CT-based radiomics nomogram analysis for assessing BRCA mutation status in patients with high-grade serous ovarian cancer.

BACKGROUND: Radiomics nomogram analysis is widely preoperatively used to assess gene mutations in various tumors. PURPOSE: To explore the value of computed tomography (CT)-based radiomics nomogram analysis for assessing BRCA gene mutation status of patients with high-grade serous ovarian cancer (HGSOC). MATERIAL AND METHODS: In total, 96 patients with HGSOC were retrospectively screened and randomly divided into primary (n = 68) and validation cohorts (n = 28). The clinical model was constructed based on clinical features and CT morphological features using univariate and multivariate logistic analyses. Maximum-relevance and minimum-redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) were performed for feature dimensionality reduction and radiomics score was calculated. The nomogram model combining the clinical model and the radiomics score was constructed using multivariate logistic regression. Receiver operating characteristic (ROC) curves were generated to assess models' performance. The calibration analysis and decision curve analysis (DCA) were also performed. RESULTS: The clinical model consisted of CA125 level and supradiaphragmatic lymphadenopathy and yielded an area under the curve (AUC) of 0.69 (primary cohort) and 0.81 (validation cohort). The radiomics model was built with seven selected features and showed an AUC of 0.87 (primary cohort) and 0.81 (validation cohort). The nomogram finally showed the highest AUC of 0.89 (primary cohort) and 0.87 (validation cohort). The nomogram presented favorable calibrations in both the primary and validation cohorts. DCA further confirmed the clinical benefits of the constructed nomogram. CONCLUSION: CT-based radiomics nomogram provides a non-invasive method to discriminate BRCA gene mutation status of HGSOC and potentially helps develop precise medical strategies.

A Na+/H+ antiporter-encoding salt overly sensitive 1 gene, LpSOS1, involved in positively regulating the salt tolerance in Lilium pumilum.

Lilium pumilum has a strong salt tolerance. However, the molecular mechanism underlying its salt tolerance remains unexplored. Here, LpSOS1 was cloned from L. pumilum and found to be significantly enriched at high NaCl concentrations (100 mM). In tobacco epidermal cells, localization analysis showed that the LpSOS1 protein was primarily located in the plasma membrane. Overexpression of LpSOS1 resulted in up-regulation of salt stress tolerance in Arabidopsis, as indicated by reduced malondialdehyde levels and Na+/K+ ratio, and increased activity of antioxidant reductases (including superoxide dismutase, peroxidase, and catalase). Treatment with NaCl resulted in improved growth, as evidenced by increased biomass, root length, and lateral root growth, in both sos1 mutant (atsos1) and wild-type (WT) Arabidopsis plants that overexpressed LpSOS1, Under NaCl treatment,atsos1 and WT Arabidopsis plants overexpressing LpSOS1 exhibited better growth, with higher biomass, root length, and lateral root quantity, whereas in the absence of LpSOS1 overexpression, the plants of both lines were wilted and chlorotic and even died under salt stress. When exposed to salt stress, the expression of stress-related genes was notably upregulated in the LpSOS1 overexpression line of Arabidopsis as compared to the WT. Our findings indicate that LpSOS1 enhances salt tolerance in plants by regulating ion homeostasis, reducing Na+/K+ ratio, thereby protecting the plasma membrane from oxidative damage caused by salt stress, and enhancing the activity of antioxidant enzymes. Therefore, the increased salt tolerance conferred by LpSOS1 in plants makes it a potential bioresource for breeding salt-tolerant crops. Further investigation into the mechanisms underlying lily's resistance to salt stress would be advantageous and could serve as a foundation for future molecular improvements.

Cinnamon and Eucalyptus Oils Suppress the Inflammation Induced by Lipopolysaccharide In Vivo.

Inflammation caused by bacterial lipopolysaccharide (LPS) disrupts epithelial homeostasis and threatens both human and animal health. Therefore, the discovery and development of new anti-inflammatory drugs is urgently required. Plant-derived essential oils (EOs) have good antioxidant and anti-inflammatory activities. Thus, this study aims to screen and evaluate the effects of cinnamon oil and eucalyptus oil on anti-inflammatory activities. The associated evaluation indicators include body weight gain, visceral edema coefficient, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitrogen monoxide (NO), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), Urea, Crea, ALT, TLR4, MyD88, NF-κB, IκB-α, iNOS, and Mn-SOD. In addition, tissue injury was determined by H&E staining. The results revealed that cinnamon oil and eucalyptus oil suppressed inflammation by decreasing SOD, TNF-α, and NF-κB levels. We also found that cinnamon oil increased the level of GSH-Px, MDA, and Mn-SOD, as well as the visceral edema coefficient of the kidney and liver. Altogether, these findings illustrated that cinnamon oil and eucalyptus oil exhibited wide antioxidant and anti-inflammatory activities against LPS-induced inflammation.

Comprehensive Analysis of Secondary Metabolites in the Extracts from Different Lily Bulbs and Their Antioxidant Ability.

The genus Lilium contains more than 100 wild species and numerous hybrid varieties. Some species of them have been used as medicine and food since ancient times. However, the research on the active components and the medical properties of lilies has only focused on a few species. In this study, the total phenolic acid content (TPC), total flavonoid content (TFC), and antioxidant capacity of 22 representative lilies were systematically investigated. The results showed that the TPC, TFC and antioxidant activity were highly variable among different lilies, but they were significantly positively correlated. Hierarchical cluster analysis indicated that L. henryi and L. regale were arranged in one group characterized by the highest TPC, TFC and antioxidant capacity, followed by Oriental hybrids and Trumpet and Oriental hybrids. The traditional edible and medicinal lilies were clustered in low TPC, TFC and antioxidant capacity group. A total of 577 secondary metabolites, including 201 flavonoids, 153 phenolic acids, were identified in the five species with great differences in antioxidant capacity by extensive targeted metabonomics. Differentially accumulated metabolites (DAMs) analysis reviewed that the DAMs were mainly enriched in secondary metabolic pathways such as isoflavonoid, folate, flavonoid, flavone, flavonol, phenylpropanoid, isoquinoline alkaloid biosynthesis, nicotinate and nicotinamide metabolism and so on. Correlation analysis identified that 64 metabolites were significantly positively correlated with antioxidant capacity (r ≥ 0.9 and p < 0.0001). These results suggested that the genus Lilium has great biodiversity in bioactive components. The data obtained greatly expand our knowledge of the bioactive constituents of Lilium spp. Additionally, it also highlights the potential application of Lilium plants as antioxidants, functional ingredients, cosmetic products and nutraceuticals.

Cytokinin Type-B Response Regulators Promote Bulbil Initiation in Lilium lancifolium.

The bulbil is an important vegetative reproductive organ in triploid Lilium lancifolium whose development is promoted by cytokinins. Type-B response regulators (RRs) are critical regulators that mediate primary cytokinin responses and promote cytokinin-induced gene expression. However, the function of cytokinin type-B Arabidopsis RRs (ARRs) in regulating bulbil formation is unclear. In this study, we identified five type-B LlRRs, LlRR1, LlRR2, LlRR10, LlRR11 and LlRR12, in L. lancifolium for the first time. The five LlRRs encode proteins of 715, 675, 573, 582 and 647 amino acids. All of the regulators belong to the B-I subfamily, whose members typically contain a conserved CheY-homologous receiver (REC) domain and an Myb DNA-binding (MYB) domain at the N-terminus. As transcription factors, all five type-B LlRRs localize at the nucleus and are widely expressed in plant tissues, especially during axillary meristem (AM) formation. Functional analysis showed that type-B LlRRs are involved in bulbil formation in a functionally redundant manner and can activate LlRR9 expression. In summary, our study elucidates the process by which cytokinins regulate bulbil initiation in L. lancifolium through type-B LlRRs and lays a foundation for research on the molecular mechanism of bulbil formation in the lily.

Progranulin Promotes Bleomycin-Induced Skin Sclerosis by Enhancing Transforming Growth Factor-ß/Smad3 Signaling through Up-Regulation of Transforming Growth Factor-ß Type I Receptor.

Progranulin (PGRN) is an autocrine growth factor with numerous physiological and pathologic roles. Previous reports demonstrated PGRN could increase dermal fibroblasts in wound healing and activate cancer-associated fibroblasts in some cancers. Because systemic sclerosis (SSc) is a prototypical fibrosis-related disorder, here, the aim was to clarify the role and mechanism of PGRN in bleomycin (BLM)-induced model of SSc for the first time. It was observed that the serum PGRN levels were increased in SSc patients compared with healthy controls. Immunohistology and quantitative RT-PCR demonstrated that PGRN was also elevated in the lesion from the mice model of BLM-induced dermal fibrosis. In addition, in BLM-treated mice, PGRN deficiency not only attenuated dermal fibrosis but also decreased the differentiation of myofibroblasts. The reduced progression of skin sclerosis in PGRN-deficient mice was associated with down-regulation of transforming growth factor (TGF)-ß receptor I (TßR I) and decreased level of phosphorylated Smad3, with correspondingly impaired expression of its downstream target gene connective tissue growth factor (CTGF) in skin lesion. In contrast, exogenous PGRN significantly increased the level of TßR I and phosphorylated Smad3 in cultured mouse fibroblasts. This study demonstrates that PGRN plays a promoting role in the development of dermal fibrosis through the activation of the TGF-ß/Smad3 signaling via up-regulation of TßR I. PGRN may be a new therapeutic target in SSc.

Tobacco rattle virus-induced PHYTOENE DESATURASE (PDS) and Mg-chelatase H subunit (ChlH) gene silencing in Solanum pseudocapsicum L.

Virus-induced gene silencing (VIGS) is an attractive tool for determining gene function in plants. The present study constitutes the first application of VIGS in S. pseudocapsicum, which has great ornamental and pharmaceutical value, using tobacco rattle virus (TRV) vectors. Two marker genes, PHYTOENE DESATURASE (PDS) and Mg-chelatase H subunit (ChlH), were used to test the VIGS system in S. pseudocapsicum. The photobleaching and yellow-leaf phenotypes of the silenced plants were shown to significantly correlate with the down-regulation of endogenous SpPDS and SpChlH, respectively (P ≤ 0.05). Moreover, the parameters potentially affecting the efficiency of VIGS in S. pseudocapsicum, including the Agrobacterium strain and the inoculation method (leaf syringe-infiltration, sprout vacuum-infiltration and seed vacuum-infiltration), were compared. The optimized VIGS parameters were the leaf syringe-infiltration method, the Agrobacterium strain GV3101 and the growth of agro-inoculated plants at 25°. With these parameters, the silencing efficiency of SpPDS and SpChlH could reach approximately 50% in S. pseudocapsicum. Additionally, the suitability of various reference genes was screened by RT-qPCR using three candidate genes, and the results demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) can serve as a suitable reference for assessing the gene expression levels of VIGS systems in S. pseudocapsicum. The proven application of VIGS in S. pseudocapsicum and the characterization of a suitable reference gene in the present work will expedite the functional characterization of novel genes in S. pseudocapsicum.

The effect of nitrobenzene on antioxidative enzyme activity and DNA damage in tobacco seedling leaf cells.

Nitrobenzene, although widely used in industry, is a highly toxic environmental pollutant. To evaluate the toxicity of nitrobenzene to tobacco seedlings, seedlings were exposed to varying concentrations of nitrobenzene (0-100 mg/L) for 24 h. The contents of reactive oxygen species (hydrogen peroxide [H(2)O(2)] and superoxide anion [O2(-)]) and the activities of antioxidative enzymes (superoxide dismutase [SOD], guaiacol peroxidase [POD], and catalase [CAT]) were measured in leaf cells. Damage to DNA was assessed by single-cell gel electrophoresis (comet assay). Compared with the control, the contents of H(2) O(2) increased significantly with nitrobenzene concentrations ranging from 5 to 100 mg/L. Activity of SOD was induced by 50 to 100 mg/L of nitrobenzene but not by 10 to 25 mg/L. Activity of POD was stimulated by nitrobenzene at 10 to 50 mg/L but inhibited at 100 mg/L. Activity of CAT was increased significantly only by 100 mg/L. Lipid peroxidation increased with 50 to 100 mg/L, which indicated that nitrobenzene induced oxidative stress in tobacco leaf cells. Comet assay of the leaf cells showed a significant enhancement of the head DNA (H-DNA), tail DNA (T-DNA), and olive tail moment (OTM) with increasing doses of nitrobenzene. The values of H-DNA, T-DNA, and OTM exhibited significant differences from the control when stress concentrations were higher than 10 mg/L. The results indicated that nitrobenzene caused oxidative stress, which may be one of the mechanisms through which nitrobenzene induces DNA damage.