TNF-α protects from exacerbated myocarditis and cardiac death by suppressing expansion of activated heart-reactive CD4+ T cells

BACKGROUND AND AIMS Tumour necrosis factor α (TNF-α) represents a classical proinflammatory cytokine and its increased levels positively correlate with the severity of many cardiovascular diseases. Surprisingly, some heart failure patients receiving high doses of anti- TNF-α antibodies showed serious health worsening. This work aimed to examine the role of TNF-α signalling on the development and progression of myocarditis and heart-specific autoimmunity. METHODS AND RESULTS Mice with genetic deletion of TNF-α (Tnf+/- and Tnf-/-) and littermate controls (Tnf+/+) were used to study myocarditis in the inducible and the transgenic T cell receptor (TCR-M) models. Tnf+/- and Tnf-/- mice immunized with α-myosin heavy chain peptide (αMyHC) showed reduced myocarditis incidence but the susceptible animals developed extensive inflammation in the heart. In the TCR-M model, defective TNF-α production was associated with increased mortality at a young age due to cardiomyopathy and cardiac fibrosis. We could confirm that TNF-α as well as the secretome of antigen-activated heart-reactive effector CD4+ T (Teff) cells effectively activated the adhesive properties of cardiac microvascular endothelial cells (cMVECs). Our data suggested that TNF-α produced by endothelial in addition to Teff cells promoted leucocyte adhesion to activated cMVECs. Analysis of CD4+ T lymphocytes from both models of myocarditis showed a strongly increased fraction of Teff cells in hearts, spleens, and in the blood of Tnf+/- and Tnf-/- mice. Indeed, antigen-activated Tnf-/- Teff cells showed prolonged long-term survival and TNF-α cytokine-induced cell death of heart-reactive Teff. CONCLUSIONS TNF-α signalling promotes myocarditis development by activating cardiac endothelial cells. However, in the case of established disease, TNF-α protects from exacerbating cardiac inflammation by inducing activation-induced cell death of heart-reactive Teff. These data might explain the lack of success of standard anti-TNF-α therapy in heart failure patients and open perspectives for T cell-targeted approaches

The effects of pesticide mixtures on degradation of pendimethalin in soils

Most agronomic situations involve a sequence of herbicide, fungicide, and insecticide application. On the other hand, use of pesticidal combinations has become a standard practice in the production of many agricultural crops. One of the most important processes influencing the behavior of a pesticide in the environment is its degradation in soil. It is known that due to several pesticide applications in one vegetation season, the pesticide may be present in mixtures with other pesticides or xenobiotics in soil. This study examines the role which a mixture of chemicals plays in pesticide degradation. The influence of other pesticides on the rate of pendimethalin (PDM) degradation in soil was measured in controlled conditions. Mixtures of PDM with mancozeb or mancozeb and thiamethoxam significantly influenced the degradation of pendimethalin under controlled conditions. The second type of mixtures, with metribuzin or thiamethoxam, did not affect the behavior of pendimethalin in soil. Also, we determined the influence of water content on the rate of pendimethalin degradation alone in two soils and compared it to the rate in three pesticide mixtures. We compared two equations to evaluate the predictors of the rate of herbicide dissipation in soil: the first-order kinetic and the non-linear empirical models. We used the non-linear empirical model assuming that the degradation rate of a herbicide in soil is proportional to the difference of the observed concentration of herbicide in soil at time and concentration of herbicide in the last day of measurement

Effects of plant extracts on angiogenic activities of endothelial cells and keratinocytes

Numerous bioactive chemical compounds of plant origin may influence the angiogenic activity of various cell types and may thus affect the formation of blood vessels. Here we present the angiogenic effects of extracts of edible plants collected in Crete, Southern Italy and Southern Spain. Extracts have been applied to cultured human microvascular endothelial cells (HMEC-1), human umbilical vein endothelial cells (HUVEC) and human keratinocytes (HaCaT). About half out of 96 extracts exerted an inhibitory effect on HMEC-1 proliferation. Additionally, we have noted the inhibitory effects of extracts on HUVEC differentiation on a Matrigel layer. None of the extracts showed a stimulatory activity. The extract of Thymus piperella exerted moderate inhibitory effect on cobalt-chloride induced VEGF synthesis, however, CoCl(2)-induced activation of hypoxia responsive element of VEGF promoter was significantly attenuated only by extract of Origanum heracleoticum. Our study indicates that extracts of local food plants, of potential value as nutraceuticals, contain chemical compounds which may inhibit angiogenesis. Demonstration of their real influence on human health requires, however, extensive animal studies and controlled clinical investigations

Recognizing the importance of near-home contact with nature for mental well-being based on the COVID-19 lockdown experience

Several urban landscape planning solutions have been introduced around the world to find a balance between developing urban spaces, maintaining and restoring biodiversity, and enhancing quality of human life. Our global mini-review, combined with analysis of big data collected from Google Trends at global scale, reveals the importance of enjoying day-to-day contact with nature and engaging in such activities as nature observation and identification and gardening for the mental well-being of humans during the COVID-19 pandemic. Home-based activities, such as watching birds from one’s window, identifying species of plants and animals, backyard gardening, and collecting information about nature for citizen science projects, were popular during the first lockdown in spring 2020, when people could not easily venture out of their homes. In our mini-review, we found 37 articles from 28 countries with a total sample of 114,466 people. These papers suggest that home-based engagement with nature was an entertaining and pleasant distraction that helped preserve mental well-being during a challenging time. According to Google Trends, interest in such activities increased during lockdown compared to the previous five years. Millions of people worldwide are chronically or temporarily confined to their homes and neighborhoods because of illness, childcare chores, or elderly care responsibility, which makes it difficult for them to travel far to visit such places as national parks, created through land sparing, where people go to enjoy nature and relieve stress. This article posits that for such people, living in an urban landscape designed to facilitate effortless contact with small natural areas is a more effective way to receive the mental health benefits of contact with nature than visiting a sprawling nature park on rare occasions