Artificial intelligence in clinical research of cancers.

Several factors, including advances in computational algorithms, the availability of high-performance computing hardware, and the assembly of large community-based databases, have led to the extensive application of Artificial Intelligence (AI) in the biomedical domain for nearly 20 years. AI algorithms have attained expert-level performance in cancer research. However, only a few AI-based applications have been approved for use in the real world. Whether AI will eventually be capable of replacing medical experts has been a hot topic. In this article, we first summarize the cancer research status using AI in the past two decades, including the consensus on the procedure of AI based on an ideal paradigm and current efforts of the expertise and domain knowledge. Next, the available data of AI process in the biomedical domain are surveyed. Then, we review the methods and applications of AI in cancer clinical research categorized by the data types including radiographic imaging, cancer genome, medical records, drug information and biomedical literatures. At last, we discuss challenges in moving AI from theoretical research to real-world cancer research applications and the perspectives toward the future realization of AI participating cancer treatment.

Optimized production of full-length PCV2d virus-like particles in Escherichia coli: A cost-effective and high-yield approach for potential vaccine antigen development.

Porcine circovirus type 2 (PCV2) is a globally prevalent infectious pathogen affecting swine, with its capsid protein (Cap) being the sole structural protein critical for vaccine development. Prior research has demonstrated that PCV2 Cap proteins produced in Escherichia coli (E. coli) can form virus-like particles (VLPs) in vitro, and nuclear localization signal peptides (NLS) play a pivotal role in stabilizing PCV2 VLPs. Recently, PCV2d has emerged as an important strain within the PCV2 epidemic. In this study, we systematically optimized the PCV2d Cap protein and successfully produced intact PCV2d VLPs containing NLS using E. coli. The recombinant PCV2d Cap protein was purified through affinity chromatography, yielding 7.5 mg of recombinant protein per 100 ml of bacterial culture. We augmented the conventional buffer system with various substances such as arginine, ß-mercaptoethanol, glycerol, polyethylene glycol, and glutathione to promote VLP assembly. The recombinant PCV2d Cap self-assembled into VLPs approximately 20 nm in diameter, featuring uniform distribution and exceptional stability in the optimized buffer. We developed the vaccine and immunized pigs and mice, evaluating the immunogenicity of the PCV2d VLPs vaccine by measuring PCV2-IgG, IL-4, TNF-α, and IFN-γ levels, comparing them to commercial vaccines utilizing truncated PCV2 Cap antigens. The HE staining and immunohistochemical tests confirmed that the PCV2 VLPs vaccine offered robust protection. The results revealed that animals vaccinated with the PCV2d VLPs vaccine exhibited high levels of PCV2 antibodies, with TNF-α and IFN-γ levels rapidly increasing at 14 days post-immunization, which were higher than those observed in commercially available vaccines, particularly in the mouse trial. This could be due to the fact that full-length Cap proteins can assemble into more stable PCV2d VLPs in the assembling buffer. In conclusion, our produced PCV2d VLPs vaccine elicited stronger immune responses in pigs and mice compared to commercial vaccines. The PCV2d VLPs from this study serve as an excellent candidate vaccine antigen, providing insights for PCV2d vaccine research.

A Multi-Scale Natural Scene Text Detection Method Based on Attention Feature Extraction and Cascade Feature Fusion.

Scene text detection is an important research field in computer vision, playing a crucial role in various application scenarios. However, existing scene text detection methods often fail to achieve satisfactory results when faced with text instances of different sizes, shapes, and complex backgrounds. To address the challenge of detecting diverse texts in natural scenes, this paper proposes a multi-scale natural scene text detection method based on attention feature extraction and cascaded feature fusion. This method combines global and local attention through an improved attention feature fusion module (DSAF) to capture text features of different scales, enhancing the network's perception of text regions and improving its feature extraction capabilities. Simultaneously, an improved cascaded feature fusion module (PFFM) is used to fully integrate the extracted feature maps, expanding the receptive field of features and enriching the expressive ability of the feature maps. Finally, to address the cascaded feature maps, a lightweight subspace attention module (SAM) is introduced to partition the concatenated feature maps into several sub-space feature maps, facilitating spatial information interaction among features of different scales. In this paper, comparative experiments are conducted on the ICDAR2015, Total-Text, and MSRA-TD500 datasets, and comparisons are made with some existing scene text detection methods. The results show that the proposed method achieves good performance in terms of accuracy, recall, and F-score, thus verifying its effectiveness and practicality.

Tumor-suppressive miR-323a inhibits pancreatic cancer cell proliferation and glycolysis through targeting HK-2.

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 85% of all malignant pancreatic exocrine tumors and is one of the main causes of cancer-related fatalities. PDAC is characterized by a high glycolytic rate to ensure its survival as a result of hypovascularization and the desmoplastic reaction. In this study, microRNA 323a (miR-323a) was shown to be downregulated within pancreatic cancer tissues and cells, and enriched in the glucose metabolism pathway. In vitro, overexpression of miR-323a suppressed cell viability, DNA synthesis, and colony formation; in vivo, miR-323a overexpression suppressed the tumor growth within a xenograft mouse model. Regarding cellular glycolysis, miR-323a overexpression decreased glucose-6-phosphate levels, inhibited glucose uptake, and reduced lactate and adenosine triphosphate production. miR-323a was found to directly target hexokinase 2 (HK-2) and negatively regulated HK-2 expression. HK-2 overexpression exerted oncogenic effects on pancreatic cancer cells and promoted cellular glycolysis; more importantly, HK-2 overexpression partially eliminated the effects of miR-323a overexpression. In conclusion, miR-323a is downregulated within pancreatic cancer and serves as a tumor-suppressive miRNA through inhibiting cancer cell proliferation and glycolysis. miR-323a exerts its tumor-suppressive effects through targeting HK-2.

Exosome circCMTM3 promotes angiogenesis and tumorigenesis of hepatocellular carcinoma through miR-3619-5p/SOX9.

AIM: As one of the most common and lethal carcinomas, hepatocellular carcinoma (HCC) is a global health concern and affects millions of people worldwide. Current treatments for HCC are very limited due to its unclear pathogenesis. Here, we aim to further investigate the role of circCMTM3/microRNA (miR)-3619-5p in HCC. METHODS: Human blood samples were collected from HCC patients and healthy people. Quantitative reverse transcription-polymerase chain reaction and western blot analysis were undertaken to measure levels of circCMTM3, miR-3619-5p, SOX9, and exosome markers. The MTT, colony formation, and Transwell assays were used to examine the viability, migration, and invasion of human umbilical vein endothelial cells (HUVECs), respectively. Tube formation assay was used to assess angiogenesis. Dual luciferase assay was used to validate circCMTM3/miR-3619-5p and miR-3619-5p/SOX9 interactions. A nude mouse xenograft model was used to test the role of circCMTM3 in HCC in vivo. RESULTS: Levels of circCMTM3 in exosomes from HCC patients and cells were elevated. Knockdown of circCMTM3 greatly decreased viability, migration, and invasion of HUVECs, as well as angiogenesis. CircCMTM3 acted as a miR-3619-5p sponge and miR-3619-5p inhibitor reversed the effects of si-circCMTM3 on angiogenesis. MiR-3619-5p directly targeted SOX9 and modulated angiogenesis through SOX9. Furthermore, knockdown of circCMTM3 suppressed angiogenesis and HCC tumor growth in vivo. CONCLUSION: The exosome circCMTM3/miR-3619-5p/SOX9 axis from HCC cells promotes angiogenesis and thus contributes to HCC tumorigenesis.

[Expression of ZNF207 in hepatocellular carcinoma and its significance].

OBJECTIVE: To investigate the expression of zinc finger protein 207 (ZNF207) in hepatocellular carcinoma (HCC) tissues, and analyze the correlation of ZNF207 with clinicopathological factors and HCC patients' survival.
 Methods: Real-time PCR was used to detect ZNF207 mRNA expression in 10 paired fresh HCC and adjacent non-tumor liver tissue samples. Immunohistochemical (IHC) analysis was used to detect ZNF207 protein expression in 135 cases of randomly selected paraffin-embedded HCC tissues. The correlation of ZNF207 expression with clinicopathological factors and survival of HCC was analyzed.
 Results: The ZNF207 mRNA expression level in HCC was significantly higher than that in the adjacent non-tumor liver tissue (P<0.01). IHC results showed that ZNF207 protein level was elevated in HCC tissues and ZNF207 expression was correlated with cirrhosis, nodule number, tumor capsule, vascular invasion, and TNM stage (P<0.05). Survival analysis showed that patients with high ZNF207 expression had poorer overall survival (OS) and disease-free survival (DFS) than those with the low ZNF207 expression (P<0.01), and ZNF207 was an independent risk factor for OS and DFS of HCC (P<0.05).
 Conclusion: ZNF207 expression is elevated in HCC and associated with adverse clinicopathological factors, indicating poor prognosis for HCC.

Long Stress Induced Non-Coding Transcripts 5 (LSINCT5) Promotes Hepatocellular Carcinoma Progression Through Interaction with High-Mobility Group AT-hook 2 and MiR-4516.

BACKGROUND Long non-coding RNAs (lncRNAs) have been implicated in various human cancer types. However, the underlying mechanisms involved in hepatocellular carcinoma (HCC) progression remain poorly understood. MATERIAL AND METHODS In this study, lncRNA array was used to identify HCC related lncRNAs. RNA immunoprecipitation (RIP) followed mass spectrometry was used to explore lncRNA binding proteins. Western blot, quantitative PCR, tumor sphere formation, migration and viability assay were performed to evaluate the oncogenic role of lncRNAs. RESULTS We identified a novel lncRNA named long stress induced non-coding transcripts 5 (LSINCT5) which facilitates HCC progression. LSINCT5 was significantly upregulated in both HCC specimens and cell lines and correlates with poor survival. In vitro experiments showed that LSINCT5 promoted migration and viability of HepG2 and Huh7 cells. The in vivo xenograft mouse model also confirmed an oncogenic role for LSINCT5. RIP in combination with mass spectrometry identified HMGA2 as the LSINCT5 binding partner. LSINCT5 could bind to HMGA2 and decrease proteasome-mediated HMGA2 degradation leading to EMT activation. LSINCT5 also served as a competing endogenous RNA (ceRNA) for miR-4516, resulting in increased STAT3/BclxL expression and attenuated apoptosis. CONCLUSIONS Our data have collectively established a lncRNA LSINCT5 mediated process during HCC carcinogenesis and might have provided novel insight into therapeutic targeting.

[Correlation of retinol binding protein 4 with metabolic indexes of glucose and lipid, bile cholesterol saturation index].

OBJECTIVE: To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 METHODS: A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 RESULTS: The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P<0.01). There was no significant difference in the serum total bile acid (TBA), serum triglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations showed that HOMA-IR was the strongest correlation factor with RBP4.
 CONCLUSION: RBP4 concentrations in serum and bile in the diabetes group are significantly higher than those in the control group. HOMA-IR, BMI and WC are independently correlated with the level of bile RBP4. HOMA-IR and WC are independently correlated with the serum RBP4 level. HOMA-IR is the strongest correlation factor with RBP4. RBP4 might play an important role in the course of gallstone formation in Type 2 diabetes mellitus.

The in vitro biological properties of Mg-Zn-Sr alloy and superiority for preparation of biodegradable intestinal anastomosis rings.

BACKGROUND: Magnesium (Mg) alloy is a metal-based biodegradable material that has received increasing attention in the field of clinical surgery, but it is currently seldom used in intestinal anastomosis. This study was conducted to comprehensively assess a ternary magnesium (Mg)-zinc (Zn)-strontium (Sr) alloy's biological superiorities as a preparation material for intestinal anastomosis ring. MATERIAL AND METHODS: Mouse L-929 fibroblasts were cultured with Mg-Zn-Sr alloy extract and compared with both positive (0.64% phenol) and negative (original broth culture) controls. The cell morphology of different groups was examined using microscopy, and a cytotoxicity assessment was performed. Fresh anticoagulated human blood was mixed with Mg-Zn-Sr alloy extract and compared with both positive (distilled water) and negative (normal saline) controls. The absorbance of each sample at 570 nm was used to calculate the Mg-Zn-Sr alloy hemolysis ratio in order to test the Mg alloy's blood compatibility. Bacterial cultures of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were added to Mg-Zn-Sr alloy block samples and compared with positive (Ceftazidime), negative (316LSS stainless steel), and blank controls. The broth cultures were sampled to compare their bacterial colony counts so as to evaluate the antibacterial properties of the Mg-Zn-Sr alloy. The Mg-Zn-Sr alloy was surface-coated with a layer of poly(lactic-co-glycolic acid) carrying everolimus. The surface morphology and degradability of the coating were examined so as to demonstrate feasibility of coating, which can release the drug evenly. RESULTS: The experiments proved that Mg-Zn-Sr alloy has good biocompatible, antibacterial, and drug-loaded coating performances, which are lacking in existing intestinal anastomosis devices/materials. CONCLUSIONS: The Mg-Zn-Sr alloy increases biocompatibility, and yields a safer and better therapeutic effect; therefore, it is a novel biomaterial that is feasible for use when preparing biodegradable intestinal anastomosis rings.

Feasibility and Advantages of Large Liver Hemangioma Treated with Laparoscopic Microwave Ablation.

BACKGROUND/AIMS: To evaluate feasibility and superiority of large liver hemangioma treated with laparoscopic microwave ablation. METHODOLOGY: Between March 2006 and May 2013, 47 patients with liver hemangioma (5-10 cm) were surgically treated in our department, and were randomly divided into three groups, laparoscopic microwave ablation group (treatment group), traditional opening group, and laparoscopic resection group. Three groups were compared in respect of postoperative ambulation time, gastrointestinal function recovery time, postoperative liver function recovery time, intraoperative blood loss, postoperative hospital stay, using SPSS13.0 software and analysis of variance, P < 0.05 indicates significant, then adopting Student-Newman-Keuls method to compare mean value of every two groups. And the treatment group of patients were tracked and reviewed. RESULTS: With regard to above aspects, treatment group and two control groups were compared, P < 0.05 was considered statistically significant, then the result of S-N-K method showed that the treatment group was far better than the control group in the above four areas, however compared with traditional opening group laparoscopic resection group did not demonstrate any superiority. Tracking the patients of treatment group proved no recurrence, and one case's CT films before and after surgery were compared, further confirming the feasibility of microwave ablation. CONCLUSIONS: To large hepatic hemangioma, laparoscopic microwave ablation in respect of intraoperative injury, postoperative recovery and costs is superior to other methods, and the treatment effect is certain, it's feasible and worthy of promotion.

16S rRNA Gene Amplicon Sequencing of Gut Microbiota Affected by Four Probiotic Strains in Mice.

Probiotics, also referred to as "living microorganisms," are mostly present in the genitals and the guts of animals. They can increase an animal's immunity, aid in digestion and absorption, control gut microbiota, protect against sickness, and even fight cancer. However, the differences in the effects of different types of probiotics on host gut microbiota composition are still unclear. In this study, 21-day-old specific pathogen-free (SPF) mice were gavaged with Lactobacillus acidophilus (La), Lactiplantibacillus plantarum (Lp), Bacillus subtilis (Bs), Enterococcus faecalis (Ef), LB broth medium, and MRS broth medium. We sequenced 16S rRNA from fecal samples from each group 14 d after gavaging. According to the results, there were significant differences among the six groups of samples in Firmicutes, Bacteroidetes, Proteobacteria, Bacteroidetes, Actinobacteria, and Desferribacter (p < 0.01) at the phylum level. Lactobacillus, Erysipelaceae Clostridium, Bacteroides, Brautella, Trichospiraceae Clostridium, Verummicroaceae Ruminococcus, Ruminococcus, Prevotella, Shigella, and Clostridium Clostridium differed significantly at the genus level (p < 0.01). Four kinds of probiotic changes in the composition and structure of the gut microbiota in mice were observed, but they did not cause changes in the diversity of the gut microbiota. In conclusion, the use of different probiotics resulted in different changes in the gut microbiota of the mice, including genera that some probiotics decreased and genera that some pathogens increased. According to the results of this study, different probiotic strains have different effects on the gut microbiota of mice, which may provide new ideas for the mechanism of action and application of microecological agents.

Biological Characterization and Whole-Genome Analysis of Bacillus subtilis MG-1 Isolated from Mink Fecal Samples.

Bacillus subtilis is an important part of the gut microbiota and a commonly used probiotic. In the present study, to assess the biological characteristics and probiotic properties of B. subtilis derived from mink, we isolated B. subtilis MG-1 isolate from mink fecal samples, characterized its biological characteristics, optimized the hydrolysis of casein by its crude extract, and comprehensively analyzed its potential as a probiotic in combination with whole-genome sequencing. Biological characteristics indicate that, under low-pH conditions (pH 2), B. subtilis MG-1 can still maintain a survival rate of 64.75%; under the conditions of intestinal fluid, gastric acid, and a temperature of 70 °C, the survival rate was increased by 3, 1.15 and 1.17 times compared with the control group, respectively. This shows that it can tolerate severe environments. The results of hydrolyzed casein in vitro showed that the crude bacterial extract of isolate MG-1 exhibited casein hydrolyzing activity (21.56 U/mL); the enzyme activity increased to 32.04 U/mL under optimized reaction conditions. The complete genome sequencing of B. subtilis MG-1 was performed using the PacBio third-generation sequencing platform. Gene annotation analysis results revealed that B. subtilis MG-1 was enriched in several Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways, and most genes were related to Brite hierarchy pathways (1485-35.31%) and metabolism pathways (1395-33.17%). The egg-NOG annotation revealed that most genes were related to energy production and conversion (185-4.10%), amino acid transport and metabolism (288-6.38%), carbohydrate transport and metabolism (269-5.96%), transcription (294-6.52%), and cell wall/membrane/envelope biogenesis (231-5.12%). Gene Ontology (GO) annotation elucidated that most genes were related to biological processes (8230-45.62%), cellular processes (3582-19.86%), and molecular processes (6228-34.52%). Moreover, the genome of B. subtilis MG-1 was predicted to possess 77 transporter-related genes. This study demonstrates that B. subtilis MG-1 has potential for use as a probiotic, and further studies should be performed to develop it as a probiotic additive in animal feed to promote animal health.

A new model based inflammatory index and tumor burden score (TBS) to predict the recurrence of hepatocellular carcinoma (HCC) after liver resection.

To establish a model based on inflammation index and tumor burden score (TBS) to predict recurrence of hepatocellular carcinoma (HCC) after liver resection. A retrospective study was performed on 217 patients who diagnosed HCC underwent liver resection at Xiangya Hospital Central South University from June 1, 2017 to June 1, 2019. According to the receiver operating characteristic (ROC) curve, the optimal cut-off value of inflammatory index and the TBS was determined by the Youden index. Prediction performance was compared by the area under the receiver operating characteristic curve (AUC). Cox regression analysis was used to determine the risk factors for the recurrence of HCC after liver resection. According to the independent risk factors of the patients, a prediction model for HCC was established based on inflammation index and tumor burden score (TBS).The prediction performance of the model was compared with single index (TBS group and NLR group) and traditional HCC stage models (TNM stage and BCLC stage). MLR = 0.39, NLR = 2.63, PLR = 134, SII = 428 and TBS = 8.06 are the optimal cut-off values. AUC of SII, PLR, NLR, MLR and TBS were 0.643, 0.642, 0.642, 0.618 and 0.724respectively. MVI (P = 0.005), satellite nodule (P = 0.017), BCLC B-C stage (P = 0.013), NLR > 2.63 (P = 0.013), TBS > 8.06 (P = 0.017) are independent risk factors for the recurrence of HCC after liver resection. According to this study, the optimal inflammatory index NLR combined with TBS was obtained. The AUC of NLR-TBS model was 0.762, not only better than NLR group (AUC = 0.630) and TBS group (AUC = 0.671), also better than traditional BCLC (AUC = 0.620) and TNM (AUC = 0.587) stage models. Interestingly, we found that NLR and TBS should be good prognostic factor for recurrence of HCC after liver resection. The NLR-TBS model based the best inflammatory index (NLR) and TBS have a better prediction performance and the prediction performance of NLR-TBS model not only better than NLR group and TBS group, but better than BCLC and TNM stage models.

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) has increased in these years. DNA damage repair (DDR) pathway is required in response to DNA damage Gene mutations in DDR pathway play an important role in different stages of tumorigenesis and development. Based on the importance of DDR pathway in precision therapy of multiple cancers, we analyzed DDR gene mutations in Chinese patients with HCC. The results showed that (tumor mutation burden) TMB was significantly higher in HCC patients who carried somatic mutations in DDR than in non-carriers, and TMB in patients with DS, MMR mutations and DDR genes mutations such as RAD50, MLH1, MSH2, CHEK2 was significantly higher than that in wild-type patients. Based on the results of next-generation sequencing (NGS) testing, we are trying to provide clues for targeted therapy and provide feasible basis for PD-1/PD-L1 immune checkpoint inhibitor therapy.

Atractylenolide III predisposes miR-195-5p/FGFR1 signaling axis to exert tumor-suppressive functions in liver cancer.

BACKGROUND: Antineoplastic activity of atractylenolide III (ATL) has been reported in several malignant tumors. However, its activity has not been completely clarified in hepatocellular carcinoma (HCC). Herein, anticancer effects and underlying molecular mechanisms of ATL were investigated in HCC cells in vitro. METHODS: Cell viability was evaluated by CCK-8 assay. Cell migration and invasion were evaluated using the transwell assay. TUNEL staining was performed to evaluate cell apoptosis. Protein expression was measured by western blotting analysis. Online database TargetScan and luciferase reporter gene analysis were performed to validate FGFR1 as a target of miR-195-5p. RESULTS: HepG2 and SMMC7721 cell growth, migration, and invasion were inhibited by ATL treatment in a dose-dependent pattern. ATL treatment-induced apoptosis of HepG2 and SMMC7721 cells. Intriguingly, ATL treatment unexpectedly inhibited FGFR1 protein expression in HepG2 and SMMC7721 cells. Knockdown of FGFR1 inhibited proliferation, migration, and invasion, and evoked apoptosis of HepG2 and SMMC7721 cells. We also found that ATL treatment could increase the expression of miR-195-5p, which as a posttranscriptional targeted FGFR1. In HCC tissues, miR-195-5p expression is negatively correlated with FGFR1. Furthermore, the antiproliferative and proapoptotic roles of miR-195-5p were neutralized by overexpressed FGFR1 in HCC cells. CONCLUSION: ATL effectively repressed growth and induced apoptosis of human HCC cells through the upregulation of miR-195-5p to downregulate FGFR1 expression. PRACTICAL APPLICATIONS: Atractylenolide III as a bioactive anticancer adjuvant medication will provide chemosensitization strategy for reversing the drug resistance of HCC.

Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis.

OBJECTIVES: Pancreatic carcinoma (PC) has become the fourth leading cause of cancer deaths. Long noncoding RNA DUXAP8 has also been reported to play a regulatory role in PC progression. However, its molecular mechanism in PC is not fully elucidated. METHODS: Quantitative real-time polymerase chain reaction was used to detect the levels of DUXAP8, microRNA (miR)-448, Wilms tumor 1-associating protein (WTAP), focal adhesion kinase (Fak), and matrix metallopeptidase 2/9. Western blotting was carried out to detect matrix metallopeptidase 2/9, WTAP, Fak, and p-Fak. The interaction between DUXAP8 and miR-448 as well as WTAP and miR-448 was validated by bioinformatics and dual-luciferase reporter assays. Transwell assay was used to analyze cell invasion and migration. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to analyze cell proliferation. RESULTS: DUXAP8 was upregulated, whereas miR-448 was downregulated in PC tissue and cells. Meanwhile, DUXAP8 knockdown or miR-448 overexpression inhibited migration, invasion, and proliferation of PC cells. DUXAP8 directly targeted miR-448, and miR-448 directly bound to WTAP. Downregulation of miR-448 reversed the inhibition of migration and invasion of PC cells by DUXAP8 knockdown. CONCLUSIONS: DUXAP8 sponges miR-448 to modulate migration, invasion, and proliferation of PC cells, indicating a novel mechanistic role of DUXAP8 in the regulation of PC progression.

piR-19166 inhibits migration and metastasis through CTTN/MMPs pathway in prostate carcinoma.

Tumor metastasis is one of death causes for patients of prostate carcinoma. PIWI-interacting RNAs (piRNAs) are a subtype of noncoding protein RNAs that are involved in tumorigenesis, but the effect of piRNAs in prostate carcinoma (PCa) remains unclear. This article showed the identification of piRNAs was performed using a piRNA microarray screen in PCa tissues and several piRNAs were identified as dysregulated. The two up-regulated piRNAs (piR-19004 and piR-2878) and one down-regulated piR-19166 have been validated in the tissues and cell lines of PCa using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Further studies showed that piR-19166 is transfected into PCa cells to suppress its migration and metastasis. Mechanistically, cortactin (CTTN) 3' untranslated region (UTR) was complementary combined with piR-19166 by bioinformatic prediction and identified as a direct target of piR-19166 through dual-luciferase reporter assay. Over-expression and knockdown of CTTN could respectively rescue and simulate the effects induced by piR-19166. Finally, piR-19166 suppresses migration and metastasis by the CTTN/matrix metalloproteinases (MMPs) pathway in PCa cells. Thus, these findings suggested that piR-19166 targets the CTTN of prostate cancer cells to inhibit migration and distant metastasis, and may represent a new marker of diagnosis and treatment for PCa patients in early stages.

The design, development, and in vivo performance of intestinal anastomosis ring fabricated by magnesium­zinc­strontium alloy.

In the current work, an intestinal anastomosis ring made of magnesium­zinc­strontium (Mg-Zn-Sr) alloy was developed and fabricated in order to take advantages of the appropriate biocompatibility and degradability of Mg-based alloys. As-fabricated anastomosis rings were implanted into the intestinal tracts of Bama miniature pigs to evaluate their biological performance in vivo. At the injury site, the formation of edema and granulation tissue was observed for 2 weeks after surgery. Till week 4, the edema transformed to firm scar tissue, which reached the healing standard of intestinal tissue. The levels of biochemical indicators such as blood routine, liver and kidney functions as well as electrolytes were all under normal conditions, indicating that the implantation of Mg alloy did not have remarkable influence on the blood system as well as liver and kidney functions. Pathological results revealed that no obvious abnormality was found in heart, liver, spleen, lung, kidney and brain tissues. The Mg ions were found to be excreted from the body through urine. The intestinal anastomosis ring could be discharged through excretion around 2 weeks after surgery, of which the surface was corroded and covered by a layer of Ca- and P-containing minerals. According to histological images, a mild inflammatory response was noticed on week 2. At this stage, dilated and congested capillaries were found in the muscular layer. Moreover, the mucosal layer and villi at the injury site were disordered. Till week 4, the muscular and mucosal layer were similar to their healthy counterparts even though the villi were slightly shorter than normal ones. Together, the results indicate that Mg-Zn-Sr alloy is a promising candidate for the fabrication of biodegradable intestinal anastomosis ring.

Evaluating the osteoimmunomodulatory properties of micro-arc oxidized titanium surface at two different biological stages using an optimized in vitro cell culture strategy.

It is known that introducing a porous ceramic coating on titanium (Ti) implant surface fabricated by micro-arc oxidation (MAO) could enhance the differentiation of osteoblasts. However, the osteogenic capacity of MAO-fabricated coating still remains unknown when immune cells especially macrophages are involved. The influence of the inflammatory microenvironment and the co-influence of the inflammatory microenvironment and surface characteristics of MAO-fabricated coating on osteoblast response need to be explored. In this study, a new in vitro cell culture strategy is proposed by mimicking the biological events happened after implantation based on the recruitment of osteoblasts to biomaterial surfaces to investigate biological performances of MAO-modified Ti surface. It is found that macrophages grown on MAO-modified Ti surface were switched to M1-like phenotype, evidenced by the promoted expressions of inflammatory genes (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß) and production of pro-inflammatory cytokine TNF-α. Moreover, the inflammatory microenvironment created by macrophage/MAO-modified Ti surface interactions could promote the collagen syntheses and matrix mineralization of osteoblast-like cells grown tissue culture plate. When osteoblasts were cultured on MAO-modified Ti surface and cultured by macrophage/MAO-modified Ti surface conditioned medium (CM), the alkaline phosphatase (ALP) activity and collagen synthesis of osteoblast-like cells were promoted. This study suggests that MAO-modified Ti surface is beneficial for osteogenesis at both stages after implantation (before and after osteoblast recruitment to biomaterial surfaces).

Blood exosomal micro ribonucleic acid profiling reveals the complexity of hepatocellular carcinoma and identifies potential biomarkers for differential diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a shortage of effective biomarkers for its diagnosis. AIM: To explore blood exosomal micro ribonucleic acids (miRNAs) as potential biomarkers for HCC diagnosis. RESULTS: The principal component analysis suggested that daily alcohol consumption could alter the blood exosomal miRNA profiles of hepatitis B virus positive non-HCC patients through miR-3168 and miR-223-3p. The miRNA profiles also revealed the tumor stages of HCC patients. High expression of miR-455-5p and miR-30c-5p, which significantly correlated with better overall survival in tumor tissues, could also be detected in blood exosomes. Two pairs of miRNAs (miR-584-5p/miR-106-3p and miR-628-3p/miR-941) showed a 94.1% sensitivity and 68.4% specificity to differentiate HCC patients from non-HCC patients. The specificity of the combination was substantially influenced by alcohol consumption habits. CONCLUSION: This study suggested that blood exosomal miRNAs can be used as new non-invasive diagnostic tools for HCC. However, their accuracy could be affected by tumor stage and alcohol consumption habits.