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PubMed1978

Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester.

This paper reports the effect of vitamin A and its derivatives, the retinoids, on plasminogen activator (PA) synthesis in chick embryo fibroblast cultures (CEF). Low concentrations of retinoic acid (RA) (10(-6)-10(-10) M) and the retinoids stimulated PA synthesis in CEF; the maximal stimulation achieved, 9--10 fold, was somewhat lower than that obtained with optimal concentrations of the potent tumor promoter phorbol myristate acetate (PMA). This action of RA required protein and mRNA synthesis but, in contrast to enzyme induction by PMA and/or sarcoma virus transformation, retinoid effects were not significantly inhibited by elevated concentrations of cAMP. In inducing and/or stimulating PA production, the effects of RA and sarcoma virus transformation were synergistic rather than additive. Analogous synergism was observed between RA and PMA, but only at suboptimal concentrations of the latter. RA did not affect PA production in normal or transformed cultures maximally stimulated by PMA. These findings may help to elucidate the role of retinoids in promoting tumor growth, tissue remodeling and teratogenesis.

Animals↗
PubMed2026

Influence of nicotine on protein expression around hydrophilic osseointegrated implants: A proteomic study in male rats.

OBJECTIVE: To ensure the success of dental implant treatment, various factors must be considered, including osseointegration and systemic conditions. There is evidence in the literature that smokers may exhibit alterations in tissue healing, which can compromise the success of implant rehabilitation. Therefore, this study aimed to investigate the influence of nicotine on the protein profile of bone tissue around hydrophilic implants during the osseointegration process in rats. DESIGN: Bone tissue samples from the control and nicotine groups (n = 3 per group) were subjected to protein extraction, mass spectrometry, and bioinformatic analyses. Protein identification was performed using Proteome Discoverer 2.1 software and the SEQUEST algorithm, and the protein data were compared with those of a protein database of Rattus norvegicus obtained from UniProt. RESULTS: A total of 740 proteins were detected in both the control group and the nicotine-exposed group. Among them, the proteins biglycan, periostin and histone H4 were highlighted because of their higher abundance in the healthy implant group, while they were reduced in the nicotine-exposed group. CONCLUSIONS: Nicotine has the potential to alter the protein profile of bone tissue around hydrophilic implants during osseointegration, which may impair tissue remodeling and healing.

Animals↗
PubMed2026

The IL-1 system in inflammation and cancer.

Inflammation is a pathogenetic driver of several pathological conditions, including cancer. The tumor microenvironment, which includes cellular, molecular, and structural components, is an essential component of cancer, involved in tumor promoting or controlling processes. In particular, inflammatory players contribute to the establishment of a tumor-promoting microenvironment, which affects all stages of tumor development, from initiation to metastasis, as well as response to therapy. The IL-1 system includes two large sets of structurally related ligands and receptors, with agonist or regulatory activity, playing non-redundant roles in inflammation and immunity. Each of them has specific functions in tissue homeostasis, inflammation, innate and adaptive immune responses, and potentially contributes to processes related to carcinogenesis and metastasis, or immune-mediated control of cancer cells. Depending on the context and cellular target, IL-1 family members may play dual roles in cancer, driving both pro- or anti-tumor processes. IL-1α and IL-1β can directly promote cancer cell proliferation, survival, and plasticity, in addition to contribute to the establishment of a pro-inflammatory environment that promotes tissue remodeling, cellular stress responses, and genomic instability. On the other hand, IL-1 is a lymphoproliferative and activating molecule in innate and adaptive responses, thus contributing to anti-tumor immune mediated responses. In addition, members of the IL-1 system act as regulators of mechanisms involved in cancer, including emergency hematopoiesis, trained immunity, and metabolism. Here, we will provide an overview of the IL-1 system in cancer and discuss the functional complexity of IL-1 family cytokines, which orchestrate both protective and pro-tumorigenic responses, by directly acting on cancer cells and by driving environmental stimuli which indirectly act on cancer cells.

Humans↗
PubMed2026

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗
PubMed2026

Wound healing in Atlantic spiny dogfish sharks.

Field observations and limited experimental studies indicate that elasmobranchs can repair substantial skin injuries, but the temporal course and cellular composition of wound healing in Atlantic spiny dogfish remain poorly characterized. We conducted an exploratory laboratory study in 20 female Atlantic spiny dogfish (Squalus acanthias) using standardized full-thickness skin wounds monitored by serial photography for 35 days, histological analysis at defined post-injury time points, and pooled single-nucleus RNA sequencing of intact and wounded skin. A continuous neoepithelial layer covered all examined wound beds by Day 1, whereas macroscopic wound area decreased progressively over 35 days and dermal denticles remained absent from the repaired surface. Histological examination showed progressive neoepidermal maturation, basement-membrane reformation, collagen deposition, and granulation-tissue organization, indicating that epithelial coverage preceded restoration of normal skin architecture. Single-nucleus RNA sequencing identified epithelial, stromal, vascular, pigment, neural, and immune-cell populations. T and B cells were detected in intact skin, and their relative abundance, together with that of several other leukocyte populations, increased at Day 1 and generally declined by Day 14. Because samples were pooled by time point, these transcriptomic changes are descriptive. These findings characterize rapid early reepithelialization followed by slower tissue remodeling in Atlantic spiny dogfish and provide a foundation for future comparative studies of elasmobranch skin repair.

Animals↗
PubMed2025

Molecular profiling of exhaled breath condensate in respiratory diseases.

BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways. AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19). RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors. CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.

Humans↗
PubMed1979

Intracellular collagen in recurrent ameloblastic fibroma.

Electron microscopic examination of tissue from a twice recurrent ameloblastic fibroma revealed the presence of intracellular collagen fibres in fibroblasts active in protein synthesis. The intracellular fibres were morphologically identical to collagen fibres located extracellularly. The literature on intracellular collagen in biological systems and pathological states has been reviewed, and attention is focussed on collagen phagocytosis and degradation by fibroblasts which are currently considered to represent the basis of connective tissue remodelling and turnover.

Ameloblasts↗
PubMed2026

The Puerperium in the Modern Dairy Cow: A Review.

The puerperium represents a critical physiological period during which the bovine reproductive tract transitions from pregnancy to renewed fertility. In the modern high-producing dairy cow, this transition is challenged by profound metabolic, endocrine, immunological, and structural demands that collectively influence uterine health, ovarian function, and subsequent reproductive performance. This review examines current understanding of the physiology of the puerperium in dairy cattle, with particular emphasis on uterine involution, immune clearance of postpartum contamination, endocrine regulation, and resumption of ovarian cyclicity. Further, it contrasts high-yielding Holsteins with fertility selected dairy populations. Normal uterine involution involves coordinated myometrial contraction, tissue remodelling, endometrial regeneration, and tightly regulated inflammatory responses. Failure of these processes predisposes cows to postpartum uterine disorders, including retained fetal membranes, metritis, endometritis (purulent vaginal discharge with cytological confirmation), and pyometra, which remain major contributors to subfertility and economic loss. Central to the pathophysiology of puerperal disease is negative energy balance, which disrupts immune competence, alters hepatic steroid metabolism, impairs ovarian signalling, and compromises oocyte and embryo quality. Emerging evidence highlights the complex interplay between metabolism, immunity, and the uterine microbiome, shifting current perspectives away from pathogen-centric models toward host resilience. Advances in biomarkers, genomic selection, and precision monitoring offer new opportunities for targeted reproductive management. Ultimately, optimisation of transition period management remains the cornerstone of supporting physiological puerperal recovery and sustaining reproductive efficiency in modern dairy systems.

Animals↗
PubMed2025

Distinct transcriptional and epigenomic programs define Hofbauer cells in term placenta.

Hofbauer cells (HBCs) are fetal macrophages located in the placenta that contribute to antimicrobial defense, angiogenesis, tissue remodeling, and metabolic processes within the chorionic villi. Although their roles in placental biology are increasingly recognized, the mechanisms that regulate HBC identity and function are not yet fully defined. This study aimed to define the core transcriptomic and epigenomic features of HBCs in term placentas and to examine their capacity for transcriptional responsiveness and phenotypic variation. Using chromatin accessibility profiling and bulk RNA-seq, we found that HBCs exhibit a unique gene expression and chromatin accessibility profile compared with other fetal and adult macrophages. We identified a coordinated transcriptional network involving nuclear receptors (NRs) NR4A1-3, the glucocorticoid receptor, and RFX family members (RFX1, RFX2, RFX5) that appears to shape HBC identity, particularly through pathways linked to lipid metabolism and angiogenesis. Although exploratory in nature, in vitro stimulation studies showed that HBCs exhibited increased transcriptional activity in response to combined IL-4 and rosiglitazone treatment, including induction of the lipid transporter CD36. Mass cytometry analysis revealed surface markers indicative of both immature and mature macrophage states. These results together indicate that HBCs are a distinct and diverse population of macrophages with a specialized, adaptable regulatory program in the human placenta.

Female↗
PubMed2026

Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. We used a targeted proteomic approach (Olink Cardiovascular panel III, targeting 92 proteins) to characterize the proteomic profile of cardiovascular resilience in T1D by comparing 92 patients with long-standing T1D (age 59.8 [53.2, 69.1], duration 40.0 [35.0, 45.2] years) free from macrovascular complications or nephropathy against a reference group of 57 T1D patients with accelerated vascular pathology (age 42.0 [32.0, 56.0], duration 22.0 [18.0, 27.0] years), proliferative retinopathy and/or nephropathy in relation to diabetes duration, termed Rapid Progressors (RP). Twenty proteins differed significantly between RP and Escapers (False Discovery Rate [FDR]&#x2009;<&#x2009;0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: +&#xa0;2.12 Normalized Protein eXpression [NPX], p&#x2009;<&#x2009;0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+&#x2009;1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+&#x2009;0.82 NPX) (all p&#x2009;<&#x2009;0.001). PECAM-1 (+&#x2009;0.55 NPX) and TNFRSF14 (+&#x2009;0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+&#x2009;0.53 NPX) and Fatty Acid Binding Protein 4 (+&#x2009;0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (-&#xa0;1.35 NPX, p&#x2009;<&#x2009;0.001) and Paraoxonase 3 (PON3) was lower in RP (-&#xa0;0.34 NPX, p&#x2009;=&#x2009;0.003). In conclusion, escaping complications in long-term T1D appears to be associated with active molecular mechanisms. Progression is marked by apoptosis (Caspase-3), fibrosis (CHI3L1) and platelet activation (GP6), whereas resilience is associated with a distinct signature involving higher vWF and PON3. These findings highlight a profound biological divergence between extreme T1D phenotypes and provide a foundation for further research into vascular resilience.

Humans↗
PubMed1975

Indoluble collagen II. The use of fluorescein labelled polymeric collagen fibrils in a very sensitive assay procedure for enzymes degrading insoluble collagen.

98% of the collagen in mature connective tissue is in the form of insoluble collagen fibers, consisting of bundles of polymeric collagen (PC) fibrils. The enzymes concerned in connective tissue remodeling degrade PC rather than tropocollagen (TC). TC is the most usual substrate for collagenase assays, and we believe it is essential to employ PC in any study of the activity of collagenolytic enzymes. In order to facilitate the study of enzymic degradation of PC we have labelled PC with fluorescein iso-thiocyanate to produce F-PC fibrils, containing 5 fluorescein labelled epilson-NH2 groups of lysine per TC molecule within the PC. The fluorescent F-PC is degraded at the same rate as PC with the release of hydroxyprolyl peptides but has the great advantage that the solubilised F-peptides can be quantitated by their fluorescent emission. The technique is described in detail employing bacterial collagenase and mammalian collagenase preparations to illustrate the methodology. The advantages of the fluorescent technique over the collagenolytic assay methods currently in use are outlined.

Animals↗
PubMed2026

Bayesian Genome-Wide Association Study of Feed Efficiency Traits in Pigs.

Feed efficiency traits are increasingly important in pig production for improving profitability and environmental sustainability. Understanding their genetic basis is crucial for uncovering underlying biological mechanisms and informing selection strategies. In this study, we analyzed residual feed intake (RFI), feed conversion ratio (FCR), and average daily feed intake (ADFI) in 201 animals. Three separate Bayesian GWASs were conducted using 29,844 SNPs in a case-control design, with the lowest and highest 15% of the phenotypic distribution selected as controls and cases (N = 30 per group), respectively, for each trait. The results confirmed the polygenic nature of the traits, identifying 4 SNPs for RFI on Sus scrofa chromosomes (SSC) 3, 13, and 15 with high posterior probability for the direction of their effects; 4 SNPs for FCR on SSC 8, 14, and 17; and 8 SNPs for ADFI on SSC 1, 2, 6, 8, and 11. A candidate gene search identified 41 potential genes involved in diverse biological processes, including feed efficiency, intestinal development, tissue remodeling and integrity, nutrient transport and absorption, metabolic homeostasis, cellular signaling, energy sensing, and neurological regulation. These genes formed a highly interconnected network, highlighting the complexity of feed efficiency and the interplay among multiple physiological, metabolic, and regulatory pathways.

Bayesian analysis↗
PubMed1975

Mixed-image planimetry. Assessment of a new method for stereometric analysis in microscopy.

A new method for stereometric measurement of surface area in microscopy is described, based on the mixed-image principle. The measurement was accomplished by observing the area on which was superimposed the image of a miniature electric lamp attached to an ordinary planimeter. Mixed-image planimetric measurements were more easily made and required much less time than area calculation by an integrating eyepiece, by weight or by ordinary planimetric measurements of photomicrographs or tracings of the area. Mixed-image planimetric measurements of a finite area varied less than 1 per cent. Such precision was not obtained with the other methods. The new method was devised in vivo stereometric measurements of bone tissue remodelling in rabbit ear chambers, but should find a much wider application in quantitative microscopy of both finite and extensive objects.

Animals↗
PubMed1977

The remodeling of human gingival tissues following gingivectomy.

A total of 30 facial gingivectomies were carried out for reduction of suprabony pockets (mean +/- S.D. preoperative pocket depth 2.8 mm +/- 0.3 mm). Remodeling of the gingival margin was monitored by clinical measurements. The following techniques were utilized: A polyvinyl stent was constructed for each surgical quadrant. This stent covered the occlusal margins of the involved teeth and contained the fixed point of reference. Preoperatively, the following measurements were taken: the distance from the fixed point to (a) the height of the free gingival margin, and (b) the base of the clinical pocket. For control purposes similar measurements were taken at the facial surface of an adjacent tooth. A standard gingivectomy to the base of the clinical pocket was then performed and a periodontal dressing was applied for 1 week. Utilizing the stent (fixed point of reference), measurements were taken of the healing margin and control sites inn the same manner as preoperatively; 1,4,8 and 12 weeks after surgery. Our findings indicate that 12 weeks after gingivectomy, the newly formed free gingival margin was located coronally to the line of incision in all cases. The mean pocket depth at 12 weeks after surgery was 0.7 mm +/- 0.2 mm. However, the mean gain in coronal marginal height was 1.2 mm +/- 0.3 mm. Thus, a clinical coronal pocket closure of about 0.5 mm seemed to have taken place at the soft tissue-tooth interface. Measurements at the nonoperated control site showed no significant variations in crevicular depth during the experimental period. We therefore conclude that the excisional reduction of a crevice to 0 mm depth was altered by gingival remodeling during the healing phase. In our experience, this remodeling took place within 3 months after surgery and clinically appeared as a limited coronal pocket closure and gain of marginal height.

Adult↗
PubMed1977

Sutural development: structure and its response to rapid expansion.

This fine structural study of the suture, its development, structure, and response to rapid expansion has shown that the sutural complex is best described in terms of the functional activity of two cell populations, namely, the osteocytic and fibrocytic series, which have the ability to remodel the tissues which they form. It is suggested that the previous detailed descriptions of differences in fiber orientation and vascular distribution reflect functional activity of a suture at any given time rather than immutable anatomic characteristics. Development of the suture and its rapid expansion showed many similarities in that growth during development and orthopedic expansion both separate the joint. If the initial inflammatory aspect of rapid expansion is ignored, the response of the suture is one of osteogenesis and fibrillogenesis, followed finally by remodeling. It is also suggested that sutural expansion involves injury followed by a proliferative repair phenomenon which, in other tissues, usually leads to the formation of scar tissue. However, the ability of sutural connective tissue fibroblasts to remodel ultimately leads to regeneration of the suture. Finally, programmed cell death has been shown to be an important feature in the development of the suture.

Activator Appliances↗
PubMed2026

The gonadal matrisome and its correlation with sex change in the ricefield eel Monopterus albus.

The matrisome is a comprehensive list of genes in the genome of an organism, which encodes proteins constituting or interacting with the extracellular matrix (ECM). The gonadal ECM is important for folliculogenesis and spermatogenesis. This study characterized the composition of the matrisome and the expression of matrisome genes in the gonad of ricefield eel, a protogynous sex-changing teleost, during sex change. A total of 838 matrisome genes were identified in the genome of ricefield eel through an in-silico orthology-based approach, of which 482, 443, 429, and 570 matrisome genes were shown to be expressed in the gonads of female (F), early intersexual (EI), mid-intersexual (MI), and late intersexual (LI) fish, respectively. Differentially expressed matrisome genes (DEMGs) were observed across all the sexual stages as well as in each category of ECM components. Analysis of DEMGs in the comparison between EI and F revealed dramatic upregulation of adam8a, mmp9, and s100a11 while downregulation of col4a5, col15a1b, clec3ba, f13a1, and ccl44, which were further confirmed by qPCR analysis. Together, these findings revealed significant changes in the expression of many matrisome genes, particularly three regulator genes, adam8a, mmp9 and f13a1, as female ricefield eels initiate sex change, suggesting that gonadal tissues undergo dramatic remodeling involving the regression of ovarian tissues and the development of testicular tissues to facilitate this process. These data provide valuable resources for further unraveling the roles of matrisome genes in gonadal development of ricefield eel and other vertebrates.

Animals↗