Background Astragalus polysaccharide (APS) is a key active ingredient isolated from Astragalus membranaceus that has been reported to be a potential treatment for obesity and diabetes by regulating lipid metabolism and adipogenesis, alleviating inflammation, and improving insulin resistance. However, whether APS regulates lipid metabolism in the context of cachexia remains unclear. Therefore, this study analysed the effects of APS on lipid metabolism and adipose expenditure in a heart failure (HF)-induced cardiac cachexia rat model.  Methods A salt-sensitive hypertension-induced cardiac cachexia rat model was used in the present study. Cardiac function was detected by echocardiography. The histological features and fat droplets in fat tissue and liver were observed by H&E staining and Oil O Red staining. Immunohistochemical staining, Western blotting and RT‒qPCR were used to detect markers of lipolysis and adipose browning in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Additionally, sympathetic nerve activity and inflammation in adipose tissue were detected. Results Rats with HF exhibited decreased cardiac function and reduced adipose accumulation as well as adipocyte atrophy. In contrast, administration of APS not only improved cardiac function and increased adipose weight but also prevented adipose atrophy and FFA efflux in HF-induced cachexia. Moreover, APS inhibited HF-induced lipolysis and browning of white adipocytes since the expression levels of lipid droplet enzymes, including HSL and perilipin, and beige adipocyte markers, including UCP-1, Cd137 and Zic-1, were suppressed after administration of APS. In BAT, treatment with APS inhibited PKA-p38 MAPK signalling, and these effects were accompanied by decreased thermogenesis reflected by decreased expression of UCP-1, PPAR-γ and PGC-1α and reduced FFA β-oxidation in mitochondria reflected by decreased Cd36, Fatp-1 and Cpt1. Moreover, sympathetic nerve activity and interleukin-6 levels were abnormally elevated in HF rats, and astragalus polysaccharide could inhibit their activity. Conclusion APS prevented lipolysis and adipose browning in WAT and decreased BAT thermogenesis. These effects may be related to suppressed sympathetic activity and inflammation. This study provides a potential approach to treat HF-induced cardiac cachexia.

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Background Huangqi Guizhi Wuwu decoction (HQGZWWD) is a traditional Chinese herbal medicine formulation with significant anti-inflammatory activity. However, its underlying mechanism remains unknown. Through network pharmacology and experimental validation, this study aimed to examine the potential mechanism of HQGZWWD in regulating macrophage polarization and inflammation. Methods The active components were obtained from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP), whereas the corresponding targets were obtained from the TCMSP and Swiss Target Prediction database. The GeneCards database identified targets associated with macrophage polarization and inflammation. Multiple networks were developed to identify the key compounds, principal biological processes, and pathways of HQGZWWD that regulate macrophage polarization and inflammation. Autodock Vina is utilized to assess the binding ability between targets and active compounds. Finally, confirm the experiment’s central hypothesis. Human histiocytic lymphoma (U-937) cells were transformed into M1 macrophages following stimulation with Lipopolysaccharide (LPS) to evaluate the effect of HQGZWWD drug-containing mouse serum (HQGZWWD serum) on regulating macrophage polarization and inflammation. Results A total of 54 active components and 859 HQGZWWD targets were obtained. There were 9972 targets associated with macrophage polarization and 11,109 targets associated with inflammation. After screening, 34 overlapping targets were identified, of which 5 were identified as central targets confirmed by experiments, including the α7 nicotinic acetylcholine receptor (α7 nAchR), interleukin 6 (IL-6), Interleukin-1 beta (IL-1β), interleukin 10 (IL-10) and growth factor beta (TGF-β1). Pathway enrichment analysis revealed that 34 overlapping targets were enriched in multiple pathways associated with macrophage polarization and inflammation, including the TGF beta signaling pathway, NF-kappa B signaling pathway, JAK-STAT signaling pathway, and TNF signaling pathway. Molecular docking confirmed that the majority of HQGZWWD’s compounds can bind to the target. In vitro experiments, HQGZWWD serum was shown to up-regulate the expression of α7 nAchR, reduce the number of M1 macrophages, stimulate the production of M2 macrophages, inhibit the expression of pro-inflammatory cytokines IL-6 and IL1-β, and increase the expression of anti-inflammatory cytokines IL-10 and TGF-β1. Conclusion HQGZWWD can regulate the number of M1/M2 macrophages and the level of inflammatory cytokines, and the underlying mechanism may be related to the up-regulation of α7 nAchR expression.

Home noninvasive ventilation (NIV) equipment is often observed to be dirty, potentially increasing patients' risk of respiratory infection. This study aimed to describe the cleaning practices of home NIV patients. Methods: This single-site, cross-sectional, observational study surveyed 100 patients from the respiratory failure clinic regarding cleaning instructions, cleaning habits, barriers, and motivators to cleaning. Open-ended responses were analyzed with basic content analysis and closed categorical responses with frequencies and percentages. Results: Of 100 participants, 77% responded. Cleaning instructions most commonly recalled included cleaning with soapy water for masks (26/47, 55%), head straps (19/47, 40%), and tubing (21/47, 45%); vinegar solution for humidifiers (9/39, 23%); and replacing filters (14/39, 36%). Fourteen respondents reported barriers to cleaning, including forgetfulness (7/14, 50%) and physical difficulties (6/14, 43%). Commonly reported cleaning practices included soapy water to soak masks (28/77, 36%) and tubing (35/77, 46%), weekly masks (34/77, 44%) and tubing cleaning (29/77, 38%), vinegar solution to clean humidifiers for the 36 humidifier users (15/36, 44%), monthly humidifier cleaning (13/36, 36%), and monthly filter cleaning/replacement (36/77, 47%). Conclusion: Few respondents could recall specific instructions about when and how to clean their equipment. Many reported routine cleaning, with varied methods and frequencies. Our results will inform future NIV equipment cleaning educational package design.

Background The circadian clock is involved in lipid metabolism in adipocytes. The impairment of circadian clocks is a major cause of metabolic diseases, but the pathophysiological role of the circadian clock in adipose tissue depletion, in cachexia, remains unclear. To address this issue, we investigated the effects of circadian clock misalignment on adipose tissue metabolism in cardiac cachexia. Methods We produced cardiac cachexia rat models through injection of monocrotaline (MCT), which caused pulmonary hypertension-induced heart failure (HF). Cardiac function was measured by echocardiography. The histological features in fat and liver tissue were observed by H&E staining, Oil Red O staining and Picrosirius red staining. Immunohistochemical staining, Western blotting and RT‒qPCR were used to detect markers of lipolysis, lipogenesis and beiging of adipose tissue in white adipose tissue (WAT) and thermogenesis in brown adipose tissue (BAT). Results We found that rats with MCT injection exhibited right and left ventricular dysfunction. Compared with rats in the control group, rats housed in the light: dark cycle (LD group) exhibited disrupted circadian rhythm reflected by increased BMAL1 protein and decreased REV-ERBα. Meanwhile, these rats displayed decreased adipose mass and increased ectopic lipid deposition; moreover, smaller adipocytes and reduced lipid contents as well as increased extracellular matrix were found. In WAT, rats in the LD group exhibited elevated PKA-mediated lipolysis and WAT browning, while lipid storage was decreased as lipogenesis was inhibited. Meanwhile, in BAT, PKA-mediated thermogenesis was increased. NT-proBNP levels in blood and NE and IL-6 contents in adipose tissue were higher in the LD group than in the control group. Remarkably, compared with rats in the LD group, rats with circadian misalignment in the DL group and LV-Bmal1 shRNA group exhibited aggravated lipolysis and WAT browning, inhibited lipid storage in WAT, and elevated PKA-mediated thermogenesis in BAT. Moreover, rats in the DL group and LV-Bmal1 shRNA group showed higher levels of NT-proBNP in blood and NE and IL-6 contents in adipose tissue than rats in the LD group. Conclusion Our study suggested that a disrupted circadian rhythm aggravated fat wasting in patients with HF-induced cachexia by increasing lipolysis, preventing lipid storage in WAT and promoting beiging/brown adipocyte thermogenesis. This result indicated that stabilizing adipose tissue rhythms may help to combat disrupted energy homeostasis and alleviate excessive adipose tissue expenditure in HF-induced cachexia.