Six new macrolides named myrothecines D–G (1–4), 16-hydroxymytoxin B (5), and 14′-dehydrovertisporin (6), including four 10,13-cyclotrichothecane derivatives, in addition to 12 known compounds ...(7–18), were isolated from three endophytic Myrothecium roridum, IFB-E008, IFB-E009, and IFB-E012. The isolated compounds were characterized by MS, NMR, CD, and single-crystal X-ray crystallography. The isolated macrolides exhibited an antiproliferation effect against chronic myeloid leukemia K562 and colorectal carcinoma SW1116 cell lines. Compounds 1–6 were cytotoxic, with IC50 values ranging between 56 nM and 16 μM. Since slight structural changes led to obvious activity differences, the CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) methods were then used to explore the 3D QSAR (three-dimensional quantitative structure–activity relationship) of these macrolides. The result showed that the steric, electrostatic, hydrophobic, and H-bond acceptor factors were involved in their cytotoxicity and provided an in-depth understanding of the structure–activity relationships of these metabolites.
Lithium has numerous neuroplastic and neuroprotective effects in patients with stroke. Here, we evaluated whether delayed and short-term lithium treatment reduces brain infarction volume and improves ...electrophysiological and neurobehavioral outcomes following long-term recovery after cerebral ischemia and the possible contributions of lithium-mediated mechanisms of neuroplasticity.
Male Sprague Dawley rats were subjected to right middle cerebral artery occlusion for 90 min, followed by 28 days of recovery. Lithium chloride (1 mEq/kg) or vehicle was administered via intraperitoneal infusion once per day at 24 h after reperfusion onset. Neurobehavioral outcomes and somatosensory evoked potentials (SSEPs) were examined before and 28 days after ischemia-reperfusion. Brain infarction was assessed using Nissl staining. Primary cortical neuron cultures were exposed to oxygen-glucose deprivation (OGD) and treated with 2 or 20 μM lithium for 24 or 48 h; subsequent brain-derived neurotrophic factor (BDNF), growth-associated protein-43 (GAP-43), postsynaptic density-95 (PSD-95), and synaptosomal-associated protein-25 (SNAP-25) levels were analyzed using western blotting.
Compared to controls, lithium significantly reduced infarction volume in the ischemic brain and improved electrophysiological and neurobehavioral outcomes at 28 days post-insult. In cultured cortical neurons, BDNF, GAP-43, and PSD-95 expression were enhanced by 24- and 48-h treatment with lithium after OGD.
Lithium upregulates BDNF, GAP-43, and PSD-95, which partly accounts for its improvement of neuroplasticity and provision of long-term neuroprotection in the ischemic brain.
Abbreviations: BDNF: brain-derived neurotrophic factor; ECM: extracellular matrix; EDTA: ethylenediaminetetraacetic acid; GAP-43: growth-associated protein-43; GSK-3β: glycogen synthase kinase-3β; HBSS: Hank's balanced salt solution; LCBF: local cortical blood perfusion; LDF: laser-Doppler flowmetry; MCAO: middle cerebral artery occlusion; MMP: matrix metalloproteinase; NMDA: N-methyl-D-aspartate; NMDAR: N-methyl-D-aspartate receptor; OCT: optimal cutting temperature compound; OGD: oxygen-glucose deprivation; PSD-95: postsynaptic density-95; SDS: sodium dodecyl sulfate; SNAP-25: synaptosomal-associated protein-25; SSEP: somatosensory evoked potential
Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel ...antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.
Long non-coding RNAs (lncRNAs) play important roles in human diseases. They control gene expression levels and influence various biological processes through multiple mechanisms. Functional ...abnormalities in lncRNAs are strongly associated with occurrence and development of various diseases. LINC00472, which is located on chromosome 6q13, is involved in several human diseases, particularly cancers of the breast, lung, liver, osteosarcoma, bladder, colorectal, ovarian, pancreatic and stomach. Importantly, LINC00472 can be used as a biomarker for breast cancer cell sensitivity to chemotherapeutic regimens, including doxorubicin. LINC00472 is regulated by microRNAs and several signaling pathways. However, the significance of LINC00472 in human diseases has not been clearly established. In this review, we elucidate on the significance of LINC00472 in various human diseases, indicating that LINC00472 may be a diagnostic, prognostic as well as therapeutic target for these diseases.
Abstract We presented our experience in chronic myeloid leukemia (CML) patients who conceived children and/or became pregnant while receiving tyrosine kinase inhibitor (TKI). Among 7 male patients, 7 ...pregnancies resulted in the birth of 7 healthy babies. Among 18 female patients, 8 ended in elective abortion; 3 had spontaneous abortion, and 7 carried to term, resulting in the birth of 8 healthy babies. All children have normal growth and development. All patients remain in TKI therapy and in good response. It is suggested that female patients are advised to practice adequate contraception. No special precautions apply for male patients receiving TKI.
Superparamagnetic iron oxide （SPIO） nanoparticle clusters are one unique form which can enhance magnetic relaxivity and improve the magnetic resonance imaging contrast at the same iron concentration, ...comparing to single SPIO nanoparticles. Controlling of cluster size and other structural parameters have drawn great interests in this field to further improve their magnetic properties. In this study, we investigated how the interparticle distance （also known as neighbor distance） of SP10 nanocrystals within clusters affect their magnetic relaxation behaviors. To adjust the neighbor distance, different amount of cholesterol （CHO） was chosen as model spacers embedded into SPIO nanocluster systems with the help of amphiphilic diblock copolymer poly（ethylene glyco）-polyester. Small- angle X-ray scattering was applied to quantify the neighbor distance of SPIO clusters. The results demonstrated that the averaged SPIO nanocrystal neighbor distance of nan- oclusters increased with higher amount of added CHO. Moreover, these SPIO nanocrystal clusters had the promi- nent magnetic relaxation properties. Simultaneously, con- trolling of SPIO nanocrystal neighbor distance can regulate the saturation magnetization （Ms） and magnetic resonance （MR） T2 relaxation of the aggregation, and ultimately obtain better MR contrast effects with decreased neighbor distance.
In this paper, we propose a fuzzy logic algorithm to recognize the types of hydrometeors by using Ka and Ku reflectivity factors, temperature thresholds and an asymmetric i-form membership function. ...The identifiable types of hydrometeors include snow, graupel, mixed-phase particles, large raindrops, and small raindrops. The reflectivity detection data of Ka and Ku with attenuation correction is from dual-frequency precipitation radar onboard the global precipitation measurement satellite. The temperature data from the European Centre for Medium-range Weather Forecasts are used to identify the hydrometeors, and the identified hydrometeors are compared with the vertical profiles of phase from official level-2 DPR products. The results show that the identified hydrometeors are reasonable and reveal the evolution process of tropical cyclones, which can be further applied to the study of precipitation microphysical process and artificial precipitation.
β-defensin 2 is a small antimicrobial peptide of the innate immune system and has been thought to regulate anti-tumor immunity. However, little is known on whether β-defensin 2 could modulate ...melanoma-specific NK and T cell responses. In this study, we first cloned the murine β-defensin 2 gene by RT-PCR and generated the β-defensin 2 stably expressing B16 cells (B16-mBD2). Subsequently, we evaluated whether vaccination with irradiated B16-mBD2 could modulate the growth of implanted B16 cells and determined the potential mechanisms underlying the action of B16-mBD2 vaccine in modulating the growth of B16 tumors in C57BL/6. We found that vaccination with irradiated B16-mBD2, but not with control B16-p or parental B16, inhibited the development and progression of B16 tumors, and prolonged the survival of tumor-bearing mice. However, vaccination with irradiated B16-mBD2 failed to inhibit the development of B16 tumors in the CD4(+)- or CD8(+)-depleted recipients. Furthermore, vaccination with irradiated B16-mBD2 stimulated strong NK activity and promoted potent B16-specific CTL responses, accompanied by augmenting IFN-γ and IL-12, but not IL-4, responses in the recipient mice. Moreover, vaccination with irradiated B16-mBD2 promoted the infiltration of CD8(+) and CD4(+) T, NK cells and macrophages in the tumor tissues. These data suggest β-defensin 2 may act as a positive regulator, promoting anti-tumor NK and T cell responses in vivo. Therefore, β-defensin 2 may be used for the development of immunotherapy for the intervention of melanoma.
In high-frequency (HF) hybrid sky-surface wave radar, the first-order sea clutter broadening is severe under the action of ionospheric phase disturbance and bistatic angles. In this paper, a cascaded ...method is described to suppress the spread sea clutter. Firstly, the radar configuration and sea clutter broadening model are introduced based on the newly developed integrated HF sky-surface wave experimental system. In the cascaded processing method, a new ionospheric decontamination method based on general parameterized time-frequency (GPTF) analysis is proposed to estimate or correct the ionospheric phase distortion with large amplitude. Then, the forward-backward linear prediction (FBLP) algorithm is used to suppress the spread sea clutter caused by bistatic angle. Simulation results show that such ionospheric decontamination method based on GPTF is helpful for the large-amplitude ionospheric contamination when the target masking effect happens even after ionospheric phase decontamination. Finally, the proposed method is examined by the measured data. Experimental results indicate that the proposed method can well suppress the broadening sea clutter for HF hybrid sky-surface wave radars.
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