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Biomaterials Jun 2024Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment...
Extracellular matrix (ECM) scaffold membranes have exhibited promising potential to better the outcomes of wound healing by creating a regenerative microenvironment around. However, when compared to the application in younger individuals, the performance of the same scaffold membrane in promoting re-epithelialization and collagen deposition was observed dissatisfying in aged mice. To comprehensively explore the mechanisms underlying this age-related disparity, we conducted the integrated analysis, combing single-cell RNA sequencing (scRNA-Seq) with spatial transcriptomics, and elucidated six functionally and spatially distinctive macrophage groups and lymphocytes surrounding the ECM scaffolds. Through intergroup comparative analysis and cell-cell communication, we characterized the dysfunction of Spp1+ macrophages in aged mice impeded the activation of the type Ⅱ immune response, thus inhibiting the repair ability of epidermal cells and fibroblasts around the ECM scaffolds. These findings contribute to a deeper understanding of biomaterial applications in varied physiological contexts, thereby paving the way for the development of precision-based biomaterials tailored specifically for aged individuals in future therapeutic strategies.
PubMed: 38944969
DOI: 10.1016/j.biomaterials.2024.122685 -
Mutation Research Jun 2024Reactive aldehydes, for instance, formaldehyde and acetaldehyde, are important endogenous or environmental mutagens by virtue of their abilities to produce a DNA lesion... (Review)
Review
Reactive aldehydes, for instance, formaldehyde and acetaldehyde, are important endogenous or environmental mutagens by virtue of their abilities to produce a DNA lesion called interstrand crosslink (ICL). Aldehyde-metabolizing enzymes such as aldehyde dehydrogenases (ALDHs) and the Fanconi anemia (FA) pathway constitute the main defense lines against aldehyde-induced genotoxicity. Biallelic mutations of genes in any one of the FA complementation groups can impair the ICL repair mechanism and cause FA, a heterogeneous disorder manifested by bone marrow failure (BMF), congenital abnormality and a strong predisposition to cancer. The defective ALDH2 polymorphism rs671 (ALDH2*2) is a known risk and prognostic factor for alcohol drinking-associated cancers. Recent studies suggest that it also promotes BMF and cancer development in FA, and its combination with alcohol dehydrogenase 5 (ADH5) mutations causes aldehyde degradation deficiency syndrome (ADDS), also known by its symptoms as aplastic anemia, mental retardation, and dwarfism syndrome. ALDH2*2 and another pathogenic variant in the alcohol-metabolizing pathway, ADH1B1*1, is prevalent among East Asians. Also, other ALDH2 genotypes with disease-modifying potentials have lately been identified in different populations. Therefore, it would be appropriate to summarize current knowledge of genotoxic aldehydes and defense mechanisms against them to shed new light on the pathogenic effects of ALDH2 variants together with other genetic and environmental modifiers on cancer and inherited BMF syndromes. Lastly, we also presented potential treatment strategies for FA, ADDS and cancer based on the manipulation of aldehyde-induced genotoxicity.
PubMed: 38944932
DOI: 10.1016/j.mrfmmm.2024.111870 -
Experimental & Molecular Medicine Jul 2024Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system.... (Review)
Review
Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body's defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease.
PubMed: 38945951
DOI: 10.1038/s12276-024-01261-8 -
Soins. Psychiatrie 2024In a child psychiatry unit, where it is said that men are reassuring and women are mothering, the group experience of carers on the function of their gender in child... (Review)
Review
In a child psychiatry unit, where it is said that men are reassuring and women are mothering, the group experience of carers on the function of their gender in child care was explored. Gender is relevant to institutional care, but creates a divide. Representations focus on fear, sexuality, violence and fragility. Caregivers, ambivalent about neutralising gender, suffer from representations of what it does to children and to the institution.
Topics: Humans; Male; Female; Child; Caregivers; Adult; Child, Preschool; France; Adolescent; Mother-Child Relations; Gender Identity; Mental Disorders
PubMed: 38944538
DOI: 10.1016/j.spsy.2024.05.011 -
Soins. Psychiatrie 2024Peer support is based on the mirror effect between the peer carer and the person being supported, which is a powerful lever for recovery. Through their work, peer...
Peer support is based on the mirror effect between the peer carer and the person being supported, which is a powerful lever for recovery. Through their work, peer helpers also hold up a mirror to "non-peer" carers. The reflection they see is a litmus test that can lead to changes in care practices, but it can also generate defensive reactions.
Topics: Humans; Peer Group; Mental Disorders; Social Support; Psychiatric Nursing; France; Caregivers; Defense Mechanisms
PubMed: 38944532
DOI: 10.1016/j.spsy.2024.05.005 -
Genomics Jun 2024Understanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding...
Understanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding phytohormone-mediated tolerance pathways under salt stress in Elymus sibiricus, an important species for forage and ecological restoration, remains limited. In this study, transcriptomic and metabolomic approaches uncover the dynamics of phytohormonal signaling in Elymus sibiricus under salt stress. Notably, four hours after exposure to salt, significant activity was observed in the ABA, JA, IAA, and CTK pathways, with ABA, JA, JA-L-Ile, and IAA identified as key mediators in the response of Elymus sibiricus' to salinity. Moreover, SAPK3, Os04g0167900-like, CAT1, MKK2, and MPK12 were identified as potential central regulators within these pathways. The complex interactions between phytohormones and DEGs are crucial for facilitating the adaptation of Elymus sibiricus to saline environments. These findings enhance our understanding of the salt tolerance mechanisms in Elymus sibiricus and provide a foundation for breeding salt-resistant varieties.
PubMed: 38944355
DOI: 10.1016/j.ygeno.2024.110893 -
Antiviral Research Jun 2024Influenza A virus (IAV) continuously poses a considerable threat to global health through seasonal epidemics and recurring pandemics. IAV RNA-dependent RNA polymerases...
Influenza A virus (IAV) continuously poses a considerable threat to global health through seasonal epidemics and recurring pandemics. IAV RNA-dependent RNA polymerases (FluPol) mediate the transcription of RNA and replication of the viral genome. Searching for targets that inhibit viral polymerase activity helps us develop better antiviral drugs. Here, we identified heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) as an anti-influenza host factor. hnRNPAB interacts with NP of IAV to inhibit the interaction between PB1 and NP, which is dependent on the 5-amino-acid peptide of the hnRNPAB C-terminal domain (aa 318-322). We further found that the 5-amino-acid peptide blocks the interaction between PB1 and NP to destroy the FluPol activity. In vivo studies demonstrate that hnRNPAB-deficient mice display higher viral burdens, enhanced cytokine production, and increased mortality after influenza infection. These data demonstrate that hnRNPAB perturbs FluPol complex conformation to inhibit IAV infection, providing insights into anti-influenza defense mechanisms.
PubMed: 38944160
DOI: 10.1016/j.antiviral.2024.105925 -
Veterinary Immunology and... Jun 2024Mastitis, an inflammation of the mammary gland affecting milk production and quality in dairy herds, is often associated with Staphylococcus spp. in goats. Neutrophils...
Mastitis, an inflammation of the mammary gland affecting milk production and quality in dairy herds, is often associated with Staphylococcus spp. in goats. Neutrophils are crucial in combating infections by migrating into milk and deploying various defense strategies, including the release of neutrophil extracellular traps (NETs) composed of DNA, histones, and bactericidal proteins. This study investigated whether NETs are released by goat neutrophils stimulated in vitro by Staphylococcus aureus and Staphylococcus warneri, two common pathogens of goat mastitis. PMNs were isolated from blood from healthy adult goats. We evaluated goat NET formation by stimulating cells with: phorbol 12-myristate 13-acetate (PMA) as a positive control, cytochalasin for inhibition of actin polymerization, S. aureus, and S. warneri. NET formation was observed in response to chemical stimulation and bacterial presence, effectively trapping pathogens. Variations in NET formation between S. aureus and S. warneri suggest pathogen-specific responses. These findings suggest that the formation of NETs may be an important complementary mechanism in the defense against mastitis in goats. In conclusion, this study unveils a novel defense mechanism in goats, indicating the role of NETs against S. aureus and S. warneri in mastitis.
PubMed: 38943998
DOI: 10.1016/j.vetimm.2024.110793 -
Journal of Hazardous Materials Jun 2024As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic...
Insight into the surface discharge cold plasma efficient inactivation of Pseudomonas fluorescens in water based on exogenous reactive oxygen and nitrogen species: Synergistic mechanism and energy benefits.
As well known, surface discharge cold plasma has efficient inactivation ability and a variety of RONS are main active particles for inactivation, but their synergistic mechanism is still not clear. Therefore, surface discharge cold plasma system was applied to treat Pseudomonas fluorescens to study bacterial inactivation mechanism and energy benefit. Results showed that energy efficiency was directly proportional to applied voltage and inversely proportional to initial concentration. Cold plasma treatment for 20 min was inactivated by approximately > 4-logPseudomonas fluorescens and application of •OH and O scavengers significantly improved survival rate. In addition, •OH and O destroyed cell membrane structure and membrane permeability, which promoted diffusion of RONS into cells and affecting energy metabolism and antioxidant capacity, leading to bacterial inactivation. Furthermore, accumulation of intracellular NO and ONOOH was related to infiltration of exogenous RNS, while accumulation of •OH, HO, O, O was the result of joint action of endogenous and exogenous ROS. Transcriptome analysis revealed that different RONS of cold plasma were responsible for Pseudomonas fluorescens inactivation and related to activation of intracellular antioxidant defense system and regulation of genes expression related to amino acid metabolism and energy metabolism, which promoting cellular process, catalytic activity and other biochemical pathways.
PubMed: 38943891
DOI: 10.1016/j.jhazmat.2024.134984 -
Database : the Journal of Biological... Jun 2024Drug transporters, integral membrane proteins found throughout the human body, play critical roles in physiological and biochemical processes through interactions with...
Drug transporters, integral membrane proteins found throughout the human body, play critical roles in physiological and biochemical processes through interactions with ligands, such as substrates and inhibitors. The extensive and disparate data on drug transporters complicate understanding their complex relationships with ligands. To address this challenge, it is essential to gather and summarize information on drug transporters, inhibitors and substrates, and simultaneously develop a comprehensive and user-friendly database. Current online resources often provide fragmented information and have limited coverage of drug transporter substrates and inhibitors, highlighting the need for a specialized, comprehensive and openly accessible database. ISTransbase addresses this gap by amassing a substantial amount of data from literature, government documents and open databases. It includes 16 528 inhibitors and 4465 substrates of 163 drug transporters from 18 different species, resulting in a total of 93 841 inhibitor records and 51 053 substrate records. ISTransbase provides detailed insights into drug transporters and their inhibitors/substrates, encompassing transporter and molecule structure, transporter function and distribution, as well as experimental methods and results from transport or inhibition experiments. Furthermore, ISTransbase offers three search strategies that allow users to retrieve drugs and transporters based on multiple selectable constraints, as well as perform checks for drug-drug interactions. Users can also browse and download data. In summary, ISTransbase (https://istransbase.scbdd.com/) serves as a valuable resource for accurately and efficiently accessing information on drug transporter inhibitors and substrates, aiding researchers in exploring drug transporter mechanisms and assisting clinicians in mitigating adverse drug reactions Database URL: https://istransbase.scbdd.com/.
Topics: Humans; Membrane Transport Proteins; Internet; Databases, Protein; Databases, Factual; Animals; Databases, Pharmaceutical
PubMed: 38943608
DOI: 10.1093/database/baae053