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(1) Background: Cystic echinococcosis (CE) is an Echinococcus granulosus-induced worldwide parasitic zoonosis and is a recognized public health and socio-economic concern. The liver is the major target organ for CE's infective form protoscolex (PSCs), which causes serious liver damage and endangers the host's life. Reports show that PSC infection causes liver cell Fe²⁺ metabolism disorder and abnormal deposition of Fe²⁺ in liver cells and results in liver cell death. However, whether PSC-induced liver cell death is associated with ferroptosis remains to be clarified. (2) Methods: Using both an in vivo rat model and an in vitro co-culture of PSCs and the cell system, we studied the histopathological progress of PSCs infection and the cytopathogenesis of PSC-induced cell death in the liver. Hepatic-injury-related ferroptosis signaling pathways were identified by proteomics analysis at various stages of PSCs infection, and physiological and the biochemical indexes and expression of pathway proteins related to hepatic ferroptosis were studied. Ferrostatin-1, a ferroptosis inhibitor, was employed for in vivo interference with early protoscolices infection in rats, and the effects of the inhibition of hepatocyte ferroptosis on hepatocyte injury and the generation of fibrotic cysts were investigated. Additionally, PSCs were exposed to in vitro co-culture with BRL, a rat hepatocyte line, to clarify the direct influences of PSCs on BRL ferroptosis. (3) Results: The results of our in vivo studies revealed that PSCs infection induced Fe²⁺ enrichment in liver cells surrounding the PSCs cysts, cellular oxidation, and liver tissue damage along with the prolongation of PSCs parasitism. The results of our in vitro studies verified the ability of PSCs to directly induce ferroptosis, the formation of fibrotic cysts, and alteration of the iron metabolism of liver cells. The analysis of KEGG signaling pathways revealed that ferroptosis- and ROS-related pathways were significantly induced with PSCs infection. Using Ferrostatin-1 effectively blocked ferroptosis, reversed Fe²⁺ content, reduced liver cell oxidation, and reduced PSC-induced fibrosis cysts. (4) Conclusions: Our study reveals the histopathological progress of PSC infection and the cytopathogenesis of PSC-induced ferroptosis. Ferrostatin-1 effectively blocked PSCs infection and PSC-induced cell death in vivo and in vitro. Accordingly, the inhibition of PSC-induced hepatocyte ferroptosis may be an effective method in the control of Echinococcus granulosus infection and should be seriously considered in clinical studies.

Deleterious molecules or factors produced by pathogens can hinder the normal physiological functioning of organisms. In response to these survival challenges, organisms rely on innate immune signaling as their first line of defense, which regulates immune-responsive genes and antimicrobial peptides to protect against pathogenic infections. These genes are under the control of transcription factors, which are known to regulate the transcriptional activity of genes after binding to their regulatory sequences. Previous studies have employed Caenorhabditis elegans as a host-pathogen interaction model to demonstrate the essential role of different transcription factors in the innate immunity of worms. In this review, we summarize the advances made regarding the functioning of distinct transcription factors in the innate immune response upon pathogen infection. Finally, we discuss the open questions in the field, whose resolutions have the potential to expand our understanding of the mechanisms underlying the innate immunity of organisms.

Endometriosis is a chronic gynecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. A common feature of this pathology is the impaired decidualization of endometrial stromal cells, a critical process that prepares the uterus for embryo implantation. This decidualization defect has been mechanistically linked to progesterone resistance in endometriotic lesions. However, the presence and underlying mechanisms of decidualization defects in the eutopic endometrium of women with endometriosis remain controversial. The aim of the present study is to integrate and discuss molecular evidence from both in vivo and in vitro studies examining decidualization alterations in the eutopic endometrium of patients with endometriosis. Multiple studies have demonstrated impaired decidualization in the eutopic endometrium of women with endometriosis. These alterations have been reported on multiple genes, signaling pathways, and epigenetic processes. However, additional functional studies are warranted to elucidate whether these decidualization defects directly contribute to endometriosis-associated infertility. A better understanding of the decidualization process and its dysregulation in endometriosis will not only advance the development of targeted fertility treatments but also facilitate the design of more effective therapeutic strategies for managing this chronic condition.

Patient-derived xenograft (PDX) models are powerful tools in cancer research, offering an accurate platform for evaluating cancer treatment efficacy and predicting responsiveness. However, these models necessitate surgical techniques for tumor tissue transplantation and face challenges with non-uniform tumor growth among animals. To address these issues, we attempted to develop a new PDX modeling method using high-grade serous ovarian cancer (HGSC), a fatal disease with a 5-year survival rate of 29%, which requires personalized research due to its morphological, genetic, and molecular heterogeneities. In this study, we developed a new patient-derived cancer cell xenograft (PDCX) model with high engraftment efficiency (64%) that utilizes primary cancer cells instead of patient tissues. Primary cancer cells can be stably cryopreserved for extended periods (up to 485 days), and when transplanted into female NSGA mice, they maintain morphological and molecular characteristics without significant genetic differences compared to their original primary tumors. Furthermore, PDCX models can be easily produced using a syringe, allowing for uniform tumor sizes across multiple animals. Additionally, M2 PDCXs exhibited a significantly faster growth rate compared to M2 PDTXs. Consequently, our PDCX model offers a streamlined approach for evaluating personalized cancer treatments with minimal experimental variability.

Background: Skeletal muscle wasting is commonly observed in aging, immobility, and chronic diseases. In pathological conditions, the impairment of skeletal muscle and immune system often occurs simultaneously. Recent studies have highlighted the initiative role of skeletal muscle in interactions with immune cells. However, the impact of skeletal muscle wasting on macrophage inflammatory responses remains poorly understood.

Methods: To investigate the effect of atrophic myotubes on the inflammatory response of macrophages, we established two in vitro models to induce myotube atrophy: one induced by D-galactose and the other by starvation. Conditioned medium (CM) from normal and atrophic myotubes were collected and administered to bone marrow-derived macrophages (BMDMs) from mice. Subsequently, lipopolysaccharide (LPS) stimulation was applied, and the expression of inflammatory cytokines was measured via RT-qPCR.

Results: Both D-galactose and starvation treatments reduced myotube diameter and upregulated muscle atrophy-related gene expression. CM from both atrophic myotubes models augmented the gene expression of pro-inflammatory factors in BMDMs following LPS stimulation, including Il6, Il1b, and Nfkb1. Notably, CM from starvation-induced atrophic myotubes also enhanced Il12b, Tnf, and Nos2 expression in BMDMs after stimulation, a response not observed in D-galactose-induced atrophic myotubes.

Conclusions: These findings suggest that CM from atrophic myotubes enhanced the expression of LPS-induced pro-inflammatory mediators in macrophages.

Fabry disease (FD) is a lysosomal disorder due to alpha-galactosidase-A enzyme deficiency, accumulation of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) which lead to proinflammatory effects. Males develop progressive hypertrophic cardiomyopathy (HCM) followed by fibrosis; females develop nonconcentric hypertrophy and/or early fibrosis. The inflammatory response to Gb3/lyso-Gb-3 accumulation is one of the suggested pathogenic mechanisms in FD cardiomyopathy when the secretion of inflammatory and transforming growth factors with infiltration of lymphocytes and macrophages into tissue promotes cardiofibrosis. This study aims to evaluate inflammation-driving cytokines and cardio-hypertrophic remodeling biomarkers contributing to sex-specific HCM progression. Biomarkers were studied in 20 healthy subjects and 45 FD patients. IL-2, IL-10, TNF-α, and IFN-γ were elevated in all patients, while IL-1α, MCP-1, and TNFR2 showed sex-specific differences. The increased cytokines were associated with the NF-kB pathway in FD males with HCM, revealing a correlation between MCP-1, IFN-γ, VEGF, GM-CSF, IL-10, and IL-2. In female patients, the impaired TNFα/TNFR2/TGFβ cluster with correlations to MCP-1, VEGF, GM-CSF, and IL-1α was observed. The activation of cytokines and the NF-kB pathway indicates significant inflammation during HCM remodeling in FD males. The TNFα/TNFR2/TGFβ signaling cluster may explain early fibrosis in females with FD cardiomyopathy. Sex-specific inflammatory responses in FD influence the severity and progression of HCM.

Brain injuries can result from accidents, warfare, sports injuries, or brain diseases. Identifying regeneration-associated genes (RAGs) during epigenome remodeling upon brain injury could have a significant impact on reducing neuronal death and subsequent neurodegeneration for patients with brain injury. We previously identified several WNT genes as RAGs involved in the neurite regrowth of injured cortical neurons. Among them, the expression of the Wnt8a gene increased most significantly during neurite regrowth, indicating its potential to promote neuronal regeneration. In this study, we investigated the regulatory mechanism of Wnt8a transcription. An algorithm was developed to predict the novel enhancer regions of candidate genes. By combining active enhancer marks, histone H3 lysine 27 acetylation (H3K27ac), and histone H3 lysine 4 mono-methylation (H3K4me1), we identified a candidate enhancer region for Wnt8a located 1.7 Mb upstream and 0.1 Mb downstream of the Wnt8a gene. This region was organized into enhancers (Ens) 1-15. Enhancer RNA expression from the predicted En1-15 regions, DNA topological dynamics, and the activity of predicted enhancers were analyzed to validate the candidate active enhancers. Our findings showed that the En8, 9, 10, 14, and 15 regions expressed higher eRNAs during neurite regrowth. Notably, the En8-2 and En14-2 subregions showed significantly up-regulated H3K4me1 modification during neurite regrowth. Using chromatin conformation capture assays and enhancer-reporter assays, we delineated that the molecular regulation of Wnt8a transcription during neurite regrowth occurs through looped En8-promoter interplay.

Perineuronal nets (PNNs) are specialized extracellular matrix structures that predominantly surround inhibitory neurons in the central nervous system (CNS). They have been identified as crucial regulators of synaptic plasticity and neuronal excitability. This literature review aims to summarize the current state of knowledge about PNNs, their molecular composition and structure, as well as their functional roles and involvement in neurological diseases. Furthermore, future directions in PNN research are proposed, and the therapeutic potential of targeting PNNs to develop novel treatment options for various neurological disorders is explored. This review emphasizes the importance of PNNs in CNS physiology and pathology and underscores the need for further research in this area.

Osteoarthritis (OA) is one of the most common degenerative diseases in dogs and humans, which can lead to articular cartilage deterioration, chronic pain, and decreased quality of life. The anti-inflammatory, anti-fibrotic, analgesic, and cartilage regeneration properties of mesenchymal stem cell (MSC) therapy provide a new direction for the treatment development of OA in the future. Currently, MSC therapy lacks confirmed ideal sources, dosages, formulations, and specific characteristics. In this study, we evaluated the efficacy of multiple canine adipose-derived mesenchymal stem cell (ADSC) injections on anti-inflammation and joint cartilage damage in a canine OA model. Considering animal ethics, we simulated the effects of inflammation and cartilage repair during treatment through a mouse OA model. In the mouse OA model, through the detection of cartilage repair and inflammation-related key factors via histology and molecular biology, it was found that MSC therapy has a certain repair effect on cartilage, but the anti-inflammatory effect is time-dependent. In the canine OA model, we verified the feasibility of multiple injections of ADSCs. Compared with the control group, the cartilage repair effect of the treatment group was obvious, and the inflammatory factors decreased, showing an obvious therapeutic effect. This study demonstrates that multiple intra-articular injections of canine ADSCs could be effective in treating OA symptoms.

Heart failure (HF) is a prominent fatal cardiovascular disorder afflicting 3.4% of the adult population despite the advancement of treatment options. Therefore, a better understanding of the pathogenesis of HF is essential for exploring novel therapeutic strategies. Hypertrophy and fibrosis are significant characteristics of pathological cardiac remodeling, contributing to HF. The mechanisms involved in the development of cardiac remodeling and consequent HF are multifactorial, and in this review, the key underlying mechanisms are discussed. These have been divided into the following categories thusly: (i) mitochondrial dysfunction, including defective dynamics, energy production, and oxidative stress; (ii) cardiac lipotoxicity; (iii) maladaptive endoplasmic reticulum (ER) stress; (iv) impaired autophagy; (v) cardiac inflammatory responses; (vi) programmed cell death, including apoptosis, pyroptosis, and ferroptosis; (vii) endothelial dysfunction; and (viii) defective cardiac contractility. Preclinical data suggest that there is merit in targeting the identified pathways; however, their clinical implications and outcomes regarding treating HF need further investigation in the future. Herein, we introduce the molecular mechanisms pivotal in the onset and progression of HF, as well as compounds targeting the related mechanisms and their therapeutic potential in preventing or rescuing HF. This, therefore, offers an avenue for the design and discovery of novel therapies for the treatment of HF.