Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Municipal solid waste management under Covid-19: Challenges and recommendations

Covid-19 is proving to be an unprecedented disaster for human health, social contacts and the economy worldwide. It is evident that SARS-CoV-2 may spread through municipal solid waste (MSW), if collected, bagged, handled, transported or disposed of inappropriately. Under the stress placed by the current pandemic on the sanitary performance across all MSW management (MSWM) chains, this industry needs to re-examine its infrastructure resilience with respect to all processes, from waste identification, classification, collection, separation, storage, transportation, recycling, treatment and disposal. The current paper provides an overview of the severe challenges placed by Covid-19 onto MSW systems, highlighting the essential role of waste management in public health protection during the ongoing pandemic. It also discusses the measures issued by various international organisations and countries for the protection of MSWM employees (MSWEs), identifying gaps, especially for developing countries, where personal protection equipment and clear guidelines to MSWEs may not have been provided, and the general public may not be well informed. In countries with high recycling rates of MSW, the need to protect MSWEs' health has affected the supply stream of the recycling industry. The article concludes with recommendations for the MSW industry operating under public health crisis conditions

Comparison of the effects of synthetic and plant-derived mTOR regulators on healthy human ovarian cells

The aim of the present in vitro study was to compare the effects of synthetic and plant-derived mTOR regulators on healthy human ovarian cells. We compared the effect of two synthetic mammalian mTOR blockers MC2141 and MC2183 with that of natural/plant-derived mTOR blocker rapamycin and mTOR activator resveratrol on cultured human ovarian granulosa cells. We evaluated the accumulation of markers for the mTOR system (sirtuin 1; SIRT 1), proliferation (PCNA), and apoptosis (caspase 3) along with the expression of the transcription factor p53 by quantitative immunocytochemistry. It was observed that MC2183 but not MC2141 or rapamycin reduced SIRT 1 accumulation. MC2141, MC2183, and rapamycin inhibited the accumulation of PCNA, caspase 3, and p53. On the contrary, resveratrol promoted the accumulation of SIRT-1, PCNA, caspase 3, and p53. We have demonstrated the involvement of the mTOR system in the regulation of healthy human ovarian cell proliferation and apoptosis for the first time and indicated that the action of mTOR regulators on ovarian cell apoptosis can be mediated by p53. We have further shown that mTOR regulators can affect ovarian functions without any changes in SIRT-1 accumulation and that the stimulatory effects of resveratrol on analyzed ovarian cell functions are opposite to the inhibitory effects of rapamycin and synthetic mTOR blockers

Fiber Quality of Hemp (Cannabis sativa L.) Grown in Soil Irrigated by Landfill Leachate Water

Hemp (Cannabis sativa L.) for industrial use is often considered as a renewable resource for cultivation in polluted areas, on one hand, for the purpose of possible remediation of soil and, on the other hand, for wide options of the possible use of plant material after the harvest in such areas, namely hemp fiber. This study summarizes the effects of landfill leachate irrigation on agronomic parameters and fiber properties in two cultivars of hemp has grown and harvested in two consecutive seasons. Cultivar Bialobrzeskie shows more promising results in terms of total fiber content and phloem fiber content, while it tends to sacrifice the density of both xylem and phloem fiber in comparison to cultivar Monoica. The two cultivars also demonstrate different sensitivity and responses to the presence of heavy metals, namely zinc and chromium