Effects of Lithium Ions on tPA-Induced Hemorrhagic Transformation under Stroke.

Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but their effects on HT mechanisms are still unknown. In our study, we use the models of photothrombosis (PT)-induced brain ischemia and oxygen-glucose deprivation (OGD) to investigate the effect of Li+ on tPA-induced changes in brain and endothelial cell cultures. We found that tPA did not affect lesion volume or exacerbate neurological deficits but disrupted the blood-brain barrier. We demonstrate that poststroke treatment with Li+ improves neurological status and increases blood-brain barrier integrity after thrombolytic therapy. Under conditions of OGD, tPA treatment increased MMP-2/9 levels in endothelial cells, and preincubation with LiCl abolished this MMP activation. Moreover, we observed the effect of Li+ on glycolysis in tPA-treated endothelial cells, which we hypothesized to have an effect on MMP expression.

Biomarkers of the End-Stage Renal Disease Progression: Beyond the GFR.

Chronic kidney disease can progress to the end-stage renal disease (ESRD) characterized by a high risk of morbidity and mortality. ESRD requires immediate therapy or even dialysis or kidney transplantation, therefore, its timely diagnostics is critical for many patients. ESRD is associated with pathological changes, such as inflammation, fibrosis, endocrine disorders, and epigenetic changes in various cells, which could serve as ESRD markers. The review summarizes information on conventional and new ESRD biomarkers that can be assessed in kidney tissue, blood, and urine. Some biomarkers are specific to a particular pathology, while others are more universal. Here, we suggest several universal inflammatory, fibrotic, hormonal, and epigenetic markers indicative of severe deterioration of renal function and ESRD progression for improvement of ESRD diagnostics.

Intraoperative assessment of resection margins by Raman spectroscopy to guide oral cancer surgery.

Patients with oral cavity cancer are almost always treated with surgery. The goal is to remove the tumor with a margin of more than 5 mm of surrounding healthy tissue. Unfortunately, this is only achieved in about 15% to 26% of cases. Intraoperative assessment of tumor resection margins (IOARM) can dramatically improve surgical results. However, current methods are laborious, subjective, and logistically demanding. This hinders broad adoption of IOARM, to the detriment of patients. Here we present the development and validation of a high-wavenumber Raman spectroscopic technology, for quick and objective intraoperative measurement of resection margins on fresh specimens. It employs a thin fiber-optic needle probe, which is inserted into the tissue, to measure the distance between a resection surface and the tumor. A tissue classification model was developed to discriminate oral cavity squamous cell carcinoma (OCSCC) from healthy oral tissue, with a sensitivity of 0.85 and a specificity of 0.92. The tissue classification model was then used to develop a margin length prediction model, showing a mean difference between margin length predicted by Raman spectroscopy and histopathology of -0.17 mm.

Effects of Ketogenic Diet on Muscle Metabolism in Health and Disease.

Dietary intervention is widely used as a therapeutic approach ranging from the treatment of neurological disorders to attempts to extend lifespan. The most important effect of various diets is a change in energy metabolism. Since muscles constitute 40% of total body mass and are one of the major sites of glucose and energy uptake, various diets primarily affect their metabolism, causing both positive and negative changes in physiology and signaling pathways. In this review, we discuss changes in the energy metabolism of muscles under conditions of the low-carbohydrate, high-fat diet/ketogenic diet (KD), fasting, or administration of exogenous ketone bodies, which are all promising approaches to the treatment of various diseases. KD's main influence on the muscle is expressed through energy metabolism changes, particularly decreased carbohydrate and increased fat oxidation. This affects mitochondrial quantity, oxidative metabolism, antioxidant capacity, and activity of enzymes. The benefits of KD for muscles stay controversial, which could be explained by its different effects on various fiber types, including on muscle fiber-type ratio. The impacts of KD or of its mimetics are largely beneficial but could sometimes induce adverse effects such as cardiac fibrosis.

Light guidance up to 6.5†µm in borosilicate soft glass hollow-core microstructured optical waveguides.

Limited operating bandwidth originated from strong absorption of glass materials in the infrared (IR) spectral region has hindered the potential applications of microstructured optical waveguide (MOW)-based sensors. Here, we demonstrate multimode waveguide regime up to 6.5 µm for the hollow-core (HC) MOWs drawn from borosilicate soft glass. Effective light guidance in central HC (diameter ∼240 µm) was observed from 0.4 to 6.5 µm despite high waveguide losses (0.4 and 1 dB/cm in near- and mid-IR, respectively). Additional optimization of the waveguide structure can potentially extend its operating range and decrease transmission losses, offering an attractive alternative to tellurite and chalcogenide-based fibers. Featuring the transparency in mid-IR, HC MOWs are promising candidates for the creation of MOW-based sensors for chemical and biomedical applications.