The prevalence and the effect of interferon -γ in the comorbidity of rheumatoid arthritis and depression.

BACKGROUND: Depression is the most common comorbidities associated with rheumatoid arthritis (RA). We aimed to explore the mechanism of association between RA and depression. METHODS: 120 subjects were enrolled and depression was diagnosed and assessed using DSM-5 and 24-item version of Hamilton Depression Scale. Pain intensity and joint function in patients with RA were assessed using the visual analog scale (VAS) and health assessment questionnaire (HAQ). Serum levels of interferon-gamma (IFN-γ), indoleamine 2,3-dioxygenase (IDO), kynurenine (KYN), tryptophan (TRP), and quinolinic acid (QUIN)were detected. In animal experiments, K/BxN mice with RA-like phenotype was used and depressive behavior was observed. The protein expression level of N-methyl -D- aspartate receptor 2B (NR2B) in the hippocampus was detected. RESULTS: In this study, 36.67 % of patients with RA also had depression. The working status, month family income, tender joint count, the VAS and HAQ score were the main factors influencing the depression in RA patients. HAQ score was found to be an independent risk factor for depression in RA. Serum IDO, IFN-γ, KYN were increased and TRP contents were decreased in RA group. K/BxN mice with RA-like phenotype showed depressive behavior. However, injection of IFN-γ neutralizing antibody could inhibit kynurenine pathway and reverse the depressive behavior in mice. The levels of QUIN in the neurotoxic metabolic pathway were increased and N-methyl -D- aspartate receptors (NMDAR) were activated, which may be the mechanism behind the onset of depression. CONCLUSIONS: From clinical and preclinical aspects, the occurrence of depression in RA was explored and the related mechanism was revealed.

Peptide-based Nanomaterials: Self-assembly and Applications.

The self-assembly behavior of polypeptides is common in nature. Compared with monopeptides, polypeptide-based self-assembled nanomaterials with ordered structures have good thermal stability, mechanical stability, semi-conductivity, piezoelectric and optical properties. In recent years, the self-assembly of polypeptides has become a hot topic in the material science and biomedical field. By reasonably adjusting the molecular structure of the polypeptide and changing the external environment of the polypeptide, the polypeptide can be self-assembled or triggered by non-covalent bonding forces such as hydrogen bond, hydrophobicity, and π - π accumulation to form specific polypeptide assemblies such as nanoparticles, hydrogels, nanofibers, and micelles. Due to good biocompatibility and controllable degradability, polypeptide-based self-assembled nanomaterials have been widely used in the fields of nanotechnology, imaging technology, biosensor, and biomedical science. As a new drug delivery system, the polypeptide-drug conjugate has the advantages of low toxicity, high efficiency, enhanced drug stability, and avoiding side effects. This paper reviews the research progress of polypeptide-drug self-assembly nanostructure in recent years. Several structural models of polypeptide self-assembly technology and the mechanism of polypeptide self-assembly are introduced. Then the assembly form of polypeptide-drug self-assembly and the application of selfassembly compound therapy is described.

IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway.

Liver fibrosis is an excessive accumulation of extracellular matrix (ECM) due to chronic liver injury. In recent years, the mechanism of liver fibrosis has been extensively studied. Hepatic stellate cells (HSCs) play an important role in the occurrence and development of liver fibrosis because activated hepatic stellate cells could synthesize a large number of ECM and thus participate in the process of liver fibrosis. Interleukin-8 (IL-8) (deletion in mice) is a versatile chemokine that promotes inflammation and affects cell growth by activating related pathways and plays an important role in the development and progression of a variety of diseases. Notably, the expression level of IL-8 was significantly higher in patients with liver fibrosis, suggesting that it may be related to the pathogenesis of liver fibrosis. In this study, we used hydrodynamic injection to deliver the lentiviral vector LV5-hIL-8 into mice. We found that hIL-8 could aggravate carbon tetrachloride (CCl4)-induced liver fibrosis through the PI3K/Akt/HIF-1α pathway. It is characterized by excessive accumulation of ECM as well as a significant increase in markers of liver injury. In addition, in PDGF-induced HSCs, we also demonstrated that hIL-8 could aggravate ECM accumulation through the PI3K/Akt/HIF-1α pathway. In conclusion, the results of this study on hIL-8 may help to identify potential targets for the clinical treatment of liver fibrosis.

Antithrombotic strategies after transcatheter aortic valve implantation: A systematic review and network meta-analysis of randomized controlled trials.

AIMS: Meta-analyses comparing different antithrombotic strategies were conducted to determine the optimal therapeutic regimen post transcatheter aortic valve implantation (TAVI). However, there were restricted high-quality direct comparisons across the different antithrombotic therapeutic regimens. We sought to explore the safety and efficacy of different antithrombotic therapy strategies after TAVI using network meta-analyses of randomized controlled trials (RCTs). METHODS: We searched CENTRAL, PubMed, Embase and Medline through August 2021 for RCTs that directly compared different antithrombotic schemes in adults who had undergone TAVI. We conducted a pairwise and network meta-analysis measuring all-cause mortality, stroke, myocardial infarction, all bleeding and life-threatening or major bleeding events. The surface under the cumulative ranking (SUCRA) curve was estimated to rank the therapies. We evaluated the risk of bias and graded the quality of the evidence using established methods. RESULTS: Six RCTs of 2824 patients who underwent TAVI were analysed. The risk of all bleeding [relative risk (RR) 1.88 (1.34-2.64)] and life-threatening or major bleeding [RR 2.03 (1.27-3.24)] was significantly higher for dual antiplatelet therapy (DAPT) than single antiplatelet therapy (SAPT), whereas there was no significant difference in the risk of all-cause mortality [RR 1.01 (0.61-1.68)] between DAPT and SAPT. Oral anticoagulant (OAC) + SAPT (OACSAPT) had significantly higher rates of all bleeding and life-threatening or major bleeding events compared with SAPT ([RR 3.46 (2.23-5.36)], [RR 2.86 (1.50-5.45)]). The risk of all-cause mortality [RR 1.72 (1.14-2.59)] and all bleeding [RR 1.84 (1.38-2.44)] were significantly higher for OACSAPT than DAPT, whereas there was no significant difference in the risk of life-threatening or major bleeding events [RR 1.41 (0.89-2.23)] between DAPT and OACSAPT. There was no significant difference in stroke or myocardial infarction among the different antithrombotic strategies (SAPT, DAPT and OACSAPT). Additionally, patients receiving OACSAPT had the highest risks for all-cause mortality (SUCRA 3.5%) and life-threatening or major bleeding (SUCRA 2.3%). SAPT seemed to be superior to DAPT in terms of all-cause mortality (SUCRA SAPT: 76.7%, DAPT: 69.8%) and stroke (SUCRA 69.6%, 59.7%). CONCLUSIONS: Except for OACSAPT having a higher all-cause mortality than DAPT, patients who underwent TAVI had similar all-cause mortality, stroke and myocardial infarction rates among different antithrombotic regimens. Patients on SAPT had a significantly lower bleeding risk than those on DAPT and OACSAPT. Our study indicates that SAPT is the preferred therapeutic strategy when there is no indication for OAC or DAPT. Furthermore, the application of OACSAPT was ranked the worst among all antithrombotic regimens and should be averted due to an increased risk of all-cause mortality and all bleeding.

Self-assembly of amino acids toward functional biomaterials.

Biomolecules, such as proteins and peptides, can be self-assembled. They are widely distributed, easy to obtain, and biocompatible. However, the self-assembly of proteins and peptides has disadvantages, such as difficulty in obtaining high quantities of materials, high cost, polydispersity, and purification limitations. The difficulties in using proteins and peptides as functional materials make it more complicate to arrange assembled nanostructures at both microscopic and macroscopic scales. Amino acids, as the smallest constituent of proteins and the smallest constituent in the bottom-up approach, are the smallest building blocks that can be self-assembled. The self-assembly of single amino acids has the advantages of low synthesis cost, simple modeling, excellent biocompatibility and biodegradability in vivo. In addition, amino acids can be assembled with other components to meet multiple scientific needs. However, using these simple building blocks to design attractive materials remains a challenge due to the simplicity of the amino acids. Most of the review articles about self-assembly focus on large molecules, such as peptides and proteins. The preparation of complicated materials by self-assembly of amino acids has not yet been evaluated. Therefore, it is of great significance to systematically summarize the literature of amino acid self-assembly. This article reviews the recent advances in amino acid self-assembly regarding amino acid self-assembly, functional amino acid self-assembly, amino acid coordination self-assembly, and amino acid regulatory functional molecule self-assembly.

Triptolide regulates oxidative stress and inflammation leading to hepatotoxicity via inducing CYP2E1.

Triptolide (TP), the main active compound extracted from medicine-tripterygium wilfordii Hook f. (TWHF). It has anti-tumor and immunomodulatory properties. Our study aimed to investigate the mechanisms of hepatotoxicity treated with TP in vivo and in vitro, as well as their relationship with the NF-κB (p65) signal pathway; and to assess TP-induced hepatotoxicity after CYP2E1 modulation by the known inhibitor, clomethiazole, and the known inducer, pyrazole. Mice were given TP to cause liver injury and IHHA-1 cells were given TP to cause hepatocyte injury. The enzyme activity and hepatotoxicity changed dramatically when the CYP2E1 inhibitor and inducer were added. In comparison to the control group, the enzyme inducer increased the activity of CYP2E1, whereas the enzyme inhibitor had the opposite effect. Our findings suggest that TP is an inducer of CYP2E1 via a time-dependent activation mechanism. In addition, TP can promote oxidative stress, inflammatory and involving the NF-κB (p65) signal pathway. Therefore, we used triptolide to stimulate C57 mice and IHHA-1 cells to determine whether TP can promote oxidative stress and inflammation by activating CYP2E1 in response to exacerbated liver damage and participate in NF-κB (p65) signaling pathway.

IL-8 exacerbates alcohol-induced fatty liver disease via the Akt/HIF-1α pathway in human IL-8-expressing mice.

Alcoholic fatty liver disease (AFLD) is a disease that causes liver damage due to chronic heavy drinking. AFLD is related to lipid accumulation in liver cells caused by alcohol intake. Interleukin-8 (IL-8) is an inflammatory cytokine associated with chemotaxis (deletion in mice) that has robust effects on the occurrence and development of disease by activating related signal transduction pathways to promote inflammation and cell proliferation. There is significantly increased IL-8 expression in liver disease, which may be related to the pathogenesis of AFLD. In this study, we used hydrodynamic injection to deliver the liver-specific expression vector pLIVE-hIL-8 into mice. We found that hIL-8 can exacerbate alcohol-induced fatty liver disease via the Akt/HIF-1α pathway. Exacerbated liver lipid degeneration in mice, which is characterized by excessive accumulation of triglycerides, and liver damage markers were significantly increased. Moreover, hIL-8 could increase the alcohol-induced release of ROS in fatty liver caused by alcohol and exacerbate fatty liver disease. The expression of liver lipid metabolism-related gene sterol regulatory element-binding protein-1c (SREBP-1c) was increased. Furthermore, the expression of peroxisome proliferator-activated receptor alpha (PPARα), which is related to liver fatty acid oxidation, was decreased. The findings obtained in this study of hIL-8 will help identify a potential target for the clinical treatment of AFLD.