The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

Investigating the active chemical constituents and pharmacology of Nanocnide lobata in the treatment of burn and scald injuries.

OBJECTIVE: To identify the most effective fraction of Nanocnide lobata in the treatment of burn and scald injuries and determine its bioactive constituents. METHODS: Chemical identification methods were used to analyze solutions extracted from Nanocnide lobata using petroleum ether, ethyl acetate, n-butanol using a variety of color reactions. The chemical constituents of the extracts were identified by ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS). A total of 60 female mice were randomly divided into the following 6 groups: the petroleum ether extract-treated group; the ethyl acetate extract-treated group; the n-butanol extract-treated group; the model group; the control group; and the positive drug group. The burn/scald model was established using Stevenson's method. At 24 hours after modeling, 0.1 g of the corresponding ointment was evenly applied to the wound in each group. Mice in the model group did not undergo treatment, while those in the control group received 0.1 g of Vaseline. Wound characteristics, including color, secretions, hardness, and swelling, were observed and recorded. Photos were taken and the wound area calculated on the 1st, 5th, 8th, 12th, 15th, 18th and 21st days. Hematoxylin-eosin (HE) staining was utilized to observe the wound tissue of mice on the 7th, 14th, and 21st days. An enzyme-linked immunosorbent assay (ELISA) kit was used to measure the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-10, vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-ß1. RESULTS: The chemical constituents of Nanocnide lobata mainly include volatile oils, coumarins, and lactones. UPLC-MS analysis revealed 39 main compounds in the Nanocnide lobata extract. Among them, ferulic acid, kaempferitrin, caffeic acid, and salicylic acid have been confirmed to exhibit anti-inflammatory and antioxidant activity related to the treatment of burns and scalds. HE staining revealed a gradual decrease in the number of inflammatory cells and healing of the wounds with increasing time after Nanocnide lobata extract administration. Compared with the model group, the petroleum ether extract-treated group showed significant differences in the levels of TNF-α (161.67±4.93, 106.33±3.21, 77.67±4.04 pg/mL) and IL-10 (291.77±4.93, 185.09±9.54, 141.33±1.53 pg/mL) on the 7th, 14th, and 21st days; a significant difference in the content of TGF-ß1 (75.68±3.06 pg/mL) on the 21st day; and a significant difference in the level of VEGF (266.67±4.73, 311.33±10.50 pg/mL) on the 7th and 14th days respectively. CONCLUSION: Petroleum ether Nanocnide lobata extract and the volatile oil compounds of Nanocnide lobata might be effective drugs in the treatment of burn and scald injuries, as they exhibited a protective effect on burns and scalds by reducing the expression of TNF-α, IL-10 and TGF-ß1 and increasing the expression of VEGF. In addition, these compounds may also exert pharmacological effects that promote wound tissue repair, accelerate wound healing, and reduce scar tissue proliferation, inflammation and pain.

3D Printed Skull Cap and Benchtop Fabricated Microwire-Based Microelectrode Array for Custom Rat Brain Recordings.

Microwire microelectrode arrays (MEAs) have been a popular low-cost tool for chronic electrophysiological recordings and are an inexpensive means to record the electrical dynamics crucial to brain function. However, both the fabrication and implantation procedures for multi-MEAs on a single rodent are time-consuming and the accuracy and quality are highly manual skill-dependent. To address the fabrication and implantation challenges for microwire MEAs, (1) a computer-aided designed and 3D printed skull cap for the pre-determined implantation locations of each MEA and (2) a benchtop fabrication approach for low-cost custom microwire MEAs were developed. A proof-of-concept design of a 32-channel 4-MEA (8-wire each) recording system was prototyped and tested through Sprague Dawley rat recordings. The skull cap design, based on the CT-scan of a single rat conforms well with multiple Sprague Dawley rats of various sizes, ages, and weight with a minimal bregma alignment error (A/P axis standard error of the mean = 0.25 mm, M/L axis standard error of the mean = 0.07 mm, n = 6). The prototyped 32-channel system was able to record the spiking activities over five months. The developed benchtop fabrication method and the 3D printed skull cap implantation platform would enable neuroscience groups to conduct in-house design, fabrication, and implantation of customizable microwire MEAs at a lower cost than the current commercial options and experience a shorter lead time for the design modifications and iterations.

Manufacturing Processes of Implantable Microelectrode Array for In Vivo Neural Electrophysiological Recordings and Stimulation: A State-Of-the-Art Review.

Electrophysiological recording and stimulation of neuron activities are important for us to understand the function and dysfunction of the nervous system. To record/stimulate neuron activities as voltage fluctuation extracellularly, microelectrode array (MEA) implants are a promising tool to provide high temporal and spatial resolution for neuroscience studies and medical treatments. The design configuration and recording capabilities of the MEAs have evolved dramatically since their invention and manufacturing process development has been a key driving force for such advancement. Over the past decade, since the White House Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative launched in 2013, advanced manufacturing processes have enabled advanced MEAs with increased channel count and density, access to more brain areas, more reliable chronic performance, as well as minimal invasiveness and tissue reaction. In this state-of-the-art review paper, three major types of electrophysiological recording MEAs widely used nowadays, namely, microwire-based, silicon-based, and flexible MEAs are introduced and discussed. Conventional design and manufacturing processes and materials used for each type are elaborated, followed by a review of further development and recent advances in manufacturing technologies and the enabling new designs and capabilities. The review concludes with a discussion on potential future directions of manufacturing process development to enable the long-term goal of large-scale high-density brain-wide chronic recordings in freely moving animals.

Uncovering the molecular mechanism of Gynostemma pentaphyllum (Thunb.) Makino against breast cancer using network pharmacology and molecular docking.

Because of their strong anti-cancer efficacy with fewer side effects, traditional Chinese medicines (TCM) have attracted considerable attention for their potential application in treating breast cancer (BC). However, knowledge about the underlying systematic mechanisms is scarce. Gynostemma pentaphyllum (Thunb.) Makino (GP), a creeping herb, has been regularly used as a TCM to prevent and treat tumors including BC. Again, mechanisms underlying its anti-BC properties have remained elusive. We used network pharmacology and molecular docking to explore the mechanistic details of GP against BC. The TCM systems pharmacology database and analysis platform and PharmMapper Server database were used to retrieve the chemical constituents and potential targets in GP. In addition, targets related to BC were identified using DrugBank and Therapeutic Target Database. Protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of crucial targets were performed using the Search Tool for the Retrieval of Interacting Genes/Proteins and database for annotation, visualization, and integrated discovery databases, whereas the network visualization analysis was performed using Cytoscape 3.8.2. In addition, the molecular docking technique was used to validate network pharmacology-based predictions. A comparison of the predicted targets of GP with those of BC-related drugs revealed 26 potential key targets related to the treatment of BC, among which ALB, EGFR, ESR1, AR, PGR, and HSP90AA1 were considered the major potential targets. Finally, network pharmacology-based prediction results were preliminarily verified by molecular docking experiments. In addition, chemical constituents and potential target proteins were scored, followed by a comparison with the ligands of the protein. We provide a network of pharmacology-based molecular mechanistic insights on the therapeutic action of GP against BC. We believe that our data will serve as a basis to conduct future studies and promote the clinical applications of GP.

CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway.

OBJECTIVES: This study was designed to determine whether xanthine oxidoreductase (XOR) is involved in Isosorbide- 5-mononitrate (IS-5-MN) metabolism, and to elucidate the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the IS-5-MN response. METHODS: In 15 Chinese volunteers, we observed the relationship between baseline XOR-mRNA expression in peripheral blood mononuclear cells (PBMCs) and the response to 20 mg IS-5-MN. IS-5-MN pharmacokinetics profiles, changes in plasma concentrations of CGRP, and CGRPmRNA expression in PBMCs were assessed in vivo and in vitro. RESULTS: Individuals with a lower baseline XOR-mRNA expression showed lower plasma XOR activity and significantly greater changes in SBP (ΔSBP) after IS-5-MN administration. Individuals with a lower baseline XOR-mRNA expression also showed significantly greater increases in plasma concentrations of CGRP. There were no differences in IS-5-MN AUC between the two groups. IS-5-MN significantly up-regulated the expression of CGRP α- and CGRP ß-mRNA in PBMCs, which were not affected by the XOR inhibitor allopurinol. CONCLUSIONS: Our study suggests that CGRP may contribute to the response to IS-5 MN in a XOR-independent pathway.

[Pharmacognostical study on cultivated Fritillaria taipaiensis].

OBJECTIVE: To study on the pharmacognostical characteristics of cultivated Fritillaria taipaiensis for providing basis for further development and research. METHODS: Botanical, macroscopic and microscopic identifications, and determination of the content of extract, total saponins and total alkaloids were carried out. RESULTS: Because of various growing years, cultivated Fritillaria taipaiensis had diffferent properties,in addition to tip slightly resembling songbei's tip "embracing the moon", there were greatly different characteristics in the rest of specifications comparing with the traditional Fritillaria cirrhosa. Some were shallow conical or cylindrical, some had slightly rough surface,and some bases were constricted, bitter in taste. There were great differences in its extract and total alkaloids con-tent,and no obvious differences in the content of total saponins. CONCLUSION: The experimental results show that the extract,total saponins and total alkaloids content are not positively correlated or relevant with the current classification of Fritillariae Cirrhosae Bulbus. To consider the medicinal appearance diameter and length, the grade classification should be based on different application requirements, and combined with the evaluation of active ingredients.

The CD40/CD40L system: a new therapeutic target for disease.

The role of CD40/CD40 ligand (CD40L) interactions in atherothrombosis, in the response of the immune system to pathogens and in thrombosis is now widely accepted. A role for CD40-CD40L interactions has been identified in atherosclerosis (AS), and such interactions are known to destabilize atherosclerotic plaques by inducing the expression of cytokines, chemokines, growth factors, matrix metalloproteinases and pro-coagulant factors. CD40/CD40L interactions have also been implicated in immune system disorders. Recent studies have suggested that CD40/CD40L interactions regulate oxidative stress and affect various signaling pathways in both the immunological and the cardiovascular systems. Here, we discuss the current drugs that target the CD40/CD40L system, as understanding the roles and regulations of CD40/CD40L-mediated signal pathways by these drugs could facilitate the development of therapeutics that target diverse diseases.