aqueous ZIBs. The as-prepared 3D CNF-Zn with a porous interconnected network significantly decreases the local current density, and the functional Zn seeds provide uniform nuclei to guide the uniform Zn deposition. Benefiting from the synergistic effect of Zn seeds and the 3D porous framework in the flexible CNF-Zn host, the electrochemical performance of the as-constructed ZIBs is significantly improved. This flexible 3D CNF-Zn host delivers a high and stable CE of 99.5% over 450 cycles, ensuring outstanding rate performance and a long cycle life of over 500 cycles at 4 A g–1 in the CNF-Zn@Zn//NaV3O8·1.5H2O full battery. More importantly, owing to the flexibility of the 3D CNF-Zn host, the as-assembled pouch cell shows outstanding mechanical flexibility and excellent energy storage performance. This strategy of producing readily accessible carbon from biomass can be employed to develop advanced functional nanomaterials for next-generation flexible energy storage devices.
Non-small cell lung cancer (NSCLC) represents more than about 80% of the lung cancer. The early stages of NSCLC can be treated with complete resection with a good prognosis. However, most cases are ...detected at late stage of the disease. The average survival rate of the patients with invasive lung cancer is only about 4%. Adenocarcinoma in situ (AIS) is an intermediate subtype of lung adenocarcinoma that exhibits early stage growth patterns but can develop into invasion.
In this study, we used RNA-seq data from normal, AIS, and invasive lung cancer tissues to identify a gene module that represents the distinguishing characteristics of AIS as AIS-specific genes. Two differential expression analysis algorithms were employed to identify the AIS-specific genes. Then, the subset of the best performed AIS-specific genes for the early lung cancer prediction were selected by random forest. Finally, the performances of the early lung cancer prediction were assessed using random forest, support vector machine (SVM) and artificial neural networks (ANNs) on four independent early lung cancer datasets including one tumor-educated blood platelets (TEPs) dataset.
Based on the differential expression analysis, 107 AIS-specific genes that consisted of 93 protein-coding genes and 14 long non-coding RNAs (lncRNAs) were identified. The significant functions associated with these genes include angiogenesis and ECM-receptor interaction, which are highly related to cancer development and contribute to the smoking-free lung cancers. Moreover, 12 of the AIS-specific lncRNAs are involved in lung cancer progression by potentially regulating the ECM-receptor interaction pathway. The feature selection by random forest identified 20 of the AIS-specific genes as early stage lung cancer signatures using the dataset obtained from The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples. Of the 20 signatures, two were lncRNAs, BLACAT1 and CTD-2527I21.15 which have been reported to be associated with bladder cancer, colorectal cancer and breast cancer. In blind classification for three independent tissue sample datasets, these signature genes consistently yielded about 98% accuracy for distinguishing early stage lung cancer from normal cases. However, the prediction accuracy for the blood platelets samples was only 64.35% (sensitivity 78.1%, specificity 50.59%, and AUROC 0.747).
The comparison of AIS with normal and invasive tumor revealed diseases-specific genes and offered new insights into the mechanism underlying AIS progression into an invasive tumor. These genes can also serve as the signatures for early diagnosis of lung cancer with high accuracy. The expression profile of gene signatures identified from tissue cancer samples yielded remarkable early cancer prediction for tissues samples, however, relatively lower accuracy for boold platelets samples.
Fraxinus hubeiensis
is a plant endemic to China and widely used as folk medicine to treat various diseases. However, its chemical constituents have never been reported sufficiently. Thus, the primary ...objective of this study was to investigate the phytochemical constituents and biological activities of
F. hubeiensis
leaves. Hence, combined column chromatographic and spectroscopic techniques were used to identify and characterize the secondary metabolites such as a pair of 3-keto-glycoside epimers (
1
) and (
2
), along with five known compounds (
3
~
7
). The results of α-glucosidase inhibitory activity exhibited that
1
and
2
had moderate activity with IC
50
values of 359.50 and 468.43 µM, respectively, compared to a positive control acarbose with the IC
50
value of 164.08 µM. However, Compounds
1
–
6
were shown to be inactive against the tested microbes.
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•The macrocyclic polyketide, hainanmycin A, possessed a novel carbon skeleton.•Hainanmycin A was isolated from the mangrove-derived Streptomyces sp. 219807.•Hainanmycin A featured a ...cyclo-heptadeca framework.•Hainanmycin A has a 4-hydroxy-2-pyrone unit in conjunction with a 2-cyclopentenone.•Absolute configuration of hainanmycin A was established by TDDFT-ECD method.
A macrocyclic polyketide with novel carbon skeleton, namely hainanmycin A, was isolated from the mangrove-derived Streptomyces sp. 219807. This polycyclic compound featured a cyclo-heptadeca framework possessing a 5,6-disubstituted-4-hydroxy-2-pyrone moiety in conjunction with a 2-cyclopentenone residue. The structure was established by spectroscopic analyses, and the stereochemistry was determined by NMR chemical shifts calculations and time-dependent density functional theory (TDDFT) calculation of electronic circulardichroism (ECD). A possible biogenetic pathway for hainanmycin A was proposed.
Background Transurethral resection of the bladder tumor （TURBT） remains the gold standard for non-muscle-invasive bladder cancer （NMIBC）. Laser techniques have been widely used in urology. This ...analysis aimed to assess the safety and efficacy of holmium resection of the bladder tumor （HoLRBT）vs. TURBT. Methods A systemic search of MEDLINE, Embase, Web of Science, and The Cochrane Library as well as manual bibliography searches were performed to identify the relevant studies. The pooled estimates of operation time, obturator nerve reflex rate, bladder perforation rate, bladder irrigation rate, catheterization time, hospital stay, and one- and two-year recurrence free survivals were calculated. Results Five studies were enrolled into our meta-analysis. No significant difference was observed in the operation time between groups （weighted mean difference （WMD） 1.01, 95% confidential interval （95% CI） -3.52-5.54, P=0.66）. The significant difference in the obturator nerve reflex （OR 0.05, 95% CI 0.01-0.04, P=0.004）, bladder perforation （OR 0.14, 95% CI 0.03-0.61, P=-0.009）, bladder irrigation （OR 0.13, 95% CI 0.04-0.45, P=0.001）, catheterization time （WMD -0.96, 95% C1-1.11 to-0.82, P 〈0.00001）, and hospital stay （WMD-1.46, 95% C1-1.65 to-1.27, P 〈0.00001）showed advantages of HoLRBT over TURBT. The 2-year recurrence free survival rate favors the HoLRBT group （OR 1.46, 95% CI 1.02-2.11, P=-0.04）. Conclusions As a promising technique, HoLRBT is safe and efficient, and showed several advantages over TURBT. HoLRBT can be used as an alternative procedure for TURBT in terms of low-grade papillary urothelial carcinoma or low-grade early TNM-stage urothelial carcinoma.
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