Functional identification of the different regions in B-class floral homeotic MADS-box proteins IiAP3 and IiPI from Isatis indigotica.

APETALA3 (AP3) and PISTILLATA (PI) are B-class MADS-box floral homeotic genes of Arabidopsis and are involved in specifying the identity of petals and stamens. In the present work, IiAP3 and IiPI, the respective orthologous genes of AP3 and PI, were cloned from Isatis indigotica. By expressing in ap3-6 and pi-1 homozygous mutant and in wild-type Arabidopsis under the control of AP3 promoter or CaMV 35S promoter, we demonstrated that IiAP3 and IiPI were functionally equivalent to AP3 and PI of Arabidopsis. Referring to previous reports and the research results in the present work, expression patterns of AP3 and PI homologs are not the same in different angiosperms possessing diverse floral structures. It suggests that the alterations in expression may contribute to the changing morphology of flowers. To further determine the relationship between IiAP3 and IiPI, the coding sequences of the different structural regions in these two proteins were swapped with each other, and the data collected from transgenic Arabidopsis plants of the chimeric constructs suggested that MADS domain was irreplaceable for the function of IiAP3, K domain of IiAP3 was involved in specifying the identity of stamens, K domain of IiPI was mainly related to the formation of petals, and C-terminal region of IiPI was involved in characterization of stamens. In addition, a complete KC region of these two proteins was more effective in phenotypic complementation of the mutants.

Author Correction: AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition.

Deregulated Polycomb repressive complex 2 (PRC2) is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. Disrupting the EZH2-EED interaction, which is required for PRC2 enzymatic activity, is a promising strategy for cancer treatment. However, this kind of inhibitors are still limited. The in-cell protein-protein interaction screening was conducted for approximately 1300 compounds by NanoBRET technology. Co-immunoprecipitation (Co-IP), protein thermal shift assay (PTSA), and cellular thermal shift assay (CETSA) were performed to investigate the regulation of PRC2 by AZD9291. The anti-tumor effects of AZD9291 on breast cancer (BC) cells and diffuse large B-cell lymphoma (DLBCL) cells were detected. MicroRNA array assay, luciferase reporter assay, and qRT-PCR were conducted to identify the interaction and regulation among AZD9291, EZH2, and miR-34a. We discovered that, AZD9291, a potent and selective EGFR inhibitor, disrupted the interaction of EZH2-EED, leading to impairment of PRC2 activity and downregulation of EZH2 protein. In addition, AZD9291 declined EZH2 mRNA expression via upregulating the expression of a tumor suppressor, miR-34a. Our results suggest that AZD9291 can serve as a lead compound for further development of antagonist of PRC2 protein-protein interactions and EZH2 mRNA may be a direct target of miR-34a through non-canonical base pairing.

Older adults show less interference from task-irrelevant social categories: evidence from the garner paradigm.

Though age-related difference in most cognitive performance has been found, there was no previous research examining age difference in multiple social categorizations. Using faces as stimuli and Garner Selective Attention Paradigm, this study explored the different characteristics of implicit and explicit social categorization between young and older adults. The results showed that young perceivers explicitly categorized gender and age of the faces faster and more readily than older perceivers did. When young adults judged specific category (gender category in Experiment 1; age category in Experiment 2), they were interfered from the completing irrelative category; however, irrelative category could not capture older adults' attention. These results first suggest perceivers' age indeed plays an important role in multiple social categorizations.

Effect of iron on cholesterol 7α-hydroxylase expression in alcohol-induced hepatic steatosis in mice.

Both iron and lipids are involved in the progression of alcoholic fatty liver disease (AFLD), but the interaction between iron and lipids in AFLD is unclear. Here, we tested the hypothesis that iron regulates the expression of genes involved in lipid metabolism through iron regulatory proteins (IRPs), which interact with the iron-responsive elements (IREs) in the untranslated regions (UTRs) of genes, resulting in lipid accumulation. Using "RNA structure software", we predicted the mRNA secondary structures of more than 100 genes involved in lipid metabolism to investigate whether the IRE structure exists in novel mRNAs. Cholesterol 7α-hydroxylase (Cyp7a1) has an IRE-like stem-loop, a noncanonical IRE structure, in its 3'-UTR. Cyp7a1 expression can be regulated by in vivo and in vitro iron treatment. In addition, the noncanonical IRE motif can efficiently bind both to IRP1 and IRP2. The results indicate that hepatic iron overloading in AFLD mice decreased Cyp7a1 expression and resulted in cholesterol accumulation, providing a new mechanism of iron-regulated gene transcription and translation through the interaction between iron and a noncanonical IRE structure in Cyp7a1 mRNA. This finding has significant implications in studying a proposed mechanism for the regulation of cholesterol homeostasis by an Fe/IRP/noncanonical IRE axis.

Mesomorphism Modulation of Perfluorinated Janus Triphenylenes by Inhomogeneous Chain Substitution Patterns.

Two isomeric series of compounds with "inverted" chains' substitution patterns, 7,10-dialkoxy-1,2,3,4-tetrafluoro-6,11-dimethoxytriphenylene and 6,11-dialkoxy-1,2,3,4-tetrafluoro-7,10-dimethoxytriphenylene, labelled respectively p-TPFn and m-TPFn, and two non-fluorinated homologous isomers, 3,6-dibutoxy-2,7-dimethoxytriphenylene and 2,7-dibutoxy-3,6-dimethoxytriphenylene, p-TP4 and m-TP4, respectively, were synthesized in three steps and obtained in good yields by the efficient transition-metal-free, fluoroarene nucleophilic substitution via the reaction of appropriate 2,2'-dilithium biphenylenes with either perfluorobenzene, C6 F6 , to yield p-TPFn and m-TPFn, or o-difluorobenzene, C6 H4 F2 , for p-TP4 and m-TP4, respectively. The single-crystal structures of p-TPF4, m-TPF4 and p-TP4, unequivocally confirmed that the cyclization reactions occurred at the expected positions, and that the fluorinated molecules stack up into columns with short separation, a propitious situation for the emergence of columnar mesophases. The mesomorphous properties were found to be greatly affected by both chains' length and positional isomerism: a Colhex phase is found for p-TPF4 and m-TPF4, but mesomorphism vanishes in p-TPF6, and changes for the isomeric homologs m-TPFn, with the induction for n≥6 of a lamello-columnar phase, LamColrec . As expected, both non-fluorinated compounds are deprived of mesomorphism. These compounds emit blue-violet colour in solution, independently of the chains' substitution pattern, and the absolute fluorescence quantum yields can reach up to 46 %. In thin films, fluorescence is slightly redshifted.

Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies.

Objective: VATER/VACTERL-like association is associated with adverse pregnancy outcomes. Genetic evidence of this disorder is sporadic. In this study, we aimed to provide genetic insights to improve the diagnosis of VACTERL. Methods: We have described a Chinese family in which four members were affected by renal defects or agenesis, anal atresia, and anovaginal fistula, which is consistent with the diagnosis of a VACTERL-like association. Pedigree and genetic analyses were conducted using genome and exome sequencing. Results: Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals, harboring a 196-380 kb microdeletion on Xq27.1, which was identified by familial exome sequencing. Genome sequencing was performed on the affected male, confirming a -196 kb microdeletion in Xq27.1, which included a 28% loss of the CDR-1 gene. Four family members were included in the co-segregation analysis, and only VACTERL-like cases with microdeletions were reported in X27.1. Conclusion: These results suggest that the 196-380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like association. However, further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

[Application of DNA methyltransferase inhibitors for myelodysplastic syndrome].

Epigenetic research plays an important role in the malignant tumor genotyping and tumor clinical treatment recently. Epigenetics is the study of changes in gene function that are mitotically and/or meiotically heritable and that do not entail a change in DNA sequence, including DNA methylation and histone modifications. DNA methylation is one of the most important epigenetic modifications often occurring on the cytosine of CpG islands located in gene promoter regions, which is thought to be closely correlated with tumorigenesis. The inducibility and reversibility of DNA methylation provide us an insight into tumor development and treatment. Aberrant DNA hypermethylation is associated with the progress of myelodysplastic syndrome (MDS). The DNA methyltransferase inhibitors (azacytidine and decitabine) have achieved suc-cess in treating high-and intermediate-risk MDS. This will bring new ideas to understand the cause and develop the treat-ment of MDS. This review mainly introduces the latest progress of the action mechanism of those two medicines, the clini-cal effect and new problems during the clinical application on MDS.

Xylem formation of Populus euphratica and its response to water-heat factors in the lower reaches of Tarim River, China.

To deeply understand the effects of water and temperature factors on the xylem formation of Populus euphratica, taking the Yingsu section in the lower reaches of Tarim River as an example, we selected micro-coring samples of P. euphratica around monitoring wells F2 and F10 in the 100 and 1500 m distance from the channel of Tarim River. We used wood anatomy method to analyze the xylem anatomy of P. euphratica and its response to water and temperature factors. The results showed that the changes of the total anatomical vessel area and the vessel number of P. euphratica in the two plots were basically consistent during the whole growing season. The vessel number of xylem conduits of P. euphratica increased slowly with the increases of groundwater depth, while the total conduit area increased firstly and then decreased. The total vessel area, minimum vessel area, average vessel area, and maximum vessel area of P. euphratica xylem increased significantly with the increases of temperature in the growing season. The contribution of groundwater depth and air temperature to P. euphratica xylem varied among different growth stages. In the early growing season, air temperature had the largest contribution to the number and total area of xylem conduits of P. euphratica. During the middle growing season, air temperature and groundwater depth jointly affected the parameters of each conduit. During the later growing season, groundwater depth had the largest contribution to the number and total area of conduits. Results of the sensitivity analysis indicated that the groundwater depth sensitive to xylem vessel number change of P. euphratica was 5.2 m and that to the change in the total conduit area was 5.9 m. The temperature sensitive to total vessel area of P. euphratica xylem was 22.0 ℃, and that to average vessel area was 18.5 ℃. Therefore, the sensitive groundwater depth affecting xylem growth was at the range of 5.2-5.9 m, and the sensitive temperature was at the range of 18.5-22 ℃. This study could provide scientific basis for the restoration and protection of P. euphratica forest in the lower reaches of Tarim River.

The incidence of vasovagal reactions during earlobe piercing.

Background: Vasovagal reactions are common amongst patients with a fear of needles receiving injections or during venipuncture, but they are rarely studied in healthy people undergoing earlobe piercing. The purpose of this prospective study was to evaluate the incidence and the features of vasovagal reactions observed during earlobe piercing. Methods: Thousand eight hundred and sixty six participants aged older than 13 years had their earlobes pierced in our department from January 2020 to January 2022. When vasovagal reactions occurred during the procedure (e.g., dizziness, pallor, diaphoresis, and faintness, etc.), they were recorded and more detailed demographic information was collected. Results: A total of 196 cases of vasovagal reactions were reported in females amongst 1,866 participants, including 58 who actually lost consciousness during earlobe piercing. The incidence of vasovagal reactions and vasovagal syncope was 10.5 and 3.11% respectively. All syncopal reactions occurred in persons younger than 30 years. Conclusion: Vasovagal syncope is often very sudden and occurs without warning. Practitioners need to be familiar with these reactions, and prevent people from an unpredictable fall and subsequent injury during ear piercing.

SEPALLATA--like genes of Isatis indigotica can affect the architecture of the inflorescences and the development of the floral organs.

BACKGROUND: The architecture of inflorescence and the development of floral organs can influence the yield of seeds and have a significant impact on plant propagation. E-class floral homeotic MADS-box genes exhibit important roles in regulation of floral transition and differentiation of floral organs. Woad (Isatis indigotica) possesses unique inflorescence, floral organs and fruit. However, very little research has been carried out to determine the function of MADS-box genes in this medicinal cruciferous plant species. RESULTS: SEPALLATA orthologs in I. indigotica were cloned by degenerate PCR. The sequence possessing the highest identity with SEP2 and SEP4 of Arabidopsis were named as IiSEP2 and IiSEP4, respectively. Constitutive expression of IiSEP2 in Columbia (Col-0) ecotype of Arabidopsis led to early flowering, and the number of the flowers and the lateral branches was reduced, indicating an alteration in architecture of the inflorescences. Moreover, the number of the floral organs was declined, the sepals were turned into carpelloid tissues bearing stigmatic papillae and ovules, and secondary flower could be produced in apetalous terminal flowers. In 35S::IiSEP4-GFP transgenic Arabidopsis plants in Landsberg erecta (Ler) genetic background, the number of the floral organs was decreased, sepals were converted into curly carpelloid structures, accompanied by generation of ovules. Simultaneously, the size of petals, stamens and siliques was diminished. In 35S::IiSEP4-GFP transgenic plants of apetalous ap1 cal double mutant in Ler genetic background, the cauliflower phenotype was attenuated significantly, and the petal formation could be rescued. Occasionally, chimeric organs composed of petaloid and sepaloid tissues, or petaloid and stamineous tissues, were produced in IiSEP4 transgenic plants of apl cal double mutant. It suggested that overexpression of IiSEP4 could restore the capacity in petal differentiation. Silencing of IiSEP4 by Virus-Induced Gene Silencing (VIGS) can delay the flowering time, and reduce the number and size of the floral organs in woad flowers. CONCLUSION: All the results showed that SEPALLATA-like genes could influence the architecture of the inflorescence and the determinacy of the floral meristems, and was also related to development of the floral organs.

Organ-specific cholesterol metabolic aberration fuels liver metastasis of colorectal cancer.

Rationale: Metastasis, the development of secondary malignant growth at a distance from a primary tumor, is the main cause of cancer-associated death. However, little is known about how metastatic cancer cells adapt to and colonize in the new organ environment. Here we sought to investigate the functional mechanism of cholesterol metabolic aberration in colorectal carcinoma (CRC) liver metastasis. Methods: The expression of cholesterol metabolism-related genes in primary colorectal tumors (PT) and paired liver metastases (LM) were examined by RT-PCR. The role of SREBP2-dependent cholesterol biosynthesis pathway in cell growth and CRC liver metastasis were determined by SREBP2 silencing in CRC cell lines and experimental metastasis models including, intra-splenic injection models and liver orthotropic injection model. Growth factors treatment and co-culture experiment were performed to reveal the mechanism underlying the up-regulation of SREBP2 in CRC liver metastases. The in vivo efficacy of inhibition of cholesterol biosynthesis pathway by betulin or simvastatin were evaluated in experimental metastasis models. Results: In the present study, we identify a colorectal cancer (CRC) liver metastasis-specific cholesterol metabolic pathway involving the activation of SREBP2-dependent cholesterol biosynthesis, which is required for the colonization and growth of metastatic CRC cells in the liver. Inhibiting this cholesterol biosynthesis pathway suppresses CRC liver metastasis. Mechanically, hepatocyte growth factor (HGF) from liver environment activates SREBP2-dependent cholesterol biosynthesis pathway by activating c-Met/PI3K/AKT/mTOR axis in CRC cells. Conclusion: Our findings support the notion that CRC liver metastases show a specific cholesterol metabolic aberration. Targeting this cholesterol biosynthesis pathway could be a promising treatment for CRC liver metastasis.

Tobacco NtabSPL6-2 can enhance local and systemic resistances of Arabidopsis thaliana to bacterial and fungal pathogens.

NtabSPL6-2 of Nicotiana tabacum was introduced into Arabidopsis by Agrobacterium-mediated floral-dip method. Compared to wild-type Col-0 plants, the arrangement of cauline leaves in NtabSPL6-2 transgenic plants was converted into opposite from simple and alternate, and the margin of rosette leaves was serrated. NtabSPL6-2 transgenic plants possessed a significantly greater fresh weight. Subcellular localization by fusion with GFP confirmed that the encoded product of NtabSPL6-2 existed in the nucleus. The leaves of NtabSPL6-2 transgenic plants exhibited an enhanced capacity to restrain the bacterial reproduction after infection by Pseudomonas syringae, accompanied by higher expression of the pathogenesis-related gene PR1 in the infiltrated leaves, indicating NtabSPL6-2 could improve the defense response of Arabidopsis to P. syringae at the local sites. Similarly, it was confirmed that NtabSPL6-2 could enhance the systemic acquired resistance of Arabidopsis in response to P. syringae. In addition, the area of necrotic plaque appearing on the transgenic leaves inoculated with Botrytis cinerea was smaller and accompanied by an upregulation of PR1 and PR5, indicating NtabSPL6-2 transgenic leaves were less susceptible to the fungal pathogen. Moreover, there was less accumulation of reactive oxygen species (H2O2 and O2-) and malondialdehyde in the local infected sites of transgenic plants, whereas the wild-type Col-0 plants were more oxidatively injured after infestation by B. cinerea.

Herbivore-induced rice resistance against rice blast mediated by salicylic acid.

In agro-ecosystems, plants are important mediators of interactions between their associated herbivorous insects and microbes, and any change in plants induced by one species may lead to cascading effects on interactions with other species. Often, such effects are regulated by phytohormones such as jasmonic acid (JA) and salicylic acid (SA). Here, we investigated the tripartite interactions among rice plants, three insect herbivores (Chilo suppressalis, Cnaphalocrocis medinalis or Nilaparvata lugens), and the causal agent of rice blast disease, the fungus Magnaporthe oryzae. We found that pre-infestation of rice by C. suppressalis or N. lugens but not by C. medinalis conferred resistance to M. oryzae. For C. suppressalis and N. lugens, insect infestation without fungal inoculation induced the accumulation of both JA and SA in rice leaves. In contrast, infestation by C. medinalis increased JA levels but reduced SA levels. The exogenous application of SA but not of JA conferred resistance against M. oryzae. These results suggest that pre-infestation by C. suppressalis or N. lugens conferred resistance against M. oryzae by increasing SA accumulation. These findings enhance our understanding of the interactions among rice plant, insects and pathogens, and provide valuable information for developing an ecologically sound strategy for controlling rice blast.

Methylation-associated silencing of S100A4 expression in human epidermal cancers.

S100A4 appears important for cancer metastasis and its overexpression is common in a variety of human malignancies, but its status in epidermal cancers remains lesser known. Likewise, E-cadherin downregulation and Wingless (Wnt) activation are frequent cancer-associated alterations, whereas their potential correlations with S100A4 expression in skin lesions have not been characterized. These issues were addressed in the present study using tissue microarray-based immunohistochemical staining, reverse transcriptase polymerase chain reaction and western blotting. Meanwhile, the underlying epigenetic mechanism leading to the altered S100A4 expression in epidermal tumors was elucidated. Immunohistochemistry revealed that S100A4 expression frequencies were 100% (8/8) in normal epidermis, 80.6% (25/31) in tumor-surrounding non-cancerous epidermis, 66.7% (10/15) in premalignant diseases, 8.3% (1/11) in Bowen's disease and 7.7-26.3% in different cancer tissues. The incidence of S100A4 detection in the normal and non-cancerous epidermis was significantly different from that of epidermal cancers (P = 0.000). Accordingly, human immortalized keratinocyte line HaCat but not skin squamous cell carcinoma (SCC) line colo16 was positive in S100A4 expression. S100A4 downregulation, E-cadherin reduction and Wnt activation coexisted in most of epidermal cancers but unnecessarily overlapped. Methylation DNA sequencing revealed methylation of four critical (cytosine and guanine separated by a phosphate or -C-phosphate-G-) CpG sites within S100A4 intron first in S100A4-negative colo16 cells and skin SCCs, and demethylator/5-aza-2'-deoxycytidine treatment efficiently recovered S100A4 expression in colo16 cells. Our findings demonstrate that S100A4 downregulation, as the consequence of DNA methylation, is closely correlated with skin tumor formation. Wnt activation and E-cadherin reduction and S100A4 down-regulation are paralleled molecular events in skin tumors, which may serve as the biomarkers for predicting epidermal cancer risk.

[Modified tunnel technique applied in the treatment of gingival recessions with non-carious cervical lesion].

OBJECTIVE: This study aimed to investigate the clinical effect of modified tunnel technique (MTUN) in the treatment of gingival recession with non-carious cervical lesion (NCCL). METHODS: Forty-two teeth with Miller I degree gingival recession were divided into the NCCL group or control group depending on whether NCCL was present. Both groups were treated with MTUN plus subepithelial connective tissue. The periodontal probing depth (PD), gingival recession height (GRH), gingival recession width (GRW), attached gingival width (AGW), and clinical attachment loss (CAL) were recorded before and at 3 and 6 months after operation. The mean root coverage (MRC) at 6 months after operation was calculated and analyzed. A root coverage esthetic scoring system was used to record aesthetic scores. RESULTS: GRH, GRW, and CAL of the two groups after surgery were significantly lower than those before surgery, and no significant changes in PD and AGW were observed. The MRC in the NCCL group was 63.40%±28.02%, whereas that in the control group was 67.00%±21.72%; no significant difference between the two groups was found. In terms of aesthetic outcomes, no significant difference between groups was reported. CONCLUSIONS: MTUN can effectively improve gingival recession, and the presence of shallow NCCL (≤1 mm) will not affect the surgical effect of MTUN.

Resveratrol Reverses Retinoic Acid Resistance of Anaplastic Thyroid Cancer Cells via Demethylating CRABP2 Gene.

Background: Cellular retinoic acid binding protein 2 (CRABP2) mediates retinoic acid/RA anti-cancer pathways. Resveratrol effectively reverses RA tolerance and upregulates CRABP2 expression of anaplastic thyroid cancer cell line THJ-11T. As DNA methylation is responsible for CRABP2 silencing, the CRABP2 methylation status of THJ-11T cells and the demethylating effect of resveratrol on this gene are elucidated. Materials and methods: The statuses of CRABP2 expression and methylation and the levels of DNA methyltransferases (DNMTs) DNMT1, DNMT3A, and DNMT3B of THJ-11T cells were examined before and after resveratrol treatment via multiple experimental methods. The human medulloblastoma UW228-2 cell line was cited as the control of CRABP2 methylation and gemcitabine as the demethylator control. Results: RT-PCR, immunocytochemical staining and Western blotting showed that resveratrol significantly increased the CRABP2 expression and RA sensitivity of THJ-11T and UW228-2 cells. Bisulfite sequencing showed five CpG methylation sites at the CRABP2 promoter region of both cell lines, which were partially (3/5) demethylated by resveratrol and totally (5/5) by gemcitabine. DNMT1, DNMT3A, and DNMT3B were reduced in UW228-2 cells and DNMT1 and DNMT3A were reduced in THJ-11T cells after resveratrol treatment in a time-related fashion. Conclusion: Resveratrol is able to erase CRABP2 methylation and can thereby increase the RA sensitivity of THJ-11T and UW228-2 cells. This study demonstrates the additional value of the natural polyphenolic compound resveratrol as a demethylator in cancer treatments.

Synthesis of Graphene Oxide Modified Magnetic Chitosan Having Skin-Like Morphology for Methylene Blue Adsorption.

In this work, a novel magnetic biomass adsorbent was synthesized by a simple method. The adsorbent prepared from chitosan, graphene oxide and CoFe2O4 with a 'skin-like' morphology had a strong adsorption capacity for methylene blue adsorption and was easily separated from the liquid. The synthesized samples were characterized by scanning electron microscope, energy dispersive spectroscopy, fourier transform infrared spectroscopy and X-ray diffractomer. The adsorption capacity of the adsorbent was evaluated. The various factors affecting the adsorption performance were explored. Meanwhile, the adsorption process was simulated by five kinetic models and four isotherm models. The adsorption process was well described by the Pseudo-second-order kinetic model and the Freundlich isotherm model. ΔG < 0, ΔH < 0 and ΔS < 0 indicate that the adsorption process was a spontaneous, exothermic and randomness decrease process. The adsorbents loaded with methylene blue could be desorbed by soaking in dilute hydrochloric acid. The adsorption-desorption cycle experimental results showed that the adsorbent had good reusability performance.

ACOT12-Dependent Alteration of Acetyl-CoA Drives Hepatocellular Carcinoma Metastasis by Epigenetic Induction of Epithelial-Mesenchymal Transition.

Metabolic reprogramming plays an important role in supporting tumor growth. However, little is known about the metabolic alterations that promote cancer metastasis. In this study, we identify acyl-CoA thioesterase 12 (ACOT12) as a key player in hepatocellular carcinoma (HCC) metastasis. The expression of ACOT12 is significantly down-regulated in HCC tissues and is closely associated with HCC metastasis and poor survival of HCC patients. Gain- and loss-of-function studies demonstrate that ACOT12 suppresses HCC metastasis both in vitro and in vivo. Further mechanistic studies reveal that ACOT12 regulates the cellular acetyl-CoA levels and histone acetylation in HCC cells and that down-regulation of ACOT12 promotes HCC metastasis by epigenetically inducing TWIST2 expression and the promotion of epithelial-mesenchymal transition. Taken together, our findings link the alteration of acetyl-CoA with HCC metastasis and imply that ACOT12 could be a prognostic marker and a potential therapeutic target for combating HCC metastasis.

Correlative analyses of notch signaling with resveratrol-induced differentiation and apoptosis of human medulloblastoma cells.

Altered Notch signaling seems linked with medulloblastoma (MB) formation and resveratrol exhibits anti-medulloblastoma effects. However, the influence of resveratrol in Notch signaling of MB cells has not been described. This issue was addressed here by checking Notch1 and Notch2 statuses in three MB cell lines with and without resveratrol treatment. Notch1 and Notch2 were detected in the cytoplasm of three cell lines under normal condition, which were up-regulated by resveratrol along with differentiation, apoptosis and enhanced Hes1 nuclear translocation. Nevertheless, blockage of Notch enzymatic cleavage with gamma-seacretase inhibitors, DAPT and L-685,458, neither interrupted resveratrol-caused cellular events nor affected MB cell growth. These results demonstrate that Notch signaling has little relevance with resveratrol-induced differentiation and apoptosis and may not be a universal critical factor of MB cells.