Gallic acid pretreatment mitigates parathyroid ischemia-reperfusion injury through signaling pathway modulation.

Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract-gallic acid (GA)-with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA's modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.

Functional magnetic resonance imaging reveals dysfunction of the paraspinal muscles in patients with chronic low back pain: a cross-sectional study.

Background: Patients with chronic low back pain (CLBP) undergo structural changes of the paraspinal muscles; however, it is unclear if functional changes also occur. This study aimed to examine the metabolic and perfusion function changes in the paraspinal muscles of patients with CLBP as indirectly reflected by blood oxygen level-dependent (BOLD) imaging and T2 mapping. Methods: All participants were consecutively enrolled at our local hospital from December 2019 to November 2020. Patients were diagnosed with CLBP in the outpatient clinic, and asymptomatic participants were considered to be those with no CLBP or other diseases. This study was not registered on a clinical trial platform. Participants underwent BOLD imaging and T2 mapping scans at the L4-S1 disc level. The effective transverse relaxation rate (R2* values) and transverse relaxation time (T2 values) of the paraspinal muscles were measured on the central plane of the L4/5 and L5/S1 intervertebral discs. Finally, the independent samples t-test was used to assess the differences in R2* and T2 values between the 2 groups, while Pearson correlation analysis was used to determine their correlation with age. Results: A total of 60 patients with CLBP and 20 asymptomatic participants were enrolled. The paraspinal muscles of the CLBP group had higher total R2* values [46.7±2.9 vs. 44.0±2.9 s-1; 95% confidence interval (CI): 1.2-4.2; P=0.001] and lower total T2 values (45.4±4.2 vs. 47.1±3.7 ms; 95% CI: -3.8 to 0.4; P=0.109) than did the asymptomatic participants. For the different muscles, R2* values for the erector spinae (ES) (L4/5: 45.5±2.6 vs. 43.0±3.0 s-1, 95% CI: 1.1-4.0, P=0.001; L5/S1: 48.5±4.9 vs. 45.9±4.2 s-1; 95% CI: 0.2-5.1; P=0.035) and the R2* values of the multifidus (MF) muscles (L4/5: 46.4±2.9 vs. 43.7±3.5 s-1, 95% CI: 1.1-4.3, P=0.001; L5/S1: 46.3±3.5 vs. 42.5±2.8 s-1, 95% CI: 2.1-5.5, P<0.001) of the CLBP group at both spinal levels were higher than those of the asymptomatic participants. In the patients with CLBP, the R2* values at the L4/5 (45.9±2.1 s-1) were lower than those at the L5/S1 (47.4±3.6 s-1; 95% CI: -2.6 to -0.4; P=0.007). The R2* values were positively correlated with age in both groups (CLBP group: r=0.501, 95% CI: 0.271-0.694, P<0.001; asymptomatic group: r=0.499, 95% CI: -0.047 to 0.771; P=0.025). Conclusions: The R2* values were higher in the paraspinal muscles of patients with CLPB and may suggest metabolic and perfusion dysfunction of the paraspinal muscles in these patients.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation.

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.

Replicability in cancer omics data analysis: measures and empirical explorations.

In biomedical research, the replicability of findings across studies is highly desired. In this study, we focus on cancer omics data, for which the examination of replicability has been mostly focused on important omics variables identified in different studies. In published literature, although there have been extensive attention and ad hoc discussions, there is insufficient quantitative research looking into replicability measures and their properties. The goal of this study is to fill this important knowledge gap. In particular, we consider three sensible replicability measures, for which we examine distributional properties and develop a way of making inference. Applying them to three The Cancer Genome Atlas (TCGA) datasets reveals in general low replicability and significant across-data variations. To further comprehend such findings, we resort to simulation, which confirms the validity of the findings with the TCGA data and further informs the dependence of replicability on signal level (or equivalently sample size). Overall, this study can advance our understanding of replicability for cancer omics and other studies that have identification as a key goal.

Pyolysin of Trueperella pyogenes Induces Pyroptosis and IL-1ß Release in Murine Macrophages Through Potassium/NLRP3/Caspase-1/Gasdermin D Pathway.

Trueperella pyogenes (T. pyogenes) is a commensal and an opportunistic pathogen of animals. This organism can cause inflammatory diseases, such as pneumonia, mastitis and endometritis in hosts. However, the molecular basis for the pro-inflammatory properties of this organism is still largely unknown. In the current study, using murine macrophages as model, the ability of T. pyogenes to induce pyroptosis was first determined. Then, pyolysin (PLO), a cholesterol-dependent cytolysin secreted by T. pyogenes, was found to be closely related to T. pyogenes-induced pyroptosis. Next, our work showed that PLO can form pores in the cell membrane, leading to the efflux of potassium (K+), NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated caspase-1 activation, and gasdermin D (GSDMD) cleavage. Inhibition of the K+/NLRP3/caspase-1/GSDMD pathway abolished T. pyogenes and PLO-induced IL-1ß release. Taken together, these results indicate T. pyogenes-induced inflammation is related to PLO-induced pyroptosis and IL-1ß release. Our work shed light on the pathogenesis of T. pyogenes and the interaction between T. pyogenes and hosts' immune system.