Tissue Defense Research Articles

Ultraflat, Monolithic, Highly Stable Supercontinuum Source Based on Fluorotellurite Fiber

Supercontinuum (SC) sources covering near‐infrared and midinfrared region have attracted enormous interest and found significant applications in tissue imaging, sensing, spectroscopy, defense, and environmental monitoring. Herein, an 8.45 W all‐fiber ultraflat SC source with a spectral range of 1.01–4.05 μm using a flat high‐power 1.9–2.7 μm SC fiber source to pump a piece of fluorotellurite fiber is presented. The SC spectrum exhibits a 3 dB bandwidth of 1850 nm, ranging from 1870 to 3720 nm, and a 10 dB bandwidth of 2770 nm, ranging from 1120 to 3890 nm. The measured power stability is 0.19% (root mean square) for 5 h of continuous operation, proving the excellent power stability of the system. To the best of knowledge, the SC spectrum exhibits the widest reported 3 and 10 dB bandwidths for 1–4 μm SC sources.

At2-MMP is required for attenuation of cell proliferation during wound healing in incised Arabidopsis inflorescence stems.

Wound healing of partially incised Arabidopsis inflorescence stems constitutes cell proliferation that initiates mainly in pith tissues about three days after incision, and that the healing process completes in about seven days. Although the initiation mechanisms of cell proliferation have been well documented, the suppression mechanisms remain elusive. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases well-known as proteolytic enzymes in animal systems functioning in extracellular matrix remodeling during physiological and pathological processes, including tissue differentiation, growth, defense, wound healing, and control of cancer growth. In this study, we report At2-MMP might contribute to the suppression mechanism of cell proliferation during tissue-repair process of incised inflorescence stems. At2-MMP transcript was gradually upregulated from day 0 to 5 after incision, and slightly decreased on day 7. Morphological analysis of incised stem of defected mutant at2-mmp revealed significantly enhanced cell proliferation around the incision site. Consistent with this, semi-quantitative analysis of dividing cells displayed a significant increment in the number of dividing cells in at2-mmp as compared to WT. These results showed that the upregulation of At2-MMP at the later stage of wound-healing process is likely to be involved in the completion of the process by attenuating the cell proliferation.

GFI1B specifies developmental potential of innate lymphoid cell progenitors in the lungs.

Tissue-resident innate lymphoid cells (ILCs) play a vital role in the frontline defense of various tissues, including the lung. The development of type 2 ILCs (ILC2s) depends on transcription factors such as GATA3, RORα, GFI1, and Bcl11b; however, the factors regulating lung-resident ILC2s remain unclear. Through fate mapping analysis of the paralog transcription factors GFI1 and GFI1B, we show that GFI1 is consistently expressed during the transition from progenitor to mature ILC2s. In contrast, GFI1B expression is limited to specific subsets of bone marrow progenitors and lung-resident ILC progenitors. We found that GFI1B+ lung ILC progenitors represent a multi-lineage subset with tissue-resident characteristics and the potential to form lung-derived ILC subsets and liver-resident ILC1s. Loss of GFI1B in bone marrow progenitors led to the selective loss of lung-resident IL-18R+ ILCs and mature ILC2, subsequently preventing the emergence of effector ILCs that could protect the lung against inflammatory or tumor challenge.

What could be the function of the spinal muscular atrophy-causing protein SMN in macrophages?

Spinal Muscular Atrophy (SMA), a neurodegenerative disorder, extends its impact beyond the nervous system. The central protein implicated in SMA, Survival Motor Neuron (SMN) protein, is ubiquitously expressed and functions in fundamental processes such as alternative splicing, translation, cytoskeletal dynamics and signaling. These processes are relevant for all cellular systems, including cells of the immune system such as macrophages. Macrophages are capable of modulating their splicing, cytoskeleton and expression profile in order to fulfil their role in tissue homeostasis and defense. However, less is known about impairment or dysfunction of macrophages lacking SMN and the subsequent impact on the immune system of SMA patients. We aimed to review the potential overlaps between SMN functions and macrophage mechanisms highlighting the need for future research, as well as the current state of research addressing the role of macrophages in SMA.

Assessing Aluminum Stress Resilience in Common Bean Roots: Phenotypic, Histochemical, and PvGST/PvPOD Gene Expression Analysis

Common bean (Phaseolus vulgaris L.) is grown in various parts of the world. Aluminum (Al) toxicity poses a significant and widespread challenge in marginal areas with unfavorable soil qualities where common bean is grown. In acidic soils, stable forms of Al dissolve into the soil solution and inhibit root growth and function by injuring the root apex with phytotoxic ions. This leads to the development of a smaller root system, adversely affecting crop yield. In this study, the phenotypic evaluation for relative root elongation of 10 common bean genotypes/cultivars under Al stress (50 µM), the impact of Al toxicity using different histochemical dyes (Evan’s blue and Schiff’s reagent) and the expression levels of PvGST (Glutathione S-transferases) and PvPOD (peroxidase) genes in the root tissues of the most resistant/sensitive common beans under Al stress (50 µM) and control conditions (0 µM) were investigated. The maximum relative root elongation value (71.9%) was found in Önceler-98 cultivar, while the lowest value (14.1%) was obtained from Blksr-19 genotype. Histochemical applications used in the study supported phenotypic results. The cracks at the root tip and high blue color intensity were detected in Schiff’s reagent and Evan’s blue dyes in the Blksr-19, respectively. The expression levels of PvGST and PvPOD genes in the root tissue of the Blksr-19 (Al-sensitive) were highly upregulated at 24 h of Al stress treatment. The results revealed that these genes might be involved in the common bean root tissue's defense mechanism against Al stress for the first time. The findings herein will help plant breeders develop common bean cultivars tolerant to Al toxicity.

DEPENDENCE OF OXIDATIVE BALANCE AND CHOLESTEROL METABOLISM IN MUSCLE TISSUE ON EXERCISE INTENSITY

Intriduction. Changes in oxidative balance and lipid metabolism have the leading role in performance limitation, adaptation and maladaptation to physical activity. It is especially important to analyse the direction of metabolic changes at the subcellular level. The aim of the study is to examine the state of oxidative balance and cholesterol metabolism in muscle tissue at moderate and maximal swim-ming load. Material and methods. A comprehensive study of indicators for free-radical oxidation (content of diene conjugates, TBA-active products, chemilu-minescence intensity), antioxidant defense (total antioxidant activity, antiradical activity) and cholesterol metabolism in tissues of heart muscle and thigh muscle of white male rats at moderate and maximum swimming load was carried out. Results. The patterns of metabolic changes in muscle tissue depending on the intensity of muscular work have been established: these are the forms of compensated oxidative stress at moderate and decompensated at maximum load, against the background of decreasing cholesterol content. In cardiac tissue oxidative stress phenomena were less expressed, and changes in cholesterol content were multidirectional: a tendency to decrease at moderate load and a significant increase at maximum load. Conclusion. The reduction of antioxidant defence resources and intensification of free-radical oxidation reactions constitute one of the leading mecha-nisms for metabolic disorders due to extreme physical load, which is confirmed by reliable changes in the studied parameters. The complex study of indicators characterizing the processes of free-radical oxidation, antioxidant protection and cholesterol content is an informative criterion for the influ-ence of physical exercise on the organism. The obtained data allow us to recommend the inclusion of antioxidants in the complex prevention and ther-apy of acute physical overstrain.

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis.

Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b+ LY6Chigh). Furthermore, both CD11b+ Ly6Clow F4/80high macrophages (MΦ) and recently differentiated CD11b+ Ly6Chigh F4/80high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206high) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.

Not an immune cell, but they may act like one-cells with immune properties outside the immune system.

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll-like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD-like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where "typical" immune cells normally do not have access. In this paper, we present immune-like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly-derived cells).

Current Development and Application on Inclusion of Herbal Phytochemicals in Novel Herbal Drug Delivery System

Abstract: Herbal phytochemicals as secondary metabolites are present in herbal medicines. Herbal medicines can be used to treat a wide range of illnesses and diseases. The Novel herbal drug delivery system approach includes transfersomes, ethosomes, microspheres, phytosomes, liposomes, polymeric nanoparticles, and nanocapsules. The novel herbal drug delivery systems have several benefits over conventional herbal remedies. Herbal medicines are less expensive and have fewer serious side effects than generic medications. The novel herbal drug delivery systems have several benefits over conventional herbal remedies. These include improved solubility and bioavailability, protection from side effects, improved pharmacological action, increased stability, better delivery to tissue macrophages, consistent delivery, and defense against active ingredients' physical and chemical breakdown. There is a need for a novel method of active components of drugs to apply on target organs or sites of the human body to avoid repeated administration of dosage forms and enhance patient adherence. Scientists have tried to focus on advanced mechanisms or processes for delivering herbal components into the human body. Novel Herbal Drug Delivery System helps to boost drug efficacy by lessening side effects and enhancing the blood level of the drug. Novel herbal formulations can reduce recurrent administration of medicines and noncompliance of patients.

Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions.

Curcumin is known for its antioxidant properties. This study aimed to investigate the impact of curcumin on acrylamide (ACR)-induced alterations in the first-line antioxidant defense of ovarian tissue. Female Balb/c mice were divided into control, ACR (50 mg/kg), ACR/CUR100 (received Acr + curcumin100 mg/kg), and ACR/CUR200 (Acr + curcumin 200 mg/kg) groups, and received oral treatments for 35 days. Evaluation of antioxidant enzyme expression (Sod, Cat, Gpx genes), pro-apoptotic gene expressions (Bax, Caspase 3), and anti-apoptotic gene expression (Bcl2l1) at mRNA and protein levels was done. Percentage of apoptotic cells using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. The model group (ACR) showed decreased mRNA expression of Sod, Cat, and Gpx genes compared with the control group. Treatment with two different doses of curcumin (CUR100 and CUR200) significantly increased Sod, Cat, and Gpx gene expression, with CUR200 demonstrating significant recovery. SOD, CAT, and GPX protein levels were similar to mRNA expression trends, significantly increased with curcumin administration. Acrylamide exposure significantly increased Bax and Caspase 3 expression and decreased Bcl2l1 gene expression leading to a notable rise in apoptosis in ACR group as compared to the control group. Conversely, curcumin administration, significantly reduced Bax and Caspase 3 expressions, with an increase in Bcl2l1expression, though not statistically significant. TUNEL assay revealed a substantial decrease in apoptosis in curcumin-received groups. In our study, ACR exposure adversely affected ovarian antioxidant defense thereby leading to increased pro-apoptotic markers. Notably, curcumin treatment effectively mitigated these effects, restored antioxidant potential, and reduced acrylamide-induced toxicity in female mouse ovaries.

From monocyte-derived macrophages to resident macrophages-how metabolism leads their way in cancer.

Macrophages are innate immune cells that play key roles during both homeostasis and disease. Depending on the microenvironmental cues sensed in different tissues, macrophages are known to acquire specific phenotypes and exhibit unique features that, ultimately, orchestrate tissue homeostasis, defense, and repair. Within the tumor microenvironment, macrophages are referred to as tumor-associated macrophages (TAMs) and constitute a heterogeneous population. Like their tissue resident counterpart, TAMs are plastic and can switch function and phenotype according to the niche-derived stimuli sensed. While changes in TAM phenotype are known to be accompanied by adaptive alterations in their cell metabolism, it is reported that metabolic reprogramming of macrophages can dictate their activation state and function. In line with these observations, recent research efforts have been focused on defining the metabolic traits of TAM subsets in different tumor malignancies and understanding their role in cancer progression and metastasis formation. This knowledge will pave the way to novel therapeutic strategies tailored to cancer subtype-specific metabolic landscapes. This review outlines the metabolic characteristics of distinct TAM subsets and their implications in tumorigenesis across multiple cancer types.

Can blood morphology, oxidative stress, and cholinesterase activity determine health status of pigeon Columba livia f. urbana?

Environmental studies in Northern Poland are example of the functioning of ecophysiological relationships under anthropogenic impact. The aim of our studies was to investigate sex-dependent effects on the alterations in the concentration of chemical elements in soil samples collected from habitats of feral pigeon Columba livia f. urbana from Northern Poland, as well as feathers, biomarkers of oxidative stress, antioxidant defense, and total cholinesterase activity in tissues (liver, kidney, brain). Concentration of Si, Zn, and Pb in feathers of pigeons was significant. The levels of Si and Zn were higher in feathers of females from non-polluted, while higher Pb levels were found only in females from polluted areas (p = 0.000). This was confirmed by MANOVA of biomarkers of antioxidant defense, elements concentration, and revealing the order of effects: tissue type > environment > sex. Erythrocytes of males living in polluted areas were more fragile to hemolytic agents resulting in a higher percentage of hemolyzed erythrocytes. The effects of polluted environment on the level of carbonyl derivatives of oxidatively modified proteins compared to the effects of sex were more pronounced in the case of kidney (p = 0.000) and hepatic tissues (p = 0.000). Polluted areas were associated with significant increase in SOD activity in the brain and hepatic tissues of pigeons (p = 0.000). Health status of feral pigeons is significantly different in conditions of environmental destabilization.

The chromosome-level genome of the submerged plant Cryptocoryne crispatula provides insights into the terrestrial-freshwater transition in Araceae.

Plant terrestrialization (i.e. the transition to a terrestrial environment) is a significant evolutionary event that has been intensively studied. While certain plant lineages, particularly in angiosperms, have re-adapted to freshwater habitats after colonizing terrene, however, the molecular mechanism of the terrestrial-freshwater (T-F) transition remains limited. Here, the basal monocot Araceae was selected as the study object to explore the T-F transition adaptation mechanism by comparative genomic analysis. Our findings revealed that the substitution rates significantly increased in the lineage of freshwater Araceae, which may promote their adaptation to the freshwater habitat. Additionally, 20 gene sets across all four freshwater species displayed signs of positive selection contributing to tissue development and defense responses in freshwater plants. Comparative synteny analysis showed that genes specific to submerged plants were enriched in cellular respiration and photosynthesis. In contrast, floating plants were involved in regulating gene expression, suggesting that gene and genome duplications may provide the original material for plants to adapt to the freshwater environment. Our study provides valuable insights into the genomic aspects of the transition from terrestrial to aquatic environments in Araceae, laying the groundwork for future research in the angiosperm.

Identifying and Validating Extracellular Matrix-Related Gene CTSH in Diabetic Foot Ulcer Using Bioinformatics and Machine Learning.

Diabetic foot ulcer (DFU) is a serious clinical problem with high amputation and mortality rates, yet there is a lack of desirable therapy. While the extracellular matrix (ECM) contributes significantly to wound healing, ECM-related biomarker for DFU is still unknown. The study was designed to identify ECM-related biomarker in DFU using bioinformatics and machine learning and validate it in STZ-induced mice models. GSE80178 and GSE134431 microarray datasets were fetched from the GEO database, and differentially expressed genes (DEGs) analysis was performed, respectively. By analyzing DEGs and ECM genes, we identified ECM-related DEGs, and functional enrichment analysis was conducted. Subsequently, three machine learning algorithms (LASSO, RF and SVM-RFE) were applied to filter ECM-related DEGs to identify key ECM-related biomarkers. Next, we conducted immune infiltration analysis, GSEA, and correlation analysis to explore the hub gene underlying mechanism. A lncRNA-miRNA-mRNA and drug regulatory network were constructed. Finally, we validated the key ECM-related biomarker in STZ-induced mice models. One hundred and forty-five common DEGs in adult DFU between the two datasets were identified. Taking the intersection of 145 common DEGs and 964 ECM genes, we identified 13 ECM-related DEGs. Thirteen ECM-related DEGs were mainly enriched in pathways associatedwith tissue remodeling, inflammation and defense against infectious agents. Ultimately, CTSH was identified as the key ECM-related biomarker. CTSH was associated with difference immune cells during the occurrence and development of DFU, and it influenced hedgehog, IL-17 and TNF signaling pathway. Additionally, CTSH expression is correlated with many ECM- and immune-related genes. A lncRNA-miRNA-mRNA and drug regulatory network were constructed with 10 lncRNAs, 2 miRNAs, CTSH and 1 drug. Finally, CTSH was validated as a key biomarker for DFU in animal models. Our study found that CTSH can be used for both diagnostic and prognostic purposes and might be a potential therapeutic target.

KIDNEYS INVOLVEMENT INTO THE THYROID GLAND BURNING PATHOGENETIC MECHANISMS

Background. Burn injuries considered to be the most common and severe diseases in people, positioned second place after traffic injuries. The thyroid gland, taking into account the wide range of thyroid hormones physiological activity, its structural and functional organization and morpho-functional features as well as large-scale duplicative mechanisms of regulatory feedback, is one of the first which receives the alterative thermal influence. Thyroid gland and other organs of the body dysfunction or pathological dysregulation occurs as a result of thermal exposure “triggers” systemic dysfunctions via the “vicious circle” and positive feedback mechanisms and systemic-antisystemic regulation which cannot be ignored by the majority of internal organs and organ systems resulting ion their functional disorders. We decided to test the assumptions regarding the kidneys participation in thyroid burning pathological process manifestation.
 Aim: to investigate the changes in lipid peroxidation and antioxidant defense in erythrocytes and kidney tissue and to investigate the kidneys functional activity throughout the thyroid gland thermal.
 Materials and methods. The malondialdehyde concentration and antioxidant enzymes activity - glutathione, catalase, superoxide dismutase and glutathione peroxidase - were determined in white Wistar rats’ erythrocytes and kidney homogenate 1, 3, 7, 14, 21, and 30 days after the thyroid gland burning. Diuresis was calculated in rats during induced water diuresis and both the protein and creatinine content in urine was determined during the indicated periods after thyroid gland burning
 Results. The significant accumulation of lipoperoxidation intermediate products and the antioxidant enzymes activity suppression in erythrocytes and in the kidney parenchyma are registered in rats during the post-burn period. The postburn period course is characterized by diuresis decrease. The urine protein level increased and the rate of protein excretion also increased in conditions of thyroid gland burning
 Conclusion. Significant accumulation of lipoperoxidation intermediate products and the antioxidant enzymes activity suppression in erythrocytes and in the liver parenchyma is recorded in thyroid gland burning dynamics which we consider as evidence of erythrocytes and kidney involvement in the specified pathological process mediation. The expressed renal dysfunction develops with thyroid gland thermal damage which is manifested by kidneys both excretory and filtering functions impairment. The data obtained we consider as the experimental background for kidney involvement into the thyroid gland burning pathogenetic mechanisms and the pathological dysregulation of organs and organ systems formation in these pathological conditions.

Local Defense Factors in Cleft-Affected Palate in Children before and during Milk Dentition Age: A Pilot Study.

One of the most frequent congenital orofacial defects is the cleft lip and palate. Local tissue defense factors are known to be important in immune response and inflammatory and healing processes in the cleft tissue; however, they have only been researched in older children during mixed dentition. Thus, the aim of this study is to assess the distribution of LL-37, CD-163, IL-10, HBD-2, HBD-3, and HBD-4 in children before and during milk dentition. The unique and rare material of palate tissue was obtained from 13 patients during veloplastic surgeries during the time span of 20 years. Immunohistochemistry, light microscopy, semi-quantitative evaluation, and non-parametric statistical analysis were used. A significant decrease in HBD-3 and HBD-4 in the connective tissue was found, as well as several mutual statistically significant and strong correlations between HBD-2, HBD-3, HBD-4, and LL-37. Deficiency of HBD-3 and HBD-4 suggests promotion of chronic inflammation. The scarcity of HBD-4 could be connected to the different signaling pathways of dental pulp cells. Mutual correlations imply changes in the epithelial barrier, amplified healing efficiency, and increased antibacterial line of defense. Deprivation of changes in IL-10 quantity points to possible suppression of the factor. The presence of similar CD-163 immunoreactive substances produced by M2 macrophages was also observed.

Oxidative stress, gene expression and histopathology of cultured gilthead sea bream (Sparus aurata) naturally co-infected with Ergasilus sieboldi and Vibrio alginolyticus

BackgroundParasitic and bacterial co-infections have been associated with increasing fish mortalities and severe economic losses in aquaculture through the past three decades. The aim of this study was to evaluate the oxidative stress, histopathology, and immune gene expression profile of gilthead sea bream (Sparus aurata) co-infected with Ergasilus sieboldi and Vibrio alginolyticus.ResultsVibrio alginolyticus and Ergasilus sieboldi were identified using 16 S rRNA and 28 S rRNA sequencing, respectively. The collagenase virulence gene was found in all Vibrio alginolyticus isolates, and the multiple antimicrobial resistance index ranged from 0.286 to 0.857. Oxidant-antioxidant parameters in the gills, skin, and muscles of naturally infected fish revealed increased lipid peroxidation levels and a decrease in catalase and glutathione antioxidant activities. Moreover, naturally co-infected gilthead sea bream exhibited substantial up-regulation of il-1β, tnf-α, and cyp1a1. Ergasilus sieboldi encircled gill lamellae with its second antennae, exhibited severe gill architectural deformation with extensive eosinophilic granular cell infiltration. Vibrio alginolyticus infection caused skin and muscle necrosis in gilthead sea bream.ConclusionThis study described some details about the gill, skin and muscle tissue defense mechanisms of gilthead sea bream against Ergasilus sieboldi and Vibrio alginolyticus co-infections. The prevalence of co-infections was 100%, and no resistant fish were detected. These co-infections imbalance the health status of the fish by hampering the oxidant-antioxidant mechanisms and proinflammatory/inflammatory immune genes to a more detrimental side. Our results suggest that simultaneous screening for bacterial and parasitic pathogens should be considered.

Effect of climate change on hematotoxicity/hepatoxicity oxidative stress, Oncorhynchus mykiss, under controlled conditions.

Described as the 'main ecological factor', temperature, strongly affects the physiological stress responses of fish. In order to evaluate the effects of temperature variations on fish culture and food value chain, the present study was designed as a climate change model. Furthermore, the present study provides a theoretical basis for a better understanding of the mechanisms of the environmentally induced changes. In this direction, we examined the blood physiology and oxidative stress responses induced by temperature variation in the rainbow trout, a temperature-sensitive cold-water fish. The obtained results showed that climate changes promoted the inhibited activities' expressions and the development of potential tissue and hematological defense mechanisms against temperature-induced toxic damage. This study showed that climate change could be a subset of the studies on the stress physiology in aquaculture, which can be developed for new experimental designs and research collaborations. Furthermore, it highlights knowledge gaps to guide future research in this emerging field.

Copper – a scoping review for Nordic Nutrition Recommendations 2023

Copper functions as a structural component in many proteins involved in energy and iron metabolism, production of neurotransmitters, formation of connective tissue and endogenous antioxidant defence. Several biochemical indices have been suggested and used to assess copper status, but none of these has been found suitable for the detection of marginal copper deficiency or marginal copper toxicity. Copper imbalances have been linked to the pathogenesis of several chronic inflammatory diseases. During the last decade, a number of meta-analyses and systematic reviews have been published shedding light on the association between copper imbalances and some of these pathologies. Most of these meta-analyses are based on case–control studies. All show that blood copper concentrations are higher in cases than in controls, but there is inconclusive evidence to change the recommendations.

Gasdermin D is the only Gasdermin that provides protection against acute Salmonella gut infection in mice.

Gasdermins (GSDMs) share a common functional domain structure and are best known for their capacity to form membrane pores. These pores are hallmarks of a specific form of cell death called pyroptosis and mediate the secretion of pro-inflammatory cytokines such as interleukin 1β (IL1β) and interleukin 18 (IL18). Thereby, Gasdermins have been implicated in various immune responses against cancer and infectious diseases such as acute Salmonella Typhimurium (S.Tm) gut infection. However, to date, we lack a comprehensive functional assessment of the different Gasdermins (GSDMA-E) during S.Tm infection in vivo. Here, we used epithelium-specific ablation, bone marrow chimeras, and mouse lines lacking individual Gasdermins, combinations of Gasdermins or even all Gasdermins (GSDMA1-3C1-4DE) at once and performed littermate-controlled oral S.Tm infections in streptomycin-pretreated mice to investigate the impact of all murine Gasdermins. While GSDMA, C, and E appear dispensable, we show that GSDMD i) restricts S.Tm loads in the gut tissue and systemic organs, ii) controls gut inflammation kinetics, and iii) prevents epithelium disruption by 72 h of the infection. Full protection requires GSDMD expression by both bone-marrow-derived lamina propria cells and intestinal epithelial cells (IECs). In vivo experiments as well as 3D-, 2D-, and chimeric enteroid infections further show that infected IEC extrusion proceeds also without GSDMD, but that GSDMD controls the permeabilization and morphology of the extruding IECs, affects extrusion kinetics, and promotes overall mucosal barrier capacity. As such, this work identifies a unique multipronged role of GSDMD among the Gasdermins for mucosal tissue defense against a common enteric pathogen.