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Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation.

Multiple myeloma is an incurable cancer of plasma cells that is predominantly located in the bone marrow. Multiple myeloma cells are characterized by distinctive biological features that are intricately linked to their core function, the assembly and secretion of large amounts of antibodies, and their diverse interactions with the bone marrow microenvironment. Here, we provide a concise and introductory discussion of major metabolic hallmarks of plasma cells and myeloma cells, their roles in myeloma development and progression, and how they could be exploited for therapeutic purposes. We review the role of glucose consumption and catabolism, assess the dependency on glutamine to support key metabolic processes, and consider metabolic adaptations in drug-resistant myeloma cells. Finally, we examine the complex metabolic effects of proteasome inhibitors on myeloma cells and the extracellular matrix, and we explore the complex relationship between myeloma cells and bone marrow adipocytes.

Multiple myeloma (MM) is a haematological malignancy characterised by the proliferation and accumulation of terminally differentiated abnormal plasma cells in the bone marrow. Patients suffer from bone pain, factures, anaemia, osteolytic lesions and renal failure. Despite recent advancement in therapy MM remains an incurable disease due to the emergences of drug resistance and frequent relapse. For many decades, research has been heavily focused on understanding the relationship between bone cells such as osteoblast, osteocytes and osteoclasts and the infiltrating tumour cells. However, it is now clear that the tumour-supportive bone microenvironment including cellular and non-cellular components play an important role in driving MM progression and bone disease. One of the most abundant cell types in the bone microenvironment is the bone marrow adipocyte (BMAd). Once thought of as inert space filling cells, they have now been recognised as having specialised functions, signalling in an autocrine, paracrine and endocrine manner to support normal systemic homeostasis. BMAds are both an energy store and a source of secreted adipokines and bioactive substances, MM cells are able to hijack this metabolic machinery to fuel migration, growth and survival. With global obesity on the rise, it has never been more important to further understand the contribution these cells have in both normal and disease settings. The aim of this review is to summarise the large body of emerging evidence supporting the interplay between BMAds and MM cells and to delineate how they fit into the vicious cycle of disease.

and Executive SummaryWhen it comes to pandemics such as the currently present COVID-19 [1], various issues and problems arise for infrastructures and institutions. Due to possible extreme effects, such as hospitals potentially running out of beds or medical equipment, it is essential to lower the infection rate to create enough space to attend to the affected people and allow enough time for a vaccine to be developed. Unfortunately, this requires that measures put into place are upheld long enough to reduce the infection rate sufficiently.In this paper, we describe research simulating the influences of the contact rate on the spread of the pandemic using New York City as an example (Section IV) and especially already observed effects of contact rate increases during holidays [2-4] (Section V). In multiple simulations scenarios for Passover and Easter holidays, we evaluated 25%, 50%, 75%, and 100% temporary increases in contact rates using a scenario close to the currently reported numbers as reference and contact rates based on bioterrorism research as a “normal” baseline for NYC.The first general finding from the simulations is that singular events of increased visits/contacts amplify each other disproportionately if they are happening in close proximity (time intervals) together. The second general observation was that contact rate spikes leave a permanently increased and devastating infection rate behind, even after the contact rate returns to the reduced one. In case of a temporary sustained increase of contact rate for just three days in a row, the aftermath results in an increase of infection rate up to 40%, which causes double the fatalities in the long run.In numbers, given that increases of 25% and 50% seem to be most likely given the data seen in Germany for the Easter weekend for example [2, 3], our simulations show the following increases (compared to the realistic reference run): for a temporary 25% surge in contact rate, the total cases grew by 215,880, the maximum of required hospitalizations over time increased to 63,063, and the total fatalities climbed by 8,844 accumulated over 90 days. As for the 50% surge, we saw the total number of cases rise by 461,090, the maximum number of required hospitalizations increase to 79,733, and the total number of fatalities climb by 19,125 over 90 days in NYC.All in all, we conclude that even very short, temporary increases in contact rates can have disproportionate effects and result in unrecoverable phenomena that can hardly be reversed or managed later. The numbers show possible phenomena before they might develop effects in reality. This is important because phenomena such as the described blip can impact the hospitals in reality. Therefore, we warn that a wave of infections due to increased contact rates during Passover/Easter might come as a result!

This study investigated the health care and social service needs, barriers to care and satisfaction with services among American Indians with HIV/AIDS in a western tribe. Individual interviews were conducted with 28 respondents, which constituted nearly the entire population obtaining HIV/AIDS medical services from the IHS in the target area. The survey found that expressed need for services in this frontier rural area were lower than urban counterparts, but that access to needed services was lower. Common unmet medical needs include mental health services, eye and dental care, traditional Native medicine, and substance abuse treatment. Common unmet social service needs include housing assistance, help obtaining food and clothing, and transportation. Limited access to essential services impedes the ability of American Indians with HIV/AIDS to maintain effective medical regimens.