3D amide proton transfer-weighted imaging may be useful for diagnosing early-stage breast cancer: a prospective monocentric study.

BACKGROUND: We investigated the value of three-dimensional amide proton transfer-weighted imaging (3D-APTWI) in the diagnosis of early-stage breast cancer (BC) and its correlation with the immunohistochemical characteristics of malignant lesions. METHODS: Seventy-eight women underwent APTWI and dynamic contrast-enhanced (DCE)-MRI. Pathological results were categorized as either benign (n = 43) or malignant (n = 37) lesions. The parameters of APTWI and DCE-MRI were compared between the benign and malignant groups. The diagnostic value of 3D-APTWI was evaluated using the area under the receiver operating characteristic curve (ROC-AUC) to establish a diagnostic threshold. Pearson's correlation was used to analyze the correlation between the magnetization transfer asymmetry (MTRasym) and immunohistochemical characteristics. RESULTS: The MTRasym and time-to-peak of malignancies were significantly lower than those of benign lesions (all p < 0.010). The volume transfer constant, rate constant, and wash-in and wash-out rates of malignancies were all significantly greater than those of benign lesions (all p < 0.010). ROC-AUCs of 3D-APTWI, DCE-MRI, and 3D-APTWI+DCE to differential diagnosis between early-stage BC and benign lesions were 0.816, 0.745, and 0.858, respectively. Only the difference between AUCAPT+DCE and AUCDCE was significant (p < 0.010). When a threshold of MTRasym for malignancy for 2.42%, the sensitivity and specificity of 3D-APTWI for BC diagnosis were 86.5% and 67.6%, respectively; MTRasym was modestly positively correlated with pathological grade (r = 0.476, p = 0.003) and Ki-67 (r = 0.419, p = 0.020). CONCLUSIONS: 3D-APTWI may be used as a supplementary method for patients with contraindications of DCE-MRI. MTRasym can imply the proliferation activities of early-stage BC. RELEVANCE STATEMENT: 3D-APTWI can be an alternative diagnostic method for patients with early-stage BC who are not suitable for contrast injection. KEY POINTS: • 3D-APTWI reflects the changes in the microenvironment of early-stage breast cancer. • Combined 3D-APTWI is superior to DCE-MRI alone for early-stage breast cancer diagnosis. • 3D-APTWI improves the diagnostic accuracy of early-stage breast cancer.

Identification of a comprehensive alternative splicing function during epithelial-mesenchymal transition.

Epithelial-to-mesenchymal transition (EMT) is the underlying mechanism for tumor metastasis and shows the metastatic potential of tumor cells. Although the transcriptional regulation of EMT has been well studied, the role of alternative splicing (AS) regulation in EMT remains largely uncharacterized. The rapid accumulation of RNA-seq datasets has provided the opportunities for developing computational methods to associate mRNA isoform variations with EMT. In this study, we propose regularization models to identify significant AS events during EMT. Our experimental results confirm that the predicted AS events are closely related to apoptosis, focal adhesion-invadopodium shift and tight junction formation that are essential during EMT. Therefore, our study highlights the broad role of posttranscriptional regulation during EMT and identifies key subsets of AS events serving as distinct regulatory nodes.

Early detection and serial monitoring during chemotherapy-radiation therapy: Using T1 and T2 mapping cardiac magnetic resonance imaging.

Purpose: To confirm the ability of native T1 and T2 values in detecting and monitoring early myocardial injuries of chest radiotherapy in neoplasm patients. Materials and methods: Fifteen participants received non-anthracycline chemotherapy and chest radiotherapy, and 30 age/gender-matched controls were enrolled in this prospective study. Cardiac magnetic resonance scans were performed within 2 days, 3 months, and 6 months after chest radiotherapy. Myocardial native T1 and T2 values were measured in irradiated and nonirradiated areas. Meanwhile, the parameters of left ventricular function and left ventricular myocardial strain were obtained. Results: There were no significant differences in left ventricular function, native T1, T2, and strain between patients and controls before chest radiotherapy. In 15 participants who were followed up for 6 months, there was a significant change only in left ventricular ejection fraction (LVEF) among baseline and the first follow-up (P = 0.021), while the adjusted P-value was higher than 0.05 after Bonferroni correction, as well as other parameters. Native T1 values were elevated at 3 and 6 months in irradiated areas compared with baseline (1,288.72 ± 66.59 ms vs. 1,212.51 ± 45.41 ms; 1,348.01 ± 54.16 ms vs. 1,212.51 ± 45.41 ms; P < 0.001 for both). However, T2 values only changed at 3 months in irradiated areas compared with baseline (44.21 ± 3.35 ms vs. 39.14 ± 1.44 ms; P = 0.006). Neither the native T1 nor T2 values changed in nonirradiated areas during the follow-up period (all P > 0.05). There were no significant differences in strain changes during the follow-up period (all P > 0.05). Conclusion: Native T1 and T2 values elevated at 3 months after chest radiotherapy, whereas LVEF showed no significant change during the 6-month follow-up.

Bisbenzylisoquinoline alkaloids from Plumula Nelumbinis inhibit vascular smooth muscle cells migration and proliferation by regulating the ORAI2/Akt pathway.

Plumula Nelumbinis, the embryo of the seed of Nelumbo nucifera Gaertn, is commonly used to make tea and nutritional supplements in East Asian countries. A bioassay-guided isolation of Plumula Nelumbinis afforded six previously undescribed bisbenzylisoquinoline alkaloids, as well as seven known alkaloids. Their structures were elucidated by extensive analysis of HRESIMS, NMR, and CD data. Pycnarrhine, neferine-2α,2'ß-N,N-dioxides, neferine, linsinine, isolinsinine, and nelumboferine, at 2 µM significantly suppressed the migration of MOVAS cells with inhibition ratio above 50%, more active than that of the positive control cinnamaldehyde (inhibition ratio 26.9 ± 4.92%). Additionally, neferine, linsinine, isolinsinine, and nelumboferine, were also active against the proliferation of MOVAS cells with inhibition ratio greater than 45%. The preliminary structure-activity relationships were discussed. Mechanism studies revealed that nelumboferine inhibited the migration and proliferation of MOVAS cells by regulating ORAI2/Akt signaling pathway.

Steroidal Saponins from the Rhizomes of Smilax china and Their Inhibitory Effects on Lipopolysaccharide-Induced Proinflammatory Cytokines Expression.

Four new furostanol saponins (1:  - 4: ) and a new pregane-type saponin (5: ) along with six known steroidal saponins (6:  - 11: ) were isolated from the rhizomes of Smilax china. The structures of 1:  - 5: were elucidated by extensive analysis of NMR and HR-ESI-MS data in addition to enzymatic hydrolysis and other chemical methods. Compounds 1, 4: , and 11: showed inhibitory activity against the expression of proinflammatory mediators, inducible nitric oxide synthase, interleukin-1ß, interleukin-6, and tumor necrosis factor-α in lipopolysaccharide-induced RAW264.7 cells. Compound 1: , at a concentration of 20 µM, decreased the production of inducible nitric oxide synthase, interleukin-1ß, interleukin-6, and tumor necrosis factor-α by 36, 62, 72, and 67%, respectively, which is comparable to that of the positive control dexamethasone.

A new polyhydroxylated oleanane triterpenoid from the roots of Rhodomyrtus tomentosa.

A new oleanane triterpenoid, 2α,3ß,6ß,23,29-pentahydroxyolean-12-en-28- oic acid (1), was isolated from the roots of Rhodomyrtus tomentosa, together with four known oleanane triterpenoids (2-5) and two known ursane triterpenoids (6-7). The structure of compound 1 was determined by extensive NMR and HR-ESI-MS data analysis. Compounds 4-5 showed cytotoxicity against PC12 cell lines at a concentration of 50 µM, and compound 1 exhibited moderate neuroprotective activity against corticosterone induced PC12 cell death at the same concentration.

Phomopsols A and B from the Mangrove Endophytic Fungus Phomopsis sp. xy21: Structures, Neuroprotective Effects, and Biogenetic Relationships.

A polyketide-derived alkaloid featuring a unique 3,4-dihydro-2H-indeno[1,2-b]pyridine 1-oxide motif, named phomopsol A (1), and a highly oxidized polyketide containing a new 3,5-dihydro-2H-2,5-methanobenzo[e][1,4]dioxepine moiety, named phomopsol B (2), were isolated from the Thai mangrove endophytic fungus Phomopsis sp. xy21, together with the related biosynthetic polyketide 3. The structures of 1-3 were unambiguously established by single-crystal X-ray diffraction analysis (Cu Kα), and their neuroprotective effects in PC12 cells were evaluated. The biosynthetic origins of 1-3 are proposed.

Anti-inflammatory furostanol saponins from the rhizomes of Smilax china L.

Seven new furostanol saponins (1-7), chongrenosides A-G, were isolated from the rhizomes of Smilax china L., together with nine known furostanol saponins (8-16). The structures of the new furostanol saponins (1-7) were elucidated by extensive spectroscopic data analyses (1D and 2D NMR, HRESIMS) and chemical evidence. Compounds 1-6 and 8-16 were evaluated for TNF-α mRNA expression inhibitory activity on LPS induced RAW264.7 cells. Of them, 1, 4, 6, and 11 inhibited the TNF-α mRNA expression by 88%, 87%, 67%, and 93%, respectively, at the concentration of 10 µM.

ApoE secretion modulating bromotyrosine derivative from the Australian marine sponge Callyspongia sp.

High throughput screening of a pre-fractionated natural product library identified 11 active fractions showing ApoE modulation activity. Mass-directed fractionation of one active crude extract from the Australian marine sponge Callyspongia sp. resulted in the isolation of 13 metabolites, including three new bromotyrosine derivatives, callyspongic acid (1), 3,5-dibromo-4-methoxyphenylpyruvic acid (2), N-acetyl-3-bromo-4-hydroxylphenylethamine (3), and ten known compounds (4-13). The structure elucidation of compounds 1-3 was based on their 1D and 2D NMR and MS spectroscopic data. 3,5-Dibromo-4-methoxyphenylpyruvic acid (2) showed weak activity in increasing the apolipoprotein E secretion from human CCF-STTG1 cells at the concentration of 40 µM.

Aplysinellamides A-C, bromotyrosine-derived metabolites from an Australian Aplysinella sp. marine sponge.

Mass-directed fractionation of an extract from the Australian marine sponge Aplysinella sp., from the Great Barrier Reef, resulted in the isolation of four new bromotyrosine derivatives, aplysinellamides A-C (1-3) and aplysamine-1-N-oxide (4), along with six known compounds (5-10). The structure elucidation of compounds 1-4 was based on their 1D and 2D NMR and MS spectroscopic data. Aplysamine-1 (6) increased the apolipoprotein E secretion from human CCF-STTG1 astrocytoma cells by 2-fold at the concentration of 30 µM.

Phenolic compounds from the branches of Eucalyptus maideni.

Three new phenolic compounds, eucalmaidin F (1), (3S)-5-guaiacyl-3-hydroxypentanoic acid (2), and 8-ß-C-glucopyranosyl-5,7-dihydroxy-2-isobutylchromone (3), were isolated from the branches of E. maideni, together with 30 known compounds, including four phenylpropanoids, three lignans, four phloroglucinol glucosides, five dihydroflavonoids, seven simple phenolic compounds, six terpenoids, and glycerol. The new structures were established by spectroscopic studies (MS, and 1D- and 2D-NMR), chemical degradation, and modified Mosher's method. Compounds 3, guaiacylglycerol, 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, caffeic acid, (2E)-3-(4-hydroxyphenyl)prop-2-enoic acid, (7'S,8R,8'R)-lyoniresinol, (+)-lyoresinol 3α-O-α-L-rhamnopyranoside, garcimangosone, phlorocetophenone 2'-glucopyranoside, (+)-taxifolin 3α-O-α-L-rhamnopyranoside, (+)-aromadendrin, (+)-taxifolin, resveratrol, piceatannol, 3,4,5-trihydroxyphenol. Tachiaside, gallic acid, macrocapals A und G, and oleuropeic acid were evaluated for their cytotoxicities against five human cancer cell lines. Resveratrol, piceatannol, gallic acid, and macrocapal G exhibited moderate inhibitory effects on human myeloid heukemia HL-60 cell, with IC(50) values of 22.05, 22.05, 7.75, and 31.93 µM, respectively; and only macrocapal G showed inhibitory effect on hepatocellular carcinoma SMMC-7721 cell, with an IC(50) value of 26.75 µM.