Biomedicines

23 pages, 1512 KB

Open AccessReview

Beyond Acute Infection: A Conceptual Framework Linking Zoonotic Bacterial Pathogens to Pulmonary Fibrosis and Lung Carcinogenesis

by Ju Hee Lee, Nam Yee Kim, Chang-Min Choi and Minjeong Yeon

Biomedicines 2026, 14(8), 1776; https://doi.org/10.3390/biomedicines14081776 - 6 Aug 2026

Abstract

Zoonotic bacterial pathogens are transmitted through various routes and are traditionally associated with acute febrile illnesses that may include pulmonary complications. However, in some survivors, the disease extends beyond the acute phase, leading to the remodeling of pulmonary architecture and driving progressive fibrosis. [...] Read more.

Zoonotic bacterial pathogens are transmitted through various routes and are traditionally associated with acute febrile illnesses that may include pulmonary complications. However, in some survivors, the disease extends beyond the acute phase, leading to the remodeling of pulmonary architecture and driving progressive fibrosis. Although no direct cases have been reported, these pathogens may plausibly predispose injured lungs to carcinogenesis, similar to the well-recognized phenomenon of tuberculosis-associated scar cancer. As such long-term sequelae remain largely overlooked in current clinical practice, their potential contribution to fibrotic and malignant lung disease represents a critical and underexplored knowledge gap. This review proposes a unified mechanistic framework linking acute pathogen-mediated alveolar damage to chronic pulmonary fibrosis and subsequent lung carcinogenesis. We delineate four convergent biological pillars driving this continuum: (1) pathogen persistence establishing chronic Interleukin-1β (IL-1β)/Tumor necrosis factor-α (TNF-α)-mediated inflammation; (2) sustained TGF-β signaling and mechanotransduction driving progressive extracellular matrix remodeling; (3) unresolved reactive oxygen species (ROS) generation causing profound oxidative DNA damage; and (4) aberrant epithelial–mesenchymal transition (EMT) that perpetuates fibrosis and generates pre-malignant cell populations. Together, these sequelae alter lung biomechanics, suppress local immune surveillance, and create a mutagenic environment that is highly conductive to malignant transformation. Although direct epidemiological data remain emerging, the significant mechanistic overlap with idiopathic pulmonary fibrosis (IPF) presents a compelling rationale for shared oncogenic risk. We advocate for a paradigm shift in clinical practice, emphasizing the potential value of long-term surveillance for survivors of severe pulmonary infections. By integrating infectious diseases, pulmonology, and oncology, this framework highlights a neglected cause of fibrotic lung disease and establishes a foundation for future translational research. Full article

(This article belongs to the Special Issue Host–Pathogen Interactions, Immune Modulation, and Translational Therapeutics)

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16 pages, 1782 KB

Open AccessArticle

Impact of Antenatal Corticosteroids on Respiratory and Neurodevelopmental Outcomes in the FGR Rabbit Model

by Katerina Zapletalova, Marnel Greyling, Yannick Regin, Ignacio Valenzuela, Ladislav Krofta, Jan Deprest and Johannes van der Merwe

Biomedicines 2026, 14(8), 1775; https://doi.org/10.3390/biomedicines14081775 - 6 Aug 2026

Abstract

Background/Objectives: Antenatal corticosteroids (ACSs) are widely used to improve outcomes in preterm infants, but their effects in the context of fetal growth restriction (FGR) remain incompletely understood. This study investigated the impact of ACSs on pulmonary and neurodevelopmental outcomes using a rabbit [...] Read more.

Background/Objectives: Antenatal corticosteroids (ACSs) are widely used to improve outcomes in preterm infants, but their effects in the context of fetal growth restriction (FGR) remain incompletely understood. This study investigated the impact of ACSs on pulmonary and neurodevelopmental outcomes using a rabbit mod (K.Z.el) of FGR. Methods: FGR was induced at a gestational age (GA) of 25 days (term 31.5 days) by partial uteroplacental vessel ligation (UPVL) in one uterine horn, with the contralateral horn serving as a control. Dams received intramuscular betamethasone (0.1 mg/kg) or saline 24 and 12 h before expected delivery. At GA 30 days, offspring were delivered by caesarean section and allocated to four groups for pulmonary function testing or neurobehavioral assessment on postnatal day 1, followed by histological analyses of the brain, lungs, and placenta. Results: ACSs improved respiratory mechanics, particularly static and dynamic compliance, in FGR offspring. PND 1 survival showed a concerning pattern, with numerically lower model-estimated survival in both ACS-exposed groups, although the only statistically significant adjusted comparison was between Control/NoACS and FGR/ACS offspring. Neurobehavioral testing showed lower neurosensory performance after ACS exposure within both control and FGR offspring. Lung morphometry and apoptosis were not significantly altered, while neuronal density and astrogliosis showed isolated regional differences. Placental histology showed a higher junctional zone proportion in untreated FGR placentas than in untreated controls. Conclusions: ACSs improved short-term respiratory mechanics without detectable alveolar structural benefit. The observed PND 1 survival pattern and lower neurobehavioral performance warrant cautious interpretation, and these animal findings should not be directly extrapolated to clinical ACS decision-making in FGR pregnancies. Full article

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

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25 pages, 624 KB

Open AccessReview

Management of Crohn’s Disease in Adult Patients: A Contemporary Surgical Perspective

by Constant Delabays, Emilie Zhu, Amaniel Kefleyesus, William Perry, James Ansell, Alain Schoepfer and Fabian Grass

Biomedicines 2026, 14(8), 1774; https://doi.org/10.3390/biomedicines14081774 - 6 Aug 2026

Abstract

Introduction: Crohn’s disease (CD) remains associated with long-term morbidity despite biologic therapies. Surgery, historically considered a last-resort option, is increasingly integrated into disease management earlier. This review examines the evolving role of surgery in the biologic era. Methods: A focused narrative [...] Read more.

Introduction: Crohn’s disease (CD) remains associated with long-term morbidity despite biologic therapies. Surgery, historically considered a last-resort option, is increasingly integrated into disease management earlier. This review examines the evolving role of surgery in the biologic era. Methods: A focused narrative review of randomized controlled trials, meta-analyses, observational studies, and international guidelines addressing contemporary surgical strategies in CD was performed. Results: The LIR!C trial demonstrated that early ileocecal resection provides durable remission and improves long-term outcomes compared with biologic therapy in selected patients. The PISA II trial supported an early combined surgical and medical approach for perianal fistulizing disease. Preoperative optimization, including nutritional support and adjustment of immunosuppressive therapy, has become a cornerstone of perioperative management. Laparoscopic surgery remains the preferred approach whenever feasible, while robotic surgery is emerging as a promising platform that is expected to play an increasingly important role in the surgical management of CD. Postoperative recurrence remains a major challenge, prompting the development of innovative surgical strategies. Although the Kono-S anastomosis initially showed promising reductions in recurrence, recent prospective studies failed to confirm superiority over conventional techniques. Similarly, extended mesenteric excision did not demonstrate improved outcomes despite increasing evidence implicating the mesentery in CD pathogenesis. Strictureplasty remains an effective option for selected fibrotic small-bowel strictures. Conclusions: Surgery remains central to multidisciplinary CD management and offers the potential to modify disease when performed early in selected patients. The impact of innovative surgical strategies on postoperative recurrence remains uncertain, and ongoing trials are expected to further help with surgical decision-making. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (4th Edition))

21 pages, 752 KB

Open AccessArticle

A Shared Systemic Metabolic Signature Across the Neurological Disease Spectrum: A Summary-Level Analysis of 274,241 UK Biobank Participants

by Likun Yang, Wei Lin and Seyed M. Mirsattari

Biomedicines 2026, 14(8), 1773; https://doi.org/10.3390/biomedicines14081773 - 6 Aug 2026

Abstract

Background: Neurological diseases share overlapping systemic and molecular features, but the specificity and interpretation of cross-disease metabolomic signatures remain uncertain. Methods: We analyzed summary-level Nightingale NMR metabolomic and genetic data from 274,241 UK Biobank participants across eight neurological endpoints. The disease rankings used [...] Read more.

Background: Neurological diseases share overlapping systemic and molecular features, but the specificity and interpretation of cross-disease metabolomic signatures remain uncertain. Methods: We analyzed summary-level Nightingale NMR metabolomic and genetic data from 274,241 UK Biobank participants across eight neurological endpoints. The disease rankings used here were derived from baseline plasma metabolites predicting future incident disease rather than from contemporaneous diagnostic case–control contrasts. Results: Among 57 priority metabolites with genome-wide significant instruments (2472 SNPs; mean F = 162.4), nine ranked in the top 30 for at least seven of the eight endpoints, defining a shared pre-diagnostic neurological signature confirmed as non-random cross-endpoint convergence by permutation testing (p < 0.0001). Because we did not perform a quantitative non-neurological disease control analysis, this signature should not be interpreted as neurologically specific and may partly reflect systemic morbidity, renal function, body composition, or frailty-related physiology. Forward Mendelian randomization across 45 metabolite–disease pairs found no Bonferroni-significant causal effects; three nominal protective associations are consistent with the number of false-positive findings expected under multiple testing and require replication. Conclusions: These results support a shared systemic, pre-diagnostic metabolic signature across the neurological disease spectrum, while the null MR findings and specificity limitations favor interpretation as a biomarker or prodromal downstream signal rather than a proven causal mechanism. External prospective validation is essential. Full article

(This article belongs to the Special Issue Neurodegenerative Diseases: From Mechanisms to Therapeutic Approaches, 2nd Edition)

13 pages, 1435 KB

Open AccessArticle

Zona Pellucida Thickness, Reproductive Aging, and Oocyte Competence in Women with Diminished Ovarian Reserve Undergoing ICSI

by Elif Yelda Bayar, Ömer Faruk Öz, Hatice Şiyzen Çoban, Özgür Uzun and Belgin Devranoğlu

Biomedicines 2026, 14(8), 1772; https://doi.org/10.3390/biomedicines14081772 - 6 Aug 2026

Abstract

Background/Objectives: The zona pellucida (ZP) is an extracellular matrix surrounding the oocyte. It is unclear whether mean ZP thickness is associated with reproductive age or developmental competence in women with diminished ovarian reserve (DOR). We examined pre-ICSI ZP thickness in relation to age, [...] Read more.

Background/Objectives: The zona pellucida (ZP) is an extracellular matrix surrounding the oocyte. It is unclear whether mean ZP thickness is associated with reproductive age or developmental competence in women with diminished ovarian reserve (DOR). We examined pre-ICSI ZP thickness in relation to age, ovarian response, and early reproductive outcomes. Methods: This prospective observational study included 255 women aged 22–46 years with clinically diagnosed DOR who underwent intracytoplasmic sperm injection. ZP thickness was measured at three equidistant points before injection, independently verified by two observers, and summarized as the patient-level mean across the available metaphase II oocytes. Women aged <35 and ≥35 years were compared. The association between ZP thickness and chronological age was also evaluated using Spearman correlation. A transfer-adjusted logistic regression model evaluated beta-hCG positivity using age group, mean ZP thickness, laser-assisted hatching, day-5 transfer, and metaphase II oocyte count. Results: Median patient-level mean ZP thickness was similar in women aged <35 and ≥35 years (36.99 [34.90–40.61] vs. 36.91 [34.04–40.87] µm; p = 0.875). Mean ZP thickness was not correlated with chronological age (Spearman’s ρ = −0.059; p = 0.347). Younger women had higher AMH levels, antral follicle counts, retrieved oocyte counts, and metaphase II oocyte counts. Beta-hCG positivity was also higher in younger women (31.8% vs. 14.6%; p = 0.006). In the adjusted model, ZP thickness was not independently associated with beta-hCG positivity (OR 1.03 per µm, 95% CI 0.95–1.11; p = 0.487), whereas age ≥ 35 years was associated with lower odds of beta-hCG positivity. Conclusions: In this DOR cohort, mean pre-ICSI ZP thickness was not associated with chronological age, either as a continuous variable or after categorization at 35 years. It was also not independently associated with beta-hCG positivity. These findings do not exclude age-related changes in other structural, mechanical, or dynamic properties of the ZP that were not measured in this study. Full article

(This article belongs to the Special Issue New Advances in Human Reproductive Biology (2nd Edition))

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30 pages, 1479 KB

Open AccessReview

Cardiovascular Risk Stratification and Surveillance in Cardio-Oncology: Mechanistic Foundations and Future Directions

by Aryan Gajjar, Syed Asfand Yar Shah, Amani Gajjar, Krishna C. Allam, Bryce Beeach, Andrew Pfaff, Claiborne Brochu, Sourbha Dani and Sanju Ganatra

Biomedicines 2026, 14(8), 1771; https://doi.org/10.3390/biomedicines14081771 - 6 Aug 2026

Abstract

Cardio-oncology has emerged as a critical discipline in modern medicine due to the growing population of cancer survivors and the increasing recognition of cardiovascular disease as a major cause of morbidity and mortality in this population. While there have been significant advances in [...] Read more.

Cardio-oncology has emerged as a critical discipline in modern medicine due to the growing population of cancer survivors and the increasing recognition of cardiovascular disease as a major cause of morbidity and mortality in this population. While there have been significant advances in chemotherapy such as advances in chemotherapy, targeted therapies, immunotherapies, and radiation therapy, these treatments are linked to a wide range of cardiovascular toxicities such as myocarditis, arrhythmias, and progressive fibrotic remodeling. These toxicities tend to be caused by interrelated and multifactorial cellular processes including endothelial damage, immunological dysregulation and mitochondrial dysfunction. Therefore, early diagnosis of subclinical harm using multimodal surveillance strategies integrating clinical risk assessment, specialized clinical imaging, and circulating biomarkers has replaced reactive care of overt cardiotoxicity in modern cardio-oncology. Echocardiographic techniques such as longitudinal strain, with the help of biomarker-guided surveillance of natriuretic peptides and cardiac troponins, have made the early detection of cardiac dysfunction more effective. However, the current prediction risk models are still constrained and limited by their dependence on static clinical variables and their partial integration of biological mechanisms. This review examines the current methods for risk stratification and surveillance throughout the cancer care continuum, including baseline assessment, monitoring during active therapy, and long-term survivorship surveillance. Future approaches for tailored cardiovascular care are also highlighted, including new advances in precision cardio-oncology such as multi-omics profiling, molecular biomarkers, artificial intelligence, and mechanism-guided preventative strategies. Therefore, advancing biologically informed and risk-adapted monitoring frameworks may enhance early diagnosis, maximize cardioprotective measures, and lower long-term cardiovascular consequences. Full article

(This article belongs to the Section Endocrinology and Metabolism Research)

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31 pages, 1406 KB

Open AccessReview

Challenges and Opportunities of γδ T Cell-Based Immunotherapy for Glioblastoma

by Chun-Chieh Chao, Hsieh-Tsung Ethan Shen, Bo-Xiang Benjamin Zhang, Ting-Hsuan Collette Chao, Ching-Dong William Wang and Chung-Che Wu

Biomedicines 2026, 14(8), 1770; https://doi.org/10.3390/biomedicines14081770 - 6 Aug 2026

Abstract

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. [...] Read more.

Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article

(This article belongs to the Special Issue New Trends in Cancer Immunotherapy)

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14 pages, 3462 KB

Open AccessArticle

PKC Inhibition by Gö6976 Promotes Osteogenic Differentiation of Dental Follicle Cells Involving Rho-Dependent Pathway Dynamics

by Christian Morsczeck, Anja Reck, Theresa Bodensteiner, Torsten E. Reichert and Hans Christian Beck

Biomedicines 2026, 14(8), 1769; https://doi.org/10.3390/biomedicines14081769 - 6 Aug 2026

Abstract

Background: Dental follicle cells (DFCs) are promising candidates for regenerative medicine due to their osteogenic potential. While the protein kinase C (PKC) inhibitor Gö6976 is known to enhance DFC differentiation, the underlying molecular mechanisms remain partially understood. Methods: A phosphoproteomic analysis of DFCs [...] Read more.

Background: Dental follicle cells (DFCs) are promising candidates for regenerative medicine due to their osteogenic potential. While the protein kinase C (PKC) inhibitor Gö6976 is known to enhance DFC differentiation, the underlying molecular mechanisms remain partially understood. Methods: A phosphoproteomic analysis of DFCs after 14 days of osteogenic induction was performed. Cells treated with osteogenic differentiation medium (ODM) were compared to those in control medium and ODM supplemented with Gö6976. Reactome pathway analysis identified the RhoGTPase signaling pathway as significantly regulated. This pathway was further validated using PCR arrays, Western blotting, and functional assays (ALP activity, Alizarin Red staining). The impact of RhoGTPase signaling was tested using inhibitors (NSC23766, Y27632, Rhosin) and the activator Geranylgeranyl pyrophosphate (GGPP). Results: Phosphoproteomic data highlighted RhoGTPase signaling as a regulatory node. While protein expression of RhoGTPases remained relatively stable, RhoA PCR arrays revealed significant transcriptional regulation after induction of osteogenic differentiation. However, functional inhibition via NSC, Y27632, or Rhosin did not significantly impair basal ODM-induced differentiation; however, Y27632 notably induced SOST expression. Conversely, activation of RhoGTPases via GGPP increased ALP activity and downregulated SOST, suggesting a supportive role of active Rho signaling during differentiation. Crucially, we demonstrated that Gö6976-enhanced mineralization is linked to the activation of RhoA and RhoB. This was confirmed by simvastatin-mediated regulation of Rho expression, which was fully reversed by simultaneous treatment with Gö6976. Furthermore, Rhosin effectively counteracted the pro-osteogenic effects of Gö6976 by inhibiting ALP activity and mineralization while inducing SOST, which is normally suppressed by Gö6976. Conclusions: These findings indicate that RhoGTPase signaling, particularly RhoA, is a critical downstream mediator required specifically for the Gö6976-enhanced osteogenic effect in DFCs. We conclude that Gö6976 exerts its stimulatory effect on mineralization by activating RhoGTPases and suppressing the osteogenesis inhibitor SOST, providing a context-dependent mechanism for accelerated differentiation rather than driving basal osteogenesis. Full article

(This article belongs to the Section Cell Biology and Pathology)

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19 pages, 291 KB

Open AccessReview

Speech-Language Pathology-Related Disorders in Adults with Brain Tumours: A Narrative Review

by Sara Nordio and Pier Franco Conte

Biomedicines 2026, 14(8), 1768; https://doi.org/10.3390/biomedicines14081768 - 6 Aug 2026

Abstract

Brain tumours frequently involve eloquent cortical and subcortical networks, leading to speech-language pathology (SLP) disorders, including aphasia, dysarthria, and dysphagia. Evidence remains fragmented and largely derived from stroke-based frameworks that may not fully reflect neuro-oncological populations. This review synthesised literature on SLP disorders [...] Read more.

Brain tumours frequently involve eloquent cortical and subcortical networks, leading to speech-language pathology (SLP) disorders, including aphasia, dysarthria, and dysphagia. Evidence remains fragmented and largely derived from stroke-based frameworks that may not fully reflect neuro-oncological populations. This review synthesised literature on SLP disorders in adults with primary brain tumours across the pre-operative, peri-operative, and post-operative phases. Studies were identified through searches of PubMed/MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science (2000–2026) and narratively synthesised by domain and clinical contexts. Aphasia is the most studied domain and is typically mild and anomic, particularly in low-grade gliomas. Dysarthria commonly arises from damage to the ventral premotor cortex, periventricular white matter, and corticobulbar fibres, with articulatory severity correlating with subcortical tract involvement. Although less frequently investigated, dysphagia emerges as a clinically relevant complication, especially in posterior fossa and brainstem tumours, where upper oesophageal sphincter dysfunction and aspiration risk may occur. Intra-operative mapping improves functional outcomes, but tumour-specific assessment tools are lacking across all domains. SLP disorders in patients with brain tumours differ substantially from those observed after stroke and have significant consequences for communication, swallowing, and quality of life. There is a critical need for standardised, neuro-oncology-specific assessment and rehabilitation frameworks. Full article

(This article belongs to the Special Issue Neurological Complications in Oncology: From Pathogenesis to Therapy)

20 pages, 721 KB

Open AccessArticle

Evaluation of Selected Laboratory Parameters as Predictive Biomarkers of Clinical Response to Dupilumab Therapy in Patients with Atopic Dermatitis

by Katarzyna Waligóra-Dziwak, Piotr Jerzy Skrzypczak and Dorota Jenerowicz

Biomedicines 2026, 14(8), 1767; https://doi.org/10.3390/biomedicines14081767 - 6 Aug 2026

Abstract

Background: Clinical response to dupilumab in patients with atopic dermatitis is variable, and no established laboratory biomarkers currently enable reliable identification of patients likely to achieve a predictable response prior to treatment initiation or early during therapy. Methods: This prospective, real-world study conducted [...] Read more.

Background: Clinical response to dupilumab in patients with atopic dermatitis is variable, and no established laboratory biomarkers currently enable reliable identification of patients likely to achieve a predictable response prior to treatment initiation or early during therapy. Methods: This prospective, real-world study conducted in a Polish population evaluated the discriminative capacity of selected laboratory biomarkers for predicting short- and long-term clinical response to dupilumab in patients with atopic dermatitis. Results: Lactate dehydrogenase (LDH) was the most consistently informative continuous baseline biomarker (area under the receiver operating characteristic curve [AUC] for at least 75% improvement in the Eczema Area and Severity Index [EASI-75] at week 16: 0.60; EASI-90 at week 16: 0.63; EASI-75 at week 40: 0.66; EASI < 7 at week 40: 0.64). The systemic inflammatory response index (SIRI) was the second most stable baseline predictor (AUC = 0.63 and 0.64 for EASI-75 and EASI < 7 at week 40, respectively) and demonstrated the highest overall discriminative performance among week 16 biomarkers. Conclusions: LDH and SIRI appear to be the most promising candidates for further evaluation in larger cohorts owing to their cross-outcome and cross-time consistency rather than a single dominant AUC value. The predictive potential of individual biomarkers, while detectable, remained below the threshold of clinical utility for every biomarker–outcome combination examined. Composite multi-biomarker models may be required to achieve clinically meaningful predictive accuracy. Full article

(This article belongs to the Special Issue Atopic Dermatitis in the Precision Medicine Era: Immunological Mechanisms, Biomarkers, and Therapeutic Innovations)

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22 pages, 46427 KB

Open AccessArticle

Quercetin Alleviates Neuroinflammation in Chronic Insomnia by Modulating the RAGE/NF-κB Signaling Pathway: Insights from Network Pharmacology and In Vitro Validation

by Guangming Liu, Nianshan Cai, Haiyi Wang, Miaomiao Liu, Wenjing Yan, Yiru Zhao, Meng Cui, Xiangpan Kong, Hongxu Sun and Peng Zhao

Biomedicines 2026, 14(8), 1766; https://doi.org/10.3390/biomedicines14081766 - 5 Aug 2026

Abstract

Background: Chronic insomnia (CI) is increasingly recognized to be closely associated with neuroimmune dysregulation and neuroinflammation. While the dietary flavonoid quercetin exhibits known broad-spectrum anti-inflammatory properties, its specific multi-target network and underlying mechanisms concerning CI-associated neuroinflammation remain systematically unmapped. Therefore, this study [...] Read more.

Background: Chronic insomnia (CI) is increasingly recognized to be closely associated with neuroimmune dysregulation and neuroinflammation. While the dietary flavonoid quercetin exhibits known broad-spectrum anti-inflammatory properties, its specific multi-target network and underlying mechanisms concerning CI-associated neuroinflammation remain systematically unmapped. Therefore, this study integrated network pharmacology with in vitro experimental validation to elucidate the specific targets and mechanistic pathways of quercetin against neuroinflammatory responses implicated in CI. Methods: Potential targets of quercetin were predicted using the SwissTargetPrediction and SEA platforms, while CI-associated targets were curated from GeneCards, OMIM, and CTD. To bridge computational predictions with physiological relevance, protein–protein interaction (PPI) and functional enrichment analyses were integrated with molecular docking to assess the binding landscape of key candidates. Subsequently, to empirically validate these network-derived mechanistic hypotheses, in vitro experiments were conducted using an LPS-stimulated BV2 microglial model. Pro-inflammatory mediators were quantified via qRT-PCR, and the regulatory dynamics of the RAGE/NF-κB axis were evaluated by Western blotting. Results: Fifty-five overlapping targets were identified, prioritizing six hub genes (e.g., TNF, AKT1, IL6). By harmonizing the predicted network topology with experimental observations in the BV2 microglial framework, our results provide a unified mechanism linking quercetin to the suppression of central neuroinflammation. Enrichment highlighted the AGE-RAGE and IL-17 pathways as central mechanistic nodes. Molecular docking confirmed high-strength affinities between Quercetin and core targets. In the in vitro neuroinflammation model, quercetin (10, 30, and 60 μM) exerted a dose-responsive suppression of TNF-α, IL-1β, IL-6, and iNOS, while concurrently elevating anti-inflammatory IL-10 levels. Mechanistically, Quercetin significantly downregulated RAGE expression and blunted the phosphorylation of P65 and IκB, leading to significant reductions in p-P65/P65 and p-IκB/IκB ratios. Conclusions: Our findings demonstrate that Quercetin may attenuate neuroinflammatory responses associated with CI through modulation of the RAGE/NF-κB signaling axis, as indicated by network pharmacology prediction and further supported by validation in an LPS-stimulated BV2 microglial model. While these in vitro anti-inflammatory effects provide a robust mechanistic basis for targeting neuroimmune dysregulation, further in vivo behavioral studies are necessary to evaluate its direct therapeutic efficacy against chronic insomnia. Full article

(This article belongs to the Special Issue Neuroinflammation: From Mechanisms to Therapeutic Approaches)

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13 pages, 350 KB

Open AccessArticle

Physical Function and Daily Living in Postmenopausal Women with Osteoporotic Vertebral Fractures: A Cross-Sectional Study

by Ngoc Quyen Nguyen, Hong Van Vu, Viet Ha Pham and Thi Thu Thuy Nguyen

Biomedicines 2026, 14(8), 1765; https://doi.org/10.3390/biomedicines14081765 - 5 Aug 2026

Abstract

Background/Objectives: Osteoporotic vertebral fractures (OVFs) can cause persistent pain and loss of independence. This study quantified impairment in basic and instrumental activities of daily living and identified independent cross-sectional correlates in postmenopausal women with OVFs. Methods: This cross-sectional analysis included 184 postmenopausal women [...] Read more.

Background/Objectives: Osteoporotic vertebral fractures (OVFs) can cause persistent pain and loss of independence. This study quantified impairment in basic and instrumental activities of daily living and identified independent cross-sectional correlates in postmenopausal women with OVFs. Methods: This cross-sectional analysis included 184 postmenopausal women from a 200-patient OVF cohort at a spine clinic in Vietnam. Functional status was assessed using the Barthel Index (BI) and Lawton Instrumental Activities of Daily Living (IADL) scale. Primary analyses used multivariable linear regression with HC3 robust inference; ordered-logistic and model-specification analyses assessed robustness. Results: Mean age was 69.95 ± 7.78 years and mean visual analog scale (VAS) pain score was 6.69 ± 1.58. Basic-activity dependence was present in 81.5% of participants (mean BI, 82.96 ± 16.45), and 66.8% had at least one IADL limitation (mean IADL, 5.84 ± 2.04). In the adjusted BI model, higher VAS pain intensity was the strongest observed correlate of poorer function (B = −7.996; β = −0.769; p < 0.001), and higher body mass index was associated with lower BI. In the adjusted IADL model, higher VAS pain intensity (B = −0.694; β = −0.538; p < 0.001) and older age were associated with lower scores. Ordinal sensitivity analyses confirmed the pain association, whereas the BMI finding was attenuated. Conclusions: Pain intensity was the strongest observed cross-sectional correlate of both functional domains. The findings support comprehensive functional assessment and hypothesis-driven longitudinal studies, but they do not establish that pain reduction will cause functional recovery. Full article

(This article belongs to the Special Issue Insights into Musculoskeletal Diseases)

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22 pages, 870 KB

Open AccessSystematic Review

MicroRNAs as Biomarkers for Adenomyosis: A Systematic Review

by Paula Buehler, Angela Vidal, Cloé Vaineau, Tanya Karrer and Michael Mueller

Biomedicines 2026, 14(8), 1764; https://doi.org/10.3390/biomedicines14081764 - 5 Aug 2026

Abstract

Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence [...] Read more.

Background/Objectives: Adenomyosis is a chronic gynecological disorder characterized by the presence of endometrial tissue within the myometrium, causing pelvic pain, abnormal uterine bleeding, and infertility. Despite its high prevalence, the molecular mechanisms underlying disease initiation and progression remain incompletely understood. Current evidence implicates disruption of the endometrial–myometrial interface, epithelial–mesenchymal transition, and progesterone resistance in driving tissue invasion and remodeling. Diagnosis relies mainly on imaging modalities, while reliable non-invasive biomarkers are lacking. MicroRNAs, as stable post-transcriptional regulators of gene expression, have emerged as key modulators of proliferation, inflammation, and hormonal signaling, and represent promising candidates for novel diagnostic strategies. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD42025637752). A comprehensive search of the Medline, Embase, Scopus, and Cochrane databases was performed in April 2025. Studies investigating miRNA expression in patients with adenomyosis compared with controls were included. The quality of the studies and the risk of bias were assessed using the Newcastle–Ottawa scale. Two reviewers independently performed study selection, data extraction, and quality assessment. Results: Twenty-seven studies published between 2015 and 2025 met the inclusion criteria. Thirty-nine distinct miRNAs were reported as significantly dysregulated in adenomyosis. Recurrently altered miRNAs included let-7a, miR-145, miR-10b, miR-30c-5p, miR-141-3p, miR-143, and miR-191. Functional analyses have consistently implicated miRNAs in key pathogenic pathways, including Hippo-YAP, PI3K/AKT, MAPK/ERK, JAK/STAT, and Wnt/β-catenin signaling. These alterations were associated with enhanced epithelial–mesenchymal transition, increased cellular proliferation and migration, progesterone resistance, chronic inflammation, and immune modulation. Emerging evidence highlights exosomal and circulating miRNAs as promising non-invasive biomarkers, with a few studies already demonstrating diagnostic potential using serum, plasma, or urine samples. However, substantial heterogeneity in tissue types, sampling timing, and analytical methods precluded meta-analysis. Conclusions: MiRNAs play a central role in the molecular pathogenesis of adenomyosis and show strong potential as non-invasive diagnostic biomarkers. However, large-scale validation studies and standardized methodologies are required before clinical implementation. Full article

(This article belongs to the Special Issue Advanced Research of Non-Coding RNAs in Health and Disease)

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30 pages, 44705 KB

Open AccessArticle

From Oncolysis to Adaptive Immunity: Yellow Fever Virus 17D and Ruxolitinib Activate Antitumor Immune Responses in Pancreatic Cancer Models

by Kirill N. Trachuk, Yulia K. Biryukova, Vitalii A. Kapranov, Alina S. Nazarenko, Ekaterina A. Orlova, Grigory L. Kozhemyakin, Grigory A. Demyashkin, Ilya V. Gordeychuk, Aydar A. Ishmukhametov and Nadezhda M. Kolyasnikova

Biomedicines 2026, 14(8), 1763; https://doi.org/10.3390/biomedicines14081763 - 5 Aug 2026

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a five-year survival rate of less than 12%. Oncolytic viruses are considered a promising immunotherapeutic approach, but their effectiveness is often limited by the innate interferon response, which is [...] Read more.

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a five-year survival rate of less than 12%. Oncolytic viruses are considered a promising immunotherapeutic approach, but their effectiveness is often limited by the innate interferon response, which is the main antiviral barrier in resistant tumors. A combination of an oncolytic virus with JAK/STAT pathway inhibitors has been proposed to overcome this resistance. Methods: In this study, we investigated the oncolytic and immunotherapeutic potential of the attenuated yellow fever vaccine strain YFV 17D in combination with the JAK1/JAK2 inhibitor ruxolitinib in a panel of six PDAC cell lines with diverse genetic profiles and JAK/STAT signaling activities and in a syngeneic immunocompetent PAN02 mouse model. Results: In vitro, we identified three distinct response patterns: synergistic enhancement of viral replication and cytopathic effect, lack of synergism due to absent interferon signaling, and increased viral replication without cytopathic effect. Despite different cell mutation profiles, the cell response patterns were determined by the basal JAK/STAT activity of each cell line rather than by specific KRAS or TP53 mutation. In vivo, the combination therapy significantly extended median survival compared to YFV 17D monotherapy and the control group and induced tumor regression in 62.5% of animals. Since no difference in intratumoral viral RNA was detected between the combination and monotherapy groups, we suggest that the antitumor effect in vivo was mediated not by enhanced viral replication, but by activation of adaptive immunity. This is indirectly suggested by increased intratumoral IL-12, a fourfold increase in CD8⁺ T cell infiltration, a reduction in CD4⁺ cells, and the generation of virus-neutralizing antibodies. No systemic cytokine surge, neurovirulence, or viral dissemination was observed, suggesting the safety of the proposed regimen. Conclusions: These findings clarify the immune mechanisms determining the efficacy of YFV 17D combined with ruxolitinib and establish the basis for personalized patient stratification by tumor interferon signaling status. Full article

(This article belongs to the Special Issue Cancer Immunotherapy: Molecular Research and Application)

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9 pages, 987 KB

Open AccessBrief Report

Survival Analysis in Cutaneous Leishmaniasis Patients: A Retrospective Cohort Study

by José Fabrício de Carvalho Leal, Caio César Bezerra Silva, Maria Beatriz Souza Nascimento, Renata Trindade Gonçalves, Lucia Helena Gomes Fernandes, Aridne Souza Costa Campos, Fellipe Magela de Araújo, Raimunda Nonata Ribeiro Sampaio and Daniel Holanda Barroso

Biomedicines 2026, 14(8), 1762; https://doi.org/10.3390/biomedicines14081762 - 5 Aug 2026

Abstract

Background/Objectives: American Tegumentary leishmaniasis typically presents as a single ulcerative lesion, but atypical clinical forms exist with diverse physiopathology and treatment responses. Disseminated cutaneous leishmaniasis is a less common presentation that is often challenging to treat and for which evidence-based clinical decisions [...] Read more.

Background/Objectives: American Tegumentary leishmaniasis typically presents as a single ulcerative lesion, but atypical clinical forms exist with diverse physiopathology and treatment responses. Disseminated cutaneous leishmaniasis is a less common presentation that is often challenging to treat and for which evidence-based clinical decisions are scant. A better understanding of treatment response may support the development of alternative therapeutic strategies. This study reports a retrospective cohort analysis using a time-to-event outcome to compare disseminated leishmaniasis with localized cutaneous leishmaniasis using a multivariate model. Methods: A total of 366 patients were screened for inclusion between 2014 and 2024, of whom 123 met the inclusion criteria. Results: After adjustment for age and sex, patients with disseminated cutaneous leishmaniasis had a significantly longer time to healing than those with localized cutaneous leishmaniasis (HR = 0.29; p = 0.021). Conclusions: Disseminated cutaneous leishmaniasis seems to be an important predictor of poorer clinical outcomes with prolonged healing time. New therapeutic strategies are urgently needed to address this issue. Full article

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

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18 pages, 1508 KB

Open AccessArticle

Profile of People Living with HIV Switching Prior Antiretroviral Treatment to a Doravirine-Based Regimen in the Real-World Clinical Setting in Greece: The Retrospective DORAVITO Study

by Antonios Papadopoulos, Myrto Astriti, Vasileios Papastamopoulos, Vassileios Paparizos, Helen Sambatakou, Symeon Metallidis, Konstantinos Protopapas, Charalampos Moschopoulos, Georgios Adamis, Panagiota Lourida, Charisis Totsikas, Varvara Vasalou, Theofilos Chrysanthidis, Panagiotis Kollaras, Eleni Boutselakou, Dimitris Tsokos, Georgios Trimis and Lazaros Poughias

Biomedicines 2026, 14(8), 1761; https://doi.org/10.3390/biomedicines14081761 - 5 Aug 2026

Abstract

Background: Doravirine (DOR) is a new-generation non-nucleoside reverse transcriptase inhibitor, which has emerged as an option for people living with HIV (PLWH) owing to its favorable efficacy and safety profile, unique resistance pathway and limited potential for drug-drug interactions. Methods: This retrospective chart [...] Read more.

Background: Doravirine (DOR) is a new-generation non-nucleoside reverse transcriptase inhibitor, which has emerged as an option for people living with HIV (PLWH) owing to its favorable efficacy and safety profile, unique resistance pathway and limited potential for drug-drug interactions. Methods: This retrospective chart review study aimed to better understand DOR-based treatment use in Greece, PLWH characteristics, and drivers of treatment switch. Eligible individuals were adult PLWH who were switched to a DOR-based regimen based on the physician’s decision. Individuals exposed to DOR at any time prior to switching to the DOR-based regimen were excluded. Results: From 12 July 2023 to 31 October 2023, 110 PLWH were consecutively enrolled across 6 public hospital clinics. At baseline (closest prior to or on the date of first DOR prescription), the mean age of PLWH was 49.3 years, 90.9% were males, 88.2% were asymptomatic, 86.5% were virologically suppressed, 33.6% were suffering from multimorbidity (excluding infections/infestations), 45.5% were receiving comedications for their comorbidities, and 5.5% were co-infected with Hepatitis C virus. Most PLWH (98.2%) were prescribed DOR plus two nucleoside reverse transcriptase inhibitors; 87.3% were prescribed DOR/Lamivudine/Tenofovir Disoproxil Fumarate fixed-dose combination. PLWH started DOR a median of 11.7 years after first-ever antiretroviral therapy initiation, corresponding to 2nd/3rd/≥4th antiretroviral line in 33.6%/33.6%/32.7% of participants, respectively; 60.9% of them were proactively switched to a DOR-based regimen. The most common reasons for switching were ‘regimen simplification’ (42.7%), ‘tolerability’ (26.4%) and ‘prevention of toxicities’ (18.2%). Conclusions: This study highlights the patterns of DOR use in real-life clinical practice in Greece among treatment-experienced PLWH. Physicians switch HIV-1-infected individuals from prior ART to DOR-based regimens to offer a simplified regimen or to avoid or prevent toxicity. Full article

(This article belongs to the Special Issue Emerging Insights into HIV: Second Edition)

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22 pages, 29774 KB

Open AccessArticle

Evaluation of Early and Delayed Meloxicam Treatment Against Regulated Cell Death Pathways and ERK1/2 Phosphorylation in a Rat Model of Renal Ischemia–Reperfusion Injury

by Mahmut Şahin, Hasan Başçil, Alper Serhat Kumru and Mustafa Özkaraca

Biomedicines 2026, 14(8), 1760; https://doi.org/10.3390/biomedicines14081760 - 5 Aug 2026

Abstract

Objectives: Renal ischemia–reperfusion (I/R) injury is one of the most important pathological triggers of acute kidney injury. This study aimed to investigate the protective effects of meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, against renal I/R injury through specific cell death pathways including [...] Read more.

Objectives: Renal ischemia–reperfusion (I/R) injury is one of the most important pathological triggers of acute kidney injury. This study aimed to investigate the protective effects of meloxicam, a selective cyclooxygenase-2 (COX-2) inhibitor, against renal I/R injury through specific cell death pathways including inflammation, apoptosis, necroptosis, and the MAPK/ERK pathway, which is potentially linked to regulated cell death mechanisms such as ferroptosis. Methods: Male Wistar Albino rats weighing 280–300 g were used in the study and were divided into four groups: Sham, IR (40 min ischemia + 120 min reperfusion), Meloxicam + IR, and Meloxicam + IR1. Bilateral renal ischemia was induced for 40 min via a retroperitoneal approach under anesthesia. Meloxicam was administered intravenously at a dose of 1 mg/kg at the initiation of reperfusion in the Meloxicam + IR group, whereas in the Meloxicam + IR1 group, the same dose was administered 1 h after the onset of reperfusion. Total reperfusion time was 120 min in both groups. Renal function parameters (BUN and creatinine) and oxidative stress markers (TAS and TOS) were measured. Inflammatory cytokines (IL-6, IL-1β, and IL-10), the glomerular filtration injury marker Cystatin C, the tubular injury marker KIM-1, the apoptotic marker Caspase 3, the necroptosis markers RIPK3 and MLKL, and MAPK signaling pathway alterations (ERK1/2 and pERK1/2 levels) associated with cellular survival and death signaling were evaluated. Results: Most notably, meloxicam markedly modulated apoptosis, the expression of necroptosis markers RIPK3 and MLKL, and the activation of pERK1/2, a key node in MAPK signaling that is regulatory in cell survival and cell death processes. The drug also suppressed pro-inflammatory cytokines (IL-6 and IL-1β) while preserving anti-inflammatory IL-10 levels. Furthermore, improvements were observed in the levels of KIM-1, a marker of tubular injury, and Cystatin C, a marker of glomerular filtration impairment. Consequently, meloxicam administration significantly reduced the elevated serum creatinine and TOS levels observed in the IR group, although serum BUN levels remained without notable alteration. Conclusions: The findings of this study suggest that meloxicam may extend beyond its role as a classical anti-inflammatory agent, potentially offering biochemical and functional protection against renal I/R injury in association with the modulation of specific cell death mechanisms, including necroptosis and apoptosis, as well as the MAPK signaling pathway. Full article

(This article belongs to the Special Issue Chronic Vascular Impairment in Heart, Brain, and Kidney Disorders: Molecular Mechanisms and Therapeutic Strategies)

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17 pages, 882 KB

Open AccessArticle

Short-Term Changes in Salivary IL-6, TNF-α, and Periodontal Inflammation Following Sleeve Gastrectomy in Patients with Obesity: A Randomized Controlled Pilot Study

by Felicia Gabriela Beresescu, Adriana Monea, Alina Ormenisan, Carmen Tegla, Adina Cosarca and Septimiu Voidazan

Biomedicines 2026, 14(8), 1759; https://doi.org/10.3390/biomedicines14081759 - 4 Aug 2026

Abstract

Background: Obesity and periodontitis share inflammatory pathways. This pilot randomized controlled trial evaluated salivary IL-6 and TNF-α and periodontal changes after sleeve gastrectomy (SG) versus non-surgical management (NSG). Methods: Thirty-two adults with obesity and stage I–III periodontitis were randomized to SG (n [...] Read more.

Background: Obesity and periodontitis share inflammatory pathways. This pilot randomized controlled trial evaluated salivary IL-6 and TNF-α and periodontal changes after sleeve gastrectomy (SG) versus non-surgical management (NSG). Methods: Thirty-two adults with obesity and stage I–III periodontitis were randomized to SG (n = 18) or NSG (n = 14) and assessed at baseline, 3 months, and 6 months. Primary outcomes were salivary IL-6 and TNF-α; secondary outcomes were PI, BOP, PPD, and CAL. Results: At 6 months, SG participants had lower BMI than NSG participants (32.20 ± 3.90 vs. 42.10 ± 4.30 kg/m²; p = 0.0001). Primary cytokine outcomes also favored SG: IL-6 was 3.72 ± 1.08 vs. 6.34 ± 1.37 pg/mL and TNF-α was 5.11 ± 1.29 vs. 7.71 ± 1.68 pg/mL (both p = 0.0001). PI and BOP were lower in SG than NSG (38.60 ± 9.80% vs. 60.80 ± 10.40% and 20.80 ± 7.40% vs. 39.70 ± 9.10%; both p = 0.0001), while PPD was modestly lower (2.89 ± 0.43 vs. 3.31 ± 0.46 mm; p = 0.017) and CAL was not significantly different (p = 0.15). Conclusions: These preliminary pilot findings suggest parallel reductions in salivary inflammatory markers and plaque-related/gingival-inflammatory indices after SG, but behavioral confounding, complete-case analysis, short follow-up, and absent significant CAL gain preclude causal or regenerative conclusions. Full article

(This article belongs to the Special Issue Biomarkers in Metabolic Disorders, Obesity and Type 2 Diabetes Mellitus—2nd Edition)

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22 pages, 998 KB

Open AccessReview

Bioactive Metabolites of Solanum tuberosum L. in Inflammation Modulation and Tissue Regeneration: A Scoping Review of Wound Healing Mechanisms

by Wahyu Hidayat, Mieke Hemiawati Satari, Ronny Lesmana, Solachuddin Ichwan and Irna Sufiawati

Biomedicines 2026, 14(8), 1758; https://doi.org/10.3390/biomedicines14081758 - 4 Aug 2026

Abstract

Background/Objectives: Persistent inflammation and impaired tissue regeneration delay mucosal and cutaneous wound healing. Potato (Solanum tuberosum L.) preparations contain bioactive metabolites with anti-inflammatory and regenerative potential, yet their wound-healing mechanisms have not been systematically mapped. This scoping review aimed to map potato-derived [...] Read more.

Background/Objectives: Persistent inflammation and impaired tissue regeneration delay mucosal and cutaneous wound healing. Potato (Solanum tuberosum L.) preparations contain bioactive metabolites with anti-inflammatory and regenerative potential, yet their wound-healing mechanisms have not been systematically mapped. This scoping review aimed to map potato-derived bioactive metabolites and their roles in modulating inflammation and promoting tissue regeneration during wound healing. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Articles published between 2015 and 2025 were retrieved from the Scopus, PubMed, EBSCO, and ScienceDirect databases combined with hand searching. Eligible studies included in vivo animal models; mechanistically relevant in vitro studies; and limited clinical or human skin safety studies investigating potato-derived extracts, fractions, or defined preparation effects in wound, ulcer, and burn healing. Results: Among the 583 records identified, only 15 met the inclusion criteria. These studies reported five major bioactive metabolite classes—flavonoids/anthocyanins, polyphenols, alkaloids, polysaccharides, and peptides—together with potato-derived exosomal vesicles as an extracellular vesicle/delivery system (not a metabolite class). Potato-derived preparations have been associated with accelerated wound closure, enhanced fibroblast proliferation, collagen deposition, and the attenuation of inflammatory mediators. Molecular evidence, which was included in only six studies, supported the modulation of NF-κB, STAT1/3, COX-2, iNOS, cytokines, and MMP-9. In addition, five priority gaps were identified: lack of standardization, fragmented biomarker profiling, limited compound-specific validation, scarce clinical translation, and absence of omics-based and complex wound models. Conclusions: Potato-derived bioactive metabolites show multi-target preclinical associations with wound healing and warrant further development as potential adjunctive therapies for mucosal and cutaneous wounds after standardization and clinical validation. Full article

(This article belongs to the Special Issue Integrative Roles of Natural Products in Cancer Treatment and Chronic Inflammatory Disease)

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