BACKGROUND: Flecainide is an antiarrhythmic agent that is used primarily in the treatment of cardiac arrhythmias. Some evidences also suggest that flecainide can participate in alveolar fluid clearance and inflammatory responses. This experiment was aimed to evaluate the effects of flecainide on sepsis induced acute lung injury in a rat model. METHODS: Rats were treated with subcutaneous infusion of saline or flecainide (0.1 or 0.2 mg/kg/hr) by a mini-osmotic pump. Subcutaneous infusion was started 3 hours before and continued until 8 hours after intraperitoneal injection of saline or endotoxin. Animals were sacrificed for analyses of severity of acute lung injury with wet to dry (W/D) ratio and lung injury score (LIS) in lung and inflammatory responses with level of leukocyte, polymorphonuclear neutrophils (PMNs) and inteleukin-8 (IL-8) in bronchoalveolar lavages fluid (BALF). RESULTS: Flecainide markedly improved dose dependently sepsis induced acute lung injury as analysed by W/D ratio (from 2.24 ± 0.11 to 1.76 ± 0.09, p < 0.05) and LIS (from 3 to 1, p < 0.05), and inflammatory response as determined by leukocyte (from 443 ± 127 to 229 ± 95, p < 0.05), PMNs (from 41.43 ± 17.63 to 2.43 ± 2.61, p < 0.05) and IL-8 (from 95.00 ± 15.28 to 40.00 ± 10.21, p < 0.05) in BALF. CONCLUSIONS: Flecanide improve sepsis induced acute lung injury in rats by controlling inflammatory responses.
Acute Lung Injury* ; Animals ; Arrhythmias, Cardiac ; Bronchoalveolar Lavage ; Flecainide* ; Infusions, Subcutaneous ; Injections, Intraperitoneal ; Interleukin-8 ; Leukocytes ; Lung ; Lung Injury ; Models, Animal ; Neutrophils ; Rats ; Sepsis*

The heterogeneity of cancer makes it difficult to predict the prognosis of treatment. There is still a lack of preclinical model systems that reflect the clinical characteristics of patients who have heterogenetic tumors. Advances in 3-dimentional (3D) cell culture are leading to discoveries that occur in the development and progression of cancer that has not been known. There are many models including patient-derived xenograft, patient-derived organoid and spheroid, patient-derived explant, scaffold-based model, and system-based model. Each 3D model has its strengths and limitations. One model cannot answer every question, so it seems most reasonable to approach multiple models when studying cancer heterogeneity. Hopefully, 3D tumor modeling will make tremendous progress on this path by fusion of innovative biomaterials and advanced modeling techniques that can partially mimic the heterogeneous environment of real tumors.

No abstract available.
Hyalin* ; Salivary Glands*

BACKGROUND/OBJECTIVES: This study was performed to investigate the in vitro antioxidant and cytoprotective effects of fermented sesame sauce (FSeS) against hydrogen peroxide (H2O2)-induced oxidative damage in renal proximal tubule LLC-PK1 cells. MATERIALS/METHODS: 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical (*OH), and H2O2 scavenging assay was used to evaluate the in vitro antioxidant activity of FSeS. To investigate the cytoprotective effect of FSeS against H2O2-induced oxidative damage in LLC-PK1 cells, the cellular levels of reactive oxygen species (ROS), lipid peroxidation, and endogenous antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) were measured. RESULTS: The ability of FSeS to scavenge DPPH, *OH and H2O2 was greater than that of FSS and AHSS. FSeS also significantly inhibited H2O2-induced (500 microM) oxidative damage in the LLC-PK1 cells compared to FSS and AHSS (P < 0.05). Following treatment with 100 microg/mL of FSeS and FSS to prevent H2O2-induced oxidation, cell viability increased from 56.7% (control) to 83.7% and 75.6%, respectively. However, AHSS was not able to reduce H2O2-induced cell damage (viability of the AHSS-treated cells was 54.6%). FSeS more effectively suppressed H2O2-induced ROS generation and lipid peroxidation compared to FSS and AHSS (P < 0.05). Compared to the other sauces, FSeS also significantly increased cellular CAT, SOD, and GSH-px activities and mRNA expression (P < 0.05). CONCULUSIONS: These results from the present study suggest that FSeS is an effective radical scavenger and protects against H2O2-induced oxidative damage in LLC-PK1 cells by reducing ROS levels, inhibiting lipid peroxidation, and stimulating antioxidant enzyme activity.
Animals ; Catalase ; Cats ; Cell Survival ; Glutathione Peroxidase ; Hydrogen Peroxide ; Hydrogen* ; Hydroxyl Radical ; Lipid Peroxidation ; LLC-PK1 Cells ; Oxidative Stress ; Reactive Oxygen Species ; RNA, Messenger ; Sesamum* ; Superoxide Dismutase ; Swine

Background: Some working conditions may pose a higher physical or psychological demand to pregnant women leading to increased risks of pregnancy complications. Objectives: We assessed the association of woman's employment status and the industrial classification with obstetric complications. Methods: We conducted a national population study using the National Health Information Service database of Republic of Korea. Our analysis encompassed 1,316,310 women who experienced first-order live births in 2010–2019. We collected data on the employment status and the industrial classification of women, as well as their diagnoses of preeclampsia (PE) and gestational diabetes mellitus (GDM) classified as A1 (well controlled by diet) or A2 (requiring medication). We calculated odds ratios (aORs) of complications per employment, and each industrial classification was adjusted for individual risk factors. Results: Most (64.7%) were in employment during pregnancy. Manufacturing (16.4%) and the health and social (16.2%) work represented the most prevalent industries. The health and social work exhibited a higher risk of PE (aOR = 1.11, 95% confidence interval [CI]: 1.03–1.21), while the manufacturing industry demonstrated a higher risk of class A2 GDM (1.20, 95% CI: 1.03–1.41) than financial intermediation. When analyzing both classes of GDM, women who worked in public administration and defense/social security showed higher risk of class A1 GDM (1.04, 95% CI: 1.01, 1.07). When comparing high-risk industries with nonemployment, the health and social work showed a comparable risk of PE (1.02, 95% CI: 0.97, 1.07). Conclusion Employment was associated with overall lower risks of obstetric complications. Health and social service work can counteract the healthy worker effect in relation to PE. This highlights the importance of further elucidating specific occupational risk factors within the high-risk industries.

The aim of study was to explore the effect of mesenchymal stem cells (MSC) transfected with recombinant adenovirus-mediated human vascular endothelium growth factor 165 (ad-vegf-165) on treating ischemic necrosis limbs. Adult SD rats were selected for study. Limb ischemic necrosis model was established by right femoral artery ligation in SD rats. 7 days after ligation, MSC, ad-h-vegf-165-MSC and ad-LacZ-MSC labelled by DAPI were injected into ischemic necrosis limb in rats respectively. One week after injection, the expression of VEGF in ischemic necrosis limbs was detected by Western blot. And at 1, 2 or 4 weeks after injection, the expressions of FVIII and myosin on MSC were evaluated by immunohistochemistry. The results indicated that the MSC labelled by DAPI could be found in the transplantation site of ischemic necrosis limbs under fluorescent microscope. And the number of MSC in MSC-vegf group was more than that in MSC and MSC-LacZ groups. The VEGF expression in MSC-vegf group was higher than that in MSC and MSC-LacZ groups. More importantly, the number of endothelial cells demonstrated characteristic FVIII positive MSC in MSC-vegf group was more than that in MSC and MSC-LacZ group after injections of 1, 2 and 4 weeks. However, the number of myosin positive MSC among MSC-vegf, MSC and MSC-LacZ groups showed no significant difference. It is concluded that MSC transfected with Ad-vegf promotes angiogenesis to repair ischemic necrosis limbs through the increased expression of VEGF.
Adenoviridae ; genetics ; Animals ; Hindlimb ; blood supply ; Humans ; Ischemia ; pathology ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Necrosis ; Neovascularization, Physiologic ; genetics ; Rats ; Rats, Sprague-Dawley ; Transfection ; Vascular Endothelial Growth Factor A ; genetics

Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging eff ect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral defi cits on the rotarod test were signifi cantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant eff ect and can be used as a potential therapeutic agent against HD.
Animals ; Astrocytes ; Body Weight ; Cell Death ; Dimethyl Sulfoxide ; Glial Fibrillary Acidic Protein ; Humans ; Huntington Disease ; Male ; Mice ; Microglia ; Models, Chemical ; Mortality ; Neurons ; Neuroprotective Agents* ; Rotarod Performance Test ; Urticaria

OBJECTIVES: Limited evidence is available regarding the impact of paternal occupation and its combined effect with maternal occupation on preterm birth. Therefore, we assessed the association of maternal and paternal occupations with preterm birth. METHODS: We used the national birth data of Korea between 2010 and 2020. Parental occupations were divided into 5 categories: (1) managers; (2) professionals, technicians, and related workers; (3) clerks and support workers; (4) service and sales workers; and (5) manual workers. A multinomial logistic regression model was used to calculate the adjusted odds ratios (aORs) of extremely, very, and moderate-to-late preterm births per occupational category considering individual risk factors. RESULTS: For the 4,004,976 singleton births, 40.2% of mothers and 95.5% of fathers were employed. Compared to non-employment, employment was associated with a lower risk of preterm birth. Among employed mothers, service and sales occupations were associated with a higher risk of preterm birth than managerial occupations (aOR, 1.06; 95% confidence interval [CI], 1.01 to 1.10 for moderate-to-late preterm births). The father’s manual occupation was associated with a higher risk of preterm birth (aOR, 1.09; 95% CI, 1.05 to 1.13 for moderate-to-late preterm) than managerial occupations. When both parents had high-risk occupations, the risk of preterm birth was higher than in cases where only the mother or neither of the parents had a high-risk occupation. CONCLUSIONS Paternal occupation was associated with preterm birth regardless of maternal employment and occupation and modified the effect of maternal occupation. Detailed occupational environment data are needed to identify the paternal exposures that increase the risk.

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by CCl4 treatment to the control level. Hepatic injury induced by CCl4 was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by CCl4.
Alkanes ; Animals ; Antioxidant Response Elements ; Carbon ; Carbon Tetrachloride ; Chrysanthemum ; Glutathione Transferase ; Kidney ; Liver ; Luciferases ; Methanol ; Mice ; NAD(P)H Dehydrogenase (Quinone) ; Stomach ; Transcriptional Activation