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Abstract Tumor is a representative of cell immortalization, while senescence irreversibly arrests cell proliferation. Although tumorigenesis and senescence seem contrary to each other, they have similar mechanisms in many aspects. Pancreatic ductal adenocarcinoma (PDA) is highly lethal disease, which occurs and progresses through a multi-step process. Senescence is prevalent in pancreatic premalignancy, as manifested by decreased cell proliferation and increased clearance of pre-malignant cells by immune system. However, the senescent microenvironment cooperates with multiple factors and significantly contributes to tumorigenesis. Evidently, PDA progression requires to evade the effects of cellular senescence. This review will focus on dual roles that senescence plays in PDA development and progression, the signaling effectors that critically regulate senescence in PDA, the identification and reactivation of molecular targets that control senescence program for the treatment of PDA.

Objective: Study on the non-alkaloid chemical constituents with novel structure and their biological activities from the w-butanol fraction of the leaves of Rauvolfia vomitoria. Methods: The w-butanol fraction of R. vomitoria was separated by silica gel, ODS, and Sephadex LH-20 chromatography column, as well as semi-preparative HPLC to obtain five compounds. Their structures were identified by extensive spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and ECD analysis. All the isolated compounds were evaluated their AChE inhibitory activities by Ellman’s method with slight modification, their vasorelaxant activities against phenylephrine-induced contraction of rat mesenteric arteries, and their inhibitory activity of a-glucosidase employing pNPG as substrate. Results: Two new phenylpropanoids (1-2) along with three known compounds, methyl trans-3,4,5-trimethoxycinnamate (3), methyl cis-3,4,5-trimethoxycinnamate (4), and 3,4,5-trimethoxybenzoic acid methyl ester (5), were isolated from the leaves of R.vomitoria. The five isolated compounds did not show significant tested activity. Conclusion: Chemical investigation of the leaves of R. vomitoria led to the isolation and identification of two new phenylpropanoids (1–2), expanding the study of non-alkaloids in the genus of Rauvolfia and enriching the chemical diversity of this genus.

The genetic relationships among the species in Scutellaria genus remain unclear because of the variation in the number of species and complex trait. The usage of S. baicalensis and its four substitute medicinal species (S. amoena, S. hypericifolia, S. likiangensis, and S. viscidula) in traditional medicines make their specialized metabolism important in China, but interspecific genetic and chemical differences have rarely been reported for these species. In this study, the chloroplast genomes of four substitute species for S. baicalensis were assembled, and comparative and phylogenetic analyses were performed with these species and other Scutellaria relatives. In addition, metabolomics analyses were performed and the contents of the main active compounds were determined to reveal the interspecific chemical diversity of S. baicalensis and its four substitute species. The full lengths of their chloroplast genomes ranged from 151,574 to 151,816 bp with an average GC content of 38.34%, and a total of 113 genes were annotated. In the chloroplast genomes of S. baicalensis and its four substitutes, one hypervariable region (petA-psbL) is proposed as a potential DNA barcode. Phylogenetic analysis showed that the subdivision of the genus Scutellaria should be reconsidered. The metabolomics and content determination analyses showed that the four species exhibit a metabolism similar to that of S. baicalensis in different parts. Except for the roots of S. likiangensis, all parts of the substitute species showed high contents of baicalin. Genetic and chemical analyses of four substitute medicinal species for S. baicalensis were performed here for the first time, and their pharmacophylogenetic relationships were further explored, providing a scientific basis for the subsequent development of the medicinal value and resource utilization of Scutellaria.

Objective: Synaptic plasticity is critical for neurorehabilitation after focal cerebral ischemia. Connexin 43 (Cx43), the main component of the gap junction, has been shown to be pivotal for synaptic plasticity. The objective of this study was to investigate the role of the Cx43 inhibitor (Gap26) and gap junction modifier (GAP-134) in neurorehabilitation and to study their contribution to synaptic plasticity after focal ischemia.Methods: Time course expression of both total and phosphorylated Cx43 (p-Cx43) were detected by western blotting at 3, 7, and 14 d after focal ischemia. Gap26 and GAP-134 were administered starting from 3 d post focal ischemia. Neurological performances were evaluated by balance beam walking test and Y-maze test at 1, 3, and 7 d. Golgi staining and transmission electron microscope (TEM) detection were conducted at 7 d for observing dendritic spine numbers and synaptic ultrastructure, respectively. Immunofluorescent staining was used at 7 d for detection of synaptic plasticity markers, including synaptophysin (SYN) and growth-associated protein-43 (GAP-43).Results: Expression levels of both total Cx43 and p-Cx43 were increased after focal cerebral ischemia, peaking at 7 d. Compared with the MCAO group, Gap26 worsened the neurological behavior and decreased the dendritic spine number while GAP-134 improved the neurobehavior and increased the number of dendritic spines. Moreover, Gap26 further destroyed the synaptic structure, concomitant with downregulated SYN and GAP-43, whereas GAP-134 alleviated synaptic destruction and upregulated SYN and GAP-43.Conclusion: These findings suggested that Cx43 or the gap junction was involved in synaptic plasticity, thereby promoting neural recovery after ischemic stroke. Treatments enhancing gap junctions may be potential promising therapeutic measures for neurorehabilitation after ischemic stroke.

One new monoterpene alkaloid (1) and eight known compounds (2–9), belonging to two monoterpene alkaloids (1–2), one pyridine alkaloid (3), four phenylpropanoid derivatives (4–7), and two matrine-type alkaloids (8–9), were isolated from Rauvolfia vomitoria Afzel. The structure of new compound 1 was determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. Notably, this is the first reported monoterpene alkaloids from R. vomitoria. Besides, compounds 3, 5, and 7–9 were first discovered in the Apocynaceae family and compounds 4 and 6 were first reported in the Rauvolfia genus. This is also the first example of matrine-type alkaloids reported in the Apocynaceae family, indicating that matrine-type alkaloids are not unique to the Leguminosae/Fabaceae family. All isolated compounds were evaluated for their anti-acetylcholinesterase, anti-α-glucosidase, and antioxidant activities. Compound 6 showed significant α-glucosidase inhibitory activity and remarkable DPPH radical scavenging capacity, both of which are superior to the positive controls. Molecular docking of compound 6 with α-glucosidase was further performed, suggesting that compound 6 could form hydrogen bonds with residues ALA-292, ASN-259, and ARG-263. [ABSTRACT FROM AUTHOR]

The article discusses antibiotic resistance has a major threat to human health, and one approach to combating threat has to develop resistance-resistant antibiotics. Topics include the oligomer exhibited excellent effectiveness in various model systems, killing extracellular or intracellular bacteria in the presence of mammalian cells, removing all bacteria; and antibiotic resistance has an emerging threat to public health and to the global economy.