Life | July 2026 - Browse Articles

15 pages, 847 KB

Open AccessArticle

Clinical Evaluation of Low-Dose Magnesium Carbonate as a Phosphate Binder in Chronic Hemodialysis Patients

by Valeri Tzekov, Tanya Kostadinova, Elizabet Artinyan, Rumyana Stoyanova, Evelina Valcheva and Nikolay Dimov

Life 2026, 16(7), 1213; https://doi.org/10.3390/life16071213 - 22 Jul 2026

Viewed by 985

Abstract

Background and Objectives: Hyperphosphatemia is a key component of chronic kidney disease-mineral and bone disorder and is associated with higher rates of cardiovascular events and mortality in patients undergoing dialysis. Phosphate binders are essential for phosphorus reduction, and their evaluation relies on several [...] Read more.

Background and Objectives: Hyperphosphatemia is a key component of chronic kidney disease-mineral and bone disorder and is associated with higher rates of cardiovascular events and mortality in patients undergoing dialysis. Phosphate binders are essential for phosphorus reduction, and their evaluation relies on several factors, such as chemical composition, binding capacity, and safety profile. Unfortunately, long-term management is hindered by high pill burden and poor adherence. Magnesium phosphate binders have proven effectiveness in reducing phosphate levels. Nevertheless, despite their efficacy, they are not widely used in clinical settings because of concerns related to their use. This study assessed the efficacy of low-dose magnesium carbonate as a phosphate binder in patients undergoing chronic dialysis, focusing on its biochemical control, tolerability, and cost-effectiveness. Materials and Methods: A prospective observational study was conducted on 54 hemodialysis patients with end-stage renal disease at a single dialysis center. Patients were taking either 250 mg magnesium carbonate or 2400 mg sevelamer carbonate for 3 months. Results: Both groups showed decreased phosphorus levels, with a 14.2% significant reduction in the magnesium carbonate group (p < 0.001) and a 5.1% reduction in the sevelamer carbonate group. At the end of the study, no significant differences were observed between the groups (p = 0.682). In the magnesium carbonate group at month 3, compared to baseline, no significant differences were detected in other laboratory parameters reflecting calcium–phosphorus metabolism (Ca—p = 0.681, PTH—p = 0.126). Simultaneously, good compliance without clinically relevant gastrointestinal side effects was observed, including the absence of clinically significant hypermagnesemia. Conclusions: The phosphorus-lowering potential of low-dose magnesium carbonate is non-inferior to that of low-dose sevelamer carbonate. However, its favorable safety profile, low incidence of adverse effects, and cost-effectiveness make it a promising option in clinical practice, further highlighting the need for better recognition by physicians. Full article

(This article belongs to the Special Issue Advances in Dialysis Pathology: Insights into Peritoneal and Hemodialysis Complications)

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18 pages, 3632 KB

Open AccessArticle

Biochemical Characterization and Active-Site Analysis of N-Acetylornithine Aminotransferase from Crocosphaera subtropica ATCC 51142

by Liyang Huang, Zhi-Min Li, Luna Gao, Siqi Wang, Zhifeng Wu and Zhimin Li

Life 2026, 16(7), 1212; https://doi.org/10.3390/life16071212 - 22 Jul 2026

Viewed by 488

Abstract

N-acetylornithine aminotransferase (AcOAT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes a key transamination step in arginine biosynthesis. In cyanobacteria, arginine metabolism is closely associated with nitrogen assimilation and storage, yet biochemical information on cyanobacterial AcOATs remains limited. In this study, the [...] Read more.

N-acetylornithine aminotransferase (AcOAT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that catalyzes a key transamination step in arginine biosynthesis. In cyanobacteria, arginine metabolism is closely associated with nitrogen assimilation and storage, yet biochemical information on cyanobacterial AcOATs remains limited. In this study, the AcOAT encoded by the cce_3094 gene from Crocosphaera subtropica ATCC 51142 (CsAcOAT) was cloned, heterologously expressed, purified, and systematically characterized. Recombinant CsAcOAT was obtained as a soluble protein with an apparent molecular mass of approximately 43 kDa. Steady-state kinetic analysis showed that CsAcOAT catalyzed transamination between N-acetylornithine (AcOrn) and α-ketoglutarate (α-KG), with apparent K_M values of 0.17 ± 0.03 mM for AcOrn and 0.020 ± 0.003 mM for α-KG, indicating a higher affinity for α-KG. The enzyme exhibited optimal activity at pH 8.5 and 30 °C, retained relatively high activity over a broad temperature range of 0–50 °C, and was activated by Zn²⁺ and Co²⁺ but inhibited by Ni²⁺. Structural analysis based on homology modeling, molecular docking, and molecular dynamics simulations suggested a conserved PLP-dependent aminotransferase fold and a stable binding mode for the PLP-AcOrn complex in the active-site pocket. Site-directed mutagenesis further demonstrated that Gly114, Asp239, Lys268, and Thr296 are indispensable for catalytic activity, whereas Ser113, Ala115, and Gln242 make important contributions to catalytic turnover and cofactor-assisted catalysis. These results provide biochemical and structural characterization of CsAcOAT, expand current knowledge of cyanobacterial AcOATs, and offer a useful basis for future studies on arginine metabolism and nitrogen storage in diazotrophic cyanobacteria. Full article

(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)

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17 pages, 951 KB

Open AccessArticle

From Susceptibility to Disease Severity: Re-Discovering the Clinical Role of MMP-12 Genotypes in Asthma

by Shou-Cheng Wang, Te-Chun Hsia, Te-Chun Shen, Liang-Wen Hang, Jie-Long He, Ding-Han Chen, Kai-Ling Huang, Chia-Wen Tsai, Wen-Shin Chang and Da-Tian Bau

Life 2026, 16(7), 1211; https://doi.org/10.3390/life16071211 - 22 Jul 2026

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Abstract

Asthma is a chronic inflammatory airway disorder influenced by genetic and environmental factors. Matrix metalloproteinase-12 (MMP-12) plays a key role in airway remodeling and inflammation, but its genetic contribution to asthma remains unclear. This study investigated the associations of MMP-12 rs2276109 and rs652438 [...] Read more.

Asthma is a chronic inflammatory airway disorder influenced by genetic and environmental factors. Matrix metalloproteinase-12 (MMP-12) plays a key role in airway remodeling and inflammation, but its genetic contribution to asthma remains unclear. This study investigated the associations of MMP-12 rs2276109 and rs652438 polymorphisms with asthma susceptibility and severity in 198 Taiwanese asthma patients and 453 controls. Genotypes were determined by PCR-RFLP, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Neither MMP-12 rs2276109 nor rs652438 was significantly associated with overall asthma susceptibility. For rs2276109, the CT and CC genotypes yielded ORs of 1.06 (95% CI = 0.56–2.00, p = 0.9913) and 6.98 (95% CI = 0.72–67.59, p = 0.0857), respectively. However, among individuals aged 25–40 years, rs652438 CT and CC genotypes were associated with elevated asthma risk (OR = 1.86, 95% CI = 1.14–3.04, p = 0.0100; OR = 3.60, 95% CI = 1.11–11.65, p = 0.0494). Furthermore, MMP-12 rs652438 was significantly associated with asthma severity under both the CT genotype (OR = 2.32, 95% CI = 1.16–4.62, p = 0.0250) and dominant models (OR = 2.45, 95% CI = 1.28–4.72, p = 0.0106). Although MMP-12 polymorphisms do not appear to influence overall asthma susceptibility, rs652438 may serve as a genetic marker for disease severity and clinical stratification in asthma. Full article

(This article belongs to the Special Issue Pathology, Diagnosis, and Treatments of Airway Diseases)

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20 pages, 1616 KB

Open AccessArticle

Early Pulmonary Stress During Intra-Abdominal Hypertension and Hypervolemia: Surfactant Protein A1 and Multi-Compartment Biomarker Responses in Rats

by Mert Canbaz, Halim Ulugöl, Gülsüm Karduz, Kübra Vardar, Mukadder Orhan Sungur, Evren Şentürk, Uğur Aksu, Pınar Fırat, Perihan Ergin Özcan, Fevzi Toraman, Mert Şentürk and on behalf of the Istanbul Research and Education in Anesthesia NETwork (IREANETwork) Experimental Working Group

Life 2026, 16(7), 1210; https://doi.org/10.3390/life16071210 - 22 Jul 2026

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Abstract

Conventional endpoints may overlook pulmonary biological stress during abdominal mechanical loading and volume expansion. This controlled experimental study evaluated whether intra-abdominal hypertension (IAH), hypervolemia (HV), or their combination induces early pulmonary biochemical, permeability, oxidative–ischemic, inflammatory, and structural responses, with particular focus on surfactant [...] Read more.

Conventional endpoints may overlook pulmonary biological stress during abdominal mechanical loading and volume expansion. This controlled experimental study evaluated whether intra-abdominal hypertension (IAH), hypervolemia (HV), or their combination induces early pulmonary biochemical, permeability, oxidative–ischemic, inflammatory, and structural responses, with particular focus on surfactant protein A1 (SP-A1). Thirty-five male Wistar rats were randomized to Sham, HV, IAH, or IAH + HV groups. IAH was induced by CO₂ pneumoperitoneum at 12–15 mmHg, and HV by 6% hydroxyethyl starch infusion until hematocrit decreased to approximately 25%; animals were followed for 120 min. Physiological variables, blood gases, wet-to-dry ratio, ATS-based histopathology, and biomarkers in plasma, bronchoalveolar lavage (BAL) fluid, and lung tissue were assessed. The dominant finding was a compartment-specific SP-A1 response: plasma SP-A1 was highest in the IAH group, whereas BAL fluid SP-A1 increased in both HV and IAH groups. These changes occurred without significant alterations in MAP, HR, SpO₂, wet-to-dry ratio, or ATS lung injury score. Permeability index was higher in HV-containing groups, and sialic acid and oxidative–ischemic markers showed compartment-dependent changes, whereas TNF-α, IL-6, HA, and ANP did not differ significantly. These exploratory, hypothesis-generating findings suggest that SP-A1 may reveal early pulmonary epithelial/barrier stress before overt physiological or structural injury becomes apparent. Full article

(This article belongs to the Special Issue Pulmonary Disease and Transplant Pathology: From Molecular Mechanisms to Diagnosis)

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34 pages, 2019 KB

Open AccessReview

Beyond Hemostasis: Platelets’ Multifaceted Functions in Immune Responses

by Woo Kyung Lee Doolittle, Elizabeth L. Walters and Robert W. Maitta

Life 2026, 16(7), 1209; https://doi.org/10.3390/life16071209 - 21 Jul 2026

Viewed by 1343

Abstract

Platelets are anucleated cell fragments representing the second most abundant blood element in circulation, with approximately 100 billion new platelets released from the bone marrow daily in a healthy individual. For over a century, their hemostatic role was considered their primary function; however, [...] Read more.

Platelets are anucleated cell fragments representing the second most abundant blood element in circulation, with approximately 100 billion new platelets released from the bone marrow daily in a healthy individual. For over a century, their hemostatic role was considered their primary function; however, the past few decades of research have revealed significant immunological functions in both innate and adaptive immunity. Through the release of mediators stored in platelet granules and the expression and realignment of a diverse array of surface receptors, platelets influence immune cells while simultaneously recognizing, reacting to, and phagocytosing offending pathogens such as viruses and bacteria. Their activation initiates signaling cascades that either amplify platelet responses or drive the activation, recruitment, migration, and maturation of immune cells to sites of infection. This narrative review synthesizes platelet biology, receptor signaling, granule physiology, and platelet interactions with innate and adaptive immune cells to provide an integrated perspective on platelet immunologic function. We examine platelets as frontline immune sentinels and evaluate their capacity to regulate both innate and adaptive immune responses, detailing specific receptors and granule contents as the mechanistic foundation for their immunologic roles. We further explore the molecular mechanisms by which platelets interact with pathogens and immune cells to drive pathogen clearance, inflammation modulation, and the interplay between thrombosis and immunity, including their contributions to chronic inflammatory disease and tumorigenesis. Full article

(This article belongs to the Special Issue Thrombosis and Blood Disorders: Mechanisms and Management)

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25 pages, 3561 KB

Open AccessArticle

Gait Biomechanics, Symmetry Restoration, and Functional Recovery Following Total Knee Arthroplasty: A Prospective Longitudinal Cohort Study

by Giada Baroni, Elena Lucchesini, Roland Fazakas, Dan Fruja, Laura Ioana Bondar, Ana-Liana Bouroș-Tataru, Csongor Toth, Nicoleta Anamaria Pascalau, Liliana-Oana Pobirci and Alexandru Pop

Life 2026, 16(7), 1208; https://doi.org/10.3390/life16071208 - 21 Jul 2026

Viewed by 528

Abstract

Background/Objectives: Total knee arthroplasty (TKA) is the standard surgical treatment for end-stage knee osteoarthritis (KOA); however, restoration of normal gait biomechanics remains an important challenge. Objective assessment of gait recovery may provide valuable information beyond conventional clinical outcome measures. This study aimed to [...] Read more.

Background/Objectives: Total knee arthroplasty (TKA) is the standard surgical treatment for end-stage knee osteoarthritis (KOA); however, restoration of normal gait biomechanics remains an important challenge. Objective assessment of gait recovery may provide valuable information beyond conventional clinical outcome measures. This study aimed to evaluate changes in spatiotemporal gait parameters, symmetry restoration, and functional recovery during the first year following primary TKA, and to identify predictors of postoperative gait performance. Methods: A prospective longitudinal cohort study was conducted in 150 patients undergoing primary unilateral TKA for end-stage KOA. Spatiotemporal gait parameters, symmetry-related variables, and functional outcomes were assessed preoperatively and at 3, 6, and 12 months postoperatively. Gait analysis included walking speed, step length, cadence, stance phase symmetry, symmetry index (SI), loading asymmetry, and single-limb support time. Functional evaluation included the Timed Up and Go (TUG) test, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Society Score (KSS). Repeated-measures analysis of variance (ANOVA), Pearson correlation analysis, and multivariate linear regression were performed. Results: Significant improvements were observed in all gait and functional parameters throughout follow-up (all p < 0.001). Walking speed increased from 0.84 ± 0.16 m/s preoperatively to 1.21 ± 0.18 m/s at 12 months, while step length increased from 49.8 ± 7.4 cm to 64.0 ± 6.4 cm and cadence from 91 ± 10 to 108 ± 8 steps/min. SI improved from 73 ± 11% to 93 ± 6%, whereas loading asymmetry decreased from 18.2 ± 6.1% to 4.8 ± 2.3%. Walking speed demonstrated strong correlations with WOMAC score (r = −0.74, p < 0.001) and TUG performance (r = −0.79, p < 0.001). Multivariate regression analysis identified preoperative walking speed (β = 0.47, p < 0.001) as the strongest predictor of postoperative gait recovery, while age and body mass index (BMI) were significant negative predictors. Conclusions: Patients undergoing primary TKA demonstrated substantial improvements in gait biomechanics, symmetry restoration, and functional performance during the first postoperative year. Objective gait assessment was strongly associated with clinical outcomes and may facilitate identification of patients at risk of delayed recovery. Incorporating quantitative gait analysis into postoperative evaluation may support individualized rehabilitation strategies aimed at optimizing functional outcomes following TKA. Full article

(This article belongs to the Section Medical Research)

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11 pages, 1204 KB

Open AccessCase Report

Presumed Amniotic Fluid Embolism Complicated by Disseminated Intravascular Coagulation and Refractory Postpartum Hemorrhage: A Case Report and Narrative Review

by Yasmin Schäffter, David Schmidbauer, José Valles Fons, Helena Schäffter, Jonah Bosserhoff and Erika-Gyöngyi Bán

Life 2026, 16(7), 1207; https://doi.org/10.3390/life16071207 - 21 Jul 2026

Viewed by 683

Abstract

Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric emergency characterized by sudden cardiorespiratory collapse, disseminated intravascular coagulation (DIC), and a high case-fatality rate. Because no confirmatory test exists, the diagnosis remains clinical and one of exclusion. We report a case of [...] Read more.

Amniotic fluid embolism (AFE) is a rare but catastrophic obstetric emergency characterized by sudden cardiorespiratory collapse, disseminated intravascular coagulation (DIC), and a high case-fatality rate. Because no confirmatory test exists, the diagnosis remains clinical and one of exclusion. We report a case of presumed AFE in a 39-year-old primigravida with uterine myomas, obesity, and chronic hypertension who underwent an elective primary cesarean delivery under spinal anesthesia. During manipulation of the placenta, the patient developed abrupt cardiovascular collapse requiring cardiopulmonary resuscitation, with return of spontaneous circulation followed by profound coagulopathy and refractory uterine atony. Management included goal-directed transfusion within a massive transfusion protocol, uterotonic therapy, a failed B-Lynch suture, supracervical hysterectomy, and a subsequent right oophorectomy for an ovarian-vein hemorrhage identified on imaging. Laboratory studies demonstrated an overt consumptive coagulopathy consistent with the International Society on Thrombosis and Haemostasis (ISTH) criteria, while a normal serum tryptase argued against an anaphylactic mechanism. The neonate was delivered in good condition (Apgar scores 9, 10, and 10 at 1, 5, and 10 min; umbilical-artery pH 7.38) and required no neonatal intensive care. The mother achieved full hemodynamic and neurological recovery. This case illustrates that survival from presumed AFE is achievable through early recognition, high-quality resuscitation, prompt correction of coagulopathy, and decisive surgical hemostasis, and it highlights the diagnostic reasoning required to distinguish AFE from its principal differential diagnoses. Full article

(This article belongs to the Special Issue Advanced Research in Obstetrics and Gynecology)

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21 pages, 6218 KB

Open AccessReview

A Comprehensive Review on the Pharmacological Activities and Biosynthetic Strategies of Protocatechuic Acid

by Chongde Lai, Hailin Xia, Yuhuan Zhang, Yutong He, Xiaoyu Wu, Bangce Ye, Hui Yang and Bin Zhang

Life 2026, 16(7), 1206; https://doi.org/10.3390/life16071206 - 21 Jul 2026

Cited by 1 | Viewed by 655

Abstract

Protocatechuic acid (PCA) is a simple natural phenolic acid widely distributed in plants. It is recognized as an active constituent of numerous traditional herbal medicines and serves as an important metabolic intermediate of polyphenolic compounds such as anthocyanins and proanthocyanidins. At present, PCA [...] Read more.

Protocatechuic acid (PCA) is a simple natural phenolic acid widely distributed in plants. It is recognized as an active constituent of numerous traditional herbal medicines and serves as an important metabolic intermediate of polyphenolic compounds such as anthocyanins and proanthocyanidins. At present, PCA production relies on plant extraction and microbial fermentation. Among these, microbial fermentation has emerged as an attractive approach for industrial development owing to its process controllability, environmentally benign nature, and potential for high productivity. This review systematically summarizes the major pharmacological properties of PCA, including its antioxidant, anti-inflammatory, antimicrobial, antiviral, anti-aging, neuroprotective, and hepatoprotective activities. It further highlights the therapeutic potential of PCA in the prevention and management of various chronic diseases, such as cancer, diabetes, Alzheimer’s disease, and hypertension. Furthermore, this review summarizes the representative microbial biosynthetic pathways for PCA and discusses recent progress in metabolic engineering strategies aimed at enhancing its microbial production. These strategies include reinforcing precursor supply, redirecting metabolic flux toward the shikimate pathway, blocking PCA degradation routes, relieving intracellular feedback regulation, improving host tolerance, and optimizing fermentation processes to achieve higher PCA productivity and yield. Finally, the major bottlenecks limiting PCA biomanufacturing are discussed, and prospective directions for future research are proposed. Full article

(This article belongs to the Special Issue Microbial Biosynthesis of Aromatic Compounds)

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15 pages, 710 KB

Open AccessSystematic Review

Patient-Derived Functional Models for Prediction of Radiotherapy Response in Rectal Cancer: A Systematic Review and Exploratory HSROC Meta-Analysis

by Stefan Morarasu, Sorinel Lunca, Andrei-Nicolae Ceobanu, Alexandru-Florin Braniste and Gabriel Mihail Dimofte

Life 2026, 16(7), 1205; https://doi.org/10.3390/life16071205 - 21 Jul 2026

Viewed by 448

Abstract

Background: Patient-derived functional models have emerged as promising translational platforms capable of reproducing tumour-specific treatment sensitivity patterns, which could be used to personalise neoadjuvant treatment for patients with rectal cancer. Herein, we aimed to summarise the current comparative evidence in a meta-analytical framework [...] Read more.

Background: Patient-derived functional models have emerged as promising translational platforms capable of reproducing tumour-specific treatment sensitivity patterns, which could be used to personalise neoadjuvant treatment for patients with rectal cancer. Herein, we aimed to summarise the current comparative evidence in a meta-analytical framework on radiotherapy response between preclinical platforms and matched patient data. Methods: A systematic review was performed according to PRISMA principles to identify studies evaluating patient-derived functional models for the prediction of radiotherapy or chemoradiotherapy response in rectal cancer. Study characteristics, experimental protocols, predictive performance and clinical correlations were extracted. An exploratory hierarchical summary receiver operating characteristic (HSROC) meta-analysis was performed using studies providing sufficient data. Results: Eight studies involving patient-derived organoids and zebrafish patient-derived xenograft models were included. Most studies evaluated locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. The included studies demonstrated concordance rates ranging from 78% to 100% between ex vivo functional responses and matched clinical treatment outcomes. Reported predictive performance was favourable, with Yao et al. demonstrating 85.0% concordance, 78.0% sensitivity and 92.0% specificity, while Hsu et al. reported 87.5% sensitivity and 100% specificity using radiobiological modelling. Exploratory HSROC analysis demonstrated overall favourable discriminatory performance for prediction of treatment resistance and poor response. Conclusions: Patient-derived functional models, particularly PDOs, demonstrate promising potential as predictive biomarkers for radiotherapy and chemoradiotherapy response in rectal cancer. Although the current evidence remains exploratory and is limited by methodological heterogeneity and small cohorts, these platforms represent a promising translational strategy in precision radiation oncology, warranting prospective multicentre validation. Full article

(This article belongs to the Section Radiobiology and Nuclear Medicine)

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13 pages, 7843 KB

Open AccessArticle

Degradation, Osmosis and the Emergence of Basic Functionalities in Abiotic Synthetic Life-like Chemical Systems

by Chenyu Lin and Juan Pérez-Mercader

Life 2026, 16(7), 1204; https://doi.org/10.3390/life16071204 - 21 Jul 2026

Viewed by 429

Abstract

Autonomous and interconnected multiscale out-of-equilibrium processes, including chemical and physical feedbacks, occur at the micron and lower scales during the heterotrophic synthesis of simple abiotic protocells, such as the ones developed in our group, with primitive life-like properties. These processes provide a solution [...] Read more.

Autonomous and interconnected multiscale out-of-equilibrium processes, including chemical and physical feedbacks, occur at the micron and lower scales during the heterotrophic synthesis of simple abiotic protocells, such as the ones developed in our group, with primitive life-like properties. These processes provide a solution to the autopoiesis and concentration problems in life’s origin. They also underlie the emergence of whole-vesicle functionalities like chemotaxis and self-reproduction involving dissipation and degradation which are integrated into our life-like abiotic systems. Such abiotic systems can be considered simple examples in the ontological classification of “life beyond biochemistry” (LBB), as they are based on carbon chemistry and, by design, do not use any biochemical compounds to integrate the basic system-level properties of natural life. This contribution analyzes a class of highly-out-of-equilibrium LBB systems we call “phoenix” and connects degradation pathways due to the presence of oxygenic species to enabling basic functionalities in these simple life beyond biochemistry systems such as protocell self-reproduction and the mechano-chemical squirting out into the medium of a fraction of their partially reacted lumen that enables heritable variation in our systems. We conclude that degradation within the lumen of mature micelles turning into vesicles may also be considered as a driving force for chemical evolution due to the number of new proximate reaction pathways it can open up. Full article

(This article belongs to the Special Issue The 15th Anniversary of Life—Alternatives to RNA World)

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12 pages, 373 KB

Open AccessArticle

Trajectories in Oxidative Stress and Corticosteroids Insensitivity in Patient with High Risk of Severe Asthma: Use of FeNO as Biomarker of Respiratory Epithelial Barrier Distress

by Cristiano Caruso, Ilaria Baglivo, Emanuele Cataldo, Ludovica Fabbroni, Maria Antonietta Zavarella, Stefania Colantuono, Gianna Camiciottoli, Giovanna Elisiana Carpagnano, Antonio Di Marco, Loreta Di Michele, Fabiana Furci, Chiara Magni, Laura Martino, Alessandro Mastinu, Corrado Micucci, Nicola Scichilone, Roberto Tazza, Rodolfo Pacilio and Michele Miraglia Del Giudice

Life 2026, 16(7), 1203; https://doi.org/10.3390/life16071203 - 21 Jul 2026

Viewed by 444

Abstract

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six [...] Read more.

Background: Precision medicine targets clinical remission, but traditional symptom-based frameworks often ignore the biological pathways driving the disease. Adequate T2 biomarker interpretation is crucial to identify phenotypes where FeNO reflects epithelial barrier distress. We investigated the “clinical-biological gap” through the analysis of six groups to distinguish profiles of symptomatic resilience from biological insensitivity to corticosteroids. Methods: Real-world study of 292 patients stratified into six groups based on BEC (≥250 cells/microL), FeNO (≥25 ppb), and IgE (≥100 kU/L). ACT, BMI, FEV1, comorbidities, and therapeutic burden were analyzed. Results: The EoS+ IgE+ group showed “symptomatic resilience”: apparent clinical control (54.5% ACT ≥ 20) supported by a critical pharmacological burden (90% salbutamol, 80% OCS ≥ 7.5 mg). The Triple Positive and EoS+ FeNO+ groups depicted “Maximum Steroid Insensitivity,” characterized by poor control despite maximal ICS/OCS regimens. FeNO could appear like the primary driver of instability, reflecting a trajectory of oxidative stress not altered by steroids. Conclusions: T2 biomarkers provide a unique prognostic value unidentifiable by standard clinical assessment. FeNO monitoring unmasks silent distress in resilient patients and identifies the “therapeutic wall” in refractory profiles. Therefore biological remission could represents the only effective target to modify the natural history of the disease. Full article

(This article belongs to the Special Issue Management of Inflammatory Airway Diseases)

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26 pages, 2222 KB

Open AccessArticle

A Candidate Salivary miRNA Panel for Bronchopulmonary Dysplasia in Very and Extremely Low-Birth-Weight Preterm Infants: A Pilot Exploratory Study

by Arailym Abilbayeva, Elmira Bitanova, Iskander Isgandarov, Beibitgul Bizhigitova, Dinara Yelyubayeva, Kristina Kovaleva, Zhanar Akhmetova, Ismira Gassanova, Balaussa Seitkhan, Indira Baibolsynova, Aibek Smagul, Zhuldyz Zhoshiyeva and Nishankul Bozhbanbayeva

Life 2026, 16(7), 1202; https://doi.org/10.3390/life16071202 - 21 Jul 2026

Viewed by 470

Abstract

Introduction: Bronchopulmonary dysplasia (BPD) remains the most significant complication of extreme prematurity, affecting long-term respiratory outcomes. Because current diagnostic criteria identify only established lesions at 36 weeks postmenstrual age, early non-invasive biomarkers are needed. This pilot study aimed to identify a candidate salivary [...] Read more.

Introduction: Bronchopulmonary dysplasia (BPD) remains the most significant complication of extreme prematurity, affecting long-term respiratory outcomes. Because current diagnostic criteria identify only established lesions at 36 weeks postmenstrual age, early non-invasive biomarkers are needed. This pilot study aimed to identify a candidate salivary miRNA panel associated with BPD risk and to explore its pathogenetic relevance through in silico analysis. Methods: Saliva was collected from 20 preterm infants (10 with BPD and 10 controls), and miRNA expression was profiled using the GeneChip™ miRNA 4.1 Array Plate. Discriminatory performance was explored by ROC analysis within this discovery cohort, together with power and Spearman correlation analyses. Results: Expression of hsa-let-7b-5p, hsa-let-7c-5p, and hsa-miR-4454 was significantly elevated in the BPD group (p < 0.05, log₂FC ≥ 1.0), with no significant correlation with gestational age or birth weight. Bootstrap-corrected AUC values ranged from 0.905 to 0.937 and were supported by leave-one-out cross-validation. All three miRNAs showed very large effect sizes exceeding the minimum detectable effect at 80% power. Conclusions: In this pilot study, salivary miRNAs represent a hypothesis-generating candidate biomarker signal for BPD that requires external validation in larger, independent cohorts before any diagnostic or prognostic application can be considered. Full article

(This article belongs to the Section Medical Research)

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19 pages, 313 KB

Open AccessArticle

Determinants of High Salt Intake in Croatian Adults: Evidence from 24-Hour Urinary Sodium Excretion in the EH-UH 2 Study

by Bojan Jelaković, Mihaela Marinović Glavić, Ana Stupin, Marija Domislović, Ana Jelaković, Lovorka Bilajac, Andrej Belančić, Matea Bilobrk, Marta Bolješić Dumančić, Mirjana Fuček, Lana Gellineo, Andrea Gross Bošković, Josipa Josipović, Verica Kralj, Sanja Kolarić Kravar, Ivan Pećin, Vladimir Prelević, Danilo Radunović, Petar Šušnjara, Vanja Vasiljev, Marijana Živko, Donatella Verbanac and Željko Reiner Show full author list Hide full author list

Life 2026, 16(7), 1201; https://doi.org/10.3390/life16071201 - 20 Jul 2026

Viewed by 431

Abstract

Although significant progress has been made in reducing salt consumption over the past decade, most Croatian adults still exceed the recommended intake. This study aimed to identify demographic, socioeconomic, lifestyle, and clinical factors associated with high salt intake in the general adult population [...] Read more.

Although significant progress has been made in reducing salt consumption over the past decade, most Croatian adults still exceed the recommended intake. This study aimed to identify demographic, socioeconomic, lifestyle, and clinical factors associated with high salt intake in the general adult population of Croatia. We included a random sample of 1067 adults with reliable 24-h urine samples. A structured questionnaire was used to collect sociodemographic, lifestyle, and clinical data. Anthropometric and blood pressure (BP) measurements were performed. Laboratory analyses included the measurement of sodium, potassium, and creatinine in adequate 24-h urine samples, as well as relevant cardiometabolic and kidney-related biomarkers. Participants consuming > 10 g/day of salt were older and had higher systolic blood pressure, fasting glucose, serum uric acid, and triglyceride levels, lower HDL cholesterol levels, and greater BMI. High salt intake was more common among men, ex-smokers, participants with diabetes, and those with lower socioeconomic status (SES). In multinomial logistic regression analysis, male sex, diabetes, higher systolic BP, more frequent processed meat consumption, lower fish consumption, residence outside the Adriatic region, and higher ePWV were associated with high salt intake. High salt intake was associated with lower socioeconomic status, residence in rural and continental areas, obesity, former smoking, and less favorable dietary patterns. Conversely, lower salt intake was associated with residence in the Adriatic region and dietary patterns characterized by more frequent consumption of fish and olive oil. Full article

(This article belongs to the Section Epidemiology)

30 pages, 6532 KB

Open AccessArticle

Mitochondrial and Nuclear Markers Reveal Contrasting Patterns of Genetic Diversity in the Red Palm Weevil (Rhynchophorus ferrugineus) from Qassim Province, Saudi Arabia

by Saleh S. Alhewairini, Medhat Rehan, Mohamed I. Motawei, Mahmoud Alazzazy and Nagdy F. Abdel-Baky

Life 2026, 16(7), 1200; https://doi.org/10.3390/life16071200 - 20 Jul 2026

Viewed by 544

Abstract

The red palm weevil, Rhynchophorus ferrugineus (Olivier), is among the most destructive invasive pests of date palms worldwide. In this study, mitochondrial cytochrome c oxidase subunit I (COI) and nuclear internal transcribed spacer (ITS) markers were analyzed in parallel to comparatively assess [...] Read more.

The red palm weevil, Rhynchophorus ferrugineus (Olivier), is among the most destructive invasive pests of date palms worldwide. In this study, mitochondrial cytochrome c oxidase subunit I (COI) and nuclear internal transcribed spacer (ITS) markers were analyzed in parallel to comparatively assess genetic diversity and haplotype variation in R. ferrugineus populations from Qassim Province, Saudi Arabia. Sequencing success rates reached 96.5% and 93.0% for COI and ITS, respectively. COI sequences exhibited very low nucleotide divergence among Qassim specimens (0.0–0.0077), indicating a highly conserved mitochondrial background and close phylogenetic similarity (p-distance = 0.0–0.0078) with an Egyptian reference haplotype (GU581319) and the reference R. ferrugineus mitochondrion (KT428893). In contrast, ITS analyses revealed substantially greater nuclear variation, identifying multiple haplotype groups with divergence levels of 10–19%. Haplotype diversity was higher in ITS (Hd = 0.876 ± 0.041) than in COI (Hd = 0.663 ± 0.068), while nucleotide diversity in ITS (π = 0.0387 ± 0.0013) was 36.9-fold greater than in COI (π = 0.00105 ± 0.00025; Z = 27.66, p < 0.001). Phylogenetic reconstruction showed greater population structuring in ITS than in COI. Integrated mitochondrial and nuclear markers improve genetic resolution and species identification in R. ferrugineus. Full article

(This article belongs to the Section Biodiversity, Ecology and Evolution)

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22 pages, 2348 KB

Open AccessReview

Challenges in Differential Diagnosis and Management of Lymphoepithelial Sialadenitis (LESA): A Scoping Review

by Miruna Bratiloveanu, Mihai Dumitru, Bogdan Banica, Oana Maria Patrascu, Crenguta Serboiu, Andreea Marinescu, Alina Oancea, Daniela Vrinceanu and Adrian Costache

Life 2026, 16(7), 1199; https://doi.org/10.3390/life16071199 - 20 Jul 2026

Viewed by 1104

Abstract

Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone [...] Read more.

Background: Lymphoepithelial sialadenitis (LESA) is a chronic lymphoid-rich inflammatory disorder of the salivary glands that is strongly associated with Sjögren’s disease and may overlap clinically, radiologically, and histopathologically with IgG4-related sialadenitis, HIV-associated lymphoepithelial lesions, chronic sialadenitis, salivary gland tumors, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Objective: This scoping review mapped current evidence on diagnostic challenges, differential diagnostic criteria, management strategies, and surveillance considerations for LESA. Eligibility criteria: Sources were selected using the Population–Concept–Context framework and included the literature addressing salivary gland lymphoepithelial lesions, LESA, Sjögren’s disease-associated salivary gland involvement, or related lymphoid-rich salivary gland disorders published from 2010 onward. Sources of evidence and charting methods: Google Scholar was searched, records were screened in sequential stages, and relevant data were charted narratively across clinical, serological, imaging, histopathological, immunophenotypic, molecular, therapeutic, and follow-up domains. Results: Thirty-seven sources were included. The evidence indicates that LESA is usually characterized by chronic lymphoplasmacytic inflammation, acinar atrophy, lymphoepithelial lesions, and preserved lobular architecture; however, these findings may overlap with early or established MALT lymphoma. Immunohistochemistry, assessment of light-chain restriction, clonality testing, serological markers, and imaging are useful adjuncts, but no single test is independently definitive. Conservative management and symptomatic care are appropriate for stable disease, whereas corticosteroids, immunomodulatory therapy, sialendoscopy, surgery, radiotherapy, or systemic lymphoma therapy may be considered according to clinical context. Conclusions: LESA requires integrated clinicopathological interpretation and multidisciplinary follow-up. Key evidence gaps include the absence of standardized LESA-specific diagnostic criteria, limited validation of molecular and flow cytometric approaches in salivary gland specimens, and lack of consensus surveillance protocols. Full article

(This article belongs to the Special Issue The Oral-Systemic Link in Chronic Mucosal Diseases)

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21 pages, 54141 KB

Open AccessArticle

Protective Effects of 5-MTP in a Rat Model of Diabetic Cardiomyopathy Through Anti-Inflammatory, Anti-Apoptotic, and Antifibrotic Mechanisms

by Susetyo Atmojo, Bambang Budi Siswanto, Nurjati Chairani Siregar, Aria Kekalih, Fadlina Chany Saputri, Budi Susetyo Pikir, Deni Noviana, Apridya Nurhafizah, Wilbert Huang and Puspita Eka Wuyung

Life 2026, 16(7), 1198; https://doi.org/10.3390/life16071198 - 20 Jul 2026

Viewed by 394

Abstract

Background: Diabetic cardiomyopathy (DCM) is characterized by myocardial inflammation, apoptosis, and fibrosis that contribute to ventricular remodeling and dysfunction. We investigated the effects of 5-methoxytryptophan (5-MTP) on histopathological and molecular markers of myocardial remodeling in a rat model of DCM. Methods: Forty-eight Sprague–Dawley [...] Read more.

Background: Diabetic cardiomyopathy (DCM) is characterized by myocardial inflammation, apoptosis, and fibrosis that contribute to ventricular remodeling and dysfunction. We investigated the effects of 5-methoxytryptophan (5-MTP) on histopathological and molecular markers of myocardial remodeling in a rat model of DCM. Methods: Forty-eight Sprague–Dawley rats with DCM induced by a high-fat high-fructose diet and low-dose streptozotocin (25 mg/kg) were randomized to control or 5-MTP treatment (25, 50, or 100 mg/kg) and evaluated after 8, 16, and 32 days. Histopathological assessment using hematoxylin–eosin and Masson’s trichrome staining, along with immunohistochemical analysis of inflammatory, apoptotic, and fibrotic markers, was performed. Results: Myocardial inflammatory histopathological scores did not differ significantly among groups. Myocardial fibrosis assessed by Masson’s trichrome staining was significantly reduced at day 16 (p = 0.020), with all 5-MTP doses demonstrating lower fibrosis scores than DCM controls. Collagen I expression did not differ significantly. Caspase-3 expression was significantly reduced in all treatment groups at day 16 (p = 0.029), with persistent reduction at day 32 only in the 100 mg/kg group (p = 0.004). Early molecular modulation was observed through reduced TGF-β expression at day 8 in the 25 mg/kg and 50 mg/kg groups, followed by reduced SMAD3 expression at day 16 in the 25 mg/kg and 100 mg/kg groups. At day 16, AKT expression increased in the 25 mg/kg group, while cytoplasmic NF-κB expression decreased in the 25 mg/kg and 100 mg/kg groups. Conclusion: 5-MTP demonstrated time-dependent changes in molecular and histopathological markers associated with myocardial remodeling in experimental DCM. Full article

(This article belongs to the Special Issue New Insights and Advances in Heart Failure Research)

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24 pages, 374 KB

Open AccessEditorial

Metabolic Health: The Interplay Between NAFLD, MAFLD, MASLD, and Cardiovascular Disease

by Monika Różycka-Kosmalska and Marcin Kosmalski

Life 2026, 16(7), 1197; https://doi.org/10.3390/life16071197 - 20 Jul 2026

Viewed by 611

Abstract

The last decade has transformed the conceptual landscape of fatty liver disease in three ways [...] Full article

(This article belongs to the Special Issue Metabolic Health: The Interplay Between NAFLD, MAFLD, MASLD and Cardiovascular Disease)

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Graphical abstract

2 pages, 128 KB

Open AccessEditorial

New Diagnostic and Therapeutic Developments in Eye and Systemic Diseases

by Zhihong Jewel Hu

Life 2026, 16(7), 1196; https://doi.org/10.3390/life16071196 - 20 Jul 2026

Viewed by 382

Abstract

The rapid evolution of diagnostic and therapeutic technologies continues to reshape ophthalmology and its interface with systemic diseases [...] Full article

(This article belongs to the Special Issue New Diagnostic and Therapeutic Developments in Eye and Systemic Diseases)

11 pages, 1073 KB

Open AccessFeature PaperArticle

The Effectiveness of Pleural Cholesterol Levels in Differentiating Transudate from Exudate and Comparison with Light’s Criteria

by Aziz Gumus, Elvan Senturk Topaloglu, Neslihan Ozcelik, Abdurrahman Kotan, Hasan Veysel Keskin, Omer Topaloglu and Songul Ozyurt

Life 2026, 16(7), 1195; https://doi.org/10.3390/life16071195 - 19 Jul 2026

Viewed by 783

Abstract

Background: Differentiating exudative from transudative pleural effusions is essential for accurate diagnosis and management. Although Light’s criteria remain the standard diagnostic method, they may incorrectly classify a substantial proportion of transudative effusions as exudates. This study aimed to evaluate the diagnostic performance of [...] Read more.

Background: Differentiating exudative from transudative pleural effusions is essential for accurate diagnosis and management. Although Light’s criteria remain the standard diagnostic method, they may incorrectly classify a substantial proportion of transudative effusions as exudates. This study aimed to evaluate the diagnostic performance of pleural fluid cholesterol and compare it with Light’s criteria. Methods: This retrospective study included 751 patients with pleural effusion who underwent diagnostic evaluation between 2015 and 2024 and had a definitive etiological diagnosis. All patients underwent ultrasound-guided thoracentesis with simultaneous pleural fluid and serum biochemical analyses. Based on final etiological diagnosis, effusions were classified as transudative or exudative. Results: The mean age was 68.6 ± 15.8 years. Of the pleural effusions, 516 (68.7%) were exudative and 235 (31.3%) were transudative. Malignant pleural effusion was the most common cause of exudates, whereas congestive heart failure predominated among transudates. Pleural fluid cholesterol levels were significantly higher in exudative than transudative effusions (91.1 ± 30.7 vs. 28.9 ± 13.5 mg/dL, p < 0.001). Receiver operating characteristic (ROC) analysis demonstrated excellent diagnostic performance for pleural fluid cholesterol (AUC = 0.976, 95% CI 0.965–0.987, p < 0.001). A pleural cholesterol cut-off value of ≥50 mg/dL demonstrated 92.2% sensitivity, 94.9% specificity, 97.5% positive predictive value, and 84.8% negative predictive value for identifying exudative effusions. Light’s criteria showed higher sensitivity (99.2%) but lower specificity (84.4%). Light’s criteria misclassified 15.6% of transudative effusions as exudates, whereas pleural cholesterol misclassified only 5.1%. Conclusions: Pleural fluid cholesterol measurement demonstrated high diagnostic accuracy in differentiating exudative and transudative pleural effusions and substantially reduced false exudate classification compared with Light’s criteria. Routine assessment of pleural cholesterol may improve the diagnostic evaluation of pleural effusions. Full article

(This article belongs to the Special Issue Molecular Signatures and Biomarkers in Human Diseases)

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15 pages, 3031 KB

Open AccessArticle

Community Structure and Functional Prediction of Gut Microbiota in Mandarin Fish (Siniperca Chuatsi) Under Different Culture and Feeding Conditions

by Yayu Wang, Chen Niu, Xiaoyu Jiang, Jinpeng Zhang, Shu Wang, Cuiping Gong and Dayan Hu

Life 2026, 16(7), 1194; https://doi.org/10.3390/life16071194 - 19 Jul 2026

Viewed by 438

Abstract

This study investigated the effects of culture systems and feed types on the gut microbiota of mandarin fish (Siniperca chuatsi), using three production culture modes: pond–live bait (CE), pond–artificial feed (CS), and RAS–artificial feed (GS). Under identical pond culture conditions, CS [...] Read more.

This study investigated the effects of culture systems and feed types on the gut microbiota of mandarin fish (Siniperca chuatsi), using three production culture modes: pond–live bait (CE), pond–artificial feed (CS), and RAS–artificial feed (GS). Under identical pond culture conditions, CS fish fed compound feed had higher relative abundances of carbohydrate-metabolizing Bacteroidota and Firmicutes than CE. The CS group showed higher α-diversity, but β-diversity analysis indicated no significant community difference (p = 0.36), demonstrating that feed replacement only induced mild microbial shifts. LEfSe analysis uncovered 17 differential taxa: homeostasis-related genera enriched in CS, while the lipid-adapted Macellibacteroides prevailed in CE. Under identical artificial feed conditions, switching culture mode from pond (CS) to industrial RAS (GS) drastically reduced gut microbial diversity and simplified community structure. GS exhibited a sharp rise in Fusobacteriota, with Cetobacterium (64.94%) becoming the single dominant genus. α-diversity was lower in GS than CS, and β-diversity confirmed highly distinct community profiles between the two groups (p = 0.004). LEfSe detected 43 differential taxa with diverse metabolic genera abundant in CS. No PICRUSt2-inferred KEGG pathways remained significant after FDR correction in the above two comparison groups, so these functional trends are only for reference. Full article

(This article belongs to the Special Issue Responses of Aquatic Organisms to Environmental Stress)

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18 pages, 17724 KB

Open AccessArticle

Prognostic Value of Exportin-7 and Its Association with KRAS Status and Autophagy Markers in Small Intestinal Adenocarcinoma

by Jeong Won Kim, Kris Ylaya, Eun Joo Chung, Sun-Young Jun, Seung-Mo Hong and Joon-Yong Chung

Life 2026, 16(7), 1193; https://doi.org/10.3390/life16071193 - 19 Jul 2026

Viewed by 433

Abstract

Small intestinal adenocarcinoma (SIAC) is a rare malignancy with a rising incidence and poor prognosis. Although exportin-7 (XPO7) is typically characterized as a tumor suppressor, recent evidence suggests context-dependent oncogenic functions, yet its role in SIAC remains unexplored. This study evaluated the clinicopathological [...] Read more.

Small intestinal adenocarcinoma (SIAC) is a rare malignancy with a rising incidence and poor prognosis. Although exportin-7 (XPO7) is typically characterized as a tumor suppressor, recent evidence suggests context-dependent oncogenic functions, yet its role in SIAC remains unexplored. This study evaluated the clinicopathological significance of XPO7 expression and its association with KRAS status, autophagy, and cancer stemness in 191 surgically resected primary SIAC cases using immunohistochemistry and automated digital quantification. XPO7 was significantly upregulated in SIAC compared to normal mucosa (p < 0.001). High XPO7 expression, observed in 27.2% of cases, correlated with higher histological grade (p = 0.023) and was identified as an independent predictor of poor overall survival (hazard ratio = 1.703; p = 0.008). Subgroup analysis revealed that high XPO7 levels were associated with significantly shorter median overall survival specifically in cases featuring lymphovascular invasion, nodal metastasis, and KRAS mutations. Furthermore, XPO7 expression demonstrated a significant positive correlation with autophagy markers (LC3B and p62) but not with stemness markers (Sox2, Oct4, and Nanog). In conclusion, XPO7 serves as a significant independent prognostic biomarker for SIAC, and its correlation with autophagy markers in aggressive subgroups highlights its potential as a promising therapeutic target. Full article

(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)

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29 pages, 32928 KB

Open AccessArticle

Subchondral Bone Regeneration of the Porcine Knee Joint Using α-TCP Biocement Enriched with Manuka Honey—Qualitative Pilot Study

by Filip Korim, Katarína Vdoviaková, Lenka Krešáková, Filip Humeník, Ján Danko, Zuzana Čriepoková, Jozef Bíreš, Kristína Čurgali, Zuzana Fagová, Marko Vrzgula, Mária Giretová, Ľubomír Medvecký, Radoslava Štulajterová, Roman Totkovič and Pavol Rusnák

Life 2026, 16(7), 1192; https://doi.org/10.3390/life16071192 - 19 Jul 2026

Viewed by 391

Abstract

The treatment of osteochondral defects still poses a challenge, despite the fact that there are currently many methods and various materials designed for the regeneration of these tissues. The aim of our study was to evaluate the biocompatibility and bioactive potential of an [...] Read more.

The treatment of osteochondral defects still poses a challenge, despite the fact that there are currently many methods and various materials designed for the regeneration of these tissues. The aim of our study was to evaluate the biocompatibility and bioactive potential of an innovative biocement enriched with manuka honey and α-tricalcium phosphate in a porcine model, with a focus on subchondral bone regeneration. Osteochondral defects of the medial femoral condyle were treated with the tested biocement in five animals, and five additional animals served as controls (untreated defect). After six months of observation, the regenerative potential of the therapeutic strategy was evaluated macroscopically, using imaging methods (X-ray, CT, and MRI) and histological examination. The studied biomaterial showed no cytotoxicity and proved to be biocompatible. In the in vivo system, based on imaging and histological methods, a typical trabecular organization with cellular elements has been observed in all animals treated with the tested biocement, indicating active remodeling and maturation processes. In animals with untreated defects, incomplete healing of the bone defect occurred, with limited areas of trabecular bone and incomplete boundaries between the cartilage and subchondral bone. Our pilot study, employing a multi-method approach to investigate the in vivo effects of a novel biocement on bone tissue regeneration, may highlight the potential contribution of biomaterials to the development of new therapeutic strategies in the context of osteochondral regeneration. Full article

(This article belongs to the Special Issue Reconstruction of Bone Defects)

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14 pages, 653 KB

Open AccessArticle

Early Identification of Low Bone Density Risk Using a Radiofrequency Echographic Multi Spectrometry-Based Prediction Model

by Elena Bischoff, Stoyanka Vladeva, Nikola Kirilov and Fabian Bischoff

Life 2026, 16(7), 1191; https://doi.org/10.3390/life16071191 - 18 Jul 2026

Viewed by 393

Abstract

Osteoporosis is a major public health problem characterized by reduced bone mineral density (BMD) and increased fracture risk. Early identification of individuals with low bone density remains essential for prevention. This study aimed to evaluate a multivariable logistic regression-based model integrating clinical and [...] Read more.

Osteoporosis is a major public health problem characterized by reduced bone mineral density (BMD) and increased fracture risk. Early identification of individuals with low bone density remains essential for prevention. This study aimed to evaluate a multivariable logistic regression-based model integrating clinical and Radiofrequency Echographic Multi Spectrometry (REMS)-derived parameters for the detection of low bone density in women. A total of 324 women undergoing REMS assessment of the lumbar spine and hip were included. Clinical variables (age, body mass index [BMI], menopausal status, and lifestyle factors) and REMS-derived measurements were analyzed. Binary logistic regression was used to identify independent factors associated with low BMD (T-score < −1 SD). Model performance was assessed using odds ratios (ORs), omnibus chi-square testing, pseudo-R² statistics, and classification accuracy. The Youden index was applied to determine optimal cut-off values. Age, menopausal status, BMI, and basal metabolic rate (BMR) were identified as independent factors associated with low lumbar spine and femoral neck BMD. Increasing age and menopause were associated with higher odds of low bone density, whereas higher BMI and BMR were inversely associated with low bone density. In conclusion, a logistic regression model combining clinical and REMS-derived parameters demonstrated the ability to identify women with low bone density, supporting improved individualized risk stratification in clinical practice. Full article

(This article belongs to the Section Radiobiology and Nuclear Medicine)

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22 pages, 7480 KB

Open AccessArticle

Preliminary Molecular Characterization and Antimicrobial Activity of Enterococcus faecium Strains Isolated from Algerian Camel Milk

by Yasmine Saidi, Mohamed Merzoug, Chaimaà Naila Brakna, Keltoum Bendida, Soheir Bouzidi, Marwa Aireche, Hayet Messaoui, Amaria Ilhem Hammadi, Yasmine Zohra Zater, Hadjer Bouderbala, Svetoslav Dimitrov Todorov and Djamel Saidi

Life 2026, 16(7), 1190; https://doi.org/10.3390/life16071190 - 18 Jul 2026

Viewed by 485

Abstract

This study characterized six Enterococcus faecium strains isolated from Algerian camel milk to assess their molecular features and antimicrobial potential as food-associated isolates. Identification was performed using phenotypic tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Strain [...] Read more.

This study characterized six Enterococcus faecium strains isolated from Algerian camel milk to assess their molecular features and antimicrobial potential as food-associated isolates. Identification was performed using phenotypic tests, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 16S rRNA gene sequencing. Strain diversity was assessed by repetitive sequence-based polymerase chain reaction (rep-PCR), including (GTG)₅-PCR, BOX-PCR, and enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). Polymerase chain reaction (PCR) screening for selected virulence-associated and antimicrobial resistance genes showed that the two selected isolates were negative for the targeted markers, indicating a preliminary molecular profile of interest but not allowing definitive safety conclusions without whole-genome sequencing and phenotypic antimicrobial susceptibility testing. Both strains showed antimicrobial activity against Gram-positive and Gram-negative indicators. Strain 9 showed notable inhibition against Klebsiella pneumoniae subsp. pneumoniae ATCC 13883, with an inhibition zone of 23.4 ± 2.3 mm using native supernatant, which increased after concentration. Trypsin treatment abolished activity, supporting the proteinaceous nature of the inhibitory compounds. The enterocin genes entA and entB were detected in strains 9 and 13, indicating genetic potential only. Further genomic, safety, and functional investigations are required. Full article

(This article belongs to the Section Microbiology)

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16 pages, 281 KB

Open AccessArticle

Predictors of 90-Day Mortality and the Association of Reperfusion Therapy with 90-Day Mortality in Intermediate-High and High-Risk Pulmonary Embolism: A Real-World Multidisciplinary Cohort Study

by Özgür Batum, Merve Ayık Türk, Yelda Varol, Muhammed Emin Arslan, Cenk Sarı, Sami Deniz, Nigar Dirican, Kutluhan Eren Hazır and Sibel Doruk

Life 2026, 16(7), 1189; https://doi.org/10.3390/life16071189 - 17 Jul 2026

Viewed by 344

Abstract

Background: Intermediate-high and high-risk pulmonary embolism (PE) are associated with substantial mortality despite anticoagulation. While reperfusion therapies may improve outcomes, real-world evidence comparing treatment strategies and identifying predictors of mid-term mortality remains limited. We aimed to evaluate predictors of 90-day mortality and the [...] Read more.

Background: Intermediate-high and high-risk pulmonary embolism (PE) are associated with substantial mortality despite anticoagulation. While reperfusion therapies may improve outcomes, real-world evidence comparing treatment strategies and identifying predictors of mid-term mortality remains limited. We aimed to evaluate predictors of 90-day mortality and the impact of reperfusion therapy in patients with intermediate-high and high-risk PE managed within a multidisciplinary Pulmonary Embolism Response Team (PERT). Methods: This retrospective cohort study included 114 consecutive patients with intermediate-high or high-risk acute PE admitted to a tertiary referral center between October 2023 and December 2024. Risk stratification was performed according to ESC guidelines, and simplified Pulmonary Embolism Severity Index (sPESI) scores were calculated. Treatment strategies included anticoagulation alone or reperfusion therapy (systemic thrombolysis or catheter-directed therapy). The primary endpoint was all-cause 90-day mortality. Multivariate logistic regression was performed to identify independent predictors of mortality. Results: The mean age was 68 ± 16 years, and 88% had at least one comorbidity. Reperfusion therapy was administered to 27% of patients. Mortality rates were 1% at 24 h, 6% at 7 days, 17% at 30 days, and 25% at 90 days. In multivariate analysis, hemoglobin ≤ 11.7 g/dL (OR 5.06, 95% CI 1.58–16.17, p = 0.006), sPESI > 2 (OR 4.86, 95% CI 1.49–15.84, p = 0.009), prior stroke (OR 11.59, 95% CI 2.08–64.51, p = 0.005), and high 30-day mortality risk classification (OR 14.14, 95% CI 1.19–167.89, p = 0.036) were independent predictors of mortality. Reperfusion therapy was independently associated with a significant reduction in 90-day mortality (OR 0.05, 95% CI 0.003–0.65, p = 0.022). The regression model demonstrated good explanatory power (Nagelkerke R² = 0.487). Conclusions: In this real-world cohort of intermediate-high and high-risk PE, reperfusion therapy was independently associated with lower 90-day mortality and low bleeding risk. In addition to established predictors, sPESI retained strong prognostic value beyond its traditional 30-day timeframe. These findings support risk-adapted reperfusion strategies guided by multidisciplinary teams and reinforce the role of integrated clinical risk assessment in optimizing outcomes. Full article

(This article belongs to the Special Issue Advances in Pulmonology: Transforming Diagnosis and Treatment of Lung Diseases)

24 pages, 4408 KB

Open AccessHypothesis

Calpains as Potential Regulators of Microtubule-Associated Cytokinesis: A Cross-Eukaryotic Unifying Hypothesis

by Jennifer C. Fletcher, Mary A. Biggs and Hilde-Gunn Opsahl-Sorteberg

Life 2026, 16(7), 1188; https://doi.org/10.3390/life16071188 - 17 Jul 2026

Viewed by 738

Abstract

Calpains constitute an ancient, extensive family of calcium-dependent cysteine proteases found in some bacteria and most eukaryotes. They are involved in a wide variety of developmental and cellular processes and are implicated in major human diseases, but whether they share an ancestral or [...] Read more.

Calpains constitute an ancient, extensive family of calcium-dependent cysteine proteases found in some bacteria and most eukaryotes. They are involved in a wide variety of developmental and cellular processes and are implicated in major human diseases, but whether they share an ancestral or broadly conserved cellular role remains unknown. Beyond their core CysPc catalytic domain, calpains contain diverse domain combinations and can be either cytosolic or membrane bound. Here, we develop the hypothesis that both cytosolic and transmembrane calpains may contribute to cytokinesis through positional anchoring and organization of microtubules (MTs). We propose that during plant cell division, the singular transmembrane calpain DEK1 plays a role in localizing and organizing the array of cortical MTs from the microtubule organizing center (MTOC) and may thereby position the cell division plane, potentially affecting preprophase band placement and subsequent cell plate formation. Similarly, during cell division in animals, their cytosolic calpains may be involved in setting the point of membrane invagination via their association with membrane-bound proteins. We discuss this novel model for calpain activity in the context of data from the animal and plant literature, as well as of our discovery of putative calpain sequences in both brown and red algal genomes. These findings are consistent with the view that calpains were present early in eukaryotic evolution and diversified alongside distinct modes of cell division. Finally, we consider the possibility that early calpain functions may have been linked to the formation and function of MT arrays in flagella and cilia, from which later roles in cytokinesis might have evolved. This model is intended as a testable framework for future studies of calpain function across eukaryotes. Full article

(This article belongs to the Section Cell Biology and Tissue Engineering)

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16 pages, 9864 KB

Open AccessArticle

A Modern Framework for Identifying Novel Environmental Legionella Species

by Karla Vasari, Maja Kovačević, Niko Kasalo, Snježana Kazazić, Ivan Mijakovic, Göran Klobučar, Damjan Franjevic, Josip Skejo, Tomislav Domazet-Lošo, Brian G. Shelton, Marina Santic and Roberta Sauerborn Klobucar

Life 2026, 16(7), 1187; https://doi.org/10.3390/life16071187 - 17 Jul 2026

Viewed by 528

Abstract

Accurate species-level identification of Legionella during routine environmental surveillance remains challenging, as standard proteomic screening methods like MALDI-TOF MS often lack the resolution to distinguish closely related taxa. This study introduces a novel, cost-effective, and stepwise taxonomic framework that bridges routine environmental monitoring [...] Read more.

Accurate species-level identification of Legionella during routine environmental surveillance remains challenging, as standard proteomic screening methods like MALDI-TOF MS often lack the resolution to distinguish closely related taxa. This study introduces a novel, cost-effective, and stepwise taxonomic framework that bridges routine environmental monitoring with multi-layered, genome-resolved analysis. We expanded upon our previous screening of four novel candidate lineages by focusing on the three remaining, uncharacterized environmental isolates, while using the recently validly described Legionella sheltonii (strain PATHC038) as a reference framework control. By applying nucleotide- and protein-based overall genomic relatedness indices (ANI, dDDH, AAI, and POCP) alongside core-genome phylogenomics, our framework independently confirmed the genomic distinctiveness of the three isolates, which exhibited AAI values of 94.3–96.6% and POCP values of 86.5–91.0%, with POCP values lying close to the proposed species delineation threshold. By defining clear criteria for escalating isolates from culture to targeted sequencing, this workflow prevents diagnostic misidentification during epidemiological outbreak investigations and provides public health agencies with a scalable tool to monitor hidden Legionella diversity, ultimately enhancing proactive water safety and risk assessment. Full article

(This article belongs to the Special Issue Novel Environmental Microbial Species and Genomic Characteristics)

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15 pages, 12185 KB

Open AccessCase Report

DNAJB9 in Fibrillary Glomerulonephritis: Diagnostic Biomarker, Putative Autoantigen, or Disease-Associated Scaffold? A Case-Based Narrative Review

by Larrisa Lebedev, Mahmud Mansur, Mustafa Seh, Elena Rotshild, Ornit Itzhaki, Alexander Wechsler, Anna Tobar and Nomy Levin Iaina

Life 2026, 16(7), 1186; https://doi.org/10.3390/life16071186 - 17 Jul 2026

Viewed by 509

Abstract

Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily [...] Read more.

Fibrillary glomerulonephritis (FGN) is an uncommon glomerular deposition disease characterized by randomly oriented, nonbranching fibrils that are usually Congo-red-negative and larger than amyloid fibrils on electron microscopy. The discovery of DNAJ homolog subfamily B member 9 (DNAJB9) has transformed FGN from a primarily ultrastructural diagnosis into a molecularly recognizable disease. However, the pathogenic significance of DNAJB9 remains unresolved: it may represent a highly specific biomarker, a putative autoantigen, a chaperone-associated scaffold, or a marker of disturbed protein quality control. We report two patients with positive glomerular DNAJB9 staining and markedly divergent clinical phenotypes. The first patient, a 58-year-old man, presented with severe acute kidney injury, nephritic urinary sediment, severe hypertension, crescentic immune-complex glomerulonephritis, and dialysis-requiring kidney failure. Electron microscopy and IgG subclass staining were unavailable; therefore, the findings were interpreted as probable rather than definitive DNAJB9-positive FGN. Diagnostic and causal interpretation was further complicated by concurrent Klebsiella pneumoniae urinary tract infection, mild bilateral hydronephrosis, acute tubulointerstitial injury, and severe hypertension. Kidney function did not recover despite glucocorticoids and cyclophosphamide, but the adverse outcome and treatment response cannot be attributed to FGN alone. The second patient, a 66-year-old woman, presented with chronic proteinuria, preserved kidney function, inactive urinary sediment, and lupus-like serologic findings. Electron microscopy demonstrated randomly arranged, nonbranching 13–19 nm fibrils, and DNAJB9 staining confirmed FGN. She was managed with angiotensin receptor blockade and dapagliflozin, with reduction of proteinuria to below 1 g/day. Together with previously published cohorts, these cases illustrate the diagnostic value of DNAJB9 staining and the potential clinicopathologic heterogeneity of FGN. However, Case 1 should be considered a clinically confounded, hypothesis-generating example and not definitive evidence that FGN alone caused the crescentic presentation, dialysis dependence, or lack of response to immunosuppression. Full article

(This article belongs to the Special Issue Pathogenesis and Novel Treatment for Kidney Diseases)

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24 pages, 337 KB

Open AccessReview

Analgosedation in Neonatal Intensive Care: Current Strategies, Challenges, and Future Perspectives

by Leonardo Detto, Eleonora Alfieri, Anna Munerati, Serafina Perrone and Susanna Esposito

Life 2026, 16(7), 1185; https://doi.org/10.3390/life16071185 - 16 Jul 2026

Viewed by 509

Abstract

Pain and stress are frequent and clinically relevant challenges in neonatal intensive care, particularly among preterm and critically ill newborns exposed to repeated invasive procedures, mechanical ventilation, surgery, and advanced life-support interventions. Effective analgosedation is essential to reduce discomfort, attenuate physiological instability, improve [...] Read more.

Pain and stress are frequent and clinically relevant challenges in neonatal intensive care, particularly among preterm and critically ill newborns exposed to repeated invasive procedures, mechanical ventilation, surgery, and advanced life-support interventions. Effective analgosedation is essential to reduce discomfort, attenuate physiological instability, improve tolerance of intensive care procedures, and potentially limit adverse neurodevelopmental consequences. However, neonatal pain and analgosedation management remain complex because of developmental immaturity, pharmacokinetic and pharmacodynamic variability, and the need to balance adequate analgosedation against treatment-related complications. This narrative review summarizes current evidence on analgosedation in the Neonatal Intensive Care Unit, focusing on clinical indications, pharmacological agents, non-pharmacological strategies, monitoring tools, adverse effects, and future perspectives. Opioids, benzodiazepines, dexmedetomidine, and ketamine each have specific potential benefits and limitations, requiring individualized selection, careful titration, and continuous reassessment. Non-pharmacological interventions, including oral sucrose, non-nutritive sucking, facilitated tucking, breastfeeding, skin-to-skin care, and environmental modulation, should be integrated into multimodal pain-management protocols. Validated instruments such as COMFORTneo, N-PASS, and PIPP-R support standardized assessment and guide therapeutic decisions. Future advances may derive from objective monitoring technologies, artificial intelligence, developmental pharmacology, and precision-medicine approaches. A multidisciplinary, protocol-driven, and family-centered strategy is essential to optimize neonatal comfort while minimizing avoidable drug exposure. Full article

(This article belongs to the Special Issue Recent Advances in Diagnostics, Monitoring and Management of Neonatal Diseases)

13 pages, 1440 KB

Open AccessArticle

Abiraterone Acetate Affects Gene Expression Profile in a Human Male Neuronal Cell Line: Potential Mechanism for Cognitive Deficits with Prostate Cancer Therapy

by Shelly Gulkarov, Allison B. Reiss, Ankita Srivastava, Jasper Lim-Goyette, Heather A. Renna, Andrew Laccetti and Aaron E. Katz

Life 2026, 16(7), 1184; https://doi.org/10.3390/life16071184 - 16 Jul 2026

Viewed by 572

Abstract

Background and Objectives: Cornerstone therapies for metastatic prostate cancer include androgen deprivation and androgen receptor pathway inhibition, but cognitive impairment is a recognized, life-altering potential adverse effect of this treatment. Abiraterone acetate (AA), an androgen receptor pathway and CYP17A1 inhibitor, suppresses androgen synthesis [...] Read more.

Background and Objectives: Cornerstone therapies for metastatic prostate cancer include androgen deprivation and androgen receptor pathway inhibition, but cognitive impairment is a recognized, life-altering potential adverse effect of this treatment. Abiraterone acetate (AA), an androgen receptor pathway and CYP17A1 inhibitor, suppresses androgen synthesis and may contribute to cognitive changes. This cell culture-based study uses the BE(2)M17 human male neuroblastoma model to investigate AA-induced alterations in gene and protein expression that may underlie cognitive decline, laying the foundation for a mechanistic investigation aimed at identifying molecular targets to mitigate cognitive impairment in men with prostate cancer receiving androgen-directed therapies. Materials and Methods: BE(2)M17 cells were pretreated for 12 h with dihydrotestosterone (DHT; 5 nM) or vehicle control, then exposed to AA (0, 5, 10 µM, 24 h). RNA and protein were analyzed by qRT-PCR and Western blot for markers of amyloid processing, neuronal health, and mitochondrial function. Results: AA significantly altered multiple neurobiological markers. BACE1 mRNA increased in DHT + 10 µM AA compared to control and DHT alone (p = 0.0416 and p = 0.0118). However, BACE1 protein decreased in 10 µM AA + DHT versus DHT alone (p = 0.0132). Immunoblot revealed reduced amyloid precursor protein (APP) in 10 µM AA versus control (p = 0.0057) and 10 µM versus 5 µM (p = 0.0263). APP was reduced in 10 µM AA + DHT versus control (p = 0.0015) and versus DHT alone (p = 0.0467). LRP1 and BDNF were significantly reduced with 10 µM AA versus 5 µM AA (p = 0.0092 and p = 0.0081), while synaptophysin decreased in 10 µM AA + DHT versus DHT alone (p = 0.0049). BDNF also declined in 10 µM AA + DHT compared to 5 µM AA + DHT (p = 0.0301). PGC1α mRNA increased in AA + DHT versus DHT alone (p = 0.0332). MitoTracker analysis showed reduced fluorescence with 5 µM AA alone but increased fluorescence with 5 µM AA + DHT relative to control and DHT (p = 0.0019; p < 0.0001), while 10 µM AA + DHT reduced fluorescence compared to 5 µM AA + DHT (p = 0.0003). Conclusions: AA, alone or combined with DHT, disrupts key pathways involved in neuronal health, amyloid processing, and mitochondrial function. These findings suggest a potential mechanistic link between AA treatment and cognitive impairment. Full article

(This article belongs to the Special Issue Prostate Cancer: 4th Edition)

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Life, Volume 16, Issue 7 (July 2026) – 174 articles

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