114 research outputs found
C to U editing at position 32 of the anticodon loop precedes tRNA 5′ leader removal in trypanosomatids
In all organisms, precursor tRNAs are processed into mature functional units by post-transcriptional changes. These involve 5′ and 3′ end trimming as well as the addition of a significant number of chemical modifications, including RNA editing. The only known example of non-organellar C to U editing of tRNAs occurs in trypanosomatids. In this system, editing at position 32 of the anticodon loop of tRNAThr(AGU) stimulates, but is not required for, the subsequent formation of inosine at position 34. In the present work, we expand the number of C to U edited tRNAs to include all the threonyl tRNA isoacceptors. Notably, the absence of a naturally encoded adenosine, at position 34, in two of these isoacceptors demonstrates that A to I is not required for C to U editing. We also show that C to U editing is a nuclear event while A to I is cytoplasmic, where C to U editing at position 32 occurs in the precursor tRNA prior to 5′ leader removal. Our data supports the view that C to U editing is more widespread than previously thought and is part of a stepwise process in the maturation of tRNAs in these organisms
Probiotics or pro-healers: the role of beneficial bacteria in tissue repair
Probiotics are beneficial microorganisms, known to exert numerous positive effects on human health, primarily in the battle against pathogens. Probiotics have been associated with improved healing of intestinal ulcers, and healing of infected cutaneous wounds. This article reviews the latest findings on probiotics related to their pro-healing properties on gut epithelium and skin. Proven mechanisms by which probiotic bacteria exert their beneficial effects include direct killing of pathogens, competitive displacement of pathogenic bacteria, reinforcement of epithelial barrier, induction of fibroblasts, and epithelial cells' migration and function. Beneficial immunomodulatory effects of probiotics relate to modulation and activation of intraepithelial lymphocytes, natural killer cells, and macrophages through induced production of cytokines. Systemic effects of beneficial bacteria and link between gut microbiota, immune system, and cutaneous health through gut-brain-skin axes are discussed as well. In light of growing antibiotic resistance of pathogens, antibiotic use is becoming less effective in treating cutaneous and systemic infections. This review points to a new perspective and therapeutic potential of beneficial probiotic species as a safe alternative approach for treatment of patients affected by wound healing disorders and cutaneous infections.This is the peer reviewed version of the paper: Lukic, J., Chen, V., Strahinic, I., Begovic, J., Lev-Tov, H., Davis, S. C., Tomic-Canic, M., & Pastar, I. (2017). Probiotics or pro-healers: The role of beneficial bacteria in tissue repair. Wound Repair and Regeneration, 25(6), 912–922. [https://doi.org/10.1111/wrr.12607
Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation
Hidradenitis Suppurativa (HS) is a chronic multifactorial inflammatory skin disease with incompletely understood mechanisms of disease pathology. HS is characterized by aberrant activation of the innate immune system, resulting in activation of pathways that aim to protect against pathogenic microorganisms, and also contribute to failure to resolve inflammation. Imbalance in innate immunity is evident in deregulation of host antimicrobial peptides (AMPs) and the complement system associated with the microbiome dysbiosis. The pathology is further complicated by ability of pathogens associated with HS to overcome host immune response. Potential roles of major AMPs, cathelicidin, defensins, dermcidin, S100 proteins, RNAse 7 and complement proteins are discussed. Dysregulated expression pattern of innate immunity components in conjunction with bacterial component of the disease warrants consideration of novel treatment approaches targeting both host immunity and pathogenic microbiome in HS
HOST-MICROBIOTA INTERPLAY REGULATES EPITHELIAL BARRIER FUNCTION AND WOUND HEALING
Skin microbiome emerged as an important
factor which can balance tissue repair process
and wound healing. Recent evidence suggest
that intracellular bacterial localization could be
associated with the aberrant healing observed
in patients with chronic wounds, while therapeutics
targeting intracellular bacteria remain
limited. Probiotic lactobacilli and their bioactive
lysates (postbiotics) are well known for their role
in maintenance of gut epithelial homeostasis.
Hence, in this study we focused to understand
the mechanisms of cutaneous response to fourteen
postbiotics derived from different lactobacilli
to reduce intracellular Staphylococcus aureus
colonization and promote healing. Latilactobacillus
curvatus BGMK2-41 demonstrated the
most efficient capability to reduce intracellular infection by S. aureus in keratinocytes in vitro and
infection of human skin explants. Reduction of
bacterial number was followed by upregulation
of the expression of antimicrobial response
genes. Furthermore, BGMK2-41 postbiotic treatment
stimulates keratinocyte migration in vitro
and increases expression of anti-inflammatory
cytokine IL-10, promotes wound closure and
strengthens the epidermal barrier via upregulation
of tight junction proteins in a human ex vivo
wound model. Altogether, this study provided
evidence that postbiotics could stimulate fortification
of epithelial barrier to suppress dissemination
of intracellular pathogens which can be
used as a novel approach to treat dermatologic
and wound healing disorders associated with
persistent infections.Book of abstract: From biotechnology to human and planetary health XIII congress of microbiologists of Serbia with international participation Mikromed regio 5, ums series 24: 4th – 6th april 2024, Mona Plaza hotel, Belgrade, Serbi
Angiogenin released from ABCB5+ stromal precursors improves healing of diabetic wounds by promoting angiogenesis
Severe angiopathy is a major driver for diabetes-associated secondary complications. Knowledge on the underlying mechanisms essential for advanced therapies to attenuate these pathologies is limited. Injection of ABCB5+ stromal precursors at the edge of nonhealing diabetic wounds in a murine db/db model, closely mirroring human type 2 diabetes, profoundly accelerates wound closure. Strikingly, enhanced angiogenesis was substantially enforced by the release of the ribonuclease angiogenin from ABCB5+ stromal precursors. This compensates for the profoundly reduced angiogenin expression in nontreated murine chronic diabetic wounds. Silencing of angiogenin in ABCB5+ stromal precursors before injection significantly reduced angiogenesis and delayed wound closure in diabetic db/db mice, implying an unprecedented key role for angiogenin in tissue regeneration in diabetes. These data hold significant promise for further refining stromal precursors–based therapies of nonhealing diabetic foot ulcers and other pathologies with impaired angiogenesis
Recommended from our members
28th Annual Meeting of the Wound Healing Society, SAWC-Spring/WHS Joint Meeting: Georgia World Congress Center, Atlanta, Georgia, USA, April 13-17, 2016 Abstract
Recommended from our members
CRE recombinase-based positive–negative selection systems for genetic manipulation in Trypanosoma brucei
The limited repertoire of drug-resistance markers imposes a serious obstacle to genetic manipulation of
Trypanosoma brucei. Here we describe experiments with a fusion protein that allows positive selection for genome integration followed by CRE recombinase-mediated excision of the marker cassette that can be selected by ganciclovir, although the excision event is so efficient that selection is not strictly necessary. We describe two variants of the tetracycline-inducible pLEW100-based CRE-expression vector that reduced its toxicity when stably integrated into the genome, and we demonstrate that transient transfection of circular pLEW100-CRE is highly efficient at catalyzing marker excision. We used this approach to delete the last two enzymes of the pyrimidine synthesis pathway, creating a cell line that is resistant to fluoroorotic acid, which would allow the same enzymes (PYR6-5) to be used as an alternative negative selectable marker
In vitro and in vivo activities of novel cyclic lipopeptides against staphylococcal biofilms
A worldwide public health problem has resulted from the alarming spread of multi-drug resistant bacteria combined with the frequent occurrence of biofilm-type infections, creating a growing need for new therapies. In this study, we have demonstrated that novel cyclic lipopeptides, such as 1, cyclo-[D-Ala-(12-guanidinododecanoyl)Thr-D-Val-Val-DaThr-D-Asn], and 2, cyclo-[D-Ala-(12-guanidinododecanoyl)Dap-D-Val-Val-D-aThr-D-Asn], derived from the fusaricidin/ LI-F natural products efficiently inhibit the growth of Staphylococcus aureus biofilm in vitro at their minimum inhibitory concentrations (MICs). Complete S. aureus biofilm eradication was observed at 3 x MIC for 1 and 4 x MIC for 2. Promising in vivo activity was demonstrated by the ability of depsipeptide 1 to reduce the proliferation of methicillinresistant S. aureus US300 in a porcine wound model. Due to their unique structure and potent antibacterial and antibiofilm activities, cyclic lipopeptides that belong to the fusaricidin/LI-F family of antibiotics represent particularly attractive lead structures for the development of new antibacterial agents capable of treating complicated biofilm-associated infections
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