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Purpose 6-Shogaol, an active phenolic compound from ginger ( Zingiber officinale ), can inhibit the growth of a variety of human cancer cells. Nevertheless, its underlying molecular mechanisms in cervical cancer remain unclear. In this study, we systematically examine the inhibitory effect of 6-shogaol on cervical cancer in vitro and in vivo. Methods Cell proliferation was assessed by CCK8 assay and colony formation assay in HeLa and SiHa cells. We analyzed cell cycle and apoptosis through flow cytometry. GFP-LC3 puncta and transmission electron microscopy were used to observe autophagic bodies. Wound-healing assay and transwell assay were used for evaluating the migration of cells. Western blot was applied to detect protein expression levels. Results 6-Shogaol could suppress cell proliferation and migration, cause cell cycle arrest in the G2/M phase in HeLa and SiHa cells. Moreover, 6-shogaol triggered the apoptosis process through the mitochondrial pathway by downregulating the expression levels of p-PI3K, p-Akt and p-mTOR. Further research indicated that the induction of apoptosis by 6-shogaol was remarkably decreased after the treatment of ROS scavenger and PI3K agonist. Additionally, 6-shogaol increased the number of LC3-positive puncta and autophagic bodies per cell in both HeLa and SiHa cells. Pretreatment of cells with Bafilomycin A1, an autophagy inhibitor, accelerated 6-shogaol mediated cell apoptosis, suggesting that induction of autophagy by 6-shogaol is suppressive to apoptosis. Furthermore, in vivo data revealed that 6-shogaol significantly inhibited tumor growth and cell proliferation in tumor tissues. Conclusion These findings suggested that 6-shogaol could be developed as a functional food ingredient, which is potentially used as therapeutic agents for patients with cervical cancer.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide, and its occurrence and development are intricately associated with the abnormal regulation of various genes and signaling pathways. Exosome Component 3(EXOSC3) is involved in the occurrence and growth of tumors. However, the exact mechanisms by which EXOSC3 influences HCC remain to be elucidated. Bioinformatics analysis method was used to detect the expression of EXOSC3 in HCC, qRT-PCR and Western blot were used to verify EXOSC3 expression in HCC cell lines.CCK-8 and colony formation assay was used to evaluate the effect of EXOSC3 on tumor proliferation, and validate the impact on cell migration and invasion through Transwell and Wound healing assay. Flow cytometry and Hochest staining were used to investigate the effect of EXOSC3 knockdown on the cell cycle and apoptosis of HCC. Western blot method was used to detect proteins expression. In HCC tissues, EXOSC3 mRNA and protein expression levels were notably higher than those in normal liver tissues and these levels correlated with poor prognosis. After knocking down EXOSC3, cell proliferation, colony formation, and metastasis were significantly inhibited in HCC. Flow cytometry and Western blot analyses showed that knockdown EXOSC3 promoted HCC cell apoptosis and inhibited cell cycle progression with reduced G1/S checkpoint protein expression. Furthermore, knockdown EXOSC3 activated P53 and decreased retinoblastoma protein (RB1) phosphorylation, suggesting that EXOSC3 functions via the P53 pathway in HCC. EXOSC3 has potential as a prognostic biomarker in HCC. Knockdown EXOSC3 leads to cell cycle arrest and consequently inhibits the proliferation of liver cancer cells by activating the P53 signaling pathway and concomitantly suppressing the expression of crucial regulatory proteins. These results not only establish EXOSC3 as a clinically relevant prognostic indicator but also highlight its therapeutic potential as a molecular target for HCC intervention strategies.

Oxidative stress plays an important role in the pathogenesis of virus infection and antioxidants are becoming promising candidates as therapeutic agents. This study is designed to investigate the effect of total flavonoids of Spatholobus suberectus Dunn (TFSD) on oxidative stress in mice induced by porcine circovirus type 2 (PCV2) infection. The PCV2 infection leads to significant decrease in thymus and spleen indices, elevation of xanthine oxidase (XOD) and myeloperoxidase (MPO) activities, reduction in GSH level and GSH to GSSG ratio and decline of superoxide dismutase (SOD) activity, indicating the formation of immunosuppression and oxidative stress. TFSD treatment recovered the alteration of viscera index, antioxidant content and activities of oxidative-associated enzymes to a level similar to control. Our findings suggested that PCV2 induced immunosuppression and oxidative stress in mice and TFSD might be able to protect animals from virus infection via regulation of immune function and inhibition of oxidative stress.

Urolithin A (UroA) can inhibit the growth of many human cancer cells, but it has not be reported if UroA inhibits nasopharyngeal carcinoma (NPC) cells. To explore the inhibitory effect of UroA on NPC and potential mechanism in vitro. RNA-sequencing-based mechanistic prediction was conducted by comparing KEGG enrichment of 40 μM UroA-treated for 24 h with untreated CNE2 cells. The untreated cells were selected as control. After NPC cells were treated with 20-60 μM UroA, proliferation, migration and invasion of were measured by colony formation, wound healing and transwell experiments. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) were measured by flow cytometry, Hoechst 33342, Rhodamine 123, JC-1 staining and ROS assay methods, respectively. Gene and protein expression were measured by RT-qPCR and Western blotting assay. RNA-sequencing and KEGG enrichment revealed UroA mainly altered the ECM receptor interaction pathway. UroA inhibited cells proliferation, epithelial-mesenchymal-transition pathway, migration and invasion with IC 50 values of 34.72 μM and 44.91 μM, induced apoptosis, MMP depolarization and increase ROS content at a concentration of 40 μM. UroA up-regulated E-cadherin, Bax/Bcl-2, c-caspase-3 and PARP proteins, while inhibiting COL4A1, MMP2, MMP9, N-cadherin, Vimentin and Snail proteins at 20-60 μM. Moreover, co-treatment of UroA (40 μM) and NAC (5 mM) could reverse the effect of UroA on apoptosis-related proteins. RNA-sequencing technology based on bioinformatic analyses may be applicable for studiying the mechanism of drugs for tumour treatment.

Background Hepatocellular carcinoma (HCC) is a common malignant tumor. There are few studies on EXOSC10 (exosome component 10) in HCC; however, the importance of EXOSC10 for HCC remains unclear. Methods In the study, the prognosis value of EXOSC10 and the immune correlation were explored by bioinformatics. The expression of EXOSC10 was verified by tissue samples from clinical patients and in vitro experiment (liver cancer cell lines HepG2, MHCC97H and Huh-7; normal human liver cell line LO2). Immunohistochemistry (IHC) was used to detect EXOSC10 protein expression in clinical tissue from HCC. Huh-7 cells with siEXOSC10 were constructed using lipofectamine 3000. Cell counting kit 8 (CCK-8) and colony formation were used to test cell proliferation. The wound healing and transwell were used to analyze the cell migration capacity. Mitochondrial membrane potential, Hoechst 33342 dye, and flow cytometer were used to detect the change in cell apoptosis, respectively. Differential expression genes (DEGs) analysis and gene set enrichment analysis (GSEA) were used to investigate the potential mechanism of EXOSC10 and were verified by western blotting. Results EXOSC10 was highly expressed in tissues from patients with HCC and was an independent prognostic factor for overall survival (OS) in HCC. Increased expression of EXOSC10 was significantly related to histological grade, T stage, and pathological stage. Multivariate analysis indicated that the high expression level of EXOSC10 was correlated with poor overall survival (OS) in HCC. GO and GSEA analysis showed enrichment of the cell cycle and p53-related signaling pathway. Immune analysis showed that EXOSC10 expression was a significant positive correlation with immune infiltration in HCC. In vitro experiments, cell proliferation and migration were inhibited by the elimination of EXOSC10. Furthermore, the elimination of EXOSC10 induced cell apoptosis, suppressed PARP, N-cadherin and Bcl-2 protein expression levels, while increasing Bax, p21, p53, p-p53, and E-cadherin protein expression levels. Conclusions EXOSC10 had a predictive value for the prognosis of HCC and may regulate the progression of HCC through the p53-related signaling pathway.

DNAJ heat shock protein family (Hsp40) member C1(DNAJC1) is a member of the DNAJ family. Some members of the DNAJ gene family had oncogenic properties in many cancers. However, the role of DNAJC1 in hepatocellular carcinoma (HCC) was unclear. In this study, expression and prognostic value of DNAJC1 in HCC were analyzed by bioinformatics. Quantitative real-time PCR and Western blotting were used to verify DNAJC1 expression in liver cancer cell lines. Furthermore, immunohistochemical (IHC) was used to detect DNAJC1 expression in liver cancer tissues. Subsequently, the effect of DNAJC1 on the proliferation, migration, invasion and apoptosis of HCC cells was detected by knocking down DNAJC1. Finally, gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of DNAJC1 and was verified by Western blotting. DNAJC1 was highly expressed in HCC and was significantly associated with the prognosis of patients with HCC. Importantly, the proliferation, migration and invasion of Huh7 and MHCC97H cells were inhibited by the knockdown of DNAJC1 and the knockdown of DNAJC1 promoted Huh7 and MHCC97H cell apoptosis. Furthermore, compared to the negative control group, DNAJC1 knockdown in Huh7 and MHCC97H cells promoted the expression of p21, p53, p-p53(Ser20), Bax and E-cadherin proteins, while inhibiting the expression of PARP, MMP9, Vimentin, Snai1, Bcl-2 and N-cadherin proteins. DNAJC1 had a predictive value for the prognosis of HCC. Knockdown of DNAJC1 may inhibit HCC cell proliferation, migration and invasion and promote the HCC cell apoptosis through p53 and EMT signaling pathways.

Background. To explore influence of continuous illumination, luzindole, and Tamoxifen on incidence of scoliosis model of rats. Methods. Thirty-two one-month-old female rats were rendered into bipedal rats. The bipedal rats were divided into 4 groups: group A by intraperitoneal injection of luzindole and continuous illumination; group B by intraperitoneal injection of luzindole only; group C by intraperitoneal injection of luzindole and oral administration of Tamoxifen; and group D by intraperitoneal injection of equivalent saline. Radiographs were taken at 8th week and 16th week, and incidence and the Cobb angles of scoliosis were calculated. At 16th week, all rats were sacrificed. Before the sacrifice, the levels of calmodulin were measured in each group. Results. At 8th week, scoliosis occurred in groups A and B, with an incidence of 75% and 12.5%, respectively, while rats in group C or D had no scoliosis. At 16th week, scoliosis incidences in groups A and B were 57% and 62.5%, respectively. No scoliosis occurred in group C or D. Calmodulin in platelets in group B was significantly different, compared with groups A and D. There was no significant difference in calmodulin in platelets in groups B and C. Conclusion. By intraperitoneal injection of luzindole in bipedal rats, scoliosis rat models could be successfully made. Under light, incidence of scoliosis may be increased at an early period but it is reversible. Tamoxifen can suppress natural process of scoliosis.

Background： Coronary artery perforation （CAP） is a rare but severe complication of percutaneous coronary intervention （PCI）. The aim of our study was to evaluate the effect and safety oftranscatheter embolization by autologous fat particles in the treatment of CAP. Methods： Once the CAP was confirmed, a little autologous subcutaneous fatty tissue was obtained from the groin of the patient and then was made into 1 mm × 1 mm fat particles. The perforated vessel was embolized by fat particles via a micro-catheter. There were eight patients undergoing transcatheter embolization by autologous fat particles in the treatment of CAP during PCI in Peking University Third Hospital from February 2009 to June 2014, and the clinical data of these patients were collected and analyzed retrospectively. Results： The lesion morphology of the patients was classified based on the American College of Cardiology/American Heart Association Task Force classification, there were one patient with Class B2 lesion and seven patients with Class C lesions （there were five patients with chronic total occlusion lesions）. According to the Ellis classification of CAP, there were six patients with Class Ⅱ perforations and two patients with Class III perforations. The causes of perforation included that seven patients induced by guide wire and one patient by balloon predilation. Three patients had pericardial effusion. All of the eight patients with CAP underwent transcatheter embolization by autologous fat particles. Coronary angiography confirmed that all of them were embolized successfully. There was no severe complication after the procedure. The coronary angiography of one patient at 1 week and another patient at 2 years after the embolization showed that the embolized arteries had recanalized. The median follow-up time was 20.3 months （8.8-50.2 months）, the event-free survival rate was 100%. Conclusions： Transcatheter embolization by autologous fat particles was an effective, safe, cheap, and easy way to treat the perforation of small vessels during PCI.

Clustered regularly interspaced short palindromic repeats （CRISPR）-CRISPR-associated （Cas） systems in bac- teria and archaea provide adaptive immunity against invading foreign nucleic acids. Previous studies suggest that certain bacteria employ their Type II CRISPR-Cas systems to target their own genes, thus evading host immunity. However, whether other CRISPR-Cas systems have similar functions during bacterial invasion of host cells remains unknown. Here we identify a novel role for Type I CRISPR-Cas systems in evading host defenses in Pseudomonas aeruginosa strain UCBPP-PA14. The Type I CRISPR-Cas system of PAl4 targets the mRNA of the bacterial quo- rum-sensing regulator LasR to dampen the recognition by toll-like receptor 4, thus diminishing the pro-inflammatory responses of the host in cell and mouse models. Mechanistically, this nuclease-mediated RNA degradation requires a ＂5＇-GGN-3＇＂ recognition motif in the target mRNA, and HD and DExD/H domains in Cas3 of the Type I CRIS- PR-Cas system. As LasR and Type I CRISPR-Cas systems are ubiquitously present in bacteria, our findings elucidate an important common mechanism underlying bacterial virulence.

To the Editor： Ophthalmoplegia can cause diplopia, with a lot of etiologies including cerebrovascular disease. Nuclear ophthalmoplegia resulted from brainstem infarction is often accompanied by other symptoms of brainstem dysfunction. It is fairly rare that midbrain infarction only manifests as isolated medial rectus nuclear palsy. Here, we provided such an uncommon case and discussed the possible etiology.