Case-Control Study of Occupational Acute Myeloid Leukemia in the Republic of Korea.

Background: We conducted a case-control study to identify high-risk occupations and exposure to occupational hazards for acute myeloid leukemia (AML). Methods: When patients with AML admitted to the Department of Hematology in the study hospital for the first time are referred to the Department of Occupational and Environmental Medicine, data on occupation are collected by investigators to evaluate work-relatedness. Community-based controls were recruited through an online survey agency, and four controls per case were matched. Occupational information was estimated using structured questionnaires covering 27 specific occupations and 32 exposure agents. Conditional logistic regression analysis was performed by pairing cases and controls. Results: In the analysis of the risk of AML according to occupational classification, a significant association was found in paint manufacturing or painting work (OR = 2.22, 95% CI: 1.03-4.81) and aircrew (OR = 6.00, 95% CI: 1.00-35.91) in males, and in pesticide industry (OR = 6.89, 95% CI: 1.69-28.07) and cokes and steel industry (OR = 2.00, 95% CI: 1.18-22.06) in ≥60 years old. Moreover, the risk of AML increased significantly as the cumulative exposure to thinners increased. In the analyses stratified by sex and age, the association between pesticide exposure and AML was significant in males (OR = 3.28, 95% CI: 1.10-9.77) and in ≥60 years old (OR = 6.22, 95% CI: 1.48-26.08). Conclusion: This case-control study identified high-risk occupational groups in the Republic of Korea including paint manufacturers and painters, aircrew, and those who are occupationally exposed to pesticides or paint thinners.

Administration of α-Klotho Does Not Rescue Renal Anemia in Mice.

Renal anemia is a common complication in chronic kidney disease (CKD), associated with decreased production of erythropoietin (EPO) due to loss of kidney function, and subsequent decreased red blood cell (RBC) production. However, many other factors play a critical role in the development of renal anemia, such as iron deficiency, inflammation, and elevated fibroblast growth factor 23 (FGF23) levels. We previously reported that inhibition of FGF23 signaling rescues anemia in mice with CKD. In the present study we sought to investigate whether α-Klotho deficiency present in CKD also contributes to the development of renal anemia. To address this, we administered α-Klotho to mice with CKD induced by an adenine-rich diet. Mice were sacrificed 24 h after α-Klotho injection, and blood and organs were collected immediately post-mortem. Our data show that α-Klotho administration had no beneficial effect in mice with CKD-associated anemia as it did not increase RBC numbers and hemoglobin levels, and it did not stimulate EPO secretion. Moreover, α-Klotho did not improve iron deficiency and inflammation in CKD as it had no effect on iron levels or inflammatory markers. Interestingly, Klotho supplementation significantly reduced the number of erythroid progenitors in the bone marrow and downregulated renal Epo and Hif2α mRNA in mice fed control diet resulting in reduced circulating EPO levels in these mice. In addition, Klotho significantly decreased intestinal absorption of iron in control mice leading to reduced serum iron and transferrin saturation levels. Our findings demonstrate that α-Klotho does not have a direct role in renal anemia and that FGF23 suppresses erythropoiesis in CKD via a Klotho-independent mechanism. However, in physiological conditions α-Klotho appears to have an inhibitory effect on erythropoiesis and iron regulation.

Dietary effects of sophorolipids on nutrient bioavailability and intestinal microenvironments in broiler chickens.

Using antibiotics as growth promoter has been banned in poultry feed industry, thus various researchers try to seek an alternative to replace the growth-promoting antibiotics. In this study, we aimed to evaluate the growth performance via intestinal nutrient utilization and cecal microbial composition of broiler after dietary supplementation with most commonly using antibiotics, zinc bacitracin, and sophorolipid. A total of 180 1-day-old chicks were randomly assigned, and dietary treatment was as follow: CON, basal diet; ZB, 100 ppm of zinc bacitracin supplemented diet; and SPL, 250 ppm of sophorolipid supplemented diet. Their growth performance was evaluated and the samples of blood, small intestine, and ileal and cecal digesta were collected for biochemical, histological, and genomic analyses. The body weight and average daily gain of 7-day-old chicks were higher in ZB and those in overall experimental period were improved by ZB and SPL supplementation (p < 0.05). Their intestinal characteristics were not affected by dietary treatments in duodenum and ileum. Nonetheless, villus height was increased by SPL supplementation in jejunum (p < 0.05). Moreover, dietary SPL supplementation could down-regulate the expression level of pro-inflammatory cytokine, IL-1ß (p < 0.05). mRNA levels of lipid and protein transporters did not differ among the treatments, however, relative expression levels of carbohydrate transporters, GLUT2 and SGLT1 were increased in broiler chicken's jejumum fed zinc bacitracin and sophorolipid supplemented diets (p < 0.05). Dietary zinc bacitracin supplementation could increase the population of Firmicutes in phylum level, and the portion of Turiciacter in genus level. On the other hands, the portion of Faecalibacterium was increased by dietary SPL supplementation compared to the other treatments. Our findings suggest that SPL supplementation improves growth performance through enhanced carbohydrate utilization capacity via improvement of gut morphological status and modulation of the cecal microbial population of broilers.

Curative effects of sophorolipid on physical wounds: In vitro and in vivo studies.

Early-weaning syndrome is harmful to animals because an effect on growth in the early-stage of life generally determines the overall growth rate. Sophorolipid (SPL), a surface-active glycolipid compound, has been shown to exhibit antimicrobial activity and stimulate cell proliferation. Thus, in vitro and in vivo studies were conducted to evaluate the potential of SPL on the gut turnover after the wound. The in vitro experiment with HT-29 cells showed the increased proliferation with increasing gene levels of collagenase-1 and matrilysin-1. Next, the 16-day in vivo experiment was conducted with thirty rats (14-day-old), and the allocation was performed according to their body weight (BW) into three treatments: control diet (CON), 48 ppm of oxytetracycline-supplemented diet (OTC) and 10 ppm of SPL-supplemented diet (SPL). Dietary SPL accelerates the growth of rats in overall periods, and intestinal permeability was lower in SPL at day 16. Villus:crypt ratio and the goblet cell count were also higher in SPL than in CON at day 8. Caecal Streptococcus spp. were significantly reduced with dietary SPL and OTC at day 8 and 16, and total short-chain fatty acid, acetate and butyrate levels were increased in the SPL at day 8. In conclusion, these data demonstrated that SPL could improve gut remodelling potential and modulate the gut environments, resulted in acceleration of post-weaning growth. Therefore, SPL could have a potential as a feed additive aimed at promoting repair system after wound in animal's gut.

A Prospective, Split-Face, Comparative Study of Combined Treatment With Fractional Microneedle Radiofrequency and Nonablative 1927-nm Fractional Thulium Fiber Laser for Wrinkle Treatment.

BACKGROUND: Fractional microneedle radiofrequency (FMR) and nonablative 1927-nm fractional thulium fiber laser (TFL) are widely used for skin rejuvenation treatment. OBJECTIVES: To investigate the efficacy and safety of combined treatment with both devices for wrinkles. PATIENTS AND METHODS: Twenty-five patients with wrinkles were enrolled. One side of the face was treated with FMR alone, while the other side was treated with a combination of FMR and TFL. Each treatment consisted of 3 sessions at four-week intervals and patients were followed up 12 weeks after the last treatment. Overall improvement was assessed by patient global assessment (PGA) and investigator global assessment (IGA). Depression scores for the evaluation of wrinkles were objectively assessed by Antera 3D system. RESULTS: Both sides of the face led to clinical improvement in both mean PGA and IGA. Combination treatment demonstrated a greater improvement in both mean PGA and IGA compared with FMR alone. In addition, wrinkle grading scales and depression scores showed greater improvement in the combination group than in FMR alone. CONCLUSION: This study demonstrated that FMR and TFL comprise a good combination treatment for the treatment of wrinkles because both treatments have a synergistic effect on wrinkle improvement.

Quantitative Trait Loci (QTLs) Associated with Microspore Culture in Raphanus sativus L. (Radish).

The radish is a highly self-incompatible plant, and consequently it is difficult to produce homozygous lines. Bud pollination in cross-fertilization plants should be done by opening immature pollen and attaching pollen to mature flowers. It accordingly takes a lot of time and effort to develop lines with fixed alleles. In the current study, a haploid breeding method has been applied to obtain homozygous plants in a short period of time by doubling chromosomes through the induction of a plant body in the haploid cells, in order to shorten the time to breed inbred lines. We constructed genetic maps with an F1 population derived by crossing parents that show a superior and inferior ability to regenerate microspores, respectively. Genetic maps were constructed from the maternal and parental maps, separately, using the two-way pseudo-testcross model. The phenotype of the regeneration rate was examined by microspore cultures and a quantitative trait loci (QTL) analysis was performed based on the regeneration rate. From the results of the culture of microspores in the F1 population, more than half of the group did not regenerate, and only a few showed a high regeneration rate. A total of five significant QTLs were detected in the F1 population, and five candidate genes were found based on the results. These candidate genes are divided into two classes, and appear to be related to either PRC2 subunits or auxin synthesis.

5,7-Dimethoxyflavone induces apoptotic cell death in human endometriosis cell lines by activating the endoplasmic reticulum stress pathway.

Endometriosis is a reproductive disorder characterized by the dislocation of endometrial tissues. Approximately 5-20% of women at their reproductive age are diagnosed with endometriosis, which causes chronic pain and infertility. Here, we demonstrated that the bioactive flavonoid, 5,7-dimethoxyflavone (DMF), exhibited antiproliferative and apoptotic effects in VK2/E6E7 and End1/E6E7 cells which were established from vaginal and endocervical tissue taken from a premenopausal woman undergoing hysterectomy for endometriosis. DMF treatment significantly elevated DNA fragmentation resulting in apoptotic cell death in both cell lines. Furthermore, DMF induced loss of mitochondrial membrane potential, dysregulation of intracellular calcium level, and ROS production, which accelerate apoptosis. Additionally, DMF modulated the expression of the signaling molecules related to cell survival and endoplasmic reticulum stress in VK2/E6E7 and End1/E6E7 cells. Overall, DMF may ameliorate endometriosis and can be a potential alternative to hormonal and surgical therapy for endometriosis treatment.

Inhibition of the type III secretion system of Pseudomonas syringae pv. tomato DC3000 by resveratrol oligomers identified in Vitis vinifera L.

BACKGROUND: The bacterial type III secretion system (T3SS) is one of the virulence determinants of Gram-negative bacteria through which various effector and virulence proteins are translocated into host cells. RESULTS: We constructed an assay system to screen inhibitors of hrpA gene expression (a structural gene of Hrp pili) in Pseudomonas syringae pv. tomato DC3000. In a plant extract library screening, the root extract of Vitis vinifera L. displayed the most prominent activity. Three resveratrol oligomers, hopeaphenol, isohopeaphenol and ampelopsin A, were identified in grapevine root extract, which significantly reduced the transcription levels of the hrpA, hrpL and hopP1 genes without growth retardation. Additional resveratrol derivatives identified in other plant extracts were also examined for their inhibitory effect on hrpA expression. Another resveratrol oligomer, kobophenol A, also inhibited the transcription of the hrpA gene and other T3SS-related genes, while resveratrol monomers (resveratrol and piceatannol) were not effective. The severity of bacterial specks was reduced by each hopeaphenol, isohopeaphenol and ampelopsin A treatment. CONCLUSION: These results show the potential of resveratrol derivatives as anti-virulence agents for the control of plant diseases.

Lactobacillus curvatus KFP419 and Leuconostoc mesenteroides subsp. mesenteroides KDK411 Isolated from Kimchi Ameliorate Hypercholesterolemia in Rats.

Western-style diets increase the risk for cardiovascular diseases. It is suggested that the risk could be prevented by lowering cholesterol concentrations in blood. In the present study, hypocholesterolemic effects of the probiotics isolated from kimchi (Lactobacillus curvatus KFP419, Leuconostoc paramesenteroides KJP421, and Leuconostoc mesenteroide subsp. mesenteroides KDK411) were investigated in hypercholesterolemia-induced rats. There was no difference in growth performance between the rats fed high cholesterol diet (HCD) and normal diet (ND). However, blood total cholesterol, low-density lipoprotein cholesterol, and hepatic cholesterol were elevated by the HCD compared to ND, and those concentrations were decreased by dietary supplementation of KFP419 and KDK411. It was concomitant with an increase in fecal excretion of neutral sterols (cholesterol, coprostanol, and coprostanone) in the rats fed HCD compared to ND and was even greater with KDK411 supplementation. These findings indicate that probiotics L. curvatus KFP419 and L. mesenteroide subsp. mesenteroides KDK411 isolated from kimchi ameliorate hypercholesterolemia in rats by assimilating and excreting cholesterol in feces.

Persimmon vinegar and its fractions protect against alcohol-induced hepatic injury in rats through the suppression of CYP2E1 expression.

CONTEXT: Medical therapies for alcohol-induced liver disease are often difficult to handle and limited in efficacy. OBJECTIVE: In an attempt to find natural therapeutics, here, we investigate the preventive effect of persimmon vinegar (PV) and its fractions against alcohol-induced hepatic injury, in addition to the underlying mechanism, in rats chronically administered with alcohol. MATERIALS AND METHODS: Forty male Wistar rats were randomized into five groups (n = 8 per group); normal control (NC), ethanol control (EC), ethanol + PV, ethanol + water-insoluble PV fraction (PI) and ethanol + water-soluble PV fraction (PS). PV, PI or PS was orally administrated at the level of 100 mg/kg B.W by oral gavage every day for 4 weeks prior to ethanol administration. The liver sections were stained with hematoxylin & eosin and gene expression was assessed by real-time polymerase chain reaction. RESULTS: After a 4-week treatment, histological observation revealed that PV and its fractions mitigated alcohol-induced changes in the liver. CYP2E1 expression was significantly increased in the EC group compared with the NC group, but was significantly suppressed in the PV group compared with the EC group (p = 0.044). We also found significant decreases in hepatic mRNA expression of interleukin (IL)-1ß, IL-12ß, toll-like receptor (TLR)-4 and cyclooxygenase (COX)-2 in the PV-, PI- and PS-treated groups compared with those of the EC group. DISCUSSION AND CONCLUSION: Taken together, the present findings suggest that PV and its fractions hold great promise as natural remedies with anti-inflammatory activities that alleviate alcohol-induced liver damage.

Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice.

PURPOSE: Transcranial low-level light therapy (LLLT) has gained interest as a non-invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. METHODS: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. RESULTS: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF-κB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. CONCLUSIONS: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption.

Inhibitory Effects of Scolopendra Pharmacopuncture on the Development and Maintenance of Neuropathic Pain in Rats: Possible Involvement of Spinal Glial Cells.

Scolopendra extracts were used for pharmacopuncture at the Kidney 1 acupoint to investigate the role of Scolopendra pharmacopuncture (SPP) in both the development and maintenance of neuropathic pain induced by L5 spinal nerve ligation in rats and the contribution of spinal glial cells. A single treatment and five once-daily treatments with SPP were given to evaluate its effects on the development and maintenance stages of neuropathic pain, respectively, which was followed by behavioral tests. Immunohistochemistry and Western blotting tests were also carried out. A single treatment of SPP delayed spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia and induced a profound decrease in the expression of ionized calcium binding adaptor protein in the lumbar spinal cord. Repeated SPP treatments reliably suppressed mechanical allodynia and thermal hyperalgesia at later time points, and these results correlated mainly with decreases in glial fibrillary acidic protein. Intriguingly, ionized calcium binding adaptor protein expression was also reduced after repeated SPP. These results illustrate that neuropathic pain in the development and maintenance stages is alleviated by SPP treatment, which may be ascribed principally to deactivations of microglia and astroglia, respectively. Additionally, microglial inactivation seems to be partially involved in preventing neuropathic pain in the maintenance stage.

PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid ß-Induced Cognitive Deficits through Modulation of Neuroinflammation.

PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-ß-(Aß-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Aß 25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aß expression and activation of microglia and astrocytes in the Aß 25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aß-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.