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"Li, Li-Sha"
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Cyanate Induces Oxidative Stress Injury and Abnormal Lipid Metabolism in Liver through Nrf2/HO-1
Chronic kidney disease (CKD) is problem that has become one of the major issues affecting public health. Extensive clinical data suggests that the prevalence of hyperlipidemia in CKD patients is significantly higher than in the general population. Lipid metabolism disorders can damage the renal parenchyma and promote the occurrence of cardiovascular disease (CVD). Cyanate is a uremic toxin that has attracted widespread attention in recent years. Usually, 0.8% of the molar concentration of urea is converted into cyanate, while myeloperoxidase (MPO) catalyzes the oxidation of thiocyanate to produce cyanate at the site of inflammation during smoking, inflammation, or exposure to environmental pollution. One of the important physiological functions of cyanate is protein carbonylation, a non-enzymatic post-translational protein modification. Carbamylation reactions on proteins are capable of irreversibly changing protein structure and function, resulting in pathologic molecular and cellular responses. In addition, recent studies have shown that cyanate can directly damage vascular tissue by producing large amounts of reactive oxygen species (ROS). Oxidative stress leads to the disorder of liver lipid metabolism, which is also an important mechanism leading to cirrhosis and liver fibrosis. However, the influence of cyanate on liver has remained unclear. In this research, we explored the effects of cyanate on the oxidative stress injury and abnormal lipid metabolism in mice and HL-7702 cells. In results, cyanate induced hyperlipidemia and oxidative stress by influencing the content of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), catalase (CAT) in liver. Cyanate inhibited NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the phosphorylation of adenosine 5′monophosphate-activated protein kinase (AMPK), activated the mTOR pathway. Oxidative stress on the cells reduced significantly by treating with TBHQ, an antioxidant, which is also an activator of Nrf2. The activity of Nrf2 was rehabilitated and phosphorylation of mTOR decreased. In conclusion, cyanate could induce oxidative stress damage and lipid deposition by inhibiting Nrf2/HO-1 pathway, which was rescued by inhibitor of Nrf2.
Journal Article
Numerical Simulation of Contact Explosion on Reinforced Concrete Slabs Based on Different Algorithms
The explosion dynamics process is complex and difficult to carry out accurate analytical analysis. Numerical simulation with controllable boundary conditions and initial conditions can continuously and repeatedly display the explosion development process over time. In this paper, we take a single‐layer reinforced concrete slab contact explosion as an example and use Lagrange method, Arbitrary Lagrangian–Eulerian (ALE) method, and smoothed particle hydrodynamics (SPH) method in LS‐DYNA software to simulate the explosion of explosives. The results show that Lagrange method can display a clear material interface, but the explosives elements in the simulation of explosion process could cause serious distortion easily leading to the termination of the calculation; the explosives and air in the ALE method are Eulerian materials, there is no element distortion, but the number of the explosives and air elements that need to be established is relatively large; SPH algorithm can simulate the large deformations caused by explosion, making it more realistic in simulating the splashing of explosive materials. In the comparison of three algorithms, the ALE algorithm matches the experimental results the best.
Journal Article
The Association Between Intestinal Bacteria and Allergic Diseases—Cause or Consequence?
The incidence of allergic disorders has been increasing over the past few decades, especially in industrialized countries. Allergies can affect people of any age. The pathogenesis of allergic diseases is complex and involves genetic, epigenetic, and environmental factors, and the response to medication is very variable. For some patients, avoidance is the sole effective therapy, and only when the triggers are identifiable. In recent years, the intestinal microbiota has emerged as a significant contributor to the development of allergic diseases. However, the precise mechanisms related to the effects of the microbiome on the pathogenesis of allergic diseases are unknown. This review summarizes the recent association between allergic disorders and intestinal bacterial dysbiosis, describes the function of gut microbes in allergic disease development from both preclinical and clinical studies, discusses the factors that influence gut microbial diversity and advanced techniques used in microbial analysis. Ultimately, more studies are required to define the host-microbial relationship relevant to allergic disorders and amenable to new therapeutic interventions.
Journal Article
Mechanical force modulates periodontal ligament stem cell characteristics during bone remodelling via TRPV4
Objectives Mechanical force plays an important role in modulating stem cell fate and behaviours. However, how periodontal ligament stem cells (PDLSCs) perceive mechanical stimulus and transfer it into biological signals, and thereby promote alveolar bone remodelling, is unclear. Materials and Methods An animal model of force‐induced tooth movement and a compressive force in vitro was used. After force application, tooth movement distance, mesenchymal stem cell and osteoclast number, and proinflammatory cytokine expression were detected in periodontal tissues. Then, rat primary PDLSCs with or without force loading were isolated, and their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation and immunoregulatory properties were evaluated. Under compressive force in vitro, the effects of the ERK signalling pathway on PDLSC characteristics were evaluated by Western blotting. Results Mechanical force in vivo induced PDLSC proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation; the force‐stimulated PDLSCs showed greater clonogenicity and proliferation, reduced differentiation ability, improved induction of macrophage migration, osteoclast differentiation and proinflammatory factor expression. The biological changes induced by mechanical force could be partially suppressed by TRPV4 inhibition. Mechanistically, force‐induced activation of TRPV4 in PDLSCs regulated osteoclast differentiation by affecting the RANKL/OPG system via ERK signalling. Conclusions Taken together, we show here that TRPV4 activation in PDLSCs under mechanical force contributes to changing their stem cell characteristics and modulates bone remodelling during tooth movement. Mechanical force in vivo induced periodontal ligament stem cell proliferation, which was accompanied with inflammatory cytokine accumulation, osteoclast differentiation and TRPV4 activation. The activation of TRPV4 in PDLSCs under mechanical force contributes to the changes in their stem cell characteristics including clonogenicity, proliferation, multipotent differentiation, and immunoregulation and modulates bone remodelling during tooth movement.
Journal Article
Circulating Level of Neutrophil Extracellular Traps Is Not a Useful Biomarker for Assessing Disease Activity in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA. The activity of DNase I was quantified using radial enzyme-diffusion method. Associations between circulating levels of NETs with clinico-pathological parameters were analyzed. Serum levels of NETs in active AAV patients were significantly higher than those in healthy controls, and the level of cell free DNA correlated with C-reactive protein (CRP). However, no correlation was found between MPO-DNA complexes or cit-H3-DNA complexes level and CRP. Also there was no significant correlation between NETs level and initial serum creatinine, estimated glomerular filtration rate (eGFR), crescents formation or Birmingham Vasculitis Activity Score (BVAS). Furthermore, there was no significant difference of serum levels of cell free DNA or MPO-DNA complexes between active stage and remission of AAV. In conclusion, circulating levels of NETs cannot be used as a biomarker to assess disease activity in AAV patients.
Journal Article
Mid-Upper Arm Circumference as an Alternative Screening Instrument to Appendicular Skeletal Muscle Mass Index for Diagnosing Sarcopenia
Mid-upper arm circumference (MUAC) is a simple, noninvasive anthropometric indicator. This study evaluated the applicability of MUAC as an alternative screening instrument to appendicular skeletal muscle mass index (ASMI) for detecting sarcopenia, and determined the optimal MUAC cutoff values.
A total of 4509 subjects ≥50 years of age from the West China Health and Aging Trend study were included in the present study. ASM was measured by bioelectrical impedance analysis. MUAC, calf circumference (CC), and grip strength were evaluated and the Short Physical Performance Battery and 3-m timed up-and-go test were administered. Low muscle mass was diagnosed based on Asian Working Group for Sarcopenia 2019 (AWGS2019) and updated European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria.
ASMI was positively correlated with MUAC in both men (r=0.726, P<0.001) and women (r=0.698, P<0.001). The area under the receiver operating characteristic curve (AUC) for MUAC as an indicator of low muscle mass in men and women was 0.86 (95% confidence interval [CI]: 0.85-0.88) and 0.85 (95% CI: 0.84-0.86), respectively, according to AWGS2019 criteria; and 0.86 (95% CI: 0.85-0.88) and 0.86 (95% CI: 0.85-0.88), respectively, according to EWGSOP2 criteria. Optimal MUAC cutoff values for predicting low muscle mass were ≤28.6 cm for men and ≤27.5 cm for women. There was no significant difference between the AUCs of MUAC and CC in men according to the 2 reference standards (P=0.809), whereas the AUC of CC was superior to that of MUAC in women according to AWGS2019 (P<0.001) and EWGSOP2 (P=0.008) criteria.
MUAC is strongly correlated with ASMI among community-dwelling middle-aged and older adults in China. MUAC can be used as a simple screening instrument to ASMI for diagnosing sarcopenia, especially in men.
Journal Article
Causal relationship between obesity, lifestyle factors and risk of benign prostatic hyperplasia: a univariable and multivariable Mendelian randomization study
Background
Obesity (waist circumference, body mass index (BMI)) and lifestyle factors (dietary habits, smoking, alcohol drinking, Sedentary behavior) have been associated with risk of benign prostatic hyperplasia (BPH) in observational studies, but whether these associations are causal is unclear.
Methods
We performed a univariable and multivariable Mendelian randomization study to evaluate these associations. Genetic instruments associated with exposures at the genome-wide significance level (
P
< 5 × 10
–8
) were selected from corresponding genome-wide associations studies (n = 216,590 to 1,232,091 individuals). Summary-level data for BPH were obtained from the UK Biobank (14,126 cases and 169,762 non-cases) and FinnGen consortium (13,118 cases and 72,799 non-cases). Results from UK Biobank and FinnGen consortium were combined using fixed-effect meta-analysis.
Results
The combined odds ratios (ORs) of BPH were 1.24 (95% confidence interval (CI), 1.07–1.43,
P
= 0.0045), 1.08 (95% CI 1.01–1.17,
P
= 0.0175), 0.94 (95% CI 0.67–1.30,
P
= 0.6891), 1.29 (95% CI 0.88–1.89,
P
= 0.1922), 1.23 (95% CI 0.85–1.78,
P
= 0.2623), and 1.04 (95% CI 0.76–1.42,
P
= 0.8165) for one standard deviation (SD) increase in waist circumference, BMI, and relative carbohydrate, fat, protein and sugar intake, 1.05 (95% CI 0.92–1.20,
P
= 0.4581) for one SD increase in prevalence of smoking initiation, 1.10 (95% CI 0.96–1.26,
P
= 0.1725) and 0.84 (95% CI 0.69–1.02,
P
= 0.0741) for one SD increase of log-transformed smoking per day and drinks per week, and 1.31 (95% CI 1.08–1.58,
P
= 0.0051) for one SD increase in sedentary behavior. Genetically predicted waist circumference (OR = 1.26, 95% CI 1.11–1.43,
P
= 0.0004) and sedentary behavior (OR = 1.14, 95% CI 1.05–1.23,
P
= 0.0021) were associated with BPH after the adjustment of BMI.
Conclusion
This study supports independent causal roles of high waist circumference, BMI and sedentary behavior in BPH.
Journal Article
Early transcriptomic profiling variation caused by cluster allergen immunotherapy
Laboratory tests showed a positive intradermal test for Artemisia pollen (Allergen extract preparation room, Peking Union Medical College Hospital, Beijing, China) and a serum specific immunoglobulin E (sIgE) against Artemisia pollen of 5.61 kUA/L (ImmunoCAP, Thermo Fisher Scientific, Waltham, MA, USA). For the down-regulated genes, the top five most enriched pathways were cilium assembly, SUMOylation of ubiquitination proteins, DNA repair, synthesis of plasma membrane intrinsic proteins at the plasma membrane, and low-density lipoprotein clearance [Supplementary Figure 1B, http://links.lww.com/CM9/A226]. Yang et al[4] reported that the co-administration of Galectin-1 and allergen immunotherapy significantly inhibited allergic responses in the mouse intestine by suppressing mast cell activation and facilitating Treg development.
Journal Article
Flexible Asymmetric Supercapacitors Constructed by Reduced Graphene Oxide/MoO3 and MnO2 Electrochemically Deposited on Carbon Cloth
A flexible asymmetric supercapacitor (ASC) is successfully developed by using the composite of MoO3 and graphene oxide (GO) electrochemically deposited on carbon cloth (CC) (MoO3/rGO/CC) as the cathode, the MnO2 deposited on CC (MnO2/CC) as the anode, and Na2SO4/polyvinyl alcohol (PVA) as the gel electrolyte. The results show that the introduction of the GO layer can remarkably increase the specific capacitance of MoO3 from 282.7 F g−1 to 341.0 F g−1. Furthermore, the combination of such good electrode materials and a neutral gel electrolyte renders the fabrication of high-performance ASC with a large operating potential difference of 1.6 V in a 0.5 mol L−1 Na2SO4 solution of water. Furthermore, the ASCs exhibit excellent cycle ability and the capacitance can maintain 87% of its initial value after 6000 cycles. The fact that a light-emitting diode can be lit up by the ASCs indicates the device’s potential applications as an energy storage device. The encouraging results demonstrate a promising application of the composite of MoO3 and GO in energy storage devices.
Journal Article