Two new iridoid glycosides from the whole plant of Rehmania piasezkii.

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage.

Seven new pentasaccharides from the roots of Rehmannia glutinosa.

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.

Four new iridoid glycosides from the roots of Rehmannia glutinosa.

Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.

Four pairs of tautomers from rhizomes of Acorus calamus and fruits of Cornus officinalis.

A pair of new guaiane-type sesquiterpene tautomers (1) was isolated from rhizomes of Acorus calamus. Meanwhile, three pairs of known compounds, including a pair of dihydroflavone glycoside tautomers (2), a pair of 4-hydroxybenzoic acid ester glycoside tautomers (3), as well as a pair of secoiridoid glycoside tautomers (4) were isolated from fruits of Cornus officinalis. Their structures were elucidated by extensive spectroscopic and computational methods. Furthermore, the tautomeric mechanisms were discussed.

Three new pyridine alkaloids and one new iridoid analogue from the leaves of Rehmannia glutinosa.

As part of an ongoing project on Rehmannia species, three new pyridine alkaloides (glutinosines A - C), and one new iridoid analogue (rehmaglutin E), were isolated from the leaves of Rehmannia glutinosa. The structures of the new compounds were established by extensive spectroscopic analysis and electronic circular dichroism calculations.

Four ionones and ionone glycosides from the whole plant of Rehmannia piasezkii.

Four new ionones and ionone glycosides (1-4) were isolated from the whole plant of Rehmannia piasezkii Maxim. Their planar structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. Compounds 1-4 were tested for their cytotoxicity against five human tumor cell lines and ability to inhibit LPS-activated NO production in the BV2 cell line.

TRIP13 knockdown inhibits the proliferation, migration, invasion, and promotes apoptosis by suppressing PI3K/AKT signaling pathway in U2OS cells.

BACKGROUND: Although osteosarcoma (OS) is the most common malignant bone tumor, the biological mechanism underlying its incidence and improvement remains unclear. This study investigated early diagnosis and treatment objectives using bioinformatics strategies and performed experimental verification. METHODS AND RESULTS: The top 10 OS hub genes-CCNA2, CCNB1, AURKA, TRIP13, RFC4, DLGAP5, NDC80, CDC20, CDK1, and KIF20A-were screened using bioinformatics methods. TRIP13 was chosen for validation after reviewing literature. TRIP13 was shown to be substantially expressed in OS tissues and cells, according to Western blotting (WB) and quantitative real-time polymerase chain reaction data. Subsequently, TRIP13 knockdown enhanced apoptosis and decreased proliferation, migration, and invasion in U2OS cells, as validated by the cell counting kit-8 test, Hoechst 33,258 staining, wound healing assay, and WB. In addition, the levels of p-PI3K/PI3K and p-AKT/AKT in U2OS cells markedly decreased after TRIP13 knockdown. Culturing U2OS cells, in which TRIP13 expression was downregulated, in a medium supplemented with a PI3K/AKT inhibitor further reduced their proliferation, migration, and invasion and increased their apoptosis. CONCLUSIONS: TRIP13 knockdown reduced U2OS cell proliferation, migration, and invasion via a possible mechanism involving the PI3K/AKT signaling pathway.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study.

BACKGROUND: Brain metastasis is an important cause of breast cancer-related death. AIM: We evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan-Meier method was used to compare survival outcomes according to breast cancer subtype. RESULTS: Among 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99-3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2-, 19 months for HR+/HER2+, 11 months for HR-/HER2+, and 6 months for HR-/HER2- (P < .0001). Relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy (p for interaction = .005). CONCLUSIONS: Breast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.

Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma.

The spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

Bioactive prenylated C6-C3 derivatives from the stems and leaves of Illicium fargesii.

Seventeen new prenylated C6-C3 derivatives, namely, illifargeins A-M (1-13), including three pairs of enantiomers (1, 5, and 12) and one norillifargeal A (14), together with eight known analogues (15-22), were isolated from the stems and leaves of Illicium fargesii. The structures of the new compounds were elucidated using spectroscopic data (UV, IR, 1D and 2D NMR, and HRESIMS). Their absolute configurations were determined by using experimental and calculated ECD data analysis, as well as a modified Mosher's method. Compounds 1a, 1b, 2, 3, 5a, 7, 10, 11, 15, 16, 19, and 20 showed potential activity against Coxsackie virus B3, with IC50 values ranging from 6.23 to 33.33 µM. Compounds 9 and 15 exhibited potential activity against influenza virus A, with IC50 values of 11.11 and 19.24 µM, respectively. Compounds 2, 3, and 18 exhibited potential anti-oxidant activity, with IC50 values ranging from 1.43 to 6.71 µM.

Five new iridoids from the whole plants of Rehmannia henryi.

Five new iridoids (1-5), jiohenrins A-E, together with sixteen known compounds (6-21), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data.

Rearranged iridal-type triterpenoids from Iris tectorum.

Three new iridal-type triterpenoids (1-3) featuring a rearranged homofarnesylside chain were isolated from the rhizomes of Iris tectorum. Compounds 2 and 3 were found to be a pair of epimers. Their structures were elucidated on the basis of comprehensive spectroscopic analysis. A possible biosynthetic pathway for them was postulated. Moreover, the mixture of compounds 2 and 3 exhibited moderate neuroprotective activity against serum deprivation-induced PC12 cell death.

Nine new compounds from the whole plants of Rehmannia henryi.

Eight new iridoids (1-8) and an ionone glucoside (9), together with 31 known compounds (10-40), were isolated from the whole plants of Rehmannia henryi. The structures of these compounds were elucidated on the basis of their spectroscopic data and chemical evidence.

Two new iridal-type triterpenoids from Iris forrestii.

Two new iridal-type triterpenoids, named forrestins A and B (1 and 2), were isolated from Iris forrestii Dykes by comprehensive chromatographic methods. The structures of 1 and 2 were elucidated by interpretation of extensive spectroscopic data including 1D and 2D NMR and HRESIMS.

Belamchinenin A, an unprecedented tricyclic-fused triterpenoid with cytotoxicity from Belamcanda chinensis.

Belamchinenin A (1), an unprecedented 6/5/6-fused tricyclic triterpenoid with a novel carbon skeleton, has been isolated from the rhizomes of Belamcanda chinensis. Compound 1 features a half-caged tricyclic nucleus with a flexible geranyl side chain. Its structure was determined by the interpretation of spectroscopic data. The absolute configuration of tricyclic nucleus system of 1 was unequivocally assigned by ECD calculation. Geometries optimization indicated that the tricyclic nucleus system is rigid. Compound 1 showed cytotoxic activities against five cells with IC50 values from 2.29 to 4.47 µM.

Heliojatrones A and B, Two Jatrophane-Derived Diterpenoids with a 5/10 Fused-Ring Skeleton from Euphorbia helioscopia: Structural Elucidation and Biomimetic Conversion.

Heliojatrones A and B (1 and 2), two jatrophane-derived diterpenoids with an unprecedented trans-bicyclo[8.3.0]tridecane core, were isolated from the whole plants of Euphorbia helioscopia. Their structures and absolute configurations were unequivocally determined by a combination of spectroscopic data, electronic circular dichroism calculations, biomimetic conversion, and X-ray diffraction analyses. Their plausible biosynthetic pathways were also proposed. Compounds 1 and 2 were biomimetically synthesized from 3 and 4 through a photochemical rearrangement reaction of ß,γ-unsaturated ketone, respectively. Compound 2 showed significant P-glycoprotein inhibitory activity compared with the positive control (cyclosporine A).

A Chemical Investigation of the Leaves of Morus alba L.

The leaves of Morus alba L. are an important herbal medicine in Asia. The systematic isolation of the metabolites of the leaves of Morus alba L. was achieved using a combination of liquid chromatography techniques. The structures were elucidated by spectroscopic data analysis and the absolute configuration was determined based on electronic circular dichroism (ECD) spectroscopic data and hydrolysis experiments. Their biological activity was evaluated using different biological assays, such as the assessment of their capacity to inhibit the aldose reductase enzyme; the determination of their cytotoxic activity and the evaluation of their neuroprotective effects against the deprivation of serum or against the presence of nicouline. Chemical investigation of the leaves of Morus alba L. resulted in four new structures 1⁻4 and a known molecule 5. Compounds 2 and 5 inhibited aldose reductase with IC50 values of 4.33 µM and 6.0 µM compared with the potent AR inhibitor epalrestat (IC50 1.88 × 10−3 µM). Pretreatment with compound 3 decreased PC12 cell apoptosis subsequent serum deprivation condition and pretreatment with compound 5 decreased nicouline-induced PC12 cell apoptosis as compared with control cells (p < 0.001).

Secoheliosphanes A and B and Secoheliospholane A, Three Diterpenoids with Unusual seco-Jatrophane and seco-Jatropholane Skeletons from Euphorbia helioscopia.

Secoheliosphanes A (1) and B (2) and secoheliospholane A (3), possessing an unusual 7,8-seco-jatrophane skeleton and an unprecedented 9,10-seco-7,10-epoxyjatropholane skeleton, respectively, were isolated from the whole plants of Euphorbia helioscopia, along with two biogenetically precursors, a new jatrophane diterpene, 2-epi-euphornin I (4) and a known jatrophane diterpene, euphoscopin A (5). Structures of 1-4 including absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallography, and chemical conversion. Compounds 1 and 2 were prepared from 4 and 5, respectively, confirming their structural assignments. Notably, 1 and 2 presented the first examples of seco-jatrophane-type diterpenoids and 3 featured a novel 5/6/7/7-fused tetracyclic ring skeleton. Among them, compound 2 showed modest activity against HSV-1 with IC50 value of 6.41 µM.

Heliosterpenoids A and B, two Novel Jatrophane-Derived Diterpenoids with a 5/6/4/6 Ring System from Euphorbia helioscopia.

Heliosterpenoids A and B (1 and 2), two unprecedented jatrophane-derived diterpenoid esters with a novel 5/6/4/6-fused tetracyclic ring skeleton, were isolated from the whole plants of Euphorbia helioscopia. The structures of 1 and 2 were elucidated by extensive spectroscopic methods and electronic circular dichroism (ECD) analyses. The plausible biogenetic pathways of 1 and 2 were postulated. 1 and 2 were found to be potent inhibitors of P-glycoprotein (ABCB1) and 1 also exhibited cytotoxicity against MDA-MB-231 cell lines.

Three new triterpenoids from Ganoderma theaecolum.

Three new triterpenoids (1-3), together with four known triterpenoids (4-7), were isolated from the fruiting bodies of Ganoderma theaecolum. Their structures were elucidated on the basis of their spectroscopic data and chemical evidence. Compounds 4 and 6 exhibited antitumor activities against H460 cells with IC50 values of 22.4 and 43.1 µM, respectively. And the cytotoxic activities of compounds 4 and 5 against MDA-MB-231 cancer cell lines were assayed with IC50 values of 49.1 and 75.8 µM, respectively.