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Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they must fulfil critical immunological function(s). MAIT cells are defined by their expression of a semi-invariant αβ TCR which recognises biosynthetic derivatives of riboflavin synthesis presented on MR1. Initial studies focused on their role in detecting predominantly intracellular bacterial and mycobacterial infections. However, it is now recognised that there are several modes of MAIT cell activation and these are related to activation of distinct transcriptional programmes, each associated with distinct functional roles. In this minireview, we summarise current knowledge from human and animal studies of MAIT cell activation induced 1) in an MR1-TCR dependent manner in the context of inflammatory danger signals and associated with antibacterial host defence; 2) in an MR1-TCR independent manner by the cytokines interleukin(IL)-12 / -15 / -18 and type I interferon, which is associated with antiviral responses; and 3) a recently-described TCR-dependent ‘tissue repair’ programme which is associated with accelerated wound healing in the context of commensal microbiota. Because of this capability for diverse functional responses in diverse immunological contexts, these intriguing cells now appear to be multifunctional effectors central to the interface of innate and adaptive immunity.

Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases. Yihuo Huatan Formula (YHF), as a proven Chinese Herbal Medicine (CHM), has been verified to be effective in the treatment of stable COPD through years’ of practice. Nevertheless, its working mechanism is still unclear. We sought to systematically decipher the mechanism of YHF for treating stable COPD using systems pharmacology-based method that integrates pharmacokinetic screening, target prediction, network analyses, GO and KEGG enrichment analyses. Firstly, a total of 1267 chemicals out of 15 herbal components were included in YHF chemical database. Among them, 180 potential active molecules were screened out through pharmacokinetic evaluation. Then 258 targets of the active molecules were predicted, of which 84 were chosen for further analyses. Finally, the network analyses and GO and KEGG enrichment methods suggested a therapeutic effect of YHF on the alleviation of airway inflammation, decrease of mucus secretion, maintenance of immune homeostasis and benefit of COPD comorbidities, by regulating multiple targets and pathways. The systems pharmacology-based approach helps to understand the underlying working mechanism of YHF in stable COPD from a holistic perspective, and offers an exemplification for systematically uncovering the action mechanisms of CHM.

Ethnopharmacological relevance Mucus hypersecretion (MH) is recognized as a key pathophysiological and clinical feature of many airway inflammatory diseases. MUC5AC is a major component of airway mucus. Tanreqing injection (TRQ) is a widely used herbal formula for the treatment of respiratory inflammations for years in China. However, a holistic network pharmacology approach to understanding its therapeutic mechanisms against MH has not been pursued. Aim of the study This study aimed to explore the systems-level potential active compounds and therapeutic mechanisms of TRQ in the treatment of MH. Materials and methods We established systems pharmacology-based strategies comprising compound screenings, target predictions, and pathway identifications to speculate the potential active compounds and therapeutic targets of TRQ. We also applied compound-target and target-disease network analyses to evaluate the possible action mechanisms of TRQ. Then, lipopolysaccharide (LPS)-induced Sprague-Dawley (SD) rat model was constructed to assess the effect of TRQ in the treatment of MH and to validate the possible molecular mechanisms as predicted in systems pharmacology approach. Results The comprehensive compound collection successfully generated 55 compound candidates from TRQ. Among them, 11 compounds with high relevance to the potential targets were defined as representative and potential active ingredients in TRQ formula. Target identification revealed 172 potential targets, including pro-inflammatory cytokines of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-8. Pathway analyses uncovered the possible action of TRQ in the regulation of IL-17 signaling pathway and its downstream protein MUC5AC. Then in vivo experiment indicated that TRQ could significantly inhibit LPS stimulated MUC5AC over-production as well as the expression of TNF-α, IL-6, IL-8, and IL-17A, in both protein and mRNA levels. Conclusions Based on the systems pharmacology method and in vivo experiment, our work provided a general knowledge on the potential active compounds and possible therapeutic targets of TRQ formula in its anti-MH process. This work might suggest directions for further research on TRQ and provide more insight into better understanding the chemical and pharmacological mechanisms of complex herbal prescriptions in a network perspective.

The east-Ujimqin complex located north of the Erenhot-Hegenshan ophiolite belt in North China is composed of extensive Carboniferous and Permian magmatic rock suites, which preserve the records of an extensional tectonic regime following collision. These rocks provide important clues to the closure of the Hegenshan ocean and intraplate processes. Here we investigate the diorite dyke swarms in association with granitic rocks from the Xing'an-Mongolian Orogenic Belt (XMOB) through field investigations, petrology, geochemistry, zircon U-Pb and Lu-Hf studies, to gain insights into the timing, magma source and tectonic setting during Late Carboniferous and Early Permian. The diorite rocks display sub-alkaline, calc-alkaline, and high-K calc-alkaline features. Their extensional setting is suggested by plots in the fields of within plate basalt and active continental margin + alkaline oceanic arc. Zircon U-Pb data on magmatic zircons indicate that the granitoids crystallized at ca. 301 Ma, whereas the diorite dykes were emplaced at 286 Ma. Xenocryst zircon grains with 320 to 300 Ma ages in the dyke samples suggest incorporation from the surrounding granites. Zircon Lu-Hf isotopic data show consistently positive eHf(t) values (5.3 to 10.8) and plot between CHUR (Chondritic Uniform Reservoir) and depleted mantle lines suggesting that depleted mantle sources contributed significantly to the magma source. The computed model ages suggest that the magma source involved Neoproterozoic juvenile components. We propose a model where the magmatism occurred within an extensional tectonic setting caused by asthenosphere upwelling and lithospheric thinning. Our study also constrains the timing of Early Permian extension which suggests that the Hegenshan Ocean, as part of the Central Asian Orogenic Belt closed prior to 286 Ma.

Chinese herbal medicine (CHM) has been widely used in the treatment of advanced non-small-cell lung cancer (NSCLC), but their efficacy and safety remain controversial. We sought to comprehensively aggregate and evaluate the available evidence on the efficacy and safety of the combination treatment with CHM and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients. Our exhausted and systematical searching strategy yielded 64 related randomized controlled trials involving 4384 patients. Compared with EGFR-TKIs therapy alone, meta-analysis showed significant differences favoring the combination treatment in progression-free survival ([Formula: see text]), median survival time ([Formula: see text]), one-year survival rate ([Formula: see text]), two-year survival rate ([Formula: see text]), probability of severe toxicities ([Formula: see text]), objective response rate ([Formula: see text]), Karnofsky performance status ([Formula: see text]), and improvement in percentage of CD3[Formula: see text] T lymphocyte ([Formula: see text]) and CD4[Formula: see text] T lymphocyte ([Formula: see text]). Though these results require further confirmation, they are prone to show a potential therapeutic value of CHM in improving the clinical effect, overcoming the drug resistance and toxicities as an adjunctive therapy to EGFR-TKIs.