Plant J. 2025 Jun;122(6):e70279. doi: 10.1111/tpj.70279.

ABSTRACT

Glycosyl inositol phospho ceramides (GIPC) are the predominant glycosphingolipids in plant membranes, essential for their membrane stability, cell signaling, stress adaptation, and pathogen resistance. However, their complex structures, characterized by a ceramide backbone and a glycan head group, have challenged comprehensive analysis using traditional methods, which often rely on separate glycan or lipid profiling. To overcome these limitations, we developed a glycosphingolipidomics assay using reversed-phase high-resolution mass spectrometry including multistage fragmentation (RP-HRMSn). This method enables direct, detailed structural characterization of GIPC in plants, combining advanced chromatographic separation, multistage fragmentation, and automated annotation using decision rule-based criteria. Applied to barley grains, the assay identified 102 GIPC species, including A-, B-, C-, and D-series GIPC, previously unreported glycan branching fragments (421 and 403 m/z), and a huge structural variety in the ceramide moiety. Profiling at different development stages revealed dynamic GIPC regulation during grain development, with an upregulation of B- and C-series towards mature development stages. The application of heat stress induced significant remodeling of GIPC profiles, mainly through upregulation of B-series species, which emphasizes their roles in maintaining membrane stability and functionality under abiotic stress conditions. The presented glycosphingolipidomics assay enables the first automated analysis of complex GIPC through a decision rule-based identification approach. By resolving GIPC to the molecular lipid species level, the method provides novel insights into GIPC diversity, homeostasis, and their critical roles in membrane dynamics, stress adaptation, and pathogen resistance, paving the way for advanced research in plant lipidomics and stress biology.

PMID:40570361 | DOI:10.1111/tpj.70279

J Assist Reprod Genet. 2025 Jun 26. doi: 10.1007/s10815-025-03557-8. Online ahead of print.

ABSTRACT

PURPOSE: Recent studies emphasize the role of neuroendocrine dysfunctions and sirtuins in polycystic ovarian syndrome (PCOS). We investigated whether altered SIRT1 and SIRT3 levels contribute to brain changes and oxidative stress, identifying these pathways as potential therapeutic targets for PCOS-related complications.

METHODS: Using a DHEA-induced PCOS mouse model, we examined brain expression of pathways related to SIRT1 and SIRT3 and to oxidative/glycative stress changes. SH-SY5Y cells treated with DHEA were used to confirm direct neuronal effects.

RESULTS: We found decreased levels of Sirt1 and Sirt3 transcripts but increased protein expression and activity of both sirtuins in brains of DHEA-treated mice. The DHEA group showed elevated oxidative and glycative stress, including an overall increased lipid peroxidation and DNA damage, as well as accumulation of advanced glycation endproducts (AGEs) in isocortices. Differences in Cpt1 isoform expressions suggested disrupted metabolic processing in the PCOS brains. Neuronal degeneration was also observed, alongside unchanged Bdnf and TrkB mRNA levels in DHEA brains. Exposure of differentiated SH-SY5Y neuron-like cells to high concentrations (≥ 100 µM) led to increased oxidative stress, altered sirtuins expression, and ultimately cell toxicity. While low concentrations of DHEA (1 µM) did not elicit such responses.

CONCLUSIONS: These findings reveal a complex interplay between oxidative stress, metabolic dysregulation, and neuronal health in PCOS brain, underscoring the need for further investigations into the underlying mechanisms, including research in genetic components. This research provides foundational insights into how PCOS may influence neurobiological processes and helps clarify some aspects of its pathogenesis.

PMID:40569550 | DOI:10.1007/s10815-025-03557-8

Integr Comp Biol. 2025 Jun 24:icaf085. doi: 10.1093/icb/icaf085. Online ahead of print.

ABSTRACT

Historically, organismal biologists have studied the organism's response to environmental variation from two complementary perspectives: one has focused on "stability" and the capacity of organisms to maintain a constant internal state (e.g., homeostasis) across environments, whereas the other has focused on "change" and how the expression of traits varies as a function of a continuous environmental factor (e.g., performance curves). While these approaches differ, they rely on the same fundamental principles dispersed across cell biology, physiology, endocrinology, ecology, and evolution and thus could be better integrated. Through the lens of systems biology, we offer a perspective that explores the idea that organisms maintain stability of critical physiological functions during environmental change through changes of lower-level traits within physiological regulatory networks. We assert that such network thinking and an emphasis on the cost of homeostatic systems are critical when relating the physiological responses of cells, tissues, hormones, etc to whole-organism performance and the ecological context in which the responses occur. We suggest that such an approach has the potential of transcending levels of biological organization by connecting approaches typically studied in isolation of each other and that this will help the organismal biologist relate physiological responses measured in the lab to performance and fitness in natural settings. To illustrate our perspective and aid in our presentation of practical tips for the experimental biologist, we use examples from our own research on osmoregulation in euryhaline fish.

PMID:40569264 | DOI:10.1093/icb/icaf085

FASEB J. 2025 Jul 15;39(13):e70771. doi: 10.1096/fj.202500686RR.

ABSTRACT

Regulation of aquaporin-2 (Aqp2) gene is essential for body water homeostasis. This study investigated how TAZ (a transcriptional coactivator with PDZ-binding motif, Wwtr1) controls vasopressin-driven AQP2 expression. AQP2 expression was studied using collecting duct-specific TAZ-knockout (TAZf/f; HoxB7Cre) mice and siRNA-mediated knockdown of TAZ in vasopressin-responsive mpkCCDc11 cells. Downstream factors of TAZ were identified using transcriptomics and bioinformatics. The TAZf/f; HoxB7Cre mice demonstrated polyuria and a significant decrease in AQP2 abundance in the kidney cortex and the outer medulla. dDAVP treatment (10-9 M, 24 h) on mpkCCDc11 cells significantly increased AQP2 mRNA and protein levels. However, siRNA-mediated TAZ knockdown (TAZ-KD) markedly attenuated these effects without affecting cAMP levels. Immunocytochemical analysis revealed a substantial decrease in AQP2 immunolabeling intensity in TAZ-KD cells following dDAVP stimulation. RNA sequencing analysis identified 1370 and 1985 differentially expressed genes in TAZ-KD cells under basal conditions and after dDAVP treatment, respectively. Among 17 previously identified transcription factor (TF) candidates, seven (Nr4a1, Cebpb, Mef2d, Elf3, Klf5, Junb, Stat3) were significantly upregulated by dDAVP in either control or TAZ-KD conditions. Among them, RT-qPCR analysis identified Nr4a1 as a TAZ-dependent TF, and immunoblotting revealed reduced NR4A1 protein levels in TAZ-KD cells upon dDAVP stimulation. This finding suggests its role as a TAZ-regulated target in dDAVP response pathway. Accordingly, Nr4a1-KD reduced the dDAVP-induced upregulation of Aqp2 mRNA and protein. KEGG pathway enrichment analysis revealed that HIF-1 signaling and glycolysis as central pathways affected by TAZ. TAZ-NR4A1 axis acts as a novel transcriptional regulatory mechanism in controlling vasopressin-mediated AQP2 expression.

PMID:40569148 | DOI:10.1096/fj.202500686RR

Adv Sci (Weinh). 2025 Jun 26:e07210. doi: 10.1002/advs.202507210. Online ahead of print.

ABSTRACT

SYNTAXIN 12/13 (STX12), a member of the syntaxin protein family enriched in the brain and heart, plays important roles in vesicle recycling. Currently, the role of STX12 in cardiovascular physiology remains unclear. Using zebrafish and mice, it is shown that STX12 loss leads to pericardial edema, cardiac malformations, and heart failure. Stx12 depletion disrupts mitochondrial morphology, reduces iron and zinc levels, and impairs ATP production. Stx12-deficient cardiomyocytes exhibit prolonged repolarization due to decreased sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Treatment with rapamycin, an mTOR inhibitor, restores mitochondrial protein expression and function by prompting the TFEB-PGC1α axis, enhances SERCA activity via the CAMKII-phospholamban pathway, and reduces the expression of stress markers. These findings suggest that STX12 plays an important role in the energy metabolism and metal homeostasis of cardiomyocytes. Enhancing mitochondrial function, autophagy, and SERCA activity through the administration of rapamycin may provide a potential therapeutic approach for cardiomyopathies associated with STX12 deficiency and hypometabolism.

PMID:40568929 | DOI:10.1002/advs.202507210

J Phys Chem B. 2025 Jun 26. doi: 10.1021/acs.jpcb.5c02054. Online ahead of print.

ABSTRACT

Neutral fats in living organisms are stored in lipid droplets, intracellular organelles enveloped by a phospholipid monolayer. The fusion of these lipid droplets is vital for numerous physiological functions and is regulated by specific proteins and lipids. Dysregulation of this process, leading to excessive droplet growth, is associated with various pathological conditions. Notably, changes in the lipid composition of the boundary monolayers can significantly influence the fusion rate, mirroring fusion dynamics of membranous compartments surrounded by lipid bilayers. In this study, we conducted a theoretical and computational analysis of monolayer fusion, extending the established bilayer fusion model to this context. We characterize the energy trajectory associated with monolayer fusion, tracing the process from the initial unperturbed state to the formation of physical contact between monolayers, and subsequently to the expansion of this structure, which we refer to as the monolayer stalk, analogous to bilayer fusion. Unlike bilayer fusion, monolayer fusion features a single energy barrier, determining the process efficiency. Once this barrier is overcome, further droplet merging occurs spontaneously, highlighting the dynamic nature of lipid droplet interactions. We analyze how lipid composition influences this energy barrier and explore the effects of factors such as Gaussian curvature and hydration-induced repulsion on the energy landscape. Our calculations reveal that Gaussian curvature energy significantly contributes to barrier height. An increase in the proportion of lipids exhibiting large negative spontaneous curvature, which enhances fusion likelihood, can substantially decrease this barrier. Our findings are consistent with existing experimental data and allow us to quantify the barrier height as a function of lipid composition. Specifically, we demonstrate that incorporating 50 mol % of dioleoylphosphatidylethanolamine (DOPE) into pure dioleoylphosphatidylcholine (DOPC) monolayers reduces the energy barrier height by approximately 16 kBT - half of this reduction attributed to changes in spontaneous curvature, with the other half due to modification in hydration repulsion parameters. These findings provide quantitative insights into lipid droplet fusion mechanisms, advancing our understanding of lipid metabolism and its physiological regulation.

PMID:40566901 | DOI:10.1021/acs.jpcb.5c02054

Biol Chem. 2025 Jun 27. doi: 10.1515/hsz-2025-0109. Online ahead of print.

ABSTRACT

Stress responses in biological systems arise from complex, dynamic interactions among genes, proteins, and metabolites. A thorough understanding of these responses requires examining not only changes in individual molecular components but also their organization into interconnected pathways and networks that collectively maintain cellular homeostasis. This review provides an overview of computational strategies designed to capture these multifaceted processes. First, we discuss the importance of data analysis in uncovering how stress adaptation unfolds, highlighting both classical approaches (e.g., ANOVA, t-tests) and more advanced methods (e.g., clustering, smoothing splines) that handle strong temporal dependencies. We then explore how enrichment analyses can contextualize these dynamic changes by linking regulated molecules to broader biological functions and processes. The latter half of the review focuses on network-based modeling techniques, emphasizing the construction and refinement of de novo networks to identify stress-specific regulatory networks. Pairwise approaches are discussed alongside advanced methods that include multi-omics data, literature knowledge, and machine learning. Finally, we address comparative network analyses, which facilitate cross-condition studies, revealing both conserved and distinct features that shape resilience. With continued advances in high-throughput experimentation and computational modeling, these methods will deepen our insights into how cells detect and counteract stress.

PMID:40566726 | DOI:10.1515/hsz-2025-0109

Int J Mol Sci. 2025 Jun 16;26(12):5772. doi: 10.3390/ijms26125772.

ABSTRACT

Tumor development is mainly marked by the gradual transformation of cells that acquire capacities such as sustained growth signaling, evasion of growth suppression, resistance to cell death, and induction of angiogenesis, achieving replicative immortality and activating invasion and metastasis. How different epigenetic alterations like m1A, m5C, and m6A contribute to tumor development is a field that still needs to be investigated. The immune modulators, CD70, CD80, and TIGIT, mainly regulate T-cell activation and consequently the immune evasion of tumors. Here, we explored the presence and the potential consequences of RNA modifications in these regulators in pan-cancer. Our findings highlight the critical role of the m6A, m5C, and m1A in regulating CD70, CD80, and TIGIT across multiple solid tumors. By combining epitranscriptomics data with functional enrichment and survival modeling, we show that RNA modification enzymes not only modulate immune-related gene expression but also serve as potential biomarkers for patient prognosis. By constructing a robust four-gene prognostic signature involving YTHDF3, RBM15B, IGF2BP2, and TRMT61A, we demonstrate that RNA modification profiles can accurately stratify patients into risk groups with distinct overall survival outcomes. The performance of this model across eight cancer types underscores the translational promise of epitranscriptomic markers in both mechanistic understanding and personalized oncology. Altogether, our study bridges the gap between the mechanistic regulation of immune checkpoints and their clinical utility, offering novel insights into how the epitranscriptome can be leveraged to improve cancer prognosis and potentially enhance immunotherapeutic strategies.

PMID:40565233 | DOI:10.3390/ijms26125772

Int J Mol Sci. 2025 Jun 13;26(12):5671. doi: 10.3390/ijms26125671.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure. Despite advances in understanding its genetic basis, particularly mutations in Chromosome 9 Open Reading Frame 72 (C9orf72), superoxide dismutase 1 (SOD1), TAR DNA-binding protein (TARDBP), and Fused in Sarcoma (FUS) gene, current diagnostic methods result in delayed intervention, and available treatments offer only modest benefits. This review examines innovative approaches transforming ALS research and clinical management. We explore emerging biomarkers, including the fluid-based markers such as neurofilament light chain, exosomes, and microRNAs in biological fluids, alongside the non-fluid-based biomarkers, including neuroimaging and electrophysiological markers, for early diagnosis and patient stratification. The integration of multi-omics data reveals complex molecular mechanisms underlying ALS heterogeneity, potentially identifying novel therapeutic targets. We highlight current gene therapy strategies, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and CRISPR/Cas9 gene editing systems, alongside advanced delivery methods for crossing the blood-brain barrier. By bridging molecular neuroscience with bioengineering, these technologies promise to revolutionize ALS diagnosis and treatment, advancing toward truly disease-modifying interventions for this previously intractable condition.

PMID:40565135 | DOI:10.3390/ijms26125671

Int J Mol Sci. 2025 Jun 11;26(12):5599. doi: 10.3390/ijms26125599.

ABSTRACT

Peptaibols are linear fungal peptides featuring α,α-dialkylated amino acids (e.g., α-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus Trichodema sp. SK1-7, isolated from decaying wood, revealed the production of previously described trichorozin IV (1), along with novel SF4-type peptaibol 2 (trichorozin V). The structures of these compounds were elucidated through MS analysis, NMR study and advanced Marfey's method. The genome of Trichoderma sp. SK1-7 harbors two PKS-NRPS hybrid gene clusters containing 14 and 18 adenylation domains. Analysis of the modular architecture suggested that trichorozins are synthesized by a 14-module protein via a module skipping mechanism. Genome mining revealed several types of short peptaibol synthase architectures (10-14 adenylation domains) across various Trichoderma species, accompanied by similar long peptaibol synthases. Furthermore, putative Aib/Iva biosynthesis machinery in Trichoderma was identified, showing specific architectures potentially involved in regulating peptaibol biosynthesis. Feeding experiments demonstrated that peptaibol production depends on the ratio of Iva/Aib. The isolated compounds exhibited moderate antibacterial and cytotoxic activities along with a synergistic effect when combined with membrane-targeting antibiotics. Our findings suggest that genome-guided approaches hold promise for further development of peptabiotics with a wide range of applications, including antibiotic adjuvants.

PMID:40565070 | DOI:10.3390/ijms26125599

Int J Mol Sci. 2025 Jun 10;26(12):5532. doi: 10.3390/ijms26125532.

ABSTRACT

Retinal dysfunction is emerging as a potential early marker of neurodegenerative diseases. Within the retina, the dopaminergic circuit, comprising dopaminergic amacrine cells, dopamine synthesis and turnover, and dopamine receptor signalling, is essential for visual processing, particularly colour contrast perception. Disruption of this circuit may underline early retinal alterations observed in Huntington's disease (HD) and Alzheimer's disease (AD). In this study, we systematically analysed retinal dopaminergic dysfunction in murine models of HD (genetic origin) and AD (sporadic), across different disease stages. We assessed dopamine levels, turnover, tyrosine hydroxylase expression, D1 and D2 receptor gene expression, and neurotransmitter balance. HD mice showed early and marked alterations: reduced dopamine content, decreased tyrosine hydroxylase, increased turnover, and downregulation of D1 receptor expression-all preceding motor symptoms and detectable brain pathology. In contrast, AD mice showed only mild changes at later stages; however, clinical evidence suggests that similar dysfunction may occur earlier in human AD. These findings position retinal dopaminergic disruption as a potential early biomarker in HD and possibly in AD. While the current study relies on invasive techniques in animal models, it lays the groundwork for non-invasive retinal assessments, such as electroretinography or optical coherence tomography, as promising tools for early diagnosis and disease monitoring in neurodegeneration.

PMID:40564996 | DOI:10.3390/ijms26125532

Int J Mol Sci. 2025 Jun 10;26(12):5529. doi: 10.3390/ijms26125529.

ABSTRACT

The multiple health benefits of regular physical activity are well known and are the results of exercise adaptations. The study of physical training biology is not straightforward since it involves organ crosstalk and depends on numerous variables, such as type of exercise or individual physiology. A multiomic approach allows us to analyze proteins, metabolites, lipids, and epigenetic modifications on a wide scale, so it is a valid tool to identify numerous patterns and clarify how exercise exerts its beneficial effects. Stimuli given by physical activity lead the body to re-establish a new dynamic balance at the level of redox homeostasis and metabolic state. Evaluating the effect of specific training is important for maximizing the beneficial effects of physical activity. In this review we provide a brief overview of different omics technologies used in this field. For each "omics" we analyzed studies published in the last 10 years and highlighted the main molecules identified with that approach. We then described future challenges in their application from the perspective of using new bioinformatics and artificial intelligence tools.

PMID:40564993 | DOI:10.3390/ijms26125529

Int J Mol Sci. 2025 Jun 9;26(12):5516. doi: 10.3390/ijms26125516.

ABSTRACT

Diabetic cardiomyopathy (DCM) is a significant complication of diabetes, particularly affecting East Asian populations with a high prevalence of the ALDH2*2 (Glu504Lys) genetic variant. This variant impairs aldehyde detoxification, leading to increased oxidative stress, mitochondrial dysfunction, and chronic inflammation, exacerbating cardiac damage and fibrosis. This review aimed to systematically delineate the pathological role of ALDH2 enzyme deficiency in DCM by integrating clinical observations with mechanistic insights from experimental models and evaluating emerging therapies for genetically susceptible populations. In vitro and in vivo studies demonstrate that ALDH2*2 amplifies oxidative stress and disrupts mitochondrial homeostasis under hyperglycemic conditions, leading to enhanced cardiac fibrosis and functional decline. Additionally, ALDH2*2 carriers show heightened susceptibility to metabolic stress, further aggravating DCM. Given the high prevalence of ALDH2*2 in East Asian populations, targeted therapeutic strategies are urgently needed. Promising approaches include ALDH2 activators (e.g., Alda-1) that enhance detoxification of reactive aldehydes, and SGLT2 inhibitors (e.g., empagliflozin) that improve mitochondrial function and reduce oxidative damage. These therapies can mitigate oxidative stress and preserve cardiac function in ALDH2*2 carriers, thereby potentially reducing DCM burden, especially in high-risk East Asian populations. Further clinical investigations are warranted to validate these therapeutic approaches and optimize management for ALDH2-deficient individuals.

PMID:40564981 | DOI:10.3390/ijms26125516

Int J Mol Sci. 2025 Jun 7;26(12):5473. doi: 10.3390/ijms26125473.

ABSTRACT

This study looked into the underlying mechanisms and causal relationship between alcoholic liver disease (ALD) and the blood metabolite uridine using a variety of analytical methods, such as Mendelian randomization and molecular dynamics simulations. We discovered uridine to be a possible hepatotoxic agent aggravating ALD by using Mendelian randomization (MR) analysis with genome-wide association study (GWAS) data from 1416 ALD cases and 217,376 controls, as well as with 1091 blood metabolites and 309 metabolite concentration ratios as exposure factors. According to network toxicology analysis, uridine interacts with important targets such as SRC, FYN, LYN, ADRB2, and GSK3B. The single-cell RNA sequencing analysis of ALD tissues revealed that SRC was upregulated in hepatocytes and activated hepatic stellate cells. Subsequently, we determined the stable binding between uridine and SRC through molecular docking and molecular dynamics simulation (RMSD = 1.5 ± 0.3 Å, binding energy < -5.0 kcal/mol). These targets were connected to tyrosine kinase activity, metabolic reprogramming, and GPCR signaling by Gene Ontology (GO) and KEGG studies. These findings elucidate uridine's role in ALD progression via immunometabolic pathways, offering novel therapeutic targets for precision intervention. These findings highlight the necessity of systems biology frameworks in drug safety evaluation, particularly for metabolites with dual therapeutic and toxicological roles.

PMID:40564937 | DOI:10.3390/ijms26125473

Cancers (Basel). 2025 Jun 9;17(12):1921. doi: 10.3390/cancers17121921.

ABSTRACT

BACKGROUND: Standard treatment for patients with early-stage estrogen receptor-positive (ER+) breast cancer often includes sequential adjuvant radiation and endocrine therapies. Unfortunately, ~1/3 of patients eventually experience disease recurrence, partly due to residual disease in the form of drug-tolerant persister cancer cells. The anti-cancer efficacy of radiation therapy is partly attributable to the production of oxyradicals that damage biomolecules. We previously showed that endocrine therapy increases mitochondrial content in ER+ breast cancer cells; we postulated that this may also increase oxidative stress.

METHODS: Herein, we tested the efficacy of concurrent endocrine and radiation therapies, including both conventional (CDR) and ultra-high dose rate (UHDR) radiation.

RESULTS: We found that estrogen deprivation and radiation inhibit cell growth, induce apoptosis, and force cells into an oxidatively stressed state. DNA damage was almost exclusive to cells treated with the combination of endocrine and radiation therapy. Radiation slowed tumor growth in two xenograft models, and combination with estrogen deprivation prolonged the time to regrowth in ZR75-1 tumors.

CONCLUSIONS: These findings indicate that simultaneous treatment with endocrine and radiation therapies can be advantageous, warranting further evaluation to identify tumor features predictive of response to individual and combination treatments.

PMID:40563571 | DOI:10.3390/cancers17121921

Biomolecules. 2025 May 24;15(6):758. doi: 10.3390/biom15060758.

ABSTRACT

The tumor suppressor gene NKX3.1 and the LPL gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of LPL loss may be misinterpreted due to its co-deletion with NKX3.1, a well-established event in prostate carcinogenesis. This study investigates whether LPL deletion represents a biologically relevant event or occurs merely as a bystander to NKX3.1 loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed LPL deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of NKX3.1 and LPL in 54 patients. Notably, NKX3.1 loss without accompanying LPL deletion was observed in eight additional cases. These findings suggest that LPL deletion is a passenger event secondary to NKX3.1 loss and underscore the importance of cautious interpretation of cytogenetic findings involving the LPL locus.

PMID:40563400 | DOI:10.3390/biom15060758

Antioxidants (Basel). 2025 Jun 4;14(6):682. doi: 10.3390/antiox14060682.

ABSTRACT

Wound healing is a very complex process composed of several phases in which precise events occur, both temporally and specially. However, when these processes go awry, biofilm-forming bacteria become installed in the healing tissue, and the patient has comorbidities, so the wounds do not heal and become chronic. In this review, we describe the importance of high levels of oxidative stress (OS) and bacteria from the skin microbiome in the initiation and development of chronic wounds. The skin microbiome is diverse in humans, and its composition is dependent on the environment in the specific areas of the body. OS is critical for wound healing as it stimulates the immune system to destroy pathogens and secrete cytokines and growth factors that stimulate healing. When OS levels become high in the wound and the bacteria of the skin install themselves in the wound, chronicity ensues. However, neither OS nor the bacteria of the skin alone can initiate chronicity. However, when present together, chronic wounds develop. Given the complexity of chronic wound initiation, developing treatment for these wounds has been difficult. Here, we also discuss the challenges of treating chronic wounds and offer a potential sequence of approaches to treating these wounds after debridement.

PMID:40563316 | DOI:10.3390/antiox14060682

Bioinformatics. 2025 Jun 25:btaf370. doi: 10.1093/bioinformatics/btaf370. Online ahead of print.

ABSTRACT

MOTIVATION: High-throughput sequencing is a modern sequencing technology used to profile microbiomes by sequencing thousands of short genomic fragments from the microorganisms within a given sample. This technology presents a unique opportunity for artificial intelligence to comprehend the underlying functional relationships of microbial communities. However, due to the unstructured nature of high-throughput sequencing data, nearly all computational models are limited to processing DNA sequences individually. This limitation causes them to miss out on key interactions between microorganisms, significantly hindering our understanding of how these interactions influence the microbial communities as a whole. Furthermore, most computational methods rely on post-processing of samples which could inadvertently introduce unintentional protocol-specific bias.

RESULTS: Addressing these concerns, we present SetBERT, a robust pre-training methodology for creating generalized deep learning models for processing high-throughput sequencing data to produce contextualized embeddings and be fine-tuned for downstream tasks with explainable predictions. By leveraging sequence interactions, we show that SetBERT significantly outperforms other models in taxonomic classification with genus-level classification accuracy of 95%. Furthermore, we demonstrate that SetBERT is able to accurately explain its predictions autonomously by confirming the biological-relevance of taxa identified by the model.

AVAILABILITY AND IMPLEMENTATION: All source code is available at https://github.com/DLii-Research/setbert. SetBERT may be used through the q2-deepdna QIIME 2 plugin whose source code is available at https://github.com/DLii-Research/q2-deepdna.

SUPPLEMENTARY INFORMATION: Supplementary data, figures, and results are available online.

PMID:40563247 | DOI:10.1093/bioinformatics/btaf370

Chin Med. 2025 Jun 26;20(1):92. doi: 10.1186/s13020-025-01152-8.

ABSTRACT

Traditional Chinese medicine (TCM) has become a standardized medical system through systematic development across global healthcare practices. However, concerns persist regarding the safety, efficacy and quality of traditional medicinal products. Traditional Chinese medicine regulatory science (TCMRS) has emerged as an interdisciplinary field to address these challenges. This discipline integrates multidisciplinary knowledge to develop new tools, standards and approaches for systematic evaluation of benefit-risk profiles. This approach aims to ensure the quality, safety, and efficacy of TCM products, while also supporting the development of scientifically grounded regulatory frameworks that accommodate traditional medicine's distinctive characteristics. Through comprehensive quality management from raw material sourcing to production processes and clinical validation, developing and adopting TCMRS is entrusted to significantly strengthen its regulatory oversight. This review examines the critical scientific challenges in the modernization process of TCM, analyzes the conceptual foundations of TCMRS, evaluates its pivotal role in pharmaceutical transformation, and highlights its essential function in preserving traditional knowledge while fostering therapeutic innovation. Key challenges for TCMRS implementation include reconciling traditional epistemologies with modern pharmaceutical paradigms, standardizing complex herbal formulations, and developing rigorous evaluation protocols for decoctions and compound preparations. The integration of advanced methodologies, including systems biology, network pharmacology, artificial intelligence, and nanotechnology, into regulatory frameworks, combined with enhanced international cooperation, remains a crucial strategy for tackling global public health challenges. Future development trajectories for TCMRS will prioritize lifecycle management strategies, technology-driven innovation systems, and global knowledge-sharing initiatives, propelled by advancements in life sciences and information technology. This evolution requires careful balancing of three fundamental elements: theoretical development in traditional medicine, integration of emerging technologies, and maintenance of regulatory system stability. It is crucial to innovate the working mechanisms of the TCMRS researcher alliance and the global policy-coordination mechanism for TCM regulation, enhance the conversion of basic disciplines into regulatory applications, and support the establishment of an excellent TCM regulatory system with scientific decision-making. These efforts are essential for promoting the high-quality development of the TCM industry and boosting its international influence and presence.

PMID:40563101 | DOI:10.1186/s13020-025-01152-8

NPJ Microgravity. 2025 Jun 25;11(1):23. doi: 10.1038/s41526-025-00463-2.

ABSTRACT

Cultivation of microorganisms in space has enormous potential to enable in-situ resource utilization (ISRU) Here, we develop an autonomous payload with fully programmable serial passaging and sample preservation, termed the Modular Open Biological Platform (MOBP), and flight-test the MOBP aboard the International Space Station (ISS) by conducting enzymatic and microbial plastics upcycling experiments. The MOBP is a compact, modular bioreactor system that allows for sustained microbial growth via automated media transfers, such as those for sample collection and storage for terrestrial analyses, and precise data monitoring from integrated sensors. The MOBP was flight-tested with two experiments designed to evaluate biological upcycling of the plastic poly(ethylene terephthalate) (PET). The bioproduct βKA can be polymerized into a nylon-6,6 analog with improved properties for use in the production of a variety of materials. We posit the MOBP will aid in democratizing the execution of synthetic biology in spaceflight towards enabling ISRU.

PMID:40562752 | DOI:10.1038/s41526-025-00463-2