The Relation between Worker Protection System in the Interpersonal Service and Workplace Violence as Well as Workers' Depression.

Background: We aimed to confirm the effect of interpersonal service worker protection system on workplace violence and depression and to determine the relationship among the protection system, workplace violence, and depression. Methods: Self-reporting survey was conducted for approximately a month beginning on 2 March 2020, among members selected using the convenience sampling method from seven labor unions in South Korea to which interpersonal service workers belonged. The questionnaire consisted of questions regarding the subjects' general characteristics, worker protection system, workplace violence, and depression. Overall, 1,541 workers participated in this study. Results: The basic model was used to test the relationship between the protection system and depression, with a mediating effect of workplace violence. Three of the hypothesized paths were significant (P<.001), but the basic model did not fit the data. In the revised model, the direct path from the protection system to depression was deleted. Path coefficient of the direct effect of the protection system on violence was -0.05, the direct effect of the violence on depression was 0.77, and the indirect effect of the protection system on depression was -0.04. The fit of this model was acceptable. Conclusion: Organizational interventions have an indirect effect on reducing depression by preventing workplace violence; however, there was no direct effect on reducing the depression of the workers. These results justify the need to invest in strengthening workplace protection systems for the interpersonal service workers.

PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal.

Impaired neurogenesis has been associated with several brain disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The role of peroxiredoxin 6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the role of PRDX6 in neurogenesis, we compared the neurogenesis ability of PRDX6-overexpressing transgenic (Tg) mice and wild-type mice and studied the involved molecular mechanisms. We showed that the neurogenesis of neural stem cells (NSCs) and the expression of the marker protein were lower in PRDX6 Tg-mice than in wild-type mice. To determine the factors involved in PRDX6-related neural stem cell impairment, we performed a microarray experiment. We showed that the expression of WDFY1 was dramatically decreased in PRDX6-Tg mice. Moreover, WDFY1 siRNA decreases the differentiation ability of primary neural stem cells. Interestingly, WDFY1 reportedly recruits the signaling adaptor TIR-domain-containing adapter-inducing interferon-ß (TRIF) to toll-like receptors (TLRs); thus, we showed the relationship among TLRs, PRDX6, and WDFY1. We showed that TLR4 was dramatically reduced in PRDX6 Tg mice, and reduced TLR4 expression and neurogenesis was reversed by the introduction of WDFY1 plasmid in the neural stem cells from PRDX6 Tg mice. This study indicated that PRDX6 inhibits the neurogenesis of neural precursor cells through TLR4-dependent downregulation of WDFY1 and suggested that the inhibitory effect of PRDX6 on neurogenesis play a role in the development of neurodegenerative diseases in the PRDX6 overexpressing transgenic mice.

Estrogen deficiency exacerbates Aß-induced memory impairment through enhancement of neuroinflammation, amyloidogenesis and NF-ĸB activation in ovariectomized mice.

Estrogen is well known to have a preventative effect in Alzheimer's disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aß)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aß (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks. Memory impairment, neuroinflammatory protein expression, and amyloidogenic pathways were then measured. Ovariectomized mice demonstrated severe memory impairment, Aß accumulation, neprilysin downregulation, and activation of NF-ĸB signaling compared to sham-control mice. In vitro experiments demonstrated that ß-estradiol (10 µM) inhibited Aß (1 µM)-induced neuroinflammation in microglial BV-2 cells and prevented Aß-induced cell death in primary cultured neuronal cells. As in in vivo experiments, NF-ĸB activation was significantly upregulated in in vitro experiments. Furthermore ß-estradiol treatment inhibited NF-ĸB activation in both of microglial BV-2 cells and cultured neuronal cells. These findings suggest that estrogen may protect against memory impairment through the regulation of Aß accumulation and neurogenic inflammation by inhibiting NF-κB activity.

Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway.

The purpose of this study was to evaluate the anticancer efficacy of cetuximab combined with cisplatin (combination treatment) on colon cancer growth, as well as its underlying action mechanism. Combination treatment synergistically potentiated the effect of cetuximab on cell growth inhibition and apoptosis induction in HCT116 and SW480 cells. Combination treatment further suppressed the expression of the activated form of epidermal growth factor receptor (EGFR) and MAP kinase (p-ERK and p-p38) and also significantly inhibited the activity of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). Additionally, the expression of cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) mRNA was significantly reduced by the combination treatment as compared to the expression seen for treatment with cetuximab or cisplatin alone. We found that the synergistic inhibitory effects of cetuximab and cisplatin on AP-1 and NF-κB activation, as well as on cell viability, were reversed by pretreatment with an ERK inhibitor. Results demonstrate that combined treatment with cetuximab and cisplatin exerts synergistic anticancer effects on colon cancer cells and also suggest that the ERK pathway plays a critical role in these effects via the suppression of the EGFR signaling pathway, along with the inhibition of COX-2, IL-8, and AP-1 and NF-κB.

Low-temperature growth and direct transfer of graphene-graphitic carbon films on flexible plastic substrates.

We demonstrate low-temperature growth and direct transfer of graphene-graphitic carbon films (G-GC) onto plastic substrates without the use of supporting materials. In this approach, G-GC films were synthesized on copper layers by using inductively coupled plasma enhanced chemical vapor deposition, enabling the growth of few-layer graphene (G) on top of Cu and the additional growth of graphitic carbon (GC) films above the graphene layer at temperatures as low as 300 °C. The patterned G-GC films are not easily damaged or detached from the polymer substrates during the wet etching and transfer process because of the van der Waals forces and π-π interactions between the films and the substrates. Raman spectroscopy reveals the two-dimensional hexagonal lattice of carbon atoms and the crystallinity of the G-GC films. The optical transparency and sheet resistance of the G-GC films are controlled by modulating the film thickness. Strain sensors are successfully fabricated on plastic substrates, and their resistance modulation at different strains is investigated.

S-Adenosyl-L-methionine ameliorates TNFalpha-induced insulin resistance in 3T3-L1 adipocytes.

An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The IkappaB kinase-beta (IKK-beta)/ nuclear factor-kappaB (NF-kappaB) pathway is a molecular mediator of insulin resistance. S-Adenosyl-L-methionine (SAM) has both antioxidative and anti-inflammatory properties. We investigated the effects of SAM on the glucose transport and insulin signaling impaired by the tumor necrosis factor alpha (TNFalpha) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNFalpha. The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. In addition, SAM significantly attenuated the TNFalpha-induced degradation of IkappaB-alpha and NF-kappaB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-beta in vitro. These results suggest that SAM can alleviate TNFalpha mediated-insulin resistance by inhibiting the IKK-beta/NF-kappaB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.

Synthesis of 5-(4-alkylsulfanyl-[1, 2, 5]thiadiazol-3-yl)-3-methyl-1, 2, 3, 4-tetrahydropyrimidine oxalate salts and their evaluation as muscarinic receptor agonists.

The synthesis and biological test of 5-(4-alkylsulfanyl-[1, 2, 5]thiadiazol-3-yl)-3-me-thyl-1, 2, 3, 4-tetrahydropyrimidine oxalate salts 7 as muscarinic receptor agonists are described. The key intermediate 4 was obtained by a modified Strecker reaction and cyclization, and the 3-methyl-1, 2, 3, 4-tetrahydropyrimidines were obtained by subsequent substitution, quarternization, and reduction. The final products 7 were obtained as oxalic acid salts. The prepared compounds were examined in vitro for their binding affinities to the cloned human muscarinic receptor by the [(3)H]-NMS binding assay.

Pharmacokinetics and bioavailability of oral cephalosporins, KR-984055 and its prodrugs, KR-999001 and KR-999002, in the rat.

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR-999002, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (i.v.) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examined in vitro. The degree of protein binding of KR-984055 was in the range of 92.09-94.77%. KR-984055 exhibited poor oral bioavailability (7.02 +/- 1.58%). The observed oral bioavailabilities of KR-984055 from KR-999001 and KR-999002 were 38.77 +/- 2.81% and 39.81 +/- 5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR-999001 and KR-999002 appear to be an efficient oral prodrug of KR-984055 that deserved further clinical evaluation in human.