Translational research : the journal of laboratory and clinical medicine
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Acute respiratory distress syndrome (ARDS), replacing the clinical term acute lung injury, involves serious pathophysiological lung changes that arise from a variety of pulmonary and nonpulmonary injuries and currently has no pharmacological therapeutics. RNA interference (RNAi) has the potential to generate therapeutic effects that would increase patient survival rates from this condition. It is the purpose of this review to discuss potential targets in treating ARDS with RNAi strategies, as well as to outline the challenges of oligonucleotide delivery to the lung and tactics to circumvent these delivery barriers.
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Pancreatic cancer is characterized by extremely high mortality and poor prognosis and is projected to be the leading cause of cancer deaths by 2030. Due to the lack of early symptoms and appropriate methods to detect pancreatic carcinoma at an early stage as well as its aggressive progression, the disease is often quite advanced by the time a definite diagnosis is established. The 5-year relative survival rate for all stages is approximately 8%. ⋯ The present review critically discusses the latest developments in biosensors for the early diagnosis of pancreatic cancer. Protein and microRNA biomarkers of pancreatic cancer and corresponding biosensors for pancreatic cancer diagnosis have been reviewed, and all these cases demonstrate that the emerging biosensors are becoming an increasingly relevant alternative to traditional techniques. In addition, we discuss the existing problems in biosensors and future challenges.
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Substantial growth in the biosensor research has enabled novel, sensitive and point-of-care diagnosis of human diseases in the last decade. This paper presents an overview of the research in the field of biosensors that can potentially predict and diagnosis of common placental pathologies. A survey of biomarkers in maternal circulation and their characterization methods is presented, including markers of oxidative stress, angiogenic factors, placental debris, and inflammatory biomarkers that are associated with various pathophysiological processes in the context of pregnancy complications. ⋯ New trends in organ-on-a-chip based placental disease models are highlighted to illustrate the capability of these in vitro disease models in better understanding the complex pathophysiological processes, including mass transfer across the placental barrier, oxidative stress, inflammation, and malaria infection. Biosensor technologies that can be potentially embedded in the placental models for real time, label-free monitoring of these processes and events are suggested. Merger of cell culture in microfluidics and biosensing can provide significant potential for new developments in advanced placental models, and tools for diagnosis, drug screening and efficacy testing.
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Increased renal cellular senescence in murine high-fat diet: effect of the senolytic drug quercetin.
Obesity and dyslipidemia can be associated with cellular senescence, and may impair kidney function. However, whether senescence contributes to renal dysfunction in these conditions remains unclear. Quercetin is an abundant dietary flavonoid that selectively clears inhibiting PI3K/AKT and p53/p21/serpines and inducing apoptosis. ⋯ Quercetin treatment also increased renal cortical oxygenation and decreased plasma creatinine levels in obese mice, whereas body weight and cholesterol levels were unaltered. Therefore, murine obesity and dyslipidemia induce renal tissue senescence and impairs kidney function, which is alleviated by chronic senolytic treatment. These findings implicate senescence in loss of kidney function in murine dyslipidemia and obesity, and support further studies of senolytic therapy in obesity.
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During fibrinolysis a 28-amino-acid peptide is generated besides other degradation products of fibrin. This peptide, called Bβ15-42, which is cleaved by plasmin from the end of the fibrin Bβ-chain, is protective in myocardial and renal ischemia/reperfusion injury and improves the outcome in experimental sepsis. Bβ15-42 has been shown to mediate different beneficial effects in endothelial cells through binding to vascular endothelial-cadherin. ⋯ Silencing CBPM with siRNA reduced the protective potential of Bβ15-42 against tubular cell stress. Bβ15-42 inhibited the enzymatic activity of CBPM and modified the impact of CBPM on bradykinin signaling. We conclude that beneficial properties of Bβ15-42 are not restricted to endothelial cells but are also active in epithelial cells where cytoprotection depends on CBPM binding.