Search Results (1,075)

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major global health challenge characterized by complex adipose–liver interactions mediated by adipokines and hepatokines. Despite rapid field evolution, a comprehensive understanding of research trends and translational advances remains fragmented. This study systematically maps the scientific landscape through bibliometric analysis, identifying emerging domains and future clinical translation directions. Methods: A comprehensive bibliometric analysis of 1002 publications from 2004 to 2025 was performed using thematic mapping, temporal trend evaluation, and network analysis. Analysis included geographical and institutional distributions, thematic cluster identification, and research paradigm evolution assessment, focusing specifically on adipokine–hepatokine signaling mechanisms and clinical implications. Results: The United States and China are at the forefront of research output, whereas European institutions significantly contribute to mechanistic discoveries. The thematic map analysis reveals the motor/basic themes residing at the heart of the field, such as insulin resistance, fatty liver, metabolic syndrome, steatosis, fetuin-A, and other related factors that drive innovation. Basic clusters include metabolic foundations (obesity, adipose tissue, FGF21) and adipokine-centered subjects (adiponectin, leptin, NASH). New themes focus on inflammation, oxidative stress, gut microbiota, lipid metabolism, and hepatic stellate cells. Niche areas show targeted fronts such as exercise therapies, pediatric/novel adipokines (chemerin, vaspin, omentin-1), and advanced molecular processes that focus on AMPK and endoplasmic-reticulum stress. Temporal analysis shows a shift from single liver studies to whole models that include the gut microbiota, mitochondrial dysfunction, and interactions between other metabolic systems. The network analysis identifies nine major clusters: cardiovascular–metabolic links, adipokine–inflammatory pathways, hepatokine control, and new therapeutic domains such as microbiome interventions and cellular stress responses. Conclusions: In summary, this study delineates current trends and emerging areas within the field and elucidates connections between mechanistic research and clinical translation to provide guidance for future research and development in this rapidly evolving area. Full article

Background: Pepper (Capsicum annuum L.) is highly susceptible to various abiotic stresses during their growth and development, leading to severe reductions in both yield and quality. β-Glucosidase (BGLU) is widely involved in plant growth and development, as well as in the response to abiotic stress. Methods: We performed a genome-wide identification of pepper BGLU (CaBGLU) genes. Phylogenetic analysis included BGLU proteins from Arabidopsis, tomato, and pepper. Gene structures, conserved motifs, and promoter cis-elements were analyzed bioinformatically. Synteny within the pepper genome was assessed. Protein-protein interaction potential was predicted. Gene expression patterns were analyzed across tissues and under abiotic stresses using transcriptomic data and qRT-PCR. Subcellular localization of a key candidate protein CaBGLU21 was confirmed experimentally. Results: We identified 32 CaBGLU genes unevenly distributed across eight chromosomes. Phylogenetic classification of 99 BGLU proteins into 12 subfamilies revealed an uneven distribution of CaBGLUs across six subfamilies. Proteins within subfamilies shared conserved motifs and gene structures. CaBGLU promoters harbored abundant light-, hormone- (MeJA, ABA, SA, GA), and stress-responsive elements (including low temperature). A duplicated gene pair (CaBGLU19/CaBGLU24) was identified. 27 CaBGLU proteins showed potential for interactions. Expression analysis indicated CaBGLU5 and CaBGLU30 were mesophyll-specific, while CaBGLU21 was constitutively high in non-leaf tissues. CaBGLU21 was consistently upregulated by cold, heat, and ABA. Subcellular localization confirmed CaBGLU21 resides in the tonoplast. Conclusions: This comprehensive analysis characterizes the pepper BGLU gene family. CaBGLU21, exhibiting constitutive expression in non-leaf tissues, strong upregulation under multiple stresses, and tonoplast localization, emerges as a prime candidate gene for further investigation into abiotic stress tolerance mechanisms in pepper. The findings provide a foundation for future functional studies and stress-resistant pepper breeding. Full article

Background: Osteogenesis imperfecta (OI) is a rare genetic connective tissue disorder characterized by bone fragility, most often caused by pathogenic variants in type I collagen genes. In this context, we aimed to describe the clinical and epidemiological characteristics of patients with OI who were hospitalized for coronavirus disease (COVID)-19 in Brazil between 2020 and 2024. Methods: We conducted a retrospective descriptive analysis using data from the Brazilian Unified Health System (SUS, which stands for the Portuguese Sistema Único de Saúde) through the Open-Data-SUS platform. Patients with a confirmed diagnosis of OI and hospitalization due to COVID-19 were included. Descriptive statistical analysis was performed to evaluate demographic, clinical, and outcome-related variables. We included all hospitalized COVID-19 cases with a confirmed diagnosis of OI between 2020 and 2024. Results: Thirteen hospitalized patients with OI and COVID-19 were identified. Most were adults (9; 69.2%), male (7; 53.8%), self-identified as White (9; 69.2%), and all were residents of urban areas (13; 100.0%). The most frequent symptoms were fever (10; 76.9%), cough (9; 69.2%), oxygen desaturation (9; 69.2%), dyspnea (8; 61.5%), and respiratory distress (7; 53.8%). Two patients had heart disease, one had chronic lung disease, and one was obese. As for vaccination status, five patients (38.5%) had been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Four patients (30.8%) required admission to an intensive care unit (ICU), and six (46.2%) required noninvasive ventilatory support. Among those admitted to the ICU, only two required invasive mechanical ventilation. The clinical outcome was death in two cases (15.4%). Both patients were male, White, and had not been vaccinated against SARS-CoV-2. One was 47 years old, was not admitted to the ICU, but required noninvasive ventilation. Despite the underlying condition most patients had favorable outcomes, consistent with an international report. Conclusions: This is the first report to describe the clinical and epidemiological profile of patients with OI hospitalized for COVID-19 in Brazil, providing initial insights into how a rare bone disorder intersects with an acute respiratory infection. The generally favorable outcomes observed—despite the underlying skeletal fragility—suggest that individuals with OI are not necessarily at disproportionate risk of severe COVID-19, particularly when appropriately monitored. The occurrence of deaths only among unvaccinated patients underscores the critical role of SARS-CoV-2 vaccination in this population. Although pharmacological treatment data were unavailable, the potential protective effects of bisphosphonates and vitamin D merit further exploration. These findings support the need for early preventive strategies, systematic vaccination efforts, and dedicated clinical protocols for rare disease populations during infectious disease outbreaks. Full article

Tissue-resident macrophages are essential for skin homeostasis. This study investigated whether lipopolysaccharide (LPS)-activated macrophages affect senescence and rejuvenation in human dermal fibroblasts. Human monocytic THP-1 cells were stimulated with Pantoea agglomerans–derived LPS (1–1000 ng/mL), and culture supernatants were collected. These were applied to two NB1RGB fibroblast populations: young, actively dividing cells (Young cells) and senescent cells with high population doubling levels and reduced proliferation (Old cells). Senescence markers P16, P21, and Ki-67 were analyzed at gene and protein levels. Conditioned medium from Old cells induced senescence in Young cells, increasing P16 and P21 expression levels. This effect was suppressed by cotreatment with LPS-activated THP-1 supernatant. Old cells treated with the LPS-activated supernatant exhibited decreased P16 and P21 levels as well as increased Ki-67 expression, indicating partial rejuvenation. These effects were not observed following treatment with unstimulated THP-1 supernatants or LPS alone. Overall, these findings suggest that secretory factors from LPS-activated macrophages can suppress cellular senescence and promote human dermal fibroblast rejuvenation, highlighting the potential role of macrophage activation in regulating cellular aging and offering a promising strategy for skin aging intervention. Full article

Unionid mussel populations in a section of the Clinch River in Virginia, USA, has declined substantially, but the causes of the decline remain unknown. To investigate this zone of decline (ZOD), we deployed juvenile freshwater mussels (Villosa iris in 2012 and Lampsilis fasciola in 2013) in both cages and silos at sites within the Clinch River System. We analyzed mussel tissues for trace element and organic contaminant concentrations, shells for trace elements, and environmental media (total water, dissolved water, particulate sediment, and bedload sediment) for both inorganic and organic contaminants. We found a few differences between mussels deployed in cages and those deployed in silos: survival was slightly lower in cages due to periodic sedimentation. Our results identified the ZOD based on the accumulation of trace elements (notably As, Cu, Fe, Mn, Ni, and Sr), polycyclic aromatic hydrocarbons (PAHs), and δ¹⁵N enrichment, with especially high concentrations found in the human-impacted tributaries, Dumps Creek and Guest River. Some correlations were found between environmental media and both mussel tissues and shells. In particular, PAHs and Mn had several significant relationships between bioaccumulated concentrations and environmental concentrations. Finally, Co, Cu, Fe, and V in soft tissues negatively correlated with mussel growth, whereas bioaccumulated PAH concentrations correlated negatively with resident mussel densities. Full article

Background: It is estimated that in Italy, there were 364,000 new diagnoses of neoplasms each year and that the overall incidence of blood cancers was 10% of these. Leukemia and lymphomas represented the ninth and eighth places, respectively, among the causes of death from neoplasia. Hematopoietic stem cell transplantation represented an effective treatment option for many of these malignancies, and not only that: benign and congenital diseases could also be treated. Objective: To assess knowledge among the Apulian population regarding stem cell donation and factors that could influence this choice, focusing especially on the knowledge of the residents of Puglia, Italy on how stem cells were harvested and their functions, their reasons for joining the National Registry, and the reasons that hold them back from making such a choice. Study Design: An observational and cross-sectional study was conducted, through snowball sampling methodology, until data saturation. An online survey was conducted, which included several Italian associations. The questionnaire administered contained five main sections, such as sociodemographic data, knowledge of the existence of National Registries and their adherence, the nationwide presence of various associations that promote donation, knowledge with respect to the structure, use and functions of stem cells, sources of procurement, such as bone marrow, peripheral blood and umbilical cord, and related procedures, beliefs, attitudes, values, and opinions of the Italian population regarding the topic, and degree of information and education regarding bone marrow donation. Results: A total of 567 Apulian citizens were enrolled. Of these, 75.3% were female and 96.8% were aged between 18 and 65 years. Most of participants were single (46.9%) and married (47.3%) and had a diploma (44.4%), and less had a degree (35.8%). Significant differences were recorded between gender, singles, and married participants, and participants with a diploma or a degree and the items proposed. Conclusions: A true culture of donation in our region was not clearly spread. Although something has been accomplished in recent years in terms of deceased donor donation, still a great deal needs to be achieved for living donation, which encountered a great deal of resistance. It has been deemed necessary to seek winning solutions to this issue in terms of communication and information campaigns, raising awareness and empowering citizens to express consciously their concerns about organs and tissues and to stand in solidarity with those who suffered. Full article

Macrophages are a heterogenous population of cells that adopt specific phenotypes in response to signals from their dynamic microenvironment. Apart from being key players in innate immunity and in the maintenance of tissue homeostasis, macrophages are also important drivers of low-grade inflammation, which is associated with different chronic conditions including stress and cancer. The activation of macrophages during chronic stress and cancer results in their multifaceted pathogenic roles. Macrophages residing in the tumor microenvironment are commonly known as tumor-associated macrophages and favor or inhibit tumor growth depending on the microenvironmental cues and their activation state. Activated macrophages display a continuum of properties rather than a distinct proinflammatory or anti-inflammatory dichotomy. Emerging evidence suggests that prolonged tissue residency restricts the plasticity of macrophages, while recruited monocytes are more plastic and their differentiation into tumor-associated macrophages during stress can result in a dual imprinting from both the existing stress-induced inflammation and the tumor microenvironment. In addition, the immunomodulation of the tumor microenvironment and reprogramming of tumor-associated macrophages toward the anti-tumor phenotypes have emerged as promising therapeutic approaches. In this review, we will focus on how the persistent inflammatory state underlying chronic stress affects macrophages as well as the macrophages’ contribution to various aspects of tumor growth and progression, highlighting a therapeutic potential of modulation of the macrophage-mediated immunosuppressive tumor microenvironment. Full article

Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, p = 1.76 × 10⁻¹⁰, OR = 1.63, 95% CI: 1.40–1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, LINC01276 and FOXP4-AS1, and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with FOXP4-AS1 and FOXP4, implying that this regulatory SNP could alter the normal cellular function of FOXP4-AS1 and FOXP4. Furthermore, rs9367106 is in eQTL with the FOXP4 gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent IFIH1/MDA5 activation, leading to suppression of host innate immune responses. LINC01276 targets the MED20 gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery. Full article

Background/Objectives: Breast cancer (BC) is the leading cause of cancer incidence and mortality among women and the recent identification of a resident mammary microbiota has highlighted its potential role in breast carcinogenesis. Given that environmental and socioeconomic factors influence both BC prevalence and tumor-associated bacterial composition, this study aimed to evaluate the compositional and functional features of the mammary microbiota in cancerous (oncobiome) and adjacent healthy BC tissues from patients living in urban and rural areas. Methods: Microbiota composition in both the oncobiome and adjacent healthy BC tissues was analyzed using 16S rRNA sequencing. Results: Significant variations in breast oncobiome composition were observed among BC patients from urban and rural areas. A statistically significant β dispersion among breast oncobiome of patients from urban or rural areas was highlighted. Specifically, the genera Selenomonas, Centipeda, Leptotrichia, Neisseria and Porphyromonas were found exclusively in BC tissues of patients from rural areas. Additionally, bacteria from the Neisseriaceae, Porphyromonadaceae, and Selenomonadaceae families, as well as the Selenomonas genus, were significantly enriched in the oncobiome of rural BC patients. Furthermore, the results of the PICRUSt2 (phylogenetic investigation of communities by reconstruction of unobserved states) revealed a significant increase in phospholipid biosynthesis pathways in breast oncobiome of patients from rural areas compared to those from urban areas. Conclusions: This study provides evidence of distinct compositional and functional differences in the breast oncobiome between BC patients from rural and urban areas. These findings suggest that environmental factors influence local microbiome composition, potentially contributing to BC development and/or progression. Full article

Next to adrenergic signalling, purinergic pathways mediated by extracellular adenine nucleotides have been described to shape thermogenic and metabolic functions in brown adipose tissue (BAT). Here we describe high expression of P2X5 that is activated by ATP in mature adipocytes of BAT and differentiated brown adipocytes in vitro. The levels of other P2X family members were much lower, or expression was restricted to tissue-resident macrophages or endothelial cells. Global and brown adipocyte-specific P2rx5 deficiency resulted in lower expression of the uncoupling protein 1 (UCP1). However, indirect calorimetry studies showed that P2X5 did not affect systemic energy expenditure. Of note, glucose tolerance was impaired under chow and obesogenic high-fat diet conditions, which can be explained by lower glucose disposal into BAT but not into other organs. In summary, these data indicate a modulatory role of P2X5 in systemic and BAT-specific glucose metabolism. Full article

Background: Vitamin D has anti-inflammatory and immunomodulatory properties that may influence the pathophysiology of endometriosis. This study investigated the association between vitamin D levels and endometriosis, and vitamin D receptor (VDR) expression in endometriotic tissue. Methods: A cross-sectional study was conducted involving 36 patients with endometriosis and 72 healthy control women, matched for age and BMI. Serum 25-hydroxyvitamin D levels were measured and categorized into four statuses (normal, insufficiency, deficiency, and severe deficiency). Endometriotic tissue samples were examined for VDR expression using immunohistochemistry and qualitatively quantified using histo-scores (H-scores). Endometriosis severity was assessed using the revised criteria of the American Society for Reproductive Medicine (rASRM). Results: No statistically significant difference in vitamin D levels between the groups (20.45 vs. 21.10 ng/dL, p = 0.190) was observed, even after adjusting for residence, body sunscreen use, pregnancy, and contraceptive use. VDR expression exhibited significantly higher H-scores in endometriotic epithelial cells than in stromal cells (209.51 vs. 73.32; p < 0.001). Additionally, the VDR H-score in both cell compartments showed no significant difference according to vitamin D status. No statistically significant association was found between vitamin D levels, VDR expression, or disease severity. The odds of severe endometriosis were 2.17 (95% CI: 0.14–33.80) for vitamin D insufficiency and 4.33 (95% CI: 0.24–115.67) for deficiency compared with normal vitamin D. Conclusions: There was no statistically significant association between vitamin D levels and endometriosis and VDR. Full article

Deciduous teeth accumulate toxic metals until fully mineralized, making them a stable biological matrix for assessing chronic exposure during fetal and early postnatal life. Their metal content is influenced by environmental factors (e.g., industrial areas, mining sites) and individual factors (e.g., maternal diet, early nutrition, passive smoking). The aim of this study was to evaluate the toxic metal content in deciduous teeth and to identify factors contributing to its accumulation, as well as possible health implications. A systematic review was conducted in accordance with the PRISMA guidelines and following the PICO framework. Quality assessment was assessed using the Joanna Briggs Institute (JBI) checklist for quasi-experimental studies. The literature search was carried out in the PubMed, Scopus, and Web of Science databases using the following keywords: deciduous, milk, primary, decidua, teeth, dentition, heavy metal, toxic metals. A total of 134 articles were initially identified, with 95 remaining after duplicate removal. After screening, 75 articles were excluded: 71 did not meet the inclusion criteria, 3 were not available in English, and 1 lacked full-text access. Ultimately, 20 studies were included in the review. Toxic metal concentrations were determined using various analytical techniques, mainly inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS). Higher levels of metals, especially lead, were observed in the teeth of children residing in industrial areas, near mines, or in regions affected by armed conflict. Although two out of five studies indicated a possible link between fathers’ smoking habits and elevated lead concentrations, no definitive relationship was established between secondhand smoke exposure and the levels of lead and cadmium found in dental tissue. Similarly, no definitive relationship was identified between mercury and lead content and the prevalence of autism. However, lower manganese levels were associated with the presence of autistic traits, weaker verbal performance, and reduced memory capacity. In conclusion, deciduous teeth represent a valuable biological material for assessing chronic prenatal and early postnatal exposure to toxic metals, which may serve as a starting point for further research into diseases of unknown etiology, such as autism, and in the future may have clinical significance in their prevention and treatment. And it is also important for monitoring environmental pollution levels. Full article

Melanoma is the most aggressive form of skin cancer, and despite significant therapeutic advances over the past decade, a substantial number of patients still progress to a fatal outcome. The initiation and progression of melanoma are strongly influenced by interactions between melanoma cells and other components of the tumor microenvironment (TME). In this review, we focus on the interplay between fibroblasts resident in the tumor microenvironment and tumor cells. In particular, we examine the molecular mechanisms through which melanoma cells induce the transformation of resident fibroblasts into their active form, known as cancer-associated fibroblasts (CAFs). We also explore the role of CAFs in shaping the melanoma microenvironment (MME) and in organizing the pre-metastatic niche, a specialized microenvironment that forms in distant organs or tissues to support the survival and expansion of metastatic melanoma cells. Finally, we discuss emerging therapeutic strategies aimed at disrupting the interactions between CAFs, melanoma cells, and other components of the tumor microenvironment to improve treatment outcomes. Full article

Colletotrichum fructicola is a member of the gloeosporioides complex and can act as a pathogen, causing anthracnose in various plants and as an endophyte residing in healthy plants. As a plant pathogen, C. fructicola has been frequently reported to cause anthracnose in chili fruit and tea plants, bitter rot in apples and pears, crown rot in strawberries, and Glomerella leaf spot in apples, which are the most common diseases associated with this pathogen. Over the years, C. fructicola has been reported to infect a wide range of plants in tropical, subtropical, and temperate regions, including various types of fruit crops, ornamental and medicinal plants, tree nuts, peanuts, and weeds. Several reports have also been made regarding endophytic C. fructicola recovered from different plant parts. Endophytic C. fructicola has the ability to switch to a pathogenic state, which may contribute to the infection of host and other susceptible plants. Due to the economic importance of C. fructicola infections, the present review highlighted C. fructicola as a plant pathogen and endophyte, providing a summary of its infections in various plants and endophytic ability to inhabit plant tissues. Several control measures for managing C. fructicola infections have also been provided. Full article

Lactic acid bacteria are components of the gastrointestinal tract microbiota in both humans and animals and are widely used as probiotics. Lactobacillus is the most closely related genus to probiotic activity. It is capable of releasing membrane microvesicles (MVs), whose primary functions include carrying and transmitting antigens to host tissues and modulating host defense responses. In the present study, MVs were isolated from Lactobacillus acidophilus resident in the ileum of free-living rats, and their immunostimulant effect was evaluated in two biological models. MVs were characterized using SDS-PAGE electrophoresis, electron microscopy, and nanoparticle tracking analysis. In the first model, the immunostimulatory effect of MVs was evaluated on ovine abomasal explants, which had been previously stimulated with MVs and then challenged with third-stage larvae of Haemonchus contortus. This resulted in a decrease in the percentage of larval association and favored the migration of inflammatory cells to the infection site. In the second model, the macrophage cell line RAW 264.7 was stimulated with MVs to evaluate the expression of transcripts encoding IL-1β and TNF-α. MVs isolated from L. acidophilus demonstrate immunostimulatory and probiotic effects in the two biological models assessed. This suggested that the MVs possess similar immunostimulatory effects as those reported for the parent bacteria. Full article