cytokines metabolic

Acute liver failure (ALF) is an infrequent, but serious complication subsequent to severe acute liver injury (sALI) due to various hepatotoxic agents such as hepatotropic virus(es) and drugs such as anti-tubercular medications, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics and anti-cancer and anti-epileptic therapy and due to metabolic and autoimmune disease flares. ALF after sALI presents with encephalopathy associated with prolonged international normalized ratio (INR). Mortality in ALF is high and ranges between 50% and 80%...

BACKGROUND AND PURPOSE: In this study, we examined the impact of Zn-bioMOF structures on the physical and chemical characteristics as well as the in vitro biocompatibility of a matrix composed of semi-interpenetrating polymeric networks (semi-IPN) made from collagen and L-tyrosine-based polyelectrolytes. EXPERIMENTAL APPROACH: We hydrothermally synthesized L-1, ZIF-8H Zn-bioMOFs, and the Zn-(L-His)2 complex, utilizing L-histidine, a bioactive amino acid, as a ligand...

Diabetes mellitus (DM) is a collection of metabolic disorder that is characterized by chronic hyperglycemia. Recent studies have demonstrated the crucial involvement of oxidative stress (OS) and inflammatory reactions in the development of DM. Curcumin (CUR), a natural compound derived from turmeric, exerts beneficial effects on diabetes mellitus through its interaction with the nuclear factor kappa B (NF-κB) pathway. Research indicates that CUR targets inflammatory mediators in diabetes, including tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), by modulating the NF-κB signaling pathway...

Fibroblast growth factors (FGFs) and their receptors (FGFRs) constitute plasma-membrane localized signaling hubs that transmit signals from the extracellular environment to the cell interior, governing pivotal cellular processes like motility, metabolism, differentiation, division and death. FGF/FGFR signaling is critical for human body development and homeostasis; dysregulation of FGF/FGFR units is observed in numerous developmental diseases and in about 10% of human cancers. Glycosylation is a highly abundant posttranslational modification that is critical for physiological and pathological functions of the cell...

Microplastics (MPs) are widespread environmental contaminants that have been detected in animals and humans. However, their toxic effects on terrestrial mammals and the underlying mechanisms are still not well understood. Herein, we explored the role of gut microbiota in mediating the toxicity of micro- and nano-sized polystyrene plastics (PS-MPs/PS-NPs) using an antibiotic depleted mice model. The results showed that PS-MPs and PS-NPs exposure disrupted the composition and structure of the gut microbiota. Specifically, these particles led to an increase in pathogenic Esherichia-shigella, while depleting probiotics such as Akkermansia and Lactobacillus...

Inflammation is a key mechanism underlying the adverse health effects of exposure to fine particulate matter (PM2.5 ). Bioactive lipids in the arachidonic acid (ARA) pathway are important in the regulation of inflammation and are reportedly altered by PM2.5 exposure. Ceramide-1-phosphate (C1P), a class of sphingolipids, is required to initiate ARA metabolism. We examined the role of C1P in the alteration of ARA metabolism after PM2.5 exposure and explored whether changes in the ARA pathway promoted systemic inflammation based on a panel study involving 112 older adults in Beijing, China...

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1β induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death...

Osteoarthritis (OA) is a chronic degenerative disease with a significant prevalence that causes cartilage damage and can lead to disability. The main factors contributing to the onset and progression of OA include inflammation and degeneration of the extracellular matrix. Cathelicidin-BF (BF-30), a natural peptide derived from Bungarus fasciatus venom, has shown multiple important pharmacological effects. However, the action mechanism of BF-30 in OA treatment remains to be elucidated. In this research, X-ray and Safranin O staining were employed to evaluate the imageology and histomorphology differences in the knee joints of mice in vivo...

Chimeric antigen receptor (CAR)-T cell therapy shows impressive efficacy treating hematologic malignancies but requires further optimization in solid tumors. Here, we developed a TMIGD2 optimized potent/persistent (TOP) CAR that incorporated the costimulatory domain of TMIGD2, a T and NK cell costimulator, and monoclonal antibodies targeting the IgV domain of B7-H3, an immune checkpoint expressed on solid tumors and tumor vasculature. Comparing second- and third-generation B7-H3 CARs containing TMIGD2, CD28, and/or 4-1BB costimulatory domains revealed superior antitumor responses in B7-H3...

Palmitoylation is an essential post-translational modification in Leishmania donovani , catalyzed by enzymes called palmitoyl acyl transferases (PATs) and has an essential role in virulence. Due to the toxicity and promiscuity of known PAT inhibitors, identification of new molecules is needed. Herein, we identified a specific novel de novo peptide inhibitor, PS1, against the PAT6 Leishmania donovani palmitoyl acyl transferase ( Ld PAT6). To demonstrate specific inhibition of Ld PAT6 by PS1, we employed a bacterial orthologue system and metabolic labeling-coupled click chemistry where both Ld PAT6 and PS1 were coexpressed and displayed palmitoylation suppression...

Innate lymphoid cells (ILCs), strategically positioned throughout the body, undergo population declines over time. A solution to counteract this problem is timely mobilization of multipotential progenitors from the bone marrow. It remains unknown what triggers the mobilization of bone marrow ILC progenitors (ILCPs). We report that ILCPs are regulated by the circadian clock to emigrate and generate mature ILCs in the periphery. We found that circadian-clock-defective ILCPs fail to normally emigrate and generate ILCs...

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine-metabolic disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovaries, with hyperandrogenism being the most prominent feature of PCOS patients. However, whether excessive androgens also exist in the ovarian microenvironment of patients with PCOS, and their modulatory role on ovarian immune homeostasis and ovarian function, is not clear. METHODS: Follicular fluid samples from patients participating in their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were collected...

OBJECTIVE: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. METHODS: In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status...

Patients with pituitary neuroendocrine tumors (PitNETs) often experience neuropsychiatric disorders due to factors such as hormonal imbalances, and inadequate management of medications, surgeries, and radiation therapies. Commonly observed disorders include depression, anxiety, and cognitive dysfunction, which significantly impact patients' quality of life and prognosis. PitNETs have a significant presence of immune cells within the tumor microenvironment (TME), predominantly macrophages and T lymphocytes. These immune cells secrete a variety of cytokines, growth factors, and chemokines, which regulate the biological behaviors of PitNETs, including tumor initiation, proliferation, migration, invasion, and angiogenesis...

The prevalence of fragrances in various hygiene products contributes to their sensorial allure. However, fragrances can induce sensitization in the skin or respiratory system, and the mechanisms involved in this process are incompletely understood. This study investigated the intricate mechanisms underlying the fragrance's effects on sensitization response, focusing on the interplay between CYP450 enzymes, a class of drug-metabolizing enzymes, and the adaptive immune system. Specifically, we assessed the expression of CYP450 enzymes and cytokine profiles in culture of BEAS-2B and mature dendritic cells (mDC) alone or in co-culture stimulated with 2 mM of a common fragrance, cinnamyl alcohol (CA) for 20 h...

BACKGROUND: Tumor growth is closely linked to the activities of various cells in the tumor microenvironment (TME), particularly immune cells. During tumor progression, circulating monocytes and macrophages are recruited, altering the TME and accelerating growth. These macrophages adjust their functions in response to signals from tumor and stromal cells. Tumor-associated macrophages (TAMs), similar to M2 macrophages, are key regulators in the TME. METHODS: We review the origins, characteristics, and functions of TAMs within the TME...

OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches...

A study of the mechanism of and metabolic regulation of brown adipose tissue (BAT) production is important for improving the survival rate of young animals. In the present study, we observed that perirenal adipose tissue in goats undergoes a rapid BAT whitening after birth. However, the underlying regulatory mechanism remains unknown. To address this further, we investigated the role of miRNAs in regulating the whitening process of BAT in goats. First, we identified the dynamic expression profiles of miRNAs during the whitening of BAT in Dazu black goat using RNA-seq...

ACKGROUND: Diabetes mellitus (DM) frequently results in Diabetic Nephropathy (DN), which has a significant negative impact on the quality of life of diabetic patients. Sphingolipid metabolism is associated with diabetes, but its relationship with DN is unclear. Therefore, screening biomarkers related to sphingolipid metabolism is crucial for treating DN. METHODS: To identify Differentially Expressed Genes (DEGs) in the GSE142153 dataset, we conducted a differential expression analysis (DN samples versus control samples)...

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function mutations in the DYSTROPHIN gene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of TGFβ family of cytokines. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation of Smad8 transcription. However, the role of BMP4 in severely affected DMD skeletal muscle is unknown. We hypothesized that transcriptomic signatures in severely affected human DMD skeletal muscle are driven by BMP4 signaling...