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[Display omitted] • Amphiphilic peptidomimetic compounds are broad-spectrum antibacterial agents disrupting cell membranes and cause cell death. • Compound 20 exhibited excellent antibacterial activities against a panel of bacteria strains (clinical strains included) and do not induce resistance. • Compound 20 could remove intracellular infection and exhibited excellent in vivo efficacy in a mice model. The gradual depletion of antibiotic discovery pipeline makes the antibiotic resistance a difficult clinical problem and a global health emergency. The membrane-active antimicrobial peptides (AMPs) attracted much attention due to a lower tendency to bacterial resistance than traditional antibiotics. However, some immanent drawbacks of AMPs may hamper their application in combating antibiotic resistance in the long run, such as susceptible to enzymatic degradation and low cell permeability. Herein, we report the design and synthesis of a novel series of amphiphilic peptidomimetics, from which we identified compounds that exhibited potent antimicrobial activity against a panel of clinically relevant Gram-positive and Gram-negative bacteria strains. The most potent compound 20 (SD-110 - 12) is able to kill intracellular bacterial pathogens and prevent the development of bacterial resistance under the tested conditions by targeting cell membranes. Additionally, compound 20 (SD-110 - 12) obtains good in vivo efficacy that is comparative to vancomycin by eradicating MRSA and suppressing inflammation in a mice infected skin wound model, demonstrating its promising therapeutic potential. [ABSTRACT FROM AUTHOR]

White spot disease caused by white spot syndrome virus (WSSV) is responsible for harming shrimp aquaculture industry and results in a pandemic throughout the world. Cathelicidin 5 treatment enhanced immune parameters including antioxidant enzyme activity and immune-related genes expression in shrimp Exopalaemon modestus. Shrimp treated with cathelicidin 5 and inoculated with white spot syndrome virus (WSSV) exhibited a significantly lower mortality rate and lower viral VP28 amplification and expression than control. This study addresses the role of cathelicidin 5 in immune stimulatory and antiviral activities that could protect E. modestus from WSSV infection. • There is no Cytotoxicity of cathelicidin 5 in vitro and in vivo. • Cathelicidin 5 could inhibit WSSV infection in vivo. • Cathelicidin 5 could protect hepatopancreas during WSSV challenge. • Cathelicidin 5 could increase caridean shrimp antioxidant enzyme activity. • Cathelicidin 5 could up-regulate caridean shrimp immune-related genes expression. [ABSTRACT FROM AUTHOR]

Antibiotic-resistant bacteria are severe threats to aquaculture industry. Boosting and modulating host immune responses has been proved to be an effective strategy to combat with bacterial infections and there is an urgent need for novel immunomodulators. Cathelicidins is an important family of host defense peptides (HDPs) that possess direct antimicrobial activities and potent immunomodulatory properties. Several cathelicidins have been identified and characterized from diverse fish species. Considering the relatively conserved immune systems between different fish species, it is reasonable to speculate that cathelicidins from different fish species possess immunomodulating functions on the other fish species. In the present study, two fish-derived cathelicidins (CATH_BRALE and codCath1) were selected to investigate their protective effect on zebrafish with bacterial infections. They exhibited potent and broad-spectrum antimicrobial activities against the tested aquatic Gram-positive and Gram-negative pathogenic bacteria, with MIC values ranging 2.34–18.75 μg/ml for CATH_BRALE and 2.34–37.5 μg/ml for codCath1. And their antimicrobial effect is so rapid that they killed the bacteria within 60 min. Unlike conventional antibiotics, they kill bacteria by inducing bacterial membrane permeabilization and cell disruption. Besides direct antimicrobial activity, CATH_BRALE and codCath1 exhibited potent immunomodulatory functions by both inhibiting bacteria induced zebrafish pro-inflammatory cytokine gene (TNF-α, IL-1β, and IL-6) expression and stimulating zebrafish chemokine gene IL-8 expression. In vivo challenge test proved that they could significantly decrease the bacterial numbers and enhance the survival rates of zebrafish. All the results above imply the great potential of CATH_BRALE and codCath1 as novel peptide immunomodulators in fish aquaculture industry. • Two fish-derived cathelicidins exhibited potent antimicrobial activities against aquatic pathogenic bacteria. • CATH_BRALE and codCath1 kill bacteria by inducing bacterial membrane permeabilization and cell disruption. • CATH_BRALE and codCath1 exhibited potent immunomodulatory function. • CATH_BRALE and codCath1 significantly decreased the bacterial number and enhanced the survival rate of zebrafish. • CATH_BRALE and codCath1 possess great potential to be novel peptide immunomodulators in fish aquaculture industry. [ABSTRACT FROM AUTHOR]

Host defense peptides (HDPs), a class of conserved components of animal innate immune system, possess direct antimicrobial activities against invading pathogens and broadly participate in boosting and modulating host immune responses. Cathelicidins is an important family of HDPs that has been identified exclusively in vertebrates. Considering the relatively conserved innate immune system between invertebrates and vertebrates, it is speculated that HDPs from vertebrates may also possess modulating functions on invertebrate innate immune system. In the present study, two novel cathelicidins (As-CATH4 and 5), which had been identified from the Chinese alligator in our previous study, were employed to investigate their functions as novel peptide immunostimulants in Chinese mitten crab. As-CATH4 and 5 exhibited potent, broad-spectrum, and rapid antimicrobial activities against all the tested aquatic pathogenic bacteria. Unlike traditional antibiotics, they target on bacterial cell membrane, induce membrane permeabilization and cell disruption, and ultimately result in cell death. The antimicrobial effect is far more rapid than traditional antibiotics. Therefore they are unlikely to induce bacteria resistance. After the crabs were administered with As-CATH4 and 5, the activities of lysozyme, acid phosphatase and alkaline phosphatase were significantly enhanced, which indicated that the immune system of crabs could be activated by As-CATH4 and 5. In bacteria challenge test, As-CATH4 and 5 could significantly decrease the bacterial numbers in crabs, and increase the survival rates of crabs in both pre-stimulation and co-stimulation groups. All of the results above indicated the great potential of As-CATH4 and 5 as novel peptide immunostimulants in the crab aquaculture. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) have been established to participate in various biological processes that are crucial for development and differentiation. However, the roles of lncRNAs in the mechanisms of human bone marrow mesenchymal stem cells (MSCs) differentiation are not completely understood. The purpose of the study was to investigate the expression profiles of lncRNAs during the chondrogenic differentiation of human bone marrow MSCs, with a view to studying the biological function of lncRNAs and their involvement in the mechanism of differentiation. We compared the lncRNAs expression profiles of undifferentiated and differentiated cells during chondrogenic differentiation by microarray. 3638 differentially expressed lncRNAs were identified (fold-change >2.0 or <−2.0, P < 0.05), consisting of 2166 up-regulated and 1472 down-regulated. Microarray data were validated using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Bioinformatic analyses were applied for further study of these differentially expressed lncRNAs. Among these lncRNAs, ZBED3-AS1 and CTA-941F9.9 were further analyzed with co-expression network and target prediction analysis. The results showed that the two up-regulated lncRNAs are likely to play important roles in chondrogenic differentiation process. In conclusion, the expression profile of lncRNAs was significantly altered during differentiation process. It provided a new insight on complicated regulation mechanisms of human bone marrow MSCs chondrogenic differentiation. [ABSTRACT FROM AUTHOR]

Thick-lipped lenok, Brachymystax lenok is one of the ancient fish species in China and northeast Asia countries. Due to the overfishing, the population of lenok has been declined significantly. Cathelicidins are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. This report identifies and characterizes the salmonoid cathelicidin (CATH_BRALE) from this ancient fish. It consists of open reading frame (ORF) of 886 bp encoding the putative peptide of 199 amino acids. Sequence alignment with other representative salmonid cathelicidins displayed two distinctive features of current lenok cathelicidin: high level of arginine, resulting in high positive charge and glycine residues, which is significantly different from most acknowledged types of cathelicidins; and the six-amino-acid tandem repeated sequence of RPGGGS detected in a variable number of copies among fish cathelicidins, suggesting the existence of a genetically unstable region similar to that found in some mammalian cathelicidins. Expression of CATH_BRALE is predominantly found in gill, with lower levels in the gastrointestinal tract and spleen. The homology modeled structure of CATH_BRALE exhibits structural features of antiparallel β-sheets flanked by α-helices that are representative of small cationic cathelicidin family peptides. CATH_BRALE possesses much stronger antimicrobial activity against gram-negative bacteria than that of the human ortholog, LL-37. The growth of two typical fish bacterial pathogens, gram-negative bacterium of Aeromonas salmonicida and Aeromonas hydrophila was substantially inhibited by synthetic CATH_BRALE, with both MICs as low as 9.38 μM. [ABSTRACT FROM AUTHOR]

Abstract: Much attention has been paid on amphibian peptides for their wide-ranging pharmacological properties, clinical potential, and gene-encoded origin. More than 300 antimicrobial peptides (AMPs) from amphibians have been studied. Peptidomics and genomics analysis combined with functional test including microorganism killing, histamine-releasing, and mast cell degranulation was used to investigate antimicrobial peptide diversity. Thirty-four novel AMPs from skin secretions of Rana nigrovittata were identified in current work, and they belong to 9 families, including 6 novel families. Other three families are classified into rugosin, gaegurin, and temporin family of amphibian AMP, respectively. These AMPs share highly conserved preproregions including signal peptides and spacer acidic peptides, while greatly diversified on mature peptides structures. In this work, peptidomics combined with genomics analysis was confirmed to be an effective way to identify amphibian AMPs, especially novel families. Some AMPs reported here will provide leading molecules for designing novel antimicrobial agents. [Copyright &y& Elsevier]