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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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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Despite the success of anti-retroviral therapy (ART) in transforming HIV into a manageable disease, it has become evident that long-term ART will not eliminate the HIV reservoir and cure the infection. Alternative strategies to eradicate HIV infection, or at least induce a state of viral control and drug-free remission are therefore needed. Therapeutic vaccination aims to induce or enhance immunity to alter the course of a disease. In this review we provide an overview of the current state of therapeutic HIV vaccine research and summarize the obstacles that the field faces while highlighting potential ways forward for a strategy to cure HIV infection.
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The development of organ fibrosis has garnered rising attention as multiple diseases of increasing and/or high prevalence appear to progress to the chronic stage. Such is the case for heart, kidney, liver, and lung where diseases such as diabetes, idiopathic/autoimmune disorders, and nonalcoholic liver disease appear to notably drive the development of fibrosis. Noteworthy is that the severity of these pathologies is characteristically compounded by aging. ⋯ In vitro studies and transgenic animals models have also been used in an attempt to understand the role that sex hormones and related receptors play in the development of fibrosis. However, in the setting of chronic disease in some organs such as the heart older (postmenopausal) women within a few years can quickly approach men in disease severity and develop significant degrees of fibrosis. This review summarizes the current body of relevant literature and highlights the imperative need for a major focus to be placed on understanding the manner in which sex and the presence or absence of related hormones modulates cell phenotypes so as to allow for fibrosis to develop.
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Management of advanced prostate cancer remains complex, with substantial changes in treatment options emerging in recent years having implications for treatment selection and sequencing. Recognition of the importance of androgen signaling has led to life-prolonging treatments, as well as "liquid biopsy" techniques to guide these treatments in some settings. Therapies that target estrogen receptor signaling are efficacious but infrequently used options for treatment of castration-resistant prostate cancer. ⋯ Constitutively activating gene alterations can potentially lead to ER activation and subsequently promote cancer progression. The identification of these aberrations may help identify cancer phenotypes that are susceptible or resistant to therapies involved in ER signaling. This review outlines the current literature regarding ER signaling in prostate cancer, and provides background for exploration of potentially useful ER signaling biomarkers in advanced prostate cancer.