CHES1 modulated tumorigenesis and senescence of pancreas cancer cells through repressing AKR1B10.

Pancreatic ductal adenocarcinoma (PDAC), is characteristic by a heterogeneous tumor microenvironment and gene mutations, conveys a dismal prognosis and low response to chemotherapy and immunotherapy. Here, we found that checkpoint suppressor 1 (CHES1) served as a tumor repressor in PDAC and was associated with patient prognosis. Functional experiments indicated that CHES1 suppressed the proliferation and invasion of PDAC by modulating cellular senescence. To further identify the downstream factor of CHES1 in PDAC, label-free quantitative proteomics analysis was conducted, which showed that the oncogenic Aldo-keto reductase 1B10 (AKR1B10) was transcriptionally repressed by CHES1 in PDAC. And AKR1B10 facilitated the malignant activity and repressed senescent phenotype of PDAC cells. Moreover, pharmaceutical inhibition of AKR1B10 with Oleanolic acid (OA) significantly induced tumor regression and sensitized PDAC cells to gemcitabine, and this combined therapy did not cause obvious side effects. Rescued experiments revealed that CHES1 regulated the tumorigenesis and gemcitabine sensitivity through AKR1B10-mediated senescence in PDAC. In summary, this study revealed that the CHES1/AKR1B10 axis modulated the progression and cellular senescence in PDAC, which might provide revenues for drug-targeting and senescence-inducing therapies for PDAC.

Enhanced biodegradation activity toward polyethylene by fusion protein of anchor peptide and Streptomyces sp. strain K30 latex clearing protein.

Polyethylene is the most commonly used plastic product, and its biodegradation is a worldwide problem. Latex clearing protein derived from Streptomyces sp. strain K30 (LcpK30) has been reported to be able to break the carbon-carbon double bond inside oxidized polyethylene and is an effective biodegradation enzyme for polyethylene. However, the binding of the substrate to the enzyme was difficult due to the hydrophobic nature of polyethylene. Therefore, to further improve the efficiency of LcpK30, the effect of different anchor peptides on the binding capacity of LcpK30 to the substrate was screened in this study. The results of fluorescence confocal microscopy showed that the anchoring peptide LCI had the most significant improvement in effect and was finally selected for further application in a UV-irradiated PE degradation system. The degradation results showed that LCI was able to improve the degradation efficiency of LcpK30 by approximately 1.15 times in the presence of equimolar amounts of protein compared with wild-type. This study further improves the application of LcpK30 in the field of polyethylene degradation by modification.

Acetylation of Checkpoint suppressor 1 enhances its stability and promotes the progression of triple-negative breast cancer.

Checkpoint suppressor 1 (CHES1), a transcriptional regulator, had been dysregulated in many types of malignancies including breast cancer, and its expression level is strongly associated with progression and prognosis of patients. However, the underlying regulatory mechanisms of CHES1 expression in the breast cancer and the effects of post-translational modifications (PTMs) on its functional performance remain to be fully investigated. Herein, we found that CHES1 had a high abundance in triple-negative breast cancer (TNBC) and its expression was tightly associated with malignant phenotype and poor outcomes of patients. Furthermore, we confirmed that CHES1 was an acetylated protein and its dynamic modification was mediated by p300 and HDAC1, and CHES1 acetylation enhanced its stability via decreasing its ubiquitination and degradation, which resulted in the high abundance of CHES1 in TNBC. RNA-seq and functional study revealed that CHES1 facilitated the activation of oncogenic genes and pathways leading to proliferation and metastasis of TNBC. Taken together, this research established a novel regulatory role of acetylation on the stability and activity of CHES1. The results demonstrate the significance of CHES1 acetylation and underlying mechanisms in the progression of TNBC, offering new potential candidate for molecular-targeted therapy in breast cancer.

Degradation of UV-pretreated polyolefins by latex clearing protein from Streptomyces sp. Strain K30.

Plastic products made of polyethylene (PE), polypropylene (PP), and polystyrene (PS) are widely used in daily life and industrial production. Polyolefins-which have a very stable structure and do not contain any active molecular groups-are difficult to degrade and pose a serious global environment threat. This study selected latex clearing protein (LcpK30) derived from Streptomyces sp. Strain K30. The natural substrate of the enzyme is rubber (cis-1, 4-polyisoprene), and the site of action is the carbon­carbon double bond. LcpK30 was incubated with UV-irradiated polyolefin PE, PP and PS (UV-PE, UV-PP, and UV-PS containing carbon­carbon double bonds) for 5 d at 37 °C. The results showed that UV-PE-LcpK30 was more fragmented than UV-PE-blank; the Fourier transform infrared spectroscopy results showed that UV-PE-LcpK30 and UV-PP-LcpK30 produced new active groups (e.g., -OH and -C=O); however, the effect on UV-PS was not significant. Scanning electron microscopy results showed that the treated group had more obvious roughness, cracks, and pits than the control group. The results of high-temperature gel permeation chromatography showed that the average molecular weight (Mw) of UV-PE-LcpK30 and UV-PP-LcpK30 decreased; the Mw of UV-PE5-LcpK30 was reduced by 42.02%. The results of gas chromatography-mass spectrometry showed the production of ketones. Therefore, the LcpK30 latex clearing protein degrade UV-oxidized polyolefin plastics and has great potential for PE and PP degradation but may not be suitable for PS. Furthermore, other Lcps (such as LcpNRRL, LcpNVL3) can also degrade UV-PE.

Comparison of diffusion-weighted imaging mono-exponential mode with diffusion kurtosis imaging for predicting pathological grades of clear cell renal cell carcinoma.

PURPOSE: To evaluate the role of diffusion kurtosis imaging (DKI1) in the characterization of clear cell renal cell carcinoma (ccRCC2) compared with standard diffusion-weighted imaging (DWI3). METHODS: 89 patients with histologically proven ccRCC were evaluated by DKI and DWI on a 3-T scanner. All ccRCCs were classified as grade 1-4 according to the Fuhrman classification system. The apparent diffusion coefficient (ADC4), fractional anisotropy (FA5), mean diffusivity (MD6), mean kurtosis (MK7), axial kurtosis (Ka8) and radial kurtosis (Kr9) values were recorded. The differences in DWI and DKI parameters were evaluated by independent-sample t test and a receiver operating characteristic (ROC10) analysis was performed. The DeLong test was performed to compare the ROCs. RESULTS: Compared to normal renal parenchyma, ADC and MD values of ccRCC decreased and MK, Ka, and Kr values increased (p < 0.05). ADC and MD values of ccRCC decreased with the increase in pathological grade, while MK, Ka, and Kr values were increased (p < 0.05). ADC could discriminate G1 vs G3, G1 vs G4, G2 vs G3, G2 vs G4, and G3 vs G4 (p < 0.05) except for G1 vs G2 (p > 0.05). Ka and Kr could discriminate G1 vs G2, G1 vs G3, G1 vs G4, G2 vs G4, and G3 vs G4 (p < 0.05) except for G2 vs G3 (p > 0.05). MD and MK could discriminate G1 vs G2, G1 vs G3, G1 vs G4, G2 vs G3, G2 vs G4, and G3 vs G4 (p < 0.05). The AUC of MK was the highest. The DeLong test showed that there were significant differences regarding ROCs between ADC/MK, ADC/Ka, ADC/Kr in grading G1/G2, and ADC/MK, MK/Ka in grading G3/G4 (p < 0.05). CONCLUSION: DKI was superior compared to the mono-exponential mode of DWI in grading ccRCC.

MicroRNA-15a Inhibits Proliferation and Induces Apoptosis in CNE1 Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a highly metastatic cancer, frequently occurring in Southeast Asia and Southern China. Several microRNAs (miRNAs) have been shown to have an inhibitive effect on NPC, while the effect of miR-15a on NPC remains unclear. Thus, our study aimed to investigate the potential effect of miR-15a on NPC cell proliferation, apoptosis, and possible functional mechanism. Human NPC CNE1 cells were transfected with miR-15a mimics, miR-15a inhibitors, or a control. Afterward, cell viability and apoptosis were assayed by using CCK-8, BrdU assay, and flow cytometry. Moreover, Western blot was used to detect the expression changes of proliferation and apoptosis of related proteins. As a result, miR-15a overexpression significantly reduced cell proliferation (p < 0.01 or p < 0.001) and induced cell apoptosis (p < 0.001), while miR-15a suppression got the opposite result for cell proliferation and apoptosis. In addition, miR-15a overexpression upregulated the protein levels of p27, GSK-3ß, Bax, procaspase 3, and active caspase 3, whereas miR-15a suppression downregulated these proteins. The protein level of p21 was not significantly regulated by miR-15a overexpression or suppression. These results indicated that miR-15a played a role for inhibition of proliferation and induction of apoptosis in CNE1 cells.

[Cervical vestibular evoked myogenic potential elicited by different types air conducted sounds among normal young Chinese people].

OBJECTIVE: To observe waveform difference among cervical vestibular evoked myogenic potentials (cVEMP) elicited with different types of air conducted sound in normal young Chinese subjects. METHOD: Twenty adult volunteers (40 ears) were recruited as research subjects including 10 males and 10 females aged between 19 and 30.500 Hz Tone Burst, 1000 Hz Tone Burst and Click were employed as stimulus for conventional air conducted sound-cVEMP (ACS-cVEMP) examinations in bilateral ears of each subject. The response rate, threshold, P1 latency, N1 latency, P1-N1 latency interval, amplitude and inter-aural asymmetry were recorded and compared among groups. RESULT: The response rate was 97.5% in 500Hz Tone Burst (39/40), 87.5% in 1 000Hz Tone Burst (35/40)and 67.5% in Click (27/40), There were no statistically significant difference between 500Hz Tone Burst and 1000Hz Tone Burst (P > 0.05) but there were statistically significant difference between click and the other groups (P < 0.05). We collected the waveform parameters (the threshold, P1 latency, N1 latency, P1-N1 latency interval, amplitude) which had statistically significant difference between 500 Hz Tone Burst and the other groups (P < 0.05). The inter-aural asymmetrys had no statistically significant differents among groups. CONCLUSION: The response rate and parameter could be affected by different types of air conducted sound in normal young Chinese subjects. 500 Hz Tone Burst was the best stimulus of type what we have known.

Polysaccharide of Boschniakia rossica induces apoptosis on laryngeal carcinoma Hep2 cells.

The aim of this study was to explore the anti-tumor potential of a polysaccharide isolated from Boschniakia rossica (BRP) in Hep2 human larynx squamous carcinoma cells. High performance size-exclusion chromatography analysis showed that BRP was a homogeneous polysaccharide and had a molecular weight of 22 kDa. Total carbohydrate content in BRP was determined to be 96.9%, without the presence of protein and nucleic acid. BRP suppressed the proliferation of Hep2 cells in a time- and dose-dependent manner. Cell cycle analysis revealed that exposure to BRP (200 µg/ml) caused a G0/G1 cell cycle arrest in Hep2 cells. Moreover, treatment with BRP at 100-400 µg/ml for 24h induced a significant apoptosis Hep2 cells compared to untreated control cells, as determined by flow cytometry with annexin-V/propidium iodide double staining. Additionally, BRP treatment promoted the cleavage of pro-caspase-3, pro-caspase-8, and pro-caspase-9, coupled with increased expression of death receptor DR5 and Bax and reduced expression of Bcl-2. Taken together, our data demonstrate that BRP shows potent anti-tumor activity in human larynx squamous carcinoma, largely through induction of G0/G1 cell cycle arrest and apoptosis. Activation of both mitochondria-mediated and death receptor-mediated apoptosis pathways is involved in the cytotoxicity of BRP.