Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses.

Moringa oleifera Lam. (MO) is called the "Miracle Tree" because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

Mutant soluble ectodomain of fibroblast growth factor receptor-2 IIIc attenuates bleomycin-induced pulmonary fibrosis in mice.

We have developed a strong inhibitor (S252W mutant soluble ectodomain of fibroblast growth factor recptor-2 IIIc, msFGFR2) that binds FGFs strongly and blocks the activation of FGFRs. In vitro, msFGFR2 could inhibit the promoting effect of transforming growth factor (TGF)-ß1 on the proliferation of primary lung fibroblasts. In vivo, msFGFR2 alleviated lung fibrosis through inhibiting the expression of α-smooth muscle actin (SMA) and collagen deposit. In Western blotting of the right lung tissues and immunohistochemical assay, we found the level of p-FGFRs, p-mitogen activated protein kinase (MAPK) and p-Smad3 in the mice of bleomycin (BLM) group treated with msFGFR2 was down dramatically compared with the mice of BLM group, which suggested the activations of FGF and TGF-ß signals were blocked meanwhile. In summary, msFGFR2 attenuated BLM-induced fibrosis and is an attractive therapeutic candidate for human pulmonary fibrosis.

Analysis of Cucurbita ficifolia (Cucurbitaceae) chloroplast genome and its phylogenetic implications.

The figleaf gourd (Cucurbita ficifolia Bouché), is a member of the Cucurbitaceae. Figleaf gourd genotypes are exclusively used as a rootstock for cucumber owing to their high physiological compatibility with cucumber. In this study, the complete chloroplast (cp) genome of C. ficifolia was assembled. The cp genome of C. ficifolia was 157,631 bp in length, it consists of a pair of inverted repeats (IRa and IRb) regions (25,638 bp) separated by the large single-copy (LSC, 88,211 bp) and small single-copy (SSC, 18,144 bp) regions. The cp genome encodes 111 unique genes, including 80 protein-coding genes, 27 transfer RNA genes, and four ribosomal RNA genes. The overall GC content of C. ficifolia cp genome was 37.2%. The phylogenetic tree of Cucurbitaceae showed that C. ficifolia was clustered into genus Cucurbita and the bootstrap value is 100%.

Characteristic and phylogenetic analyses of chloroplast genome for Mentha haplocalyx (Lamiaceae).

Mentha haplocalyx is an important medicinal and edible plant. Now, the complete chloroplast (cp) genome of M. haplocalyx was assembled and annotated. The cp genome of M. haplocalyx was 152,048 bp and contained two short inverted repeat regions (25,608 bp) which were separated by a small single copy region (17,654 bp) and a large single copyregion (83,179 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that M. haplocalyx and M. spicata formed a monophyletic clade and clustered together with genus Dracocephalum.

Chloroplast genome for Crataegus pinnatifida (Rosaceae) and phylogenetic analyses with its coordinal species.

Crataegus pinnatifida is an important medicinal and edible plant. Now, the complete chloroplast (cp) genome of C. pinnatifida was assembled and annotated. The cp genome of C. pinnatifida was 159,898 bp and contained two short inverted repeat regions (26,540 bp) which were separated by a small single copy region (19,219 bp) and a large single copyregion (87,599 bp). The cp genome encodes 109 unique genes, including 75 protein-coding genes, 30 transfer RNA genes and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that C. pinnatifida has a close relationship with species Eriobotrya, Sorbus, Pyrus, Mulus, and Chaenomeles.

Phylogenetic analyses of Lycium chinense (Solanaceae) and its coordinal species applying chloroplast genome.

Lycium chinense is an important edible and medicinal plant. Now, the complete chloroplast (cp) genome of L. chinense was assembled based on the Illumina sequencing reads. The cp genome of L. chinense was 155,736 bp long and contained two short inverted repeat regions (25,469 bp), which were separated by a small single-copy region (18,206 bp) and a large single-copy region (86,592 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that L. chinense is closely clustered with species Lycium ruthenicum and Lycium barbarum.

Chloroplast genome and phylogenetic analyses of Morus alba (Moraceae).

Morus alba is an important medicinal plant that is used to treat human diseases. The complete chloroplast (cp) genome of M. alba was assembled based on the Illumina sequencing reads. The cp genome of M. alba was 159,290 bp and contained two short inverted repeat regions (25,690 bp) which were separated by a small single copy region (19,845 bp) and a large single copy region (88,065 bp). The cp genome encodes 111 unique genes, including 77 protein-coding genes, 30 transfer RNA genes and four ribosomal RNA genes. The topology of the phylogenetic tree showed that M. alba is closely clustered with species M. cathayana and M. mongolica.

Chloroplast genome and phylogenetic analyses of Poncirus trifoliata (Rutaceae).

Poncirus trifoliata is an important medicinal plant that is used to treat human diseases. In this study, the complete chloroplast (cp) genome of P. trifoliata was assembled based on the Illumina sequencing reads. The cp genome of P. trifoliata was 160,260 bp and contained two short inverted repeat regions (27,029 bp) which were separated by a small single copy region (18,760 bp) and a large single copy region (87,442 bp). The cp genome encodes 113 unique genes, including 79 protein-coding genes, 30 transfer RNA genes and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that P. trifoliata is closely clustered with genus Citrus.

Characteristic and phylogenetic analyses of chloroplast genome for an endangered species Manglietia lucida (Magnoliaceae).

Manglietia lucida is a threatened horticultural plant in Yunnan province of China. Now, the complete chloroplast (cp) genome of M. lucida was assembled. The cp genome of M. lucida was 160,134 bp in length and contained two short inverted repeat regions (26,595 bp), which were separated by a small single copy region (18,825 bp) and a large single copy region (88,119 bp). The cp genome encodes 108 unique genes, including 74 protein-coding genes, 30 transfer RNA genes and 4 ribosomal RNA genes. The topology of the phylogenetic tree showed that M. lucida was not formed a monophyletic clade but clustered together with genus Magnolia.

Analysis of Poncirus polyandra (Rutaceae) chloroplast genome and its phylogenetic implications.

Poncirus polyandra is a threatened plant in China Now, the complete chloroplast (cp) genome of P. polyandra was assembled. The cp genome of P. polyandra was 160,212 bp in length, it consists of a pair of inverted repeats ((IRa and IRb) regions (27,016 bp) separated by the large single-copy (LSC, 87,407 bp) and small single-copy (SSC, 18,775 bp) regions. The cp genome encodes 105 unique genes, including 70 protein-coding genes, 30 transfer RNA genes, 4 ribosomal RNA genes, and 1 pseudogene. The phylogenetic tree of Rutaceae showed that P. polyandra was clustered together with genus Citrus and Poncirus.

Environmental and Historical Determinants of Patterns of Genetic Differentiation in Wild Soybean (Glycine soja Sieb. et Zucc).

Wild soybean, the direct progenitor of cultivated soybean, inhabits a wide distribution range across the mainland of East Asia and the Japanese archipelago. A multidisciplinary approach combining analyses of population genetics based on 20 nuclear microsatellites and one plastid locus were applied to reveal the genetic variation of wild soybean, and the contributions of geographical, environmental factors and historic climatic change on its patterns of genetic differentiation. High genetic diversity and significant genetic differentiation were revealed in wild soybean. Wild soybean was inferred to be limited to southern and central China during the Last Glacial Maximum (LGM) and experienced large-scale post-LGM range expansion into northern East Asia. A substantial northward range shift has been predicted to occur by the 2080s. A stronger effect of isolation by environment (IBE) versus isolation by geographical distance (IBD) was found for genetic differentiation in wild soybean, which suggested that environmental factors were responsible for the adaptive eco-geographical differentiation. This study indicated that IBE and historical climatic change together shaped patterns of genetic variation and differentiation of wild soybean. Different conservation measures should be implemented on different populations according to their adaptive potential to future changes in climate and human-induced environmental changes.

Nucleotide Sequence Diversity and Linkage Disequilibrium of Four Nuclear Loci in Foxtail Millet (Setaria italica).

Foxtail millet (Setaria italica (L.) Beauv) is one of the earliest domesticated grains, which has been cultivated in northern China by 8,700 years before present (YBP) and across Eurasia by 4,000 YBP. Owing to a small genome and diploid nature, foxtail millet is a tractable model crop for studying functional genomics of millets and bioenergy grasses. In this study, we examined nucleotide sequence diversity, geographic structure, and levels of linkage disequilibrium at four nuclear loci (ADH1, G3PDH, IGS1 and TPI1) in representative samples of 311 landrace accessions across its cultivated range. Higher levels of nucleotide sequence and haplotype diversity were observed in samples from China relative to other sampled regions. Genetic assignment analysis classified the accessions into seven clusters based on nucleotide sequence polymorphisms. Intralocus LD decayed rapidly to half the initial value within ~1.2 kb or less.

Antitumor activity of a recombinant soluble ectodomain of mutant human fibroblast growth factor receptor-2 IIIc.

The fibroblast growth factor (FGF) signaling pathway is a recognized target of cancer therapy. We have developed a strong inhibitor (S252W mutant soluble ectodomain of FGF recptor-2 IIIc, msFGFR2) that binds FGFs and blocks the activation of FGFRs. Thermodynamic binding studies indicated that msFGFR2 bound FGF-2 16.9 times as strongly as wild-type soluble FGFR2IIIc ectodomain (wsFGFR2). It successfully suppressed the growth, angiogenesis, and metastasis of two tumor cell lines in vitro and in vivo, and it potently inhibited cancer cell proliferation but not normal cell proliferation. Therefore, msFGFR2 is a useful probe for FGF-dependent signaling pathways and a potential broad-spectrum antitumor agent.