Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

Unraveling the Contribution of MulSOS2 in Conferring Salinity Tolerance in Mulberry (Morus atropurpurea Roxb).

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.

Simulation of a Temperature-Compensated Voltage Sensor Based on Photonic Crystal Fiber Infiltrated with Liquid Crystal and Ethanol.

A simulated design for a temperature-compensated voltage sensor based on photonic crystal fiber (PCF) infiltrated with liquid crystal and ethanol is presented in this paper. The holes distributed across the transverse section of the PCF provide two channels for mode coupling between the liquid crystal or ethanol and the fiber core. The couplings are both calculated accurately and explored theoretically using the finite element method (FEM). The influence of voltage on the alignment of the liquid crystal molecules and confinement loss of the fiber mode are studied. Liquid crystal molecules rotate which changes its properties as the voltage changes. As the characteristics of the liquid crystal will be affected by temperature, therefore, we further fill using ethanol, which is merely sensitive to temperature, into one hole of the PCF to realize temperature compensation. The simulated results show that the sensitivity is up to 1.29977 nm/V with the temperature of 25 °C when the voltage ranges from 365 to 565 V. The standard deviation of the wavelength difference is less than 2 nm within the temperature adjustment from 25 to 50 °C for temperature compensation. The impacts of the construction parameters of the PCF on sensing performances of this voltage sensor are also analyzed in this paper.

Detection of anti-kelch-like 12 and anti-hexokinase 1 antibodies in primary biliary cholangitis patients in China.

OBJECTIVES: primary biliary cholangitis (PBC) is a chronic cholestatic disease, characterized by positive anti-mitochondrial autoantibodies (AMA) in 90-95 % patients. Anti-kelch-like 12 (anti-KLHL12) and anti-hexokinase1 (anti-HK1) antibodies have been identified as the two new serum markers in recent years, which are used in the diagnosis of AMA-negative PBC patients. The objective of the study was to examine the performance of these two new biomarkers in China. METHODS: a total of 192 patients were enrolled and screened for anti-KLHL12 and anti-HK1 antibodies and AMA by ELISA. Receiver operating characteristic (ROC curve) analysis was applied to examine the diagnostic importance of AMA, anti-KLHL12 and anti-HK1 antibodies. Furthermore, correlation analysis between some important biochemical indexes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], bilirubin, gamma-glutamil transferasa [γ-GT]), staging of pathological changes of the liver and the expression of novel antibodies in PBC patients were also examined. RESULTS: the positivity of the anti-HK1 antibody in AMA-positive PBC patients and AMA-negative patients was 44.7 % and 33.3 %, respectively. The specificity, proportion of positive patients (PPV) and proportion of negative patients (NPV) were 93 %, 89 % and 53 %, respectively. In contrast, the positivity to the anti-KLHL12 antibody in AMA-positive and negative PBC patients was 41.2 % and 22.2 %, respectively. Specificity, PPV and NPV were 98 %, 95 % and 52 %, respectively. The area under the curve (AUC) with anti-HK1 and anti-KLHL12 antibodies were 0.720 and 0.703. With the combination with anti-HK1 and anti-KLHL12 antibodies, the AUC of AMA increased from 0.889 to 0.891, increasing the sensitivity from 0.764 to 0.836. Anti-KLHL12 and anti-HK1-positive patients had higher serum levels of ALP, γ-GT and bilirubin, with statistically significant differences (p < 0.01) compared with anti-KLHL12 or anti-HK1-negative patients. Notably, correlation analysis showed a significant positive correlation between antibody expression and ALP, γ-GT and bilirubin serum levels (r = 0.735, 0.491, 0.466; p < 0.01). CONCLUSIONS: anti-HK1 and anti-KLHL12 antibodies have been identified as two significant biomarkers in PBC patients. Furthermore, the presence of these antibodies is likely to correlate with the severity of PBC.

Long Non-Coding RNA CRNDE Regulates Angiogenesis in Hepatoblastoma by Targeting the MiR-203/VEGFA Axis.

OBJECTIVE: MiR-203 has been shown to participate in multiple malignancies, but the role of miR-203 in hepatoblastoma (HB) remains unclear. The aim of our study was to investigate the effects of miR-203 in HB. METHODS: A total of 15 pairs of HB tissues and para-tumour normal tissues were collected for the experiments. RT-qPCR and Western blotting were performed to detect the expression of CRNDE, miR-203, and VEGFA at the mRNA and/or protein levels, respectively. A dual luciferase assay verified the target relationship between miR-203 and the 3'UTR of VEGFA as well as miR-203 and CRNDE. In addition, MTT, wound healing, and tube formation assays were performed to assess the effects of miR-203, VEGFA, and CRNDE on cell proliferation, migration, and angiogenesis, respectively. RESULTS: Our data revealed that miR-203 expression was decreased in HB tissues, while long non-coding RNA (lncRNA) CRNDE expression was increased. The dysregulation of miR-203 and CRNDE was closely related to tumour size and stage. Moreover, overexpression of miR-203 inhibited angiogenesis. A dual luciferase assay verified that VEGFA is a direct target of miR-203 and that CRNDE binds to miR-203. Furthermore, our results showed that miR-203 suppressed cell viability, migration, and angiogenesis by regulating VEGFA expression. Additionally, it was confirmed that CRNDE promoted angiogenesis by negatively regulating miR-203 expression. CONCLUSION: lncRNA CRNDE targets the miR-203/VEGFA axis and promotes angiogenesis in HB. These results provide insight into the underlying mechanisms of HB and indicate that CRNDE and miR-203 might be potential targets for HB therapy.

Integrated Phloem Sap mRNA and Protein Expression Analysis Reveals Phytoplasma-infection Responses in Mulberry.

To gain insight into the response of mulberry to phytoplasma-infection, the expression profiles of mRNAs and proteins in mulberry phloem sap were examined. A total of 955 unigenes and 136 proteins were found to be differentially expressed between the healthy and infected phloem sap. These differentially expressed mRNAs and proteins are involved in signaling, hormone metabolism, stress responses, etc. Interestingly, we found that both the mRNA and protein levels of the major latex protein-like 329 (MuMLPL329) gene were increased in the infected phloem saps. Expression of the MuMLPL329 gene was induced by pathogen inoculation and was responsive to jasmonic acid. Ectopic expression of MuMLPL329 in Arabidopsis enhances transgenic plant resistance to Botrytis cinerea, Pseudomonas syringae pv tomato DC3000 (Pst. DC3000) and phytoplasma. Further analysis revealed that MuMLPL329 can enhance the expression of some defense genes and might be involved in altering flavonoid content resulting in increased resistance of plants to pathogen infection. Finally, the roles of the differentially expressed mRNAs and proteins and the potential molecular mechanisms of their changes were discussed. It was likely that the phytoplasma-responsive mRNAs and proteins in the phloem saps were involved in multiple pathways of mulberry responses to phytoplasma-infection, and their changes may be partially responsible for some symptoms in the phytoplasma infected plants.

Gene coexpression networks reveal key drivers of phenotypic divergence in porcine muscle.

BACKGROUND: Domestication of the wild pig has led to obese and lean phenotype breeds, and evolutionary genome research has sought to identify the regulatory mechanisms underlying this phenotypic diversity. However, revealing the molecular mechanisms underlying muscle phenotype variation based on differentially expressed genes has proved to be difficult. To characterize the mechanisms regulating muscle phenotype variation under artificial selection, we aimed to provide an integrated view of genome organization by weighted gene coexpression network analysis. RESULTS: Our analysis was based on 20 publicly available next-generation sequencing datasets of lean and obese pig muscle generated from 10 developmental stages. The evolution of the constructed coexpression modules was examined using the genome resequencing data of 37 domestic pigs and 11 wild boars. Our results showed the regulation of muscle development might be more complex than had been previously acknowledged, and is regulated by the coordinated action of muscle, nerve and immunity related genes. Breed-specific modules that regulated muscle phenotype divergence were identified, and hundreds of hub genes with major roles in muscle development were determined to be responsible for key functional distinctions between breeds. Our evolutionary analysis showed that the role of changes in the coding sequence under positive selection in muscle phenotype divergence was minor. CONCLUSIONS: Muscle phenotype divergence was found to be regulated by the divergence of coexpression network modules under artificial selection, and not by changes in the coding sequence of genes. Our results present multiple lines of evidence suggesting links between modules and muscle phenotypes, and provide insights into the molecular bases of genome organization in muscle development and phenotype variation.

Characterization and Genome Sequencing of a Novel Bacteriophage PH101 Infecting Pseudoalteromonas marina BH101 from the Yellow Sea of China.

A novel Pseudoalteromonas marina bacteriophage, PH101, specifically infecting Pseudoalteromonas BH101 was isolated from the water sample of the Yellow Sea of China using the agar overlay method. 16S rDNA sequence identification was used to identify the host bacteria. Efficiency of infection, multiplicity of infection value, morphological characterization, one-step growth curve, and host range of the bacteriophage were determined. Purified PH101 genomic DNA was extracted and its genome was completely sequenced and analyzed. The phage morphology showed that PH101 belongs to the Myoviridae family with a head of 60 nm in diameter and a tail of 40 nm with a tail fiber of 10-20 nm. Microbiological characterization demonstrated that phage PH101 is stable at a wide range of temperatures (0-70 °C) and showed acid and alkaline resistance (pH 3-12). The one-step growth curve showed a latent period of about 20 min, a rise period of 20 min, and a burst size of about 31.6 virions. The genome sequencing and bioinformatic analysis shows that phage PH101 was a novel bacteriophage which was found to consist of a linear, double-stranded 131,903-bp DNA molecule with a GC content of 37.36 % and 228 putative open reading frames without RNA, which were classified into seven functional groups, including phage structure, adsorption, packaging, gene transfer protease, terminase, DNA binding, and regulation.

Effect of acupuncture at neck-Jiaji (EX-B 2) and tuina on the cognitive function in the patients with subjective cognitive decline. / é’ˆåˆºé¢ˆå¤¹è„Šç©´è”åˆæŽ¨æ‹¿å¯¹ä¸»è§‚è®¤çŸ¥ä¸‹é™æ‚£è€ è®¤çŸ¥åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To observe the effects on cognitive function, sleep quality and hemodynamics in the patients with subjective cognitive decline (SCD) after treated with acupuncture at neck-Jiaji (EX-B 2) and tuina on the base of healthy lifestyle education and meta-memory training. METHODS: Sixty SCD patients were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 3 cases dropped out). In the control group, the healthy lifestyle education and meta-memory training was performed, twice daily, 15 min each time; the 5-day intervention was delivered a week, lasting consecutively 4 weeks. On the base of the intervention as the control group, in the observation group, acupuncture at neck-Jiaji (EX-B 2) and tuina was conducted. First, one-finger pushing and plucking method of tuina was exerted on the neck region along the running courses of the bladder meridian of foot-taiyang and the governor vessel, for 10 min to 15 min; afterwards, acupuncture was delivered at bilateral neck-Jiaji (EX-B 2), from C1 to C7; and the needles were retained for 30 min. This intervention was given once daily, 5 times a week, for consecutive 4 weeks. Before and after treatment, the score of the mini-mental state examination (MMSE), the score of full scale memory quotient (FSMQ) were assessed by Wechsler memory scale-fourth edition (WMS-Ⅳ) and the score of the Pittsburgh sleep quality index (PSQI) was compared between the two groups. Using transcranial Doppler ultrasound, the hemodynamic indexes (the mean velocity [Vm] and pulsatility index [PI] of the left vertebral artery [LVA], the right vertebral artery [RVA] and the basilar artery [BA]) were determined in the two groups. RESULTS: After treatment, the scores of MMSE and FSMQ increased compared with those before treatment in the two groups (P<0.05, P<0.001), PSQI score was lower (P<0.05) and Vm of BA was higher (P<0.001) in the observation group when compared with those before treatment. The scores of MMSE and FSMQ, as well as Vm of BA were higher (P<0.05, P<0.001), and PSQI score was decreased (P<0.05) in the observation group when compared with the control group. CONCLUSIONS: The combined therapy of acupuncture at neck-Jiaji (EX-B 2) and tuina is more advantageous to improving cognitive function, relieving chronic emotional stress and ameliorating sleeping quality in the patients with subjective cognitive decline, which may be achieved by improving the blood supply of the basilar artery.

Topical halometasone cream combined with fire needle pre-treatment for treatment of primary cutaneous amyloidosis: Two case reports.

BACKGROUND: Primary cutaneous amyloidosis (PCA) is a chronic metabolic skin disease that has a detrimental impact on physical and mental health. It appears as mossy papules and severe itching, which is long-term and recurrent. Traditional treatments are unsatisfactory, especially for refractory cases. Fire needle therapy, which is widely used in China, has shown good clinical efficacy, as well as advantages concerning safety and cost. Clinical reports about fire needle treatment of this disease are few at present. CASE SUMMARY: We report two older men who had developed maculopapules with itchiness on the trunk and arms for more than 10-15 years. Due to the dermatopathological findings, PCA was our primary consideration. They received topical halometasone cream and pretreatment with fire needle for 8-16 wk. Both patients showed significant improvement of lesions. Neither patient had recurrence with a minimum of 2 years of follow-up. CONCLUSION: Topical halometasone cream and pretreatment with fire needle could be a fast, safe, and economic treatment for PCA.

Effects of Dicer1 targeted by EBV-miR-BART6-5p on biological properties and radiosensitivity of nasopharyngeal carcinoma.

OBJECTIVE: To discuss the effects of Epstein-Barr virus (EBV)-encoded BamHI A rightward transcript (BART) microRNA (miR-BART6-5p) by targeting Dicer1 on biological properties and radiosensitivity of nasopharyngeal carcinoma (NPC). METHODS: NPC patients (n = 96) treated with radiotherapy were collected from Jan 2010 to Jan 2011. Real-time quantitative PCR (qRT-PCR) and western blot were carried out to measure the expression of miR-BART6-5p and Dicer1. Dual luciferase reporter gene assay verified that miR-BART6-5p targeted Dicer1. CCK8, wound-healing, Transwell and Annexin-FITC/PI were employed to evaluate the effects of Dicer1 mediated by miR-BART6-5p on biological characteristics of NPC cells. The radiosensitivity of miR-BART6-5p targeting Dicer1 was assessed in vitro and in vivo. RESULTS: Increased miR-BART6-5p and decreased Dicer1 were discovered in NPC patients, displaying a close association with T-stage, clinical stage, as well as Pre-DNA of NPC. While elevated Dicer1 and miR-BART6-5p down-regulation in NPC patients were found after effective radiotherapy. Both miR-BART6-5p and Dicer1 were prognostic factors of NPC. Down-regulation of miR-BART6-5p could enhance Dicer1 expression and inhibit NPC cell proliferation, invasion and migration with promoted apoptosis. Clone formation assay also showed miR-BART6-5p down-regulation reduced planting efficiency (PE), which further decreased with the increased dose of irradiation. Injection with miR-BART6-5p inhibitors in nude mice after 6-Gy irradiation contributed to the overexpression of Dicer1 and the inhibition of tumor growth. CONCLUSIONS: EBV-miR-BART6-5p may target Dicer1 to facilitate proliferation and metastasis of NPC cells and suppress apoptosis, thus being a new target for NPC therapy.

Therapeutic effectiveness of slow-release PLGA-oxaliplatin microsphere on human colorectal tumor-bearing mice.

The aim was to develop a slow-release poly-lactic-coglycolic acid (PLGA)-oxaliplatin microsphere and to assess the therapeutic effectiveness and safety of this preparation on colorectal tumor in vivo. The PLGA-oxaliplatin microsphere was prepared based on a spray-drying method, and the drug loading and in-vitro oxaliplatin release profile were carried out using high performance liquid chromatography. The inhibiting effect on tumor growth was examined using in-vivo subcutaneously inoculated colorectal tumor models of nude mice. The size of the microsphere was less than 100 microm, drug loading was 18-22% and drug release time lasted as long as 30 days. PLGA-oxaliplatin microspheres significantly restrained tumor growth and this effect correlated with decreased expression of proliferating cell nuclear antigen and increased expression of terminal deoxynucleotidyltransferase dUTP nick end labeling in tumor cells. Bodyweight measurement and blood analysis did not suggest significant adverse effects on the mice during the study. The PLGA-oxaliplatin microsphere developed here was suitable for regional use; it appears safe and effective in controlling the tumor growth. This preparation shows promise in reducing local recurrence of colorectal cancer after resection, but needs further investigation.

Mesenchymal stem cell-derived exosomes: Toward cell-free therapeutic strategies in regenerative medicine.

Mesenchymal stem cells (MSCs) are multipotent stem cells with marked potential for regenerative medicine because of their strong immunosuppressive and regenerative abilities. The therapeutic effects of MSCs are based in part on their secretion of biologically active factors in extracellular vesicles known as exosomes. Exosomes have a diameter of 30-100 nm and mediate intercellular communication and material exchange. MSC-derived exosomes (MSC-Exos) have potential for cell-free therapy for diseases of, for instance, the kidney, liver, heart, nervous system, and musculoskeletal system. Hence, MSC-Exos are an alternative to MSC-based therapy for regenerative medicine. We review MSC-Exos and their therapeutic potential for a variety of diseases and injuries.

Organic cation directed one-dimensional cuprous halide compounds: syntheses, crystal structures and photoluminescence properties.

In recent years, organic-inorganic hybrid metal halides have emerged as a highly promising class of semiconducting light emitting diodes (LEDs) due to their fascinating photoluminescence properties. Here, by specifically selecting different organic cations as templates, a series of new hybrid cuprous halides have been solvothermally prepared, namely [Me-Py]CuI2 (1), [(Me)2-DABCO]Cu2I4 (2), [Me-MePy]Cu2I3 (3), and [H2DABCO]Cu3X5 (X = I (4) and Br (5)). These hybrid cuprous halides feature one-dimensional (1D) [CuI2]-, [Cu2I3]- and [Cu3X5]2- (X = Br, I) chains surrounded and charge-balanced by organic cations. Under UV photoexcitation, these hybrid cuprous halides exhibit strong tunable photoluminescence from cyan (480 nm) to red (675 nm) emissions with large Stokes shifts (345 nm). The intrinsic nature of PL emissions is also investigated based on temperature-dependent PL emission, lifetime, photoluminescence quantum efficiencies, etc.

Effects of polaprezinc on gastric mucosal damage and neurotransmitters in a rat model of chemotherapy-induced vomiting.

Objective To investigate the effects of polaprezinc (PZ) on cyclophosphamide (CTX)- or cisplatin (DDP)-induced gastric mucosal injury and on a rat model of neurotransmitter-mediated vomiting. Methods Sprague-Dawley rats were divided at random into Control, CTX, DDP, PZ+CTX, and PZ+DDP groups. After 20 days, brain tissues and sera were analyzed for the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and nuclear factor kappa B (NF-κB). Hematoxylin and eosin-stained sections of stomach, intestine, and brain tissues were examined using light microscopy. Results The levels of DA, 5-HT, and NF-κB in brain and serum samples of rats treated with CTX or DDP were significantly increased compared with those of rats in the Control group. There was a significant decrease in these values in the PZ group. Moreover, PZ reduced damage to brain tissue caused by CTX or DDP. Conclusions PZ decreased the levels of DA, 5-HT, and NF-κB in blood and brain tissues caused by CTX or DDP and reduced the chemotherapy-induced damage to the small intestine, stomach, and brain. These findings can be translated to the clinic to enhance the efficacy and safety of chemotherapy.

High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers.

Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients.

High TGF-ß1 expression predicts poor disease prognosis in hepatocellular carcinoma patients.

Transforming growth factor beta (TGF-ß) promotes the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between TGF-ß1 expression and clinicopathological parameters in HCC patients from The Cancer Genome Atlas (TCGA), as well as the prognostic power of TGF-ß1 expression. Eligible studies were retrieved from several databases, and effects (hazard ratios (HRs) with 95% confidence intervals (CIs)) for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free survival (MFS), and progression-free survival (PFS) were pooled to assess the prognostic ability of TGF-ß1 expression in HCC patients. Twelve qualified articles and our TCGA data comprising 2,021 HCC patients were incorporated. In the TCGA analysis, HCC patients with higher TGF-ß1 expression presented a shorter OS than those with lower TGF-ß1 expression (HR = 1.42, p < 0.05). In the meta-analysis, univariate analyses showed that HCC patients with higher TGF-ß1 expression had a shorter OS (pooling HR = 1.71, p < 0.01) and DFS/RFS/MFS/PFS (pooling HR = 1.60, p < 0.01) than those with lower TGF-ß1 expression. In conclusion, our results suggested that high TGF-ß1 expression promotes a poor prognosis in HCC patients.

Cryptotanshinone Induces Pro-death Autophagy through JNK Signaling Mediated by Reactive Oxygen Species Generation in Lung Cancer Cells.

Cryptotanshinone (CTS), a natural product isolated from Salvia miltiorrhiza Bunge, demonstrates anticancer effect. Previous reports showed that CTS induced caspase-independent cell death. Here, we reported that CTS induced pro-death autophagy in human lung cancer cells. CTS inhibited the proliferation of A549 cells in a time- and concentration- dependent manner. CTS triggered autophagy as confirmed by monodansylcadaverine staining, transmission electron microscopy analysis, as well as western blot detection of microtubule-associated protein light-chain 3 (LC3). CTS induced intracellular reactive oxygen species (ROS) formation in a concentration- and time-dependent manner, which was reversed by N-acetyl-L-cysteine (NAC), catalase, diphenyleneiodonium (DPI), pyrrolinodimethylthiocarbamate (PDTC), and dicumarol. Furthermore, CTS-induced autophagy was inhibited by NAC, JNK siRNA and SP600125. NAC reversed CTS-induced JNK phosphorylation. NAC, 3-methyladenine (3-MA), and SP600125 partly reversed CTS-induced cell death. In addition, CTS (10 mg/kg) dramatically inhibited tumor growth by 48.3% in A549 xenograft nude mice, which was completely reversed by NAC (50 mg/kg) co-treatment. Our findings showed that CTS induced pro-death autophagy through activating JNK signaling mediated by increasing intracellular ROS production.

Low-Frequency Ultrasound Enhances Paclitaxel Efficacy in EMT6 Subcutaneous Tumors in Balb/c Mice.

BACKGROUND: The objective of this study was to explore the effects of 30 kHz ultrasound on the efficacy of paclitaxel in subcutaneous breast tumors in Balb/c mice in vivo. MATERIALS AND METHODS: 40 Balb/c female mice were divided into 5 groups: model control group, paclitaxel intraperitoneal (ip) group (20 mg/kg, ip, at 3 day intervals for a total of 3 doses (q3d×3)), paclitaxel intratumoral (it) group (20 mg/kg, it, q3d×3), paclitaxel intraperitoneal (20 mg/kg, ip, q3d×3) combined with low-frequency ultrasound (LFU) group, and paclitaxel intratumoral (20 mg/kg, it, q3d×3) combined with LFU group. Ultrasound parameters were 30 kHz, 200 MW intensity, 15 min, q3d×3. The antitumoral effect was determined by examining the tumor weight in subcutaneously inoculated EMT6 breast carcinoma models in Balb/c mice. All subcutaneous tumors were examined using high performance liquid chromatography (HPLC) upon completion of the experiments. Drug concentrations in the subcutaneous tumors were also analyzed using HPLC. Finally, paraffin sections of the subcutaneous tumors were made, and after hematoxylin and eosin staining, the tumor morphology was examined under a light microscope. RESULTS: LFU combined with paclitaxel significantly restrained tumor growth in transplanted subcutaneous EMT6 tumors in Balb/c mice, and this effect correlated with increased local concentrations of paclitaxel in the tumors. Body weight measurement did not reveal significant adverse effects on the Balb/c mice during the study. CONCLUSION: LFU combined with paclitaxel has a significant synergistic effect in the treatment of breast cancer.