Assessing the health hazards of low-dose ethylmercury: Neurochemical and behavioral impacts in neonatal mice through matrix metalloproteinase activation and brain-derived neurotrophic factor release.

Ethylmercury (EtHg) primarily enters the body through contaminated fish and mercury-containing vaccines, raising concerns about its neurotoxic risks, particularly for infants and young children. Although its neurodevelopmental impact has been suggested, research remains inconclusive. Given that neurite outgrowth, matrix metalloproteinase (MMP) activity, and brain-derived neurotrophic factor (BDNF) expression play critical roles in brain development and synaptic plasticity, we hypothesized that EtHg exposure disrupts these processes, leading to behavioral abnormalities.

Thyroid cancer risk associated with perfluoroalkyl carboxylate exposure: Assessment using a human dermal fibroblast-derived extracellular matrix-based thyroid cancer organoid.

The burgeoning incidence of thyroid cancer globally necessitates a deeper understanding of its etiological factors. Emerging research suggests a link to environmental contaminants, notably perfluoroalkyl carboxylates (PFACs). This study introduces a novel biomaterial-based approach for modeling thyroid cancer and assesses PFAC exposure-related health risks.

Bisphenol A is more potent than bisphenol S in influencing the physiological and pathological functions of lungs via inducing lung fibrosis and stimulating metastasis.

Bisphenol A (BPA) is widely used in the production of plastics, food containers, and receipt ink globally. However, research has identified it as an endocrine disruptor, affecting the hormonal balance in living organisms. Bisphenol S (BPS), one of the alternative substances, was developed, but its effects on human health and the underlying mechanisms remain unclarified.

Long-chain perfluoroalkyl carboxylates induce cytoskeletal abnormalities and activate epithelial-mesenchymal transition in both renal cell carcinoma 3D cultures and Caki-1 xenografted mouse model.

Exposure to perfluorooctanoate (PFOA; a type of perfluoroalkyl carboxylates [PFACs]) may be correlated with the incidence of kidney cancer in individuals exposed to high levels of PFOA. However, mechanistic studies on the influence of PFACs on renal cell carcinoma (RCC) development are lacking. We explored the effects of five types of PFACs on RCC using in vitro and in vivo models to fill this knowledge gap and provide information for environmental/usage regulations.

Bisphenol A impairs renal function by reducing Na/K-ATPase and F-actin expression, kidney tubule formation in vitro and in vivo.

The kidney proximal tubule is responsible for reabsorbing water and NaCl to maintain the homeostasis of the body fluids, electrolytes, and nutrients. Thus, abnormal functioning of the renal proximal tubule can lead to life-threatening imbalances. Bisphenol A (BPA) has been used for decades as a representative chemical in household plastic products, but studies on its effects on the kidney proximal tubule are insufficient.

Characteristics of Extracellular Vesicles and Preclinical Testing Considerations Prior to Clinical Applications.

Cell therapy products have significant limitations, such as storage instability, difficulties with transportation, and toxicity issues such as tumorigenicity and immunogenicity. Extracellular vesicles (EVs) secreted from cells show potential for therapeutic agent development. EVs have not been widely examined as investigational drugs, and non-clinical studies for the clinical approval of EV therapeutic agents are challenging.

Role of zinc dyshomeostasis in inflammasome formation in cultured cortical cells following lipopolysaccharide or oxygen-glucose deprivation/reperfusion exposure.

Exposure of mouse mixed cortical cell cultures to lipopolysaccharide (LPS) resulted in inflammasome formation in neurons and astrocytes, as indicated by increases in the levels of NLRP3, ASC, caspase-1, and IL-1β. LPS exposure concurrently increased the level of free zinc in the cytosol of both cell types. Addition of the membrane-permeant zinc chelator TPEN blocked the increases in the levels of NLRP3 and caspase-1 as well as the release of inflammatory cytokines, indicating a role for increased zinc in LPS-induced inflammasome formation.

Autism phenotypes in ZnT3 null mice: Involvement of zinc dyshomeostasis, MMP-9 activation and BDNF upregulation.

To investigate the role of synaptic zinc in the ASD pathogenesis, we examined zinc transporter 3 (ZnT3) null mice. At 4-5 weeks of age, male but not female ZnT3 null mice exhibited autistic-like behaviors. Cortical volume and neurite density were significantly greater in male ZnT3 null mice than in WT mice.

Abnormalities in the zinc-metalloprotease-BDNF axis may contribute to megalencephaly and cortical hyperconnectivity in young autism spectrum disorder patients.

Whereas aberrant brain connectivity is likely the core pathology of autism-spectrum disorder (ASD), studies do not agree as to whether hypo- or hyper-connectivity is the main underlying problem. Recent functional imaging studies have shown that, in most young ASD patients, cerebral cortical regions appear hyperconnected, and cortical thickness/brain size is increased. Collectively, these findings indicate that developing ASD brains may exist in an altered neurotrophic milieu.

Acridine yellow G blocks glioblastoma growth via dual inhibition of epidermal growth factor receptor and protein kinase C kinases.

Amplification of the epidermal growth factor receptor (EGFR), frequently expressed as a constitutively active deletion mutant (EGFRvIII), occurs commonly in glioblastoma multiformes (GBM). However, blockade of EGFR is therapeutically disappointing for gliomas with PTEN deletion. To search for small molecules treating this aggressive cancer, we have established a cell-based screening and successfully identified acridine yellow G that preferentially blocks cell proliferation of the most malignant U87MG/EGFRvIII cells over the less malignant U87MG/PTEN cells.

Akt-phosphorylated PIKE-A inhibits UNC5B-induced apoptosis in cancer cell lines in a p53-dependent manner.

UNC5B acts as a tumor suppressor, and it induces apoptosis in the absence of its cognate ligand netrins. UNC5B is a direct transcriptional target of p53 upon UV stimulation. Here we show that Akt phosphorylates PIKE-A and regulates its association with UNC5B and inhibits UNC5B-provoked apoptosis in a p53-dependent manner.

Insulin increases retinal hemorrhage in mild oxygen-induced retinopathy in the rat: inhibition by riluzole.

Purpose: Although hyperglycemia is likely the main stimulus for VEGF induction in diabetic retinopathy (DR), a switch from oral hypoglycemic therapy to parenteral insulin injection, despite producing better glucose control, sometimes paradoxically aggravates DR. The induction of VEGF by insulin, as observed in certain conditions, may be a plausible mechanism for this phenomenon. In the present study, to determine the role of insulin in proliferative diabetic retinopathy, the authors examined whether insulin treatment affected the outcome of oxygen-induced retinopathy (OIR) in rats and whether the anti-amyotrophic lateral sclerosis (ALS) drug riluzole with protein kinase C-inhibiting activity can attenuate the effects of insulin.

Riluzole inhibits VEGF-induced endothelial cell proliferation in vitro and hyperoxia-induced abnormal vessel formation in vivo.

Purpose: The present study examined the effects of riluzole, a Food and Drug Administration-approved drug for amyotrophic lateral sclerosis, on VEGF-stimulated endothelial cell proliferation in culture, and on neovascularization in a rat model of retinopathy of prematurity (ROP).

Methods: Human umbilical vein endothelial cell and bovine retinal endothelial cell cultures were treated with VEGF to induce endothelial cell proliferation in the presence or absence of riluzole. Activation of PKC betaII was examined by quantifying its phosphorylated form on immunoblots.

Protection by pyruvate of rat retinal cells against zinc toxicity in vitro, and pressure-induced ischemia in vivo.

Purpose: To examine whether zinc accumulation occurs during retinal neuronal death after pressure-induced ischemia in rats and whether pyruvate protects against such death.

Methods: To induce transient retinal ischemia, intraocular pressure was increased above systolic pressure for 65 minutes. Pyruvate was administered through the tail vein for 12 hours after ischemia to determine its effect on degeneration of retinal neurons.