Adipokines Regulate the Expression of Tumor-Relevant MicroRNAs

Background: Increasing prevalence of obesity requires the investigation of respective comorbidities, including tumor diseases like colorectal, renal, post-menopausal breast, prostate cancer, and leukemia. To date, molecular mechanisms of the malignant transformation of these peripheral tissues induced by obesity remain unclear. Adipose tissue secretes factors with hormone-like functions, the adipokines, and is therefore categorized as an endocrine organ. Current research demonstrates the ability of adipose tissue to alter DNA methylation and gene expression in peripheral tissues, probably affecting microRNA (miR) expression. Methods: Literature was analyzed for adipokine-regulated miRs. Many of these adipokine upregulated or downregulated miRs exert either oncogenic or anti-tumoral potential. Results: The three selected and analyzed adipokines, adiponectin, leptin, and resistin, induce more strongly oncogenic miRs and simultaneously reduce anti-tumoral miRs than vice versa. This effect is not only true for the pure number of regulated miRs, it is also the case by consideration of the abundance of the respective miR expression based on actual data sets derived from next-generation sequencing. Conclusion: The link of obesity and cancer is analyzed under the aspect of adipokine-regulated miRs. At the same time the impact of miR abundance is considered as a regulatory variable. This context offers new strategies for tumor therapy and diagnostics

Human NK Cell Subset Functions Are Differentially Affected by Adipokines

Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS). Results: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), granzyme A (GzmA) and interferon (IFN)-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56dim NK cells. The production of GzmA in CD56bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R), TRAIL and IFN-γ were species-specific. Conclusion: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation

Studies on the influence of ochratoxin A administration on Salmonella typhimurium infection in pigs

The aim of the study was to assess whether immunomodulating effects produced by ochratoxin A (OTA) may influence the course of an experimental infection of pigs with Salmonella Typhimurium 27 Nat (STM 27 Nair). 8-week old pigs were administered 50 g OTA per kg body weight per day via feed. Either 7 or 14 days after beginning of OTA application, these pigs and untreated controls were challenged orally with STM 27 Nair. Different systemic immune parameters in blood and OT A concentration in serum and organs were examined. The number of STM 27 Nair was detected in faecal samples of the pigs. Despite high concentrations of OTA in sera and organs, systemic immune parameters were not modified compared with controls. Significant changes in these parameters were induced only by the Salmonella infection. Pigs pretreated with OTA excreted STM 27 Nair in slightly higher (not significant) concentrations than untreated controls. As the immunomodul ating effects produced by OT A after oral administration seem to be considerably lower than the effects induced by a challenge with Salmonella Typhimurium in a high dose, experiments using reduced doses for infection should give further information on the effect on Salmonella shedding

An International Partnership of 12 Anatomy Departments - Improving Global Health through Internationalization of Medical Education

Background: At a time of global interconnectedness, the internationalization of medical education has become important. Anatomy as an academic discipline, with its close connections to the basic sciences and to medical education, can easily be connected with global health and internationalization of medical education. Here the authors present an international program based on a partnership between twelve anatomy departments in ten countries, on four continents. Details of a proposed plan for the future direction of the program are also discussed. Objective: The aim is to improve global healthcare by preparing future global healthcare leaders via early international networking, international collaboration and exchange, intercultural experience, and connecting two seemingly distant academic disciplines - anatomy and global health - via internationalization of medical education. Methods: Based in the anatomy course, the program involved early international collaboration between preclinical medical and dental students. The program provided a stepwise progression for learning about healthcare and intercultural topics beyond pure anatomy education - starting with virtual small groups of international students, who subsequently presented their work to a larger international audience during group videoconferences. The above progressed to in-person visits for research internships in the basic sciences within industrialized countries. Findings: Students appreciated the international and intercultural interaction, learned about areas outside the scope of anatomy (e.g., differences in healthcare education and delivery systems, Public and Global Health challenges, health ethics, and cultural enrichment), and valued the exchange travel for basic sciences research internships and cultural experience. Conclusions: This unique collaboration of international anatomy departments can represent a new role for the medical anatomy course beyond pure anatomy teaching - involving areas of global health and internationalization of medical education - and could mark a new era of international collaboration among anatomists.Peer reviewe

Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM) in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity

Alternatives to Student Outbound Mobility-Improving Students' Cultural Competency Skills Online to Improve Global Health Without Travel.

INTRODUCTION: Student outbound mobility is a major element in internationalization of medical education and global health education. However, this approach is often criticized, as it is inherently inequitable. Internationalization at home is a newer concept that aims to provide students with international skills and experiences without exchange travel. We report detailed outcomes of an international online program during the COVID-19 pandemic, which aimed to include acquisition of cultural awareness and competency-similar to what the students would have obtained if they had travelled abroad. METHOD: Sixty-eight students from 12 international universities participated in international small peer group collaborative work, and online networking. Perceived improvement of cultural competency using Likert scale and open-ended questions was used as a measure of success. Furthermore, students' definition of cultural competency in the different countries was obtained. RESULTS: Students improved their cultural competency skills. Data analysis supported statistically significant improvement of the above skills after the program, in comparison to the start of the program. DISCUSSION: Internationalization of medical education can be achieved at home-via structured online peer exchanges-and can provide students with intercultural skills and networking opportunities that are typically achieved via international in-person travel. The above represents a socially just and equitable way to reach all students and can result in improvement of their cultural competency, preparing them for their work in global health, and thereby resulting in improvement of global health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01332-9

Fetal Development in Anatomical Preparations of Ruysch and the Meckels in Comparison

Anatomical collections have been used for centuries for research and teaching purposes. By the example of selected preparations of fetal development from the Ruysch collection (17th–18th centuries) and the Meckel collections (18th–19th century), this article aims to trace the changing purposes, specifics and methods of creating specimens as well as the development of anatomy during that period. The selected specimens are compared and analyzed implementing the historical-critical method. Regarding the appearance of the preparations, we see a transition from the visually aesthetic specimens (Ruysch) to exact ones (Meckel collections). If Ruysch’s preparations were compared in his time to works of art, specimens created by three anatomists of the Meckel dynasty were primarily created for teaching and research purposes. However, Ruysch’s preparations tracing fetal circulation were scientific discoveries of the time. As for preparations of fetal development from the Meckel collections, we see both specimens of physiological processes already known at that time and experimental ones. Regarding teratology, Ruysch and Meckel the Younger tried to explain malformations, but their anatomical preparations could hardly give answers to the cause of deviations from the norm. The differences between the collections can be explained by the different stages of development of anatomy of the time and by the research interests of the anatomists themselves

A comparative study of bone biopsies from the iliac crest, the tibial bone, and the lumbar spine

Abstract Background Patients with an impaired renal function show a high incidence of bone and mineral disturbances. These ‘chronic kidney disease – mineral and bone disorders’ (CKD-MBD) range from high turnover osteoporosis to adynamic bone disease. Currently, the histomorphometric analysis of a bone biopsy taken from the iliac crest is viewed as the gold standard for CKD-MBD subtype differentiation. However, the clinical relevance of such a biopsy is questionable since iliac crest fractures are an extremely rare finding. Therefore, we aimed to elucidate if the histomorphometric parameter ‘trabecular bone volume (BV/TV)’ from the iliac crest is representative for other biopsy locations. We chose two skeletal sites of higher fracture risk for testing, namely, the tibial bone and the lumbar spine, to examine if the current gold standard of bone biopsy is indeed golden. Methods Bone biopsies were taken from 12 embalmed body donors at the iliac crest, the proximal tibia, and the lumbar vertebral body, respectively. Masson-Goldner stained sections of methyl methacrylate embedded biopsies were used for trabecular bone volume calculation. Furthermore, exemplary μ-computed tomography (XtremeCT) scans with subsequent analysis were performed. Results Median values of trabecular bone volume were comparable between all body donors with median (interquartile range, IQR) 18.3% (10.9–22.9%) at the iliac crest, 21.5% (9.5–40.1%) at the proximal tibia, and 16.3% (11.4–25.0%) at the lumbar spine. However, single values showed extensive intra-individual variation, which were also confirmed by XtremeCT imaging. Conclusions Distinct intra-individual heterogeneity of trabecular bone volume elucidate why a bone biopsy from one site does not necessarily predict patient relevant endpoints like hip or spine fractures. Physicians interpreting bone biopsy results should know this limitation of the current gold standard for CKD-MBD diagnostic, especially, when systemic therapeutic decisions should be based on it

A Missing Posterior Division of the Internal Iliac ArteryWhat this paper adds

Introduction: To date, multiple variations in the pelvic vasculature have been reported. In this case report, a rare, so far unreported, branching anomaly of the internal iliac artery on the left side of a male human pelvis is described. Report: The complete posterior division of the internal iliac artery was shown to be missing on dissection of a 73 year old male cadaver. The iliolumbar artery, the lateral sacral arteries, and the superior gluteal artery originated unilaterally (on the left pelvis) directly from the common iliac artery. Discussion: No alteration was observed in the supplied structures of the left pelvic region, including the respective muscles, the sacrum, or the hip joint. Keywords: Branching anomaly, Common iliac artery, Internal iliac artery, Pelvic vasculatur