A Unified Atlas of T cell Glycophysiology.

Glycans are emerging as important regulators of T cell function but remain poorly characterized across the functionally distinct populations that exist in vivo . Here, we couple single-cell analysis technologies with soluble lectins and chemical probes to interrogate glycosylation patterns on major T cell populations across multiple mouse and human tissues. Our analysis focused on terminal glycan epitopes with immunomodulatory functions, including sialoglycan ligands for Siglecs. We demonstrate that glycosylation patterns are diverse across the resting murine T cell repertoire and dynamically remodelled in response to antigen-specific stimulation. Surprisingly, we find that human T cell populations do not share the same glycoprofiles or glycan remodelling dynamics as their murine counterparts. We show that these differences can be explained by divergent regulation of glycan biosynthesis pathways between the species. These results highlight fundamental glycophysiological differences between mouse and human T cells and reveal features that are critical to consider for glycan-targeted therapies.

Evaluations of Andrographolide-Rich Fractions of Andrographis paniculata with Enhanced Potential Antioxidant, Anticancer, Antihypertensive, and Anti-Inflammatory Activities.

Andrographis paniculata is widely used as a traditional medicine in Asian countries. It has been classified as a safe and non-toxic medicine by traditional Chinese medicine. The investigation of the biological activities of A. paniculata is still focused on the crude extract and isolation of its main active compound, andrographolide, and its derivatives. However, the use of andrographolide alone has been shown to exacerbate unwanted effects. This highlights the importance of developing a fraction of A. paniculata with enhanced efficacy as an herbal-based medicine. In this study, the extraction and fractionation of A. paniculata, followed by quantitative analysis using high-performance liquid chromatography coupled with a DAD detector, were established to quantify the andrographolide and its derivative in each fraction. Biological activities, such as antioxidant, anticancer, antihypertensive, and anti-inflammatory activities, were evaluated to study their correlations with the quantification of active substances of A. paniculata extract and its fractions. The 50% methanolic fraction of A. paniculata exhibited the best cytotoxic activities against CACO-2 cells, as well as the best anti-inflammatory and antihypertensive activities compared to other extracts. The 50% methanolic fraction also displayed the highest quantification of its main active compound, andrographolide, and its derivatives, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and andrograpanin, among others.

Secondary Metabolites from Marine-Derived Fungi and Actinobacteria as Potential Sources of Novel Colorectal Cancer Drugs.

Colorectal cancer is one of the most common cancers diagnosed in the world. Chemotheraphy is one of the most common methods used for the pharmacological treatment of this cancer patients. Nevertheless, the adverse effect of chemotherapy is not optimized for improving the quality of life of people who are older, who are the most vulnerable subpopulation. This review presents recent updates regarding secondary metabolites derived from marine fungi and actinobacteria as novel alternatives for cytotoxic agents against colorectal cancer cell lines HCT116, HT29, HCT15, RKO, Caco-2, and SW480. The observed marine-derived fungi were from the species Aspergillus sp., Penicillium sp., Neosartorya sp., Dichotomomyces sp., Paradendryphiella sp., and Westerdykella sp. Additionally, Streptomyces sp. and Nocardiopsis sp. are actinobacteria discussed in this study. Seventy one compounds reviewed in this study were grouped on the basis of their chemical structures. Indole alkaloids and diketopiperazines made up most compounds with higher potencies when compared with other groups. The potency of indole alkaloids and diketopiperazines was most probably due to halogen-based functional groups and sulfide groups, respectively.

Antiviral Activities of Andrographolide and Its Derivatives: Mechanism of Action and Delivery System.

Andrographispaniculata (Burm.f.) Nees has been used as a traditional medicine in Asian countries, especially China, India, Vietnam, Malaysia, and Indonesia. This herbaceous plant extract contains active compounds with multiple biological activities against various diseases, including the flu, colds, fever, diabetes, hypertension, and cancer. Several isolated compounds from A. paniculata, such as andrographolide and its analogs, have attracted much interest for their potential treatment against several virus infections, including SARS-CoV-2. The mechanisms of action in inhibiting viral infections can be categorized into several types, including regulating the viral entry stage, gene replication, and the formation of mature functional proteins. The efficacy of andrographolide as an antiviral candidate was further investigated since the phytoconstituents of A. paniculata exhibit various physicochemical characteristics, including low solubility and low bioavailability. A discussion on the delivery systems of these active compounds could accelerate their development for commercial applications as antiviral drugs. This study critically reviewed the current antiviral development based on andrographolide and its derivative compounds, especially on their mechanism of action as antiviral drugs and drug delivery systems.

Cembranoids of Soft Corals: Recent Updates and Their Biological Activities.

Soft corals are well-known as excellent sources of marine-derived natural products. Among them, members of the genera Sarcophyton, Sinularia, and Lobophytum are especially attractive targets for marine natural product research. In this review, we reported the marine-derived natural products called cembranoids isolated from soft corals, including the genera Sarcophyton, Sinularia, and Lobophytum. Here, we reviewed 72 reports published between 2016 and 2020, comprising 360 compounds, of which 260 are new compounds and 100 are previously known compounds with newly recognized activities. The novelty of the organic molecules and their relevant biological activities, delivered by the year of publication, are presented. Among the genera presented in this report, Sarcophyton spp. produce the most cembranoid diterpenes; thus, they are considered as the most important soft corals for marine natural product research. Cembranoids display diverse biological activities, including anti-cancer, anti-bacterial, and anti-inflammatory. As cembranoids have been credited with a broad range of biological activities, they present a huge potential for the development of various drugs with potential health and ecological benefits.

Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates.

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007-2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.

Advice from the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons on riot control agents in connection to the Chemical Weapons Convention.

Compounds that cause powerful sensory irritation to humans were reviewed by the Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) in response to requests in 2014 and 2017 by the OPCW Director-General to advise which riot control agents (RCAs) might be subject to declaration under the Chemical Weapons Convention (the "Convention"). The chemical and toxicological properties of 60 chemicals identified from a survey by the OPCW of RCAs that had been researched or were available for purchase, and additional chemicals recognised by the SAB as having potential RCA applications, were considered. Only 17 of the 60 chemicals met the definition of a RCA under the Convention. These findings were provided to the States Parties of the Convention to inform the implementation of obligations pertaining to RCAs under this international chemical disarmament and non-proliferation treaty.

Toxicological findings in driver and motorcyclist fatalities in Scotland 2012-2015.

Fatal motor vehicle crashes (MVCs) continue to be a common occurrence worldwide. This paper presents a retrospective analysis of the toxicological investigation of drivers and motorcyclists fatally injured in MVCs in Scotland from 2012 to 2015. One hundred and eighteen cases with full toxicological analysis, i.e., alcohol, drugs of abuse and prescription drugs, were examined. Of those 118 MVC cases, 74 (63%) were car drivers, 32 (27%) were motorcyclists and the remaining were drivers of other vehicles such as large goods vehicles. The majority of deceased drivers and motorcyclists were male (N=104, 88%). For the toxicological findings, 51 (43%) of the cases were negative, and of the 67 (57%) positive cases, alcohol and cannabinoids were the most frequently detected substances, followed by opioids and benzodiazepines. Fifteen percent of all drivers and motorcyclists were over the prescribed blood alcohol limit at the time of analysis. In comparison to previous reports of drug use by drivers in Scotland, benzodiazepines and new psychoactive substances were less common findings in fatally injured drivers and motorcyclists than in drivers suspected of being impaired.