Single and repeated-dose toxicity studies by intravaginal administration of ATG-K2 powder in female rats.

Bacterial vaginosis (BV) is a microbial dysbiosis that shifts the paradigms of vaginal flora from lactobacilli to opportunistic pathogens. Globally, BV is treated with antibiotic therapy and recurrence rates are > 70% occurring within 6 months due to antibiotic resistance against pathogenic bacteria. An incorporation of orally or intravaginally for the recolonization of healthy microbes in vagina is the suggested course of treatment.

Evaluation of subchronic oral dose toxicity and allergen of freeze-dried powder of (Orthoptera: Acrididae) as a novel food source.

The migratory locust, (Orthoptera: Acrididae), is a well-known edible insect which may serve as new source of human food and animal feed. However, potential toxicity and food safety of had not been investigated extensively until now. Therefore, in this study, we aimed to investigate toxicity of freeze-dried powder of (fdLM) and identify allergic components in ELISA and PCR techniques.

Local lymph node assay: 5-bromo-d-deoxyuridine-ELISA method for comparative study in assessing chemical potencies and skin sensitization in BALB/c and CBA/J strains.

Local lymph node assay (LLNA) is a predictive method to provide estimates of relative potency and to contribute to risk assessment/risk management regarding skin sensitizing potency of chemicals and formulations as a stand-alone alternative test. In addition, LLNA is relatively rapid and cost-effective compared to the Buehler method (Guinea pig test), and confers important animal welfare benefits. CBA/J and BALB/c strains are widely commercially available and have been evaluated by formal LLNA validation studies.

Evaluation of Subchronic Toxicity and Genotoxicity of Ethanolic Extract of Leaves and Stems.

, a traditional plant on Ulleung Island in the Republic of Korea, has been recognized for its multiple medicinal properties. However, potential toxicity and safety analyses of have not been previously investigated. Therefore, this study aimed to evaluate the safety profile of ethanolic extract of leaves and stems (EAG) in terms of genotoxicity and subchronic oral animal toxicity under OECD guidelines and GLP conditions.

Electrophysiological Properties of Ion Channels in Ascaris suum Tissue Incorporated into Planar Lipid Bilayers.

Ion channels are important targets of anthelmintic agents. In this study, we identified 3 types of ion channels in Ascaris suum tissue incorporated into planar lipid bilayers using an electrophysiological technique. The most frequent channel was a large-conductance cation channel (209 pS), which accounted for 64.

Evaluation of Subchronic Oral Dose Toxicity of Freeze-Dried Skimmed Powder of Larvae (frpfdZAL) in Rats.

(Coleoptera: ), the giant mealworm beetle, is known as an edible insect containing a high protein content which may serve as new sources of human food and animal feed. However, potential toxicity and food safety analyses of have not been previously investigated. Therefore, in this study, we aimed to evaluate toxicity of freeze-dried skimmed powder of larvae (frpfdZAL), known as the super mealworm.

Toxicological evaluation of exosomes derived from human adipose tissue-derived mesenchymal stem/stromal cells.

Several studies report that the therapeutic mechanism of action of mesenchymal stem/stromal cells (MSCs) is mainly mediated by paracrine factors that are released from MSCs such as exosomes. Exosomes are nano-sized extracellular vesicles that are transferred to target cells for cell-to-cell communication. Although MSC-derived exosomes (MSC-exosomes) are suggested as novel cell-free therapeutics for various human diseases, evaluation studies for the safety and toxicity of MSC-exosomes are limited.

Genotoxicity and acute toxicity evaluation of the three amino acid additives with biomass.

l-threonine, l-tryptophan and l-valine play a fundamental role in animal and human nutrition as essential amino acids required for normal growth. In addition, each amino acid is codified as a generally recognized as safe (GRAS) amino acid for the use in animal feed additives and presents no exposure risk from animal to humans consuming tissues or products from the target animal. Taking into account the important role of mutagenicity and genotoxicity in the risk of the three amino acid additives (l-threonine, l-tryptophan, and l-valine) fermentation products and other unknown impurities and derivatives from (), the safety evaluation of these amino acid additives is not performed.

A variant associated with sagittal nonsyndromic craniosynostosis alters the regulatory function of a non-coding element.

Craniosynostosis presents either as a nonsyndromic congenital anomaly or as a finding in nearly 200 genetic syndromes. Our previous genome-wide association study of sagittal nonsyndromic craniosynostosis identified associations with variants downstream from BMP2 and intronic in BBS9. Because no coding variants in BMP2 were identified, we hypothesized that conserved non-coding regulatory elements may alter BMP2 expression.

Trapidil, a platelet-derived growth factor antagonist, inhibits osteoclastogenesis by down-regulating NFATc1 and suppresses bone loss in mice.

Trapidil, a platelet-derived growth factor antagonist, was originally developed as a vasodilator and anti-platelet agent and has been used to treat patients with ischemic coronary heart, liver, and kidney disease. In this study, we investigated the effects of trapidil on osteoclastogenesis and elucidated the possible mechanism of action of trapidil. Trapidil strongly inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblasts without affecting receptor activator of NF-κB ligand (RANKL) or osteoprotegerin expression in osteoblasts.

MAPK/ERK Signaling Pathway Analysis in Primary Osteoblasts From Patients With Nonsyndromic Sagittal Craniosynostosis.

Objective: The MAPK/ERK signaling pathway has been implicated in several craniosynostosis syndromes and represents a plausible target for therapeutic management of craniosynostosis. The causes of sagittal nonsyndromic craniosynostosis (sNSC) have not been well understood and the role that MAPK/ERK signaling cascade plays in this condition warrants an investigation. We hypothesized that MAPK-signaling is misregulated in calvarial osteoblasts derived from patients with sNSC.

Leucine-rich repeat, immunoglobulin-like and transmembrane domain 3 (LRIT3) is a modulator of FGFR1.

Fibroblast growth factor receptors (FGFRs) play critical roles in craniofacial and skeletal development via multiple signaling pathways including MAPK, PI3K/AKT, and PLC-?. FGFR-mediated signaling is modulated by several regulators. Proteins with leucine-rich repeat (LRR) and/or immunoglobulin (IG) superfamily domains have been suggested to interact with FGFRs.

The [corrected] SEC23-SEC31 [corrected] interface plays critical role for export of procollagen from the endoplasmic reticulum.

COPII proteins are essential for exporting most cargo molecules from the endoplasmic reticulum. The membrane-facing surface of the COPII proteins (especially SEC23-SEC24) interacts directly or indirectly with the cargo molecules destined for exit. As we characterized the SEC23A mutations at the SEC31 binding site identified from patients with cranio-lenticulo-sutural dysplasia, we discovered that the SEC23-SEC31 interface can also influence cargo selection.

Property of large conductance Ca(2+)-activated K+ channels from Fasciola hepatica incorporated into planar lipid bilayer.

Fasciola hepatica causes biliary epithelial hyperplasia and obstructive jaundice in humans and animals. Using a planar lipid bilayer technique, we further characterized the single channel property of large conductance K(+)-permeable channels that were previously identified from F. hepatica.

Activation of protease-activated receptor1 mediates induction of matrix metalloproteinase-9 by thrombin in rat primary astrocytes.

Thrombin plays an important role in diverse neurological processes such as proliferation, cell migration, differentiation and neuroinflammation. In this study, we investigated the effect of thrombin on matrix metalloprotease-9 (MMP-9) expression in rat primary astrocytes. Thrombin (1-10U/ml) induced a significant increase in MMP-9 activity as measured by gelatin zymography.

Sequence analyses of presenilin mutations linked to familial Alzheimer's disease.

Familial Alzheimer's disease (FAD)-linked presenilin (PS) mutations show gain-of-toxic-function characteristics. These FAD PS mutations are scattered throughout the PS molecule, reminiscent of the distribution of cystic fibrosis transmembrane conductance regulator and p53 mutations. Because of the scattered distribution of PS mutations, it is difficult to infer mechanistic insights about how these mutations cause the disease similarly.

Inhibition of GSK-3beta mediates expression of MMP-9 through ERK1/2 activation and translocation of NF-kappaB in rat primary astrocyte.

Glycogen synthase kinase (GSK)-3beta and extracellular signal-regulated kinase (ERK) regulate several cellular signaling pathways in common, including embryonic development, cell differentiation and apoptosis. In this study, we investigated whether GSK-3beta inhibition is involved in ERK activation, which affects the activation of NF-kappaB and induction of MMP-9 in cultured rat primary astrocytes. Here, we found that GSK-3beta inhibition using GSK-3beta inhibitor TDZD-8 increased the phosphorylation of GSK-3beta at Ser9 site as well as the phosphorylation of ERK1/2 and Akt at Ser473 site.

Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis.

Cd induces oxidative stress and apoptosis in various cells by activating mitogen-activated protein kinases (MAPKs), but the precise signaling components of the MAPK cascade and their role in neuronal apoptosis are still unclear. Here, we report that Cd treatment of SH-SY5Y cells caused apoptosis through sequential phosphorylation of the apoptosis signal regulating kinase 1, MAPK kinase 4, c-Jun N-terminal kinase (JNK), and c-Jun as determined by overexpression of dominant negative (DN) constructs of these genes or using a specific JNK inhibitor SP600125. Both Cd-induced JNK and c-Jun phosphorylation and apoptosis were inhibited dramatically by N-acetyl-L-cysteine, a free radical scavenger.

Protective effects of N-acetylcysteine and selenium against doxorubicin toxicity in rats.

To investigate the neutralizing effect of N-acetylcysteine (NAC) and selenium (Se) against doxorubicin (DOX) toxicity in rats, NAC (140 mg/kg, p.o.) and Se (0.

Serum deprivation increases the expression of low density lipoprotein receptor-related protein in primary cultured rat astrocytes.

The low density lipoprotein receptor (LDLR)-related protein (LRP) is a multifunctional receptor which mediates the endocytic uptake of several ligands implicated in Alzheimer's disease pathophysiology. Although LRP, as a member of the LDLR family, is likely to be regulated in response to various cellular stresses, this regulation has not been fully understood yet. In the present study we studied the regulation of LRP expression in primary cultured rat astrocytes in response to serum deprivation as a general cellular stress.