Biomedicines

56 pages, 74797 KB

Open AccessReview

Demystifying Nanotherapeutic Modalities: Unravelling the Mysteries from Antibiofilm Mechanisms to Regenerative and Clinical Translation

by Muhammad Umar Javed, Changying Zhang, Zhengwei Huang and Bing Guo

Biomedicines 2026, 14(9), 2030; https://doi.org/10.3390/biomedicines14092030 (registering DOI) - 9 Sep 2026

Abstract

Dental infections continue to pose a major health concern worldwide, driven by persistent microbial biofilms, dysregulated host responses, and suboptimal efficacy of conventional antimicrobial therapies. The emergence of nanotechnology has facilitated the development of therapeutic approaches that offer spatiotemporal, minimally invasive, and resistance-preventing [...] Read more.

Dental infections continue to pose a major health concern worldwide, driven by persistent microbial biofilms, dysregulated host responses, and suboptimal efficacy of conventional antimicrobial therapies. The emergence of nanotechnology has facilitated the development of therapeutic approaches that offer spatiotemporal, minimally invasive, and resistance-preventing alternatives for treating complex dental infections. This review critically assesses novel nanomaterial-based therapies designed to directly eradicate pathogenic microorganisms involved in periodontal disease, dental caries, oral candidiasis and endodontic infections. We first explore the roles of microbial dysbiosis and biofilm-associated pathogenicity as key factors in disease progression, thereby providing a biological rationale for targeted therapies. Particular emphasis is placed on pathogen-directed modalities such as photodynamic, photothermal, sonodynamic, chemodynamic, and nanozyme-based therapies, which allow localized microbial eradication while reducing antibiotic resistance. The design and effectiveness of multifunctional nanomaterials, ranging from bioactive nanoparticles and polymeric hydrogels to microsphere-based delivery systems and implant surface modifications, are analysed in the context of antimicrobial efficacy, biofilm disruption, and compatibility with regenerative processes. Meanwhile, recent advances in integration with tissue regeneration and the potential of artificial intelligence in diagnosis, treatment strategies and materials design are explored as complementary strategies that could improve therapeutic outcomes. By consolidating mechanistic and translational insights, this review highlights how pathogen-targeted nanotherapeutics are revolutionizing the treatment of dental infections with more effective and clinically viable solutions. Full article

(This article belongs to the Section Nanomedicine and Nanobiology)

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4 pages, 183 KB

Open AccessEditorial

Allergic Rhinitis: From Pathology to Novel Therapeutic Approaches

by Shiwang Tan and Shaoqing Yu

Biomedicines 2026, 14(9), 2029; https://doi.org/10.3390/biomedicines14092029 (registering DOI) - 9 Sep 2026

Abstract

Allergic rhinitis (AR) is a common chronic inflammatory disorder of the upper airway in which allergen sensitization interacts with epithelial, neural, and immune responses, as well as comorbidity and treatment context, to shape clinical expression[...] Full article

(This article belongs to the Special Issue Allergic Rhinitis: From Pathology to Novel Therapeutic Approaches)

15 pages, 1575 KB

Open AccessArticle

Complementary Regulation of Inflammatory, Catabolic, and PPARγ Signaling by Dexamethasone and Decanoic Acid in Donor-Specific Human Chondrocyte Models

by Gregory W. Thomas, Jason Williams, Raphael Bar-Or, Melissa A. Hausburg, Kaysie Banton and David Bar-Or

Biomedicines 2026, 14(9), 2028; https://doi.org/10.3390/biomedicines14092028 - 9 Sep 2026

Abstract

Background/Objectives: This study examined whether dexamethasone (Dex) and decanoic acid (DA) exert complementary effects on inflammatory signaling, catabolic gene expression, and peroxisome proliferator-activated receptor gamma (PPARγ) activation in human chondrocytes. Methods: Two donor-specific primary human chondrocyte models, each derived from a single knee [...] Read more.

Background/Objectives: This study examined whether dexamethasone (Dex) and decanoic acid (DA) exert complementary effects on inflammatory signaling, catabolic gene expression, and peroxisome proliferator-activated receptor gamma (PPARγ) activation in human chondrocytes. Methods: Two donor-specific primary human chondrocyte models, each derived from a single knee donor, were used, in which cells were treated with Dex (≤0.1 µM), DA (≤500 µM), or combinations thereof. Acute Interleukin-1β(IL-1β)-induced PGE₂ release was evaluated in normal donor cells, whereas prolonged transcriptional responses and PPARγ DNA-binding activity were evaluated in OA donor cells. IL-1β-induced prostaglandin E₂ (PGE₂) release was measured by competitive ELISA after 24 h. Glyceraldehyde-3-phosphate dehydrogenase-normalized transcription of Collagen type II alpha 1, Collagen type I alpha 1, Aggrecan, SRY-Box Transcription Factor 9, Runt-Related Transcription Factor 2, and Matrix Metalloproteinase 13 (MMP13) was assessed by qRT-PCR at 7, 10–14, and 20–28 days. In addition, PPARγ DNA-binding activity was measured after 1 week. Interactions were evaluated by Loewe additivity and highest single agent (HSA) analyses. Results: Dex and DA each reduced PGE₂ release, whereas co-treatment increased potency and maximal inhibition, with a Loewe combination index of 0.4 at 1 nM Dex plus 19 µM DA. In the temporal analysis, Dex plus DA showed a positive MMP13 ΔCt difference versus Dex at 10–14 days (2.42 ± 2.14; p = 0.065) and a more consistent difference at 20–28 days (1.11 ± 0.25; p = 0.016). This agreed with fixed-dose HSA findings at 14 and 28 days (ΔHSA ≈ −75 for 0.1 µM Dex plus 100 µM DA versus Dex). Co-treatment was also associated with increased PPARγ activation beyond the HSA reference (ΔHSA ≈ 0.09 for 0.1 µM Dex plus 100–250 µM DA versus Dex). Conclusions: Dex plus DA co-treatment produced complementary effects on acute PGE₂ inhibition, as well as late-onset MMP13 suppression and PPARγ activity in the donor-specific chondrocyte models studied. These hypothesis-generating findings provide an in vitro rationale for future evaluation of this combination as a corticosteroid-sparing strategy. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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22 pages, 2871 KB

Open AccessReview

Essential Oil-Loaded Lipid Nanocarriers with Anti-Inflammatory Activity: Quality Control, Safety, and Efficacy

by Pedro Paulo de Melo Ferreira, Ana Clara Santiago Bastos, Fernanda Nervo Raffin and Lígia Nunes de Morais Ribeiro

Biomedicines 2026, 14(9), 2027; https://doi.org/10.3390/biomedicines14092027 - 9 Sep 2026

Abstract

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, [...] Read more.

Inflammation is a complex biological response involved in the pathophysiology of several chronic diseases. Although conventional anti-inflammatory therapies are effective, their prolonged use can be associated with relevant adverse effects. Although non-steroidal anti-inflammatory drugs and glucocorticoids are widely used, these agents cause gastrointestinal, renal, cardiovascular, hepatic and metabolic adverse effects. Essential oils (EO) exhibit relevant anti-inflammatory potential. However, their pharmaceutical application is limited by volatility, hydrophobicity, physicochemical instability and potentially low bioavailability. This review evaluated EO-loaded lipid nanocarriers for anti-inflammatory applications, with emphasis on physicochemical quality attributes, stability, safety and efficacy. Literature searches were carried out through PubMed/MEDLINE, PubMed Central, ScienceDirect, SciELO, Virtual Health Library, and Google Scholar websites, based on works published between 2021 and 2026. The investigated systems included liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions. Different formulations were found regarding EO nature, nanocarrier type, administration route and biological models used, predominantly involving preclinical assays. Nanoencapsulation was frequently associated with suitable physicochemical properties and release profiles, but direct comparisons with the corresponding free EO and control nanocarriers were not consistently performed. Safety findings were mainly based on cytotoxicity, local tolerability and short-term assays, with limited repeated-dose and long-term toxicological data. Several formulations showed anti-inflammatory activity in acute, subacute, or chronic experimental models. In selected works using the same experimental conditions, some formulations produced responses of similar magnitude to hydrocortisone, diclofenac, or other anti-inflammatory drugs, but these results cannot be directly correlated with therapeutic equivalence. The reported mechanisms involved modulation of the NF-κB, MAPK and Keap1/Nrf2/HO-1 signaling pathways. Overall, lipid-based nanocarriers represent platforms for investigating the stability, delivery and biological performance of EO. However, further standardization and controlled assays are required to determine their therapeutic and translational potential. Full article

(This article belongs to the Special Issue Advanced Development on Lipid Nanoparticles)

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19 pages, 866 KB

Open AccessArticle

Serum Alpha-Klotho and Coronary Atherosclerosis: Associations with Coronary CT Angiography Findings and Atherogenic Indices

by Ayça Tuzcu, Mustafa Gök, Kenan Yörük, Mustafa Yılmaz, Ali Alkaşi and Göksel Tuzcu

Biomedicines 2026, 14(9), 2026; https://doi.org/10.3390/biomedicines14092026 - 9 Sep 2026

Abstract

Background/Objectives: Alpha-Klotho is a circulating protein with anti-aging and vasculoprotective properties that may play a role in vascular calcification. This study aimed to investigate the association between serum alpha-Klotho levels and coronary atherosclerotic burden assessed by the Agatston score and CAD-RADS grading, [...] Read more.

Background/Objectives: Alpha-Klotho is a circulating protein with anti-aging and vasculoprotective properties that may play a role in vascular calcification. This study aimed to investigate the association between serum alpha-Klotho levels and coronary atherosclerotic burden assessed by the Agatston score and CAD-RADS grading, as well as cardiometabolic risk indices. Methods: This single-center, prospective, cross-sectional study included 86 patients undergoing coronary computed tomography angiography. Serum alpha-Klotho levels were measured by ELISA. Associations with imaging and metabolic variables were assessed using Spearman correlation and age-adjusted partial correlation analyses. Independent associations were evaluated using multivariable linear regression with HC3-robust standard errors. Binary and ordinal logistic regression models with CAD-RADS as the dependent variable and receiver operating characteristic (ROC) analysis were additionally performed. Results: Serum Klotho levels were negatively correlated with age (ρ = −0.598), Agatston score (ρ = −0.540), and CAD-RADS (ρ = −0.549) (all p < 0.001). Associations with the Agatston score and CAD-RADS remained significant after age adjustment (ρ = −0.348 and −0.352, respectively). AIP also remained independently associated with Klotho after age adjustment (ρ = −0.289, p = 0.007), whereas associations with TyG and METS-IR were attenuated. Multivariable models explained 50–52% of the variance in Klotho. In ordinal logistic regression, Klotho remained independently associated with CAD-RADS severity after adjustment for age, sex, BMI, and AIP (OR = 0.525, p = 0.033). ROC analysis demonstrated moderate discrimination for the presence of coronary atherosclerosis, defined as Agatston score > 0 (equivalently, CAD-RADS > 0 in this cohort) (AUC = 0.754, 95% CI 0.654–0.855); an exploratory, internally derived cutoff of ≤823 pg/mL—not a clinically validated threshold—yielded 72.0% sensitivity and 75.0% specificity (bootstrap-validated optimism-corrected: 69.3% and 72.5%). Conclusions: Lower serum alpha-Klotho levels were independently associated with greater coronary atherosclerotic burden and showed moderate discriminative ability for its presence. These findings are preliminary and support further investigation of alpha-Klotho as a candidate circulating biomarker of coronary atherosclerosis, pending validation in larger, prospective cohorts. Full article

(This article belongs to the Special Issue Imaging Technology for Human Diseases: 2nd Edition)

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11 pages, 621 KB

Open AccessArticle

PLTP Variants rs6065904 and rs378114 Are Associated with Acute Coronary Syndrome Risk and Altered Glucose and Triglyceride Levels in a Mexican Population

by Gilberto Vargas-Alarcón, Oscar Pérez-Méndez, Rosalinda Posadas-Sánchez, Julio Cesar Domínguez-Méndez, Marva Arellano-González, Galileo Escobedo, Teresa Juárez-Cedillo and José Manuel Fragoso

Biomedicines 2026, 14(9), 2025; https://doi.org/10.3390/biomedicines14092025 - 9 Sep 2026

Abstract

Background: Phospholipid transfer protein (PLTP) facilitates lipid transfer among plasma lipoproteins, but the contribution of this protein to coronary heart disease (CHD) remains controversial. In this context, evaluating single nucleotide polymorphisms (SNPs) in the PLTP gene, specifically rs6065904 A/G and rs378114 T/C [...] Read more.

Background: Phospholipid transfer protein (PLTP) facilitates lipid transfer among plasma lipoproteins, but the contribution of this protein to coronary heart disease (CHD) remains controversial. In this context, evaluating single nucleotide polymorphisms (SNPs) in the PLTP gene, specifically rs6065904 A/G and rs378114 T/C, may hold clinical utility for predicting CHD risk. Nevertheless, currently evidence on the association between these variants and cardiovascular outcomes remains scarce. To address this gap, we investigated whether the rs6065904 A/G and rs378114 T/C SNPs of the PLTP gene are associated with the incidence of acute coronary syndrome (ACS) and explored whether this potential relationship is mediated by plasma lipid levels. Methods: This study included 2377 Mexican Mestizos (1378 ACS patients and 999 control individuals). The PLTP SNPs (rs6065904 A/G, and rs378114 T/C) were genotyped using TaqMan assays on Real-Time PCR equipment, following the manufacturer’s cycling protocol. Results: Logistic regression analysis under different inheritance models revealed that homozygosity for the rs6065904 AA and rs378114 TT genotypes was associated with a significant increased risk of ACS. In subgroup analysis restricted to ACS patients, both genotypes were also significantly associated with altered triglyceride and glucose levels. Complementary bioinformatic analysis using the Genotype-Tissue Expression (GTEx) Project suggested that these genotype–phenotype associations might be mechanistically linked to reduced PLTP mRNA expression. Conclusions: In summary, the rs6065904 A/G and rs378114 T/C SNPs in the PLTP gene are associated with ACS risk, and with circulating triglyceride and glucose levels. Full article

(This article belongs to the Special Issue Risk Factors and Molecular Mechanisms in Diabetes and Cardiovascular Complications)

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21 pages, 2413 KB

Open AccessArticle

Concurrent Alterations in Selected mRNAs and miR-30 Family Members in Canine Osteoarthritic Joint Tissues

by Gabriella Guelfi, Vicente F. Ratto, Camilla Capaccia, Francesco Ciancabilla, David Forti, Leonardo Leonardi, Antonello Bufalari, Arcangelo Liso and Margherita Maranesi

Biomedicines 2026, 14(9), 2024; https://doi.org/10.3390/biomedicines14092024 - 9 Sep 2026

Abstract

Background: Osteoarthritis (OA) is a chronic whole-joint disease involving extracellular matrix remodeling, inflammatory signaling, immune–stromal interactions, and sensory-associated processes. MicroRNAs (miRNAs) may contribute to post-transcriptional regulation within these interconnected molecular domains, but concurrent mRNA and miRNA expression patterns remain insufficiently characterized in naturally [...] Read more.

Background: Osteoarthritis (OA) is a chronic whole-joint disease involving extracellular matrix remodeling, inflammatory signaling, immune–stromal interactions, and sensory-associated processes. MicroRNAs (miRNAs) may contribute to post-transcriptional regulation within these interconnected molecular domains, but concurrent mRNA and miRNA expression patterns remain insufficiently characterized in naturally occurring canine OA. Methods: A total of 12 formalin-fixed, paraffin-embedded (FFPE) canine tissue specimens were classified as osteoarthritic joint tissues (OA; n = 7) and control joint tissues without radiographic or histopathological evidence of OA (C-JT; n = 5). RT-qPCR was used to quantify 17 selected mRNAs involved in extracellular matrix remodeling, chronic inflammatory signaling, immune–stromal interactions, and neuroinflammatory and sensory-associated processes, together with five miR-30 family members. Statistical comparisons were performed on ΔCq values using two-sided unpaired Welch’s t-tests followed by Benjamini–Hochberg false discovery rate correction. Results: Compared with C-JT, OA tissues showed significantly higher expression of ADAMTS5, MMP2, MMP13, COL2A1, SPARC, HP, VEGFA, IGFBP6, and ASIC3 after false discovery rate correction. MMP9, IL1B, IL1R1, IL1RAP, JAK2, TYK2, NGFB, and NTRK1 did not differ significantly between the two joint-tissue groups. MiR-30b was significantly downregulated in OA, whereas miR-30c, miR-30d, and miR-30e were significantly upregulated; miR-30a did not differ significantly. Exploratory database-supported miRNA–gene connectivity was used for candidate prioritization but was not interpreted as evidence of direct regulation in canine joint tissue. Conclusions: Canine osteoarthritic capsulosynovial tissues exhibit concurrent alterations in selected mRNAs and miR-30 family members across matrix-remodeling, immune–stromal, and sensory-associated molecular domains. These findings identify OA-associated expression patterns but do not establish pathway activation, direct miRNA–mRNA regulation, or disease progression. They provide a focused molecular basis for future mechanistic studies of post-transcriptional regulation in naturally occurring canine OA. Full article

(This article belongs to the Special Issue Translational and Precision Medicine in Osteoarthritis, Bone Healing and Musculoskeletal Diseases)

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1 pages, 142 KB

Open AccessCorrection

Correction: Borgonetti, V.; Galeotti, N. Rosmarinic Acid Reduces Microglia Senescence: A Novel Therapeutic Approach for the Management of Neuropathic Pain Symptoms. Biomedicines 2022, 10, 1468

by Vittoria Borgonetti and Nicoletta Galeotti

Biomedicines 2026, 14(9), 2023; https://doi.org/10.3390/biomedicines14092023 - 9 Sep 2026

Abstract

In the original publication [...] Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

15 pages, 1318 KB

Open AccessArticle

Diagnostic Performance of Serum Leucine-Rich Alpha-2-Glycoprotein 1 and Plasma Calprotectin in Adults with Suspected Acute Appendicitis: A Cross-Sectional Observational Study

by Lea Maršić, Zvjezdana Gvozdanović, Nikolina Farčić, Luka Maršić, Željka Dujmić, Željka Dragila Tomašić, Denis Klapan, Dino Vida, Josip Samardžić, Vikica Buljanović, Dag Dušanić, Andrea Saračević, Helena Čičak, Zrinka Mihaljević and Višnja Nesek Adam

Biomedicines 2026, 14(9), 2022; https://doi.org/10.3390/biomedicines14092022 - 8 Sep 2026

Abstract

Background/Objectives: This study evaluated the diagnostic performance of serum leucine-rich alpha-2-glycoprotein 1 (LRG1) and plasma calprotectin in adults with suspected acute appendicitis, compared them with routine inflammatory markers and clinical scores, and examined their association with abdominal guarding and the discrimination of uncomplicated [...] Read more.

Background/Objectives: This study evaluated the diagnostic performance of serum leucine-rich alpha-2-glycoprotein 1 (LRG1) and plasma calprotectin in adults with suspected acute appendicitis, compared them with routine inflammatory markers and clinical scores, and examined their association with abdominal guarding and the discrimination of uncomplicated from complicated appendicitis. Methods: Adults aged ≥18 years were enrolled in two Croatian emergency departments from April 2025 to March 2026. Acute appendicitis was histopathologically confirmed, whereas controls were defined by clinical follow-up or negative appendiceal histopathology. Biomarkers were measured using enzyme-linked immunosorbent assays, and diagnostic performance was assessed using receiver operating characteristic (ROC) analysis with area under the curve (AUC). Results: Among 126 patients, 62 (49.2%) had acute appendicitis and 64 (50.8%) were controls. Serum LRG1 was higher in patients with acute appendicitis than controls (27.4 μg/mL; IQR 25.3–28.0 vs. 23.2 μg/mL; IQR 17.6–27.8; p = 0.01), whereas plasma calprotectin did not differ. LRG1 was higher in cases with abdominal guarding (p = 0.02), but neither biomarker differed significantly between uncomplicated and complicated appendicitis. Conclusions: LRG1 showed limited diagnostic accuracy, while calprotectin showed no meaningful discrimination. The Adult Appendicitis Score and Appendicitis Inflammatory Response score outperformed both biomarkers. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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29 pages, 1889 KB

Open AccessReview

Handheld Bioprinters in Skin Regeneration: Current Landscape, Clinical Promise, and the Road Ahead

by Andrey Kolosov, Yana Khristidis, Daria Revokatova, Polina Bikmulina, Boris Ershov, Raisa Chilova, Anna Solovieva, Peter Timashev and Anastasia Shpichka

Biomedicines 2026, 14(9), 2021; https://doi.org/10.3390/biomedicines14092021 - 8 Sep 2026

Abstract

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their [...] Read more.

Portable handheld bioprinters represent a transformative advancement in personalized skin regeneration, bypassing the logistical constraints of stationary lab-based systems by enabling real-time, in situ fabrication of bioengineered constructs directly within the wound bed. This review aims to evaluate the current state of their development and clinical translation. One of the foci is placed on the stringent physicochemical requirements for bioinks, where we examined the critical balance between bioadhesion—facilitated by functional groups—and mechanical cohesion necessary for maintaining structural integrity during deposition, while RGD motifs are considered primarily as promoters of integrin-mediated cell adhesion. Preclinical studies have demonstrated promising effects of bioprinted constructs on wound healing and tissue organization; however, human evidence for handheld and direct in situ skin bioprinting remains limited, and clinical efficacy has yet to be established in controlled studies. Nevertheless, widespread adoption is hindered by inferior printing fidelity relative to stationary counterparts, a lack of standardized GMP-compliant bioink production, and regulatory ambiguity that impedes clear classification as either medical devices or biologics. Practical barriers, including intraoperative sterility assurance and operator training, also remain unresolved. Looking ahead, we discuss how the convergence of, in particular, artificial intelligence for real-time wound morphometry, closed-loop process control, and smart, self-healing biomaterials promises to surmount these obstacles. We conclude that these synergistic innovations may propel handheld bioprinters from experimental prototypes toward clinical tools with the potential to reshape reconstructive surgery and emergency wound care, although their clinical value will require validation in appropriately designed human studies. Full article

(This article belongs to the Special Issue Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges (2nd Edition))

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15 pages, 858 KB

Open AccessArticle

Clinical Evaluation of Postoperative Day 3 Serum Lipase in Relation to Clinically Relevant Pancreatic Fistula After Distal Pancreatectomy: A Retrospective Cohort Study

by Oliwia Grząsiak-Kraj, Tomasz Kraj, Krzysztof Poznański, Agata Grochowska, Piotr Hogendorf, Adam Durczyński and Janusz Strzelczyk

Biomedicines 2026, 14(9), 2020; https://doi.org/10.3390/biomedicines14092020 - 8 Sep 2026

Abstract

Background/Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major complication after distal pancreatectomy. Postoperative pancreatic enzyme elevation is increasingly recognized as a marker of pancreatic remnant injury, but serum lipase after distal pancreatectomy has been less well characterized than serum amylase and [...] Read more.

Background/Objectives: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major complication after distal pancreatectomy. Postoperative pancreatic enzyme elevation is increasingly recognized as a marker of pancreatic remnant injury, but serum lipase after distal pancreatectomy has been less well characterized than serum amylase and drain-fluid markers. This study evaluated postoperative day 3 (POD3) serum lipase as a routine biochemical marker associated with CR-POPF. Methods: We retrospectively analyzed 202 consecutive adults who underwent distal pancreatectomy between 2016 and 2026. CR-POPF was defined as International Study Group on Pancreatic Surgery grade B or C. POD3 lipase was available in 157 patients, including 17 CR-POPF events. Results: POD3 lipase was higher in patients with CR-POPF than in those without it (median 74 vs. 31 U/L; p < 0.001). Each doubling of lipase was associated with higher odds of CR-POPF (OR 2.59, 95% CI 1.54–4.37). The AUC was 0.79 (95% CI 0.67–0.90) and remained 0.79 after bootstrap optimism correction. At 64 U/L, the negative predictive value was 96%; at 3 × ULN, specificity was 99%. Conclusions: POD3 serum lipase provides a readily available serum biochemical marker, not requiring drain-fluid sampling, associated with CR-POPF after distal pancreatectomy. The findings are exploratory and require external validation before clinical implementation. Full article

(This article belongs to the Special Issue Advances in Gastrointestinal Diseases: From Pathogenesis to Precision Diagnostics and Personalized Therapy)

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16 pages, 9999 KB

Open AccessArticle

Bone Tumor Microenvironment Is Associated with Meningioma Enlargement and Inflammatory Transcriptional States: A Candidate Role for Macrophage-Derived IL-1β

by Kazushi Suzuki, Takanobu Kabasawa, Takumi Kitaoka, Naoya Uchiyama, Naing Ye Aung and Mitsuru Futakuchi

Biomedicines 2026, 14(9), 2019; https://doi.org/10.3390/biomedicines14092019 - 8 Sep 2026

Abstract

Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional [...] Read more.

Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional changes and tumor growth in meningioma. Methods: Human malignant meningioma cell lines, IOMM-Lee and HKBMM, were implanted over the calvarial bone (bone TME) and into the dorsal skin (non-bone TME) of BALB/c-nu/nu mice. Tumors from the IOMM-Lee model underwent bulk RNA sequencing with computational separation of human- and mouse-derived reads, enabling ligand–target interaction analysis of stromal cell-to-tumor cell signaling. Differential gene expression analysis, enrichment analysis, ligand–target interaction analysis, multiplex immunofluorescence, and immunohistochemistry were performed. Results: Tumor volume was significantly greater in the bone TME than in the non-bone TME in both models, whereas the Ki-67 labeling index was significantly reduced. Transcriptomic analysis revealed distinct tumor cell transcriptional states in the bone TME, characterized by upregulation of inflammation-related genes and enrichment of inflammatory signaling pathways, including interferon responses and NF-κB signaling. Ligand–target interaction analysis of stromal cell-to-tumor cell signaling identified stromal IL1B as a candidate regulator of inflammatory transcriptional programs in tumor cells. F4/80-positive macrophages expressed IL-1β, and tumor cells were positive for phospho-IKKα/β and phospho-IκBα in the bone TME. Conclusions: Tumor–stromal interactions potentially involving macrophage-derived IL-1β may be associated with inflammatory transcriptional programs in meningioma cells and with meningioma enlargement in the bone TME. These interactions may be therapeutically relevant in meningioma with bone involvement. Full article

(This article belongs to the Topic The Tumor Microenvironment, Immuno-Oncology, and Immune Checkpoint: Implications for Current and Emergent Immunotherapies, 2nd Edition)

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20 pages, 729 KB

Open AccessReview

Therapeutic Management of Schistosomiasis in Pregnancy: A Comprehensive Review of Praziquantel Safety and Clinical Outcomes

by Hamid Mn Mustafa, Tahani Elfaki and Ishag Adam

Biomedicines 2026, 14(9), 2018; https://doi.org/10.3390/biomedicines14092018 - 8 Sep 2026

Abstract

Background/Objectives: Schistosomiasis affects about 250 million people globally, including an estimated 40 million women of reproductive age and over 10 million pregnant women each year. Praziquantel is a key component of schistosomiasis control and is recommended by the World Health Organization (WHO) for [...] Read more.

Background/Objectives: Schistosomiasis affects about 250 million people globally, including an estimated 40 million women of reproductive age and over 10 million pregnant women each year. Praziquantel is a key component of schistosomiasis control and is recommended by the World Health Organization (WHO) for use during pregnancy; nevertheless, its use is uneven due to ongoing safety concerns. Methods: This narrative review synthesizes evidence from randomized controlled trials (with the strongest evidence for the second and third trimesters), observational studies (including limited first-trimester exposures), pharmacokinetic analyses, case series, and WHO policy documents published between 1980 and March 2026. Results: Across all major Schistosoma species, praziquantel demonstrates high efficacy in pregnancy, with cure rates comparable to those in non-pregnant populations. No increased risk of miscarriage, stillbirth, congenital anomalies, preterm birth, or low birth weight has been observed in randomized controlled trials (RCTs) or cohort studies. Treatment of S. haematobium improves maternal anemia and may confer benefits on neonatal iron status and immune development; evidence gaps remain regarding first-trimester exposures and long-term offspring outcomes. Conclusions: Aligning national policies with WHO guidance and integrating praziquantel into antenatal care could substantially reduce maternal morbidity and improve neonatal health. Full article

(This article belongs to the Special Issue Pathogenesis, Diagnostics and Therapeutics in Obsterics and Gynaecology (2nd Edition))

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23 pages, 1093 KB

Open AccessReview

Mesenteric Panniculitis and the Gut–Mesentery–Metabolic Axis: A Hypothesis-Generating Narrative Review

by Sorina Ispas, Viviana Maggio, Syed Arman Rabbani, Adil Farooq Wali, Bhoomendra A. Bhongade, Sirajunisa Talath, Imran Rashid Rangraze, Shakta Mani Satyam, Ashot Avagimyan, Karolina Hoffmann, Ioannis Ilias, Anna Paczkowska, Mohamed El-Tanani and Manfredi Rizzo

Biomedicines 2026, 14(9), 2017; https://doi.org/10.3390/biomedicines14092017 - 8 Sep 2026

Abstract

Mesenteric panniculitis (MP) is an uncommon inflammatory disorder of mesenteric adipose tissue. Its pathophysiology remains unclear. Gut dysbiosis, intestinal barrier dysfunction, metabolic endotoxemia, glycemic variability (GV), and vascular dysfunction have been implicated in inflammatory and metabolic disorders, but their specific involvement in MP [...] Read more.

Mesenteric panniculitis (MP) is an uncommon inflammatory disorder of mesenteric adipose tissue. Its pathophysiology remains unclear. Gut dysbiosis, intestinal barrier dysfunction, metabolic endotoxemia, glycemic variability (GV), and vascular dysfunction have been implicated in inflammatory and metabolic disorders, but their specific involvement in MP has not been established. This narrative review integrates MP-specific clinical evidence with indirect mechanistic evidence from related metabolic, inflammatory, and experimental settings to examine the possible relationships between these mechanisms and MP and their integration within a proposed gut–mesentery–metabolic axis. The literature was reviewed through structured searches of PubMed, Scopus, and Web of Science for relevant publications from 2018 to 2026, supplemented by earlier foundational studies identified through reference-list screening and targeted searches. Current data suggest that dysbiosis and impaired intestinal barrier function may facilitate microbial-product translocation and lipopolysaccharide-mediated inflammatory signaling, while GV may contribute to oxidative stress, endothelial dysfunction, and pro-inflammatory responses. Mesenteric vascular anatomy and impaired regional perfusion may represent additional factors influencing local tissue susceptibility. Recent randomized controlled trials of microbiome-targeted interventions in metabolic disorders have shown heterogeneous effects on glycemic, inflammatory, and microbiota-related outcomes, indicating a need for further investigation of individualized microbiome-directed strategies. Direct evidence that microbial, metabolic, or vascular mechanisms initiate or sustain MP is currently limited. Accordingly, the proposed gut–mesentery–metabolic axis should be interpreted as a hypothesis-generating framework rather than an established causal model. Prospective MP-specific studies integrating microbiome profiling, validated measures of intestinal barrier function, metabolic phenotyping, GV, vascular assessment, and imaging are required to test the proposed relationships. Full article

(This article belongs to the Special Issue Precision Microbiome Modulation for Metabolic and Inflammatory Diseases)

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16 pages, 1747 KB

Open AccessArticle

Metabolic and Lipoprotein Changes in Type 2 Diabetes Patients Treated with Empagliflozin

by Evagelia E. Habeos, Georgios K. Markantes, Anastasia Parthymou, Konstantinos Dimitropoulos, George I. Habeos, Marios Papasotiriou, Markos Marangos and Dionysios V. Chartoumpekis

Biomedicines 2026, 14(9), 2016; https://doi.org/10.3390/biomedicines14092016 - 8 Sep 2026

Abstract

Background/Objectives: This study evaluated the metabolic effects of empagliflozin, an SGLT2 inhibitor (SGLT2i), in type 2 diabetes patients. Methods: In an observational cohort study, 42 patients received empagliflozin for 1 month, with serum and urine analyzed for IL-6, NT-proBNP, iron metabolism markers, and [...] Read more.

Background/Objectives: This study evaluated the metabolic effects of empagliflozin, an SGLT2 inhibitor (SGLT2i), in type 2 diabetes patients. Methods: In an observational cohort study, 42 patients received empagliflozin for 1 month, with serum and urine analyzed for IL-6, NT-proBNP, iron metabolism markers, and electrolytes. Another group was treated for 3 months, assessing lipoprotein and glycoprotein profiles, IL-6, and NT-proBNP. Results: Empagliflozin increased serum magnesium (mean difference = 0.26 ± 0.38 mg/dL, p < 0.0001), hemoglobin (mean difference = 0.45 ± 0.78 g/dL, p = 0.0005), and hematocrit (mean difference = 1.74 ± 2.08%, p < 0.0001), while decreasing ferritin (mean difference = −29.23 ± 51.97 ng/mL) and transferrin saturation (mean difference = −3.65 ± 7.22%). NT-proBNP and IL-6 levels trended lower (non-significant). Lipoprotein profiling showed a neutral effect. Conclusions: Empagliflozin positively affected serum magnesium, iron metabolism, and inflammatory markers without altering lipoprotein profiles. Further research is needed to elucidate SGLT2i’s molecular mechanisms underlying their pleiotropic–cardioprotective effects. Full article

(This article belongs to the Special Issue Cardiometabolic Diseases: Molecular Biomarkers and Treatment Strategies)

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24 pages, 18441 KB

Open AccessArticle

Fibrin-Binding Peptide-Functionalized H₂O₂-Responsive Retinoic Acid Micelles for Attenuating Thrombosis-Associated Oxidative and Inflammatory Responses

by Junkai Zhao, Mengting Xie, Jianghao Yu, Ran Yan and Yue Wang

Biomedicines 2026, 14(9), 2015; https://doi.org/10.3390/biomedicines14092015 - 8 Sep 2026

Abstract

Background/Objectives: Thrombotic cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Current antithrombotic therapies are limited by insufficient thrombus targeting. This study aimed to develop a fibrin-binding peptide-functionalized, hydrogen peroxide (H₂O₂)-responsive polymeric micelle and to evaluate [...] Read more.

Background/Objectives: Thrombotic cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Current antithrombotic therapies are limited by insufficient thrombus targeting. This study aimed to develop a fibrin-binding peptide-functionalized, hydrogen peroxide (H₂O₂)-responsive polymeric micelle and to evaluate its physicochemical properties and biological effects under H₂O₂-induced endothelial oxidative stress and preliminary FeCl₃-induced thrombosis conditions. Methods: A fibrin-binding peptide, P2 (VTFIKC), was screened using computer-aided drug design and evaluated through microscale thermophoresis and in vitro thrombus adhesion assays. An all-trans retinoic acid (atRA)-based boronate ester prodrug, BORA, was synthesized to enable H₂O₂-triggered degradation and drug release. BORA was co-assembled with P2-modified Mal-PEG-b-PAsp to prepare P2-Mal-PEG-b-PAsp/BORA micelles. Their physicochemical properties, H₂O₂ responsiveness, H₂O₂-scavenging activity, cytocompatibility, cytoprotective effects, anti-inflammatory activity, and preliminary in vivo efficacy were evaluated. Results: The resulting micelles exhibited a suitable nanoscale size, acceptable cytocompatibility, H₂O₂-responsive changes in particle size distribution, and concentration-dependent H₂O₂-scavenging activity. In H₂O₂-stimulated human umbilical vein endothelial cells, micelle treatment was associated with improved cell viability, lower intracellular ROS-associated fluorescence, and reduced TNF-α and IL-1β concentrations. In a FeCl₃-induced rat carotid artery thrombosis model, P2-Mal-PEG-b-PAsp/BORA micelles altered platelet- and leukocyte-related hematological indices and exhibited preferential accumulation in the thrombotic carotid artery. Conclusions: P2-Mal-PEG-b-PAsp/BORA micelles combine P2-mediated fibrin-binding potential, H₂O₂-responsive release behavior, and H₂O₂-scavenging activity. The findings provide preliminary support for further investigation of this peptide-functionalized nanoplatform. Full article

(This article belongs to the Section Drug Discovery, Development and Delivery)

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15 pages, 1692 KB

Open AccessArticle

Macrophage-Rich Peritoneal Compartments and CCR2-Dependent Hematopoietic Recruitment Are Differentially Associated with Adhesion Formation After Abdominal Surgery

by Anna Woestemeier, Mariola Lysson, Lara Braun, Azin Jafari, Philipp Lingohr, Sven Wehner, Jörg C. Kalff and Gun-Soo Hong

Biomedicines 2026, 14(9), 2014; https://doi.org/10.3390/biomedicines14092014 - 8 Sep 2026

Abstract

Background: Postoperative peritoneal adhesions arise from a dysregulated wound-healing response in which macrophages may have context-dependent effects. We investigated the contribution of macrophage-rich peritoneal and mesenteric compartments, the origin of macrophage-like cells in ischemic lesions, and the association between CCR2-dependent recruitment and postoperative [...] Read more.

Background: Postoperative peritoneal adhesions arise from a dysregulated wound-healing response in which macrophages may have context-dependent effects. We investigated the contribution of macrophage-rich peritoneal and mesenteric compartments, the origin of macrophage-like cells in ischemic lesions, and the association between CCR2-dependent recruitment and postoperative inflammatory and reparative gene expression. Methods: Using a murine ischemic-button model, we assessed the effects of clodronate liposome treatment, bone marrow chimerism, and global CCR2 deficiency. Adhesion formation, F4/80+ cell accumulation, donor-marker expression, and selected inflammatory and wound-healing-associated transcripts were analyzed at predefined postoperative time points. Results: Clodronate liposome treatment was associated with reduced adhesion formation and substantial depletion of F4/80+ cells in peritoneal lavage and mesenteric tissue. However, F4/80+ cell numbers within ischemic buttons at postoperative day 3 were not significantly reduced, indicating that the depletion experiment does not establish selective depletion of all lesional macrophages. Bone marrow chimera experiments identified donor-marker-positive, F4/80+ cells within ischemic buttons, supporting recruitment of hematopoietic cells with a macrophage-like phenotype. CCR2 deficiency reduced F4/80+ cell accumulation in ischemic buttons and was associated with increased adhesion scores and altered expression of inflammatory and wound-healing-associated genes. These findings identify differential associations of clodronate-sensitive macrophage-rich compartments and CCR2-dependent hematopoietic recruitment with postoperative adhesion formation. Conclusions: Depletion of macrophage-rich peritoneal and mesenteric compartments was associated with reduced adhesion formation, whereas global CCR2 deficiency was associated with fewer lesional F4/80+ cells and greater adhesion severity. Because clodronate depletion, F4/80 staining, bone marrow chimerism, and global CCR2 deficiency do not provide cell-specific or fate-mapped resolution, these data do not establish distinct resident versus infiltrating macrophage functions or a reparative phenotype of CCR2-dependent cells. Cell-specific and temporally resolved validation is required to define the contributions and temporal relationships of individual macrophage subsets. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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33 pages, 1735 KB

Open AccessReview

Epigenetic Plasticity in Triple-Negative Breast Cancer: Mechanisms of Therapy Resistance, Biomarkers, and Therapeutic Vulnerabilities

by Abdel Raman Alaa, Salma A. B. El-Din, Mohannad A. Farrag, Youssef Ahmed, Mohamed E. Abdel Aziz, Shaimaa Abdel-Ghany, Borros Arneth and Hussein Sabit

Biomedicines 2026, 14(9), 2013; https://doi.org/10.3390/biomedicines14092013 - 8 Sep 2026

Abstract

Triple-negative breast cancer (TNBC) is an aggressive and clinically heterogeneous breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 overexpression, limited targeted treatment options, early relapse, and frequent development of therapy resistance. Although TNBC often shows initial sensitivity [...] Read more.

Triple-negative breast cancer (TNBC) is an aggressive and clinically heterogeneous breast cancer subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 overexpression, limited targeted treatment options, early relapse, and frequent development of therapy resistance. Although TNBC often shows initial sensitivity to chemotherapy, durable responses are commonly undermined by the emergence of adaptive resistant cell states rather than solely by fixed genetic mutations. This review synthesizes the role of epigenetic plasticity as a central mechanism that enables TNBC cells to dynamically reprogram transcriptional identity, survive therapeutic stress, and transition between epithelial, mesenchymal, stem-like, immune-evasive, and drug-tolerant persister phenotypes. Key epigenetic mechanisms include aberrant DNA methylation, histone acetylation and methylation, BET/BRD4-dependent transcriptional regulation, EZH2-mediated repression, SWI/SNF-dependent chromatin remodeling, non-coding RNA networks, and three-dimensional genome reorganization. These processes regulate tumor suppressor silencing, DNA-damage repair, epithelial–mesenchymal plasticity, cancer stem-cell maintenance, metabolic adaptation, immune-checkpoint regulation, and minimal residual disease. The review also highlights the translational relevance of epigenetic biomarkers, including DNA methylation signatures, circulating epigenetic markers, chromatin-accessibility profiles, and single-cell epigenomic approaches for diagnosis, prognosis, therapy prediction, and monitoring resistance evolution. Finally, therapeutic strategies targeting epigenetic plasticity are discussed, including DNMT, HDAC, BET, EZH2, KDM, and LSD1 inhibitors, with emphasis on rational combination approaches involving chemotherapy, PARP inhibitors, immunotherapy, and metabolic targeting. Overall, epigenetic plasticity represents both a major driver of TNBC resistance and a therapeutically exploitable vulnerability, provided those future strategies account for tumor heterogeneity, adaptive cell-state transitions, biomarker-guided patient selection, and combination-based treatment design. Full article

(This article belongs to the Special Issue Triple Negative Breast Cancer: From Mechanisms to Therapeutic Approaches (2nd Edition))

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30 pages, 5875 KB

Open AccessReview

Pain Mechanisms in Fibromyalgia: An Integrative Narrative Review of Central, Peripheral, Neuroimmune, and Psychobiological Factors

by Filipa Martins-Alves and Armando Almeida

Biomedicines 2026, 14(9), 2012; https://doi.org/10.3390/biomedicines14092012 - 8 Sep 2026

Abstract

Background/Objectives: Fibromyalgia is a chronic pain condition characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, cognitive dysfunction, and multisensory hypersensitivity. It is increasingly conceptualized as a heterogeneous nociplastic pain condition in which altered nociceptive processing interacts with dysfunctional pain regulation, neuroimmune mechanisms, and [...] Read more.

Background/Objectives: Fibromyalgia is a chronic pain condition characterized by widespread musculoskeletal pain, fatigue, sleep disturbance, cognitive dysfunction, and multisensory hypersensitivity. It is increasingly conceptualized as a heterogeneous nociplastic pain condition in which altered nociceptive processing interacts with dysfunctional pain regulation, neuroimmune mechanisms, and variable peripheral contributions. This integrative narrative review aims to synthesize current evidence on the major mechanisms underlying pain in fibromyalgia, with particular emphasis on central sensitization, descending pain modulation, neurochemical dysregulation, small-fiber pathology, neuroimmune processes, and psychobiological modulators. Methods: An integrative narrative review was conducted using iterative, mechanism-oriented searches of the biomedical literature, primarily in PubMed/MEDLINE and complemented by targeted bibliographic searches and reference tracking. Research published up to July 2026 was considered, with emphasis on human mechanistic studies, systematic reviews, meta-analyses, and landmark experimental evidence relevant to the major pathophysiological domains of fibromyalgia. Results: Central sensitization and altered nociceptive gain remain prominent mechanisms of pain amplification in fibromyalgia, but they do not fully account for the clinical phenotype. Evidence also supports impaired and heterogeneous descending pain modulation, neurochemical imbalance, neuroimmune activation, autonomic and stress-system dysregulation, and peripheral contributions, including small-fiber pathology in a substantial subgroup of patients. These mechanisms appear to interact rather than operate independently, while cognitive and emotional factors further modulate symptom severity, persistence, and functional impact. Conclusions: Fibromyalgia is best understood as a heterogeneous nociplastic pain syndrome arising from partially overlapping central, peripheral, neuroimmune, autonomic, and psychobiological mechanisms whose relative contribution varies across patients. Recognizing this mechanistic heterogeneity may improve phenotypic stratification, biomarker development, and the design of more individualized, mechanism-informed therapeutic strategies. Full article

(This article belongs to the Special Issue Chronic Pain: From Prevention to Therapeutic Strategies—Third Edition)

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