Transport and Toxicity of Methylmercury-Cysteine in Cultured BeWo Cells

Mercury is a heavy metal toxicant that is prevalent throughout the environment. Organic forms of mercury, such as methylmercury (MeHg), can cross the placenta and can lead to lasting detrimental effects in the fetus. The toxicological effects of MeHg on the placenta itself have not been clearly defined. Therefore, the purpose of the current study was to assess the transport of MeHg into placental syncytiotrophoblasts and to characterize the mechanisms by which MeHg exerts its toxic effects. Cultured placental syncytiotrophoblasts (BeWo) were used for these studies. The transport of radioactive MeHg was measured to identify potential mechanisms involved in the uptake of this compound. The toxicological effects of MeHg on BeWo cells were determined by assessing visible pathological change, autophagy, mitochondrial viability, and oxidative stress. The findings of this study suggest that MeHg compounds are transported into BeWo cells primarily by sodium-independent amino acid carriers and organic anion transporters. The MeHg altered mitochondrial function and viability, decreased mitophagy and autophagy, and increased oxidative stress. Exposure to higher concentrations of MeHg inhibited the ability of cells to protect against MeHg-induced injury. The findings show that MeHg is directly toxic to syncytiotrophoblasts and may lead to disruptions in the fetal/maternal transfer of nutrients and wastes.

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.

Research on the Glial–Lymphatic System and Its Relationship With Alzheimer’s Disease

Metabolic waste clearance is essential to maintain body homeostasis, in which the lymphatic system plays a vital role. Conversely, in recent years, studies have identified the glial–lymphatic system in the brain, which primarily comprises the inflow of fluid along the para-arterial space. Aquaporin-4 mediates the convection of interstitial fluid in the brain and outflow along the paravenous space. β-Amyloid deposition is a characteristic pathological change in Alzheimer’s disease, and some studies have found that the glial–lymphatic system plays an important role in its clearance. Thus, the glial–lymphatic system may influence Alzheimer’s disease severity and outcome; therefore, this review summarizes the current and available research on the glial–lymphatic system and Alzheimer’s disease.

Stiffening of the Extracellular Matrix is a Sufficient Condition for Airway Hyperreactivity.

The current therapeutic approach to asthma focuses exclusively on targeting inflammation and reducing airway smooth muscle force to prevent the recurrence of symptoms. However, even when inflammation is brought under control, airways in an asthmatic can still hyper-constrict when exposed to a low dose of agonist. This suggests that there are mechanisms at play that are likely triggered by inflammation and eventually become self-sustaining so that even when airway inflammation is brought back under control, these alternative mechanisms continue to drive airway hyperreactivity in asthmatics. In this study, we hypothesized that stiffening of the airway extracellular matrix is a core pathological change sufficient to support excessive bronchoconstriction even in the absence of inflammation. To test this hypothesis, we increased the stiffness of airway extracellular matrix by photo-crosslinking collagen fibers within the airway wall of freshly dissected bovine rings using riboflavin (vitamin B2) and Ultraviolet-A radiation. In our experiments, collagen crosslinking led to a two-fold increase in the stiffness of the airway extracellular matrix. This change was sufficient to cause airways to constrict to a greater degree, and at a faster rate when they were exposed to 10-5M acetylcholine for 5 minutes. Our results show that stiffening of the extracellular matrix is sufficient to drive excessive airway constriction even in the absence of inflammatory signals.

Molecular Mechanisms of Glial Cells Related Signaling Pathways Involved in the Neuroinflammatory Response of Depression

Dysfunction of the glial cells, such as astrocytes and microglia, is one of the pathological features in many psychiatric disorders, including depression, which emphasizes that glial cells driving neuroinflammation is not only an important pathological change in depression but also a potential therapeutic target. In this review, we summarized a recent update about several signaling pathways in which glial cells may play their roles in depression through neuroinflammatory reactions. We focused on the basic knowledge of these signaling pathways by elaborating each of them. This review may provide an updated image about the recent advances on these signaling pathways that are essential parts of neuroinflammation involved in depression.

Coccidiosis as A Predisposition Factor for Necrotic Enteritis in Poultry and Their Prevention

<p>Coccidiosis and necrotic enteritis are both affecting the digestive tract of chicken and both are major enteric disease that mainly affect poultry. Among the enteric diseases, necrotic enteritis is a major problem. Coccidiosis is caused by the protozoan of Eimeria sp, and is commonly found as a predisposition factor for necrotic enteritis caused by Clostridum perfringens. Both diseases are commonly shown similar pathological change namely necrosis of epthelial cells in the intestinal mucosa. The diseases have great economic impact in poultry productions, due to the increased mortality, decreased performance and medication costs. Control of these diseases are commonly treated with antibiotics and ionophores. However, an intensive use of these drugs in feed may cause the emergence of drug-resistance against some strains of Eimeria sp.and Cl. Perfringens and an increased chance of contamination in animal products for human consumption. The paper is discussing the occurrence of necrotic enteritis especially due to the coccidian as a major predisposition factor and the development of alternative control strategies for avian coccidiosis and necrotic enteritis, by modulating intestinal health.</p>

The Contribution of Nutrition in Compression Therapy for Chronic Venous Disease

Compression therapy is an essential step for the treatment of chronic venous disease (CVD). It is a mechanical treatment against the venous wall's persistent pathological change and the CVD created by inner metabolic substances that damage the wall and valves. The damage is possible to prevent using flavonoid drug and daily nutrition intake, which support the mechanical therapy positively.

Stiffening of the Extracellular Matrix is a Sufficient Condition for Airway Hyperreactivity

The current therapeutic approach to asthma focuses exclusively on targeting inflammation and reducing airway smooth muscle force in an effort to prevent the recurrence of symptoms. However, the treatment is not a cure and has little beneficial effect on the progression of asthma. This suggests that there are mechanisms at play that are likely triggered by inflammation and eventually become self-sustaining so that even when airway inflammation is brought back under control, these alternative mechanisms continue to drive airway hyperreactivity in asthmatics. In this study, we hypothesized that the stiffening of the airway extracellular matrix is a core pathological change sufficient to support excessive bronchoconstriction in asthmatics even when in the absence of inflammation. To test this hypothesis, we increased the stiffness of airway ECM by photo-crosslinking collagen fibers within the airway wall using riboflavin (vitamin B2) and Ultraviolet-A radiation. In our experiments, collagen crosslinking led to a three-fold increase in stiffness of the airway extracellular matrix. This change was sufficient to cause airways to constrict to a greater degree, at a faster rate when exposed to a low dose of contractile agonist. Our results highlight the need for therapeutic approaches that target matrix remodeling to develop a lasting cure for this disease.