Micropera tibetica sp. nov. (Orchidaceae) from southeastern Tibet,China

A new species of Orchidaceae, Micropera tibetica from Medog County, Tibet, China, is described and illustrated. It is morphologically similar to M. mannii, from which it differs by having creamy white flowers, not twisted column, strongly oblique lateral sepals with emarginated apex, and very small lateral lobes of the lip.     

Ultrasonic-assisted extraction of polysaccharides from Hohenbuehelia serotina by response surface methodology

An ultrasonic-assisted procedure for the extraction of polysaccharides from the fruiting body of Hohenbuehelia serotina was investigated using response surface methodology. The effects of four factors on the yield of polysaccharides were studied. The optimized conditions were extraction temperature 94°C, extraction time 3.0h, ratio of water to raw material 110:1 and ultrasonic power 480W. Under these conditions, the experimental yield of polysaccharides was 17.45±0.18%, which was well matched with the predictive yield of 17.54%. The molecular weight of polysaccharide was ranged from 1.19×10(3) to 1.55×10(4)Da. The polysaccharides were composed of ribose, arabinose, mannose, glucose and galactose in a ratio of 0.65:0.69:9.35:14.24:5.47. Then, the structural features of untreated materials, hot water extraction residue and ultrasonic-assisted extraction residue were compared by SEM. Results indicated that ultrasonic-assisted extraction technology could be an effective and advisable technique.     

Progesterone and low-dose vitamin D hormone treatment enhances sparing of memory following traumatic brain injury

Progesterone (PROG) has been shown to protect the brain from traumatic injury and is now in Phase III clinical trials. Our work shows that PROG's beneficial effects can be reduced in vitamin D hormone (VDH)-deficient subjects. VDH can modulate neuronal apoptosis, trophic factors, inflammation, oxidative stress, excitotoxicity, and myelin and axon repair. We investigated whether VDH combined with PROG could improve behavioral outcomes more than PROG alone in VDH-sufficient rats given bilateral contusions of the medial frontal cortex. PROG and different doses of VDH (1 μg/kg, VDH1; 2.5 μg/kg, VDH2; 5 μg/kg, VDH3) were injected intraperitoneally 1 h post-injury. Eight additional doses of PROG were given subcutaneously over 8 days with tapering over the last 2 days. Neurobehavioral tests, necrotic cavity, neuronal death and activation of astrocytes were evaluated 21 days post-injury. We found that PROG and PROG + VDH preserve spatial memory processing. VDH1 + PROG improved performance in acquisition more effectively than PROG alone, indicating that the low VDH dose is optimal for combination therapy. There were no significant differences in necrotic cavity size among the groups. The density of positive staining for reactive astrocytes (glial fibrillary acidic protein (GFAP)) increased and the cell bodies and processes of GFAP-positive cells were enlarged in the PROG + VDH1 group. Our data indicate that the combination of PROG and VDH is more effective than PROG alone in preserving spatial and reference memory, and that PROG plus low-dose VDH can activateGFAP reactions up to 21 days after injury. This effect may be one of the mechanisms underlying PROG's neuroprotective effects in combination with VDH.     

Whole-Genome Sequence of Staphylococcus hominis, an Opportunistic Pathogen

Staphylococcus hominis is a commensal coagulase-negative species of staphylococci. It has been considered a presumptive and opportunistic pathogen that causes nosocomial infections in humans. Here we present the draft genome sequence of S. hominis ZBW5, a multidrug-resistant strain isolated from a human skin sample, which provides opportunities to understand the mechanism and genetic basis of its pathogenesis.     

Molecular mechanisms of chromium in alleviating insulin resistance

Type 2 diabetes is often associated with obesity, dyslipidemia and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown to reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance.     

Elongator complex is critical for cell cycle progression and leaf patterning in Arabidopsis

The mitotic cell cycle in higher eukaryotes is of pivotal importance for organ growth and development. Here, we report that Elongator, an evolutionarily conserved histone acetyltransferase complex, acts as an important regulator of mitotic cell cycle to promote leaf patterning in Arabidopsis. Mutations in genes encoding Elongator subunits resulted in aberrant cell cycle progression, and the altered cell division affects leaf polarity formation. The defective cell cycle progression is caused by aberrant DNA replication and increased DNA damage, which activate the DNA replication checkpoint to arrest the cell cycle. Elongator interacts with proliferating cell nuclear antigen (PCNA) and is required for efficient histone 3 (H3) and H4 acetylation coupled with DNA replication. Levels of chromatin-bound H3K56Ac and H4K5Ac known to associate with replicons during DNA replication were reduced in the mutants of both Elongator and chromatin assembly factor 1 (CAF-1), another protein complex that physically interacts with PCNA for DNA replication-coupled chromatin assembly. Disruptions of CAF-1 also led to severe leaf polarity defects, which indicated that Elongator and CAF-1 act, at least partially, in the same pathway to promote cell cycle progression. Collectively, our results demonstrate that Elongator is an important regulator of mitotic cell cycle, and the Elongator pathway plays critical roles in promoting leaf polarity formation.     

Synthesis and evaluation of nitric oxide-releasing DDB derivatives as potential Pgp-mediated MDR reversal agents in MCF-7/Adr cells

Novel furoxan-based nitric oxide (NO)-releasing DDB derivatives (7a-j) were synthesized. Compounds 7i and 7j significantly reversed the resistance of MCF-7/Adr cells to doxorubicin in the combination treatment, and markedly increased the intracellular accumulation of doxorubicin probably via inhibiting Pgp-mediated intracellular drug efflux as well as down-regulating doxorubicin-induced Pgp expression. It was demonstrated that NO released by 7i and 7j played an important role in increasing intracellular doxorubicin accumulation and chemo-sensitizing MCF-7/Adr cells to doxorubicin, and the synergic effects of DDB and NO-donor moieties in 7i and 7j may contribute to reversing Pgp-mediated MDR in MCF-7/Adr cells to doxorubicin.     

Synthesis of 2H-benzo[b][1,4]oxazin-3(4H)-one derivatives as platelet aggregation inhibitors

Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was inhibited by 7a-g with the IC(50) value at 10.14-18.83 μmol/L. Compound 7a exhibited the most potent inhibitory effect (IC(50)=10.14 μmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18 μmol/L) and aspirin (6.07 μmol/L). The preliminary structure-activity relationship (SAR) was initially investigated in the study.     

Discovery of novel selective inhibitors for EGFR-T790M/L858R

Through a receptor-based and ligand-based combined virtual screening protocol, 21 novel compounds covering 15 scaffolds were identified as novel inhibitors for EGFR-T790M/L858R, among which, 12 of them were identified as selective inhibitors for EGFR-T790M/L858R to wild-type EGFR, and 5 of them exhibited 'dual-effective' to wild-type and mutant EGFR. Meanwhile, their antiproliferative effects toward EGFR high-expressing human lung cancer cell (A549), epidermoid carcinoma cell (A431), and the mutant EGFR-dependent cell (NCI-H1975) were also evaluated.     

New ionic derivatives of betulinic acid as highly potent anti-cancer agents

Betulinic acid is a natural compound with high in vitro cytotoxicity toward many cancer cells. However, the poor water solubility of this compound hampers an effective in vivo cancer study. We prepared new ionic derivatives of betulinic acid with higher water solubilities, without losing the structural integrity and functionality of this compound. As a result, these new ionic derivatives have shown much higher inhibitory effects against different cancer cell lines such as melanoma A375, neuroblastoma SH-SY5Y and breast adenocarcinoma MCF7. For A375 cell lines, the derivative 5 exhibited a low IC(50) value of 36 μM (vs 154 μM for betulinic acid); for MCF7 cell lines, the derivative 5 also exhibited a low IC(50) value of 25 μM (vs 112 μM for betulinic acid). The high cytotoxicity of these new derivatives can be linked to their greatly improved water solubility. Our assay method used little DMSO in aiding the dissolution of these derivatives to demonstrate the advantage of improved water solubility and to mimic the in vivo study conditions. The cell viability studies based on both MTT and LDH assay methods have confirmed the high inhibitory effect of our ionic derivatives of betulinic acid (particularly 4 and 5) against different cancer cells.