Serum ESPL1 Can Be Used as a Biomarker for Patients With Hepatitis B Virus-Related Liver Cancer: A Chinese Case-Control Study.

AIMS: To investigate the feasibility of serum extra spindle pole bodies-like 1 (ESPL1) used as a biomarker for patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: 131 chronic HBV-infection patients were recruited and divided into HBV S gene integration, non-HBV S gene integration, chronic hepatitis B (CHB), HBV-related liver cirrhosis (LC) and HBV-related HCC group, 24 non-HBV-related HCC patients were selected as HCC control group, 30 people without HBV-infection as healthy control group. Serum ESPL1 were detected and compared. RESULTS: ESPL1 level of integration group was significantly higher than that of non-integration group (346.7 vs 199.6 ng/ml, P = 0.000) and healthy control group (346.7 vs 41.3 ng/ml, P = 0.000). ESPL1 level of non-integration group was significantly higher than that of healthy control group (199.6 vs 41.3 ng/ml, P = 0.000); ESPL1 levels in chronic HBV-infection related groups were increased in turn according to CHB group (95.8 ng/ml), HBV-related LC group (268.2 ng/ml), HBV-related HCC group (279.9 ng/ml) and integration group (346.7 ng/ml). Except that there was no significant difference in ESPL1 levels between HBV-related LC and HCC group (P = 0.662), pairwise comparisons between other groups showed significant differences (P < 0.05). ESPL1 level of HBV-related HCC group was significantly higher than that of non-HBV-related HCC group (279.9 vs 46.6 ng/ml, P = 0.000), there was no noticeable difference between non-HBV-related HCC and healthy control group (46.6 vs 41.3 ng/ml, P = 0.848). ESPL1 level of HBV-related HCC group after resection was significantly lower than that of before resection (178.4 vs 260.8 ng/ml, P = 0.000). CONCLUSIONS: Chronic HBV-infection patients with high ESPL1 level may indicate HBV S gene integration and is a high-risk population for HBV-related HCC. Serum ESPL1 can be used as a biomarker for screening HBV-related HCC high-risk population and monitoring recurrence.

RNA sequencing of plasma exosomes revealed novel functional long noncoding RNAs in hepatocellular carcinoma.

Exosomal long noncoding RNA (lncRNA) has been found to be associated with the development of cancers. However, the expression characteristics and the biological roles of exosomal lncRNAs in hepatocellular carcinoma (HCC) remain unknown. Here, by RNA sequencing, we found 9440 mRNAs and 8572 lncRNAs were differentially expressed (DE-) in plasma exosomes between HCC patients and healthy controls. Exosomal DE-lncRNAs displayed higher expression levels and tissue specificity, lower expression variability and splicing efficiency than DE-mRNAs. Six candidate DE-lncRNAs (fold change 6 or more, P ≤ .01) were high in HCC cells and cell exosomes. The knockdown of these candidate DE-lncRNAs significantly affected the migration, proliferation, and apoptosis in HCC cells. In particular, a novel DE-lncRNA, RP11-85G21.1 (lnc85), promoted HCC cellular proliferation and migration by targeted binding and regulating of miR-324-5p. More importantly, the level of serum lnc85 was highly expressed in both Alpha-fetoprotein (AFP)-positive and AFP-negative HCC patients and allowed distinguishing AFP-negative HCC from healthy control and liver cirrhosis (area under the receiver operating characteristic curve, 0.869; sensitivity, 80.0%; specificity, 76.5%) with high accuracy. Our finding offers a new insight into the association between the dysregulation of exosomal lncRNA and HCC, suggesting that lnc85 could be a potential biomarker of HCC.

High Rate of Detection of Human ESPL1-HBV S Fusion Gene in Patients With HBV-related Liver Cancer: A Chinese Case-Control Study.

AIM: It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis. PATIENTS AND METHODS: Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database. RESULTS: All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001). CONCLUSION: This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.

Function of low back muscle exercise : Preventive effect of refracture analysis of postoperative vertebral fractures.

BACKGROUND: Low back muscles exercise reportedly influence the risk of osteoporotic vertebral fractures. The exact relationship between the low back muscles exercise and the incidence of vertebral refractures remain unclear. OBJECTIVE: To investigate the ability of exercise to strengthen the low back muscles to prevent vertebral refracture after surgery, through clinical analysis of the vertebral fracture risk reduction program. METHODS: In total 152 patients with vertebral fractures who had undergone percutaneous vertebroplasty (PVP) and anti-osteoporosis treatment were randomly divided into observation and control groups. The observation group performed exercises to strengthen the back muscles after surgery. The clinical efficacy and incidence of re-fractures were compared between groups. RESULTS: The observation group had reduced physical dysfunction and pain following surgery. After 3 months, the vertebral body height had significantly decreased (P < 0.05) in the control group but not in the observation group (P > 0.05). In the observation and control groups, the incidence of vertebral refractures was 9.2% (7/76) and 17.1% (13/76), respectively (P < 0.05). CONCLUSION: Postoperative exercise to strengthen the back muscles can improve physical function, relieve pain and promote the recovery of vertebral height; it can also assist in maintaining bone density, thereby significantly reducing the risk of refracture. This approach is safe and effective and can help improve the quality of life in patients with vertebral fractures.

Molecular diversity analysis, drought related marker-traits association mapping and discovery of excellent alleles for 100-day old plants by EST-SSRs in cassava germplasms (Manihot esculenta Cranz).

Cassava is the third largest food crop of the world and has strong ability of drought tolerance. In order to evaluate the molecular diversity and to discover novel alleles for drought tolerance in cassava germplasms, we examined a total of 107 abiotic stress related expressed sequence tags-simple sequence repeat (EST-SSR) markers in 134 cassava genotypes coming from planting regions worldwide and performed drought related marker-traits association mapping. As results, we successfully amplified 98 of 107 markers in 97 polymorphic loci and 279 alleles, with 2.87 alleles per locus, gene diversity of 0.48 and polymorphic information content (PIC) of 0.41 on average. The genetic coefficient between every two lines was 0.37 on average, ranging from 0.21 to 0.82. According to our population structure analysis, these samples could be divided into three sub-populations showing obvious gene flow between them. We also performed water stress experiments using 100-day old cassava plants in two years and calculated the drought tolerance coefficients (DTCs) and used them as phenotypes for marker-trait association mapping. We found that 53 markers were significantly associated with these drought-related traits, with a contribution rate for trait variation of 8.60% on average, ranging between 2.66 and 28.09%. Twenty-four of these 53 associated genes showed differential transcription or protein levels which were confirmed by qRT-PCR under drought stress when compared to the control conditions in cassava. Twelve of twenty-four genes were the same differential expression patterns in omics data and results of qRT-PCR. Out of 33 marker-traits combinations on 24 loci, 34 were positive and 53 negative alleles according to their phenotypic effects and we also obtained the typical materials which carried these elite alleles. We also found 23 positive average allele effects while 10 loci were negative according to their allele effects (AAEs). Our results on molecular diversity, locus association and differential expression under drought can prove beneficial to select excellent materials through marker assisted selection and for functional genes research in the future.

Chilling acclimation provides immunity to stress by altering regulatory networks and inducing genes with protective functions in cassava.

BACKGROUND: Stress acclimation is an effective mechanism that plants acquired for adaption to dynamic environment. Even though generally considered to be sensitive to low temperature, Cassava, a major tropical crop, can be tolerant to much lower temperature after chilling acclimation. Improvement to chilling resistance could be beneficial to breeding. However, the underlying mechanism and the effects of chilling acclimation on chilling tolerance remain largely unexplored. RESULTS: In order to understand the mechanism of chilling acclimation, we profiled and analyzed the transcriptome and microRNAome of Cassava, using high-throughput deep sequencing, across the normal condition, a moderate chilling stress (14°C), a harsh stress (4°C) after chilling acclimation (14°C), and a chilling shock from 24°C to 4°C. The results revealed that moderate stress and chilling shock triggered comparable degrees of transcriptional perturbation, and more importantly, about two thirds of differentially expressed genes reversed their expression from up-regulation to down-regulation or vice versa in response to hash stress after experiencing moderate stress. In addition, microRNAs played important roles in the process of this massive genetic circuitry rewiring. Furthermore, function analysis revealed that chilling acclimation helped the plant develop immunity to further harsh stress by exclusively inducing genes with function for nutrient reservation therefore providing protection, whereas chilling shock induced genes with function for viral reproduction therefore causing damage. CONCLUSIONS: Our study revealed, for the first time, the molecular basis of chilling acclimation, and showed potential regulation role of microRNA in chilling response and acclimation in Euphorbia.