Elevated serum HE4 levels as a novel biomarker of disease severity and hepatic fibrosis in autoimmune hepatitis.

BACKGROUND: Human epididymis protein 4 (HE4) has been identified as a biomarker for renal fibrosis. This study aimed to evaluate the role of HE4 in the diagnosis and determination of disease severity and hepatic fibrosis in autoimmune hepatitis (AIH). METHODS: Serum HE4 levels were determined via electrochemiluminescence immunoassays in 60 healthy controls and 109 AIH patients (43 without liver cirrhosis and 66 with liver cirrhosis). Liver biopsy was performed on 56 of 109 enrolled patients. We conducted a 5-year follow-up survey of 53 enrolled patients. All continuous variables were reported as median (25th-75th percentile). RESULTS: Serum HE4 levels were significantly elevated in autoimmune hepatitis with liver cirrhosis (AIH-LC) patients compared with AIH patients and healthy controls [98.60 (74.15-139.08) vs 73.50 (59.88-82.00) vs 48.75 (43.38-52.93) pmol/L, p = 0.004]. The serum HE4 levels showed a positive correlation with the METAVIR scoring system in patients with liver biopsy (r = 0.711, p < 0.001). Serum HE4 levels were significantly elevated in Child-Pugh class C patients compared with Child-Pugh class B patients and Child-Pugh class A patients [106.50 (83.46-151.25) vs 110.00 (73.83-166.75) vs 77.03 (72.35-83.33) pmol/L, p = 0.006]. The diagnostic sensitivity and specificity of serum HE4 for evaluating liver cirrhosis were 69.7 % and 79.07 %, respectively, with a cutoff value of 82.34 pmol/L in enrolled patients. The logistic regression analysis showed that high levels of HE4 (≥82.34 pmol/L) were associated with AIH-LC (OR = 8.751, 95 % CI = 1.412-54.225, p = 0.020). The Kaplan-Meier curves demonstrated that high levels of serum HE4 (≥82.34 pmol/L) were associated with poor outcome (log-rank p = 0.037, HR = 0.372, 95 % CI = 0.146-0.946). CONCLUSIONS: Serum HE4 levels were found to be elevated in AIH-LC patients and exhibited a strong correlation with the severity of hepatic fibrosis, thus supporting their potential clinical value as a novel biomarker of disease severity and hepatic fibrosis in AIH.

Mesenchymal stem cells and ferroptosis: Clinical opportunities and challenges.

Objective: This review discusses recent experimental and clinical findings related to ferroptosis, with a focus on the role of MSCs. Therapeutic efficacy and current applications of MSC-based ferroptosis therapies are also discussed. Background: Ferroptosis is a type of programmed cell death that differs from apoptosis, necrosis, and autophagy; it involves iron metabolism and is related to the pathogenesis of many diseases, such as Parkinson's disease, cancers, and liver diseases. In recent years, the use of mesenchymal stem cells (MSCs) and MSC-derived exosomes has become a trend in cell-free therapies. MSCs are a heterogeneous cell population isolated from a diverse range of human tissues that exhibit immunomodulatory functions, regulate cell growth, and repair damaged tissues. In addition, accumulating evidence indicates that MSC-derived exosomes play an important role, mainly by carrying a variety of bioactive substances that affect recipient cells. The potential mechanism by which MSC-derived exosomes mediate the effects of MSCs on ferroptosis has been previously demonstrated. This review provides the first overview of the current knowledge on ferroptosis, MSCs, and MSC-derived exosomes and highlights the potential application of MSCs exosomes in the treatment of ferroptotic conditions. It summarizes their mechanisms of action and techniques for enhancing MSC functionality. Results obtained from a large number of experimental studies revealed that both local and systemic administration of MSCs effectively suppressed ferroptosis in injured hepatocytes, neurons, cardiomyocytes, and nucleus pulposus cells and promoted the survival and regeneration of injured organs. Methods: We reviewed the role of ferroptosis in related tissues and organs, focusing on its characteristics in different diseases. Additionally, the effects of MSCs and MSC-derived exosomes on ferroptosis-related pathways in various organs were reviewed, and the mechanism of action was elucidated. MSCs were shown to improve the disease course by regulating ferroptosis.

Synthesis of Transition-State Inhibitors of Chorismate Utilizing Enzymes from Bromobenzene cis-1,2-Dihydrodiol.

In order to survive in a mammalian host, Mycobacterium tuberculosis (Mtb) produces aryl-capped siderophores known as the mycobactins for iron acquisition. Salicylic acid is a key building block of the mycobactin core and is synthesized by the bifunctional enzyme MbtI, which converts chorismate into isochorismate via a SN2″ reaction followed by further transformation into salicylate through a [3,3]-sigmatropic rearrangement. MbtI belongs to a family of chorismate-utilizing enzymes (CUEs) that have conserved topology and active site residues. The transition-state inhibitor 1 described by Bartlett, Kozlowski, and co-workers is the most potent reported inhibitor to date of CUEs. Herein, we disclose a concise asymmetric synthesis and the accompanying biochemical characterization of 1 along with three closely related analogues beginning from bromobenzene cis-1S,2S-dihydrodiol produced through microbial oxidation that features a series of regio- and stereoselective transformations for introduction of the C-4 hydroxy and C-6 amino substituents. The flexible synthesis enables late-stage introduction of the carboxy group and other bioisosteres at the C-1 position as well as installation of the enol-pyruvate side chain at the C-5 position.

IgG Antibody Response Elicited by a Fully Synthetic Two-Component Carbohydrate-Based Cancer Vaccine Candidate with α-Galactosylceramide as Built-in Adjuvant.

A fully synthetic self-adjuvanting cancer vaccine candidate was constructed through covalent conjugation of invariant natural killer T (iNKT) cell ligand α-galactosylceramide (αGalCer) with sialyl Tn (STn), a representative tumor-associated carbohydrate antigen (TACA). This two-component vaccine STn-αGalCer is devoid of antigenic peptide, featuring the well-defined structure with high simplicity. STn-αGalCer showed remarkable efficacy in inducing antibody class switching from IgM to STn-specific IgG. Subtypes of IgG antibody were primarily IgG1 and IgG3.

Structural Validity of the Pittsburgh Sleep Quality Index in Chinese Undergraduate Students.

The purpose of this study was to examine the structural validity of the Pittsburgh Sleep Quality Index (PSQI) in Chinese undergraduate students. A cross-sectional questionnaire survey with 631 Chinese undergraduate students was conducted, and the questionnaire package included a measure of demographic characteristics, PSQI, Chinese editions of Center for Epidemiologic Studies-Depression, State- Trait Anxiety Inventory, Rumination Response Scale, and Perceived Social Support Scale. Results showed that the item "use of sleep medicine" was not suitable for use with this population, that a two-factor model provided the best fit to the data as assessed through confirmatory factor analysis, and that other indices were consistently correlated with the sleep quality but not the sleep efficiency factor.

Efficient shortcuts to adiabatic passage for three-dimensional entanglement generation via transitionless quantum driving.

We propose an effective scheme of shortcuts to adiabaticity for generating a three-dimensional entanglement of two atoms trapped in a cavity using the transitionless quantum driving (TQD) approach. The key point of this approach is to construct an effective Hamiltonian that drives the dynamics of a system along instantaneous eigenstates of a reference Hamiltonian to reproduce the same final state as that of an adiabatic process within a much shorter time. In this paper, the shortcuts to adiabatic passage are constructed by introducing two auxiliary excited levels in each atom and applying extra cavity modes and classical fields to drive the relevant transitions. Thereby, the three-dimensional entanglement is obtained with a faster rate than that in the adiabatic passage. Moreover, the influences of atomic spontaneous emission and photon loss on the fidelity are discussed by numerical simulation. The results show that the speed of entanglement implementation is greatly improved by the use of adiabatic shortcuts and that this entanglement implementation is robust against decoherence. This will be beneficial to the preparation of high-dimensional entanglement in experiment and provides the necessary conditions for the application of high-dimensional entangled states in quantum information processing.