Protective Effect of the SIRT1-Mediated NF-κB Signaling Pathway against Necrotizing Enterocolitis in Neonatal Mice.

OBJECTIVE: To discover the mechanism of the sirtuin 1 (SIRT1)-mediated nuclear factor-κB (NF-κB) pathway in the protection against necrotizing enterocolitis (NEC) in neonatal mice. MATERIALS AND METHODS: Neonatal mice were treated with EX527 (an inhibitor of SIRT1) and/or pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB). The survival rate of the mice was recorded. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the intestines. Furthermore, western blotting, enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction were conducted to measure the protein and gene expression, while corresponding kits were used to detect the levels of oxidative stress indicators. RESULTS: PDTC increased the survival rate of NEC mice. When compared with the NEC+ EX527 + PDTC group, the histological NEC score was higher in the NEC + EX527 group but lower in the NEC + PDTC group. SIRT1 expression in the intestines of NEC mice was downregulated, with an increase in p65 nuclear translocation. Additionally, malondialdehyde increased and glutathione peroxidase decreased in the intestines of NEC mice, with the upregulation of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α, as well as the downregulation of ZO-1, occludin, and claudin-4 in the intestines. However, the above changes could be improved by PDTC, which could be further reversed by EX527. CONCLUSION: SIRT1 can mitigate inflammation and the oxidative stress response and improve intestinal permeability by mediating the NF-κB pathway, playing an important role in the alleviation of NEC.

[Variation Characteristics and Potential Sources of the Mt. Haituo Aerosol Chemical Composition in Different Pollution Processes During Winter in Beijing, China].

In order to investigate the chemical composition and source apportionment of aerosols during winter in the Beijing-Tianjin-Heibei region, the particular matter (PM) and aerosol chemical composition at Mt. Haituo were observed by using a GRIMM 180, a single-particle soot photometer (SP2), and a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS) from December 28, 2020 to February 3, 2021. Combining these observations with meteorological data and the HYSPLIT model, we calculated the potential source contribution factor (PSCF) and concentration weighted trajectory (CWT) and analyzed the temporal evolution and potential sources apportionment of PM and aerosol chemical composition under different pollution processes. The results showed that the dust storm process mainly affected PM10 and PM2.5 in Mt. Haituo during the winter and had a small impact on PM1; by contrast, haze pollution mainly affected PM1. Chemical components of aerosol accounted for 85.0% and 73.4% of PM1 on clean and haze days, respectively, but only 47.4% of PM1 in dust storm processes. NO3- was the chemical component with the largest mass concentration in haze, accounting for 25.2% of PM1; black carbon (BC) had the largest mass concentration on clean and dust storm days, accounting for 24.1% and 12.8% of PM1, respectively. The median diameters of BC were 209.7, 207.5, and 204.7 nm on clean, dust storm, and haze days, respectively. Dp/Dc was 2.15 in haze pollution, which was 1.38 and 1.39 times that on dust storm and clean days, respectively. Diurnal variations in PM and aerosol chemical components were different during the different processes. PM10 and PM2.5had high mass concentrations at night and low mass concentrations during the daytime on clean and dust storm days and had a unimodal distribution with a peak at 14:00 in haze. Diurnal variations in chemical composition had a unimodal distribution on clean days and a bimodal distribution on dust storm and haze days. The chemical compositions of the BC coating layer were different under different processes. The coating layers of BC were mainly NH4NO3, (NH4)2SO4, and organic matter on the clean, dust storm, and haze days, respectively. The distribution of potential sources of PM1 and its chemical components were different under different processes. The high-value area of the potential sources was mainly concentrated in the Beijing-Baoding-Shijiazhuang-Yangquan area in the southwestern portion of the site during dust storms and was mainly concentrated in Yanqing, Huailai, and Changping in the areas around the site during haze.

[Evolution and Potential Source Apportionment of Atmospheric Pollutants of Two Heavy Haze Episodes During the COVID-19 Lockdown in Beijing, China].

To control the spread of the 2019 novel coronavirus(COVID-19), China imposed rigorous restrictions, which resulted in great reductions in pollutant emissions. However, two heavy haze pollution episodes still occurred in Beijing. In this study, we use the air pollutants, aerosol number concentration, and meteorological elements data in Beijing, combined with the HYSPLIT model, to calculate the potential source contribution factor(PSCF) and concentration weight trajectory(CWT), and analyze the characteristics of evolution and potential source apportionment of atmospheric pollutants during the two episodes. The COVID-19 lockdown restrictions had great impacts on the diurnal variations of PM2.5 and black carbon(BC), while small impacts on the diurnal variations of CO, NO2, SO2, and O3. The primary pollutant was PM2.5 during the two haze pollution episodes, and the haze1 episode was mainly local pollution, while haze 2 was mainly local and external transportation pollution. The spectrum of aerosol number concentration was unimodal under different processes, with the peak located at 0.3 µm. During the haze episodes, the number concentration in the size range of 0.2-0.5 µm increased 3.3-13.6 times that of the clean days. The mass concentration contributions of BCliquid to BC in different processes were 64.8%-85.1%. This mass concentration of BCliquid ranked in the order of haze 1(5.04 µg·m-3) >haze 1(3.20 µg·m-3) >clean day(before COVID-19) (2.31 µg·m-3) >clean day(COVID-19) (0.76 µg·m-3). The characteristics of PSCF and CWT distribution of PM2.5 and BC were different in different processes. The PSCF high value areas of PM2.5 on the clean day(before COVID-19) and the clean day(COVID-19) were mainly distributed in the southwest and western of Beijing, and the weight concentration exceeded 30 µg·m-3. The PSCF high value areas of PM2.5 during haze 1 and haze 2 were mainly distributed in Beijing and its surrounding areas and southwestern, when the weight concentration exceeded 90 µg·m-3. The PSCF high value areas of BC were mainly distributed in Beijing and its surrounding areas on clean days(before COVID-19), clean days(COVID-19) and haze 1, with weighted concentrations exceeding 2.4, 0.9 and, 4.5 µg·m-3, respectively. The PSCF high value areas of BC on haze 2 was distributed in the southwest of Beijing, and the weight concentration exceeded 5 µg·m-3.

Incidence of infectious complications is associated with a high mortality in patients with hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND: In China, hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most common liver failure characterized by serious clinical syndromes of liver decompensation with a very high mortality. Bacterial and/or fungal infections are the most common complications that are associated with high short-term mortality. Bacterial translocation from the intestine, impaired hepatic clearance, and immune paralysis of circulating immune cells are thought to contribute to infectious complications in liver failure. The control of bacterial and fungal infections is the key to improving HBV-ACLF outcomes. Active prevention, early diagnosis, and timely treatment of bacterial and fungal infections are essential for treating HBV-ACLF. AIM: To investigate the frequency and role of bacterial and fungal infections in patients with HBV-ACLF. METHODS: Patients with HBV-ACLF hospitalized at Taihe Hospital, Hubei University of Medicine from January 2014 to December 2017 were retrospectively enrolled. Patient-related information was retrieved from the hospital case database, including general information, blood biochemistry, complications, etc. According to the occurrence of secondary infection or not, the patients were divided into an infection group and a non-infection group. The sites, types, and incidences of bacterial and fungal infections and the influence of infections on the prognosis of HBV-ACLF were statistically analyzed. The risk factors for infections were assessed by unconditional logistic regression. RESULTS: There were 174 cases of HBV-ACLF that met the enrollment criteria, of which 114 (65.52%) were diagnosed with infectious complications. Infections occurred in the abdominal cavity (87 cases), respiratory tract (51 cases), urinary tract (18 cases), and biliary tract (10 cases). Patients with infectious complications had a significantly higher 28-d mortality (70.18%, 80/114) than those without (40.00%, 24/60) (70.18% vs 40.00%, P < 0.05). And patients with infectious complications had a much higher incidence of non-infectious complications (54.39%, 62/114) (54.39% vs 15.00%, P < 0.05), leading to an extremely high 28-d mortality of 88.71% (55/62) (P < 0.05). The grade of liver failure, period of hospital stay ≥ 30 d, age ≥ 45 years, and percentage of neutrophils > 70% were identified as risk factors for infectious complications. CONCLUSION: The high incidence of infectious complications in patients with HBV-ACLF is associated with severity and deterioration of the disease and may contribute to the extremely high mortality of these patients.

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1ß, IL-6) and profibrogenic cytokines (TGF-ß1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

Effect of Bmi-1-mediated NF-κB signaling pathway on the stem-like properties of CD133+ human liver cancer cells.

OBJECTIVE: To investigate the impact of Bmi-1-mediated NF-κB pathway on the biological characteristics of CD133+ liver cancer stem cells (LCSCs). METHODS: Flow cytometry was used to isolate CD133+ LCSC cells from Huh7, Hep3B, SK-hep1, and PLC/PRF-5 cells. CD133+ Huh7 cells were divided into Control, Blank, Bmi-1 siRNA, JSH-23 (NF-κB pathway inhibitor), and Bmi-1 + JSH-23 groups. The properties of CD133+ Huh7 cells were detected by the colony-formation and sphere-forming assays. Besides, Transwell assay was applied for the measurement of cell invasion and migration, immunofluorescence staining for the detection of NF-κB p65 nuclear translocation, and qRT-PCR and Western blotting for the determination of SOX2, NANOG, OCT4, Bmi-1, and NF-κB p65 expression. RESULTS: CD133+ Huh-7 cells were chosen as the experiment subjects after flow cytometry. Compared with CD133- Huh-7 cells, the expression of CD133, OCT4, SOX2, NANOG, Bmi-1, and NF-κB p65, the nuclear translocation of NF-κB p65, the number of cell colonies and Sphere formation, as well as the abilities of invasion and migration were observed to be increased in CD133+ Huh-7 cells, which was inhibited after treated with Bmi-1 siRNA or JSH-23, meanwhile, the cell cycle was arrested at the G0/G1 and S phases with apparently enhanced cell apoptosis. Importantly, no significant differences in the biological characteristics of CD133 + Huh-7 cells were found between the Blank group and Bmi-1 + JSH-23 group. CONCLUSION: Down-regulating Bmi-1 may inhibit the biological properties of CD133+ LCSC by blocking NF-κB signaling pathway, which lays a scientific foundation for the clinical treatment of liver cancer.