The complete chloroplast genome sequence of traditional Chinese medicine Uncaria macrophylla (Rubiaceae).

Uncaria macrophylla (Rubiaceae) is a medicinal vine plant of the Rubiaceae family that was distributed in East Asia and Southeast Asia. The first complete chloroplast genome of Uncaria macrophylla was sequenced and assembled in this study. The genome is 155,138 bp in length and contained 129 encoded genes in total, including 79 protein-coding genes, eight ribosomal RNA genes, and 37 transfer RNA genes. The phylogenomic analysis showed that U. macrophylla was closely related to Uncaria rhynchophylla according to the current sampling extent.

Short Guanidinium-Functionalized Poly(2-oxazoline)s Displaying Potent Therapeutic Efficacy on Drug-Resistant Fungal Infections.

New antifungals are urgently needed to combat invasive fungal infections, due to limited types of available antifungal drugs and frequently encountered side effects, as well as the quick emergence of drug-resistance. We previously developed amine-pendent poly(2-oxazoline)s (POXs) as synthetic mimics of host defense peptides (HDPs) to have antibacterial properties, but with poor antifungal activity. Hereby, we report the finding of short guanidinium-pendent POXs, inspired by cell-penetrating peptides, as synthetic mimics of HDPs to display potent antifungal activity, superior mammalian cells versus fungi selectivity, and strong therapeutic efficacy in treating local and systemic fungal infections. Moreover, the unique antifungal mechanism of fungal cell membrane penetration and organelle disruption explains the insusceptibility of POXs to antifungal resistance. The easy synthesis and structural diversity of POXs imply their potential as a class of promising antifungal agents.

Secondary Amine Pendant ß-Peptide Polymers Displaying Potent Antibacterial Activity and Promising Therapeutic Potential in Treating MRSA-Induced Wound Infections and Keratitis.

Interest in developing antibacterial polymers as synthetic mimics of host defense peptides (HPDs) has accelerated in recent years to combat antibiotic-resistant bacterial infections. Positively charged moieties are critical in defining the antibacterial activity and eukaryotic toxicity of HDP mimics. Most examples have utilized primary amines or guanidines as the source of positively charged moieties, inspired by the lysine and arginine residues in HDPs. Here, we explore the impact of amine group variation (primary, secondary, or tertiary amine) on the antibacterial performance of HDP-mimicking ß-peptide polymers. Our studies show that a secondary ammonium is superior to either a primary ammonium or a tertiary ammonium as the cationic moiety in antibacterial ß-peptide polymers. The optimal polymer, a homopolymer bearing secondary amino groups, displays potent antibacterial activity and the highest selectivity (low hemolysis and cytotoxicity). The optimal polymer displays potent activity against antibiotic-resistant bacteria and high therapeutic efficacy in treating MRSA-induced wound infections and keratitis as well as low acute dermal toxicity and low corneal epithelial cytotoxicity. This work suggests that secondary amines may be broadly useful in the design of antibacterial polymers.

Traditional Chinese Medicine Regulates Notch Signaling Pathway to Prevent and Treat Renal Diseases：A Review / 中国实验方剂学杂志

As common and frequently-occurring disorders in clinic practice，renal diseases are characterized by the impairment of kidney structure and function due to a variety of reasons and can be divided into primary，secondary， and hereditary types. Clinically，the impairment of kidney structure and function is usually a chronic progressive process，and the resulting chronic renal diseases have become a major public health problem endangering human health worldwide. Notch signaling pathway affects cell proliferation，differentiation，migration，growth， and apoptosis and determines the fate of cells. Abnormal expression or gene mutation of Notch will cause tissue damage， followed by the occurrence and development of a variety of renal diseases. Traditional Chinese medicine （TCM）， as an important means to prevent and treat renal diseases，has the characteristics of acting on multiple targets and signaling pathways with multiple components，and is often used as a routine or potential complementary therapy for the treatment of chronic renal diseases and also a source of new drug discovery. In recent years， considering the limitations of western medicine in treating renal diseases，more and more scholars have begun to take Notch signaling pathway as the breakthrough point for exploring TCM prevention and treatment of renal diseases. They have conducted clinical and experimental studies on the regulation of Notch signaling pathway by a variety of individual Chinese herbs or their extracts，Chinese patent medicines， and Chinese medicinal compounds，and found that TCM exerted the renal protective effects by inhibiting the Notch signaling pathway. By collecting relevant literatures on TCM prevention and treatment of various renal diseases，especially those concerning TCM regulation of Notch signaling pathway for preventing and treating such chronic renal diseases as diabetic nephropathy，immunoglobulin A （IgA） nephropathy，renal fibrosis，membranous nephropathy，focal segmental glomerulosclerosis， and renal cell carcinoma，this paper summarized the current research status，in order to provide reference for clinical prevention and treatment of various renal diseases and build up the factual basis for the universal application of TCM.

Physicochemical properties and bioactivities of original and Se-enriched polysaccharides with different molecular weights extracted from Pleurotus ostreatus.

Three polysaccharides (WZP1, WZP2, WZP3) and their Se-enriched products (SeWZP1, SeWZP2 and SeWZP3) were obtained from Pleurotus ostreatus using a simple, rapid method and HNO3-Na2SeO3 method, respectively. The molecular weight distribution profiles of all samples except SeWZP2 showed double peaks. The average molecular weights (Mw) of WZP1-3 were 48.6 kDa, 20.2 kDa and 11.8 kDa, respectively, and of SeWZP1-3 were 19.6 kDa, 37.7 kDa, 14.5 kDa, respectively. The complexity of monosaccharide composition of WZP1-3 was inversely proportional to the ethanol concentration used in the ethanol precipitation process. Additionally, the results of biological activity tests indicated that α-glucosidase inhibitory activity of WZP1-3 was related to the molecular weight and the monosaccharide composition complexity. The selenized modification can improve the α-glucosidase-inhibiting, hydroxyl radical-scavenging activity of P. ostreatus polysaccharides. Therefore, by improving their bioactivities by selenization, the polysaccharides of P. ostreatus could be utilized as a natural health food supplement.

Practical Preparation of Infection-Resistant Biomedical Surfaces from Antimicrobial ß-Peptide Polymers.

Tackling microbial infection associated with biomaterial surfaces has been an urgent need. Synthetic ß-peptide polymers can mimic host defense peptides and have potent antimicrobial activities without driving the bacteria to develop antimicrobial resistance. Herein, we demonstrate a plasma surface activation-based practical ß-peptide polymer modification to prepare antimicrobial surfaces for biomedical materials such as thermoplastic polyurethane (TPU), polytetrafluoroethylene, polyvinyl pyrrolidone, polyvinyl chloride, and polydimethylsiloxane. The ß-peptide polymer-modified surfaces demonstrated effective killing on drug-resistant Gram-positive and Gram-negative bacteria. The antibacterial function retained completely even after the ß-peptide polymer-modified surfaces were stored at ambient temperature for at least 2 months. Moreover, the optimum ß-peptide polymer (50:50 DM-Hex)-modified surfaces displayed no hemolysis and cytotoxicity. In vivo study using methicillin-resistant Staphylococcus aureus (MRSA)-pre-incubated TPU-50:50 DM-Hex surfaces for subcutaneous implantation revealed a 3.4-log reduction of MRSA cells after the implantation for 11 days at the surrounding tissue of implanted TPU sheet and significant suppression of infection, compared to bare TPU control. These results imply promising and practical applications of ß-peptide polymer tethering to prepare infection-resistant surfaces for biomedical materials and devices.

Therapeutic efficacy of the bromodomain inhibitor OTX015/MK-8628 in ALK-positive anaplastic large cell lymphoma: an alternative modality to overcome resistant phenotypes.

Anaplastic large cell lymphomas (ALCL) represent a peripheral T-cell lymphoma subgroup, stratified based on the presence or absence of anaplastic lymphoma kinase (ALK) chimeras. Although ALK-positive ALCLs have a more favorable outcome than ALK-negative ALCL, refractory and/or relapsed forms are common and novel treatments are needed. Here we investigated the therapeutic potential of a novel bromodomain inhibitor, OTX015/MK-8628 in ALK-positive ALCLs.The effects of OTX015 on a panel of ALK+ ALCL cell lines was evaluated in terms of proliferation, cell cycle and downstream signaling, including gene expression profiling analyses. Synergy was tested with combination targeted therapies.Bromodomain inhibition with OTX015 led primarily to ALCL cell cycle arrest in a dose-dependent manner, along with downregulation of MYC and its downstream regulated genes. MYC overexpression did not compensate this OTX015-mediated phenotype. Transcriptomic analysis of OTX015-treated ALCL cells identified a gene signature common to various hematologic malignancies treated with bromodomain inhibitors, notably large cell lymphoma. OTX015-modulated genes included transcription factors (E2F2, NFKBIZ, FOS, JUNB, ID1, HOXA5 and HOXC6), members of multiple signaling pathways (ITK, PRKCH, and MKNK2), and histones (clusters 1-3). Combination of OTX015 with the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib led to cell cycle arrest then cell death, and combination with suboptimal doses of the ALK inhibitor CEP28122 caused cell cycle arrest. When OTX015 was associated with GANT61, a selective GLI1/2 inhibitor, C1156Y-resistant ALK ALCL growth was impaired.These findings support OTX015 clinical trials in refractory ALCL in combination with inhibitors of interleukin-2-inducible kinase or SHH/GLI1.

Calcium supplementation reducing the risk of hypertensive disorders of pregnancy and related problems: A meta-analysis of multicentre randomized controlled trials.

Hypertensive disorders of pregnancy are closely related to maternal mortality and morbidity. Calcium supplementation during pregnancy seems to reduce the risk of hypertensive disorders. No systematic review on multicentre RCTs of calcium supplementation during pregnancy has been published. The purpose of this study was to report a quantitative systematic review of the effectiveness of calcium supplementation during pregnancy on reducing the risk of hypertensive disorders of pregnancy and related problems. Publications over the years of 1991-2012 were searched through PubMed, Science Direct, EMBASE, CINAHL and Web of Science. The literatures were selected of the multicentre RCTs on calcium supplementation during pregnancy in prevention of hypertensive disorders and related problems. Reference lists from the studies were also examined for additional references. Studies were critically appraised by three independent reviewers, and the Cochrane Handbook was used to assess the quality of those included trials. Four studies were included in this systematic review. All included studies were high quality, with low risk of bias. There was an observed risk reduction in hypertension in calcium group. However, there was no reduction in the risk of severe gestational hypertension, pre-eclampsia, severe pre-eclampsia, preterm birth and low birthweight. Calcium supplementation appears to reduce the risk of hypertension in pregnancy.

[Studies on the chemical constituents of Portulaca oleracea].

OBJECTIVE: To study the chemical constituents of Portulaca oleracea. METHODS: The constituents were isolated by column chromatography and identified on the basis of physicochemical and spectral data. RESULTS: Five compounds were isolated from 70% ethanol extract of this plant and their structures were elucidated as cyclo (Phe-Ile) (1), cycle (Tyr-Ala) (2), adenine (3), friedelin (4) and isoselachoceric acid (5). CONCLUSION: Compounds 1-5 are isolated from Portulaca oleracea for the first time.

[Preliminary study on change of serum proteome in noxious heat blood stasis syndrome treated by radix Paeoniae rubra].

OBJECTIVE: To study the effect of red peony root (RPR) on serum proteome in rat suffering from noxious heat with blood stasis Syndrome (NH-BS). METHODS: The differences of serum proteome among rats in four groups, treated with lipopolysaccharide (LPS), RPR, LPS + RPR and saline respectively, were analyzed by bi-dimensional electrophoresis (2DE) assay. LPS was administered by intravenous injection and RPR by oral intake. RESULTS: (1) Serum of rats with LPS induced NH-BS showed significant changes in volume of serum protein (xPr) in 13 points on 2DE collagen, the volume of xPr 16 and 19 were significantly lower, volume of xPr 1, 2, 3, 4, 6, 7, 8, 9, 11, 12 and 23 were significantly higher respectively, as compared with those in the normal control group. (2) After being treated with RPR, the increased volume of xPr 1, 2, 3, 4 and 9 significantly decreased, and the decreased xPr 16 significantly increased, with xPr 2, 3 restored to normal level but the xPr16 still lower and xPr 1, 4, 9 higher than those in the normal group. RPR showed interaction with LPS on xPr 1, 3, 9, and 16. (3) For xPr 19, the interaction of RPR with LPS might be synergistic. (4) In the group treated with RPR, volumes of xPr 13 and 14 were significantly higher and those of 15, 17 were significantly lower than those in the normal group respectively, but the similar changes didn't found in the LPS group. CONCLUSION: The molecular basis of therapeutic effect of RPR on NH-BS might be through the regulation of xPr 1, 2, 3, 4, 9 and 16.

[Study on serum proteome of rat endotoxemia treated by figwort root].

OBJECTIVE: To study the serum proteome of rat endotoxemia treated by figwort root (FR). METHOD: The differences of serum proteome among rats treated with lipopolysaccharide (LPS), FR, LPS + FR and saline respectively were analyzed by two-dimensional electrophoresis (2DE) assay. RESULT: The volumes of sixteen serum proteins (xPr) in LPS induced-endotoxemia group were greatly changed compared with those of the control group. Among them, the volumes of xPr 16, 19 were significantly decreased, and the volumes of xPr 1, 2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 18, 23 were significantly increased. When treated with FR, the volumes of xPr 1, 6, 7, 8, 9, 11, 12, 14, 18, 23 were significantly decreased, and the volumes of xPr 8, 9, 11, 12, 23, 14 were back to normal level. Two factors statistic analysis showed that FR had interaction with LPS for xPr 1, 5, 8, 10, 11, 12, 18, 19, 20, 21, 22, and FR might be the functional antagonist of LPS. We also observed that the volumes of xPr 10, 13, 15, 20, 21, 22 were found to change significantly only in FR treated group but not in LPS treated group or control group. Interestingly, the volume of xPr 13, 20, 21, 22 were increased and the volume of xPr 10, 15 were decreased. CONCLUSION: The molecular basis of therapeutic effect of FR on endotoxemia might be through the regulation of xPr 1, 6, 7, 8, 9, 11, 12, 14, 18, 23. We can use proteomic techniques to study the molecular mechanisms of diseases treated by functional Chinese herbs and the combination of different herbs is necessary for the treatment of endotoxemia, as FR can not regulated all the changed proteins induced by LPS.