Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium.

AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

KIAA1429 protects hepatocellular carcinoma cells from ferroptotic cell death with a m6 A-dependent posttranscriptional modification of SLC7A11.

N6 -methyladenosine (m6 A) modification represents the most abundant internal methylation of eukaryotic RNAs. KIAA1429 acts as a key component of the m6 A methyltransferase complex, but its function and mechanism in ferroptotic cell death of hepatocellular carcinoma (HCC) are barely defined. We found that KIAA1429 suppression triggered ferroptosis in HCC cells according to increased cell death, iron and MDA levels, C11-BODIPY-positive cells, ROS production and decreased GSH level. Ferroptosis inhibitors ferrostatin-1 (0.5 µM) and liproxstatin-1 (10 µM) blocked KIAA1429 suppression-induced ferroptosis of HCC cells. In addition, overexpressed KIAA1429 notably heightened the activity of cystine/glutamate antiporter (SLC7A11). SLC7A11 up-regulation partially hindered KIAA1429 inhibition-mediated ferroptosis of HCC cells. The regulation SLC7A11 by KIAA1429 was attenuated by global m6 A inhibitor cycloleucine (40 µM). RNA immunoprecipitation confirmed the binding of KIAA1429 to m6 A on SLC7A11 transcript. Additionally, it was proven that KIAA1429 inhibition mitigated HCC growth in subcutaneous xenograft mice through SLC7A11. Altogether, our findings first propose that KIAA1429 protects HCC cells from ferroptosis with a m6 A-dependent post-transcriptional modification of SLC7A11 and offer a novel insight into the dysregulated epi-transcriptomics in the context of HCC.

Cellular senescence throws new insights into patient classification and pharmacological interventions for clinical management of hepatocellular carcinoma.

BACKGROUND: Cellular senescence, a state of stable growth arrest, is intertwined with human cancers. However, characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma (HCC) remains unexplored. AIM: To address this issue, we delineated cellular senescence landscape across HCC. METHODS: We enrolled two HCC datasets, TCGA-LIHC and International Cancer Genome Consortium (ICGC). Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes. Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system. TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry, immunoblotting and quantitative real-time polymerase chain reaction. The influence of TMF-regulated nuclear protein (TRNP)1 on HCC senescence and growth was proven via a series of experiments. RESULTS: TCGA-LIHC patients were classified as three cellular senescence subtypes, named C1-3. The robustness and reproducibility of these subtypes were proven in the ICGC cohort. C2 had the worst overall survival, C1 the next, and C3 the best. C2 presented the highest levels of immune checkpoints, abundance of immune cells, and immunogenetic indicators. Thus, C2 might possibly respond to immunotherapy. C2 had the lowest somatic mutation rate, while C1 presented the highest copy number variations. A cellular senescence-relevant gene signature was generated, which can predict patient survival, and chemo- or immunotherapeutic response. Experimentally, it was proven that TRNP1 presented the remarkable upregulation in HCCs. TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth. CONCLUSION: These findings provide a systematic framework for assessing cellular senescence in HCC, which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.

Anhydroicaritin suppresses tumor progression via the PI3K/AKT signaling pathway in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most malignant tumors. The in vitro experiments on the application of Anhydroicaritin (AHI), the active ingredient of Bushen Huayu Decoction, in HCC treatment remain limited, particularly regarding its molecular mechanism. METHODS: The TCMSP platform was used for drug ingredient screening. The GeneCards database and DisGeNET database are used to collect liver cancer targets. PPI network construction of active component-target intersection target was completed with string database. The GO and KEGG pathway analyses were performed via bioinformatics analysis. The molecular docking was used to confirm AHI's target proteins. The in vitro experiments were performed to validate the effect of AHI on HCC cell and explore the molecular mechanism by western blotting analysis. RESULTS: Through the intersection, 155 intersection targets are finally obtained. The top 15 active ingredients were quercetin, kaempferol, beta-sitosterol, luteolin, beta-carotene, Stigmasterol, naringenin, formononetin, baicalein, Anhydroicaritin, isorhamnetin, licochalcone, 7-O-methylisomucronulatol, aloe-emodin and 8-O-Methylreyusi. The molecular mocking analysis showed that the four active components (quercetin, kaempferol, luteolin and AHI) and targets had a good binding activity (affinity ≤ 5 kcal/mol). In vitro experiments reveled that AHI could suppress tumor proliferation, invasion and metastasis of HCC cells. Further analysis showed that AHI inhibited tumor growth by PI3K/AKT signal pathway in HCC. CONCLUSIONS: The Bushen Huayu Decoction and its active ingredient AHI could fight HCC. The potential mechanism may be associated with inhibiting the activation of PI3K/AKT signal pathway, which may serve as a potential treatment for HCC therapy.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PURPOSE: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. MATERIALS AND METHODS: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). RESULTS: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. CONCLUSIONS: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

LRPPRC facilitates tumor progression and immune evasion through upregulation of m6A modification of PD-L1 mRNA in hepatocellular carcinoma.

Objective: LRPPRC is a newly discovered N6-methyladenosine (m6A) modification reader, which potentially affects hepatocellular carcinoma (HCC) progression. PD-L1 in tumor cells is essential for tumor immune evasion. This work investigated the LRPPRC-mediated m6A-modification effect on PD-L1 mRNA and immune escape in HCC. Methods: Expression and clinical implication of LRPPRC and PD-L1 were measured in human HCC cohorts. The influence of LRPPRC on malignant behaviors of HCC cells was investigated through in vitro assays and xenograft tumor murine models. The posttranscriptional mechanism of LRPPRC on PD-L1 and anti-tumor immunity was elucidated in HCC cells via RIP, MeRIP-qPCR, RNA stability, immunohistochemical staining, and so forth. Results: LRPPRC exhibited the notable upregulated in human HCC tissues, which was in relation to advanced stage and worse overall survival and disease-free survival. Impaired proliferative capacity and G2/M phage arrest were found in LRPPRC-knockout cells, with increased apoptotic level, and attenuated migratory and invasive abilities. In HCC patients and murine models, LRPPRC presented a positive interaction with PD-L1, with negative associations with CD8+, and CD4+ T-cell infiltrations and chemokines CXCL9, and CXCL10. LRPPRC loss downregulated the expression of PD-L1 and its m6A level in HCC cells. Moreover, LRPPRC suppression mitigated tumor growth in murine models and improved anti-tumor immunity and immune infiltration in tumors. Conclusion: This work unveiled that LRPPRC may posttranscriptionally upregulate PD-L1 partially with an m6A-dependent manner for heightening mRNA stabilization of PD-L1 and provided a new mechanism for m6A regulator-mediated immunosuppression in HCC.

Convolutional neural network based on automatic segmentation of peritumoral shear-wave elastography images for predicting breast cancer.

Objective: Our aim was to develop dual-modal CNN models based on combining conventional ultrasound (US) images and shear-wave elastography (SWE) of peritumoral region to improve prediction of breast cancer. Method: We retrospectively collected US images and SWE data of 1271 ACR- BIRADS 4 breast lesions from 1116 female patients (mean age ± standard deviation, 45.40 ± 9.65 years). The lesions were divided into three subgroups based on the maximum diameter (MD): ≤15 mm; >15 mm and ≤25 mm; >25 mm. We recorded lesion stiffness (SWV1) and 5-point average stiffness of the peritumoral tissue (SWV5). The CNN models were built based on the segmentation of different widths of peritumoral tissue (0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm) and internal SWE image of the lesions. All single-parameter CNN models, dual-modal CNN models, and quantitative SWE parameters in the training cohort (971 lesions) and the validation cohort (300 lesions) were assessed by receiver operating characteristic (ROC) curve. Results: The US + 1.0 mm SWE model achieved the highest area under the ROC curve (AUC) in the subgroup of lesions with MD ≤15 mm in both the training (0.94) and the validation cohorts (0.91). In the subgroups with MD between15 and 25 mm and above 25 mm, the US + 2.0 mm SWE model achieved the highest AUCs in both the training cohort (0.96 and 0.95, respectively) and the validation cohort (0.93 and 0.91, respectively). Conclusion: The dual-modal CNN models based on the combination of US and peritumoral region SWE images allow accurate prediction of breast cancer.

RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

Neutrophil/lymphocyte ratio predicts lymph node metastasis in patients with gastric cancer.

OBJECTIVE: To identify the independent risk factors of gastric cancer (GC) lymph node metastasis and to determine whether the preoperative neutrophil and lymphocyte ratio (NLR) and the platelet and lymphocyte ratio (PLR) can be used as the indicators of gastric cancer lymph node metastasis. METHODS: The pathological data of 221 patients with gastric cancer were retrospectively analyzed, and the risk factors of lymph node metastasis were evaluated. The relationship between preoperative NLR and PLR and the clinical pathology of patients were analyzed, and the effect of these two indexes on lymph node metastasis was predicted through receiver operating characteristic (ROC) curve. RESULTS: Lymph node metastasis correlated with tumor diameter, depth of invasion, Tumor-Node-Metastasis (TNM) stage, preoperative NLR and preoperative PLR (all P<0.05), but not with gender, age and tumor location (all P>0.05). According to the result of multivariate analysis, the degree of differentiation, depth of invasion, TNM staging and NLR were independent risk factors for GC lymph node metastasis. CONCLUSION: The sensitivity and specificity of PLR, tumor staging and tumor size are lower than NLR. Preoperative NLR can be used as an independent risk factor for the prediction of lymph node metastasis, and one of the effective indicators for predicting the prognosis of patients. Preoperative NLR may be an effective auxiliary tool to assess lymph nodes in GC patients.

Avatrombopag for the treatment of thrombocytopenia induced by chemotherapy in patients with solid tumors: A multicenter, open-label, single-arm trial.

Objective: To explore the effect and safety of avatrombopag for chemotherapy-induced thrombocytopenia (CIT). Methods: This multicenter, open-label, single-arm trial enrolled CIT patients in eight centers from October 2020 to April 2021. The participants received avatrombopag tablets 60 mg once a day for 5-10 days. The main endpoint was the proportion of patients with platelet count ≥100×109/L or increased by ≥ 50×109/L or increased by ≥ 100% in the cycle after the start of treatment. Results: Seventy-four participants were enrolled with a mean age of 59.8 ± 11.62.2% were males. The cumulative effective rate (any criteria) was 70.3% at 4 weeks. 42 (56.8%) achieved platelet count ≥100×109/L, 44 (59.5%) increased by ≥ 50×109/L, and 27 (36.5%) increase by ≥ 100% from baseline. The duration of grade III and IV platelet reduction was 4.2 ± 5.3 days. The time of PLT recovery to ≥75×109/L was 9.4 ± 6.6 days. The time of PLT recovery to ≥100×109/L was 10.2 ± 6.4 days. The platelet count nadir was 57.9 ± 45.3×109/L. The most common adverse events were nausea (8.1%), fatigue (5.4%), and abdominal pain (1.4%). There were no cases of fever, headache, or peripheral edema. Conclusion: Although it was a single-arm trial without a control group, the application of avatrombopag in patients with CIT can increase the platelet count of the patients compared with baseline. Avatrombopag is safe and tolerable. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04609891?term=04609891&draw=2&rank=1, identifier [NCT04609891].

Suppression of AGTR1 Induces Cellular Senescence in Hepatocellular Carcinoma Through Inactivating ERK Signaling.

Objective: Cellular senescence is an effective barrier against tumorigenesis. Hence, it is of significance to characterize key features of cellular senescence and the induction of senescence in hepatocellular carcinoma (HCC) cells via pharmacological interventions. Our study determined the biological roles as well as mechanisms of angiotensin II type I receptor (AGTR1) on cellular senescence in HCC. Methods: Lentivirus vector-mediated overexpression or knockdown of AGTR1 was conducted in HCC cells, respectively. A volume of 8 µM sorafenib was used to induce cellular senescence, and ERK was activated by 30 ng/ml ERK agonist EGF. Proliferation was evaluated via clone formation assay. HCC cell senescence was examined by flow cytometry for cell cycle, senescence-associated ß-galactosidase (SA-ß-gal) staining, and senescence-associated heterochromatin foci (SAHF) analysis. AGTR1, p53, p21, extracellular signal-regulated kinase (ERK), and p-ERK expression were assessed through Western blot or immunofluorescence. Results: AGTR1-knockout HCC cells displayed the attenuated proliferative capacity, G2-M phase arrest, increased expression of p53 and p21, and elevated percentages of SA-ß-gal- and SAHF-positive cells. In sorafenib-exposed HCC cells, overexpressed AGTR1 enhanced the proliferative capacity and alleviated G2-M phase arrest as well as decreased p53 and p21 expression and the proportions of SA-ß-gal- and SAHF-positive cells. Moreover, AGTR1 knockdown attenuated the activity of p-ERK in HCC cells, and ERK agonist ameliorated AGTR1 knockdown-induced cellular senescence. Conclusion: This study demonstrates that suppression of AGTR1 induces cellular senescence in HCC through inactivating ERK signaling. The significant synergistic effect of AGTR1 suppression and sorafenib might represent a potential combination therapy for HCC.

Constructing novel molecular subtypes and an 11-gene signature based on pyroptosis signaling for lung adenocarcinoma.

Pyroptosis plays important roles in various cancers. In this study, we focused on lung adenocarcinoma (LUAD) and aimed to develop new molecular subtypes based on pyroptosis signaling. Pyroptosis-related genes were used as a basis to classify molecular subtypes through unsupervised consensus clustering. Gene set enrichment analysis was performed to characterize tumor microenvironment (TME) and functional pathways. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify prognostic genes for establishing a prognostic model. Three molecular subtypes were established with distinct overall survival, TME and enriched pathways. C3 subtype had the longest survival and the highest immune infiltration. 11 prognostic genes were screened to build a prognostic signature for predicting LUAD prognosis. This study emphasized the important role of pyroptosis in LUAD development. Pyroptosis was considered to play critical roles in regulating TME. Moreover, the 11-gene signature could serve as an indicator for predicting LUAD prognosis, and was potential targets for developing targeted drugs.

Evaluation of Tissue Stiffness Around Lesions by Sound Touch Shear Wave Elastography in Breast Malignancy Diagnosis.

The aim of the study described here was to assess the evaluation of tissue stiffness around lesions by sound touch shear wave elastography (STE) in breast malignancy diagnosis. This was an institutional ethics committee-approved, single-center study. A total of 90 women with breast masses examined with conventional ultrasound and STE were eligible for enrollment from December 2020 to July 2021. The maximum and mean elastic values of masses, Emax and Emean, were determined. Shell function was used to measure the maximum and mean elastic values of tissues around masses in annular shells 0.5, 1.0, 1.5 and 2.0 mm wide, recorded as corresponding Emax-shell and Emean-shell. All parameters were analyzed and compared with histopathologic results. Receiver operating characteristic curves were constructed to assess diagnostic performance. Logistic regression analysis was conducted to determine the best diagnostic model. Collagen fiber content of tissues around breast lesions was evaluated using Masson staining and ImageJ software. Ninety women with breast masses were included in this study; 50 had benign (mean diameter 15.84 ± 4.39 mm) and 40 had malignant (mean diameter 17.40 ± 5.42 mm) masses. The diagnostic value of Emax-shell-2.0 was the highest (area under the curve = 0.930) with a sensitivity of 87.5% and specificity of 88%. According to stepwise logistic regression analysis, Emax-shell-2.0 and age were independent predictors of malignancy. Emax-shell-2.0 was also found to be highly correlated with the collagen fiber content of tissue in the malignant group (r = 0.877). Tissue stiffness around lesions measured by STE is a useful metric in identifying malignant breast masses by reflecting collagen fiber content, and Emax-shell-2.0 performs best.

Tumor-associated fibroblasts derived exosomes induce the proliferation and cisplatin resistance in esophageal squamous cell carcinoma cells through RIG-I/IFN-ß signaling.

Esophageal squamous cell carcinoma (ESCC) is a common type of malignant cancer. There is growing evidence suggesting that exosomes may participate in the cellular communication of tumor-associated fibroblasts (TAFs). However, the cisplatin resistance of TAF-derived exosomes to ESCC cells remains to be further studied. Exosomes were isolated from TAFs and characterized with Western blot and TEM assays. ESCC cell lines (TE-1 and KYSE-150) were incubated with TAFs-derived exosomes. To explore the biological function of TAF-derived exosomes in ESCC cell proliferation, apoptosis, and chemosensitivity, we conducted MTT assays and Flow Cytometry. The effects in vivo were also verified via Xenograft mice models. We found that TAFs-derived exosomes led to enhanced cell proliferation and reduced apoptosis of cells, accompanied by increased expression of RIG-I/IFN-ß, and TAFs derived exosomes may affect the chemosensitivity to cisplatin via RIG-I/IFN-ß signaling in ESCC. Taken together, ESCC cells could communicate with TAFs cells via TAFs-derived exosomes. Our findings might represent a novel mechanism involved in ESCC and may provide a potential biomarker for ESCC.

Evaluation of Ultrasound Elastography Combined With Chi-Square Automatic Interactive Detector in Reducing Unnecessary Fine-Needle Aspiration on TIRADS 4 Thyroid Nodules.

BACKGROUND: Conventional ultrasound diagnosis of thyroid nodules (TNs) had a high false-positive rate, resulting in many unnecessary fine-needle aspirations (FNAs). OBJECTIVE: This study aimed to establish a simple algorithm to reduce unnecessary FNA on TIRADS 4 TNs using different quantitative parameters of ultrasonic elasticity and chi-square automatic interactive detector (CHAID) method. METHODS: From January 2020 to May 2021, 432 TNs were included in the study, which were confirmed by FNA or surgical pathology. Each TN was examined using conventional ultrasound, sound touch elastography, and Shell measurement function. The quantitative parameters E and E shell were recorded, and the E shell/E values were calculated for each TN. The diagnostic performance of the quantitative parameters was evaluated using the receiver operating characteristic curves. The CHAID was used to classify and analyze the quantitative parameters, and the prediction model was established. RESULTS: A total of 226 TNs were malignant and 206 were benign. E shell and E shell/E ratio were included in the classification algorithm, which showed a depth of two ramifications (E shell/E ≤ 0.988 or 0.988-1.043 or >1.043; if E shell/E ≤ 0.988, then E shell ≤ 64.0 or 64.0-74.0 or >74.0; if E shell/E = 0.988-1.043, then E shell ≤ 66.0 or > 66.0; if E shell/E >1.043, then E shell ≤ 69.0 or >69.0). The unnecessary FNAs could have been avoided in 57.3% of the cases using this algorithm. CONCLUSION: The prediction model using quantitative parameters had high diagnostic performance; it could quickly distinguish benign lesions and avoid subjective influence to some extent.

Hsa_circ_0007142 contributes to cisplatin resistance in esophageal squamous cell carcinoma via miR-494-3p/LASP1 axis.

BACKGROUND: Chemoresistance is one of the major obstacles for tumor treatment. Circular RNAs (circRNAs) have been confirmed to play vital roles in chemoresistance of cancer, including esophageal squamous cell carcinoma (ESCC). We investigated the roles and mechanisms of circ_0007142 in cisplatin (DDP) resistance of ESCC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the levels of circ_0007142, DOCK1 mRNA, microRNA-494-3p (miR-494-3p) and LIM And SH3 Protein 1 (LASP1) mRNA. RNase R assay was conducted to analyze the characteristic of circ_0007142. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate IC50 of DDP. Flow cytometry analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay and transwell assay were carried out to examine cell apoptosis, proliferation and invasion, respectively. Dual-luciferase reporter assay was employed to verify the association between miR-494-3p and circ_0007142 or LASP1. Murine xenograft assay was conducted to investigate the role of circ_0007142 in DDP resistant in vivo. The protein level of LASP1 in tumors was measured by Immunohistochemistry (IHC) analysis. RESULTS: Circ_0007142 was upregulated in DDP-resistant ESCC tissues and cells. Circ_0007142 knockdown improved DDP sensitivity, induced cell apoptosis and hampered cell proliferation and invasion in DDP-resistant ESCC cells. Circ_0007142 functioned as the sponge for miR-494-3p and miR-494-3p inhibition reversed the impacts of circ_0007142 knockdown on DDP resistance, cell apoptosis, proliferation, and invasion. LASP1 was a target of miR-494-3p, and the effects on DDP resistance, cell apoptosis, growth, and invasion mediated by LASP1 downregulation were rescued by miR-494-3p inhibition. Moreover, circ_0007142 knockdown enhanced DDP sensitivity in vivo. CONCLUSION: Circ_0007142 improved DDP resistance of ESCC by upregulating LASP1 via sponging miR-494-3p.

The Hu antigen R/interferon-ß axis modulates sensitivity of esophageal squamous cancer cells to cisplatin.

The incidence rate of esophageal squamous cell carcinoma (ESCC) has risen significantly in recent years. RNA binding protein (RBP) has been attracting increased attention in the treatment of ESCC. Therefore, the primary aim of this study was to explore the roles of the RBP Hu antigen R (HuR) in ESCC. The mRNA levels were detected via reverse transcription-quantitative PCR, while the expression levels of protein were evaluated using western blotting. Cell proliferation was estimated by cell counting kit-8 assay and colony formation assay. Flow cytometry was applied to measure cell apoptosis. Luciferase assay and RIP assay were applied to verify whether interferon-ß (IFN-ß) was targeted by HuR. The results unambiguously demonstrated that HuR was upregulated in ESCC. Overexpression of HuR alleviated chemosensitivity to cisplatin in ESCC cells, as evidenced by increased cell proliferation and decreased apoptosis. Moreover, IFN-ß was found to be a target of HuR and downregulated in ESCC cells. And overexpression of IFN-ß abrogated the effects of HuR on cisplatin-sensitivity of ESCC cells. Taken together, these findings suggested that HuR may alleviate the chemosensitivity of ESCC cells to cisplatin via binding to IFN-ß. Therefore, the HuR/IFN-ß axis may be a novel biomarker for improving the chemosensitivity of ESCC.

Novel core-shell sulfidated nano-Fe(0) particles for chromate sequestration: Promoted electron transfer and Fe(II) production.

Sulfidated nanoscale valent iron in form of FeS/Fe (0) shell-core nanoparticle has the aptitude to be a promising remediation material toward reductive removal of metal oxyanions. However, disrupted contact between Fe (0) core and FeS shell by thick iron oxides limited its reactivity improvement, and its mechanism of electron transfer remains unveiled. In this study, a novel sulfidated nZVI core-shell particles (FeS/Fe (0)) was fabricated via a modified post sulfidation approach to achieve a more uniform coverage of FeS for aqueous Cr(VI) sequestration. SEM and STEM tests confirmed the formation of the core-shell FeS/Fe (0) structure with a more solid interaction between FeS layer and Fe (0) core. The highest Cr(VI) removal rate was offered at optimal S/Fe molar ratio of 1/25 that the most chelated Fe2+ was also observed. The improved performance was due to that FeS shell with greater electronegativity could significantly accelerate the corrosion of Fe (0), facilitate the electron transfer form Fe (0) core to FeS shell according to the electrochemical tests. Moreover, FeS shell provided a protective layer for Fe (0) core so as to alleviate its anoxic passivation in water that FeS/Fe (0) had a better longevity for Cr(VI) removal than nFe (0). Characterizations of STEM and XPS revealed that Cr(VI) was reduced to Cr(III) and evenly coprecipitated with surface Fe(II)/Fe(III).

Exosomal miR-92b-3p Promotes Chemoresistance of Small Cell Lung Cancer Through the PTEN/AKT Pathway.

Resistance to first-line chemotherapy drugs has become an obstacle to improving the clinical prognosis of patients with small cell lung cancer (SCLC). Exosomal microRNAs have been shown to play pro- and anti-chemoresistant roles in various cancers, but their role in SCLC chemoresistance has never been explored. In this study, we observed that the expression of exosomal miR-92b-3p was significantly increased in patients who developed chemoresistance. Luciferase reporter analysis confirmed that PTEN was a target gene of miR-92b-3p. The PTEN/AKT regulatory network was related to miR-92b-3p-mediated cell migration and chemoresistance in vitro and in vivo in SCLC. Importantly, exosomes isolated from the conditioned medium of SBC-3 cells overexpressing miR-92b-3p could promote SCLC chemoresistance and cell migration. Furthermore, we found that plasma miR-92b-3p levels were significantly higher in patients with chemoresistant SCLC than in those with chemosensitive SCLC, but the levels were down-regulated in patients who achieved remission. Kaplan-Meier analysis showed that SCLC patients with high miR-92b-3p expression were associated with shorter progression-free survival. Overall, our results suggested that exosomal miR-92b-3p is a potential dynamic biomarker to monitor chemoresistance in SCLC and represents a promising therapeutic target for chemoresistant SCLC.

Long Noncoding RNA LINC00857 Promotes Proliferation, Migration, and Invasion of Colorectal Cancer Cell through miR-1306/Vimentin Axis.

Colorectal cancer is a commonly diagnosed cancer and the leading cause of cancer-related death which still increasing in many countries. The lack of biomarkers for early detection and clinic treatment results in high morbidity and mortality. The novel role of long noncoding RNA LINC00857 on cell proliferation migration and invasion was explored in this article. The expression level of LINC00857 in colorectal cancer tissue samples and cells was determined notably higher than normal tissue samples and cells. Silence LINC00857 can significantly inhibit colorectal cancer cell viability and metastasis in vitro. Moreover, LINC00857 depletion caused cell accumulation in the G0/G1 phase. In addition, we recognized the novel LINC00857-miR-1306-vimentin axis and demonstrated it by dual-luciferase reporter assay. And this signaling axis could be considered as the target for colorectal cancer treatment. In conclusion, LINC00857 can promote colorectal cancer progress by sponging miR-1306 and upregulate vimentin to accelerate the epithelial-mesenchymal transition process.