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11 pages, 696 KB  
Article
Microbial Reservoirs in Artisanal Dairy Products from Spain and Algeria Harbor Lactic Acid Bacteria with Significant Gluten-Degrading Activity
by Abdelhak Menasri, Rosario Lucas, Javier Rodríguez López, Antonio Gálvez, Mª José Grande and Rubén Pérez Pulido
Appl. Microbiol. 2026, 6(3), 45; https://doi.org/10.3390/applmicrobiol6030045 (registering DOI) - 15 Mar 2026
Abstract
Celiac disease (CD) is an autoimmune disorder triggered by immunogenic gluten peptides that resist gastrointestinal digestion. The only current treatment is a strict gluten-free diet, which is challenging to maintain. Lactic acid bacteria (LAB) with specific proteolytic systems offer a promising strategy for [...] Read more.
Celiac disease (CD) is an autoimmune disorder triggered by immunogenic gluten peptides that resist gastrointestinal digestion. The only current treatment is a strict gluten-free diet, which is challenging to maintain. Lactic acid bacteria (LAB) with specific proteolytic systems offer a promising strategy for gluten hydrolysis and potential reduction of immunogenicity. This study aims to isolate and characterize gluten-degrading LAB from traditional Spanish and Algerian dairy products. A total of 27 artisanal dairy samples were collected. LAB were isolated on MRS and Elliker agar. Gluten-degrading activity was screened using a well diffusion assay with cell-free supernatants and a spot assay with live cultures. Active isolates were identified by 16S rRNA gene sequencing. Out of 123 isolates, 40 (32.5%) were positive in the well assay, while 67 (54.5%) were positive in the spot assay, indicating the latter’s higher sensitivity for detecting cell-associated proteases. Halo diameters ranged from 6 to 16 mm. Algerian isolates exhibited significantly stronger activity (mean halo: 12.6 ± 2.1 mm) compared to Spanish isolates (10.2 ± 2.0 mm; p < 0.001). Molecular identification of the 32 most active isolates revealed the following dominant species: Lactiplantibacillus plantarum, L. pentosus, Levilactobacillus brevis, and Enterococcus faecium. This study confirms that artisanal dairy fermentations are rich sources of LAB with robust gluten-degrading potential. The superior activity of Lactiplantibacillus spp. aligns with their complex peptidase systems. The geographical variation highlights the influence of local fermentation practices. Selected strains represent excellent candidates for developing adjunct cultures to produce gluten-reduced foods and warrant further investigation as potential probiotics, pending safety and efficacy validation in vivo and in clinical studies. Full article
(This article belongs to the Special Issue Applied Microbiology of Foods, 3rd Edition)
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13 pages, 652 KB  
Article
The Forgotten Test: Missed Opportunities for HIV Diagnosis and Survival Outcomes in Advanced HIV Disease
by Arianna Narducci, Alessandra Vergori, Paola Borrelli, Irene Francesca Bottalico, Sergio Maria Ferrara, Chiara Grillo, Francesco Rosario Paolo Ieva, Mariacristina Poliseno, Annalisa Saracino, Antonio Cianciaruso, Riccardo Schiavoni, Laura Mezzogori, Antonio Di Biagio, Andrea Santoro, Giulia Carla Marchetti, Camilla Tincati and Sergio Lo Caputo
Viruses 2026, 18(3), 356; https://doi.org/10.3390/v18030356 (registering DOI) - 15 Mar 2026
Abstract
Background: Advanced HIV disease (AHD) remains highly prevalent and is associated with increased morbidity and mortality. Missed opportunities for early diagnosis continue to represent a major public health challenge. Methods: We conducted a multicenter retrospective cohort study including antiretroviral-naive people with HIV (PWH) [...] Read more.
Background: Advanced HIV disease (AHD) remains highly prevalent and is associated with increased morbidity and mortality. Missed opportunities for early diagnosis continue to represent a major public health challenge. Methods: We conducted a multicenter retrospective cohort study including antiretroviral-naive people with HIV (PWH) presenting with AHD (CD4 < 200 cells/µL and/or AIDS) diagnosed between 1 January 2019 and 31 December 2024 in four Italian infectious diseases units. Demographic, clinical and viro-immunological data were collected at baseline and during follow up. Information on healthcare contacts, HIV-related symptoms, and prior HIV testing in the two years preceding diagnosis was obtained through structured interviews. Results: Among 658 newly diagnosed participants with HIV, 224 (34%) presented with AHD, of whom 54% presented with AIDS. Most participants (86.2%) had never undergone HIV testing before diagnosis. In the year preceding diagnosis 29.3% accessed healthcare services for symptoms compatible with HIV infection without being tested for HIV. At one year, 84.2% achieved virological suppression, with a median CD4 count of 260 cells/µL. Overall loss to follow-up was 27.2%. Five-year survival was significantly higher in non-AIDS presenters compared with AIDS presenters (100% vs. 85%, p = 0.005). Conclusions: Missed diagnostic opportunities remain frequent among PWH presenting with AHD, despite prior healthcare contacts. Wider implementation of indicator condition-guided HIV testing is urgently needed to reduce late diagnosis and improve long-term outcomes. Full article
(This article belongs to the Special Issue Early ART Initiation: Impacts on Viral Dynamics and Clinical Outcomes)
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13 pages, 753 KB  
Article
Glycated High-Density Lipoproteins Reduce Endothelial Phenotypic Expression of Monocyte-Derived Multipotential Cells in Early Type 2 Diabetes
by Felipe Massó-Rojas, Luis Felipe Montaño-Estrada, Araceli Páez-Arenas, Juan Gabriel Juárez-Rojas, Aida Medina-Urrutia, Rafael Nambo-Venegas, Emma Rodríguez-Maldonado and Esteban Jorge-Galarza
Metabolites 2026, 16(3), 194; https://doi.org/10.3390/metabo16030194 (registering DOI) - 15 Mar 2026
Abstract
Background: High-density lipoproteins (HDL) exert protective effects on the endothelium, which are impaired in type 2 diabetes (T2D). Although monocyte-derived multipotential cells (MOMCs) can be differentiated into the endothelial lineage, it remains unclear whether HDL glycation, size, and composition could affect MOMCs [...] Read more.
Background: High-density lipoproteins (HDL) exert protective effects on the endothelium, which are impaired in type 2 diabetes (T2D). Although monocyte-derived multipotential cells (MOMCs) can be differentiated into the endothelial lineage, it remains unclear whether HDL glycation, size, and composition could affect MOMCs differentiation. Methods: Twenty normoglycemic (49 years, 35% male), 20 prediabetic (52 years, 35% male), and 20 newly diagnosed T2D participants (51 years, 50% male) were recruited. HDL were isolated from each study group. The size, composition, and early, intermediate, or advanced glycation products of HDL were determined. CD14+ MOMCs were isolated from healthy volunteers and incubated with HDL from each group. Endothelial phenotypic expression was assessed by CD14+/KDR+ expression. Results: Compared with normoglycemic and prediabetic individuals, T2D patients had higher concentrations of early (4.4, 4.6, vs. 5.2 µmol/mg of protein, respectively; p = 0.049) and advanced (7.7, 8.7, vs. 14.3 µg-BSA-AGEs/mg of protein, respectively; p < 0.02) glycation products in HDL. HDL composition was similar among groups. The CD14+/KDR+ expression in MOMCs incubated with HDL from T2D patients was lower than that observed in prediabetes and normoglycemic individuals (46% vs. 52% and 61%, respectively; p = 0.002). Advanced glycation end products in HDL inversely correlated with CD14+/KDR+ cells (r = −0.418, p = 0.002), adjusting for other HDL characteristics. Conclusions: In T2D patients, increased HDL-advanced glycation impairs the endothelial phenotypic expression of MOMCs, independently of other HDL characteristics. Since advanced glycation leads to greater biological damage, these findings highlight the importance of preserving HDL integrity in T2D patients to support endothelial repair and potentially delay vascular complications. Full article
(This article belongs to the Special Issue Role of Lipid Metabolism in Cardiovascular Health)
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22 pages, 7657 KB  
Article
Targeting the Glutamine Transporter SLC1A5 Enhances Sensitivity of Acute Myeloid Leukemia to MLN4924
by Yin Wang, Yuancheng Guo, Xiao Tang, Yu Zhu, Haiping Liang, Yali Zhang and Bei Liu
Biomedicines 2026, 14(3), 667; https://doi.org/10.3390/biomedicines14030667 (registering DOI) - 14 Mar 2026
Abstract
Background/Objectives: Acute myeloid leukemia (AML) remains a hematologic malignancy with poor prognosis. The neddylation inhibitor MLN4924 has demonstrated potent anti-leukemic activity in preclinical models, yet its clinical translation faces significant challenges. The aim of this study was to explore combination therapy strategies [...] Read more.
Background/Objectives: Acute myeloid leukemia (AML) remains a hematologic malignancy with poor prognosis. The neddylation inhibitor MLN4924 has demonstrated potent anti-leukemic activity in preclinical models, yet its clinical translation faces significant challenges. The aim of this study was to explore combination therapy strategies that could further enhance MLN4924’s anti-leukemia potential. Methods: AML cell lines used in this study were Kasumi-1 and MOLM-13. Cell viability was assessed using CCK-8 assays. mRNA and protein expression levels were determined through RT-qPCR and Western blot, respectively. Flow cytometry was employed to analyze surface markers (SLC1A5, CD11b, CD14, CD16), mitochondrial membrane potential (JC-1), and apoptosis (Annexin V-FITC/PI). In vivo efficacy was validated using an NCG mouse xenograft model. Transcriptomic profiling was performed to explore the potential mechanism by which MLN4924 in combination with V9302 inhibits leukemia. Results: Treatment with MLN4924 significantly upregulated key glutamine metabolic proteins, GLUL and the glutamine transporter SLC1A5, in AML cells. Knockdown of SLC1A5 significantly enhanced AML cell sensitivity to MLN4924. The combination of MLN4924 and the SLC1A5 inhibitor V9302 synergistically inhibited AML cell proliferation, induced monocytic differentiation, and promoted apoptosis. Transcriptomic analysis revealed that this combination therapy prominently suppressed the tricarboxylic acid (TCA) cycle. Conclusions: Neddylation inhibition induces compensatory upregulation of glutamine metabolism in AML. Co-targeting neddylation and glutamine transporter SLC1A5 synergistically exerts anti-leukemic effects, at least in part through disruption of the TCA cycle. This combination represents a novel and effective therapeutic strategy against AML. Full article
(This article belongs to the Section Molecular and Translational Medicine)
25 pages, 5765 KB  
Article
Innovative Inclusion Complexes Clotrimazole: Hydroxypropyl-β-Cyclodextrin-Modified Polyurethane Networks as Carriers for Slow Drug Delivery
by Suzana M. Cakić, Snežana S. Ilić-Stojanović, Ljubiša B. Nikolić, Vesna D. Nikolić, Ivan S. Ristić, Gordana S. Marković and Nada Č. Nikolić
Biomedicines 2026, 14(3), 666; https://doi.org/10.3390/biomedicines14030666 (registering DOI) - 14 Mar 2026
Abstract
Background/Objectives: Inclusion complexes among drugs and cyclodextrin-modified polymers are a topic of recent interest in pharmaceutical research and industry as they might expand the solubility, bioavailability, and stability of the guest molecules. Polyurethanes derived from cyclodextrins show some biomedical applications. In this [...] Read more.
Background/Objectives: Inclusion complexes among drugs and cyclodextrin-modified polymers are a topic of recent interest in pharmaceutical research and industry as they might expand the solubility, bioavailability, and stability of the guest molecules. Polyurethanes derived from cyclodextrins show some biomedical applications. In this study, two cross-linked polyurethane networks based on hydroxypropyl-β-cyclodextrin (HPβCD) and polyethylene glycols (PEG 2000 or PEG 6000) were synthesized with NCO/OH molar ratio 4.3 and 6.3 by the typical two-step polymerization method. Methods: Inclusion complexes of clotrimazole (CLOT) with two HPβCD-modified polyurethane networks and their corresponding physical mixtures were prepared using kneading methods and physical mixing in a 1:6 weight ratio of CLOT:HPβCD. Results: Obtained prepolymers, previously end-capped with isocyanate groups forming urethane links with HPβCD, which were confirmed by FTIR analysis. TGA results indicate a slight increase in thermal stability of the prepared complexes. The characteristic endothermic peak of the CLOT at around 145.90 °C did not appear in the DSC curve of the drug-loaded inclusion complexes. The XRD patterns of physical mixtures showed specific peaks corresponding to pure clotrimazole. SEM micrographs confirmed an elliptical/spherical- and plate-shaped particles without phase segregation, indirectly confirming that CLOT is not separately present due to inclusion into HPβCD and entrapment into polyurethane networks. Novel complexes PUR2/HPβCD-CLOT-IC and PUR3/HPβCD-CLOT-IC were applied as drug carriers, and diffusion-controlled kinetics of CLOT release were best described using Higuchi model. Conclusions: The obtained in vitro results showed surprisingly slow/prolonged clotrimazole release from modified polyurethane networks due to the significant influence of NCO/OH molar ratio and the chosen polyol soft segments chain length with potential in vivo applications. Full article
(This article belongs to the Special Issue Drug Delivery and Nanocarrier)
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28 pages, 4917 KB  
Article
CD127+ Natural Killer Cells Represent a Distinct, Interleukin-15-Independent and Thymus-Independent Subset in Mice
by Yuna Kim, Seon-Yeong Hwang, Young-Jin Kwon, Ji-Eun Kim, Lata Rajbongshi, Su-Rin Lee, Seongwon Joo, Seongheum Park, Sae-Ock Oh, Byoung-Soo Kim, Dongjun Lee and Sik Yoon
Int. J. Mol. Sci. 2026, 27(6), 2667; https://doi.org/10.3390/ijms27062667 (registering DOI) - 14 Mar 2026
Abstract
Natural killer (NK) cells, key effectors of innate immunity, are classically categorized into CD56dim and CD56bright subsets in humans. While murine NK cell heterogeneity has become increasingly recognized, the classification of mature NK cell subsets remains incompletely defined. Here, we comprehensively [...] Read more.
Natural killer (NK) cells, key effectors of innate immunity, are classically categorized into CD56dim and CD56bright subsets in humans. While murine NK cell heterogeneity has become increasingly recognized, the classification of mature NK cell subsets remains incompletely defined. Here, we comprehensively characterized CD127+ NK cells in mice and identified them as a distinct, mature subset, developing independently of the thymus and interleukin (IL)-15 signaling. Flow cytometric analyses revealed that CD127+ NK cells are broadly distributed across lymphoid and non-lymphoid tissues—including in C57BL/6 wild-type and athymic Foxn1−/− mice—and exhibit a surface phenotype distinct from CD127 NK and thymus-derived CD127+ NK cells. Functional assays demonstrated that CD127+ NK cells produce interferon-γ and exert cytotoxic activity, despite expressing markers typically associated with immature NK cells. CD127+ NK cells were absent in IL-7Rα−/− mice but present in IL-15−/− and IL-15Rα−/− mice, indicating a selective dependence on IL-7 signaling. IL-7 promoted their proliferation and activation both in vitro and in vivo. These findings revise current models of NK cell development by identifying a novel, IL-7-responsive, IL-15-independent, thymus-independent, and functionally competent CD127+ NK cell subset that is phenotypically distinct from helper-like innate lymphoid cells (ILCs). This study provides a framework for future investigations on NK cell heterogeneity, tissue specialization, and cytokine-mediated regulation. Full article
(This article belongs to the Special Issue Advanced Research on Immune Cells and Cytokines (3rd Edition))
20 pages, 1351 KB  
Article
Concentration and Bioavailability Analysis of Heavy Metals in Mine Tailings from Morelos, Mexico
by Patricia Mussali-Galante, Mariana Hernández-Flores, Alexis Rodríguez, Efraín Tovar-Sánchez, Hugo Albeiro Saldarriaga-Noreña, Marcos Eduardo Rosas-Ramírez and María Luisa Castrejón-Godínez
Processes 2026, 14(6), 927; https://doi.org/10.3390/pr14060927 (registering DOI) - 14 Mar 2026
Abstract
While mining is a highly important economic activity, it generates considerable environmental impact, especially during the grinding and extraction stages of metallic minerals, leading to the formation of waste known as mine tailings. These mine tailings, often abandoned in various regions of Mexico [...] Read more.
While mining is a highly important economic activity, it generates considerable environmental impact, especially during the grinding and extraction stages of metallic minerals, leading to the formation of waste known as mine tailings. These mine tailings, often abandoned in various regions of Mexico due to a lack of prior environmental regulations, contain heavy metals that pose a risk to both the environment and human health. In Huautla, Morelos, where metals such as silver (Ag), gold (Au), copper (Cu), lead (Pb), and zinc (Zn) were extracted from the 16th century until 1988, it is estimated that there are approximately 780,000 tons of mine tailings. These mine tailings are contaminated with heavy metals such as cadmium (Cd), Cu, chromium (Cr), manganese (Mn), Pb, and Zn, and the bioaccumulation and biomagnification of these metals have been documented in various plant and animal species in the region, indicating their bioavailability. The study conducted in this area consisted of determining the concentration of Cd, Cu, Cr, Mn, Pb, and Zn, as well as the sequential extraction of mine tailings 1 and 2 to identify metal bioavailability. The results showed for both mine tailings, that the metals with the highest concentrations were Pb (mine tailing 1: 1666 ± 317.7 mg/kg, mine tailing 2: 1329 ± 30.8 mg/kg) and Zn (mine tailing 1: 1327 ± 314.9 mg/kg, mine tailing 2: 1099 ± 34.3 mg/kg), found in fractions IV and VI, respectively. In mine tailings 1, the main bioavailable metals were Cd (75.3%), Mn (53%), Pb (39.8%), and Cu (36.4%), while in mine tailings 2, the bioavailable metals were Cd (56.8%), Pb (37.9%), and Cu (29.3%). In general, Cd and Pb exhibited the highest bioavailability in both mine tailings. According to the calculated risk indices, bioavailable Cd and Pb pose the highest pollution, ecological, and non-carcinogenic risk in both mine tailings, while bioavailable Cr showed the highest determined carcinogenic risk. This study demonstrated that the mining waste from Huautla contains high levels of bioavailable heavy metals, posing ecological and public health risks, and provides valuable information for the development of effective environmental remediation strategies. Full article
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23 pages, 5281 KB  
Article
Simultaneous Application of Ammonium and Nitrate Nitrogen Enhances Phytoremediation Efficiency by Mediating Biomass and Bioavailability of Lead and Cadmium in Salix linearistipularis
by Jian Zhou, Dongliu Di, Yaoyao Zhang, Zhuotian Gao, Xiaoyun Niu, Dazhuang Huang and Keye Zhu
Forests 2026, 17(3), 364; https://doi.org/10.3390/f17030364 (registering DOI) - 14 Mar 2026
Abstract
This study aims to elucidate the effects and mechanisms of ammonium (NH4+-N) and nitrate (NO3-N) nitrogen on the efficiency of Salix linearistipularis K. S. Hao in remediating heavy metal-contaminated soils. Thus, the effects of 15 fertilization treatments [...] Read more.
This study aims to elucidate the effects and mechanisms of ammonium (NH4+-N) and nitrate (NO3-N) nitrogen on the efficiency of Salix linearistipularis K. S. Hao in remediating heavy metal-contaminated soils. Thus, the effects of 15 fertilization treatments (comprising three nitrogen levels and five nitrogen form ratios) on Pb and Cd accumulation, soil properties, microbial structure, and metabolic characteristics were investigated using a pot experiment. The results indicated that Pb and Cd accumulation were the highest under the L12 treatment (60 kg N·hm−2·year−1, NH4+-N/NO3-N = 1:2), whereas nitrate-only treatments, irrespective of concentration, resulted in a decrease in accumulation. In the L12 treatment, biomass increased by 87.0%, with Pb and Cd accumulation rising by 85.71% and 80.0%, respectively, suggesting that biomass may contribute predominantly to heavy metal accumulation. Additionally, NH4+-N/NO3-N ratio had a greater effect on biomass than the nitrogen application amount. Microbial composition was altered, and the relative abundance of heavy metal-resistant microbes increased. However, the amount of nitrogen fertilizer had a stronger impact on microbial variation. Under different nitrogen application rates and NH4+-N/NO3-N ratios, the formation or disappearance of unique metabolic pathways related to amino acids and carbohydrates was observed. Furthermore, both microbial metabolism and the bioavailability of Pb and Cd were positively correlated with nitrogen levels and NH4+-N/NO3-N ratios. These findings indicate a potential association between shifts in microbial metabolism and the bioavailability of heavy metals. Therefore, the simultaneous application of ammonium and nitrate nitrogen in appropriate ratios can enhance the remediation efficiency of S. linearistipularis by boosting biomass and heavy metal bioavailability via microbial metabolism. The findings of this study not only provide novel insights into improving the phytoremediation efficiency of woody plants through fertilization strategies but also lay a theoretical foundation for the effects of nitrogen fertilization on nutrient cycling in metal-contaminated soils. Full article
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17 pages, 5235 KB  
Article
Pathologic Th1–Treg Cells Exacerbate Acute Lung Injury and Lethality in Sepsis
by Takuya Murao, Atsushi Murao, Monowar Aziz and Ping Wang
Cells 2026, 15(6), 521; https://doi.org/10.3390/cells15060521 (registering DOI) - 14 Mar 2026
Abstract
Sepsis is characterized by dysregulated immune responses induced by damage-associated molecular patterns, such as extracellular cold-inducible RNA-binding protein (eCIRP), that frequently lead to acute lung injury (ALI) and high mortality. Recently, a subset of CD4+ T cells possessing both T helper 1 [...] Read more.
Sepsis is characterized by dysregulated immune responses induced by damage-associated molecular patterns, such as extracellular cold-inducible RNA-binding protein (eCIRP), that frequently lead to acute lung injury (ALI) and high mortality. Recently, a subset of CD4+ T cells possessing both T helper 1 (Th1) and regulatory T cell (Treg) phenotypes, termed Th1-Treg cells, has been identified; however, their function in sepsis remains unknown. In this study, we investigated the dynamics, induction mechanisms, and functional roles of Th1-Treg cells in the development of sepsis-induced ALI. Polymicrobial sepsis was induced in mice using cecal ligation and puncture. In vivo, Th1-Treg cell accumulation in the lungs was analyzed in WT and CIRP−/− mice following sepsis. In vitro, isolated CD4+ T cells from WT and TLR4−/− mice were treated with eCIRP to evaluate Th1-Treg cell differentiation and downstream signaling pathways. STAT1 and STAT5 activation were evaluated, and pharmacological inhibitors were used to assess their involvement. Adoptive transfer of Th1-Treg cells was conducted to determine their functional impact on ALI and mortality in septic mice. We observed a significant accumulation of Th1-Treg cells in the lungs of WT septic mice compared to sham mice. eCIRP drove the induction of Th1-Treg cells in vitro, and CIRP−/− mice exhibited decreased Th1-Treg cell accumulation in the lungs compared to WT mice after sepsis. In parallel to Th1-Treg cell induction, eCIRP activated signal transducer and activator of transcription, STAT1 and STAT5. Both the induction of Th1-Treg cells and the activation of STAT1/5 proteins were significantly attenuated in TLR4−/− mice. Furthermore, pharmacological inhibition of STAT1/5 signaling significantly reduced eCIRP-induced Th1-Treg cell differentiation. Intriguingly, adoptive transfer of Th1-Treg cells significantly exacerbated ALI, resulting in increased mortality in sepsis. Our findings indicate Th1-Treg cells induced by the eCIRP–TLR4–STAT1/5 axis aggravate ALI, worsening mortality in sepsis. Targeting these pathogenic cells potentially alleviates sepsis-induced ALI. Full article
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16 pages, 835 KB  
Article
Follow-Up After Urgent Endodontic Care: A Retrospective Exploratory Study in a University Clinic
by Mubashir Baig Mirza, Turky AlShammeri, Saleh AlMutairi, Shahad AlBader, Abdulaziz Abdulwahed, Osamah AlQasem, Ahmed AlMokhatieb, Laila S. AlMufleh, Mohammed Ali Abuelqomsan and Qamar Hashem
Medicina 2026, 62(3), 544; https://doi.org/10.3390/medicina62030544 (registering DOI) - 14 Mar 2026
Abstract
Background and Objectives: Many patients present with urgent endodontic conditions characterized by pain and swelling, requiring prompt intervention. Failure to return for definitive root canal treatment (RCT) after urgent care can compromise tooth prognosis. This study examined the frequency and diagnostic patterns of [...] Read more.
Background and Objectives: Many patients present with urgent endodontic conditions characterized by pain and swelling, requiring prompt intervention. Failure to return for definitive root canal treatment (RCT) after urgent care can compromise tooth prognosis. This study examined the frequency and diagnostic patterns of urgent endodontic visits at a university dental college and evaluated predictors of follow-up after urgent treatment, considering demographic, anatomical, and clinical factors. Materials and Methods: A retrospective cohort analysis of 1619 patient records (August 2023–May 2025) was conducted. Data on urgency type, pulpal/periapical diagnosis, tooth characteristics, urgent treatment modality, and follow-up attendance were collected. Descriptive statistics and chi-square tests were used to assess bivariate associations. Multivariable logistic regression was performed to evaluate factors associated with completing follow-up after urgent care. Results: Approximately 50.2% of visits involved urgent endodontic care, most commonly symptomatic irreversible pulpitis (SIP) with symptomatic apical periodontitis (SAP), particularly in posterior teeth. Pulpectomy was the most frequently provided urgent treatment. Overall, 72.8% of urgent-care patients returned for completion of RCT (overall OR = 2.67). While urgency incidence and follow-up rates did not differ by gender, arch, or region, gender-stratified comparisons within urgent cases showed significant differences by arch and region. In multivariate analysis, mandibular teeth demonstrated higher odds of follow-up than maxillary teeth, whereas gender and region showed no association. Patients diagnosed with asymptomatic irreversible pulpitis (AIP)/SAP had lower odds of returning, and those treated with canal debridement with occlusal reduction (CD/OD) were also less likely to complete treatment. No other diagnostic or treatment categories showed significant associations. Conclusions: In this university-based cohort, urgent endodontic visits were common and primarily involved SIP/SAP. While the overall follow-up rate was high, certain diagnostic and treatment scenarios, specifically AIP/SAP and CD/OD, were associated with a reduced likelihood of returning for completion of RCT. Given the study’s limitations, these findings should be interpreted with caution. Full article
(This article belongs to the Section Dentistry and Oral Health)
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27 pages, 2836 KB  
Article
A Predictive Immunological Signature Associated with Pathological Response in Breast Cancer Treated with Neoadjuvant Chemotherapy
by Luis Arturo Palafox-Mariscal, Mariel García-Chagollán, Jesús García-Gómez, Fabiola Martín-Amaya-Barajas, Valeria Peña-Ruiz, Elizabeth Alvarez-Gonzalez, Eric Alfredo Aranda-Zuno, Jonathan Gallegos-Diaz-de-Leon, Aldo Antonio Alcaraz-Wong, Karina Ordoñez-Pantoja, Raquel Villegas-Pacheco, Adriana Aguilar-Lemarroy and Luis Felipe Jave-Suarez
Biomedicines 2026, 14(3), 663; https://doi.org/10.3390/biomedicines14030663 (registering DOI) - 14 Mar 2026
Abstract
Background/Objectives: Breast cancer is a heterogeneous and complex disease with significant individual differences in molecular immunophenotype, biological behavior, histopathological morphology, and response to chemotherapy. The presence of tumor-infiltrating lymphocytes (TILs) has gained considerable attention due to growing evidence of their involvement in [...] Read more.
Background/Objectives: Breast cancer is a heterogeneous and complex disease with significant individual differences in molecular immunophenotype, biological behavior, histopathological morphology, and response to chemotherapy. The presence of tumor-infiltrating lymphocytes (TILs) has gained considerable attention due to growing evidence of their involvement in therapeutic efficacy, particularly in the response to neoadjuvant chemotherapy (NACT). Different immune cell subsets’ frequency, location, and functional orientation vary substantially between tumor types and individuals with apparently identical cancers. Currently, next-generation sequencing (NGS) has provided key insights into the composition of the tumor microenvironment. Simultaneously, immunohistochemistry (IHC) of paraffin-embedded biopsies allows the visualization of marker proteins within the immune infiltrate, thereby enhancing our understanding of the role of immune cells in cancer therapy. Methods: This exploratory study evaluated immune cell tumor infiltration using NGS with immune cell deconvolution, as well as automated IHC on Tru-Cut biopsies from 57 patients with locally advanced breast cancer. Image analysis was performed using Qupath v0.6.0 software. The percentage of infiltrating CD4+ or CD8+ T cells was determined, along with the expression of the markers FoxP3, LAG3, CTLA4, PD1, and TIM-3. We aimed to gain insights into the tumor microenvironment and its influence on the response to NACT in patients with breast cancer. Results: Transcriptomic immune deconvolution approaches suggested that a biased cytotoxic tumor environment is linked to chemosensitivity. IHC assays of individual markers reveal that baseline immune cell abundance and individual checkpoint expression did not differ significantly across the response groups. However, the functional organization and coordination of the tumor immune microenvironment showed distinct associations with chemosensitivity. Conclusions: Features representing immune balance, such as CD8/CD4 ratio and T cell-contextualized metrics, emerged as candidate predictors of pathological response to NACT, outperforming molecular phenotype alone in this exploratory cohort. Full article
(This article belongs to the Special Issue Molecular Research in Breast Cancer)
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13 pages, 251 KB  
Article
Different Trends of Immune Activation Markers When Switching to Either Oral or Injectable Dual Antiretroviral Therapy Based on Integrase Inhibitors in People Living with HIV
by Matteo Vassallo, Jacques Durant, Roxane Fabre, Jacqueline Capeau, Soraya Fellahi, Jean-Philippe Bastard, Pierre Corbeau and Christian Pradier
Pathogens 2026, 15(3), 316; https://doi.org/10.3390/pathogens15030316 (registering DOI) - 14 Mar 2026
Abstract
Background: Despite improvements in life expectancy, people living with HIV (PWH) continue displaying immune activation and high rates of comorbid conditions. No comparative studies concerning activation markers exist between simplification strategies to either oral or long-acting (LA) dual ART. Methods: We prospectively collected [...] Read more.
Background: Despite improvements in life expectancy, people living with HIV (PWH) continue displaying immune activation and high rates of comorbid conditions. No comparative studies concerning activation markers exist between simplification strategies to either oral or long-acting (LA) dual ART. Methods: We prospectively collected plasma samples from PWH on successful ART, simplifying treatment from triple oral to either oral or LA dual ART based on integrase inhibitors. We measured changes in soluble CD14 (sCD14), soluble CD163 (sCD163), monocyte chemoattractant protein-1, and interleukin-6. Background measurements and markers of microbial translocation and gut integrity (I-FABP, LBP) were also collected. Results: From 2019 to 2023, 38 PWH were analyzed (mean age 52, 87% male, 21 years HIV diagnosis, CD4 730 cells/mm3, nadir CD4 317 cells/mm3, AIDS 13%). After 7.2 months, sCD14 trajectories differed according to regimen (+0.43 ng/mL, p = 0.033 for LA ART, −0.62 ng/mL, p < 0.001 for oral ART) but were not related to I-FABP or to LBP values. In case of CD4 nadir < 200 cc/mm3, AIDS, or very-low-level viremia, sCD163 values significantly increased when switching to oral but not to LA dual ART. Conclusion: We found different trends in immune activation markers and risk factors associated with PWH switching to either oral or LA ART, requiring larger studies. Full article
18 pages, 2562 KB  
Article
Evaluating Conservation Grazing Through Fine-Scale Vegetation Structure in Invaded Marsh Meadows
by Krisztina Napsugár Nagy, Zsuzsa Petra Bartal, Csilla Evelin Károlyi and László Bakacsy
Diversity 2026, 18(3), 177; https://doi.org/10.3390/d18030177 (registering DOI) - 14 Mar 2026
Abstract
Active conservation management is widely applied in ecosystems affected by biological invasions, where outcomes depend primarily on how management regimes shape the vegetation structure. Grazing is a common tool in floodplain marsh meadows, but differences between grazing regimes are rarely assessed at spatial [...] Read more.
Active conservation management is widely applied in ecosystems affected by biological invasions, where outcomes depend primarily on how management regimes shape the vegetation structure. Grazing is a common tool in floodplain marsh meadows, but differences between grazing regimes are rarely assessed at spatial scales sensitive to internal community organization. Here, we compared the fine-scale structural diversity of two Amorpha fruticosa-invaded marsh meadows managed under contrasting conservation grazing regimes differing in livestock species, grazing intensity, and grazing dynamics. Vegetation was sampled using microcoenological methods along circular transects of contiguous 5 × 5 cm microquadrats. The fine-scale structure of the vegetation was quantified using the Juhász–Nagy spatial series framework, focusing on compositional diversity (CD) and associatum (AS), complemented by Shannon diversity. Differences between grazing regimes were evaluated using nonparametric tests complemented by effect size estimation. The patterns of species occurrence and Shannon diversity were similar between sites, indicating a similar species composition. In contrast, JNP-derived structural metrics showed consistent directional differences, with moderate to large effect sizes for selected structural indicators, despite nonsignificances. These results indicate that conservation grazing primarily influences fine-scale structural organization rather than species composition, highlighting the value of structure-oriented metrics in evaluating management effects in invaded marsh meadows. Full article
(This article belongs to the Special Issue Ecology, Distribution, Impacts, and Management of Invasive Plants)
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22 pages, 1815 KB  
Article
Effect of Water Vapor Generated by Fresh-Cut Mango (Mangifera indica) on the Release of β-Carotene from β-Cyclodextrin Inclusion Complexes Under Modified-Atmosphere Packaging
by Andrés Leobardo Puebla-Duarte, Daniel Fernández-Quiroz, Ariadna Thalía Bernal-Mercado, Francisco Rodríguez-Félix, Rey David Iturralde-García, Miguel Ángel Robles-García, Saul Ruiz-Cruz, José de Jesús Ornelas-Paz, Ricardo Iván González-Vega and Carmen Lizette Del-Toro-Sánchez
Molecules 2026, 31(6), 976; https://doi.org/10.3390/molecules31060976 (registering DOI) - 14 Mar 2026
Abstract
This study evaluated the effect of water vapor generated by fresh-cut mango (Mangifera indica) on the release of β-carotene from β-cyclodextrin complexes (β-C:β-CD) under stored Modified Atmosphere Packaging (MAP) and to demonstrate β-carotene stabilization and passive–active packaging behavior under MAP conditions. [...] Read more.
This study evaluated the effect of water vapor generated by fresh-cut mango (Mangifera indica) on the release of β-carotene from β-cyclodextrin complexes (β-C:β-CD) under stored Modified Atmosphere Packaging (MAP) and to demonstrate β-carotene stabilization and passive–active packaging behavior under MAP conditions. Containers with fresh-cut mangoes, with and without MAP (4% O2, 6% CO2, 90% N2), were prepared for monitoring over 6 days at 4 °C. β-C:β-CD complexes were incorporated into the lids of containers. The physicochemical, relative humidity, antioxidant, erythroprotective, microbiological, and biofunctional qualities of freshly cut mangoes during storage were analyzed. Active metabolic respiration of plant tissue led to a progressive decrease in O2 and an increase in CO2 in sealed containers, a phenomenon intensified by cutting, high humidity, and the system’s limited gas permeability. Application of MAP effectively modulated this microenvironment, reducing respiration rate, water loss, acidification, and the degradation of bioactive compounds. Compared to treatments without MAP, mangoes stored under modified atmosphere showed greater color stability, a slower rate of change in pH and titratable acidity, less loss of antioxidant activity and phenolic compounds, and significant preservation of erythroprotective capacity. Furthermore, MAP maintained microbial counts within the limits established by current regulations until the sixth day of storage. The encapsulation of β-C in β-CD effectively protected its bioactivity from oxidation, especially under MAP, although its release into the food matrix was limited, suggesting a predominantly passive behavior of the active packaging system. Overall, the results demonstrate that the combination of MAP constitutes a promising strategy for extending the shelf life and biofunctional stability of fresh-cut mangoes and β-C into the complex. Full article
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18 pages, 673 KB  
Article
Short-Term Trace Element Distribution Following Application of Sargassum-Based Liquid Biofertilizer in a Soil–Plant–Tomato Fruit System
by Yaset Rodríguez-Rodríguez, Máximo Elías Reynoso Ortega, Pamela Tejada-Tejada, Gustavo Gandini, Luis Enrique Rodríguez de Francisco and Ulises Javier Jáuregui-Haza
Plants 2026, 15(6), 901; https://doi.org/10.3390/plants15060901 (registering DOI) - 14 Mar 2026
Abstract
The recurrent influx of pelagic Sargassum spp. along Caribbean coastlines poses a significant environmental challenge while offering potential as a resource-recovery agricultural input. However, agricultural reuse of Sargassum biomass raises concerns regarding salinity and trace-metal distribution within the soil–plant–food continuum. This study evaluated [...] Read more.
The recurrent influx of pelagic Sargassum spp. along Caribbean coastlines poses a significant environmental challenge while offering potential as a resource-recovery agricultural input. However, agricultural reuse of Sargassum biomass raises concerns regarding salinity and trace-metal distribution within the soil–plant–food continuum. This study evaluated the short-term elemental response to a Sargassum-Based Liquid Biofertilizer (SBLB) produced via controlled anaerobic fermentation, using tomato (Solanum lycopersicum L.) grown under greenhouse conditions. Raw biomass, fermented biofertilizer, irrigation water, soils, vegetative tissues, and fruits were chemically characterized. Elemental concentrations were quantified by ICP–OES and ICP-MS and treatment effects were analyzed using one-way and two-way ANOVA (p < 0.05). Anaerobic fermentation resulted in lower measured concentrations of sodium, arsenic, and selected trace elements in the liquid fraction relative to raw biomass. SBLB application increased soil macronutrient availability (N, P, K, Ca, Mg), while soil trace-metal concentrations remained within international reference ranges during the experimental period. Metals of concern (As, Cd, Pb, Ni, Cr) showed no detectable short-term enrichment in soils, vegetative tissues, or fruits relative to controls. In tomato fruits, arsenic, cadmium, and lead were below the limit of quantification across all treatments. Within the experimental timeframe, SBLB application was not associated with detectable trace-element accumulation in the soil–plant system. Long-term field studies and detailed soil physicochemical characterization are required to evaluate cumulative effects under repeated applications. Full article
(This article belongs to the Topic Plant-Soil Interactions, 2nd Volume)
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