Nutritional Composition and Modern Pharmacological Research Progress of Coicis Semen

Coicis semen has the effects of invigorating the spleen, invigorating the lungs and removing dampness, clearing heat, expelling pus, removing stagnation and stopping diarrhea. The main nutrients of Coicis semen are fatty acids, esters, polysaccharides, flavonoids, glycoproteins and other components. The results of modern pharmacological studies have shown that Coicis semen has multiple pharmacological effects such as anti-tumor, improving immunity, lowering blood sugar, anti-inflammatory and analgesic, and regulating blood lipid metabolism. By consulting relevant literature in recent years, this paper reviewed the extraction process of Coicis semen nutritional components, including fatty acids, lipids, polysaccharides, flavonoids, Coicis semen oil. Modern pharmacological effects such as anti-tumor, improving immunity, lowering blood glucose and regulating blood lipid metabolism were also included. The development directions of Coicis semen for hypoglycemic, anti-inflammatory, analgesic, osteoporosis and other related functional foods were summarized. This review could provide reference for further development and application of Coicis semen

Advances in Strain Improvement for the Production of ε-Poly-L-lysine

ε-Poly-L-lysine (ε-PL) is a novel biopolymer consisting of 25–35 L-lysine residues, which is formed by the dehydration condensation of ε-NH2 and α-COOH. ε-PL possesses many excellent characteristics, such as antimicrobial activity, edibility, water solubility, biodegradability, thermostability and nontoxicity. As a natural and safe food preservative, ε-PL possesses many excellent advantages such as thermal stability, edibility, water solubility, degradability, and broad-spectrum antibacterial activity and has been successfully utilized in Japan, South Korea, the United States, China and other countries. ε-PL is usually produced by fermentation with Streptomyces albulus, and improving ε-PL-producing stains is crucial for enhancing ε-PL production and reducing costs. At present, researchers have obtained microbial strains capable of producing high levels of ε-PL by using physicochemical mutagenesis, ribosome engineering, genome shuffling, genetic engineering and other methods. This review introduces the mechanism of ε-PL biosynthesis and recent progress in strain improvement for the production of ε-PL, and gives an overview of the fermentation process of ε-PL. Finally, this review concludes with an outlook on future research directions. We hope that this review can help promote strain improvement for green biological manufacturing of ε-poly-L-lysine

AI protein structure prediction-based modeling and mutagenesis of a protostome receptor and peptide ligands reveal key residues for their interaction

The protostome leucokinin (LK) signaling system, including LK peptides and their G protein-coupled receptors, has been characterized in several species. Despite the progress, molecular mechanisms governing LK peptide–receptor interactions remain to be elucidated. Previously, we identified a precursor protein for Aplysia leucokinin-like peptides (ALKs) that contains the greatest number of amidated peptides among LK precursors in all species identified so far. Here, we identified the first ALK receptor from Aplysia, ALKR. We used cell-based IP1 activation assays to demonstrate that two ALK peptides with the most copies, ALK1 and ALK2, activated ALKR with high potencies. Other endogenous ALK-derived peptides bearing the FXXWX-amide motif also activated ALKR to various degrees. Our examination of cross-species activity of ALKs with the Anopheles LK receptor was consistent with a critical role for the FXXWX-amide motif in receptor activity. Furthermore, we showed, through alanine substitution of ALK1, the highly conserved phenylalanine (F), tryptophan (W), and C-terminal amidation were each essential for receptor activation. Finally, we used an artificial intelligence– based protein structure prediction server (Robetta) and Autodock Vina to predict the ligand-bound conformation of ALKR. Our model predicted several interactions (i.e., hydrophobic interactions, hydrogen bonds, and amide-pi stacking) between ALK peptides and ALKR, and several of our substitution and mutagenesis experiments were consistent with the predicted model. In conclusion, our results provide important information defining possible interactions between ALK peptides and their receptors. The workflow utilized here may be useful for studying other ligand–receptor interactions for a neuropeptide signaling system, particularly in protostomes

A role of periaqueductal grey NR2B-containing NMDA receptor in mediating persistent inflammatory pain

The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain

Characterization of an Aplysia vasotocin signaling system and actions of posttranslational modifications and individual residues of the ligand on receptor activity

The vasopressin/oxytocin signaling system is present in both protostomes and deuterostomes and plays various physiological roles. Although there were reports for both vasopressin-like peptides and receptors in mollusc Lymnaea and Octopus, no precursor or receptors have been described in mollusc Aplysia. Here, through bioinformatics, molecular and cellular biology, we identified both the precursor and two receptors for Aplysia vasopressin-like peptide, which we named Aplysia vasotocin (apVT). The precursor provides evidence for the exact sequence of apVT, which is identical to conopressin G from cone snail venom, and contains 9 amino acids, with two cysteines at position 1 and 6, similar to nearly all vasopressin-like peptides. Through inositol monophosphate (IP1) accumulation assay, we demonstrated that two of the three putative receptors we cloned from Aplysia cDNA are true receptors for apVT. We named the two receptors as apVTR1 and apVTR2. We then determined the roles of post-translational modifications (PTMs) of apVT, i.e., the disulfide bond between two cysteines and the C-terminal amidation on receptor activity. Both the disulfide bond and amidation were critical for the activation of the two receptors. Cross-activity with conopressin S, annetocin from an annelid, and vertebrate oxytocin showed that although all three ligands can activate both receptors, the potency of these peptides differed depending on their residue variations from apVT. We, therefore, tested the roles of each residue through alanine substitution and found that each substitution could reduce the potency of the peptide analog, and substitution of the residues within the disulfide bond tended to have a larger impact on receptor activity than the substitution of those outside the bond. Moreover, the two receptors had different sensitivities to the PTMs and single residue substitutions. Thus, we have characterized the Aplysia vasotocin signaling system and showed how the PTMs and individual residues in the ligand contributed to receptor activity