Deleterious effects in reproduction and developmental immunity elicited by pulmonary iron oxide nanoparticles

With the extensive application of iron oxide nanoparticles (FeNPs), attention about their potential risks to human health is also rapidly raising, particularly in sensitive subgroups such as pregnant women and babies. In this study, we a single instilled intratracheally FeNPs (1, 2, and 4 mg/kg) to the male and female parent mice, mated, then assessed reproductive toxicity according to the modified OECD TG 421. During the pre-mating period (14 days), two female parent mice died at 4 mg/kg dose, and the body weight gain dose-dependently decreased in male and female parent mice exposed to FeNPs. Additionally, iron accumulation and the enhanced expression of MHC class II molecules were observed in the ovary and the testis of parent mice exposed to the highest dose of FeNPs, and the total sex ratio (male/female) of the offspring mice increased in the groups exposed to FeNPs. Following, we a single instilled intratracheally to their offspring mice with the same doses and evaluated the immunotoxic response on day 28. The increased mortality and significant hematological- and biochemical- changes were observed in offspring mice exposed at 4 mg/kg dose, especially in female mice. More interestingly, balance of the immune response was shifted to a different direction in male and female offspring mice. Taken together, we conclude that the NOAEL for reproductive and developmental toxicity of FeNPs may be lower than 2 mg/kg, and that female mice may show more sensitive response to FeNPs exposure than male mice. Furthermore, we suggest that further studies are necessary to identify causes of both the alteration in sex ratio of offspring mice and different immune response in male and female offspring mice.

Immune-Enhancement and Anti-Inflammatory Activities of Fatty Acids Extracted from Halocynthia aurantium Tunic in RAW264.7 Cells

Halocynthia aurantium, an edible ascidian species, has not been studied scientifically, even though tunicates and ascidians are well-known to contain several unique and biologically active materials. The current study investigated the fatty acid profiles of the H. aurantium tunic and its immune-regulatory effects on RAW264.7 macrophage cells. Results of the fatty acid profile analysis showed a difference in ratios, depending on the fatty acids being analysed, including those of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). In particular, omega-3 fatty acids, such as eicosatrienoic acid n-3 (ETA n-3), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), were much higher than omega-6 fatty acids. Moreover, the H. aurantium tunic fatty acids, significantly and dose-dependently, increased the NO and prostaglandin E2 (PGE2) production in RAW264.7 cells, for immune-enhancement without cytotoxicity. In addition, these fatty acids regulated the transcription of immune-associated genes, including iNOS, IL-1β, IL-6, COX-2, and TNF-α. These actions were activated and deactivated via Mitogen-activated protein kinase (MAPK)and NF-κB signaling, to regulate the immune responses. Conversely, the H. aurantium tunic fatty acids effectively suppressed the inflammatory cytokine expressions, including iNOS, IL-1β, IL-6, COX-2, and TNF-α, in LPS-stimulated RAW264.7 cells. Productions of COX-2 and PGE2, which are key biomarkers for inflammation, were also significantly reduced. These results elucidated the immune-enhancement and anti-inflammatory mechanisms of the H. aurantium tunic fatty acids in macrophage cells. Moreover, the H. aurantium tunic might be a potential fatty acid source for immune-modulation

Torsional and Bending Properties of v Taper 2H, ProTaper NEXT, NRT, and One Shape

Nickel-titanium (NiTi) rotary files have enabled efficient root canal preparations that maintain the canal center with fewer aberrations compared to hand files. However, NiTi rotary files are susceptible to fracture, which can thereby compromise root canal treatment. Therefore, NiTi files have been developed to enhance fracture resistance by modifying design and thermal treatment. The objective of this study was to compare the torsional fatigue resistance and bending resistance of NiTi files manufactured from different alloys and treatments. ProTaper NEXT X2 (PTN; M-wire), V taper 2H (V2H; controlled memory wire), NRT (heat-treated), and One Shape (OS; conventional alloy) instruments of tip size #25 were compared. Torsional fatigue was evaluated by embedding the 3 mm tip of each instrument (N = 10/brand) in resin and the repetitive application of torsional stress (300 rpm, 1.0 N·cm) by an endodontic motor with autostop when the file fractured. The number of loading cycles to fracture was recorded and analyzed by Kruskal-Wallis and Mann-Whitney U tests with Bonferroni\u27s correction. Bending resistance of the instruments was tested using a cantilever bending test to the 3 mm point from the tip (N = 10/brand). The stress was measured when deflection of 3 mm was subjected and statistically analyzed with a one-way analysis of variance and Tukey\u27s honest significance difference test (α = 0.05). V2H withstood the highest number of load applications during torsional fatigue testing (p\u3c0.05), followed by NRT, PTN, and OS, where the differences between NRT and PTN (p=0.035) and between PTN and OS (p=0.143) were not statistically significant. V2H showed the lowest bending stiffness, followed by NRT, PTN, and OS (p\u3c0.001). Thermal treatment of NiTi wire resulted in improved mechanical properties, and controlled memory wire provided improved flexibility and torsional fatigue resistance

The definition and diagnosis of cold hypersensitivity in the hands and feet: Finding from the experts survey

Background: Cold hypersensitivity in the hands and feet (CHHF) is a symptom patients usually feel cold in their hands and feet, but not dealt with a disease in western medicine. However, it is often appealed by patients at a clinic of Korean medicine (KM), considered to be a sort of key diagnostic indicator, and actively treated by physicians. Nevertheless, there is no standardized diagnostic definition for CHHF. Therefore, we surveyed KM experts’ opinions to address the clinical definition, diagnostic criteria, and other relevant things on CHHF. Methods: We developed a survey to assess the definition, diagnosis, causes, and accompanying symptoms on CHHF. 31 experts who work at specialized university hospitals affiliated with KM hospitals consented to participation. Experts responded to survey questions by selecting multiple-choice answers or stating their opinions. Results: Vast majority of experts (83.8%) agreed with our definition on CHHF (“a feeling of cold as a symptom; that one's hands or feet become colder than those of average people in temperatures that are not normally perceived as cold”). 77.4% of experts considered subjective symptoms on CHHF were more important than medical instrument results. Constitution or genetic factors (87.1%) and stress (64.5%) were the most common causes reported for CHHF. Conclusions: This study offers an expert consensus regarding the themes, opinions, and experiences of practitioners with CHHF. Our results underscore the need for standardized definitions and diagnostic criteria for CHHF. Keywords: Cold hypersensitivity, Cold extremities, Cold constitutio

Cancer Therapy-Related Cardiac Dysfunction in Patients Treated with a Combination of an Immune Checkpoint Inhibitor and Doxorubicin

Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global longitudinal strain (LVGLS). Methods: A total of 95 patients were included in this study. Echocardiography and LVGLS were evaluated at baseline and follow-up (at 3 and 6 months of chemotherapy) and compared with the doxorubicin (Dox; n = 73) and concomitant ICI with doxorubicin (Dox-ICI; n = 22) groups. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a left ventricular ejection fraction (LVEF) drop of >10% and LVEF of 10%, LVEF of ≥50%, and LVGLS relative reduction of >15% (probable CTRCD) at six months. Results: There were no significant differences in age, cumulative dose of doxorubicin, and cardiovascular risk factors between the two groups. At baseline, the LVEF was similar in the Dox and Dox-ICI groups (p = 0.493). In the Dox group, LVEF decreased to 59 ± 6% (Δ −7 ± 1.3%, p p p p p = 0.042). Serum troponin-T level was significantly higher in the Dox-ICI group than in the Dox group (53.3 vs. 27.5 pg/mL, p = 0.023). Conclusions: ICIs may increase the risk of CTRCD when used with cardiotoxic agents. CTRCD should be monitored in patients treated with ICIs by cardiac biomarkers and echocardiography, including LV-GLS