Translational research : the journal of laboratory and clinical medicine
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Extensive antibiotic use combined with poor historical drug stewardship practices have created a medical crisis in which once treatable bacterial infections are now increasingly unmanageable. To combat this, new antibiotics will need to be developed and safeguarded. An emerging class of antibiotics based upon nuclease-stable antisense technologies has proven valuable in preclinical testing against a variety of bacterial pathogens. This review describes the current state of development of antisense-based antibiotics, the mechanisms thus far employed by these compounds, and possible future avenues of research.
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Smad4 plays a central role in the regulation of extracellular matrix (ECM) protein expression and cell differentiation; however, the molecular regulation of Smad4 protein stability by a deubiquitinase has not been reported. In the current study, we reveal that a deubiquitinase USP13 stabilizes Smad4, ultimately modulating ECM protein expression in lung fibroblast cells. USP13 was increased in primary adult lung fibroblasts isolated from bleomycin-challenged mice and transforming growth factor (TGF)-β1-treated primary mouse lung fibroblasts. ⋯ Overexpression of USP13 increased FN and Smad4 protein levels in lung fibroblasts, while downregulation of USP13 reduced Smad4 protein levels, without altering Smad4 mRNA expression, suggesting that USP13 regulates Smad4 protein stability. Knockdown of USP13 decreased Smad4 half-life and promoted Smad4 ubiquitination. Both Smad4 and USP13 were co-localized in the cytoplasm in treated cell, and co-translocated into the nucleus in response to TGF-β1. The results indicate that USP13 promotes ECM expression by stabilizing Smad4 in lung fibroblasts and plays a role in the maintenance of the extracellular matrix in lungs.
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Review
Liquid biopsy for breast cancer using extracellular vesicles and cell-free microRNAs as biomarkers.
Improvement of breast cancer (BC) patient's outcome is directly related to early detection. However, there is still a lack of reliable biomarkers for diagnosis, prognosis and, treatment follow up in BC, leading researchers to study the potential of liquid biopsy based on circulating microRNAs (c-miRNAs). ⋯ In this review, we discuss new findings about c-miRNA and their potential as biomarkers for BC diagnosis, prognosis, and therapy. Additionally, we address the impact of limitations associated with the standardization of analysis techniques and methods on the implementation of these biomarkers in the clinical setting.
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Campylobacter is an enteric pathogen and a leading bacterial cause of diarrhea worldwide. It is widely distributed in food animal species and is transmitted to humans primarily through the foodborne route. While generally causing self-limited diarrhea in humans, Campylobacter may induce severe or systemic infections in immunocompromised or young/elderly patients, which often requires antibiotic therapy with the first-line antibiotics including fluoroquinolones and macrolides. ⋯ To address this concern, many studies have been conducted to advance novel and alternative measures to control antibiotic-resistant Campylobacter in animal reservoirs and in the human host. Although some of these undertakings have yielded promising results, efficacious and reliable alternative approaches are yet to be developed. In this review article, we will describe Campylobacter-associated disease spectrums and current treatment options, discuss the state of antibiotic resistance and alternative therapies, and provide an evaluation of various approaches that are being developed to control Campylobacter infections in animal reservoirs and the human host.
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Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC. ⋯ Our data support an important prognostic role of Nox4 mediated regulation of RCC independent of other competing variables. Nox4 localizes to the nucleus in high-grade, high-stage RCC. Higher nuclear Nox4 has prognostic significance for disease progression, poor survival, and development of drug resistance in RCC.