Jaboticaba (Myrciaria jaboticaba) powder consumption improves the metabolic profile and regulates gut microbiome composition in high-fat diet-fed mice

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity.This work was financially supported by Brazilian funding: FAPERJ – Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ: E-26/202.677/2018, E-26/010.002203/2019) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brazil (CAPES) – Finance code 001. Benjamin Willing was supported by the Canada Research Chair Program and his laboratory received funding from the Canadian Natural Science and Engineering Research Council (NSERC

A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00425-4

Pre-clinical study protocol:Blood transfusion in endotoxaemic shock

The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock ‘if intravenous (IV) fluids do not maintain adequate circulation’, as a supportive measure of last resort. Volume expansion using crystalloid and colloid fluid boluses for haemodynamic resuscitation in severe illness/sepsis, has been associated with adverse outcomes in recent literature. However, the volume expansion effect(s) following blood transfusion for haemodynamic circulatory support, in severe illness remain unclear with most previous studies having focused on evaluating effects of either different RBC storage durations (short versus long duration) or haemoglobin thresholds (low versus high threshold) pre-transfusion. • We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion (before any crystalloids or colloids) in a validated ovine-model of hyperdynamic endotoxaemic shock. • Additional exploration of mechanisms underlying any physiological, haemodynamic, haematological, immunologic and tissue specific-effects of blood transfusion will be undertaken including comparison of effects of short (≤5 days) versus long (≥30 days) storage duration of PRBCs prior to transfusion

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved