Transcriptome data reveal beneficial effects of Rickettsia (Rickettsiales: Rickettsiaceae) on Bemisia tabaci (Hemiptera: Aleyrodidae) through nutritional factors and defense mechanisms.

Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a destructive insect pest of many crops. Rickettsia infection in different cryptic species of B. tabaci has been observed worldwide. Understanding the interactions between these 2 organisms is critical to developing Rickettsia-based strategies to control B. tabaci and thereby reduce the transmission of related vector-borne viruses. In this study, we investigated the effects of Rickettsia infection on the biological characteristics of the Middle East Asia Minor 1 (MEAM1) strain of B. tabaci through biological analysis of infected and uninfected individuals. The results of this study suggest that Rickettsia may confer fitness benefits. These benefits include increased fertility, improved survival rates, accelerated development, and resulted in female bias. We also investigated the transcriptomics impact of Rickettsia infection on B. tabaci by performing a comparative RNA-seq analysis of nymphs and adult females, both with and without the infection. Our analysis revealed 218 significant differentially expressed genes (DEGs) in infected nymphs compared to uninfected ones and 748 significant DEGs in infected female adults compared to their uninfected whiteflies. Pathway analysis further revealed that Rickettsia can affect many important metabolic pathways in whiteflies. The results suggest that Rickettsia plays an essential role in energy metabolism, and nutrient synthesis in the B. tabaci MEAM1, and depends on metabolites obtained from the host to ensure its survival. Overall, our findings suggest that Rickettsia has beneficial effects on B. tabaci and offered insights into the potential molecular mechanisms governing the interactions between Rickettsia and B. tabaci MEAM1.

Rickettsia transmission from whitefly to plants benefits herbivore insects but is detrimental to fungal and viral pathogens.

Bacterial endosymbionts play important roles in the life histories of herbivorous insects by impacting their development, survival, reproduction, and stress tolerance. How endosymbionts may affect the interactions between plants and insect herbivores is still largely unclear. Here, we show that endosymbiotic Rickettsia belli can provide mutual benefits also outside of their hosts when the sap-sucking whitefly Bemisia tabaci transmits them to plants. This transmission facilitates the spread of Rickettsia but is shown to also enhance the performance of the whitefly and co-infesting caterpillars. In contrast, Rickettsia infection enhanced plant resistance to several pathogens. Inside the plants, Rickettsia triggers the expression of salicylic acid-related genes and the two pathogen-resistance genes TGA 2.1 and VRP, whereas they repressed genes of the jasmonic acid pathway. Performance experiments using wild type and mutant tomato plants confirmed that Rickettsia enhances the plants' suitability for insect herbivores but makes them more resistant to fungal and viral pathogens. Our results imply that endosymbiotic Rickettsia of phloem-feeding insects affects plant defenses in a manner that facilitates their spread and transmission. This novel insight into how insects can exploit endosymbionts to manipulate plant defenses also opens possibilities to interfere with their ability to do so as a crop protection strategy. IMPORTANCE: Most insects are associated with symbiotic bacteria in nature. These symbionts play important roles in the life histories of herbivorous insects by impacting their development, survival, reproduction as well as stress tolerance. Rickettsia is one important symbiont to the agricultural pest whitefly Bemisia tabaci. Here, for the first time, we revealed that the persistence of Rickettsia symbionts in tomato leaves significantly changed the defense pattern of tomato plants. These changes benefit both sap-feeding and leaf-chewing herbivore insects, such as increasing the fecundity of whitefly adults, enhancing the growth and development of the noctuid Spodoptera litura, but reducing the pathogenicity of Verticillium fungi and TYLCV virus to tomato plants distinctively. Our study unraveled a new horizon for the multiple interaction theories among plant-insect-bacterial symbionts.

Diagnostic value of matrix metalloproteinases 2, 7 and 9 in urine for early detection of colorectal cancer.

BACKGROUND: A noninvasive biomarker with high diagnostic performance is urgently needed for the early diagnosis of colorectal cancer (CRC). AIM: To evaluate the diagnostic value of matrix metalloproteinases (MMPs) 2, 7 and 9 in urine for CRC. METHODS: Of 59 healthy controls, 47 patients with colon polyps and 82 patients with CRC were included in this study. Carcinoembryonic antigen (CEA) in serum and MMP2, MMP7, and MMP9 in urine were detected. The combined diagnostic model of the indicators was established by binary logistic regression. The receiver operating characteristic curve (ROC) of the subjects was used to evaluate the independent and combined diagnostic value of the indicators. RESULTS: The MMP2, MMP7, MMP9, and CEA levels in the CRC group differed significantly from levels in the healthy controls (P < 0.05). The levels of MMP7, MMP9, and CEA also differed significantly between the CRC group and the colon polyps group (P < 0.05). The area under the curve (AUC) distinguishing between the healthy control and the CRC patients using the joint model with CEA, MMP2, MMP7 and MMP9 was 0.977, and the sensitivity and specificity were 95.10% and 91.50%, respectively. For early-stage CRC, the AUC was 0.975, and the sensitivity and specificity were 94.30% and 98.30%, respectively. For advanced stage CRC, the AUC was 0.979, and the sensitivity and specificity were 95.70% and 91.50%, respectively. Using CEA, MMP7 and MMP9 to jointly established a model distinguishing the colorectal polyp group from the CRC group, the AUC was 0.849, and the sensitivity and specificity were 84.10% and 70.20%, respectively. For early-stage CRC, the AUC was 0.818, and the sensitivity and specificity were 76.30% and 72.30%, respectively. For advanced stage CRC, the AUC was 0.875, and the sensitivity and specificity were 81.80% and 72.30%, respectively. CONCLUSION: MMP2, MMP7 and MMP 9 may exhibit diagnostic value for the early detection of CRC and may serve as auxiliary diagnostic markers for CRC.

Blood index panel for gastric cancer detection.

BACKGROUND: Gastric cancer is a common malignant tumor. Early detection and diagnosis are crucial for the prevention and treatment of gastric cancer. AIM: To develop a blood index panel that may improve the diagnostic value for discriminating gastric cancer and gastric polyps. METHODS: Thirteen tumor-related detection indices, 38 clinical biochemical indices and 10 cytokine indices were examined in 139 gastric cancer patients and 40 gastric polyp patients to build the model. An additional 68 gastric cancer patients and 22 gastric polyp patients were enrolled for validation. After area under the curve evaluation and univariate and multivariate analyses. RESULTS: Five tumor-related detection indices, 12 clinical biochemical indices and 1 cytokine index showed significant differences between the gastric cancer and gastric polyp groups. Carbohydrate antigen (CA) 724, phosphorus (P) and ischemia-modified albumin (IMA) were included in the blood index panel, and the area under the curve (AUC) of the index panel was 0.829 (0.754, 0.905). After validation, the AUC was 0.811 (0.700, 0.923). Compared to the conventional index CA724, the blood index panel showed significantly increased diagnostic value. CONCLUSION: We developed an index model that included CA724, P and IMA to discriminate the gastric cancer and gastric polyp groups, which may be a potential diagnostic method for clinical practice.

Early detection of colorectal cancer based on circular DNA and common clinical detection indicators.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, and it is the second leading cause of death from cancer in the world, accounting for approximately 9% of all cancer deaths. Early detection of CRC is urgently needed in clinical practice. AIM: To build a multi-parameter diagnostic model for early detection of CRC. METHODS: Total 59 colorectal polyps (CRP) groups, and 101 CRC patients (38 early-stage CRC and 63 advanced CRC) for model establishment. In addition, 30 CRP groups, and 62 CRC patients (30 early-stage CRC and 32 advanced CRC) were separately included to validate the model. 51 commonly used clinical detection indicators and the 4 extrachromosomal circular DNA markers NDUFB7, CAMK1D, PIK3CD and PSEN2 that we screened earlier. Four multi-parameter joint analysis methods: binary logistic regression analysis, discriminant analysis, classification tree and neural network to establish a multi-parameter joint diagnosis model. RESULTS: Neural network included carcinoembryonic antigen (CEA), ischemia-modified albumin (IMA), sialic acid (SA), PIK3CD and lipoprotein a (LPa) was chosen as the optimal multi-parameter combined auxiliary diagnosis model to distinguish CRP and CRC group, when it differentiated 59 CRP and 101 CRC, its overall accuracy was 90.8%, its area under the curve (AUC) was 0.959 (0.934, 0.985), and the sensitivity and specificity were 91.5% and 82.2%, respectively. After validation, when distinguishing based on 30 CRP and 62 CRC patients, the AUC was 0.965 (0.930-1.000), and its sensitivity and specificity were 66.1% and 70.0%. When distinguishing based on 30 CRP and 32 early-stage CRC patients, the AUC was 0.960 (0.916-1.000), with a sensitivity and specificity of 87.5% and 90.0%, distinguishing based on 30 CRP and 30 advanced CRC patients, the AUC was 0.970 (0.936-1.000), with a sensitivity and specificity of 96.7% and 86.7%. CONCLUSION: We built a multi-parameter neural network diagnostic model included CEA, IMA, SA, PIK3CD and LPa for early detection of CRC, compared to the conventional CEA, it showed significant improvement.

Evaluation of the diagnostic value of serum-based proteomics for colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a highly malignant cancer with a high incidence and mortality in China. It is urgent to find a diagnostic marker with higher sensitivity and specificity than the traditional approaches for CRC diagnosis. AIM: To provide new ideas for the diagnosis of CRC based on serum proteomics. METHODS: Specimens from 83 healthy people, 62 colon polyp (CRP) patients, and 101 CRC patients were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The diagnostic value of the profiles of differentially expressed proteins was then analyzed. RESULTS: Compared with the healthy control group, CRC patients had elevated expression of 5 proteins and reduced expression of 14 proteins. The area under the curve (AUC) for a differentially expressed protein with a mass-to-charge ratio of 2022.34 was the largest; the AUC was 0.843, which was higher than the AUC of 0.717 observed with carcinoembryonic antigen (CEA), and the sensitivity and specificity of this identified marker were 75.3% and 79.5%, respectively. After cross-validation, the accuracy of diagnosis using levels of this differentially expressed protein was 82.37%. Compared with the CRP group, the expression of 3 proteins in the serum of CRC patients was elevated and 11 proteins were expressed at reduced levels. Proteins possessing mass-to-charge ratio values of 2899.38 and 877.3 were selected to establish a classification tree model. The results showed that the accuracy of CRC diagnosis was 89.5%, the accuracy of CRP diagnosis was 81.6%, and the overall accuracy of this approach was 86.3%. The overall sensitivity and specificity of diagnosis using the proteomics approach were 81.8% and 66.75%, respectively. The sensitivities and specificities of diagnoses based on CEA and carbohydrate antigen 19-9 expression were 55.6% and 91.3% and 65.4% and 65.2%, respectively. CONCLUSION: We demonstrated that serum proteomics may be helpful for the detection of CRC, and it may assist clinical practice for CRC diagnosis.

Genome-wide methylation profiling of early colorectal cancer using an Illumina Infinium Methylation EPIC BeadChip.

BACKGROUND: DNA methylation is a part of epigenetic modification, that is closely related to the growth and development of colorectal cancer (CRC). Specific methylated genes and methylated diagnostic models of tumors have become current research focuses. The methylation status of circulating DNA in plasma might serve as a potential biomarker for CRC. AIM: To investigate genome-wide methylation pattern in early CRC using the Illumina Infinium Human Methylation 850K BeadChip. METHODS: The 850K Methylation BeadChip was used to analyze the genome-wide methylation status of early CRC patients (n = 5) and colorectal adenoma patients (n = 5). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were performed on the selected differentially methylated sites to further discover candidate methylation biomarkers in plasma. RESULTS: A total of 1865 methylated CpG sites with significant differences were detected, including 676 hypermethylated sites and 1189 hypomethylated sites. The distribution of these sites covered from the 1st to 22nd chromosomes and are mainly distributed on the gene body and gene promoter region. GO and KEGG enrichment analysis showed that the functions of these genes were related to biological regulation, molecular binding, transcription factor activity and signal transduction pathway. CONCLUSION: The study demonstrated that the Illumina Infinium Human Methylation 850K BeadChip can be used to investigate genome-wide methylation status of plasma DNA in early CRC and colorectal adenoma patients.

A reverse transcription-cross-priming amplification method with lateral flow dipstick assay for the rapid detection of Bean pod mottle virus.

Bean pod mottle virus (BPMV) is a destructive virus that causes serious economic losses in many countries every year, highlighting the importance of its effective detection. In this study, we developed a fast reverse transcription-cross-priming amplification (RT-CPA) coupled with lateral flow dipstick (LFD) diagnostic method for BPMV detection. The RT-CPA-LFD assay that targets the coat protein gene of BPMV was highly specific against diagnosing four other common viruses transmitted by soybean seeds, i.e., Southern bean mosaic virus (SBMV), Tomato ringspot virus (ToRSV), Arabis mosaic virus (ArMV), and Tobacco ringspot virus (TRSV). The sensitivities of the real-time fluorescent RT-CPA and the RT-CPA-LFD assay were at least 50 pg/µl and 500 pg/µl, respectively. Despite a compromise in the limit of detection of the RT-CPA method compared with TaqMan-MGB real-time RT-PCR, our results demonstrated a notably better performance in the detection of field samples of BPMV-infested soybean seeds. With the advantages of efficiency and convenience by visual determination, the RT-CPA-LFD assay presents a potential application for the rapid and accurate detection of BPMV in routine tests.

Whitefly-induced tomato volatiles mediate host habitat location of the parasitic wasp Encarsia formosa, and enhance its efficacy as a bio-control agent.

BACKGROUND: Whitefly Bemisia tabaci is a phloem-feeding insect and causes extensive agricultural damage around the world. Although the parasitic wasp Encarsia formosa is widely used to control B. tabaci on glasshouse tomatoes, low efficiency and discontinuity are frequently recorded. It has been well-documented that herbivore-induced plant volatiles (HIPVs) are important cues in the foraging behavior of the natural enemies of herbivores. However, the volatiles emitted from tomatoes infested by different developmental stages of B. tabaci (nymphs versus adults) have not been compared in terms of their effects on E. formosa attraction. RESULTS: Olfactometer assays with four tomato cultivars revealed that the E. formosa wasps showed a significant attraction to the volatiles from adult-infested plants (except for cv. Castlemart), but not to those from nymph-infested plants. In a close-range habitat, however, the wasps appeared to use visual or tactile cues derived from nymphs for host location. Volatile analyses and behavioral assays showed that wasp attraction was correlated with enhanced ß-myrcene and ß-caryophyllene emissions from adult-infested plants. Furthermore, the use of B. tabaci adult-induced plant cues under glasshouse conditions resulted in a higher parasitism rate by this parasitoid. CONCLUSION: Our findings confirm that E. formosa uses the HIPVs resulting from feeding of B. tabaci adults to locate host habitat. Release of ß-myrcene and ß-caryophyllene from dispensers may enhance the efficacy of E. formosa as a biological control agent against B. tabaci in glasshouse production systems.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have shown promising local benefits for advanced hepatocellular carcinoma (HCC). S-1, a composite preparation of a 5-fluorouracil prodrug, has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC. AIM: To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC. METHODS: In this single-center, open-label, prospective, randomized controlled trial, 117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with (TACE/HAIC + S-1, n = 56) or without (TACE/HAIC, n = 61) oral S-1 between December 2013 and September 2017. Two participants were excluded from final analysis for withdrawing consent. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate, disease control rate and safety. RESULTS: In total, 115 participants (100 males and 15 females; mean age, 57.7 years ± 11.9) were analyzed. The median PFS and OS were 5.0 mo (0.4-58.6 mo) (95% confidence interval (CI): 3.82 to 6.18) vs 4.4 mo (1.1-54.4 mo) (95%CI: 2.54 to 6.26; P = 0.585) and 8.4 mo (0.4-58.6 mo) (95%CI: 6.88 to 9.92) vs 8.3 mo (1.4-54.4 m) (95%CI: 5.71 to 10.96; P = 0.985) in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. The objective response rate and disease control rate were 30.9% vs 18.4% and 72.7% vs 56.7% in the TACE/HAIC + S-1 and TACE/HAIC groups, respectively. Grade 3/4 adverse events had a similar frequency in both treatment groups. CONCLUSION: No improvements in tumor response rates, PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC. Both treatment regimens had a similar safety profile.

Potential microRNA panel for the diagnosis and prediction of overall survival of hepatocellular carcinoma with hepatitis B virus infection.

BACKGROUND: In hepatocellular carcinoma (HCC), abnormal expression of multiple microRNAs (miRNAs) has been shown to be involved in the malignant biological behavior of liver cancer. The vast majority of liver cancer cases in China are closely related to hepatitis B virus (HBV) infection, but there are few studies on the changes of miRNA expression in the progression from HBV infection to hepatoma. AIM: To explore the role of miRNAs in the progression of HBV infection to cirrhosis and even to liver cancer. METHODS: We screened differentially expressed miRNAs in 40 HBV cirrhosis, 40 normal and 15 HCC tissues by using a TaqMan Low Density Array and real time quantitative polymerase chain reaction. To evaluate the power of the selected miRNAs to predict disease, we calculated the area under the receiver-operating-characteristic curves. The overall survival of HBV cirrhosis patients was analyzed via Kaplan-Meier analysis. RESULTS: The levels of miR-375, miR-122 and miR-143 were significantly lower in HBV cirrhosis tissues, while miR-224 was significantly higher than in the controls (P < 0.0001). The area under the curves of the receiver-operating-characteristic curve for the 4-miRNA panel was 0.991 (95%CI: 0.974-1). Patients with a lower expression level of miR-224 or higher expression levels of miR-375, miR-122 and miR-143 had longer overall survival. CONCLUSION: The four miRNAs (miR-375, miR-122, miR-143 and miR-224) may be helpful for early diagnosis of HBV infection, HBV cirrhosis, and prediction of its overall survival.

Evaluation of the value of multiparameter combined analysis of serum markers in the early diagnosis of gastric cancer.

BACKGROUND: In early gastric cancer (GC), tumor markers are increased in the blood. The levels of these markers have been used as important indexes for GC screening, early diagnosis and prognostic evaluation. However, specific tumor markers have not yet been discovered. Diagnosis based on a single tumor marker has limited significance. The detection rate of GC is still very low. AIM: To improve the diagnostic value of blood markers for GC. METHODS: We used a multiparameter joint analysis of 77 indexes of malignant GC and gastric polyp (GP), 64 indexes of GC and healthy controls (Ctrls). RESULTS: By analyzing the data, there are 27 indexes in the final Ctrls vs GC with P values < 0.01, the area under the curve (AUC) of albumin is the largest in Ctrls vs GC, and the AUC was 0.907. 30 indexes in GP vs GC have P values < 0.01. Among them, the D-dimer showed an AUC of 0.729. The 27 indexes in Ctrls vs GC and 30 indexes in GP vs GC were used for binary logistic regression, discriminant analysis, classification tree analysis and artificial neural network analysis model. For the ability to distinguish between Ctrls vs GC, GP vs GC, artificial neural networks had better diagnostic value when compared with classification tree, binary logistic regression, and discriminant analysis. When compared Ctrl and GC, the overall prediction accuracy was 92.9%, and the AUC was 0.992 (0.980, 1.000). When compared GP and GC, the overall prediction accuracy was 77.9%, and the AUC was 0.969 (0.948, 0.990). CONCLUSION: The diagnostic effect of multi-parameter joint artificial neural networks analysis is significantly better than the single-index test diagnosis, and it may provide an assistant method for the detection of GC.

Clinical value evaluation of serum markers for early diagnosis of colorectal cancer.

BACKGROUND: Early screening for colorectal cancer (CRC) is important in clinical practice. However, the currently methods are inadequate because of high cost and low diagnostic value. AIM: To develop a new examination method based on the serum biomarker panel for the early detection of CRC. METHODS: Three hundred and fifty cases of CRC, 300 cases of colorectal polyps and 360 cases of normal controls. Combined with the results of area under curve (AUC) and correlation analysis, the binary Logistic regression analysis of the remaining indexes which is in accordance with the requirements was carried out, and discriminant analysis, classification tree and artificial neural network analysis were used to analyze the remaining indexes at the same time. RESULTS: By comparison of these methods, we obtained the ability to distinguish CRC from healthy control group, malignant disease group and benign disease group. Artificial neural network had the best diagnostic value when compared with binary logistic regression, discriminant analysis, and classification tree. The AUC of CRC and the control group was 0.992 (0.987, 0.997), sensitivity and specificity were 98.9% and 95.6%. The AUC of the malignant disease group and benign group was 0.996 (0.992, 0.999), sensitivity and specificity were 97.4% and 96.7%. CONCLUSION: Artificial neural network diagnosis method can improve the sensitivity and specificity of the diagnosis of CRC, and a novel assistant diagnostic method was built for the early detection of CRC.

Trade-off between defense priming by herbivore-induced plant volatiles and constitutive defense in tomato.

BACKGROUND: Herbivore-induced plant volatiles (HIPVs) can prime plant defenses and enhance herbivore resistance in neighboring plants. Although a trade-off between constitutive defense and HIPV emission has been documented in many plant species, little is known about the effect of HIPV variation on defense priming, and whether there is a trade-off between defense priming and constitutive defense in neighboring plants. RESULTS: Using three tomato genotypes, including two wild types [Moneymaker (MM) and Castlemart (CM)] and one jasmonic acid (JA) overexpression 35S::prosys genotype, we investigated the effects of exposure to volatiles from plants infested by beet armyworm (Spodoptera exigua) caterpillars on the defenses and resistance of conspecific neighboring plants. We also analyzed the HIPV emissions from the three genotypes and their constitutive defense and resistance. Exposure to volatiles from S. exigua-infested MM plants primed an array of defensive responses (including the accumulation of JA and PI-II protein and the expression of the defense genes PI-I and PI-II), and enhanced plant resistance against the caterpillars. In contrast, exposure to volatiles from S. exigua-infested CM or 35S::prosys did not result in defense priming or an increase in plant resistance. Analyses of HIPVs and gene expression indicated that defense priming in MM was due to enhanced emission of ß-ocimene and linalool. We further demonstrated that levels of constitutive defense and resistance are low in MM and high in CM and 35S::prosys, suggesting a negative correlation between defense priming and constitutive defense. CONCLUSION: Our findings suggest that there is a trade-off between defense priming by HIPVs and constitutive defense in tomato. This suggests that defense priming should be used with caution in agriculture. © 2020 Society of Chemical Industry.

Airborne host-plant manipulation by whiteflies via an inducible blend of plant volatiles.

The whitefly Bemisia tabaci is one of the world's most important invasive crop pests, possibly because it manipulates plant defense signaling. Upon infestation by whiteflies, plants mobilize salicylic acid (SA)-dependent defenses, which mainly target pathogens. In contrast, jasmonic acid (JA)-dependent defenses are gradually suppressed in whitefly-infested plants. The down-regulation of JA defenses make plants more susceptible to insects, including whiteflies. Here, we report that this host-plant manipulation extends to neighboring plants via airborne signals. Plants respond to insect attack with the release of a blend of inducible volatiles. Perception of these volatiles by neighboring plants usually primes them to prepare for an imminent attack. Here, however, we show that whitefly-induced tomato plant volatiles prime SA-dependent defenses and suppress JA-dependent defenses, thus rendering neighboring tomato plants more susceptible to whiteflies. Experiments with volatiles from caterpillar-damaged and pathogen-infected plants, as well as with synthetic volatiles, confirm that whiteflies modify the quality of neighboring plants for their offspring via whitefly-inducible plant volatiles.

Dbx2 exhibits a tumor-promoting function in hepatocellular carcinoma cell lines via regulating Shh-Gli1 signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. HCC patients suffer from a high mortality-to-incidence ratio and low cure rate since we still have no specific and effective treatment. Although tremendous advances have been made in the investigation of HCC, the specific mechanisms of the progression of this disease are still only partially established. Hence, more research is needed to elucidate the underlying potential mechanisms to develop effective strategies for HCC. AIM: To determine the role of developing brain homeobox 2 (Dbx2) gene in promoting the development of HCC. METHODS: Dbx2 expression in clinical specimens and HCC cell lines was detected by Western blot (WB) and immunohistochemistry. Gain and loss of Dbx2 function assays were performed in vitro and in vivo. Cell viability assays were used to investigate cell growth, flow cytometry was employed to assess cell cycle and apoptosis, and trans-well assays were conducted to evaluate cell migration, invasion, and metastasis. The expression of key molecules in the sonic hedgehog (Shh) signaling was determined by WB. RESULTS: Compared to matched adjacent non-tumorous tissues, Dbx2 was overexpressed in 5 HCC cell lines and 76 surgically resected HCC tissues. Dbx2 overexpression was correlated with large tumor size. Both gain and loss of function assays indicated that Dbx2 promoted HCC cell proliferation by facilitating the transition from G1 to S phase, attenuating apoptosis and promoted HCC proliferation, migration, and invasion in vitro and in vivo. Mechanistically, Dbx2 modulated Shh signaling by enhancing FTCH1 and GLi1 expression in HCC cells that overexpressed Dbx2, which was reversed in HCC cells with Dbx2 knockdown. CONCLUSION: Our results indicate that Dbx2 is significantly upregulated in HCC tissues and plays significant roles in proliferation and metastasis of HCC cells by activating the Shh pathway.

Effect of primary tumor side on survival outcomes in metastatic colorectal cancer patients after hepatic arterial infusion chemotherapy.

AIM: To analyze the survival data between patients diagnosed with right-sided primary (RSP) tumors and patients diagnosed with left-sided primary (LSP) tumors after hepatic arterial infusion chemotherapy (HAIC) at our center. METHODS: A retrospective analysis of pretreated metastatic colorectal cancer patients who received HAIC from May 2006 to August 2015 was conducted. A Cox proportional hazard regression analysis was used to assess the long-term survival outcomes. The mean and median age of patients was 61 years (range 27-85 years). There were 115 males and 53 females in our study. RESULTS: One hundred sixty-eight patients were enrolled in this study. The overall response rate was 28.9% in LSP patients and 27.3% in RSP patients. The disease control rate was 76.3% in LSP patients and 69.7% in RSP patients. The median overall survival in response to HAIC was 16.3 mo in the LSP arm and 9.3 mo in the RSP arm (P = 0.164). The median progression-free survival was 5.7 mo in the LSP arm and 4.2 mo in the RSP arm (P = 0.851). CONCLUSION: There was no significant difference in survival between LSP patients and RSP patients after HAIC. Further prospective studies are needed to confirm these findings.

Jasmonic Acid-Dependent Defenses Play a Key Role in Defending Tomato Against Bemisia tabaci Nymphs, but Not Adults.

The silverleaf whitefly Bemisia tabaci is an important and invasive crop pest in many countries. Previous laboratory studies with Arabidopsis demonstrated that B. tabaci can suppress jasmonic acid (JA) defenses and thereby enhance B. tabaci performance. Whether B. tabaci can suppress JA-regulated host plant defenses in field is unknown. In the present study, we found that, relative to wild-type (WT) tomato plants, transgenic tomato mutants that activated JA defenses (35s::prosys) or impaired JA defenses (spr-2 and def-1) did not affect the survival or reproduction of B. tabaci adults in growth chamber experiments. In contrast, tomato mutants that activated JA defenses slowed B. tabaci nymphal development, while mutants that impaired JA defenses accelerated nymphal development. These effects of JA defenses on nymphal development were also documented under semi-field conditions. Changes in the expression of defense genes and in the production of phytohormones indicated that B. tabaci adults can suppress JA-dependent defenses after infestation for >72 h. The suppression of JA was correlated with the induction of salicylic acid (SA) in B. tabaci-infested leaves under laboratory and under semi-field conditions. If SA signaling was blocked, JA accumulation increased in infested leaves and B. tabaci nymphal development was delayed. These results indicate that, although JA signaling helps in mediating tomato responses against B. tabaci nymphs, B. tabaci can inhibit JA biosynthesis and its action in an SA-dependent manner.

Transforming growth factor-ß and peripheral regulatory cells are negatively correlated with the overall survival of hepatocellular carcinoma.

AIM: To understand the cellular and molecular changes in peripheral blood that can lead to the development of hepatocellular carcinoma (HCC) and provide new methods for its diagnosis and treatment. METHODS: Peripheral blood mononuclear cells were isolated from the peripheral blood of HCC patients and normal controls and then analyzed by flow cytometry. The percentage of transforming growth factor-ß (TGF-ß)+ regulatory cells (Tregs) in the peripheral blood was measured, and the expression of TGF-ß was also determined. Then, the relationship between the changes and the 5-year survival of patients was analyzed. In addition, recombinant human TGF-ß (rhTGF-ß) and recombinant human interleukin-6 were added to stimulate the cultured cells, and their effects on HCC were evaluated. RESULTS: The expression of TGF-ß and the percentage of TGF-ß+ Tregs in the peripheral blood of HCC patients increased significantly compared with normal controls. Compared with the low TGF-ß expression group, the high TGF-ß expression group had a significantly lower 5-year survival rate, and the same result was found in the two TGF-ß+ Treg groups, suggesting that TGF-ß and TGF-ß+ Tregs were negatively correlated with the overall survival of the patients. In addition, rhTGF-ß promoted the growth of tumor cells and induced high expression levels of IL-6, which further promoted tumor proliferation. CONCLUSION: The results showed that TGF-ß may promote tumor growth and proliferation by inducing the production of IL-6, and TGF-ß and TGF-ß+ Tregs may serve as new markers for predicting a poor prognosis in HCC.

Novel serum microRNAs panel on the diagnostic and prognostic implications of hepatocellular carcinoma.

AIM: To determine a panel of serum microRNAs (miRNAs) that could be used as novel biomarkers for diagnosis of hepatocellular carcinoma (HCC). METHODS: We initially screened 9 out of 754 serum miRNAs by TaqMan Low Density Array in two pooled samples respectively from 35 HCC and 35 normal controls, and then validated individually by RT-qPCR in another 114 patients and 114 controls arranged in two phases. The changes of the selected miRNAs after operation and their prognostic value were examined. RESULTS: miR-375, miR-10a, miR-122 and miR-423 were found to be significantly higher in HCC than in controls (P < 0.0001), and the area under the receiver-operating-characteristic curve for the 4-miRNA panel was 0.995 (95%CI: 0.985-1). All the four miRNAs were significantly reduced after surgical removal of the tumors (P < 0.0001), while still higher than normal controls (at least P < 0.05). CONCLUSION: The four serum miRNAs (miR-375, miR-10a, miR-122 and miR-423) could potentially serve as novel biomarkers for the diagnostic and prognostic of HCC.