Ribosomal proteins mediate non-canonical regulation of gut inflammatory signature by crop contaminant deoxynivalenol.

Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked to various inflammatory diseases, including inflammatory bowel disease (IBD). In this study, we elucidate a novel regulatory mechanism involving ribosomal proteins (RPs) RPL13A and RPS3, which mediate proinflammatory chemokine production in DON-exposed gut epithelial cells.

Leveraging Xenobiotic-Responsive Cancer Stemness in Cell Line-Based Tumoroids for Evaluating Chemoresistance: A Proof-of-Concept Study on Environmental Susceptibility.

Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated for its modulation of cancer cell stemness as a pivotal factor of tumor cell reprogramming.

Obesity-compromised immunity in post-COVID-19 condition: a critical control point of chronicity.

Post-COVID-19 condition is recognized as a multifactorial disorder, with persistent presence of viral antigens, discordant immunity, delayed viral clearance, and chronic inflammation. Obesity has emerged as an independent risk factor for both SARS-CoV-2 infection and its subsequent sequelae. In this study, we aimed to predict the molecular mechanisms linking obesity and post-COVID-19 distress.

Gut ribotoxic stress responses facilitate dyslipidemia via metabolic reprogramming: an environmental health prediction.

The gut and its accessory organ, the liver, are crucial determinants of metabolic homeostasis via the regulation of circulating lipids for cardiovascular health. In response to environmental insults, cells undergo diverse adaptation or pathophysiological processes via stress-responsive eukaryotic initiation factor 2 alpha (eIF2α) kinase signaling and subsequent cellular reprogramming. We noted that patients with inflammatory gut distress display enhanced levels of ribosomal stress-responsive eIF2α kinase, which is notably associated with lipid metabolic process genes.

Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming.

The integrated stress response (ISR) plays a pivotal role in the cellular stress response, primarily through global translational arrest and the upregulation of cellular adaptation-linked molecules. Growth differentiation factor 15 (Gdf15) is a potent stress-responsive biomarker of clinical inflammatory and metabolic distress in various types of diseases. Herein, we assess whether ISR-driven cellular stress contributes to pathophysiological outcomes by modulating Gdf15.

Gut distress and intervention communications of SARS-CoV-2 with mucosal exposome.

Acute coronavirus disease 2019 (COVID-19) has been associated with prevalent gastrointestinal distress, characterized by fecal shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA or persistent antigen presence in the gut. Using a meta-analysis, the present review addressed gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and diarrhea. Despite limited data on the gut-lung axis, viral transmission to the gut and its influence on gut mucosa and microbial community were found to be associated by means of various biochemical mechanisms.

Xenobiotic-induced ribosomal stress compromises dysbiotic gut barrier aging: A one health perspective.

Upon exposure to internal or environmental insults, ribosomes stand sentinel. In particular, stress-driven dysregulation of ribosomal homeostasis is a potent trigger of adverse outcomes in mammalians. The present study assessed whether the ribosomal insult affects the aging process via the regulation of sentinel organs such as the gut.

Critical control point-based assessment and intervention of ochratoxin A risk in Angelicae Gigantis Radix production.

Improperly practiced postharvest procedures can pose mycotoxin-related risks during medicinal herb production. As a health food material with pharmacological activities, Angelicae Gigantis Radix (AGR) has been extensively used in oriental medicine or functional foods. Compared with the official protocol, conventional practices were investigated for provisional critical control points (CCPs) in terms of ochratoxin A (OTA) contamination.

Antibiotic-disrupted ribosome biogenesis facilitates tumor chemokine superinduction.

Upon exposure to internal or external stressors, ribosomes stand sentinel via modulation of ribosome assembly and protein translation. Ribosome-dependent cellular dysfunctions have been associated with pathophysiological processes during inflammation and tumorigenesis. In the present study, ribosome biogenesis was assessed to determine its effects on tumor chemokines, potentially contributing to cancer cell malignant features.

Caveolin-1-ACE2 axis modulates xenobiotic metabolism-linked chemoresistance in ovarian clear cell carcinoma.

Among epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) remains markedly resistant to platinum-based chemotherapy, leading to poor clinical outcomes. In response to xenobiotic insults, caveolar platforms play crucial roles in modulating stress signaling responses in cancer cells. It has been hypothesized that caveolin-1 (Cav-1), a main component of the lipid raft, may regulate the response to platinum-based treatment in OCCC.

Fish Collagen Peptides Protect against Cisplatin-Induced Cytotoxicity and Oxidative Injury by Inhibiting MAPK Signaling Pathways in Mouse Thymic Epithelial Cells.

Thymic epithelial cells (TECs) account for the most abundant and dominant stromal component of the thymus, where T cells mature. Oxidative- or cytotoxic-stress associated injury in TECs, a significant and common problem in many clinical settings, may cause a compromised thymopoietic capacity of TECs, resulting in clinically significant immune deficiency disorders or impairment in the adaptive immune response in the body. The present study demonstrated that fish collagen peptides (FCP) increase cell viability, reduce intracellular levels of reactive oxygen species (ROS), and impede apoptosis by repressing the expression of Bax and Bad and the release of cytochrome c, and by upregulating the expression of Bcl-2 and Bcl-xL in cisplatin-treated TECs.

Di-(2-ethylhexyl) Phthalate Triggers Proliferation, Migration, Stemness, and Epithelial-Mesenchymal Transition in Human Endometrial and Endometriotic Epithelial Cells via the Transforming Growth Factor-β/Smad Signaling Pathway.

Di-(2-ethylhexyl) phthalate (DEHP) is a frequently used plasticizer that may be linked to the development of endometriosis, a common gynecological disorder with a profound impact on quality of life. Despite its prevalence, vital access to treatment has often been hampered by a lack of understanding of its pathogenesis as well as reliable disease models. Recently, epithelial-mesenchymal transition (EMT) has been suggested to have a significant role in endometriosis pathophysiology.

Antibiotic Exposure Aggravates -Linked Uremic Toxicity in the Gut-Kidney Axis.

Epidemiological and experimental evidence has implicated a potent link between antibiotic exposure and susceptibility to various diseases. Clinically, antibiotic treatment during platinum chemotherapy is associated with poor prognosis in patients with malignancy. In the present study, mucosal antibiotic exposure was assessed for its impact on renal distress as a sequela of platinum-based chemotherapy.

MicroRNA target-based network predicts androgen receptor-linked mycotoxin stress.

Stress-responsive microRNAs (miRNAs) contribute to the regulation of cellular homeostasis or pathological processes, including carcinogenesis, by reprogramming target gene expression following human exposure to environmental or dietary xenobiotics. Herein, we predicted the targets of carcinogenic mycotoxin-responsive miRNAs and analyzed their association with disease and functionality. miRNA target-derived prediction indicated potent associations of oncogenic mycotoxin exposure with metabolism- or hormone-related diseases, including sex hormone-linked cancers.

Mucosal ribosomal stress-induced PRDM1 promotes chemoresistance via stemness regulation.

The majorities of colorectal cancer (CRC) cases are sporadic in origin and a large proportion of etiologies are associated with environmental stress responses. In response to external and internal stress, the ribosome stands sentinel and stress-driven ribosomal dysfunction triggers the cellular decision pathways via transcriptional reprogramming. In the present study, PR domain zinc finger protein (PRDM) 1, a master transcriptional regulator, was found to be closely associated with ribosomal actions in patients with CRC and the murine models.

Probiotic Ameliorates Antibiotic-Associated Anxiety Responses in Mice.

Despite the beneficial actions of antibiotics against bacterial infections, the use of antibiotics is a crucial etiological factor influencing microbial dysbiosis-associated adverse outcomes in human health. Based on the assumption that gut microbial dysbiosis can provoke behavioral or psychological disorders, the present study evaluated anxiety-linked behavioral changes in a mouse model of streptomycin-induced dysbiosis. Measuring anxiety-like behavior using the light-dark box and elevated plus maze tests indicated that streptomycin treatment caused acute anxiety in mice.

Predictive and Preventive Mucosal Communications in Particulate Matter Exposure-Linked Renal Distress.

Despite research into the epidemiological link between exposure to particulate matter (PM) and renal disorder, there is limited information available on the etiological complexity and molecular mechanisms. Among the early responsive tissues to PM exposure, the mucosal barrier of the airway and alimentary tract may be a crucial source of pathologic mediators leading to inflammatory renal diseases, including chronic kidney disease (CKD). Given that harmful responses and products in mucosa exposed to PM may enter the circulation and cause adverse outcomes in the kidney, the aim of the present review was to address the impact of PM exposure on the mucosal barrier and the vicious feedback cycle in the mucosal environment.

Mechanistic Implications of Biomass-Derived Particulate Matter for Immunity and Immune Disorders.

Particulate matter (PM) is a major and the most harmful component of urban air pollution, which may adversely affect human health. PM exposure has been associated with several human diseases, notably respiratory and cardiovascular diseases. In particular, recent evidence suggests that exposure to biomass-derived PM associates with airway inflammation and can aggravate asthma and other allergic diseases.

Descriptive and functional characterization of epidermal growth factor‑like domain 8 in mouse cortical thymic epithelial cells by integrated analysis of gene expression signatures and networks.

Epidermal growth factor‑like domain 8 (EGFL8), a newly identified member of the EGFL family, and plays negative regulatory roles in mouse thymic epithelial cells (TECs) and thymocytes. However, the role of EGFL8 in these cells remains poorly understood. In the present study, in order to characterize the function of EGFL8, genome‑wide expression profiles in EGFL8‑overexpressing or ‑silenced mouse cortical TECs (cTECs) were analyzed.

Public Database-Driven Insights Into Aging Stress-Associated Defective Gut Barrier With Low SARS-CoV-2 Receptors.

The novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic, and resulted in high case-fatality rate in the elderly. In addition to typical respiratory responses, ~50% of clinical cases include gastrointestinal symptoms such as diarrhea, vomiting, abdominal pain, and persistent fecal shedding of the virus even after its clearance from the pulmonary system. In the present study, we assessed aging-associated gut transcriptomic responses considering the gastrointestinal symptoms contributing to COVID-19 severity.

Enterocyte-Based Bioassay via Quantitative Combination of Proinflammatory Sentinels Specific to 8-keto-trichothecenes.

Type B 8-keto-trichothecenes are muco-active mycotoxins that exist as inevitable contaminants in cereal-based foodstuffs. Gut-associated inflammation is an early frontline response during human and animal exposure to these mycotoxins. Despite various tools for chemical identification, optimized biomonitoring of sentinel response-associated biomarkers is required to assess the specific proinflammatory actions of 8-keto-trichothecenes in the gut epithelial barrier.

Caveolar communication with xenobiotic-stalled ribosomes compromises gut barrier integrity.

In response to internal and external insults, the intestinal lining undergoes various types of epithelial adaptation or pathologic distress via stress-responsive eIF2α kinase signaling and subsequent cellular reprogramming. As a vital platform for growth factor-linked adaptive signaling, caveolae were evaluated for epithelial modulation of the insulted gut. Patients under ulcerative insult displayed enhanced expression of caveolin-1, the main structural component of caveolae, which was positively associated with expression of protein kinase R (PKR), the ribosomal stress-responsive eIF2α kinase.

Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit.

Stress-driven ribosome dysfunction triggers an eIF2α-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2α kinases, protein kinase R (PKR) expression positively associates with poor prognoses for colorectal cancer (CRC) patients. We identified PKR-linked Wnt signaling networks that facilitate early inflammatory niche and epithelial-mesenchymal transitions of tumor tissues in response to ribosomal insults.

Worm-Based Alternate Assessment of Probiotic Intervention against Gut Barrier Infection.

The epithelial barrier is the frontline defense against enteropathogenic bacteria and nutrition-linked xenobiotic stressors in the alimentary tract. In particular, enteropathogenic (EPEC) insults the gut barrier and is increasingly implicated in chronic intestinal diseases such as inflammatory bowel disease. For the efficient development of intervention against barrier-linked distress, the present study provided a -based assessment instead of extensive preclinical evaluations using mammalian models.