OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

Mass spectrometry imaging and single-cell transcriptional profiling reveal the tissue-specific regulation of bioactive ingredient biosynthesis in Taxus leaves.

Taxus leaves provide the raw industrial materials for taxol, a natural antineoplastic drug widely used in the treatment of various cancers. However, the precise distribution, biosynthesis, and transcriptional regulation of taxoids and other active components in Taxus leaves remain unknown. Matrix-assisted laser desorption/ionization-mass spectrometry imaging analysis was used to visualize various secondary metabolites in leaf sections of Taxus mairei, confirming the tissue-specific accumulation of different active metabolites. Single-cell sequencing was used to produce expression profiles of 8846 cells, with a median of 2352 genes per cell. Based on a series of cluster-specific markers, cells were grouped into 15 clusters, suggesting a high degree of cell heterogeneity in T. mairei leaves. Our data were used to create the first Taxus leaf metabolic single-cell atlas and to reveal spatial and temporal expression patterns of several secondary metabolic pathways. According to the cell-type annotation, most taxol biosynthesis genes are expressed mainly in leaf mesophyll cells; phenolic acid and flavonoid biosynthesis genes are highly expressed in leaf epidermal cells (including the stomatal complex and guard cells); and terpenoid and steroid biosynthesis genes are expressed specifically in leaf mesophyll cells. A number of novel and cell-specific transcription factors involved in secondary metabolite biosynthesis were identified, including MYB17, WRKY12, WRKY31, ERF13, GT_2, and bHLH46. Our research establishes the transcriptional landscape of major cell types in T. mairei leaves at a single-cell resolution and provides valuable resources for studying the basic principles of cell-type-specific regulation of secondary metabolism.

Integrated mass spectrometry imaging and single-cell transcriptome atlas strategies provide novel insights into taxoid biosynthesis and transport in Taxus mairei stems.

Taxol, which is a widely used important chemotherapeutic agent, was originally isolated from Taxus stem barks. However, little is known about the precise distribution of taxoids and the transcriptional regulation of taxoid biosynthesis across Taxus stems. Here, we used MALDI-IMS analysis to visualize the taxoid distribution across Taxus mairei stems and single-cell RNA sequencing to generate expression profiles. A single-cell T. mairei stem atlas was created, providing a spatial distribution pattern of Taxus stem cells. Cells were reordered using a main developmental pseudotime trajectory which provided temporal distribution patterns in Taxus stem cells. Most known taxol biosynthesis-related genes were primarily expressed in epidermal, endodermal, and xylem parenchyma cells, which caused an uneven taxoid distribution across T. mairei stems. We developed a single-cell strategy to screen novel transcription factors (TFs) involved in taxol biosynthesis regulation. Several TF genes, such as endodermal cell-specific MYB47 and xylem parenchyma cell-specific NAC2 and bHLH68, were implicated as potential regulators of taxol biosynthesis. Furthermore, an ATP-binding cassette family transporter gene, ABCG2, was proposed as a potential taxoid transporter candidate. In summary, we generated a single-cell Taxus stem metabolic atlas and identified molecular mechanisms underpinning the cell-specific transcriptional regulation of the taxol biosynthesis pathway.

PHF6 promotes the progression of endometrial carcinoma by increasing cancer cells growth and decreasing T-cell infiltration.

Uterine corpus endometrial carcinoma (UCEC) is the most common cancer of the female reproductive tract. The overall survival of advanced and recurrent UCEC patients is still unfavourable nowadays. It is urgent to find a predictive biomarker and block tumorgenesis at an early stage. Plant homeodomain finger protein 6 (PHF6) is a key player in epigenetic regulation, and its alterations lead to various diseases, including tumours. Here, we found that PHF6 expression was upregulated in UCEC tissues compared with normal tissues. The UCEC patients with high PHF6 expression had poor survival than UCEC patients with low PHF6 expression. PHF6 mutation occurred in 12% of UCEC patients, and PHF6 mutation predicted favourable clinical outcome in UCEC patients. Depletion of PHF6 effectively inhibited HEC-1-A and KLE cell proliferation in vitro and decreased HEC-1-A cell growth in vivo. Furthermore, high PHF6 level indicated a subtype of UCECs characterized by low immune infiltration, such as CD3+ T-cell infiltration. While knockdown of PHF6 in endometrial carcinoma cells increased T-cell migration by promoting IL32 production and secretion. Taken together, our findings suggested that PHF6 might play an oncogenic role in UCEC patients. Thus, PHF6 could be a potential biomarker in predicting the prognosis of UCEC patients. Depletion of PHF6 may be a novel therapeutic strategy for UCEC patients.

Role of female-predominant MYB39-bHLH13 complex in sexually dimorphic accumulation of taxol in Taxus media.

Taxus trees are major natural sources for the extraction of taxol, an anti-cancer agent used worldwide. Taxus media is a dioecious woody tree with high taxol yield. However, the sexually dimorphic accumulation of taxoids in T. media is largely unknown. Our study revealed high accumulation of taxoids in female T. media trees using a UPLC-MS/MS method. Thereafter, many differential metabolites and genes between female and male T. media trees were identified using metabolomic and transcriptomic analyses, respectively. Most of the taxol-related genes were predominantly expressed in female trees. A female-specific R2R3-MYB transcription factor gene, TmMYB39, was identified. Furthermore, bimolecular fluorescence complementation and yeast two-hybrid assays suggested the potential interaction between TmMYB39 and TmbHLH13. Several taxol biosynthesis-related promoter sequences were isolated and used for the screening of MYB recognition elements. The electrophoretic mobility shift assay indicated that TmMYB39 could bind to the promoters of the GGPPS, T10OH, T13OH, and TBT genes. Interaction between TmMYB39 and TmbHLH13 transactivated the expression of the GGPPS and T10OH genes. TmMYB39 might function in the transcriptional regulation of taxol biosynthesis through an MYB-bHLH module. Our results give a potential explanation for the sexually dimorphic biosynthesis of taxol in T. media.

Metagenomic study of humic acid promoting the dechlorination of polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that degrade slowly in the environment. Humic acid (HA), the main component of soil organic matter, or more specifically, the quinone moieties in HA, is generally regarded as an "electron shuttle" between pollutants and microorganisms, which could promote microbial remediation of contamination. In this study, we examined the dechlorination of PCB153 by adding HA and anthraquinone-2,6-disulfonate (AQDS, a model compound of quinones) to systems containing PCB dechlorinators, analyzed the composition and functional gene network of the microbial community by metagenomics, and explored the role of HA by modifying or substituting carbon sources or electron donors. However, this study found that HA accelerated microbial dechlorination of PCBS, while AQDS did not. Moreover, HA without quinone activity still promoted dechlorination, but not without carbon source or electron donor. Metagenomic analysis showed that HA did not promote the growth of PCB dechlorinator (Dehalococcoides), but the transmembrane electron carriers in the HA group were higher than those in the AQDS group and the control group, so HA may have promoted the electron transport process. This study is helpful for microbial remediation of PCB contamination, and provides new insights into the role that HA plays in the biogeochemical cycle.

Forty years studies on polychlorinated biphenyls pollution, food safety, health risk, and human health in an e-waste recycling area from Taizhou city, China: a review.

E-waste generation has become a serious environmental challenge worldwide. Taizhou of Zhejiang Province, situated on the southeast coastline of China, has been one of the major e-waste dismantling areas in China for the last 40 years. In this review, we focused on the polychlorinated biphenyl (PCB) trends in environmental compartments, burden and impact to humans, food safety, and health risk assessment from Taizhou, China. The review suggested that PCBs showed dynamic trends in air, soil, water, biodiversity, and sediments. Soils and fish samples indicated higher levels of PCBs than sediments, air, water, and food items. PCB levels decreased in soils with the passage of time. Agriculture soils near the e-waste recycling sites showed more levels of total PCBs than industrial soils and urban soils. Dioxin-like PCB levels were higher in humans near Taizhou, suggesting that e-waste pollution could influence humans. Compared with large-scale plants, simple household workshops contributed more pollution of PCBs to the environment. Pollution index, hazard quotient, and daily intake were higher for PCBs, suggesting Taizhou should be given priority to manage the e-waste pollution. The elevated body burden may have health implications for the next generation. The areas with stricter control measures, strengthened laws and regulations, and more environmentally friendly techniques indicated reduced levels of PCBs. For environment protection and health safety, proper e-waste dismantling techniques, environmentally sound management, awareness, and regular monitoring are very important.

A Novel Classification of Glioma Subgroup, Which Is Highly Correlated With the Clinical Characteristics and Tumor Tissue Characteristics, Based on the Expression Levels of Gß and Gγ Genes.

PURPOSE: Glioma is a classical type of primary brain tumors that is most common seen in adults, and its high heterogeneity used to be a reference standard for subgroup classification. Glioma has been diagnosed based on histopathology, grade, and molecular markers including IDH mutation, chromosome 1p/19q loss, and H3K27M mutation. This subgroup classification cannot fully meet the current needs of clinicians and researchers. We, therefore, present a new subgroup classification for glioma based on the expression levels of Gß and Gγ genes to complement studies on glioma and Gßγ subunits, and to support clinicians to assess a patient's tumor status. METHODS: Glioma samples retrieved from the CGGA database and the TCGA database. We clustered the gliomas into different groups by using expression values of Gß and Gγ genes extracted from RNA sequencing data. The Kaplan-Meier method with a two-sided log-rank test was adopted to compare the OS of the patients between GNB2 group and non-GNB2 group. Univariate Cox regression analysis was referred to in order to investigate the prognostic role of each Gß and Gγ genes. KEGG and ssGSEA analysis were applied to identify highly activated pathways. The "estimate" package, "GSVA" package, and the online analytical tools CIBERSORTx were employed to evaluate immune cell infiltration in glioma samples. RESULTS: Three subgroups were identified. Each subgroup had its own specific pathway activation pattern and other biological characteristics. High M2 cell infiltration was observed in the GNB2 subgroup. Different subgroups displayed different sensitivities to chemotherapeutics. GNB2 subgroup predicted poor survival in patients with gliomas, especially in patients with LGG with mutation IDH and non-codeleted 1p19q. CONCLUSION: The subgroup classification we proposed has great application value. It can be used to select chemotherapeutic drugs and the prognosis of patients with target gliomas. The unique relationships between subgroups and tumor-related pathways are worthy of further investigation to identify therapeutic Gßγ heterodimer targets.

Enhancement of perchloroethene dechlorination by a mixed dechlorinating culture via magnetic nanoparticle-mediated isolation method.

Highly enriched active dechlorinating cultures are important in advancing microbial remediation technology. This study attempted to enrich a rapid perchloroethene (PCE) dechlorinating culture via magnetic nanoparticle-mediated isolation (MMI). MMI is a novel method that can separate the fast-growing and slow-growing population in a microbial community without labelling. In the MMI process, PCE dechlorination was enhanced but the subsequent trichloroethene (TCE) dechlorination was inhibited, with TCE cumulative rate reached up to 80.6% within 70 days. Meanwhile, the microbial community was also changed, with fast-growing genera like Dehalobacterium and Petrimonas enriched, and slow-growing Methanosarcina almost ruled out. Relative abundances of several major genera including Petrimonas and Methanosarcina were positively related to TCE dechlorination rate and the relative abundance of Dehalococcoides. On the other hand, Dehalobacterium was negatively related to TCE dechlorination rate and Dehalococcoides abundance, suggesting potential competition between Dehalobacterium and Dehalococcoides. The regrowth of Methanosarcina coupled well with the recovery of TCE dechlorination capacity, which implied the important role of methanogens in TCE dechlorination. Via MMI method, a simpler but more active microbial consortium could be established to enhance PCE remediation efficiency. Methanogens may act as the indicators or biomarkers for TCE dechlorination, suggesting that methanogenic activity should also be monitored when enriching dechlorination cultures and remediating PCE contaminated sites. CAPSULE: A rapid perchloroethene dechlorinator was gotten via magnetic nanoparticles and dechlorination of trichloroethene coupled well with growth of Methanosarcina.

Omic analysis of the endangered Taxaceae species Pseudotaxus chienii revealed the differences in taxol biosynthesis pathway between Pseudotaxus and Taxus yunnanensis trees.

BACKGROUND: Taxol is an efficient anticancer drug accumulated in Taxus species. Pseudotaxus chienii is an important member of Taxaceae, however, the level of six taxoids in P. chienii is largely unknown. RESULTS: High accumulation of 10-DAB, taxol, and 7-E-PTX suggested that P. chienii is a good taxol-yielding species for large-scale cultivation. By the omics approaches, a total of 3,387 metabolites and 61,146 unigenes were detected and annotated. Compared with a representative Taxus tree (Taxus yunnanensis), most of the differentially accumulated metabolites and differential expressed genes were assigned into 10 primary and secondary metabolism pathways. Comparative analyses revealed the variations in the precursors and intermediate products of taxol biosynthesis between P. chienii and T. yunnanensis. Taxusin-like metabolites highly accumulated in P. chienii, suggesting a wider value of P. chienii in pharmaceutical industry. CONCLUSIONS: In our study, the occurrence of taxoids in P. chienii was determined. The differential expression of key genes involved in the taxol biosynthesis pathway is the major cause of the differential accumulation of taxoids. Moreover, identification of a number of differentially expressed transcription factors provided more candidate regulators of taxol biosynthesis. Our study may help to reveal the differences between Pseudotaxus and Taxus trees, and promote resource utilization of the endangered and rarely studied P. chienii.

Ferroptosis-related gene signature as a prognostic marker for lower-grade gliomas.

Ferroptosis is a newly discovered form of programmed cell death, which has unique biological effects on metabolism and redox biology. In this study, the prognostic value of ferroptosis-related genes was investigated in lower-grade gliomas (LGG). We downloaded the ferroptosis-related genes from the FerrDb dataset. Univariate Cox and LASSO regression analyses were applied to identify genes correlated with overall survival (OS). Subsequently, 12 ferroptosis-related genes were screened to establish the prognostic signature using stepwise multivariate Cox regression. According to the median value of risk scores, patients were divided into low- and high-risk subgroups. The Kaplan-Meier curves showed the high-risk group had a lower OS. The predictive power of the risk model was validated using the CGGA. Functional analysis revealed that the terms associated with plasma membrane receptor complex, immune response and glutamate metabolic process were primarily related to the risk model. Moreover, we established a nomogram that had a strong forecasting ability for the 1-, 3- and 5-year OS. In addition, we compared the risk scores between different clinical features. We also detected infiltration of macrophages and monocytes in different subgroups. Overall, our study identified the prognostic signature of 12 ferroptosis-related genes, which has the potential to predict the prognosis of LGG.

Induction of Escherichia coli O157:H7 into a viable but non-culturable state by high temperature and its resuscitation.

Escherichia coli O157:H7, a causative agent of haemolytic uremic syndrome, can enter into a viable but non-culturable (VBNC) state in response to harsh stress. Bacteria in this state can retain membrane integrity, metabolic activity and virulence expression, which may present health risks. However, virulence expression and resuscitation ability of the VBNC state are not well understood. Here, we induced E. coli O157:H7 into a VBNC state by high temperature, which is commonly used to prevent the proliferation of pathogens in process of soil solarization, composting and anaerobic digestion of organic wastes. The virulence genes were highly expressed in the VBNC state and resuscitated daughter cells. The resuscitation of VBNC cells occurred after the removal of heat stress in Luria-Bertani medium. In addition, E. coli O157: H7 cells can leave the VBNC state and resuscitate with the clearance of protein aggregates. Notably, with the accumulation of protein aggregation and increased levels of reactive oxygen species, cells lost their ability to resuscitate. The results of this study not only can facilitate a better understanding of the health risks associated with the VBNC state but also have the potential to provide a theoretical basis for thermal disinfection processing.

Characterization of the Vaginal Microbiome in Women with Infertility and Its Potential Correlation with Hormone Stimulation during In Vitro Fertilization Surgery.

Perturbation of vaginal microbiome of reproductive-age women influences all the phases of a woman's reproductive life. Although studies have shown that dynamic changes in vaginal microbiome can affect pregnancy, its role in secondary infertility (i.e., inability to become pregnant or to carry a pregnancy successfully after previous success in delivering a child) and in vitro fertilization (IVF) remains to be unraveled. To determine the vaginal microbiome in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and investigate its potential correlations with hormone stimulation, we recruited 30 patients with secondary infertility and receiving IVF and 92 matched healthy women and analyzed their vaginal microbiome composition using 16S rRNA gene sequencing. Our results show that women suffering from infertility (infertile women) exhibit a significant decrease in microbiome diversity and richness compared with healthy women during the nonovulation period (follicular phase) (P < 0.01), whereas vaginal microbiome of healthy women reveals dramatic fluctuations during ovulation (P < 0.05). Interestingly, infertility patients show no change of the vaginal microbiome under conditions of gonadotropin-releasing hormone (GnRH) agonist and recombinant human chorionic gonadotropin (r-hCG) induction (P > 0.05). Moreover, our results indicate that infertile women show characteristic variations in vaginal microbiome, such as increased abundance of Atopobium, Aerococcus, and Bifidobacterium and decreased abundance of Lactobacillus and Leuconostoc IMPORTANCE The microbiome had been hypothesized to be involved in the physiology and pathophysiology of assisted reproduction before the first success in IVF, while the data supporting or refuting this hypothesis were less than conclusive. Thanks to sequencing data from the 16S rRNA subunit, we characterized the microbiome in the reproductive tract of infertile women, and we found that changes in the vaginal microbiome are related to female infertility. We also found that the characteristic microbiome bacteria are mainly members of several genera and that the vaginal microbiome of infertile women is not sensitive to hormonal changes during IVF. In conclusion, our report provides data that can be used for discovering the role of the vaginal microbiome in patients suffering from secondary infertility.

Extracellular organic matter from Micrococcus luteus containing resuscitation-promoting factor in sequencing batch reactor for effective nutrient and phenol removal.

Culture supernatant containing resuscitation-promoting factor (SRpf) from Micrococcus luteus was added to the sequencing batch reactor (SBR) for effective treatment of phenol-containing wastewater. SRpf acclimation significantly improved combined removal of phenol and nutrients. Moreover, the Illumina high-throughput sequencing analysis revealed that the SRpf boosted bacteria diversity, which enhanced the stability of the system under phenol stress. Addition of SRpf increased the abundances of Actinobacteria and Proteobacteria phyla which are involved in nutrient and phenol removal. Specifically, SRpf promoted Nitrosomonas and Nitrospira which participate in nitrification, family Comamonadaceae, genera Dechloromonas and Pseudomonas involved in denitrification, and Acinetobacter, Pseudomonas and Rhodocyclus which remove phosphorus elements. Moreover, the abundances of Bacillus and Klebsiella responsible for phenol removal as well as Pseudomonas and Acinetobacter were significantly increased after SRpf acclimation. These results show that SBR combined with SRpf acclimation provide optimal nutrient and phenol removal.

Bioactive compounds induced in Physalis angulata L. by methyl-jasmonate: an investigation of compound accumulation patterns and biosynthesis-related candidate genes.

KEY MESSAGE: We employed both metabolomic and transcriptomic approaches to explore the accumulation patterns of physalins, flavonoids and chlorogenic acid in Physalis angulata and revealed the genes associated with the biosynthesis of bioactive compounds under methyl-jasmonate (MeJA) treatment. Physalis angulata L. is an annual Solanaceae plant with a number of medicinally active compounds. Despite the potential pharmacological benefits of P. angulata, the scarce genomic information regarding this plant has limited the studies on the mechanisms of bioactive compound biosynthesis. To facilitate the basic understanding of the main chemical constituent biosynthesis pathways, we performed both metabolomic and transcriptomic approaches to reveal the genes associated with the biosynthesis of bioactive compounds under methyl-jasmonate (MeJA) treatment. Untargeted metabolome analysis showed that most physalins, flavonoids and chlorogenic acid were significantly upregulated. Targeted HPLC-MS/MS analysis confirmed variations in the contents of two important representative steroid derivatives (physalins B and G), total flavonoids, neochlorogenic acid, and chlorogenic acid between MeJA-treated plants and controls. Transcript levels of a few steroid biosynthesis-, flavonoid biosynthesis-, and chlorogenic acid biosynthesis-related genes were upregulated, providing a potential explanation for MeJA-induced active ingredient synthesis in P. angulata. Systematic correlation analysis identified a number of novel candidate genes associated with bioactive compound biosynthesis. These results may help to elucidate the regulatory mechanism underlying MeJA-induced active compound accumulation and provide several valuable candidate genes for further functional study.

Tissue-specific study across the stem of Taxus media identifies a phloem-specific TmMYB3 involved in the transcriptional regulation of paclitaxel biosynthesis.

Taxus stem barks can be used for extraction of paclitaxel. However, the composition of taxoids across the whole stem and the stem tissue-specificity of paclitaxel biosynthesis-related enzymes remain largely unknown. We used cultivated Taxus media trees for analyses of the chemical composition and protein of major stem tissues by an integrated metabolomic and proteomic approach, and the role of TmMYB3 in paclitaxel biosynthesis was investigated. The metabolomic landscape analysis showed differences in stem tissue-specific accumulation of metabolites. Phytochemical analysis revealed that there is high accumulation of paclitaxel in the phloem. Ten key enzymes involved in paclitaxel biosynthesis were identified, most of which are predominantly produced in the phloem. The full-length sequence of TmMYB3 and partial promoter sequences of five paclitaxel biosynthesis-related genes were isolated. Several MYB recognition elements were found in the promoters of TBT, DBTNBT and TS. Further in vitro and in vivo investigations indicated that TmMYB3 is involved in paclitaxel biosynthesis by activating the expression of TBT and TS. Differences in the taxoid composition of different stem tissues suggest that the whole stem of T. media has potential for biotechnological applications. Phloem-specific TmMYB3 plays a role in the transcriptional regulation of paclitaxel biosynthesis, and may explain the phloem-specific accumulation of paclitaxel.

Comparative metabolomic analysis reveals the variations in taxoids and flavonoids among three Taxus species.

BACKGROUND: Trees of the genus Taxus are highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel from Taxus trees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly among Taxus species. In our study, the metabolomes of three Taxus species have been investigated. RESULTS: A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated in T. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated in T. cuspidata and T. media. Our data suggested that there were higher-efficiency pathways to paclitaxel in T. cuspidata and T. media compared with in T. mairei. As an important class of active ingredients in Taxus trees, a majority of flavonoids were predominantly accumulated in T. mairei rather than T. media and T. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach. CONCLUSIONS: Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.

Aberrant expression of CD13 and stem cell markers in CD133-induced liver cancer in mice.

PURPOSE: The purpose of the study is to identify the Cancer Stem Cells (CSCs) and to determine their expression profiles in different pathological stages of liver cancer by using multiple markers Methods: In this study, the expression profiles of CD133 and CD13, along with those of stem cell markers Oct4 and SOX2, were analyzed using immunohistochemistry and immunoblotting to clarify the character of CSCs in different stages of liver cancer. RESULTS: CD133 liver cancer cells were injected into mice, and the tissues were processed for histology. The histological data revealed the progression of liver cancer. Immunohistochemical analysis showed the strong expression of CD133 in metastatic cancer. In contrast, the expression of CD13 in both primary and metastatic liver cancer was found to be very strong. Interestingly, the expression levels of Oct4 and SOX2 were found to be upregulated in primary tumors, but, in the metastatic stage, their expression was downregulated. The immunoblot analysis also confirmed the same result. CONCLUSIONS: Our findings demonstrate that tumor-suppressor proteins Oct4 and SOX2 have a prominent expression profile in the primary stage of cancer, but, in the metastatic stage, their expression is downregulated, leading to the failure to prevent metastatic cancer.

lncRNA UCA1 Mediates Resistance to Cisplatin by Regulating the miR-143/FOSL2-Signaling Pathway in Ovarian Cancer.

The aim of this study was to explore the roles of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) on cisplatin resistance in ovarian cancer and the underlying mechanisms. We investigated the expression of lncRNAs in 3 paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of UCA1 in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then we examined the effects of UCA1 on cisplatin resistance in vitro and in vivo. In this study, UCA1 was observed to be upregulated in cisplatin-resistant patient tissues and cell lines. Knockdown of UCA1 inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed UCA1 promoted the miR-143 expression and miR-143 could bind to the predicted binding site of UCA1. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. Importantly, we demonstrated that UCA1 was upregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that UCA1 modulates cisplatin resistance through the miR-143/FOSL2 pathway in ovarian cancer.