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Background The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582m) were determined by quantitative methylation-specific polymerase chain reaction (qMSP) and expressed in ΔCp. Receiver operating characteristic curves were used to evaluate predictive accuracy. Results The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high-grade squamous intraepithelial lesion (HSIL), and 39 (14.08%) were squamous cervical cancer (SCC). PAX1m and ZNF582m increased as lesions progressed from inflammation/LSIL, HSIL, to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared with common screening strategies, whether individually or combined. A 4.33-fold increase in the probability of inflammation/LSIL was observed in patients with lower ZNF582 methylation levels (ΔCpZNF582 ≥ 19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582 < 7.09). Conclusions DNA methylation would be an alternative screening method to triage and predict the final outcome of conization in CIN3 cases. [ABSTRACT FROM AUTHOR]

Background/Aims: In a recent study, attenuation imaging (ATI) with ultrasound was used as a new approach for detecting liver steatosis. However, although there are many studies on ATI and controlled attenuation parameter (CAP) that prove their practicability, there are few studies comparing these two methods. As such, this study compared CAP and ATI for the detection and evaluation of liver steatosis. Methods: A prospective analysis of 28 chronic liver disease patients who underwent liver biopsy, FibroScan® imaging, and ATI with ultrasound was conducted. The presence and degree of steatosis, as measured with the FibroScan® device and ATI, were compared with the pathological results obtained using liver biopsy. Results: The areas under the receiver operating characteristic curve (AUROC) of ATI and CAP for differentiating between normal and hepatic steatosis were 0.97 (95% confidence interval [CI] 0.83–1.00) and 0.96 (95% CI 0.81–0.99), respectively. ATI has a higher AUROC than CAP does in liver steatosis, at 0.99 (95% CI, 0.86–1.00) versus 0.91 (95% CI, 0.74–0.98) in grade ≥ 2 and 0.97 (95% CI, 0.82–1.00) versus 0.88 (95% CI, 0.70–0.97) in grade = 3, respectively. Conclusion: The ATI and CAP results showed good consistency and accuracy for the steatosis grading when compared with the liver biopsy results. Moreover, ATI is even better than CAP in patients with moderate or severe steatosis. Therefore, ATI represents a non-invasive and novel diagnostic tool with which to support the diagnosis of liver steatosis in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. In this study, we attempted to compare 2‐dimensional (2D) shear wave elastography (SWE), shear wave dispersion (SWD), and attenuation imaging (ATI) with transient elastography (TE) and the controlled attenuation parameter (CAP) in patients under direct‐acting antiviral (DAA) therapy. Methods: Patients with chronic hepatitis C infection undergoing DAA therapy from January 2017 to June 2020 were retrospectively examined. The results of 2D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. Results: A total of 122 patients with a median age of 61 years were investigated; among them, 121 (99.2%) achieved a sustained virologic response at 12 weeks after DAA therapy. Fibrosis 4, the aspartate aminotransferase–to–platelet ratio index, 2D SWE, and TE were reduced after DAA therapy. The CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. Two‐dimensional SWE and TE were strongly correlated (r = 0.885–0.897; P <.001). Albumin and the baseline liver stiffness measurement were independent factors of liver stiffness measurement changes after DAA therapy. Conclusions: Direct‐acting antiviral therapy can significantly decrease liver stiffness (using both 2D SWE and TE) but not SWD and ATI values in patients with hepatitis C. An increased CAP is also observed after DAA therapy. [ABSTRACT FROM AUTHOR]

Homozygous or compound heterozygous mutations of the β-globin gene lead to β-thalassemia (β-thal) major (β-TM) or β-thal intermedia (β-TI), whereas heterozygotes usually show microcytosis with negligible or no hemolysis. Certain missense mutations in exon 3, however, produce unstable globins causing a dominant β-thal phenotype or hemolytic anemia in heterozygotes. Here we report a mutation in exon 3 of the β-globin gene, which results in an unstable globin (Hb Dieppe) [β127(H5)Gln→Arg; HBB: c.383A>G] with a dominant β-thal phenotype in two generations of a Chinese family. Physicians should be alerted to this mechanism of β-thal considering its relative rarity. [ABSTRACT FROM AUTHOR]

To compare the immunogenicity and digestibility in-vitro simulated gastric fluid, the protein extracts of white-leg shrimp, Chinese shrimp (female and male shrimp were separated), Southern rough shrimp,Acetes chinensis, Mantis shrimp and crawfish were analyzed by SDS-PAGE, indirect ELISA and Western blotting. The results showed that except forAcetes chinensis, the larger proportion of molecular mass were near to 25 kDa (sarcoplasmic calcium-binding protein) and 38 kDa (tropomyosin). White-leg shrimp protein and Southern rough shrimp protein had a maximum similarity of 68.2%. White-leg shrimp protein had higher immunogenicity than others. There were much more IgE-binding bands in male Chinese shrimp protein, while Crawfish just had only one IgE-binding band (38 kDa, tropomyosin). In simulated gastric fluid system, the protein such as 25 kDa was rapidly degraded within 0.5 mins, while tropomyosin (38 kDa) was relatively resistant to pepsin digestion. The Western blotting results indicated that the allergenicity of those crustacean protein extracts still remained even they were digested with simulated gastric fluid for 60 min. [ABSTRACT FROM PUBLISHER]

In recent years, ultrasound attenuation imaging (ATI) has emerged as a new method to detect liver steatosis. However, thus far, no studies have confirmed the clinical utility of this technology. Using a retrospective database analysis of 28 patients with chronic liver disease who underwent ultrasound liver biopsy and ATI, we compared the presence and degree of steatosis measured by ATI with the results obtained through liver biopsy. The area under the receiver operating characteristic curve (AUROC) of the ATI for differentiating between normal and hepatic steatosis was 0.97 (95% confidence interval: 0.83–1.00). The AUROC of the ATI was 0.99 (95% confidence interval: 0.86–1.00) in grade ≥2 liver steatosis and 0.97 (95% confidence interval: 0.82–1.00) in grade 3. ATI showed good consistency and accuracy for the steatosis grading of liver biopsy. Therefore, ATI represents a novel diagnostic measurement to support the diagnosis of liver steatosis in non-invasive clinical practice. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. Sunitinib, a multi-targeted tyrosine kinase inhibitor, is known to selectively inhibit several growth factor receptors, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor and stem cell factor. It was reported that a patient with renal cell carcinoma (RCC) whose psoriatic lesion was resolved dramatically during treatment with Sunitinib, however, the mechanism is still unclear. We applied Sunitinib ointment to treat imiquimod-induced mouse model of psoriasis and found that Sunitinib ointment could alleviate imiquimod-induced psoriasis-like inflammation and reduce the Ki67 expression, while Sunitinib ointment couldn’t reduce imiquimod-induced splenomegaly of the mouse model, then we concentrated on studying the effect of Sunitinib on the proliferation and apoptosis of keratinocytes, we cultivated HaCaT cells with epidermal growth factor (HaCaT/E cells) to represent as a state of highly proliferative psoriatic keratinocytes. We found that Sunitinib could inhibit the proliferation of Hacat/E cell in a time and concentration dependent manner by influencing the expression level of cell cycle protein D1, cycle protein E1, in addition, Sunitinib could induce the apoptosis of Hacat/E cell and up-regulate the expression of poly ADP-ribose polymerase (PARP). Sunitinib down-regulated the expression of phosphorylated signal transduction and activator of transcription 3 (p-Stat3) of Hacat/E cells significantly. We conclude that Sunitinib alleviates imiquimod-induced psoriasis-like inflammation by regulating the proliferation and apoptosis of HaCaT cells through inhibiting the expression of p-Stat3. [ABSTRACT FROM AUTHOR]

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment. Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR. Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1β in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells. Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Xiao, Yin, Zhou, Wu, Chen, Luo, Kuang and Zhu.)

Background: Lung cancer is one of the malignancies exhibiting the fastest increase in morbidity and mortality, but the cause is not clearly understood. The goal of this investigation was to screen and identify relevant biomarkers of lung cancer., Methods: Publicly available lung cancer data sets, including GSE40275 and GSE134381, were obtained from the GEO database. The repeatability test for data was done by principal component analysis (PCA), and a GEO2R was performed to screen differentially expressed genes (DEGs), which were all subjected to enrichment analysis. Protein-protein interactions (PPIs), and the significant module and hub genes were identified via Cytoscape. Expression and correlation analysis of hub genes was done, and an overall survival analysis of lung cancer was performed. A receiver operating characteristic (ROC) curve analysis was performed to test the sensitivity and specificity of the identified hub genes for diagnosing lung cancer., Results: The repeatability of the two datasets was good and 115 DEGs and 10 hub genes were identified. Functional analysis revealed that these DEGs were associated with cell adhesion, the extracellular matrix, and calcium ion binding. The DEGs were mainly involved with ECM-receptor interaction, ABC transporters, cell-adhesion molecules, and the p53 signaling pathway. Ten genes including COL1A2, POSTN, DSG2, CDKN2A, COL1A1, KRT19, SLC2A1, SERPINB5, DSC3, and SPP1 were identified as hub genes through module analysis in the PPI network. Lung cancer patients with high expression of COL1A2, POSTN, DSG2, CDKN2A, COL1A1, SLC2A1, SERPINB5, and SPP1 had poorer overall survival times than those with low expression (p <0.05). The CTD database showed that 10 hub genes were closely related to lung cancer. Expression of POSTN, DSG2, CDKN2A, COL1A1, SLC2A1, SERPINB5, and SPP1 was also associated with a diagnosis of lung cancer (p<0.05). ROC analysis showed that SPP1 (AUC = 0.940, p = 0.000*, 95%CI = 0.930-0.973, ODT = 7.004), SLC2A1 (AUC = 0.889, p = 0.000*, 95%CI = 0.791-0.865, ODT = 7.123), CDKN2A (AUC = 0.730, p = 0.000*, 95%CI = 0.465-1.000, ODT = 6.071) were suitable biomarkers., Conclusion: Microarray technology represents an effective method for exploring genetic targets and molecular mechanisms of lung cancer. In addition, the identification of hub genes of lung cancer provides novel research insights for the diagnosis and treatment of lung cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand that activates the extrinsic apoptosis pathway of cell death receptors. This study aimed to evaluate the relationship between TRAIL and platelet-induced tumor metastasis in colorectal cancer., Methods: Platelet P-selectin (CD62P) was measured by immunohistochemistry in tumor and adjacent normal tissues from 90 patients with colorectal cancer undergoing resection. Tumor cell invasion was assessed by transwell assay in the presence of platelets with or without TRAIL. The expression of TRAIL receptors DR4 and DR5 on platelets was assessed by flow cytometry, real-time polymerase chain reaction, and western blotting., Results: P-selectin (CD62P) expression was significantly increased in tumor tissues compared with adjacent normal tissues. High CD62P expression was significantly correlated with tumor stage and vascular invasion. Tumor cell migration was increased by coculture with platelets, but this effect was inhibited by TRAIL. Transforming growth factor (TGF)-β1 secretion was significantly reduced in TRAIL-treated platelets. The TRAIL receptor DR5 but not DR4 was expressed in platelets according to flow cytometry., Conclusions: TRAIL could inhibit metastasis and colon cancer cell invasion by promoting platelet apoptosis and reducing the release of TGF-β1.

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl- L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5- Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

There is a correlation between the multidrug-resistance (MDR) of cancer cells and their enhanced invasive or metastatic potential. We studied the expression of CD147, a plasma membrane glycoprotein that plays a key role in tumor metastasis by stimulating the production of matrix metalloproteinases (MMPs), in sensitive human oral squamous KB and MDR derivative KB/V cells. Reverse transcription-PCR and flow cytometric analysis revealed that KB/V cells expressed CD147 at significantly higher levels than their parental KB cells. Using stable RNA interference, we succeeded in establishing a CD147 knock-down KB/V cell line (KB/VsiCD147). MTT colorimetric assay showed an increase in the chemosensitivity to vincristine (VCR), all transretinoic acid (ATRA), taxol, and 5-fluorouracil (5-Fu) of KB/VsiCD147 cells. Proteome analysis of KB, KB/V, and KB/VsiCD147 cell lines identified 21 differently expressed proteins. The enhanced expression of representative active proteins, GRP75 and CyPA, was confirmed by Western blotting and RT-PCR. In addition, pretreatment of KB/V cells with a CyPA-binding immunosuppressive drug, cyclosporine A (CsA), enhanced their chemosensitivity to VCR and 5-Fu. We document an abundance of molecules that interact with CD147 in the MDR of human oral squamous carcinoma cells. Additional studies are needed to investigate these novel target proteins of CD147.

Objective: To evaluate the effects of amino acids (AA) on the development of in vitro cultured preimplantation embryos of Kunming mice, and define the optimal AA concentration for embryo culture., Methods: Totally 630 zygotes were collected from the oviducts of superovulated female Kunming mice, which were cultured in protein-free potassium simplex optimized medium (mKSOM) supplemented with Eagle's essential amino acids and Eagle's non-essential amino acids of different concentrations (mKSOM, mKSOM+1/16AA, mKSOM+1/8AA, mKSOM+1/4AA, mKSOM+1/2AA, mKSOM+AA, and mKSOM+2AA)., Results: The embryos cultured with the amino acids showed higher development rate to both 8-cell embryo stage and blastocyst stage than those cultured without amino acids. The correlation of amino acid concentration with 8-cell and blastocyst development rates conformed to the cubic model, with the highest development rate to both of the two stages observed at half of the amino acid concentration., Conclusion: Amino acids can promote the development of preimplantation Kunming mouse embryos, but excessively high concentration of amino acids impair embryo development possibly because of metabolic and osmotic pressure changes of the embryos as well as toxicity of ammonium resulting from the metabolism of amino acids.