Cancer cells require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. The basis for methionine dependence in cancer cells is still not entirely clear. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) is associated with methionine auxotrophy in cancer cells, there are other causes for tumors to require exogenous methionine. Restricting methionine by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics, is a promising antitumor strategy.
Hybrid materials based on perfluorinated sulfonic acid Nafion-type membranes and poly-3,4-ethylenedioxythiophene (PEDOT) with a gradient distribution of the latter along the film length were synthesized by in situ oxidative polymerization. The initial monomer concentration (0.01 and 0.002 M) and the concentration ratio of the monomer to the oxidant (1/1.25 and 1/2.5) were varied. We studied the effect of the equilibrium and transport properties of the obtained materials on the characteristics of cross-sensitive DP-sensors (analytical signal is the Donnan potential) in aqueous solutions of procaine, lidocaine, and bupivacaine hydrochlorides, including those containing sodium chloride, in a concentration range from 1.0 × 10–4 to 1.0 × 10–2 M and pH from 2 to 6. The relative error in determining the active substance in the Novokain preparation using a DP-sensor based on the Nafion/PEDOT membrane (0.002 M, 1/2.5) was 0.4%. An array of DP-sensors based on Nafion and Nafion/PEDOT (0.002 M, 1/1.25) membranes was used to determine bupivacaine hydrochloride and sodium chloride in the Markain® Spinal preparation with an error of 11 and 6%, respectively.
The analogy between knots in mathematical knot theory and “knots” in medicine is studied for the example of a certain invariant of Legendrian knots. The connection between the “Chern class” and the “Maslov class” is analyzed. A conjecture on the connection between the “Connes–Chern character” and the “Maslov class” is proposed.
Modern trends in optical bioimaging require novel nanoproducts combining high image contrast with efficient treatment capabilities. Silicon nanoparticles are a wide class of nanoobjects with tunable optical properties, which has potential as contrasting agents for fluorescence imaging and optical coherence tomography. In this paper we report on developing a novel technique for fabricating silicon nanoparticles by means of picosecond laser ablation of porous silicon films and silicon nanowire arrays in water and ethanol. Structural and optical properties of these particles were studied using scanning electron and atomic force microscopy, Raman scattering, spectrophotometry, fluorescence, and optical coherence tomography measurements. The essential features of the fabricated silicon nanoparticles are sizes smaller than 100 nm and crystalline phase presence. Effective fluorescence and light scattering of the laser-ablated silicon nanoparticles in the visible and near infrared ranges opens new prospects of their employment as contrasting agents in biophotonics, which was confirmed by pilot experiments on optical imaging
Cerebrovascular imaging of rodents is one of the trending applications of optoacoustics aimed at studying brain activity and pathology. Imaging of deep brain structures is often hindered by sub-optimal arrangement of the light delivery and acoustic detection systems. In our work we revisit the physics behind opto-acoustic signal generation for theoretical evaluation of optimal laser wavelengths to perform cerebrovascular optoacoustic angiography of rodents beyond the penetration barriers imposed by light diffusion in highly scattering and absorbing brain tissues. A comprehensive model based on diffusion approximation was developed to simulate optoacoustic signal generation using optical and acoustic parameters closely mimicking a typical murine brain. The model revealed three characteristic wavelength ranges in the visible and near-infrared spectra optimally suited for imaging cerebral vasculature of different size and depth. The theoretical conclusions are confirmed by numerical simulations while in vivo imaging experiments further validated the ability to accurately resolve brain vasculature at depths ranging between 0.7 and 7 mm.
We report on the estimation of blood content and vessel volume fraction changes in the microcirculatory bed of human skin under controlled mechanical compression using 3-dimensional optoacoustic (OA) angiography. A consecutive decrease in the fraction of blood vessels and skin blood content as a result of an increase in pressure from 0 to 72 mmHg applied to the imaged area was demonstrated by means of an acoustical-resolution OA microscope with a spatial resolution of 50 μm. Pressures below 32 mmHg were shown to weakly affect the acquired OA angiograms. The loss of OA signal from the blood vessels was observed after a further pressure increase of up to 72 mmHg. The vascular changes observed by OA microscopy were confirmed by infrared (IR) thermometry measurements which revealed similar dynamics of microcirculation interruption in the area under pressure.
Paired-pulse transcranial magnetic stimulation (TMS) allows investigating inhibitory and excitatory interactions in the human motor cortex noninvasively. Short-interval intracortical inhibition (SICI) and facilitation (SICF) are used to measure cortico–cortical excitability in patients with, e.g., stroke, dystonia, and Parkinson’s disease. However, the role of the induced electric field (E-field) orientation remains partly unclear. Posterior–anterior (PA)-oriented E-field elicits motor evoked potentials (MEPs) with the lowest stimulus intensities due to the recruitment of corticospinal neurons, indirectly via excitatory synaptic inputs to corticospinal axons (indirect (I-) waves). Stimulation in the lateral–medial (LM) orientation directly activates corticospinal axons, which leads to the generation of both direct (D-) and I-waves. Conditioning stimulus (CS) with an intensity between 50% and 90% of resting motor threshold (RMT) induces activation of GABAA inhibitory mechanisms observed as the SICI (inhibitory) effect on MEP amplitude. In contrast, if the CS intensity is above RMT, the SICF (excitatory) phenomenon can be present due to the superposition of D- and I-waves. Our aim was to investigate the dependence of inhibitory and facilitatory mechanisms on the orientation of the induced E-field of CS and TS. We developed a multi-locus TMS (mTMS) transducer, which allowed us to control the E-field orientation independently for CS and TS at a millisecond inter-pair interval (IPI). Eight healthy subjects (five males; mean age 29, range 21–35 years) participated in the study. mTMS was applied to the hotspot of the abductor pollicis brevis (APB) muscle in the left primary motor cortex. The stimulus intensities were based on the individual RMT of APB for PA and LM orientations. TS and single pulses were administered at 110% RMT. Twenty single pulses were applied for each TS orientation and for each of the 32 paired-pulse conditions. CS and TS stimuli were applied in every combination of the PA and LM orientations with four CS intensities (50, 70, 90, and 110% RMT) and two IPIs (1.5 and 2.7 ms) in a random order. Interaction between CS orientation, IPI, and CS intensity significantly affected TS MEP amplitudes. We observed no statistically significant difference between the responses induced by PA- and LM-oriented TS. CS at 70% RMT for SICI and at 110% RMT for SICF induced similar effects regardless of the TS orientation. We established that LM-oriented CS at 90% RMT produced a greater inhibition than stimuli at the same intensity in the PA orientation. Our results emphasize the minimal influence of the CS E-field dorientation on the test pulse. Additionally, we demonstrate the pivotal role of the stimulus intensity for any CS orientation. SICI and SICF evoked using perpendicular CS and TS directions indicate that we stimulated overlapping neuronal populations with both pulses.
Two pronounced absorption peaks in blue and red ranges of the chlorin-based photosensitizer (PS) absorption spectrum provide additional benefits in photodynamic therapy (PDT) performance. Differing optical properties of biological tissues in these ranges allow for both dual-wavelength diagnostics and PDT performance. We provide a comparative analysis of different PDT regimes performed with blue and red lights and their combination, with doses varying from 50 to 150 J / cm2. The study was performed on the intact skin of a rabbit ear inner surface, with the use of chlorin e6 as a PS. PDT procedure protocol included monitoring of the treated site with fluorescence imaging technique to evaluate PS accumulation and photobleaching, as well as with optical coherence tomography (OCT) to register morphological and functional responses of the tissue. Optical diagnostic observations were compared with the results of histopathology examination. We demonstrated that PDT procedures with the considered regimes induce weaker organism reaction manifested by edema in normal tissue as compared to irradiation-only exposures with the same light doses. The light doses delivered with red light induce weaker tissue reaction as compared to the same doses delivered with blue light only or with a combination of red and blue lights in equal parts. Results of in-vivo OCT monitoring of tissue reaction are in agreement with the results of histopathology study.
Photobiological properties of phthalocyanine photosensitizers, namely, clinically approved Photosens and new compounds Holosens and Phthalosens were analyzed on transitional cell carcinoma of the urinary bladder (T24) and human hepatic adenocarcinoma (SK-HEP-1). Photosens is a sulfated aluminum phthalocyanine with the number of sulfo groups 3.4, which is characterized by a high degree of hydrophilicity, slow cellular uptake, localization in lysosomes and the lowest photodynamic activity. Holosens is an octacholine zinc phthalocyanine, a cationic compound with significant charge. Holosens more efficiently enters the cells; it is localized in Golgi apparatus in addition to lysosomes and exhibits a significant inhibitory effect on cell viability upon irradiation. The highest photodynamic activity was demostrated by Phthalosens. Phthalosens is a metal-free analog of Photosens with a number of sulfo groups 2.5, which determines its amphiphilicity. Phthalosens is characterized by the highest rate of cellular uptake through the outer cell membrane, localization in cell membrane as well as in lysosomes and Golgi apparatus, and the highest activity upon irradiation among the photosensitizers studied. In general, changes in the physicochemical properties of Holosens and Phthalosens ensured an increase in their efficiency in vitro compared to Photosens. The features of accumulation, intracellular distribution and their interrelation with photodynamic activity, revealed in this work, indicate the prospects of Phthalosens and Holosens for clinical practice.
Nucleic acids labeled with a fluorophore/quencher pair are widely used as probes in biomedical research and molecular diagnostics. Here we synthesized novel DNA molecular beacons double labeled with the identical dyes (R6G, ROX and Cy5) at 5′- and 3′-end and studied their photo physical properties. We demonstrated that fluorescence quenching by formation of the homo dimer exciton in such molecular beacons allows using them in homogeneous assays. Further, we developed and evaluated homo Yin-Yang DNA probes labeled with identical dyes and used them for detection of low copy HIV RNA by RT-qPCR. They demonstrated improved sensitivity (LLQ: 10 vs 30 copies mL-1) in comparison to commercially available Abbott RealTime HIV-1 kit based on VICBHQ dyes both for model mixtures (naive human plasma with added deactivated HIV-1 virus) and for preliminarily confirmed 36 clinical samples (4 vs 1 positive ones for low-copy samples).