Retrospective validation of ultrasound characteristics at 19-24 weeks as predictive tools for selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies: a diagnostic study.

Background: Seeking an optimal time point for ultrasound examination is important for the diagnosis of late selective intrauterine growth restriction (sIUGR) at birth in monochorionic diamniotic (MCDA) twin pregnancies. We aimed to assess the role of ultrasound characteristics at 19-24 weeks as predictive tools for late sIUGR at birth in MCDA twin pregnancies. Methods: We retrospectively recruited 32 sIUGR and 56 normal patients with MCDA twin pregnancies. Ultrasound indexes of these included subjects at 19-24 weeks, including the middle cerebral artery peak systolic velocity (MCA-PSV), umbilical artery pulsatility index (UA-PI), middle cerebral artery pulsatility index (MCA-PI), and cerebroplacental ratio (CPR) were assessed. Receiver operating characteristic (ROC) curves were used to ascertain the predictive value of ultrasound characteristics discrepancy for such complications, and the relationship between the ultrasound characteristics and sIUGR was assessed by a logistic regression analysis. Results: Differences were found in the MCA-PI, UA-PI, and CPR discordances between the normal MCDA and sIUGR subjects. CPR discordance was the most effective characteristic for predicting sIUGR [area under the ROC curve (AUC) =0.883; 95% CI: 0.795-0.948], followed by UA-PI discordance (AUC =0.772; 95% CI: 0.685-0.829), and MCA-PI discordance (AUC =0.746; 95% CI: 0.681-0.823), respectively. Additionally, the optimal cutoff value of CPR discordance was 21.65, and the corresponding sensitivity and specificity were 0.750 and 0.929, respectively. The correlation analysis revealed that gestational age (GA) at ultrasound scan but not at delivery was significantly correlated with the MCA-PSV (r=0.55, P<0.01), UA-PI (r=0.55, P<0.01), MCA-PI (r=0.49, P<0.01), and CPR (r=0.55, P<0.01) in sIUGR, while GA at both ultrasound scan and birth was significantly correlated with MCA-PSV (r=0.65, P<0.01), UA-PI (r=0.49, P<0.01), MCA-PI (r=0.48, P<0.01), and CPR (r=0.63, P<0.01) in normal MCDA. Conclusions: Increased MCA-PI, UA-PI, and CPR discordances were found in fetuses with sIUGR. CPR discordance could serve as a predictive index for sIUGR. An early ultrasound examination may be more accurate than biochemical modality for sIUGR prediction.

Silver-Templated γ-Keggin Alkyltin-Oxo Cluster: Electronic Structure and Optical Limiting Effect.

As one of the most representative polyoxometalate (POM) structures, Keggin clusters have attracted considerable attention. Nevertheless, the noble-metal-templated Keggin structure has not been reported to date. In this work, for the first time, a Ag atom was successfully incorporated to template the formation of a γ-Keggin alkytin-oxo cluster. Moreover, the central Ag atom has brought a significant heavy atom effect, showing the important influence on the electronic structure and optical properties. Theoretical calculations demonstrate that the Ag atom affects the frontier molecular orbitals and excited states of the AgSn12 cluster, and also the process of electron transfer. The solid structure of the AgSn12 cluster exhibits a significant third-order nonlinear optical (NLO) response, and an excellent optical limiting effect has been experimentally verified. The success of this work opens the way for the construction and optical properties modulation of noble metal templated Keggin structures.

Retrospective validation of 11-13 weeks' gestation ultrasound characteristics as predictive tools for twin-twin transfusion syndrome and selective intrauterine growth restriction in monochorionic diamniotic twin pregnancies.

BACKGROUND: Twin to twin transfusion syndrome (TTTS) is a serious syndrome that can affect twin pregnancies involving a single placenta, impacts some of twin gestations with monochorionic diamniotic (MCDA) placentas. We validated the ultrasound characteristics of 11-13 weeks' gestation to predict TTTS and selective intrauterine growth restriction (sIUGR) in MCDA pregnancies. METHODS: We retrospectively included all of the MCDA twin pregnancies with ultrasound characteristics, including the crown-rump length (CRL), ductus venosus pulsatility index for veins (DV PIV), and nuchal translucency (NT) thickness, at 11-13 weeks' gestation, followed by mean difference and discordance comparison. Receiver operating characteristic (ROC) curves were constructed for the comparison of values of these predictive markers for identification of MCDA pregnancies with high-risk of adverse outcomes. RESULTS: A total of 98 MCDA pregnancies were included in this study. Among the 98, 34 (34.7%) developed sIUGR, whereas 10 (10.2%) expressed TTTS. Significant differences in NT discordance were found among the normal, sIUGR, and TTTS groups; moreover, a significant difference was found between pregnancies with normal outcomes and sIUGR (P<0.001), normal and TTTS (P<0.001), and sIUGR and TTTS (P<0.001). Difference in NT was determined to be the best predictive marker for sIUGR [area under the curve (AUC) =0.769; 95% confidence interval (CI): 0.591 to 0.992], and NT discordance was considered the best predictive marker for TTTS (AUC =0.802; 95% CI: 0.485 to 0.936). CONCLUSIONS: Significant differences in NT discordance were found between the normal, sIUGR, and TTTS groups, while NT difference and NT discordance were identified as predictive markers for sIUGR and TTTS, respectively.

Diterpenoid and triterpenoid glycosides from Clinopodium chinense.

Two new compounds, including a diterpenoid glycoside (1) and a triterpenoid glycoside (6), along with six known compounds were isolated from Clinopodium chinense. The structures of the new compounds were determined on basis of extensive spectral analysis and chemical method. Compounds 1-8 were evaluated for their insulin resistance effect and cytotoxic activity against the A549 and HepG2 cancer cell lines. None of the compounds were cytotoxic (IC50 > 100 µM), while compounds 1-3 and 5 showed the activity of ameliorating insulin resistance in HepG2.

In vitro and in vivo evaluation of didymin cyclodextrin inclusion complexes: characterization and chemosensitization activity.

Didymin is a dietary flavonoid that first found in citrus fruits, and possesses antioxidant properties. Our preliminary experiments first discovered that didymin was able to sensitize the resistant cancer cells against chemotherapeutics and combat multidrug resistance. However, its poor aqueous solubility and resultant low bioavailability limit its potentials as an adjuvant phytochemical drug for chemotherapy. Thus, this study prepared the inclusion complex of didymin with ß-cyclodextrin and 2-hydroxypropyl-ß-cyclodextrin to improve its bioavailability and then evaluate their chemosensitization effects. The didymin inclusion complexes formulation was prepared and their host-guest structure was characterized by FT-IR, PXRD, DSC, and SEM techniques. In vitro/in vivo results demonstrated that didymin inclusion complex enhanced its water solubility and orally bioavailability. Furthermore, didymin inclusion complex exerted considerable chemosensitivity potency, and improve the anti-tumor effects of chemotherapeutics in vivo. Therefore, didymin inclusion complex could provide a safe, effective, economical, and adjuvant drug for future treatment of chemoresistant cancers.

Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin.

Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid glycoside first found in citrus fruits. Traditionally, this flavonoid has long been used in Asian countries as a dietary antioxidant. Recent studies have provided newer insights into this pleiotropic compound, which could regulate multiple biological activities of many important signaling molecules in health and disease. Emerging data also presented the potential therapeutic application of dietary flavonoid glycoside didymin against cancer, neurological diseases, liver diseases, cardiovascular diseases, and other diseases. In this review, we briefly introduce the source and extraction methods of didymin, and summarize its potential therapeutic application in the treatment of various diseases, with an emphasis on molecular targets and mechanism that contributes to the observed therapeutic effects. The dietary flavonoid didymin can be used to affect health and disease with multiple therapeutic targets, and it is anticipated that this review will stimulate the future development of this potential dietary medicine.

Two new flavonoid-triterpene saponin meroterpenoids from Clinopodium chinense and their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells.

Two new flavonoid-triterpene saponin meroterpenoids, clinoposides G (1) and H (2) were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated through spectroscopic and electronic circular dichroism (ECD) analyses. Compounds 1 and 2 were evaluated for their protective effects against anoxia/reoxygenation(A/R)-induced injury in H9c2 cells. A/R treatment severely injured the H9c2 cells, which was accompanied by apoptosis. Both 1 and 2 pretreatment significantly inhibited cell injury and apoptosis, improved mitochondrial membrane potential, increased activities of antioxidant enzymes, and reduced the levels of the inflammatory cytokines. In addition, the presence of 1 and 2 significantly decreased the protein level of p65 and increased the level of Nrf2 in cell nucleus. Unique chemical structure and good biological activity of 1 and 2 elucidated the potential of meroterpenoids as a promising reagent for treating heart disease.

Protective effects of total flavonoids from Clinopodium chinense (Benth.) O. Ktze on myocardial injury in vivo and in vitro via regulation of Akt/Nrf2/HO-1 pathway.

BACKGROUND: Clinopodium chinense (Benth.) O. Ktze is a traditional Chinese herbal medicine, which comprises the plant's total flavonoids. TFCC plays an important role in the treatment of cardiovascular disease. PURPOSE: The aim of the study was to study the protective effects and possible mechanism of TFCC against isoproterenol (ISO)-mediated myocardial injury in vivo and anoxia/reoxygenation (A/R)-induced H9c2 cell injury in vitro. METHODS: Male Sprague-Dawley (SD) rats were intragastrically pretreated with TFCC for 15 days. After 2 h of TFCC administration on days 14 and 15, a myocardial injury model was established with intragastric administration of 120 mg/kg of ISO daily for 2 days. The experiment was stopped 12 h after the last administration of the drugs. ECG recordings were taken after the treatment. Serum samples were assayed to determine the serum cardiac enzymes (e.g., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). The left ventricle was excised for histopathological examination, and myocardial homogenates were prepared to detection catalase, glutathione peroxidase, and superoxide dismutase. Reactive oxygen species (ROS), heme oxygenase-1(HO-1),and peroxidase were detected by the corresponding ELISA kits. H9c2 cells were pretreated with different concentrations of TFCC for 12 h before A/R exposure. Afterward, cell viability, LDH release, hoechst 33,342, and peromide iodine (PI) double staining, JC-1 staining, and ROS examination were determined. Western blot analyses of B-cell lymphoma-2, Bcl-2associated X protein, cleaved cysteinylaspartate specific protease-3 and-9, nuclear factor 2(Nrf2), HO-1 and serine/threonine protein kinase (AKT), and P-AKT were conducted. RESULTS: The pretreatment of TFCC (10, 20, and 40 mg/kg) daily for 15 days prevented ISO-induced myocardial damage, including the decrease in serum cardiac enzymes and cardiomyocyte apoptotic index and improvement in the heart rate and vacuolation. TFCC also improved the free radical scavenging and antioxidant potential, thereby suggesting that one possible mechanism of TFCC-induced cardio protection is mediated by blocking the oxidative stress. To clarify these mechanisms, we performed the in vitro study by A/R-induced cytotoxicity model in H9c2 cells. TFCC pretreatment prevented apoptosis, increased the expression of HO-1, and enhanced the nuclear translocation of Nrf2. TFCC also activated phosphorylation of AKT, whereas the addition of LY294002, which is the pharmacologic inhibitor of PI3K, blocked the TFCC-induced Nrf2/HO-1 activation and cytoprotective effect. CONCLUSIONS: TFCC protects against myocardial injury and enhances cellular antioxidant defense capacity by inducing the phosphorylation of AKT, which subsequently activated the Nrf2/HO-1 signaling pathway.

Triterpenoid saponins from Clinopodium chinense (Benth.) O. Kuntze and their biological activity.

Four new ursane-type triterpenoid saponins, clinopoursaponins A-D (1-4), six new oleanane-type triterpenoid saponins, clinopodiside VII-XII (5-10), as well as eight known triterpene analogues (11-18), were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. The structures of the new compounds were determined based on extensive spectral analyses, including 1D (1H and 13C) and 2D NMR experiments (COSY, NOESY, HSQC, 2D TOCSY, HSQC-TOCSY and HMBC), HR-ESI-MS and chemical methods. Compounds 1-18 were evaluated for their protective effects against anoxia/reoxygenation-induced apoptosis in H9c2 cells and cytotoxicities against murine mammary carcinoma cell line 4T1. Compounds 8, 9 and 18 exhibited significant protective effects, while compound 1 exhibited cytotoxic activity with IC50 value of 7.4 µm compared to 7.6 µm for the positive control 10-hydroxycamptothecin.

[Studies on chemical constituents of Clinopodium chinense].

Twenty-eight compounds were isolated and purified from Clinopodium chinense by Sephedax LH-20, ODS, MCI and preparative HPLC. Their structures were identified as apigenin (1), apigenin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucuronopyranoside (3), thellungianol (4), apigenin-7-O-ß-D-rutinoside (5), luteolin (6), luteolin-4'-O-ß-D-glucopyranoside (7), apigenin-7-O-ß-D-pyranglycuronate butyl ester (8), luteolin-7-O-ß-D-rutinoside (9), luteolin-7-O-ß-D-noehesperidoside (10), acacetin (11), acacetin-7-O-ß-D-glucuronopyranoside (12), buddleoside (13), naringenin (14), pruning (15), nairutin (16), isosakuranetin (17), isosakuranin (18), didymin (19), hesperidin (20), kaempferol (21), quercetin (22), kaempferol-3-O-α-L-rahmnoside (23), p-hydroxycinnamic acid (24), caffeic acid (25), cis-3-[2-[1-(3,4-dihydroxy-phenyl)-1 -hydroxymethyl]-1,3-ben-zodioxol-5-yl]-(E)-2-propenoic acid (26), mesaconic acid (27), gentisic acid 5-O-ß-D-(6'-salicylyl)-glucopyranoside (28). Among them, compounds 7, 9-10, 12, 23, 26-28 were isolated from the Clinopodium for the first time. The protective effects of compounds 1-6, 8-17 and 19 against H2O2-induced H9c2 cardiomyocyte injury were tested, compounds 15 exhibited significantly protective effects. Compared with the cell viability of (62.12±6.18)% in the model, pruning exhibited viabilities of (84.25±7.36)% at 25.0 mg•L⁻¹, respectively, using quercetin as a positive control [cell viability of (84.55±8.26)%, 20 mg•L⁻¹].

Soulieoside O, a new cyclolanostane triterpenoid glycoside from Souliea vaginata.

A new cyclolanostane triterpenoid glycoside, soulieoside O (1), together with 25-O-acetylcimigenol-3-O-ß-d-xylopyranoside (2) and cimigenol-3-O-ß-d-xylopyranoside (3), was isolated from the rhizomes of Souliea vaginata. Their structures were characterized by spectroscopic analysis and chemical methods. The new compound showed moderate inhibitory activity against three human cancer cell lines with IC50 values of 9.3-22.5 µM.

A new cycloartane triterpenoid glycoside from Souliea vaginata.

One new cycloartane triterpenoid glycoside, soulieoside Q (1), together with four known compounds (2-5) were isolated from the ethanolic extract of the rhizomes of Souliea vaginata Maxim. The structure of the new compound was determined by extensive spectroscopic analysis including 1D and 2D NMR and HRESIMS, as well as chemical methods. Compound 1 was evaluated for its cytotoxic activities against HepG2 and A549 cancer cell lines.

Oleanane triterpene saponins with cardioprotective activity from Clinopodium polycephalum.

Two new triterpene saponins, clinopodiside VI (1) and saikosaponin c (2), along with six known saikosaponins (3-8), were isolated from the plant of Clinopodium polycephalum. Compounds 1-3 showed moderate inhibition against H9c2 cell damage induced by H2O2.

A new phenylethanoid glycoside from Incarvillea compacta.

A new phenylethanoid glycoside, 3'''-O-methylcampneoside I (1), was isolated from the 90% ethanolic extract of the roots of Incarvillea compacta, together with three known compounds, campneoside I (2), ilicifolioside A (3), and campneoside II (4). Their structures were determined spectroscopically and compared with previously reported spectral data. Compound 1 existed as epimers and displayed better 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity using di-tert-butyl-4-methylphenol (BHT) as the positive control. In addition, pretreatment of human HepG2 cells with compound 1 significantly increased the viability on CCl4-induced cell death.

Two new abietane diterpenoid glycosides from Clinopodium chinense.

Two new abietane diterpenoid glycosides, named clinopoditerpenes B (1) and C (2), were isolated from Clinopodium chinese. The structures of the new compounds were determined on the basis of extensive spectral analysis. Compound 1 exhibited cardioprotective effect against H2O2-induced apoptosis in H9c2 cells.

[A new bisabolane-type sesquiterpenoid from Coreopsis tinctoria].

To study the chemical constituents of the inflorescences of Coreopsis tinctoria from Xinjiang, isolation and purification of constituents were carried out by column chromatography on macroporous resin (D101) , MCI gel, MDS gel, silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures of the compounds were identified by physicchemical properties and spectral data analysis. Fourteen compounds were isolated and identified as coretinterpenoid A (1), coretinphenol (2), quercetin (3), quercetin-3-O-ß-glucopyranoside (4), luteolin (5), taxifolin (6), 7, 3', 5'-trihydroxyflavanone (7), isookanin (8), isookanin-7-O-ß-D-glucopyranoside (9), 5, 7, 3', 5'-tetrahydroxyflavanone-7-O-ß-D-glucopyranoside (10), butein (11), okanin (12), sulfuretin (13), and linocinnamarin (14). Compound 1 was a new isabolane-type sesquiterpenoid and compounds 4, 10 and 13 were isolated from this plant for the first time.

Four new phenolic acid with unusual bicycle [2.2.2] octane moiety from Clerodendranthus spicatus and their anti-inflammatory activity.

Four new phenolic acids, clerodens A-D (1-4) possessing an unusual bicycle [2.2.2] octane moiety were isolated from the whole plants of Clerodendranthus spicatus. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD data. All isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and compound 4 showed significant inhibitory activities with IC50 value of 6.8 µM.

Total Flavonoids from Clinopodium chinense (Benth.) O. Ktze Protect against Doxorubicin-Induced Cardiotoxicity In Vitro and In Vivo.

Doxorubicin has cardiotoxic effects that limit its clinical benefit in cancer patients. This study aims to investigate the protective effects of the total flavonoids from Clinopodium chinense (Benth.) O. Ktze (TFCC) against doxorubicin- (DOX-) induced cardiotoxicity. Male rats were intraperitoneally injected with a single dose of DOX (3 mg/kg) every 2 days for three injections. Heart samples were collected 2 weeks after the last DOX dose and then analyzed. DOX delayed body and heart growth and caused cardiac tissue injury, oxidative stress, apoptotic damage, mitochondrial dysfunction, and Bcl-2 expression disturbance. Similar experiments in H9C2 cardiomyocytes showed that doxorubicin reduced cell viability, increased ROS generation and DNA fragmentation, disrupted mitochondrial membrane potential, and induced apoptotic cell death. However, TFCC pretreatment suppressed all of these adverse effects of doxorubicin. Signal transduction studies indicated that TFCC suppressed DOX-induced overexpression of p53 and phosphorylation of JNK, p38, and ERK. Studies with LY294002 (a PI3K/AKT inhibitor) demonstrated that the mechanism of TFCC-induced cardioprotection also involves activation of PI3K/AKT. These findings indicated the potential clinical application of TFCC in preventing DOX-induced cardiac oxidative stress.

Two new acylated flavonol glycosides from the seeds of Lepidium sativum.

Two new acylated flavonol glycosides named kaempferol-3-O-(2-O-sinapoyl)-ß-D-galactopyranosyl-(1 → 2)-ß-D-glucopyranoside-7-O-α-L-rhamnopyranoside (1) and quercetin-3-O-(6-O-benzoyl)-ß-D-glucopyranosyl-(1 → 3)-ß-D-galactopyranoside-7-O-α-L-rhamnopyranoside (2), were isolated together with six known compounds from the seeds of L. sativum. Their structures were elucidated on the basis of spectroscopic analysis and chemical methods. In vitro 1 and 2 inhibited nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values of 25.36 and 25.08 µM, respectively.