Acute ischemia reperfusion injury in skeletal muscle remains an important issue in several fields of regenerative medicine. Thus, a valid model is essential to gain deeper insights into pathophysiological relations and evaluate possible treatment options. While the vascular anatomy of mice regularly prevents sufficient vessel occlusion by invasive methods, there is a multitude of existing models to induce ischemia reperfusion injury without surgical procedures. Since there is no consensus on which model to prefer, this study aims to develop and evaluate a novel, optimized low-pressure tourniquet model. C57BL/6 mice underwent an ischemic procedure by either tourniquet or invasive artery clamping. A sham group served as control. With exception of the sham group, mice underwent 2 hours of ischemia followed by 4 hours of reperfusion. Groups were compared using microcirculatory and spectroscopic measurements, distinctions in tissue edema, histological and immunohistochemical analyses. Both procedures led to a significant decrease in tissue blood flow (- 97% vs. - 86%) and oxygenation (- 87% vs. - 75%) with a superiority of the low-pressure tourniquet. Tissue edema in the tourniquet cohort was significantly increased (+ 59%), while the increase in the clamping cohort was non-significant (+ 7%). Haematoxylin Eosin staining showed significantly more impaired muscle fibers in the tourniquet group (+ 77 p.p. vs. + 11 p.p.) and increased neutrophil infiltration/ROI (+ 51 vs. + 8). Immunofluorescence demonstrated an equal increase of p38 in both groups (7-fold vs. 8-fold), while the increase in apoptotic markers (Caspase-3, 3-Nitrotyrosine, 4-Hydroxynonenal) was significantly higher in the tourniquet group. The low-pressure tourniquet has been proven to produce reproducible and thus reliable ischemia reperfusion injury. In addition, significantly less force was needed than previously stated. It is therefore an important instrument for studying the pathophysiology of ischemia reperfusion injury and for the development of prophylactic as well as therapeutic interventions.
Ischemia reperfusion (IR) injury remains an important topic in clinical medicine. While a multitude of prophylactic and therapeutic strategies have been proposed, recent studies have illuminated protective effects of myostatin inhibition. This study aims to elaborate on the intracellular pathways involved in myostatin signaling and to explore key proteins that convey protective effects in IR injury. We used CRISPR/Cas9 gene editing to introduce a myostatin (Mstn) deletion into a C2C12 cell line. In subsequent experiments, we evaluated overall cell death, activation of apoptotic pathways, ROS generation, lipid peroxidation, intracellular signaling via mitogen-activated protein kinases (MAPKs), cell migration, and cell proliferation under hypoxic conditions followed by reoxygenation to simulate an IR situation in vitro (hypoxia reoxygenation). It was found that mitogen-activated protein kinase kinase 3/6, also known as MAPK/ERK Kinase 3/6 (MEK3/6), and subsequent p38 MAPK activation were blunted in C2C12-Mstn−/− cells in response to hypoxia reoxygenation (HR). Similarly, c-Jun N-terminal kinase (JNK) activation was negated. We also found the intrinsic activation of apoptosis to be more important in comparison with the extrinsic activation. Additionally, intercepting myostatin signaling mitigated apoptosis activation. Ultimately, this research validated protective effects of myostatin inhibition in HR and identified potential mediators worth further investigation. Intercepting myostatin signaling did not inhibit ROS generation overall but mitigated cellular injury. In particular, intrinsic activation of apoptosis origination from mitochondria was alleviated. This was presumably mediated by decreased activation of p38 caused by the diminished kinase activity increase of MEK3/6. Overall, this work provides important insights into HR signaling in C2C12-Mstn−/− cells and could serve as basis for further research.
Background: Body image research deals a lot with awareness of the body as an entity. Studies that consider individual anatomical aspects and place them in an intercultural context are rarely present. Methods: For this purpose, general data, body perception and judgment of body images from 2163 (48% female and 52% male) participants from Germany, Nigeria, the USA and Japan were evaluated as part of a survey. Results: There were clear differences in the personal body image of the participants’ own buttocks, the buttocks as a beauty ideal and the way in which dissatisfaction was dealt with in different countries. In addition to sexual well-being (importance score: 0.405 a.u.), the country of origin (0.353), media consumption (0.042) and one’s own weight (0.069) were also identified as influencing factors for satisfaction with one’s own buttocks. A clear evolution could be derived regarding a WHR (waist-to-hip ratio) of well below 0.7, which was consistently favored by the participants but also propagated by influencers through images (p < 0.001). In this context, participants who indicated celebrities as role models for the buttocks showed a correspondingly high level of dissatisfaction with their own buttocks (R = −0.207, p < 0.001, ρ = −0.218). Conclusion: Overall, a highly significant correlation was shown between the consumption frequency of Instagram, TikTok and pornography with the negative perception of women’s own buttocks.
The last century brought about more rapid new developments in the treatment of burns, which significantly lowered the mortality of burn injuries. However, burns were already treated in antiquity, where the threshold from spirituality to scientific medicine originated. The existing literature on burn treatment is very limited and there are many cross-references, some of them incorrect. The aim of this work by an interdisciplinary team of historians and physicians is to offer a more precise reproduction of the burn treatment of Greek and Roman antiquity using original texts in context and with a modern scientific background. There are many sources from ancient doctors on the subject of burn treatment, as well as the treatment of burned-out wounds and frostbite, which have not yet been mentioned. The literature research also showed an understanding of scientific contexts in ancient medicine, such as antiseptics or rheology. Interestingly, there was a change in burn medicine from everyday Greek medicine to Roman military medicine with other burn patterns. The care of patients using analgetics and the therapy of burn shock arose from the literature. The ancient world is considered to be the foundation of medicine, but it is believed to have been based mainly on shamanism rather than science. However, already more than two millennia ago, burns were correctly assessed and treated according to today’s scientific standards and scientific relationships were recognized.
Patients with diabetes suffer from poor fracture healing. Molecular reasons are not fully understood and our previous gene expression microarray analyses of regenerating bones from mice with type 2 diabetes (db−/db−) revealed accelerated activation of pathways concerning matrix metalloproteases (MMPs). Thus, we picked out the pathological MMP acceleration as a target for profound gene expression analyses and additional therapeutic intervention in the present study. In the first part, gene expression of ECM degrading proteinases and inhibitors was investigated three and seven days postoperatively. Mmp3, Mmp9, Mmp13 and gene expression of MMP inhibitor Timp2 was significantly higher in regenerating bone fractures of db−/db− compared to wild type animals. Timp1 and metalloproteinase AdamTS4 showed no differences. In the second part, we locally applied a single dose (1 µL of 5 µM solution) of the broad-spectrum molecular MMP inhibitor Marimastat on tibial defects in db−/db−. We performed immunohistochemical and histological stainings seven days post operation. Impaired bone healing, collagen content, angiogenesis, and osteoclast invasion in db−/db− were restored significantly by application of Marimastat compared to PBS controls (n = 7/group). Hence, local intervention of bone defects by the molecular MMP inhibitor Marimastat might be an alternative therapeutic intervention for bone healing in diabetes.
The mortality of severely burned patients can be predicted by multiple scores which have been created over the last decades. As the treatment of burn injuries and intensive care management have improved immensely over the last years, former prediction scores seem to be losing accuracy in predicting survival. Therefore, various modifications of existing scores have been established and innovative scores have been introduced. In this study, we used data from the German Burn Registry and analyzed them regarding patient mortality using different methods of machine learning. We used Classification and Regression Trees (CARTs), random forests, XGBoost, and logistic regression regarding predictive features for patient mortality. Analyzing the data of 1401 patients via machine learning, the factors of full-thickness burns, patient’s age, and total burned surface area could be identified as the most important features regarding the prediction of patient mortality following burn trauma. Although the different methods identified similar aspects, application of machine learning shows that more data are necessary for a valid analysis. In the future, the usage of machine learning can contribute to the development of an innovative and precise predictive score in burn medicine and even to further interpretations of relevant data regarding different forms of outcome from the German Burn registry.