The present study was conducted to evaluate the anti-inflammatory and antinociceptive activities of Clematis terniflora DC. extracts and fractions and to further support its traditional use as ...Chinese folk medicine in treatment of urinary infections, especially the disease of prostatitis.
The antinociceptive activity of its water extract (WE), 70% ethanol extract (EE), water eluted part of EE from AB-8 macroporous resin (WEPMR) and 70% ethanol eluted part of EE from AB-8 macroporous resin (EEPMR) was conducted using mice writhing test with different doses. Then the anti-inflammatory activity of the four parts was evaluated on rat models of carrageenan-induced chronic non-bacterial prostatitis (CNP). Preliminary study was taken to determine the phytochemical compositions of the four preparative extracts.
Significant writhing inhibitory effect was found with EE at small (7.5g/kg body wt.), moderate (15g/kg body wt.) and large (30g/kg body wt.) doses (doses here are presented as crude herbs) as well as EEPMR at moderate and large doses by oral administration (OA) (p≤0.01). Data from prostatic index, lecithin microsome density and white blood cell level showed that moderate dose of EE and EEPMR both had significant (p≤0.05 or p≤0.01) inhibition effect on carrageenan-induced inflammation in rat prostate. The HPLC analytical results showed that flavonoids were the main active compounds in WE, EE and EEPMR. And most flavonoids were accumulated into the part of EEPMR by AB-8 macroporous resin leaving only few compounds in WEPMR. No acute toxicity was identified in oral administration of the four parts at a dose of 100g/kg body wt.
The results described here suggest that extracts of the aerial part of Clematis terniflora DC. might be of therapeutic interest in the treatment of prostatitis.
Frontotemporal lobar degeneration is a fatal neurodegenerative disease that results in progressive decline in behavior, executive function and sometimes language. Disease mechanisms remain poorly ...understood. Recently, however, the DNA- and RNA-binding protein TDP-43 has been identified as the major protein present in the hallmark inclusion bodies of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), suggesting a role for transcriptional dysregulation in FTLD-U pathophysiology. Using the Affymetrix U133A microarray platform, we profiled global gene expression in both histopathologically affected and unaffected areas of human FTLD-U brains. We then characterized differential gene expression with biological pathway analyses, cluster and principal component analyses, and subgroup analyses based on brain region and progranulin (GRN) gene status. Comparing 17 FTLD-U brains to 11 controls, we identified 414 upregulated and 210 downregulated genes in frontal cortex (P-value < 0.001). Moreover, cluster and principal component analyses revealed that samples with mutations or possibly pathogenic variations in the GRN gene (GRN+, 7/17) had an expression signature that was distinct from both normal controls and FTLD-U samples lacking GRN gene variations (GRN-, 10/17). Within the subgroup of GRN+ FTLD-U, we found >1300 dysregulated genes in frontal cortex (P-value < 0.001), many participating in pathways uniquely dysregulated in the GRN+ cases. Our findings demonstrate a distinct molecular phenotype for GRN+ FTLD-U, not readily apparent on clinical or histopathological examination, suggesting distinct pathophysiological mechanisms for GRN+ and GRN- subtypes of FTLD-U. In addition, these data from a large number of human brains provide a valuable resource for future testing of disease hypotheses.
Objectives
The aim of this study was to explore sodium taurocholate co‐transporting polypeptide (NTCP) exerting its function with hepatitis B virus (HBV) and its targeted candidate compounds, in HBV ...therapy.
Materials and methods
Identification of NTCP as a novel HBV target for screening candidate small molecules, was used by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro virological examination, q‐PCR, western blotting and cytotoxicity studies were used for validating efficacy of the candidate compound.
Results
We used the phylogenetic analysis of NTCP and constructed its protein–protein network. Also, we screened compounds from Drugbank and ZINC, among which five were validated for their authentication in HepG 2.2.15 cells. Then, we selected compound N4 (azelastine hydrochloride) as the most potent of them. This showed good inhibitory activity against HBsAg (IC50 = 7.5 μm) and HBeAg (IC50 = 3.7 μm), as well as high SI value (SI = 4.68). Further MD simulation results supported good interaction between compound N4 and NTCP.
Conclusions
In silico analysis and experimental validation together demonstrated that compound N4 can target NTCP in HepG2.2.15 cells, which may shed light on exploring it as a potential anti‐HBV drug.
Abstract
Due to the sensitivity of the environment and immoderate human activities, the coastal zone in China is facing resource conflicts and environmental pressures. Salt marsh vegetation is ...regarded as an important measure for coastal ecological restoration. Therefore, it is of practical significance to study the influence of salt marsh vegetation on hydro-sediment dynamics. Based on the measured topography and tidal sediment data, a generalized model of salt marsh vegetation is established to study its effects on the dynamics of nearshore water and sediment. The results show that salt marsh vegetation has prominent effect of attenuating flow velocity and promoting sedimentation, and the ability differs depending on vegetation. Salt marsh vegetation can promote the development of tidal channels to shore, causing intensified erosion in the deep trough. The expansion of the vegetation area will allow the tidal channels to extend small branches to shore and connect with the vegetation front.
The voltammetric behaviors of graphite (GP) and its composites with carbon nanotube (CNT) were studied in 5
M H
2SO
4
+
1
M VOSO
4 solution with cyclic voltammetry (CV), and the surface morphology of ...the composites was observed with scanning electron microscope (SEM). The results obtained from voltammetry show that the redox couples of V(IV)/V(V) and V(II)/V(III), as positive and negative electrodes of all vanadium flow liquid battery, respectively, have good reversibility but low current on the GP electrode, and the current can be improved by CNT. It is found from the observation of SEM that the CNT is dispersed evenly on the surface of sheet GP when they are mixed together. The best composition for the positive and the negative of all vanadium flow liquid battery determined by comparing voltammetric behavior of the composite electrodes with different content of CNT is 5:95 (w
CNT/w
GP) for both positive and negative electrodes. The activity of the composite electrode can be affected by the heat treatment of CNT. CNT treated at 200
°C gives better activity to the composite electrode.
We previously demonstrated that an anti-caries DNA vaccine intranasally administered with recombinant flagellin protein as a mucosal adjuvant enhanced salivary IgA response and conferred better ...protection against caries. However, the relatively weak immunogenicity of DNA vaccines and the necessity for a large quantity of antigens remain significant challenges. Here, we fused the flagellin derived from E. coli (KF) and target antigen PAc containing the A-P fragment of PAc from S. mutans (rPAc) to produce a single recombinant protein (KF-rPAc). The abilities of KF-rPAc to induce rPAc-specific mucosal and systemic responses and protective efficiency against caries following intranasal immunization were compared with those of rPAc alone or a mixture of rPAc and KF (KF + rPAc) in rats. Results showed that KF-rPAc promoted significantly higher rPAc-specific antibodies in serum as well as in saliva than did an equivalent dose of rPAc alone or a mixture of KF + rPAc. Intranasal immunization of 8.5 µg KF-rPAc could achieve 64.2% reduction of dental caries in rats. In conclusion, our study demonstrated that flagellin and PAc fusion strategy is promising for anti-caries vaccine development, and KF-rPAc could be used as an anti-caries mucosal vaccine.
Active control of the excessively high heat and particle fluxes on the divertor target plates is of fundamental importance to the steady state operation of tokamaks, especially for fusion reactors. A ...series of experiments have been carried out on this critical issue to relieve the plasma-wall interactions in the experimental advanced superconducting tokamak (EAST) in the last ten years, not only contributing to the long pulse operation of EAST itself, but also providing physical understandings and potential techniques to the next-generation devices like ITER. We have characterized the power deposition pattern and broadened the divertor footprint width effectively. The plasma-wetted area is actively handled using either 3-dimentional edge magnetic topology or advanced plasma equilibrium, thereby peak heat flux around the strike point is reduced. Active control of detachment or radiation compatible with core plasma performance has progressed significantly in very recent years, with a series of active feedback control modules developed and utilized successfully, based on the divertor physics advances with both experiments and simulation. The upper divertor of EAST was upgraded from graphite to active water-cooling ITER-like tungsten in 2014, exhibiting much enhanced heat removal capability. As for the particle exhaust including both fueling and impurity particles, in addition to wall conditioning and impurity source control, the efficiency of particle flux exhaust is optimized by making full use of the divertor closure and the plasma drifts in both scrape-off layer and divertor volume. These heat and particle exhaust advances contribute greatly to a series of EAST achievements like H-mode operation over 100 s. A brief near-term plan on the integrated control of divertor plasma-wall interactions in long-time scale will also be introduced, aiming to provide favorable divertor operation solution for ITER and CFETR.
Protein phosphatase-2A (PP-2A) is a major serine/threonine phosphatase abundantly expressed in eukaryotes. PP-2A is a heterotrimer that contains a 65 kD scaffold A subunit, a 36 kD catalytic C ...subunit, and a regulatory B subunit of variable isoforms ranging from 54-130 kDs. The scaffold subunits, PP2A-Aα/β, act as platforms for both the C and B subunits to bind, and thus are key structural components for PP-2A activity. Mutations in both genes encoding PP2A-Aα and PP2A-Aβ lead to carcinogenesis and likely other human diseases. Our previous work showed that the gene coding for PP2A-Aα is positively regulated by multiple transcription factors including Ets-1, CREB, and AP-2α but negatively regulated by SP-1/SP-3. In the present study, we have functionally dissected the promoter of the mouse PP2A-Aβ gene. Our results demonstrate that three major cis-elements, including the binding sites for Ets-1, SP1/SP3, and RXRα/β, are present in the proximal promoter of the mouse PP2A-Aβ gene. Gel mobility shifting assays reveal that Ets-1, SP1/SP3, and RXRα/β all bind to PP2A-Aβ gene promoter. In vitro mutagenesis and reporter gene activity assays demonstrate that while Ets-1 displays negative regulation, SP1/SP3 and RXRα/β positively regulate the promoter of the PP2A-Aβ gene. Co-expression of the cDNAs encoding Ets-1, SP1/SP3, or RXRα/β and the luciferase reporter gene driven by PP2A-Aβ promoter further confirm their control over the PP2A-Aβ promoter. Finally, ChIP assays demonstrate that Ets-1, SP1/SP3, and RXRα/β can all bind to the PP2A-Aβ gene promoter. Together, our results reveal that multiple transcription factors regulate the PP2A-Aβ gene. Moreover, our results provide important information explaining why PP2A-Aα and PP2A-Aβ display distinct expression levels.
Understanding the early stages of star formation is a research field of ongoing development, both theoretically and observationally. In this context, molecular data have been continuously providing ...observational constraints on the gas dynamics at different excitation conditions and depths in the sources. We have investigated the Barnard 59 core, the only active site of star formation in the Pipe Nebula, to achieve a comprehensive view of the kinematic properties of the source. This information was derived by simultaneously fitting ammonia inversion transition lines (1, 1) and (2, 2). Our analysis unveils the imprint of protostellar feedback, such as increasing line widths, temperature, and turbulent motions in our molecular data. Combined with complementary observations of dust thermal emission, we estimate that the core is gravitationally bound following a virial analysis. If the core is not contracting, another source of internal pressure, most likely the magnetic field, is supporting it against gravitational collapse and limits its star formation efficiency.
Isochronous mass spectrometry (IMS) in storage rings is a powerful tool for mass measurements of exotic nuclei with very short half-lives down to several tens of microseconds, using a multicomponent ...secondary beam separated in-flight without cooling. However, the inevitable momentum spread of secondary ions limits the precision of nuclear masses determined by using IMS. Therefore, the momentum measurement in addition to the revolution period of stored ions is crucial to reduce the influence of the momentum spread on the standard deviation of the revolution period, which would lead to a much improved mass resolving power of IMS. One of the proposals to upgrade IMS is that the velocity of secondary ions could be directly measured by using two time-of-flight (double TOF) detectors installed in a straight section of a storage ring. In this paper, we outline the principle of IMS with double TOF detectors and the method to correct the momentum spread of stored ions.
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