Anticancer activities of natural antimicrobial peptides from animals

Cancer is the most common cause of human death worldwide, posing a serious threat to human health and having a negative impact on the economy. In the past few decades, significant progress has been made in anticancer therapies, but traditional anticancer therapies, including radiation therapy, surgery, chemotherapy, molecular targeted therapy, immunotherapy and antibody-drug conjugates (ADCs), have serious side effects, low specificity, and the emergence of drug resistance. Therefore, there is an urgent need to develop new treatment methods to improve efficacy and reduce side effects. Antimicrobial peptides (AMPs) exist in the innate immune system of various organisms. As the most promising alternatives to traditional drugs for treating cancers, some AMPs also have been proven to possess anticancer activities, which are defined as anticancer peptides (ACPs). These peptides have the advantages of being able to specifically target cancer cells and have less toxicity to normal tissues. More and more studies have found that marine and terrestrial animals contain a large amount of ACPs. In this article, we introduced the animal derived AMPs with anti-cancer activity, and summarized the types of tumor cells inhibited by ACPs, the mechanisms by which they exert anti-tumor effects and clinical applications of ACPs

Polysaccharides Derived From the Brown Algae Lessonia nigrescens Enhance Salt Stress Tolerance to Wheat Seedlings by Enhancing the Antioxidant System and Modulating Intracellular Ion Concentration

Soil salinity reduces plant growth and is a major factor that causes decreased agricultural productivity worldwide. Seaweed polysaccharides promote crop growth and improve plant resistance to abiotic stress. In this study, polysaccharides from brown seaweed Lessonia nigrescens polysaccharides (LNP) were extracted and further separated and fractionated. Two acidic polysaccharides (LNP-1 and LNP-2) from crude LNP were obtained and characterized. The latter had a lower molecular weight (MW) (40.2 kDa) than the former (63.9 kDa), but had higher uronic acid and sulfate content. Crude LNP and LNP-2 were composed of mannose, glucuronic acid, fucose, and xylose, whereas LNP-1 has little mannose. Moreover, the effects of the three polysaccharides on plant salt tolerance were investigated. The results showed that crude LNP, LNP-1, and LNP-2 promoted the growth of plants, decreased membrane lipid peroxidation, increased the chlorophyll content, improved antioxidant activities, and coordinated the efflux and compartmentation of intracellular ion. All three polysaccharides could induce plant resistance to salt stress, but LNP-2 was more effective than the other two. The present study allowed to conclude that both MW and sulfate degree contribute to salt resistance capability of polysaccharides derived from L. nigrescens

Prolonged, Low-Dose Anti-Thymocyte Globulin, Combined with CTLA4-Ig, Promotes Engraftment in a Stringent Transplant Model

Background: Despite significant nephrotoxicity, calcineurin inhibitors (CNIs) remain the cornerstone of immunosuppression in solid organ transplantation. We, along with others, have reported tolerogenic properties of anti-thymocyte globulin (ATG, Thymoglobulin®), evinced by its ability both to spare Tregs from depletion in vivo and, when administered at low, non-depleting doses, to expand Tregs ex vivo. Clinical trials investigating B7/CD28 blockade (LEA29Y, Belatacept) in kidney transplant recipients have proven that the replacement of toxic CNI use is feasible in selected populations. Methods: Rabbit polyclonal anti-murine thymocyte globulin (mATG) was administered as induction and/or prolonged, low-dose therapy, in combination with CTLA4-Ig, in a stringent, fully MHC-mismatched murine skin transplant model to assess graft survival and mechanisms of action. Results: Prolonged, low-dose mATG, combined with CTLA4-Ig, effectively promotes engraftment in a stringent transplant model. Our data demonstrate that mATG achieves graft acceptance primarily by promoting Tregs, while CTLA4-Ig enhances mATG function by limiting activation of the effector T cell pool in the early stages of treatment, and by inhibiting production of anti-rabbit antibodies in the maintenance phase, thereby promoting regulation of alloreactivity. Conclusion: These data provide the rationale for development of novel, CNI-free clinical protocols in human transplant recipients

Determination of esomeprazole in rabbit plasma by liquid chromatography-mass spectrometry and its application to a pharmacokinetic study

A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of esomeprazole in rabbit plasma was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation, and chromatography involved Agilent SB-C18 column (2.1 x 150 mm, 5.0 μm) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 198 for esomeprazole and m/z 326 for midazolam (internal standard, IS). The assay was linear over the range of 10–2000 ng/mL for esomeprazole, with a lower limit of quantitation (LLOQ) of 10 ng/mL for esomeprazole. Intra- and inter-day precisions were less than 14 % and the accuracies were in the range of 89.2-112.6 % for esomeprazole. This developed method was successfully applied for the determination of esomeprazole in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy

T-bet plays a crucial role in Th1 development. We investigated the role of T-bet in the development of allograft rejection in an established MHC class II–mismatched (bm12 into B6) model of chronic allograft vasculopathy (CAV). Intriguingly, and in contrast to IFN-γ−/− mice that are protected from CAV, T-bet−/− recipients develop markedly accelerated allograft rejection accompanied by early severe vascular inflammation and vasculopathy, and infiltration by predominantly IL-17–producing CD4 T cells. Concurrently, T-bet−/− mice exhibit a T helper type 1 (Th1)–deficient environment characterized by profound IFN-γ deficiency, a Th2 switch characterized by increased production of interleukin (IL) 4, IL-5, IL-10, and IL-13 cytokines, as well as increased production of the proinflammatory cytokines IL-6, IL-12p40, and IL-17. Neutralization of IL-17 inhibits accelerated allograft rejection and vasculopathy in T-bet−/− mice. Interestingly, CD4 but not CD8 T cell deficiency in T-bet−/− mice affords dramatic protection from vasculopathy and facilitates long-term graft acceptance. This is the first study establishing that in the absence of Th1-mediated alloimmune responses, CD4 Th17 cells mediate an aggressive proinflammatory response culminating in severe accelerated allograft rejection and vasculopathy. These results have important implications for the development of novel therapies to target this intractable problem in clinical solid organ transplantation

Penaeid shrimp genome provides insights into benthic adaptation and frequent molting

Crustacea, the subphylum of Arthropoda which dominates the aquatic environment, is of major importance in ecology and fisheries. Here we report the genome sequence of the Pacific white shrimp Litopenaeus vannamei, covering similar to 1.66 Gb (scaffold N50 605.56 Kb) with 25,596 protein-coding genes and a high proportion of simple sequence repeats (>23.93%). The expansion of genes related to vision and locomotion is probably central to its benthic adaptation. Frequent molting of the shrimp may be explained by an intensified ecdysone signal pathway through gene expansion and positive selection. As an important aquaculture organism, L. vannamei has been subjected to high selection pressure during the past 30 years of breeding, and this has had a considerable impact on its genome. Decoding the L. vannamei genome not only provides an insight into the genetic underpinnings of specific biological processes, but also provides valuable information for enhancing crustacean aquaculture

A strong sub-thermocline intrusion of the North Equatorial Subsurface Current into the Makassar Strait in 2016–2017

The poorly resolved pathway of the sub-thermocline waters (>300 m) within the Makassar Strait, the primary inflow path of the Indonesian Throughflow, is investigated using in situ mooring measurements and Argo profiles at the entrance to the Indonesian Seas. We focus on the strong subthermocline intrusion in the summer of 2016, when significant changes of sub-thermocline transport thrice as large as the interannual standard deviation occurred. Analysis suggests that the intrusion was drawn from the North Equatorial Subsurface Current (NESC) flowing westward below the North Equatorial Countercurrent, which was composed of a mixture of intermediate-depth waters from both the North and South Pacific. The anomalously strong NESC to the Makassar sub-thermocline in the summer 2016 is suggested to be in response to the 2015/2016 extreme El Niño event, forced by the trade wind anomalies over the western-central Pacific Ocean through westward and downward propagating baroclinic Rossby wav

Arbuscular mycorrhizal fungi improve selenium uptake by modulating root transcriptome of rice (Oryza sativa L.)

Although selenium (Se) is an essential trace element in humans, the intake of Se from food is still generally inadequate throughout the world. Inoculation with arbuscular mycorrhizal fungi (AMF) improves the uptake of Se in rice (Oryza sativa L.). However, the mechanism by which AMF improves the uptake of Se in rice at the transcriptome level is unknown. Only a few studies have evaluated the effects of uptake of other elements in rice under the combined effects of Se and AMF. In this study, Se combined with the AMF Funneliformis mosseae (Fm) increased the biomass and Se concentration of rice plants, altered the pattern of ionomics of the rice roots and shoots, and reduced the antagonistic uptake of Se with nickel, molybdenum, phosphorus, and copper compared with the treatment of Se alone, indicating that Fm can enhance the effect of fertilizers rich in Se. Furthermore, a weighted gene co-expression network analysis (WGCNA) showed that the hub genes in modules significantly associated with the genes that contained Se and were related to protein phosphorylation, protein serine/threonine kinase activity, membrane translocation, and metal ion binding, suggesting that the uptake of Se by the rice roots may be associated with these genes when Fm and Se act in concert. This study provides a reference for the further exploration of genes related to Se uptake in rice under Fm treatment

A Maluku Sea intermediate western boundary current connecting Pacific Ocean circulation to the Indonesian Throughflow

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Yuan, D., Yin, X., Li, X., Corvianawatie, C., Wang, Z., Li, Y., Yang, Y., Hu, X., Wang, J., Tan, S., Surinati, D., Purwandana, A., Wardana, A., Ismail, M., Budiman, A., Bayhaqi, A., Avianto, P., Santoso, P., Kusmanto, E., Dirhamsyah, Arifin, Z., & Pratt, L. A Maluku Sea intermediate western boundary current connecting Pacific Ocean circulation to the Indonesian Throughflow. Nature Communications, 13(1), (2022): 2093, https://doi.org/10.1038/s41467-022-29617-6.The Indonesian Throughflow plays an important role in the global ocean circulation and climate. Existing studies of the Indonesian Throughflow have focused on the Makassar Strait and the exit straits, where the upper thermocline currents carry North Pacific waters to the Indian Ocean. Here we show, using mooring observations, that a previous unknown intermediate western boundary current (with the core at ~1000 m depth) exists in the Maluku Sea, which transports intermediate waters (primarily the Antarctic Intermediate Water) from the Pacific into the Seram-Banda Seas through the Lifamatola Passage above the bottom overflow. Our results suggest the importance of the western boundary current in global ocean intermediate circulation and overturn. We anticipate that our study is the beginning of more extensive investigations of the intermediate circulation of the Indo-Pacific ocean in global overturn, which shall improve our understanding of ocean heat and CO2 storages significantly.This study is supported by NSFC (D.Y., Z.W., Y.L., Y.Y., S.T., J.W., and X.L.: 41720104008; D.Y., J.W., Y.L., X.L., Y.Y., S.T., X.H., and X.Y.: 91858204), the National Key Research and Development Program of China (D.Y. and X.L.: 2020YFA0608800), CAS (D.Y., Z.W., J.W., and Y.L.: XDB42000000), projects. Affiliations 1 and 2 share the first position. D.Y. is supported by QMSNL (2018SDKJ0104-02), and Shandong Provincial (U1606402) and the “Kunpeng Outstanding Scholar Program” of the FIO/NMR of China, J.W. supported by NSFC (41776011), Z.W. by NSFC (41876025)