Investigation of Murine Vaginal Creep Response to Altered Mechanical Loads

Author(s):  
Gabrielle L. Clark ◽  
Jeffrey McGuire ◽  
Laurephile Desrosiers ◽  
Leise R. Knoepp ◽  
Raffaella De Vita ◽  
...  

Abstract The vagina is a viscoelastic fibromuscular organ that provides support to the pelvic organs. The viscoelastic properties of the vagina are understudied but may be critical for pelvic stability. Most studies evaluate vaginal viscoelasticity under a single uniaxial load; however, the vagina is subjected to dynamic multiaxial loading in the body. It is unknown how varied multiaxial loading conditions affect vaginal viscoelastic behavior and which microstructural processes dictate this. Therefore, the primary objective was to develop methods using extension-inflation protocols to quantify vaginal viscoelastic creep under various circumferential and axial loads. The second objective was to quantify vaginal creep and collagen microstructure in the fibulin-5 wildtype and haploinsufficient vaginas. To evaluate pressure-dependent creep, the fibulin-5 wildtype and haploinsufficient vaginas (n=7/genotype) were subjected to various constant pressures at the physiologic length for 100 seconds. For axial length-dependent creep, the vaginas (n=7/genotype) were extended to various fixed axial lengths then subjected to the mean in vivo pressure for 100 seconds. Second harmonic generation imaging was performed to quantify collagen fiber organization and undulation (n=3/genotype). Increased pressure significantly increased creep strain in the wildtype, but not the haploinsufficient vagina. Axial length did not significantly affect the creep rate or strain in both genotypes. Collagen undulation varied through the depth of the subepithelium but not between genotypes. These findings suggest that the response to loading may vary with biological processes and pathologies, therefore, evaluating vaginal creep under various circumferential loads may be important.

Author(s):  
Melinda J. Cromie ◽  
Gabriel N. Sanchez ◽  
Mark J. Schnitzer ◽  
Scott L. Delp

Sarcomeres are the smallest contractile elements of muscle. Muscle generates force when overlapping myosin and actin filaments within the sarcomere interact to generate force. The amount of force these interactions generate depends on sarcomere length. The range of sarcomere lengths over which a muscle normally operates in the body is an important factor in analyzing a muscle’s force generating capacity. Measurement of sarcomere lengths in vivo is limited by their small size (2–4 μm) and the inability to use fluorescent dyes in humans. We recently developed a microendoscopy system to image sarcomeres in humans via Second Harmonic Generation (SHG) [1]. Here we demonstrate the use of this microendoscopy system as a robust, minimally-invasive tool for biomechanical analysis by measuring sarcomere lengths of the forearm muscle extensor carpi radialis brevis (ECRB) in 5 human subjects.


2019 ◽  
Vol 2 (2) ◽  
pp. 49 ◽  
Author(s):  
Mehdi Alizadeh ◽  
Masood Ghotbi ◽  
Pablo Loza-Alvarez ◽  
David Merino

Polarization sensitive second harmonic generation (pSHG) microscopy is an imaging technique able to provide, in a non-invasive manner, information related to the molecular structure of second harmonic generation (SHG) active structures, many of which are commonly found in biological tissue. The process of acquiring this information by means of pSHG microscopy requires a scan of the sample using different polarizations of the excitation beam. This process can take considerable time in comparison with the dynamics of in vivo processes. Fortunately, single scan polarization sensitive second harmonic generation (SS-pSHG) microscopy has also been reported, and is able to generate the same information at a faster speed compared to pSHG. In this paper, the orientation of second harmonic active supramolecular assemblies in starch granules is obtained on by means of pSHG and SS-pSHG. These results are compared in the forward and backward directions, showing a good agreement in both techniques. This paper shows for the first time, to the best of the authors’ knowledge, data acquired using both techniques over the exact same sample and image plane, so that they can be compared pixel-to-pixel.


Author(s):  
Xiao Peng ◽  
Yiwan Song ◽  
Zheng Peng ◽  
Kaixuan Nie ◽  
Hao Liu ◽  
...  

Functionalized black phosphorus (BP) nanosheets have been considered as promising nanoagents in cancer therapy due to their excellent photothermal conversion efficiency. However, it is still difficult to visually monitor the dynamic localization of BP nanoagents in cancer cells. In this paper, we systematically studied the second-harmonic generation (SHG) signals originating from exfoliated BP nanosheets. Interestingly, under the excitation of a high frequency pulsed laser at 950 nm, the SHG signals of BP nanosheets in vitro are almost undetectable because of their poor stability. However, the intracellular SHG signals from BP nanosheets could be measured by in vivo optical [Formula: see text]imaging due to the efficient enrichment of living HeLa cells. Moreover, the SHG signal intensity from BP nanosheets increases with the prolonged incubation time. It can be expected that the BP nanosheets could be a promising intracellular SHG nanoprobe employed for visually in vivo biomedical imaging in practical cancer photothermal therapy (PIT).


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.


2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>


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