Dairy: Friend or Foe? Bovine Milk-Derived Extracellular Vesicles and Autoimmune Diseases.

Due to the availability, scalability, and low immunogenicity, bovine milk-derived extracellular vesicles (MEVs) are increasingly considered to be a promising carrier of nanomedicines for future therapy. However, considering that extracellular vesicles (EVs) are of biological origin, different sources of EVs, including the host origin and the specific cells that produce the EVs, may have different effects on the structure and function of EVs. Additionally, MEVs play an important role in immune regulation, due to their evolutionary conserved cargo, such as cytokines and miRNAs.

WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells .

Background: WNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown.

Materials & Methods: Expression and function of WNT4 and FZD6 were analyzed using qRT-PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas.

Corrigendum: Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species-Evidence From Human Short- and Long-Term Pilot Studies.

[This corrects the article DOI: 10.3389/fphys.2021.

The individual and combined effects of ochratoxin A with citrinin and their metabolites (ochratoxin B, ochratoxin C, and dihydrocitrinone) on 2D/3D cell cultures, and zebrafish embryo models.

Ochratoxin A and citrinin are nephrotoxic mycotoxins produced by Aspergillus, Penicillium, and/or Monascus species. The combined effects of ochratoxin A and citrinin have been examined in more studies; however, only limited data are available regarding the co-exposure to their metabolites. In this investigation, the individual toxic effects of ochratoxin A, ochratoxin B, ochratoxin C, citrinin, and dihydrocitrinone were tested as well as the combinations of ochratoxin A with the latter mycotoxins were examined on 2D and 3D cell cultures, and on zebrafish embryos.

Physical Activity as a Preventive Lifestyle Intervention Acts Through Specific Exosomal miRNA Species-Evidence From Human Short- and Long-Term Pilot Studies.

Exercise initiates systemic adaptation to promote health and prevent various lifestyle-related chronic diseases. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. Yet to date, a comprehensive profile of the exosomal miRNA (exomiR) content released following short-term (0.

Effect of and snake venoms on apoptosis-related genes in human thymic epithelial cells.

Background: Certain environmental toxins permanently damage the thymic epithelium, accelerate immune senescence and trigger secondary immune pathologies. However, the exact underlying cellular mechanisms and pathways of permanent immune intoxication remain unknown. The aim of the present study was to demonstrate gene expressional changes of apoptosis-related cellular pathways in human thymic epithelial cells following exposure to snake venom from and

Methods: Snake venoms were characterized by analytical methods including reversed phase high-performance liquid chromatography and sodium dodecyl sulphate-polyacrylamide gel electrophoresis, then applied on human thymic epithelial cells (1889c) for 24 h at 10 μg/mL (as used in previous TaqMan Array study).

Crimean-Congo hemorrhagic fever virus infection triggers the upregulation of the Wnt signaling pathway inhibitor genes.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic agent. Thus far, vaccines and specific antiviral therapies are not available against the threat of infection. Our knowledge regarding its pathogenesis is indeed limited, and thus, developing effective antiviral therapies is hampered.

Artificial Neural Network Correlation and Biostatistics Evaluation of Physiological and Molecular Parameters in Healthy Young Individuals Performing Regular Exercise.

Studies support that regular physical activity (PA) decelerates senescence-related decline of physiological and molecular parameters in the elderly. We have addressed the other end of this spectrum: healthy and young, inactive individuals participated in a 6-month long personal trainer-guided lifestyle program. We have measured physiological and molecular parameters (differentiating high- and low responders) and their correlation with PA (sedentary status).

Analysis of Tks4 Knockout Mice Suggests a Role for Tks4 in Adipose Tissue Homeostasis in the Context of Beigeing.

Obesity and adipocyte malfunction are related to and arise as consequences of disturbances in signaling pathways. Tyrosine kinase substrate with four Src homology 3 domains (Tks4) is a scaffold protein that establishes a platform for signaling cascade molecules during podosome formation and epidermal growth factor receptor (EGFR) signaling. Several lines of evidence have also suggested that Tks4 has a role in adipocyte biology; however, its roles in the various types of adipocytes at the cellular level and in transcriptional regulation have not been studied.

"Beige" Cross Talk Between the Immune System and Metabolism.

With thymic senescence the epithelial network shrinks to be replaced by adipose tissue. Transcription factor TBX-1 controls thymus organogenesis, however, the same TBX-1 has also been reported to orchestrate beige adipose tissue development. Given these different roles of TBX-1, we have assessed if thymic TBX-1 expression persists and demonstrates this dualism during adulthood.

Transgenic Exosomes for Thymus Regeneration.

During senescence, Wnt4 expression is down-regulated (unlike their Frizzled receptors), while PPARgamma expression increases in the thymus. Together, these changes allow for thymic degeneration to occur, observed as adipose involution. However, when restored, Wnt4 can efficiently counteract PPARgamma and prevent thymic senescence from developing.

Mitochondrial dysfunction is a key determinant of the rare disease lymphangioleiomyomatosis and provides a novel therapeutic target.

Lymphangioleiomyomatosis (LAM) is a rare and progressive systemic disease affecting mainly young women of childbearing age. A deterioration in lung function is driven by neoplastic growth of atypical smooth muscle-like LAM cells in the pulmonary interstitial space that leads to cystic lung destruction and spontaneous pneumothoraces. Therapeutic options for preventing disease progression are limited and often end with lung transplantation temporarily delaying an inevitable decline.

Cigarette Smoke-Induced Pulmonary Inflammation Becomes Systemic by Circulating Extracellular Vesicles Containing Wnt5a and Inflammatory Cytokines.

Chronic obstructive pulmonary disease (COPD) is a devastating, irreversible pathology affecting millions of people worldwide. Clinical studies show that currently available therapies are insufficient, have no or little effect on elevated comorbidities and on systemic inflammation. To develop alternative therapeutic options, a better understanding of the molecular background of COPD is essential.

Effect of Snake Venom on the Human Cytokine Network.

Local inflammation is a well-known symptom of envenomation by snakes of the family , attributed primarily to the phospholipase A₂s, metalloproteinases and L-amino acid oxidases contained in their venom. The inflammatory effect of snake venoms has been associated with a marked increase of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α. To determine the impact of snake venom on the expression of inflammation-related genes, we incubated human U937 monocyte cells with dilutions of snake venom.

PPARgamma Deficiency Counteracts Thymic Senescence.

Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma.

Toxicology studies of primycin-sulphate using a three-dimensional (3D) in vitro human liver aggregate model.

Primycin-sulphate is a highly effective compound against Gram (G) positive bacteria. It has a potentially synergistic effect with vancomycin and statins which makes primycin-sulphate a potentially very effective preparation. Primycin-sulphate is currently used exclusively in topical preparations.

WNT signaling - lung cancer is no exception.

Since the initial discovery of the oncogenic activity of WNT ligands our understanding of the complex roles for WNT signaling pathways in lung cancers has increased substantially. In the current review, the various effects of activation and inhibition of the WNT signaling pathways are summarized in the context of lung carcinogenesis. Recent evidence regarding WNT ligand transport mechanisms, the role of WNT signaling in lung cancer angiogenesis and drug transporter regulation and the importance of microRNA and posttranscriptional regulation of WNT signaling are also reviewed.

Increased Wnt5a in squamous cell lung carcinoma inhibits endothelial cell motility.

Background: Angiogenesis is important both in normal tissue function and disease and represents a key target in lung cancer (LC) therapy. Unfortunately, the two main subtypes of non-small-cell lung cancers (NSCLC) namely, adenocarcinoma (AC) and squamous cell carcinoma (SCC) respond differently to anti-angiogenic e.g.

Monitoring of Venus transgenic cell migration during pregnancy in non-transgenic rabbits.

Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.

The scaffold protein Tks4 is required for the differentiation of mesenchymal stromal cells (MSCs) into adipogenic and osteogenic lineages.

The commitment steps of mesenchymal stromal cells (MSCs) to adipogenic and other lineages have been widely studied but not fully understood. Therefore, it is critical to understand which molecules contribute to the conversion of stem cells into differentiated cells. The scaffold protein Tks4 plays a role in podosome formation, EGFR signaling and ROS production.

Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis.

Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla.

Alteration in the Wnt microenvironment directly regulates molecular events leading to pulmonary senescence.

In the aging lung, the lung capacity decreases even in the absence of diseases. The progenitor cells of the distal lung, the alveolar type II cells (ATII), are essential for the repair of the gas-exchange surface. Surfactant protein production and survival of ATII cells are supported by lipofibroblasts that are peroxisome proliferator-activated receptor gamma (PPARγ)-dependent special cell type of the pulmonary tissue.

Active Wnt/beta-catenin signaling is required for embryonic thymic epithelial development and functionality ex vivo.

The Wnt/beta-catenin signaling pathway plays an important role in the commitment and development of thymic epithelial precursors. Here we document similarities of thymic epithelial development during embryogenesis in human and mouse. We stained for thymic epithelial surface markers (EpCAM1, Ly51, K8) and ligand/receptor pair (Wnt4, Fz4).

Low titer lentiviral transgenesis in rodents with simian immundeficiency virus vector.

Efficient production of transgenic animals using low-titer lentiviral constructs remains challenging. Here we demonstrate that microinjection of simian immundeficiency virus-derived lentiviral constructs can produce transgenic mice and rats with high efficiency even when using low-titer virus preparations.

Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.

The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood.