Objective The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging.Methods First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism.Results In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1.Conclusion Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.
Objective To investigate the baseline levels of microorganisms' growth on the hands of anesthesiologists and in the anesthesia environment at a cancer hospital.Methods This study performed in nine operating rooms and among 25 anesthesiologists at a cancer hospital. Sampling of the hands of anesthesiologists and the anesthesia environment was performed at a ready-to-use operating room before patient contact began and after decontamination.Results Microorganisms' growth results showed that 20% (5/25) of anesthesiologists’ hands carried microorganisms (> 10 CFU/cm2) before patient contact began. Female anesthesiologists performed hand hygiene better than did their male counterparts, with fewer CFUs (P = 0.0069) and fewer species (P = 0.0202). Our study also found that 55.6% (5/9) of ready-to-use operating rooms carried microorganisms (> 5 CFU/cm2). Microorganisms regrowth began quickly (1 hour) after disinfection, and increased gradually over time, reaching the threshold at 4 hours after disinfection. Staphylococcus aureus was isolated from the hands of 20% (5/25) of anesthesiologists and 33.3% (3/9) of operating rooms.Conclusion Our study indicates that male anesthesiologists need to pay more attention to the standard operating procedures and effect evaluation of hand hygiene, daily cleaning rate of the operating room may be insufficient, and we would suggest that there should be a repeat cleaning every four hours.
Objective We aimed to clarify the association between estimated pulse wave velocity (ePWV) and the changes in ePWV with all-cause mortality among middle-aged and elderly Chinese.Methods Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011–2018. The ePWV was calculated using an equation that included age and mean blood pressure (MBP). The ΔePWV was assessed as the difference in ePWV between the first two waves. Cox proportional hazard models were used to determine the association between ePWV and ΔePWV with all-cause mortality after adjustment for potential confounders.Results Of 13,116 participants during a median follow-up of 7.0 years, 1,356 deaths occurred. An increased ePWV was independently associated with all-cause mortality. The hazard ratio [95% confidence interval (CI)] for participants from the 1st–4th quartile groups was 1.00, 1.69 (1.31–2.18), 3.09 (2.44–3.91), and 8.54 (6.78–10.75), respectively. Each standard deviation (SD) increment of ePWV increased the risk of all-cause mortality by 132%. Furthermore, the ΔePWV was significantly associated with a 1.28-fold (95% CI, 1.18–1.38) risk of all-cause mortality per SD increment.Conclusion This cohort study provided novel evidence from a Chinese population that an increased ePWV or progression of the ePWV was independently associated with all-cause mortality, which highlighted the importance of mitigating ePWV progression in clinical practice.
Objective The Guanzhong Plain of Shaanxi Province is a severely afflicted hemorrhagic fever with renal syndrome (HFRS) epidemic area, while HFRS prevalence has decreased in most epidemic areas in China. Little information is available regarding the leading fine-scale influencing factors in this highly HFRS-concentrated area and the roles of natural environmental and socioeconomic factors. To investigate this, two regions in the Guanzhong Plain, that is, the Chang’an District and Hu County, with similar geographical environments, different levels of economic development, and high epidemic prevalence, were chosen as representative areas of the HFRS epidemic. Methods Maximum entropy models were constructed based on HFRS cases and fine-scale influencing factors, including meteorological, natural environmental, and socioeconomic factors, from 2014 to 2016. Results More than 95% of the HFRS cases in the study area were located in the northern plains, which has an altitude of less than 800 m, with topography contributed 84.1% of the impact on the spatial differentiation of the HFRS epidemic. In the northern plains, precipitation and population density jointly affected the spatial differentiation of the HFRS epidemic, with contribution rates of 60.7% and 28.0%, respectively. By comparing the influencing factors of the northern plains of Chang’an District and Hu County, we found that precipitation and the normalized difference vegetation index (NDVI) dominated the HFRS epidemic in the relatively developed Chang'an District, while land-use type, temperature, precipitation and population density dominated the HFRS epidemic in the relatively undeveloped Hu County. Conclusion Topography was the primary key factor for HFRS prevalence in the Chang’an District and Hu County, and the spatial differentiation of HFRS was dominated by precipitation and population density in the northern plains. Compared with the influencing factors of the relatively developed Chang’an District, the developing Hu County was more affected by socioeconomic factors. When formulating targeted HFRS epidemic prevention and control strategies in the targeted areas, it is crucial to consider the local economic development state and combine natural environmental factors, including the meteorological environment and vegetation coverage.
Objective This study was designed to provide the evidences on the toxicokinetics of microplastics (MPs) and nanoplastics (NPs) in the bodies of mammals.Methods 100 nm, 3 μm, and 10 μm fluorescent polystyrene (PS) beads were administered to mice once by gavage at a dose of 200 mg/kg body weight. The levels and change of fluorescence intensity in samples of blood, subcutaneous fat, perirenal fat, peritesticular fat, cerebrum, cerebellum, testis, and epididymis were measured at 0.5, 1, 2, and 4 h after administration using an IVIS Spectrum small-animal imaging system. Histological examination, confocal laser scanning, and transmission electron microscope were performed to corroborate the findings.Results After confirming fluorescent dye leaching and impact of pH value, increased levels of fluorescence intensity in blood, all adipose tissues examined, cerebrum, cerebellum, and testis were measured in the 100 nm group, but not in the 3 and 10 μm groups except in the cerebellum and testis at 4 h for the 3 μm PS beads. The presence of PS beads was further corroborated.Conclusion After a single oral exposure, NPs are absorbed rapidly in the blood, accumulate in adipose tissues, and penetrate the blood-brain/testis barriers. As expected, the toxicokinetics of MPs is significantly size-dependent in mammals.
Objective The effect of oral cadmium (Cd) intake to influence contact skin allergies was examined, since it is known that Cd is a heavy metal that affects many tissues, including the skin, in which it disturbs homeostasis, thus resulting in inflammation and injury. Methods Male rats were evoked with experimental contact hypersensitivity reaction (CHS) to hapten dinitrochlorobenzene (DNCB), after prolonged (30 day) oral exposure to an environmentally relevant Cd dose (5 ppm). The ear cell population was analyzed with flow cytometry. Cytokine production by ear skin cells and the activity of skin-draining lymph node (DLN) cells were measured using enzyme-linked immunosorbent assay (ELISA). Results Orally acquired Cd (5 ppm) increased CHS intensity only in Dark Agouti (DA) rats by affecting inflammatory responses in both the sensitization (an increase of IFN-γ and IL-17 cytokine production) and challenge (an increase of CD8+ and CD4+ cell number and TNF, IFN-γ and IL-17 cytokine production) phases. An increased CHS reaction was seen in Albino Oxford (AO) rats only at a high Cd dose (50 ppm), during the challenge phase (an increase of CD8+ and CD4+ cell number and TNF, IFN-γ and IL-17 cytokine production). Conclusion These novel data indicate that oral Cd intensifies the skin response to sensitizing chemicals such as DNCB.
Objective Vitamin D and Toll-like receptor-4 (TLR-4) inhibition are involved in the protection of keratinocytes. The effects of combination of 1,25(OH)2D3 and TLR-4 inhibitor on the protection of keratinocytes against ultraviolet radiation B (UVB) irradiation remain unclear. This study was undertaken to explore the effects of combination of 1,25(OH)2D3 and TAK-242 (TLR-4 inhibitor) on the damage to HaCaT cells caused by UVB irradiation. Methods In vitro, HaCaT cells were treated with 1,25(OH)2D3 or/and TAK-242 prior to UVB irradiation at the intensity of 20 mJ/cm2, then the production of reactive oxygen species (ROS), cell migration, apoptosis of cells, and the expression of oxidative stress, endoplasmic reticulum stress, and apoptosis related proteins were determined. Results Compared with the HaCaT cells treated with 1,25(OH)2D3 or TAK-242, the cells treated with both 1,25(OH)2D3 and TAK-242 showed, 1) significantly lower production of ROS (P < 0.05); 2) significantly less apoptosis of HaCaT cells (P < 0.05); 3) significantly lower expression of NF-κB, Caspase-8, Cyto-C, Caspase-3 (P < 0.05). Conclusion The combination of 1,25(OH)2D3 and TAK-242 could produce a better protection for HaCaT cells via inhibiting the oxidative stress, endoplasmic reticulum stress and apoptosis than 1,25(OH)2D3 or TAK-242 alone.
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