Apple polyphenols in human and animal health*

Apples contain substantial amounts of polyphenols, and diverse phenolics mainly flavonoids and phenolic acids, have been identified in their flesh and skins. This work aimed to analyze the overall landscape of the research literature published to date on apple phenolic compounds in the context of human and animal health. The Web of Science Core Collection electronic database was queried with (apple* polyphenol*) AND (health* OR illness* OR disease* OR medic* OR pharma*) to identify relevant papers covering these words and their derivatives in the titles, abstracts, and keywords. The resulted 890 papers were bibliometrically analyzed. The VOSviewer software was utilized to produce term maps that illustrate how the frequent phrases fared in terms of publication and citation data. The apple polyphenol papers received global contributions, particularly from China, Italy, the United States, Spain, and Germany. Examples of frequently mentioned chemicals/chemical classes are quercetin, anthocyanin, catechin, epicatechin, and flavonol, while examples of frequently mentioned medical conditions are cardiovascular disease, atherosclerosis, diabetes, Alzheimers disease, and obesity. The potential health benefits of apple polyphenols on humans and animals are diverse and warrant further study.Authors acknowledge the support from The National Centre for Research and Development (NCBR) of Poland (project number POIR.01.01.01-00-0593/18).info:eu-repo/semantics/publishedVersio

Expression and Localization of CLC Chloride Transport Proteins in the Avian Retina

Members of the ubiquitously expressed CLC protein family of chloride channels and transporters play important roles in regulating cellular chloride and pH. The CLCs that function as Cl−/H+ antiporters, ClCs 3–7, are essential in particular for the acidification of endosomal compartments and protein degradation. These proteins are broadly expressed in the nervous system, and mutations that disrupt their expression are responsible for several human genetic diseases. Furthermore, knock-out of ClC3 and ClC7 in the mouse result in the degeneration of the hippocampus and the retina. Despite this evidence of their importance in retinal function, the expression patterns of different CLC transporters in different retinal cell types are as yet undescribed. Previous work in our lab has shown that in chicken amacrine cells, internal Cl− can be dynamic. To determine whether CLCs have the potential to participate, we used PCR and immunohistochemical techniques to examine CLC transporter expression in the chicken retina. We observed a high level of variation in the retinal expression levels and patterns among the different CLC proteins examined. These findings, which represent the first systematic investigation of CLC transporter expression in the retina, support diverse functions for the different CLCs in this tissue

Clinical Efficacy and Safety of Bevacizumab Monotherapy in Patients with Metastatic Melanoma: Predictive Importance of Induced Early Hypertension

Background: VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy in patients with metastatic melanoma. Methods and Findings: Thirty-five patients with metastatic melanoma in progression were enrolled in this phase II, single arm clinical trial. Each patient received bevacizumab monotherapy 10 mg/kg q14 d until intolerable toxicity or disease progression occurred. Clinical efficacy was evaluated as objective response, disease control (DC), and survival. We observed one complete (3%) and 5 partial (14%) responses. In addition, 5 patients experienced stable disease >6 months (14%) while 24 patients had progressive disease (PD, 69%), corresponding to a total DC at 6 months in 11 out of 35 patients (31%). Median progression free survival (PFS) was 2.14 months and median overall survival (OS) was 9 months (1.12–49). Seven of the 11 patients experiencing DC developed early hypertension (<2 months) compared to 3/24 of patients with PD (P = 0.001), and hypertension was associated with PFS (P = 0.005) and OS (P = 0.013). Conclusion: Bevacizumab monotherapy demonstrated promising clinical efficacy in patients with metastatic melanoma with disease control in 31% of the patients. Induced early hypertension was a marker for clinical efficacy of bevacizumab

Conformation-regulated mechanosensory control via titin domains in cardiac muscle

The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

Coupled pot and lysimeter experiments assessing plant performance in microbially assisted phytoremediation

We performed an experiment at pot scale to assess the effect of plant growth-promoting bacteria (PGPB) on the development of five plant species grown on a tailing dam substrate. None of the species even germinated on inoculated unamended tailing material, prompting use of compost amendment. The effect of inoculation on the amended material was to increase soil respiration, and promote elements immobilisation at plant root surface. This was associated with a decrease in the concentrations of elements in the leaching water and an increase of plant biomass, statistically significant in the case of two species: Agrostis capillaris and Festuca rubra. The experiment was repeated at lysimeter scale with the species showing the best development at pot scale, A. capillaris, and the significant total biomass increase as a result of inoculation was confirmed. The patterns of element distribution in plants also changed (the concentrations of metals in the roots of A. capillaris and F. rubra significantly decreased in inoculated treatments, while phosphorus concentration significantly increased in roots of A. capillaris in inoculated treatment at lysimeter scale). Measured variables for plant oxidative stress did not change after inoculations. There were differences of A. capillaris plant-soil system response between experimental scales as a result of different substrate column structure and plant age at the sampling moment. Soil respiration was significantly larger at lysimeter scale than at pot scale. Leachate concentrations of As, Mn and Ni had significantly larger concentrations at lysimeter scale than at pot scale, while Zn concentrations were significantly smaller. Concentrations of several metals were significantly smaller in A. capillaris at lysimeter scale than at pot scale. From an applied perspective, a system A. capillaris-compost-PGPB selected from the rhizosphere of the tailing dam native plants can be an option for the phytostabilisation of tailing dams. Results should be confirmed by investigation at field plot scale

Endoplasmic reticulum as a potential therapeutic target for covid-19 infection management?

In December 2019, many pneumonia cases with unidentified sources appeared in Wuhan, Hubei, China, with clinical symptoms like viral pneumonia. Deep sequencing analysis of samples from lower respiratory tract revealed a novel coronavirus, called 2019 novel coronavirus (2019-nCoV). Currently there is a rapid global spread. World Health Organization declare the disease a pandemic condition. The pathologic source of this disease was a new RNA virus from Coronaviridae family, which was named COVID-19. SARS-CoV-2 entry starts with the binding of the spike glycoprotein expressed on the viral envelope to ACE2 on the alveolar surface followed by clathrin-dependent endocytosis of the SARS-CoV-2 and ACE2 complex. SARS-CoV-2 enters the cells through endocytosis process, which is possibly facilitated, via a pH dependent endosomal cysteine protease cathepsins. Once inside the cells, SARS-CoV-2 exploits the endogenous transcriptional machinery of alveolar cells to replicate and spread through the entire lung. Endosomal acidic pH for SARS-CoV-2 processing and internalization is critical. After entering the cells, it possibly activates or hijack many intracellular pathways in favor of its replication. In the current opinion article, we will explain the possible involvement of unfolded protein response as a cellular stress response to the SARS-CoV-2 infection