Lipopolysaccharide promotes cancer cell migration and invasion through METTL3/PI3K/AKT signaling in human cholangiocarcinoma.

Purpose: As a major structural component of the outer membrane of Gram-negative bacteria, lipopolysaccharide (LPS) has been detected in the blood circulation and tissues in patients with chronic diseases and cancers, which plays a critical role in the tumor formation and progression. However, the biological role of LPS in human intrahepatic cholangiocarcinoma remains unclear. The aims of this study were to investigate the role of LPS in the malignant progression of intrahepatic cholangiocarcinoma. Methods: The cell migration and invasion capacities of cholangiocarcinoma cell lines were evaluated by Boyden chamber assays. Expression levels of the key molecules involved in the PI3K/AKT signaling and METTL3 were detected by qPCR and western blot. The molecular mechanism by which LPS promotes the malignant behaviors was investigated by using siRNAs, plasmids and small molecule inhibitors. Results: In vitro experiments showed that exogenous LPS treatment promoted cell migration and invasion capacities in both QBC939 and HUCCT1 cell lines, while did not affect cell proliferation and apoptosis. Mechanistically, exogenous LPS treatment had been proved to induce the increased expression of METTL3 and activate the downstream PI3K/AKTsignaling pathway. In addition, suppression of METTL3 expression reduced cell proliferation, migration and invasion capacities in both cell lines. Furthermore, inhibition of METTL3 expression or inhibition of PI3K/AKT signaling decreased LPS-induced cell migration and invasion capacities. Moreover, knockdown of METTL3 or inhibition of METTL3 significantly inhibited LPS-induced activation of the PI3K/AKT signaling. Conclusion: In general, these results suggest that the LPS-METTL3-PI3K/AKT signal axis promotes cell migration and invasion in ICC, which contributes to a reduced overall survival in patients with ICC. It may broaden the horizon of cancer therapy with potential therapeutic targets.

An adaptive enhancement method for breast X-ray images based on the nonsubsampled contourlet transform domain and whale optimization algorithm.

We propose a new method for breast X-ray image adaptive enhancement that combines nonsubsampled contourlet transform (NSCT) with the whale optimization algorithm (WOA). First, the mammography X-ray image was processed by histogram equalization to ensure global image contrast. The processed image was then decomposed into three layers in the NSCT domain. Each layer was each decomposed into two, four, and eight directions. A median filter was used to remove noise in the first and second layers. Then, a special edge filter was adopted to enhance each sub-band image, and two parameters are involved. WOA is used to automatically search the optimal two parameters. Blind image quality index (BIQI) adaptive function was used as an objective function of WOA. Then, inverse NSCT was employed to reconstruct the processed image, generating the final adaptive enhancement image. The digital database for screening mammography (DDSM) was used to verify the performance of the proposed method. Five objective evaluation indexes, including information entropy, average gradient, standard deviation, contrast improvement index (CII), and BIQI, are combined together to construct a new comprehensive index to evaluate the visual quality of the enhanced image. The results show that the proposed method has a good enhancement effect for mammography X-ray images. The overall performance of the proposed method is better than some existing similar methods. Graphical abstract .

[Comparison of early clinical effects between Activ C cervical disc replacement and anterior cervical discectomy and fusion for single-level cervical spondylosis].

OBJECTIVE: To compare the early clinical effects of Activ C cervical disc replacement (ACDR) and anterior cervical discectomy and fusion (ACDF) in treating single-level cervical spondylosis. METHODS: The clinical data of 76 patients with single-level cervical spondylosis underwent surgery from July 2009 to September 2012 were retrospectively analyzed. Among them, 28 patients were treated with ACDR (ACDR group), including 18 males and 10 females, aged from 32 to 62 years old with an average of (45.2±6.2) years; and 48 patients were treated with ACDF (ACDF group), including 28 males and 20 females, aged from 33 to 60 years old with an average of (45.8±6.4) years. Visual analogue scale (VAS), Japanese Orthopedics Association (JOA) score, Short Form-36 (SF-36), imaging data were used to assess the clinical effects after operation. RESULTS: A total of 76 patients were followed up from 6 to 24 months with an average of 13.2 months. VAS of neck pain and brachialgia were improved in all patients after operation (P<0.05), there was no significant difference between two group (P>0.05). Somato-score and psycho-score of SF-36 of two groups were obviously increased (P<0.05), ACDR group was better than that of ACDF group (P<0.05). In ACDR group, there was no significant difference in the range of motion of surgical segments and adjacent segments between preoperative and postoperative (P>0.05); heterotopic ossification around the edge of vertebral body occurred in 1 case on the 6th month after operation, no fusion was found on the 1st year after operation. In ACDF group, the adjacent vertebral disease occurred in 1 case and the patient underwent the reoperation. CONCLUSION: Activ C cervical disc replacement can reduce the degeneration of adjacent segments and its early outcomes for the treatment of single-level cervical spondylosis are satisfactory, but the long-term effects still need study.

[Positive selection analysis of hepatitis C virus genotype 1b envelope 2 gene and its significance during natural chronic infection].

AIM: To elucidate adaptive evolution patterns and perform a positive selection analysis of hepatitis C virus(HCV) genotype 1b envelope 2 gene(E2) during natural chronic infection by a longitudinal study. METHODS: HCV E2 quasispecies profiles were derived from partially sequenced domains of 6 000 bp recombinant clones. Phylogenetic trees for HCV E2 gene were constructed by MEGA software and the specific codons undergoing diversifying positive selection were identified by FEL method. RESULTS: HCV phylogenies, coupled with the number and distribution of selected sites were differed markedly between patients. HCV quasispecies complexity during chronic infection was not associated with the evolutionary time and the dominant viriant alternation of HCV quasispecies may occur after more than six months apart. Five sites under positive selection were identified within the ectodomain of the E2 protein. CONCLUSION: A series of serum specimens for studies based on dominant viriant of HCV dynamic quasispecies is recommended to be collected at every six months. Several individual sites of HCV E2 gene are under a strong host immune pressure, position aa384, aa399 and aa410 may be involved in escape from neutralizing antibodies, while position aa475, aa522 may correlate to modulate the virus-receptor interaction which result in evading immunity.