Effects of Acetaminophen on Reproductive Activities in Male Golden Hamsters.

Acetaminophen [Paracetamol, N-acetyl-para-aminophenol (APAP)] is a common over-the- counter analgesic agent as nonsteroidal anti-inflammatory drugs (NSAIDs). The high doses or the long-term treatment of acetaminophen via usual gavage feeding resulted in damage of testicles that presented recoverable impairment, as well as liver and kidney. The influence of acetaminophen was examined in male golden hamsters treated with acetaminophen- containing diet feeding. They were divided into 5 groups and subjected to this experiment for 4 weeks: animals housed in long photoperiod (LP) as LP control, animals housed in short photoperiod (SP) for 4 weeks as SP control (SP4), and groups of animals treated with low, middle, and high concentrations of acetaminophen (Low, Middle, High groups). Also animals housed in SP for 8 weeks were included (SP8) to contrast testicular activities, if necessary. As results, spermatozoa filled the seminiferous tubules of the testicles of animals in LP control and SP4 groups. The aspects were seen in the animals taken diets of low and middle doses of acetaminophen. The animals who fed high dose of acetaminophen showed large or small testicles. The large testicles displayed all germ cells at the steps of spermatogenesis. The small testicles presented no sperm as the animals housed in SP for 8 weeks. Thus these results indicate that acetaminophen invokes the antigonadal effects and accelerates the regressing process of the testicles in the animals compared to the animals exposed to SP.

Gramicidin, a Bactericidal Antibiotic, Is an Antiproliferative Agent for Ovarian Cancer Cells.

Background and Objectives: Gramicidin, a bactericidal antibiotic used in dermatology and ophthalmology, has recently garnered attention for its inhibitory actions against cancer cell growth. However, the effects of gramicidin on ovarian cancer cells and the underlying mechanisms are still poorly understood. We aimed to elucidate the anticancer efficacy of gramicidin against ovarian cancer cells. Materials and Methods: The anticancer effect of gramicidin was investigated through an in vitro experiment. We analyzed cell proliferation, DNA fragmentation, cell cycle arrest and apoptosis in ovarian cancer cells using WST-1 assay, terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL), DNA agarose gel electrophoresis, flow cytometry and western blot. Results: Gramicidin treatment induces dose- and time-dependent decreases in OVCAR8, SKOV3, and A2780 ovarian cancer cell proliferation. TUNEL assay and DNA agarose gel electrophoresis showed that gramicidin caused DNA fragmentation in ovarian cancer cells. Flow cytometry demonstrated that gramicidin induced cell cycle arrest. Furthermore, we confirmed via Western blot that gramicidin triggered apoptosis in ovarian cancer cells. Conclusions: Our results strongly suggest that gramicidin exerts its inhibitory effect on cancer cell growth by triggering apoptosis. Conclusively, this study provides new insights into the previously unexplored anticancer properties of gramicidin against ovarian cancer cells.

A Strategic Synthesis of Fluoroethers via Ring-Opening Fluorinative Beckmann Fragmentation.

An SN1-type fluorination method for monofluoroethers is developed. The key to this reaction is fluorinative C-C bond cleavage that is driven by oxygen-assisted Beckmann fragmentation. To enable this transformation, cyclic α-aryloxyoximes derived from 3-coumaranone and 1-indanones were investigated as substrates, using N,N-diethylaminosulfur trifluoride (DAST) as a dual-role reagent of an oxime activator and fluoride donor. This method features the synthesis of an underdeveloped chemical motif with simple and mild operating conditions.

Gentian Violet Inhibits Cell Proliferation through Induction of Apoptosis in Ovarian Cancer Cells.

Gentian violet (GV) is known to have antibacterial and antifungal effects, but recent studies have demonstrated its inhibitory effects on the growth of several types of cancer cells. Here, we investigated the anticancer efficacy of GV in ovarian cancer cells. GV significantly reduced the proliferation of OVCAR8, SKOV3, and A2780 cells. Results of transferase dUTP nick and labeling (TUNEL) assay and Western blot assay indicated that the inhibitory effect of GV on ovarian cancer cells was due to the induction of apoptosis. Moreover, GV significantly increased reactive oxygen species (ROS) and upregulated the expression of p53, PUMA, BAX, and p21, critical components for apoptosis induction, in ovarian cancer cells. Our results suggest that GV is a novel antiproliferative agent and is worthy of exploration as a potential therapeutic agent for ovarian cancer.

Gold Nanoparticles as Exquisite Colorimetric Transducers for Water Pollutant Detection.

Gold nanoparticles (AuNPs) are useful nanomaterials as transducers for colorimetric sensors because of their high extinction coefficient and ability to change color depending on aggregation status. Therefore, over the past few decades, AuNP-based colorimetric sensors have been widely applied in several environmental and biological applications, including the detection of water pollutants. According to various studies, water pollutants are classified into heavy metals or cationic metal ions, toxins, and pesticides. Notably, many researchers have been interested in AuNP that detect water pollutants with high sensitivity and selectivity, while offering no adverse environmental issues in terms of AuNP use. This review provides a representative overview of AuNP-based colorimetric sensors for detecting several water pollutants. In particular, we emphasize the advantages of AuNP as colorimetric transducers for water pollutant detection in terms of their low toxicity, high stability, facile processability, and unique optical properties. Next, we discuss the status quo and future prospects of AuNP-based colorimetric sensors for the detection of water pollutants. We believe that this review will promote research and development of AuNP as next-generation colorimetric transducers for water pollutant detection.

Genetic and Clinical Characteristics of Korean Chronic Lymphocytic Leukemia Patients with High Frequencies of MYD88 Mutations.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries. However, CLL is relatively rare in Asia; its genetic features are rarely studied. Here, we aimed to genetically characterize Korean CLL patients and to elucidate the genetic and clinical associations based on data obtained from 113 patients at a single Korean institute. We used next-generation sequencing to explore the multi-gene mutational data and immunoglobulin heavy chain variable gene clonality with somatic hypermutation (SHM). MYD88 (28.3%), including L265P (11.5%) and V217F (13.3%), was the most frequently mutated gene, followed by KMT2D (6.2%), NOTCH1 (5.3%), SF3B1 (5.3%), and TP53 (4.4%). MYD88-mutated CLL was characterized by SHM and atypical immunophenotype with fewer cytogenetic abnormalities. The 5-year time to treatment (TTT) of the overall cohort was 49.8% ± 8.2% (mean ± standard deviation) and the 5-year overall survival was 86.2% ± 5.8%. Patients with SHM, isolated del(13q), TP53-wild type, and NOTCH1-wild type showed better results than those without these conditions. In the subgroup analyses, patients with SHM and L265P presented shorter TTT than patients with SHM but not L265P. In contrast, V217F was associated with a higher SHM percentage and showed a favorable prognosis. Our study revealed the distinct characteristics of Korean CLL patients with high frequencies of MYD88 mutations and their clinical relevance.

MicroRNA-22 negatively regulates LPS-induced inflammatory responses by targeting HDAC6 in macrophages.

Dysregulation of histone deacetylase 6 (HDAC6) can lead to the pathologic states and result in the development of various diseases including cancers and inflammatory diseases. The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-κB and AP-1 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. LPS-induced expression of pro-inflammatory cytokines such as TNF-α, IL-1ß, and IL-6 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. Taken together, these data provide evidence that miR-22 can downregulate LPS-induced expression of proinflammatory cytokines via suppression of NF-κB and AP-1 axis by targeting HDAC6 in macrophages. [BMB Reports 2020; 53(4): 223-228].

Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes.

Human immunodeficiency virus-1 (HIV-1) transactivator of transcription (Tat) is an important viral factor in neuroinflammation. Hindsiipropane B, present in Celastrus hindsii, possesses various biological mechanisms including antiinflammatory activity. In this report, we explored the regulatory activity of hindsiipropane B on HIV-1 Tat-mediated chemokine production and its mode of action in astrocytes. Hindsiipropane B significantly alleviated HIV-1 Tat-mediated production of inflammatory chemokines, CCL2, CXCL8, and CXCL10. Hindsiipropane B inhibited expression of HDAC6, which is important regulator in HIV-1 Tat-mediated chemokine production. Hindsiipropane B diminished HIV-1 Tat-mediated reactive oxygen species (ROS) generation and NADPH oxidase activation/expression. Furthermore, hindsiipropane B inhibited HIV-1 Tat-mediated signaling cascades including MAPK, NF-κB, and AP-1. These data suggest that hindsiipropane B exerts its inhibitory effects on HIV-1 Tat-mediated chemokine production via down-regulating the HDAC6-NADPH oxidase-MAPK-NF-κB/AP-1 signaling axis, and could serve as a therapeutic lead compound against HIV-1 Tat-associated neuroinflammation. [BMB Reports 2018; 51(8): 394-399].