FASEB J. 2025 Jun 30;39(12):e70735. doi: 10.1096/fj.202500718R.

ABSTRACT

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) and associated liver fibrosis is rapidly increasing, while pharmacological treatment options remain limited. Despite great efforts in developing novel MASH therapeutics, many investigative therapeutics that reduced fibrosis in preclinical models ultimately failed in clinical trials. To this end, we explored the possibility of predicting the efficacy of therapeutics by evaluating changes in the expression of a fibrogenic gene signature in the early stages of disease development and before effects on pathology become evident. Ldlr-/-.Leiden mice were fed a high-fat diet (HFD) to induce obesity and MASH. Mice were subsequently treated for 4 weeks with various therapeutics with established efficacy (obeticholic acid) or lack of efficacy (cenicriviroc and pioglitazone) to study their anti-fibrotic potential. Expression of a fibrogenic gene signature was evaluated, which predicts profibrotic processes before histopathologic fibrosis develops. The predictions were compared with a long-term experiment reaching histological fibrosis endpoints. Cenicriviroc and pioglitazone did not affect HFD-induced fibrosis signature, indicative of no effect of these treatments on active fibrosis processes. Consistently, in the long-term treatment study, both cenicriviroc and pioglitazone did not affect HFD-induced histologically measured fibrosis. In contrast, obeticholic acid improved the fibrogenic gene signature to a healthier state compared to untreated HFD controls. These early gene expression changes aligned with long-term histological fibrosis endpoints and clinical data on these investigative therapeutics. This study highlights the potential of using short-term studies and applying a fibrogenic gene signature as an early screening tool to investigate the efficacy of investigative drugs on MASH-associated fibrosis. This signature, which is based on the active fibrosis processes in humans, may allow rapid screening of therapeutics, or combinations thereof, when used in a translational mouse model.

PMID:40515541 | DOI:10.1096/fj.202500718R

Cancer Cell Int. 2025 Jun 13;25(1):211. doi: 10.1186/s12935-025-03843-6.

ABSTRACT

The liver exhibits extensive circadian regulation among organs. Epidemiological studies have substantiated that disruptions in circadian rhythm constitute a risk factor for the oncogenesis of liver cancer. Nonetheless, the molecular underpinnings of how circadian dysregulation influences liver cancer progression remain elusive. Our research aims to elucidate these mechanisms and develop a predictive model for prognosis and treatment responsiveness. Our multi-omics analysis revealed extensive dysregulation of liver circadian genes (LCGs) in liver cancer. Employing machine learning algorithms, we pinpointed four pivotal dysregulated LCGs. Through the integration of single-cell, bulk, and spatial transcriptomics, we further elucidated the interconnections between LCGs dysregulation and the tumor microenvironment. In vivo and in vitro experiments demonstrated that RBM17, identified as a crucial dysregulated LCG, promotes the progression of liver cancer and cisplatin resistance by facilitating cancer stem cell phenotype. The circadian prognosis scores (CPS), based on these four genes, effectively reflected the prognosis of liver cancer patients and their responses to various therapeutic interventions. Mechanism of Action (MOA) analysis suggested that high CPS level may sensitize tumors to cell cycle-targeted therapies. Collectively, our findings provide new insights into the interplay between liver circadian gene regulation and liver cancer progression, and propose novel therapeutic targets for liver cancer.

PMID:40514677 | DOI:10.1186/s12935-025-03843-6

Acta Biomater. 2025 Jun 11:S1742-7061(25)00434-9. doi: 10.1016/j.actbio.2025.06.019. Online ahead of print.

ABSTRACT

Osteogenesis (bone formation) and vascularization (blood vessel formation) are two central and interconnected physiological-relevant processes in bone formation. Prevascularization of humanized tissue-engineered bone constructs (hTEBCs) has been proposed to better mimic the human bone microenvironment by enhancing vascular integration and facilitating greater osteogenic capacity. Here, we investigated the effects of premineralization and prevascularization on bone and vasculature development in an ectopic hTEBC model using a scaffold-hydrogel composite approach. Human osteoblast cells (hOBs) were cultured under osteogenic conditions (OM), with or without a 3-day mineralization boost (OM+) period for 4 weeks prior to implantation in vivo in a supporting porous polycaprolactone (mPCL) scaffold. Separately, photocrosslinkable fish gelatin-derived hydrogels placed within supporting mPCL scaffolds showed formation of elongated vascular networks as early as day 3 with in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem/stromal cells (MSCs). The OM and OM+ cultured constructs were subcutaneously implanted into immunocompromised rats with and without the prevascular hydrogels, resulting in four subgroups: OM, OM+, OM/Vas, and OM+/Vas. Our results demonstrated that the OM+ group led to more rapid osteoinduction and enhanced osteogenic differentiation in vivo with woven bone structure and active remodeling. Conversely, prevascularization (OM/Vas, OM+/Vas groups) led to reduce in vivo bone volume and density but promoted the development of human endothelial networks and successful anastomosis with host vasculature. Our study highlights the distinct contributions of premineralization and prevascularization, where premineralization is critical for robust bone formation and prevascularization enhances vascular integration, providing important insights for advancing the physiological relevance of hTEBC models in animal hosts. STATEMENT OF SIGNIFICANCE: This study demonstrates the development of humanized tissue engineered bone constructs incorporating a vascular niche using a rat. By integrating innovative pre-mineralization and pre-vascularization techniques within scaffold-hydrogel composite, we show that premineralization accelerates bone formation, while prevascularization promotes endothelial network formation and integration with host vasculature. Photocrosslinkable, low-stiffness LunaGel™ hydrogels enhanced microcapillary-like structure formation and endothelial sprouting in in vitro co-culture. However, by combining osteogenic and vascular cues within a biodegradable composite, this work advances the bone tissue engineering field by creating a model that more accurately reflects the divergent and competing nature of vascularization and bone formation. This platform has broad applicability for studying bone-vascular interactions and may inform strategies to improve the design of biomaterials for regenerative therapies.

PMID:40514004 | DOI:10.1016/j.actbio.2025.06.019

Mol Cell Proteomics. 2025 Jun 11:101014. doi: 10.1016/j.mcpro.2025.101014. Online ahead of print.

ABSTRACT

Neuroblastoma is the most common heterogeneous solid tumor in children, and current treatment options remain limited, especially for high-risk patients. Previous studies have identified dihydroorotate dehydrogenase (DHODH), a key enzyme in pyrimidine synthesis, as a potential therapeutic target in cancer. However, none of the existing FDA-approved DHODH inhibitors have shown effective inhibition of neuroblastoma cell growth. To address this challenge, we employed virtual screening to discover potential DHODH-targeting drugs, identifying Regorafenib as a promising candidate. Regorafenib significantly inhibited neuroblastoma growth in both neuroblastoma cells and patient-derived organoids. To unravel the underlying molecular mechanisms, we conducted Tandem Mass Tag (TMT)-based quantitative proteomics using LC-MS/MS. Our proteomic profiling revealed substantial regulation of lipid metabolism proteins, specifically those in the mevalonate pathway, correlating with ferroptosis induction. Further analysis showed that DHODH inhibition led to a reduction in total cholesterol, cholesterol esters, disrupted lipid droplet formation, and significantly decreased the expression of Squalene Epoxidase (SQLE), a key enzyme in lipid metabolism. Notably, we also observed an increase in nuclear SQLE expression following DHODH inhibition. In summary, our study highlights DHODH blockade as a novel approach to induce ferroptosis through lipid metabolism reprogramming, underscoring DHODH as a viable therapeutic target for neuroblastoma treatment. These insights open new avenues for metabolic-based interventions in aggressive pediatric cancers.

PMID:40513779 | DOI:10.1016/j.mcpro.2025.101014

Cell Stem Cell. 2025 Jun 10:S1934-5909(25)00192-4. doi: 10.1016/j.stem.2025.05.012. Online ahead of print.

ABSTRACT

Repair of muscle damage declines with age due to the accumulation of dysfunctional muscle stem cells (MuSCs). Here, we uncover that aged MuSCs have blunted prostaglandin E2 (PGE2)-EP4 receptor signaling, which causes precocious commitment and mitotic catastrophe. Treatment with PGE2 alters chromatin accessibility and overcomes the dysfunctional aged MuSC fate trajectory, increasing viability and triggering cell cycle re-entry. We employ neural network models to learn the complex logic of transcription factors driving the change in accessibility. After PGE2 treatment, we detect increased transcription factor binding at sites with CRE and E-box motifs and reduced binding at sites with AP1 motifs, overcoming the changes that occur with age. We find that short-term exposure of aged MuSCs to PGE2 augments their long-term regenerative capacity upon transplantation. Strikingly, PGE2 injections following myotoxin- or exercise-induced injury overcome the aged niche, leading to enhanced regenerative function of endogenous tissue-resident MuSCs and an increase in strength.

PMID:40513560 | DOI:10.1016/j.stem.2025.05.012

J Hazard Mater. 2025 May 29;495:138785. doi: 10.1016/j.jhazmat.2025.138785. Online ahead of print.

ABSTRACT

The widespread use of p-chloro-m-xylenol (PCMX) as a broad-spectrum antimicrobial agent raises concerns about its ecological risks in ecosystems. While prior studies focused on activated sludge systems, the impacts of PCMX on marine systems remain unknown. Here, we systematically investigated the responses of marine sediment communities to PCMX (0.005-50 mg/L) exposure through integrated enzymatic assays, multi-omics, and enrichment culture approaches. High PCMX exposure (50 mg/L) significantly suppressed dehydrogenase (63.8 %) and protease (53.8 %) activity, reduced microbial diversity, and inhibited nutrient cycling and ATP production. Meanwhile, antibiotic resistance genes associated with efflux pumps were enriched. Metagenomic analysis revealed upregulated aromatic degradation pathways and stress-response mechanisms (e.g., chemotaxis and biofilm formation) under PCMX stress. A halotolerant marine consortium enriched from high-PCMX sediments demonstrated efficient PCMX degradation (50 mg/L, 72 h) across broad salinity (1.5-5.5 % NaCl) and temperature (25-40°C) ranges, with metabolite profiling suggesting ortho-cleavage pathways. This work underscores the need for regulatory measures to mitigate the ecological risks posed by PCMX in marine ecosystems, while simultaneously demonstrating the remediation potential of a halotolerant microbial consortium for remediating contaminated environments.

PMID:40513160 | DOI:10.1016/j.jhazmat.2025.138785

J Mol Model. 2025 Jun 13;31(7):188. doi: 10.1007/s00894-025-06412-w.

ABSTRACT

CONTEXT: Modern medication discovery is undergoing a paradigm change at the junction of herbal pharmacology with computational modeling informed by quantum theory. Herbal compounds, which have often been considered as complex and poorly understood entities, have historically been investigated using linear screening approaches and reductionist bioactivity models. A novel paradigm being presented in this work is herbal holography. Herbal molecules are seen by it as multi-dimensional systems best understood using holographic and quantum theories. As the pharmacological potential of plant-based compounds is under expanding research, more intricate integrated approaches are needed to grasp their bioactivities, predict their pharmacokinetics, and maximize drug lead optimization. The aim is to ascertain whether using quantum-driven methods results in a real revolution in herbal medicine or if it is really a pipe dream.

METHODS: This paper conducts a thorough examination of herbal remedies, focusing on how algorithms powered by hybrid quantum-classical simulations, deep learning models, and quantum mechanics can address the shortcomings of traditional methods. The advanced computational approaches explored in this research provide scalable models for modeling herbal compounds and assessing their pharmacological effects. Integrating views from systems biology, photochemistry, and quantum mechanics helps one to evaluate the translational usefulness of these technologies. The methodological approach using computational approaches for electronic structure prediction, network pharmacology, and bioactivity modeling draws from quantum physics, systems biology, and phytochemistry. We examine these early quantum technologies' scalable, usable benefits for interpreting herbal therapy complexity from a multidisciplinary perspective to include them into present drug development projects.

PMID:40512383 | DOI:10.1007/s00894-025-06412-w

J Gen Virol. 2025 Jun;106(6). doi: 10.1099/jgv.0.002077.

ABSTRACT

In April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking.

PMID:40512168 | DOI:10.1099/jgv.0.002077

Ann N Y Acad Sci. 2025 Jun 13. doi: 10.1111/nyas.15383. Online ahead of print.

ABSTRACT

Many species produce rhythmic sound sequences. Some purportedly speed up their vocalizations throughout a display, reminiscent of-but not necessarily equivalent to-accelerando in human music. This phenomenon has been frequently reported but rarely quantified, which limits our ability to understand its mechanism, function, and evolution. Here, we use a suite of rhythm analyses to quantify temporal and acoustic features in the ecstatic display songs of male African penguins (Spheniscus demersus). We show that songs get faster (i.e., accelerando) and louder (i.e., crescendo) as they progress. The accelerando occurs because the intersyllable silences, not the syllables themselves, predictably shorten over time. This rhythmicity is maintained even when individuals take audible breaths. Individuals also show plasticity: when they start with a slow tempo, they speed up more strongly than when they start with a fast tempo. We hypothesize that this well-timed accelerando may stem from arousal-based mechanisms, biomechanical constraints, or more complex rhythmic control. Future work should test the mechanisms behind this intra-individual rhythmic variation since nonpasserine birds are thought to have limited vocal plasticity. By integrating a rich empirical dataset with cutting-edge rhythm analyses, we establish the necessary foundation to determine how such features evolved and their role(s) across communication systems.

PMID:40511771 | DOI:10.1111/nyas.15383

Elife. 2025 Jun 13;13:RP98469. doi: 10.7554/eLife.98469.

ABSTRACT

Single-cell RNA-sequencing (scRNA-seq) coupled with robust computational analysis facilitates the characterization of phenotypic heterogeneity within tumors. Current scRNA-seq analysis pipelines are capable of identifying a myriad of malignant and non-malignant cell subtypes from single-cell profiling of tumors. However, given the extent of intra-tumoral heterogeneity, it is challenging to assess the risk associated with individual cell subpopulations, primarily due to the complexity of the cancer phenotype space and the lack of clinical annotations associated with tumor scRNA-seq studies. To this end, we introduce SCellBOW, a scRNA-seq analysis framework inspired by document embedding techniques from the domain of Natural Language Processing (NLP). SCellBOW is a novel computational approach that facilitates effective identification and high-quality visualization of single-cell subpopulations. We compared SCellBOW with existing best practice methods for its ability to precisely represent phenotypically divergent cell types across multiple scRNA-seq datasets, including our in-house generated human splenocyte and matched peripheral blood mononuclear cell (PBMC) dataset. For tumor cells, SCellBOW estimates the relative risk associated with each cluster and stratifies them based on their aggressiveness. This is achieved by simulating how the presence or absence of a specific cell subpopulation influences disease prognosis. Using SCellBOW, we identified a hitherto unknown and pervasive AR-/NElow (androgen-receptor-negative, neuroendocrine-low) malignant subpopulation in metastatic prostate cancer with conspicuously high aggressiveness. Overall, the risk-stratification capabilities of SCellBOW hold promise for formulating tailored therapeutic interventions by identifying clinically relevant tumor subpopulations and their impact on prognosis.

PMID:40511682 | DOI:10.7554/eLife.98469

J Natl Cancer Inst. 2025 Jun 13:djaf137. doi: 10.1093/jnci/djaf137. Online ahead of print.

ABSTRACT

BACKGROUND: The role of lipid-perturbing medications in cancer risk is unclear.

METHODS: We employed cis-Mendelian randomization and colocalisation to evaluate the role of 5 lipid-perturbing drug targets (ANGPTL3, ANGPTL4, APOC3, CETP, PCSK9) in risk of 5 cancers (breast, colorectal, head and neck, ovarian, prostate). We triangulated findings using pre-diagnostic protein measures in prospective analyses in EPIC (977 colorectal cancer cases, 4,080 sub-cohort members) and the UK Biobank (860 colorectal cancer cases, 50,177 controls). To gain mechanistic insight into the role of ANGPTL4 in carcinogenesis, we examined the impact of the ANGPTL4 p.E40K loss-of-function variant on differential gene expression in normal colon tissue in BarcUVa-Seq. Finally, we evaluated the association of colon tumour ANGPTL4 expression with cancer-specific mortality in TCGA.

RESULTS: In analysis of 78,473 cases and 107,143 controls, genetically-proxied circulating ANGPTL4 inhibition was associated with reduced colorectal cancer risk (ORSD decrease: 0.76,95%CI:0.66-0.89,P=5.52x10-4,PPcolocalisation=0.83). This association was replicated using pre-diagnostic circulating ANGPTL4 concentrations in EPIC (HRlog10 decrease:0.91,95%CI:0.84-0.98,P=0.01) and the UK Biobank (HRSD decrease:0.93,95%CI:0.86-0.99,P=0.03). In gene-set enrichment analysis of differential gene expression in 445 colon tissue samples, ANGPTL4 loss-of-function down-regulated several cancer-related biological pathways (P FDR<0.05), including those involved in cellular proliferation, epithelial-to-mesenchymal transition, and bile acid metabolism. In analysis of 465 colon cancer patients, lower ANGPTL4 tumour expression was associated with reduced colorectal cancer-specific mortality risk (HRlog2 decrease:0.66,95%CI:0.50-0.87,P=2.92x10-3).

CONCLUSIONS: Our integrative proteogenomic and observational analyses suggest a potential protective role of lower circulating ANGPTL4 concentrations in colorectal cancer risk. These findings support further evaluation of ANGPTL4 as a therapeutic target for colorectal cancer prevention.

PMID:40511612 | DOI:10.1093/jnci/djaf137

Front Genet. 2025 May 29;16:1627976. doi: 10.3389/fgene.2025.1627976. eCollection 2025.

NO ABSTRACT

PMID:40510812 | PMC:PMC12159017 | DOI:10.3389/fgene.2025.1627976

Open Respir Arch. 2025 May 13;6(Suppl 2):100440. doi: 10.1016/j.opresp.2025.100440. eCollection 2024 Oct.

NO ABSTRACT

PMID:40510734 | PMC:PMC12159894 | DOI:10.1016/j.opresp.2025.100440

Front Endocrinol (Lausanne). 2025 May 29;16:1576419. doi: 10.3389/fendo.2025.1576419. eCollection 2025.

ABSTRACT

Type 1 diabetes (T1D) has long been recognized as a T-cell-driven autoimmune disease. However, growing evidence highlights the involvement of metabolic, inflammatory, and gut microbiota-related factors in its progression. The endocannabinoid system (ECS), a key regulator of immune and metabolic homeostasis, has been increasingly implicated in autoimmune pathophysiology, particularly through its interactions with gut-derived metabolites. This hypothesis article underscores the need to reframe T1D pathophysiology by integrating ECS dysfunction, gut dysbiosis, and metabolic imbalances into a systems biology framework. The proposed Endocannabinoidome-Microbiota (ECBoM) model highlights a shared hallmark of autoimmunity-SCFA depletion, increased intestinal permeability, and ECS dysregulation-as key drivers of chronic inflammation and immune dysfunction. These disturbances, observed in T1D as well as in celiac disease, Hashimoto's thyroiditis, rheumatoid arthritis, and multiple sclerosis, suggest a common immune-metabolic axis across autoimmune disorders. Recognizing ECS dysregulation as a systemic feature of autoimmunity opens avenues for novel therapeutic interventions, including ECS-targeted treatments, microbiota modulation, and phytocannabinoid-based therapies. This article highlights the necessity of conducting large-scale, multi-omics studies to establish disease-specific ECS signatures, linking endocannabinoid profiling, microbiota composition, and metabolic biomarkers to disease progression. By advocating for a paradigm shift in T1D research, this article emphasizes the importance of exploring new mechanistic references to develop targeted, immune-metabolic interventions that could reshape treatment strategies and improve clinical outcomes in T1D and related autoimmune diseases.

PMID:40510476 | PMC:PMC12158731 | DOI:10.3389/fendo.2025.1576419

Int J Chron Obstruct Pulmon Dis. 2025 Jun 7;20:1829-1842. doi: 10.2147/COPD.S517864. eCollection 2025.

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disease that has a great impact on healthcare resource utilization (HRU). Large-scale real-world evidence studies evaluating the clinical and economic impact of current maintenance inhaler therapies are scarce.

OBJECTIVE: To assess annual exacerbation rate and COPD-related HRU in patients with COPD before and after initiation of an inhaled treatment regimen.

METHODS: The Optum Clinformatics® Data Mart database was used to identify inpatient, outpatient, and pharmacy claims from patients aged ≥40 years with COPD in the United States from January 2016 to June 2023. The index date was the date of the first prescription claim for a new inhaled maintenance therapy after a 12-month maintenance treatment-free baseline period. The primary outcome was the proportion of patients with ≥1 moderate/severe exacerbation within 12 months post-index. The average number of moderate/severe exacerbations per patient and the proportion of patients with inpatient, emergency department (ED), office, and outpatient visits within 12 months post-index were also assessed.

RESULTS: Of the 137,691 included patients, 51.5% were female and 74.6% were White, with a mean (standard deviation [SD]) age of 70.9 (9.49) years and a mean (SD) Elixhauser Comorbidity Index of 5.67 (3.29). Most (48.3%) patients were initiated on long-acting beta-agonists/inhaled corticosteroids (LABA/ICS). The proportions of patients with exacerbations significantly decreased overall (pre-index, 45.5%; post-index, 37.0%; P < 0.001). However, more than one-third of patients still experienced an exacerbation 12 months after initiating treatment. The proportion of patients with COPD-related HRU generally decreased; however, 5.0% and 2.9% of patients had inpatient and ED care post-index, respectively.

CONCLUSION: Despite use of inhaled treatments for COPD, patients continue to experience exacerbations and HRU. Better implementation of guideline-based COPD care and novel therapies for persistent exacerbation burden are needed to improve care of the COPD population in real-world settings.

PMID:40510054 | PMC:PMC12159538 | DOI:10.2147/COPD.S517864

Ecology. 2025 Jun;106(6):e70135. doi: 10.1002/ecy.70135.

ABSTRACT

Batesian mimicry manifests in amazing forms, yet empirical studies quantifying its efficiency in nature are virtually absent. Lepidopterans include striking mimics of aposematic hymenopterans. Imitations may include not only visual components, but also acoustic and chemical signaling. We evaluated whether hymenopteran-mimicking clearwing moths (Lepidoptera: Sesiidae) and diurnal hawkmoths (Lepidoptera: Sphingidae) complement visual anti-predator signaling with acoustical mimicry. Through field-based experiments, we then compared the response of an avian predator, the European robin (Erithacus rubecula), to hymenopteran models and their lepidopteran mimics. Our work contradicts the assumption that aposematism and Batesian mimicry provide generalized protection to insects, paving the way for comparative studies involving a broader range of predators. We verified two predictions: (1) robins discriminate among different models based on their perceived risk, with avoidance behavior occurring in response to more harmful stimuli; (2) predators respond similarly within each studied pair of model and mimic. We demonstrated a clear distinction in the reaction of robins to the hornet Vespa crabro and its mimic, the hornet clearwing Sesia apiformis, in comparison to all other tested species, strongly indicating that the presence of the hornet and hornet mimic deterred the birds.

PMID:40509703 | DOI:10.1002/ecy.70135

Materials (Basel). 2025 Jun 3;18(11):2600. doi: 10.3390/ma18112600.

ABSTRACT

Bone graft substitutes combining the mechanical features of poly-ε-caprolactone (PCL) and the bioactivity of β-tricalcium phosphate (β-TCP) have been widely reported in the literature. Surprisingly, however, very little is known about the incorporation of carbonate at a biomimicking level. The authors studied β-TCP/PCL composites at 20 wt.% and 40 wt.%, either enriched or not with sodium bicarbonate (at 2 wt.% and 4 wt.%), through SEM and EDX analyses; surface free energy estimation; pH measurement after 1, 2, and 3 days of incubation in cell media; nanoindentation; and a protein adsorption test with bovine serum albumin. The early biological response was assessed using adipose mesenchymal stem cells, as an established in vitro model, via cellular adhesion (20 min), spreading (24 h), and viability assays (1, 3, 7 days). By increasing the β-TCP content, the composites' hardnesses and Young's moduli (EiT) were improved, as well as their protein adsorption compared to neat PCL. Sodium bicarbonate increased the polar component of the surface energy, alkalinized the composite with a higher β-TCP content, and attenuated its early negative cell response. Further investigation is needed to deepen the knowledge of the mechanisms underpinning the mechanical features and long-term biological behavior.

PMID:40508598 | DOI:10.3390/ma18112600

Int J Mol Sci. 2025 May 29;26(11):5251. doi: 10.3390/ijms26115251.

ABSTRACT

Human papillomavirus (HPV) infection represents one of the most common sexually transmitted infections worldwide. However, the lack of effective therapeutic strategies to counteract viral infection and its persistence still makes the management of HPV a medical concern. Persistence is indeed a crucial issue in the context of HPV, as it may increase the risk of viral DNA integration into the host genome, thus exposing patients to tumoral progression. This clinical study aims to evaluate the effectiveness of a dietary supplement containing epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12 (B12), and hyaluronic acid (HA) in improving HPV clearance and HPV-induced cervical lesions, and in counteracting viral persistence. A total of 106 patients who tested positive for HPV DNA were enrolled in this study and were treated daily for 6 months with a tablet containing EGCG (200 mg), FA (400 μg), B12 (1 mg), and HA (50 mg) (Pervistop®, Lo.Li. Pharma, Rome, Italy). A 6-month treatment with such combined molecules demonstrated a viral clearance in 85.8% of enrolled patients, while 92.3% of participants exhibited no more cervical lesions. Furthermore, 71.8% of patients with persistent infection tested negative to HPV DNA test after 6 months of treatment. The obtained data in this large population strongly support previous evidence on the efficacy of such molecules in the management of HPV infection by improving both viral clearance and related cervical lesions, and by targeting viral persistence.

PMID:40508059 | DOI:10.3390/ijms26115251

Int J Mol Sci. 2025 May 28;26(11):5195. doi: 10.3390/ijms26115195.

ABSTRACT

Post-traumatic stress disorder (PTSD) is a complex, debilitating condition prevalent among military personnel exposed to traumatic events, necessitating biomarkers for early detection and intervention. Using data from the Millennium Cohort Study, the largest and longest-running military health study initiated in 2001, our objective was to identify specific microRNA (miRNA) expression patterns associated with distinct PTSD symptom trajectories among service members and veterans and assess their potential for predicting resilience and symptom severity. We analyzed 1052 serum samples obtained from the Department of Defense Serum Repository and linked with survey data collected at baseline and across three follow-up waves (2001-2011), using miRNA sequencing and statistical modeling. Our analysis identified five PTSD trajectories-resilient, pre-existing, new-onset moderate, new-onset severe, and adaptive-and revealed significant dysregulation of three key miRNAs (miR-182-5p, miR-9-5p, miR-204-5p) in participants with PTSD compared to resilient individuals. These miRNAs, which inhibit brain-derived neurotrophic factor (BDNF) and target pathways like NFκB, Notch, and TGF-alpha, were associated with neuronal plasticity, inflammation, and tissue repair, reflecting PTSD pathophysiology. These findings suggest that miRNA profiles could serve as biomarkers for early identification of PTSD risk and resilience, guiding targeted interventions to improve long-term health outcomes for military personnel.

PMID:40508005 | DOI:10.3390/ijms26115195

Int J Mol Sci. 2025 May 26;26(11):5094. doi: 10.3390/ijms26115094.

ABSTRACT

Bud paradormancy has been widely studied in perennial deciduous woody species, but little attention has been paid to paradormancy set and release in perennial evergreen tree species. Here, shoot bud paradormancy in Camellia sinensis cv. Huangdan was studied by untargeted metabolomics. We found that after removing the axillary floral buds for one day, the paradormancy of the axillary shoot buds was released. The paradormant shoot buds had lower glucose-1-phosphate, fructose, and D-(-)-tagatofuranose content but higher trehalose, raffinose, galactinol, and α-D-xylopyranose content. Meanwhile, high levels of asparagine were accumulated. Flavonoids were differentially accumulated, and higher levels of three flavone glycosides (C-diglucosylapigenin, apigenin 6-C-glucoside 8-C-arabinoside, and prunin) and four proanthocyanidins (Procyanidin trimer isomer 1, Galloylprocyanidin dimer, Procyanidin trimer isomer 3, and Galloylated trimeric proanthocyanidin) were accumulated in paradormant shoot buds. During the paradormancy-to-growth transition, all these metabolites were reversed. These data suggest that the reconfiguration of carbon, nitrogen, and flavonoid metabolism could be an important aspect for the paradormancy set and release of tea axillary shoot buds. This study provided novel insights into shoot bud paradormancy set and release in a perennial evergreen tree species.

PMID:40507906 | DOI:10.3390/ijms26115094