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20 pages, 713 KB

Open AccessSystematic Review

Effectiveness of Physiotherapy in Haemodialysis: Systematic Review

by Juan Rodríguez-Mansilla, Carmen Murillo-González, María Jiménez-Palomares, Elisa María Garrido-Ardila and Blanca González-Sánchez

Life 2026, 16(2), 340; https://doi.org/10.3390/life16020340 (registering DOI) - 15 Feb 2026

Abstract

Background: Chronic kidney disease (CKD) is a progressive pathology that affects millions of people worldwide, becoming a public health challenge due to its high prevalence and mortality. In its advanced stages, patients require therapies such as haemodialysis (HD), which often entails physical complications, [...] Read more.

Background: Chronic kidney disease (CKD) is a progressive pathology that affects millions of people worldwide, becoming a public health challenge due to its high prevalence and mortality. In its advanced stages, patients require therapies such as haemodialysis (HD), which often entails physical complications, so incorporating physiotherapy as an essential part of the treatment of these patients becomes evident. Objective: To analyse the effectiveness of physiotherapy in patients undergoing haemodialysis before, during and after the treatment. Methodology: This study is a systematic review conducted following the PRISMA statements. An electronic literature search was performed in the following databases: PubMed, PEDro, Chorane Library, ScienceDirect and Dialnet. The inclusion criteria were: controlled and uncontrolled clinical trials published in the last 10 years in English or Spanish, in patients with chronic kidney disease on haemodialysis treatment, aged 18 years or older. Results: 22 studies were included in this review. A total of 1786 patients participated in the included studies. Most of the investigations used cycloergometers, treadmills and bicycles. The programmes varied in types of exercise, with combinations of aerobic, endurance and inspiratory muscle training, with assessments at baseline and at the end of the intervention, some with additional measurements at 8, 12 or 16 weeks, and others with no specified follow-up time. Conclusions: The analysed literature showed that therapeutic exercise can be beneficial for haemodialysis patients, improving muscle strength, aerobic capacity and quality of life. Its implementation, both before, during and after haemodialysis sessions, also helped to reduce fatigue and depression. These results support the importance of exercise in the comprehensive treatment of patients with chronic kidney disease in haemodialysis. Full article

(This article belongs to the Section Medical Research)

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13 pages, 2132 KB

Open AccessArticle

Novel Stochastic Sensors Based on Phthalocyanine Complexes for the Detection of C-NP, IL-6, and CRP in Cardiovascular Diseases

by Ruxandra-Maria Ilie-Mihai and Raluca-Ioana Stefan-van Staden

Life 2026, 16(2), 339; https://doi.org/10.3390/life16020339 (registering DOI) - 15 Feb 2026

Abstract

The severity of cardiovascular disease is linked to C-reactive protein, interleukin 6, and C-type natriuretic peptide levels, stressing the need for a sensitive sensor that can detect these biomarkers at ultralow levels in real time. Whole blood samples from confirmed cardiovascular patients were [...] Read more.

The severity of cardiovascular disease is linked to C-reactive protein, interleukin 6, and C-type natriuretic peptide levels, stressing the need for a sensitive sensor that can detect these biomarkers at ultralow levels in real time. Whole blood samples from confirmed cardiovascular patients were analyzed for C-type natriuretic peptide, C-reactive protein, and interleukin 6 using three stochastic sensors. These sensors were designed using carbon paste matrices decorated with Ag nanoparticles (AgNPs), on which different phthalocyanines were physically immobilized. The sensors exhibited exceptionally low detection limits (1 × 10⁻²¹ g mL⁻¹) and broad linear concentration ranges (1 × 10⁻²¹ to 1 × 10⁻⁶ g mL⁻¹). The analysis conducted using the Student t-test indicated that there is no statistically significant difference between the results obtained from the three stochastic sensors used in the screening tests of whole blood, with ELISA at a confidence level of 99%. Full article

(This article belongs to the Special Issue New Screening Methods for Diagnosis of Cardiovascular Diseases)

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13 pages, 853 KB

Open AccessArticle

The Critical Role of Nutritional and Procedural Factors in CTO-PCI Patient Prognosis

by Gürkan Karaca, Ahmet Ekmekci, Ali Kimiaei, Seyedehtina Safaei, Aziz İnan Çelik and Metin Çağdaş

Life 2026, 16(2), 338; https://doi.org/10.3390/life16020338 (registering DOI) - 15 Feb 2026

Abstract

(1) Background: Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is a complex, high-risk procedure compared to standard percutaneous coronary intervention (PCI). Scoring systems such as the Japanese Chronic Total Occlusion (J-CTO), European Chronic Total Occlusion (EuroCTO), and Prospective Global Registry for the Study [...] Read more.

(1) Background: Chronic total occlusion percutaneous coronary intervention (CTO-PCI) is a complex, high-risk procedure compared to standard percutaneous coronary intervention (PCI). Scoring systems such as the Japanese Chronic Total Occlusion (J-CTO), European Chronic Total Occlusion (EuroCTO), and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS-CTO) evaluate lesion difficulty and predict outcomes. Nutritional status, measured by the Prognostic Nutritional Index (PNI), may also affect procedural success and long-term survival. The objective of this study was to evaluate the combined impact of procedural complexity and nutritional status on the clinical outcomes of patients undergoing CTO-PCI. (2) Methods: We analyzed 118 patients undergoing CTO-PCI between May 2021 and March 2022. Procedural complexity was assessed using the J-CTO, EuroCTO, and PROGRESS-CTO scores, while nutritional status was evaluated using the PNI. Primary outcomes included all-cause mortality and repeat revascularization, which were analyzed using Cox proportional hazards regression and Kaplan–Meier survival analyses. (3) Results: Adverse outcomes occurred in 25 patients (mortality: 17; revascularization: 8). Patients with adverse outcomes had significantly lower left ventricular ejection fraction (LVEF) (46 ± 13.7% vs. 52.1 ± 10.5%, p < 0.001), lower PNI (p < 0.001), and higher J-CTO, EuroCTO, and PROGRESS-CTO scores (all p < 0.05). A PNI cut-off value of 46 predicted mortality with a sensitivity of 70.6% and specificity of 75.2% (area under the curve [AUC] = 0.739, p = 0.001). Multivariable analysis identified LVEF (hazard ratio [HR] 0.966, p = 0.036), J-CTO score (HR 1.598, p = 0.027), and PNI (HR 0.925, p = 0.022) as independent predictors of mortality. (4) Conclusion: Both procedural complexity and nutritional status significantly influence outcomes following CTO-PCI. Incorporating PNI together with procedural complexity scores into pre-procedural assessments may enhance risk stratification and optimize patient management. Full article

(This article belongs to the Special Issue Innovation and Translation in Cardiovascular Interventions)

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16 pages, 734 KB

Open AccessArticle

Associations of Neutrophil-to-Lymphocyte Ratio with Cerebral Small Vessel Disease and Functional Outcome in Acute Ischaemic Stroke Patients

by Nipit Tieachanpan, Surat Tanprawate, Atiwat Soontornpun, Chayasak Wantaneeyawong, Chutithep Teekaput, Nopdanai Sirimaharaj, Angkana Nudsasarn, Withawat Vuthiwong and Kitti Thiankhaw

Life 2026, 16(2), 337; https://doi.org/10.3390/life16020337 (registering DOI) - 15 Feb 2026

Abstract

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included [...] Read more.

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included patients with AIS who had symptom onset within 72 h and underwent MRI brain between January 2019 and December 2023. The associations between tertiles (T) of the neutrophil-to-lymphocyte ratio (NLR) and CSVD markers were studied using multinomial logistic regression. Functional outcomes at discharge and 90 days, as measured by the modified Rankin Scale (mRS), were also evaluated. Results: A total of 299 eligible patients were included, with a mean age of 65.7 ± 13.8 years and 55.5% (166/299) were male, and categorised into three tertiles of NLR (T1: 101, T2: 101, T3: 97). Patients with a higher NLR tertile had more admission NIHSS (T3 vs. T1: 3 (2, 5) vs. 2 (1, 3), p = 0.005). NLR was associated with an increased risk of ≥5 lobar cerebral microbleeds (CMBs) in an unadjusted model (T3 vs. T1: relative risk ratio (RRR), 5.69 (95% confidence interval (CI) 1.21–26.68); p = 0.03); however, this was not significant when adjusted for potential confounders (RRR 3.86; 95% CI 0.79–18.89; p = 0.10). No significant associations were observed in the remaining neuroimaging markers of CSVD. Patients in the T2 of NLR had a higher likelihood of achieving an mRS of 0–1 at 90 days (RRR 2.16; 95% CI 1.05–4.44; p = 0.04) compared to those in T1. Conclusions: In AIS, admission NLR showed a possible association with higher lobar CMB burden in unadjusted analyses, but this was not robust after adjustment, and no consistent relationships were observed with other CSVD markers. Associations with functional outcomes were not uniform across tertiles, and the apparent benefit in the middle NLR tertile should be interpreted cautiously as a potentially non-linear or chance finding, indicating that NLR is not a reliable independent imaging or prognostic marker in this cohort. Full article

(This article belongs to the Section Physiology and Pathology)

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19 pages, 5869 KB

Open AccessArticle

Biomechanical Comparison of Three Fixation Constructs for Tile Type C1.2 Pelvic Ring Fractures: A Finite Element Analysis

by Adrian Claudiu Carp, Bogdan Veliceasa, Dmour Awad, Alexandru Filip, Mihaela Perțea, Norin Forna, Bogdan Puha, Ștefan Dragoș Tîrnovanu, Mihnea Theodor Sîrbu, Silviu Dumitru Pavăl and Paul Dan Sîrbu

Life 2026, 16(2), 336; https://doi.org/10.3390/life16020336 (registering DOI) - 15 Feb 2026

Abstract

Fractures of the pelvic ring are among the most severe injuries in orthopaedic practice and Tile type C lesions are characterized by complete disruption of the posterior arch with both vertical and rotational instability. The optimal construct for posterior ring fixation remains a [...] Read more.

Fractures of the pelvic ring are among the most severe injuries in orthopaedic practice and Tile type C lesions are characterized by complete disruption of the posterior arch with both vertical and rotational instability. The optimal construct for posterior ring fixation remains a matter of debate. The aim of this study was to compare, by means of finite element analysis, the biomechanical performance of three different methods of osteosynthesis for Tile type C1.2 pelvic ring fractures: a transiliac plate, one iliosacral screw and two anterior reconstruction plates on the sacroiliac joint. A three-dimensional model of an intact pelvis was reconstructed from computed tomography images of a healthy adult male. A Tile type C1.2 injury pattern was created virtually, and three fixation constructs were designed in Ansys SpaceClaim according to manufacturer specifications. All materials were assumed to be homogeneous, isotropic and linearly elastic. Vertical loads of 400 N and 800 N were applied to the sacral endplate to simulate partial and full weight bearing, while the acetabular regions were constrained to represent standing stance. In this study, mechanical stability was operationally defined as resistance to global displacement under applied vertical load, with lower displacement indicating higher construct stiffness. Construct stiffness, total deformation and von Mises stress were assessed for bone and implants. For both loading conditions, the iliosacral screw construct showed the lowest overall displacement and provided the greatest stiffness. The transiliac plate construct presented larger displacements, whereas the anterior reconstruction plate construct provided intermediate stability with higher stresses at the sacroiliac joint. Among the analyzed constructs, the iliosacral screw provided the greatest stiffness and lowest overall displacement, suggesting superior mechanical performance under vertical loading conditions. Full article

(This article belongs to the Section Physiology and Pathology)

15 pages, 1496 KB

Open AccessSystematic Review

A Meta-Analysis on the Long-Term Impact of Cytoreductive Surgery Plus HIPEC for Ovarian Cancer with Peritoneal Metastasis: Are We on the Right Path?

by Dan Brebu, Mircea Șelaru, Ionut Flaviu Faur, Mihai Cosmin Burta, Ioana Adelina Faur, Amadeus Dobrescu, Ciprian Duță, Vlad Braicu, Andreea-Adriana Neamțu and Danau Răzvan

Life 2026, 16(2), 335; https://doi.org/10.3390/life16020335 (registering DOI) - 14 Feb 2026

Abstract

Background: The benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) in ovarian cancer with peritoneal metastasis remains debated outside selected indications. We performed a systematic review and meta-analysis to quantify survival, perioperative morbidity, and completeness of cytoreduction using study-level data. [...] Read more.

Background: The benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery (CRS) in ovarian cancer with peritoneal metastasis remains debated outside selected indications. We performed a systematic review and meta-analysis to quantify survival, perioperative morbidity, and completeness of cytoreduction using study-level data. Methods: PubMed/MEDLINE, Embase, and Web of Science were searched. Eligible English-language studies included ovarian cancer patients undergoing CRS plus HIPEC and reported at least one of the following: overall survival (OS), progression-free survival (PFS), Grade III–IV complications, or CC-0 rate. Random-effects meta-analyses were conducted using inverse-variance pooling. For HR outcomes, DerSimonian–Laird τ² with Hartung–Knapp confidence intervals was applied. Proportions were pooled using logit transformation (PLOGIT) with random-effects models. Results: Twelve studies (n = 567) were included. Only two studies provided extractable HRs for OS and PFS (n = 217). CRS plus HIPEC was associated with improved OS (HR 0.68, 95% CI 0.52–0.90, p = 0.0023; I² = 0%; prediction interval 0.14–3.34) and improved PFS (HR 0.70, 95% CI 0.31–1.57, p = 0.0007; I² = 0%; prediction interval 0.18–2.66). Across 12 studies (n = 563), the pooled Grade III–IV complication rate was 0.18 (95% CI 0.14–0.22; I² = 16.3%; prediction interval 0.12–0.26). In 10 studies (n = 385), the pooled CC-0 rate was 0.87 (95% CI 0.79–0.92; I² = 46.7%; prediction interval 0.66–0.96). Conclusions: CRS plus HIPEC shows a favorable signal for OS and PFS in the limited HR-eligible evidence and appears feasible, with a pooled severe complication rate of ~18% and high CC-0 rates. Current data support HIPEC primarily as a targeted intensification strategy in carefully selected patients, while broader adoption requires additional randomized, context-specific evidence. Full article

(This article belongs to the Section Medical Research)

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12 pages, 247 KB

Open AccessArticle

Which Training Is More Effective in Post-COVID-19 Geriatric Patients with COPD: Cycle Ergometer Interval Training or Continuous Training?

by Katarzyna Bogacz, Jacek Łuniewski, Anna Szczegielniak, Danuta Lietz-Kijak and Jan Szczegielniak

Life 2026, 16(2), 334; https://doi.org/10.3390/life16020334 (registering DOI) - 14 Feb 2026

Abstract

Introduction: Respiratory rehabilitation programs for geriatric patients with chronic obstructive pulmonary disease (COPD) after COVID-19 require a precise assessment of needs and an individualized approach. However, there is a lack of specific recommendations for aerobic training in this patient group. Objective: The study [...] Read more.

Introduction: Respiratory rehabilitation programs for geriatric patients with chronic obstructive pulmonary disease (COPD) after COVID-19 require a precise assessment of needs and an individualized approach. However, there is a lack of specific recommendations for aerobic training in this patient group. Objective: The study aimed to compare two types of aerobic training—continuous and interval—and to determine which one is more effective and should be included in the respiratory rehabilitation program for geriatric patients with COPD after COVID-19. Methods: Of the 480 patients examined, 80 were included in the study. All patients underwent exercise tolerance tests (6-Minute Walk Test—6MWT) and functional performance tests (get-up-and-go test—TUG) before and after a 3-week intensive respiratory rehabilitation program. Results: Both types of training—interval and continuous—contributed to improved exercise tolerance and functional fitness in patients. However, analysis of the differences between the groups showed that continuous training with increasing exercise intensity resulted in significantly greater improvements in distance covered during the 6MWT, energy expenditure (METs), and TUG test time (p < 0.05). Conclusions: Continuous training on a cycle ergometer is more effective in the rehabilitation of geriatric patients with COPD after COVID-19 and should be included in therapeutic programs. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

2 pages, 546 KB

Open AccessCorrection

Correction: Assani et al. Beyond HOMA-IR: Comparative Evaluation of Insulin Resistance and Anthropometric Indices Across Prediabetes and Type 2 Diabetes Mellitus in Metabolic Syndrome Patients. Life 2025, 15, 1845

by Mohamed-Zakaria Assani, Lidia Boldeanu, Anda Lorena Dijmărescu, Daniel Cosmin Caragea, Ionela Mihaela Vladu, Diana Clenciu, Adina Mitrea, Alexandra-Ștefania Stroe-Ionescu, Mariana-Emilia Caragea, Isabela Siloși and Mihail Virgil Boldeanu

Life 2026, 16(2), 333; https://doi.org/10.3390/life16020333 (registering DOI) - 14 Feb 2026

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Endocrinology and Metabolic Syndrome: Epidemiology)

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9 pages, 731 KB

Open AccessSystematic Review

Standalone Transoral Robotic Surgery for Obstructive Sleep Apnoea: A Systematic Literature Review of Clinical Outcomes

by Konstantinos Chaidas and Stavroula Mouratidou

Life 2026, 16(2), 332; https://doi.org/10.3390/life16020332 (registering DOI) - 14 Feb 2026

Abstract

Transoral robotic surgery (TORS) offers a targeted surgical option for addressing base of tongue (BOT) and epiglottic obstruction in selected obstructive sleep apnoea (OSA) cases; however, most published evidence evaluates TORS within multilevel approaches, limiting understanding of single-level outcomes. A PRISMA-guided systematic review [...] Read more.

Transoral robotic surgery (TORS) offers a targeted surgical option for addressing base of tongue (BOT) and epiglottic obstruction in selected obstructive sleep apnoea (OSA) cases; however, most published evidence evaluates TORS within multilevel approaches, limiting understanding of single-level outcomes. A PRISMA-guided systematic review of PubMed, Embase, and Central Cochrane was conducted from inception to March 2025, aiming to evaluate objective sleep outcomes and patient-reported measures following single-level TORS BOT surgery. Inclusion criteria were adult patients with moderate-to-severe OSA and CPAP failure/intolerance, with evidence of BOT hypertrophy. Of 219 screened records, five studies met the inclusion criteria with 105 patients. Eighty-six (81.9%) were male with a combined mean age of 45.2 years and BMI of 28.2 kg/m². Combined mean AHI improved from 34.2 preoperatively to 14.7 events/hour postoperatively. Reported surgical success ranged from 54.2% to 100%. Where reported, ESS improved postoperatively with a combined mean reduction from 13 to 4.5. Most commonly reported complications were dysgeusia (n = 16, 15.2%), dysphagia/odynophagia (n = 14, 13.3%), and postoperative bleeding (n = 10, 9.5%). Single-level TORS BOT appears to improve objective and subjective outcomes in carefully selected patients, although heterogeneity and inconsistency of reported outcomes limit definitive conclusions and highlight the need for standardised outcome reporting and follow-up. Full article

(This article belongs to the Special Issue Update on Obstructive Sleep Apnea (OSA))

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16 pages, 774 KB

Open AccessArticle

Early Changes in Renal Function as Predictors of In-Hospital Mortality in COVID-19 Patients

by Nicu Olariu, Nilima Rajpal Kundnani, Simona Ruxanda Dragan, Luciana-Elena Marc, Victor Buciu, Delia Mira Berceanu Vaduva, Andreas Valcovici, Ioana Adela Ratiu, Petru Bucuras and Adelina Mihaescu

Life 2026, 16(2), 331; https://doi.org/10.3390/life16020331 (registering DOI) - 14 Feb 2026

Abstract

Background: Acute kidney injury (AKI) is a frequent and prognostically relevant complication of COVID-19. However, reliance on static creatinine values or binary AKI definitions may overlook clinically meaningful early renal dynamics. We evaluated whether early renal function trajectories within the first 24–48 h [...] Read more.

Background: Acute kidney injury (AKI) is a frequent and prognostically relevant complication of COVID-19. However, reliance on static creatinine values or binary AKI definitions may overlook clinically meaningful early renal dynamics. We evaluated whether early renal function trajectories within the first 24–48 h of hospitalization provide incremental prognostic information. Methods: We conducted a retrospective, single-center cohort study of adults hospitalized with laboratory-confirmed COVID-19 between December 2020 and December 2021. Early renal function patterns were defined using KDIGO-based changes in serum creatinine between admission and 24–48 h, classifying patients as stable, early improvement, or early deterioration. The primary outcome was in-hospital mortality. Multivariable logistic regression adjusted for age, sex, chronic kidney disease, comorbidities, inflammatory burden (C-reactive protein), nutritional status (albumin), pulmonary involvement, and treatment variables. Results: Among 721 patients, 65.2% had stable renal function, 22.5% had early improvement, and 12.3% had early deterioration. In-hospital mortality differed significantly across dynamic patterns (p = 0.007). Mortality was lowest in the stable group (35.1%) and higher in both early improvement (48.1%) and early deterioration (44.9%). After multivariable adjustment, early improvement remained independently associated with higher in-hospital mortality compared with stable renal function (adjusted OR 1.53, 95% CI 1.03–2.28), while early deterioration showed a directionally similar but non-significant association. Early improvement was also associated with higher AKI burden and increased need for acute de novo hemodialysis. Conclusions: Early renal function change patterns within the first 24–48 h of hospitalization carry prognostic value beyond static creatinine measures. Apparent early creatinine improvement may reflect recovery from prior injury or systemic instability rather than true renal recovery, identifying a subgroup at heightened risk. Classification based on early renal function assessment may enhance early risk stratification in hospitalized patients with COVID-19. Full article

(This article belongs to the Section Physiology and Pathology)

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12 pages, 1087 KB

Open AccessSystematic Review

Fats and Facts: A Meta-Analysis of Lipid Biomarkers in Endometrial Cancer

by Ioana Adelina Clim, Ionut Flaviu Faur, Catalin Prodan-Barbulescu, Andreea-Adriana Neamtu, Paul Pasca, Cosmin Burta, Sergiu Florin Bara, Dan Brebu, Vlad Braicu, Ciprian Duta, Bogdan Totolici, Carmen Neamtu and Amadeus Dobrescu

Life 2026, 16(2), 330; https://doi.org/10.3390/life16020330 (registering DOI) - 14 Feb 2026

Abstract

Background: Endometrial cancer (EC) represents one of the most prevalent gynecological malignancies worldwide, with increasing incidence rates attributed to rising obesity, metabolic syndrome, and demographic aging. Recent evidence suggests that dyslipidemia, including elevated triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and reduced high-density lipoprotein [...] Read more.

Background: Endometrial cancer (EC) represents one of the most prevalent gynecological malignancies worldwide, with increasing incidence rates attributed to rising obesity, metabolic syndrome, and demographic aging. Recent evidence suggests that dyslipidemia, including elevated triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and reduced high-density lipoprotein cholesterol (HDL-C), may have a significant role in the pathogenesis of EC through inflammatory, oxidative stress, and hormonal mechanisms. Objective: This meta-analysis aims to systematically evaluate the association between serum lipid biomarkers and endometrial cancer risk by synthesizing quantitative data from observational studies. Methods: We conducted a comprehensive search of five electronic databases (PubMed, Web of Science, Scopus, EMBASE, and Cochrane) to identify studies examining lipid biomarkers in patients with EC compared to healthy controls. After screening 639 articles and applying rigorous inclusion/exclusion criteria, six studies were selected for final analysis. The standardized mean differences (SMD) were calculated with 95% confidence intervals using random-effects and fixed-effects models, considering heterogeneity assessed by the I² statistic. Publication bias was evaluated using funnel plots and Egger’s regression test. Results: The meta-analysis revealed significantly elevated TG levels in EC patients compared to controls (SMD +0.87, 95% CI [+0.65, +1.10]), markedly reduced HDL-C levels (SMD −0.92, 95% CI [−1.15, −0.69]), and increased LDL-C levels (SMD +0.74, 95% CI [+0.50, +0.98]). The heterogeneity was moderate to substantial, with an I² ranging from 49% to 62%. Subgroup analyses demonstrated stronger associations in Type I EC and obese patients (BMI > 30 kg/m²). Conclusions: This meta-analysis establishes a significant association between dyslipidemia and endometrial cancer risk, with elevated triglycerides and LDL-C conferring increased risk while HDL-C appears protective. These findings support the integration of lipid profiling into EC risk assessment protocols and suggest the potential preventive value of lipid-modulating interventions. Further studies are needed to establish causality and evaluate therapeutic applications. Full article

(This article belongs to the Section Medical Research)

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20 pages, 7061 KB

Open AccessArticle

Histological and Inflammatory Changes in Thyroid Glands and Early Growth Outcomes in Offspring of Rats Exposed to Ambient Air Pollution near a Petrochemical Complex: A Preliminary Study

by Maria Angela Zaccarelli-Marino, Nuha A. Dsouki, Rodrigo P. de Carvalho, Juliana M. Veridiano and Monica A. Sato

Life 2026, 16(2), 329; https://doi.org/10.3390/life16020329 - 13 Feb 2026

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Abstract

Background: Environmental agents can disrupt thyroid function at several levels, including the synthesis, action, and excretion of thyroid hormones, and an inadequate concentration of thyroid hormones affects almost all organs and systems. Objective: The present study aimed to evaluate the histology and presence [...] Read more.

Background: Environmental agents can disrupt thyroid function at several levels, including the synthesis, action, and excretion of thyroid hormones, and an inadequate concentration of thyroid hormones affects almost all organs and systems. Objective: The present study aimed to evaluate the histology and presence of the cytokines TNFα, IL-6, and IL-10 in the thyroid gland by immunohistochemical labeling, as well as the body weight and craniocaudal length of pups of Wistar rats exposed to ambient air in the vicinity of the Capuava Petrochemical Complex (CPC), located in the Santo André and Mauá cities, at São Paulo State, Brazil. Methods: This study used Wistar rats between 14 and 16 weeks of age, distributed in couples, that were exposed to pollution from the CPC located in the regions of Santo André and Mauá, Sao Paulo State, Brazil. One couple was positioned 600 m (SS1), and another was 1000 m (SS2) from the CPC, while the control group was kept at the animal research facility of the Physiology Laboratory of the FMABC University Center, Santo André. After mating, the resulting offspring were monitored for four weeks, with their body weight and craniocaudal length measured weekly. Subsequently, the offspring’s thyroid glands were histologically analyzed using H&E staining and immunohistochemistry to detect the presence of inflammatory cytokines (TNF-α, IL-6, and IL-10). Results: In the SS1 group, the thyroid glands showed follicular heterogeneity with macrofollicles and numerous microfollicles without colloid, lined by flattened epithelial cells. In these thyroid follicles, there was intense TNFα (p = 0.002) staining, slight IL-6 staining (p = 0.042), and significantly stronger staining for IL-10 (p = 0.013) compared to that in the control group. This group also had a significantly lower body weight than the control animals on the 6th, 13th, and 20th days of life. In the SS2 group, the thyroids presented an architecture dominated by microfollicles without colloid as well as inflammatory cells in the colloid of some follicles. Immunohistochemistry revealed intense pan-follicular TNFα (p = 0.002) staining, with additional cytoplasmic staining of IL-6 (p = 0.040) and IL-10 (p = 0.006). The SS2 group also showed a more pronounced deficit compared to the SS1 group in terms of birth weight. The cranial–caudal length was shorter on the 13th and 20th days of life in the SS1 and SS2 groups compared to the control group. Conclusions: The results indicate that proximity of rats to the CPC was a determining factor in the development of histological abnormalities and increases in inflammatory cytokine markers in the thyroid glands of the offspring. In addition, the offspring born near the CPC had lower birth weights and shorter craniocaudal lengths compared to the animals in the control group. Full article

(This article belongs to the Section Physiology and Pathology)

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23 pages, 5744 KB

Open AccessArticle

Improving the Prediction of Radiation Pneumonitis: Leveraging Radiomics and Dosiomics Within IDLSS Lung Subregions

by Tsair-Fwu Lee, Wen-Ping Yun, Ling-Chuan Chang-Chien, Hung-Yu Chang, Yi-Lun Liao, Ya-Shin Kuan, Chiu-Feng Chiu, Cheng-Shie Wuu, Yang-Wei Hsieh, Liyun Chang, Yu-Chang Hu, Yu-Wei Lin and Pei-Ju Chao

Life 2026, 16(2), 328; https://doi.org/10.3390/life16020328 - 13 Feb 2026

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Abstract

Purpose: This study develops a predictive model for radiation pneumonitis (RP) risk in lung cancer patients after volume-modulated arc therapy (VMAT) that leverages high-dimensional dosiomics and dose–volume histogram (DVH) features within IDLSS (incremental-dose interval-based lung subregion) lung subregions. Methods: We retrospectively analyzed data [...] Read more.

Purpose: This study develops a predictive model for radiation pneumonitis (RP) risk in lung cancer patients after volume-modulated arc therapy (VMAT) that leverages high-dimensional dosiomics and dose–volume histogram (DVH) features within IDLSS (incremental-dose interval-based lung subregion) lung subregions. Methods: We retrospectively analyzed data from 136 lung cancer patients treated with VMAT between 2015 and 2022, including 39 patients who developed RP greater than Grade 2. Using the IDLSS method, seven regions of interest (ROIs), including the Planning Target Volume (PTV), normal lung, and five subdivided lung areas, were delineated on pretreatment Computed Tomography (CT) images. DVH, radiomics, and dosiomics features were extracted from these ROIs and organized into nine distinct feature sets. A comprehensive pipeline was applied, integrating IDLSS-defined lung subregions, high-dimensional dosiomics features, LASSO-based feature selection, and SMOTE oversampling to address class imbalance in the training data. Logistic regression, random forest, and feedforward neural networks were constructed and optimized via tenfold cross-validation. Model performance across different feature sets was evaluated via the average AUC, F1 score, and other performance metrics. Results: LASSO regression revealed that BMI and volume within the 5–10 Gy and 10–20 Gy lung subregions were significant predictors of RP. The performance evaluation demonstrated that the dosiomics features consistently outperformed the DVH features across the models. Combining radiomics and dosiomics achieved the highest predictive accuracy (AUC = 0.91, ACC = 0.89, NPV = 0.95, PPV = 0.78, F1 score = 0.82, sensitivity = 0.88, specificity = 0.90). Applying SMOTE during training significantly improved sensitivity without compromising specificity, confirming the value of balancing strategies in enhancing model performance. Incorporating all the features together did not provide additional performance gains. Conclusions: Integrating radiomics and dosiomics features extracted from IDLSS-defined lung subregions significantly enhances the ability to predict RP after VMAT, surpassing traditional DVH metrics. The substantial contribution of dosiomics features highlights the importance of spatial dose heterogeneity in RP risk assessment. Full article

(This article belongs to the Special Issue Advanced Technologies and Clinical Practice of Cancer Radiotherapy)

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39 pages, 2256 KB

Open AccessReview

From Exposure to Atherosclerosis: Mechanistic Insights into Phthalate-Driven Ischemic Heart Disease and Prevention Strategies

by Francesca Gorini, Alessandro Tonacci, Mariangela Palazzo and Andrea Borghini

Life 2026, 16(2), 327; https://doi.org/10.3390/life16020327 - 13 Feb 2026

Viewed by 44

Abstract

Despite decades of interventions targeting modifiable risk factors to reduce the burden of cardiovascular disease, ischemic heart disease (IHD) remains the leading cause of mortality and the second leading cause of disability-adjusted life-years worldwide. Growing evidence suggests that phthalates–plasticizers widely used in consumer [...] Read more.

Despite decades of interventions targeting modifiable risk factors to reduce the burden of cardiovascular disease, ischemic heart disease (IHD) remains the leading cause of mortality and the second leading cause of disability-adjusted life-years worldwide. Growing evidence suggests that phthalates–plasticizers widely used in consumer products, cosmetics, and medical devices, and therefore ubiquitous across environmental media, may contribute to IHD development. Epidemiological studies have reported associations between phthalate exposure and multiple markers of atherosclerosis, the pathological hallmark of IHD, with or without mediation by traditional cardiovascular risk factors. Experimental models support these findings, showing that phthalates can induce oxidative stress, mitochondrial dysfunction, apoptosis, lipid accumulation, and epigenetic alterations, all of which promote endothelial damage and atherogenesis. In this review, we synthesize current epidemiological findings linking phthalate exposure to IHD, describe the main cellular and molecular mechanisms involved, and outline research gaps and regulatory perspectives. We also discuss how novel analytical frameworks—including artificial intelligence—may enhance the integration of environmental, clinical, and molecular data to advance risk prediction and prevention strategies. Full article

(This article belongs to the Special Issue Environment, Genetics, and Cardiovascular Disease)

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16 pages, 588 KB

Open AccessArticle

Microvascular Dysfunction in Patients with Prediabetes: Novel Methods Identify Impaired Microcirculation

by Stamatina Lamprou, Nikolaos Evangelidis, Nikolaos Koletsos, Ioanna Zografou, Anastasia Stoimeni, Gesthimani Mintziori, Vasileios Gkolias, Christina-Maria Trakatelli, Christos Savopoulos, Michael Doumas and Areti Triantafyllou

Life 2026, 16(2), 326; https://doi.org/10.3390/life16020326 - 13 Feb 2026

Viewed by 47

Abstract

Background: Skin and myocardial microvascular dysfunction in prediabetes remains underexplored, and limited studies have investigated the microcirculation in prediabetes in multiple vascular beds. This study aimed to examine microvascular alterations in patients with prediabetes, patients with type 2 diabetes mellitus (DM), and normoglycemic [...] Read more.

Background: Skin and myocardial microvascular dysfunction in prediabetes remains underexplored, and limited studies have investigated the microcirculation in prediabetes in multiple vascular beds. This study aimed to examine microvascular alterations in patients with prediabetes, patients with type 2 diabetes mellitus (DM), and normoglycemic controls without established cardiovascular disease (CVD). Methods: In this cross-sectional study, the microcirculation was assessed using established and novel noninvasive techniques. The skin microvascular reactivity was evaluated using laser speckle contrast analysis (LASCA). The myocardial perfusion was assessed by the subendocardial viability ratio (SEVR). The retinal microvasculature was evaluated using digital nonmydriatic fundus photography, the renal microvascular damage through the urinary albumin-to-creatinine ratio (ACR), and the peripheral vasculopathy by the augmentation index (AIx). Results: Sixty-seven participants were included (22 controls, 24 with prediabetes, 21 with DM; aged: 55.9 ± 9.4 years). Patients with prediabetes and DM showed significantly reduced baseline-to-peak skin flux responses in LASCA compared with controls (p = 0.006), and lower SEVR values (p = 0.001). Moreover, no significant differences were identified in the retinal, renal, or peripheral microvascular indices. In multivariate analysis, systolic blood pressure and glucose were independently associated with skin microvascular dysfunction, while the heart rate and arteriovenous ratio were associated with the SEVR. Conclusions: In this cross-sectional study, impaired skin and myocardial microvascular function were observed in patients with prediabetes in the absence of overt CVD. These findings suggest that LASCA and the SEVR may serve as sensitive markers for the detection of early, subclinical microvascular dysfunction in prediabetes. Full article

(This article belongs to the Special Issue Microvascular Research: Advances and Perspectives)

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19 pages, 3479 KB

Open AccessArticle

Effects of Dexmedetomidine Treatment After Cerebral Ischemia/Reperfusion on Apoptosis and Oxidative Stress: A Rat Model

by Mahir Kuyumcu and Eda Yıldızhan

Life 2026, 16(2), 325; https://doi.org/10.3390/life16020325 - 13 Feb 2026

Viewed by 38

Abstract

Objectives: Cerebral ischemia/reperfusion (IR) injury is characterized by excessive oxidative stress and activation of apoptotic pathways, which play a central role in neuronal loss and poor neurological outcomes. Modulation of these mechanisms represents a clinically relevant strategy for neuroprotection. This study aimed to [...] Read more.

Objectives: Cerebral ischemia/reperfusion (IR) injury is characterized by excessive oxidative stress and activation of apoptotic pathways, which play a central role in neuronal loss and poor neurological outcomes. Modulation of these mechanisms represents a clinically relevant strategy for neuroprotection. This study aimed to investigate the neuroprotective effects of dexmedetomidine (Dex) on oxidative stress, apoptotic signaling, and neuronal integrity in an experimental rat model of cerebral IR injury. Materials and Methods: Female Wistar rats were assigned to control, IR, and IR+Dex groups. Transient cerebral ischemia was induced for 45 min followed by 2 h of reperfusion. Oxidative stress was evaluated using serum antioxidant enzyme activities (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GSH-Px]), total oxidant and antioxidant status (TOS, TAS), and lipid peroxidation levels (malondialdehyde [MDA]). Apoptotic signaling was assessed by histopathological examination, transmission electron microscopy, and immunohistochemical analysis of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and apoptotic peptidase activating factor-1 (APAF-1) expression, quantitatively evaluated using QuPath with statistical comparison between groups. Bioinformatic network analysis and molecular docking were performed to explore predicted interactions between Dex and apoptosis-related proteins. Results: Cerebral IR induced a marked oxidative imbalance, characterized by reduced antioxidant enzyme activities and increased lipid peroxidation. Dex treatment partially improved antioxidant capacity and reduced oxidative stress parameters. Histopathological and ultrastructural analyses demonstrated severe neuronal degeneration following IR, whereas Dex-treated rats exhibited attenuated neuronal damage and improved ultrastructural preservation. Immunohistochemical analysis showed increased Bax and APAF-1 expression and reduced Bcl-2 expression after IR; these alterations were significantly modulated toward control levels in the IR+Dex group. Bioinformatic analysis identified apoptosis-related pathways, including apoptosis, p53 signaling, and necroptosis, as significantly enriched, while molecular docking suggested stable predicted interactions between Dex and key apoptotic regulators. Conclusions: In this experimental rat cerebral IR model, Dex exerted partial but significant neuroprotective effects by attenuating oxidative stress, modulating apoptotic marker expression, and preserving neuronal morphology. These findings support the potential role of Dex as a neuroprotective agent in ischemia-related brain injury, warranting further translational investigation. Full article

(This article belongs to the Special Issue Neurological Diseases: Prevention, Diagnostics, Treatment and Rehabilitation)

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12 pages, 645 KB

Open AccessArticle

Transthoracic Echocardiography as a Tool for Early Detection of Atrial Fibrillation in Patients Receiving Ibrutinib

by Vittoria Gammaldi, Martina Pucci, Francesca La Rocca, Pasquale Megaro, Daniele Paoletta, Mariateresa Pontoriero, Luca Maria Capece, Roberto Luise, Marina Iacono and Roberta Esposito

Life 2026, 16(2), 324; https://doi.org/10.3390/life16020324 - 13 Feb 2026

Viewed by 41

Abstract

Background: Bruton’s tyrosine kinase inhibitors, particularly ibrutinib, have improved outcomes in patients with chronic lymphocytic leukemia but are associated with an increased risk of atrial fibrillation. The early identification of patients with increased susceptibility to atrial fibrillation remains a major challenge in [...] Read more.

Background: Bruton’s tyrosine kinase inhibitors, particularly ibrutinib, have improved outcomes in patients with chronic lymphocytic leukemia but are associated with an increased risk of atrial fibrillation. The early identification of patients with increased susceptibility to atrial fibrillation remains a major challenge in cardio-oncology. Methods: This prospective pilot study included 45 patients with chronic lymphocytic leukemia treated with ibrutinib. All patients underwent comprehensive transthoracic echocardiography at baseline and after 6 months. Left atrial structure and function were assessed, with particular emphasis on speckle-tracking-derived left atrial strain parameters, including peak atrial longitudinal strain and peak atrial contraction strain. Results: At follow-up, a modest but significant increase in indexed left atrial volume was observed, while left atrial functional parameters remained stable. Patients who developed atrial fibrillation showed significantly lower baseline Peak Atrial Contraction Strain values compared with those who remained in sinus rhythm, whereas no significant differences in Peak Atrial Longitudinal Strain were detected. Conclusions: Ibrutinib-related atrial fibrillation appears to be driven primarily by pre-existing atrial vulnerability rather than early drug-induced atrial dysfunction. The baseline impairment of left atrial contractile function may represent a candidate echocardiographic marker of atrial functional vulnerability and may inform cardiovascular surveillance and monitoring strategies in patients treated with ibrutinib. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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16 pages, 262 KB

Open AccessReview

Cardiopulmonary Complications in Obese Patients with Gynecologic Cancer: A Narrative Review

by Maria Fanaki, Nikolaos Thomakos, Vasileios Lygizos, Antonia Varthaliti, Dimitrios Haidopoulos, Dimitrios Efthimios Vlachos and Vasileios Pergialiotis

Life 2026, 16(2), 323; https://doi.org/10.3390/life16020323 - 13 Feb 2026

Viewed by 69

Abstract

Gynecologic cancer is a major global health burden, and improvements in screening, surgical techniques, and systemic therapies have significantly prolonged survival. As a result, cardiopulmonary disease has emerged as a leading non-cancer cause of morbidity and mortality among gynecologic cancer survivors. Obesity, which [...] Read more.

Gynecologic cancer is a major global health burden, and improvements in screening, surgical techniques, and systemic therapies have significantly prolonged survival. As a result, cardiopulmonary disease has emerged as a leading non-cancer cause of morbidity and mortality among gynecologic cancer survivors. Obesity, which is highly prevalent in this population, substantially increases cardiopulmonary risk by contributing to metabolic syndrome, cardiovascular disease, chronic inflammation, and reduced cardiopulmonary reserve. This narrative review summarizes current evidence on the epidemiology, pathophysiological mechanisms, and clinical spectrum of cardiopulmonary complications in obese patients with gynecologic malignancy. We review the contribution of obesity-related metabolic and endothelial dysfunction, cancer-associated hypercoagulability, and treatment-related toxicities, with particular emphasis on complications arising from surgery, chemotherapy, and radiotherapy. Epidemiologic data demonstrate a markedly increased burden of cardiovascular and pulmonary disease in obese gynecologic cancer patients, including higher rates of myocardial injury, heart failure, venous thromboembolism, and postoperative respiratory complications. Surgical treatment, although central to oncologic management, imposes substantial cardiopulmonary stress, placing obese patients at heightened perioperative risk. Future studies should focus on preoperative risk stratification, optimization of obesity-related comorbidities, and multidisciplinary perioperative management, including enhanced recovery pathways, as well as appropriate use of high-dependency or intensive care monitoring to reduce morbidity and improve both oncologic and long-term non-oncologic outcomes in this population. Full article

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

19 pages, 2100 KB

Open AccessReview

Nano-Enabled Herbal Remedies for Malaria Treatment: A Review of Recent Advances

by Chang Xu, Arooj Fatima, Mahreen Fatima, Amjad Islam Aqib, Tean Zaheer, Safia Obaidur Rab, Mohd Saeed, Zeeshan Arif and Kun Li

Life 2026, 16(2), 322; https://doi.org/10.3390/life16020322 - 12 Feb 2026

Viewed by 114

Abstract

Malaria has long been a significant global health concern, listed as a high-priority disease by several global health agencies, despite of several control measures have been put in place. Most widely utilized treatment options for malaria include chloroquine, artemisinin-based combination therapy (ACT), and [...] Read more.

Malaria has long been a significant global health concern, listed as a high-priority disease by several global health agencies, despite of several control measures have been put in place. Most widely utilized treatment options for malaria include chloroquine, artemisinin-based combination therapy (ACT), and quinine. However, challenges, such as drug resistance, misdiagnosis, and limited treatment efficacy remain major concerns. Despite ongoing efforts, the development of an effective malaria vaccine is still debatable. Many existing malaria treatments have drawbacks, such as low water solubility, poor bioavailability, and a rise in drug-resistant parasites owing to their non-judicious use, which contributes to increased malaria cases and fatalities. Nanotechnology presents a promising approach to safer and more effective malaria therapy and control. Nanoparticles offer several advantages over conventional treatments, including high drug-loading capacity, targeted delivery, improved biocompatibility, and reduced toxicity in host cells. Green nanotechnology-based antimalarial therapies have demonstrated potential therapeutic benefits, enhanced safety, and cost-effectiveness compared to traditional treatments, ultimately improving patient compliance and treatment outcomes. In this review paper, we discussed non-conventional breakpoints in the malarial life cycle, traditional herbal remedies for malaria, and nanoparticle-based delivery systems. Additionally, we reviewed the antimalarial effects of herbal nano-formulations, their pharmacological and therapeutic potential, drug-resistant malaria, preventive strategies, vector control using green nanomaterials, and the challenges associated with plant-based nanotechnologies. This review suggests nanotechnology-based therapeutics as promising candidates to treat malaria with significant room for applications and commercialization potential in the longer run. Full article

(This article belongs to the Special Issue The 15th Anniversary of Life—New Trends in Animal Health Science)

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13 pages, 759 KB

Open AccessArticle

Effect of Oxidative Stress Intensity on Inflammatory, Bone Turnover, and Haemostasis Biomarkers in Patients with Spinal Osteoarthritis

by Milan Mirković, Jelena Vekić, Nataša Bogavac-Stanojević, Jelena Kotur-Stevuljević, Neda Milinković, Anđelka Milić, Sanja Mirković, Ankica Vujović, Zoran Baščarević and Biljana Božić Nedeljković

Life 2026, 16(2), 321; https://doi.org/10.3390/life16020321 - 12 Feb 2026

Viewed by 78

Abstract

Osteoarthritis is associated with chronic inflammation, which contributes to a hypercoagulable state. Oxidative stress may further disrupt homeostatic balance, thereby promoting thrombotic events. This study evaluated the association between biomarkers of oxidative stress, inflammation, haemostasis, and bone metabolism in patients with spinal osteoarthritis. [...] Read more.

Osteoarthritis is associated with chronic inflammation, which contributes to a hypercoagulable state. Oxidative stress may further disrupt homeostatic balance, thereby promoting thrombotic events. This study evaluated the association between biomarkers of oxidative stress, inflammation, haemostasis, and bone metabolism in patients with spinal osteoarthritis. A total of 48 patients were included. The levels of inflammatory, bone turnover, haematological, and coagulation biomarkers were determined using standard laboratory methods. Redox status was assessed via prooxidant–antioxidant balance (PAB) and superoxide dismutase (SOD) activity. Patients with elevated PAB showed significantly higher erythrocyte sedimentation rate (ESR) (p = 0.005), alkaline phosphatase (ALP) (p = 0.003) and fibrinogen levels (p = 0.006) and platelet count (p = 0.040), along with lower 25-OH vitamin D levels (p = 0.045) and shortened PT (p = 0.008) and aPTT (p = 0.017). In low oxidative stress states (PAB < 100 U/L), significant correlations were observed among redox, coagulation, and bone turnover markers, whereas in high oxidative stress (PAB ≥ 100 U/L), it was characterised by predominant associations between redox and bone turnover biomarkers. Patients with grade V disc degeneration had a significantly higher probability of elevated D-dimer levels compared to those with grade IV (OR = 5.440; p = 0.009). In addition, elevated D-dimer levels were associated with increased ESR (p = 0.015), IL-6 (p = 0.016) and ALP levels (p = 0.034). The associations between biomarkers of redox status, inflammation, coagulation and bone turnover are influenced by the extent of oxidative stress. Our results suggest that PAB and D-dimer may serve as potential biomarkers for disease severity and thrombotic risk. Further studies are needed to confirm these preliminary findings. Full article

(This article belongs to the Section Medical Research)

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20 pages, 2973 KB

Open AccessArticle

Can Non-Conventional Blood Biomarkers Improve Running Performance Prediction? A Proof of Concept

by Matija Dvorski, Marija Rakovac, Tomislav Kelava, Nataša Kovačić, Darja Flegar, Sara Aničić, Ivo Krešić, Ljiljana Ćulibrk, Filip Koražija, Damjan Dimnjaković and Alan Šućur

Life 2026, 16(2), 320; https://doi.org/10.3390/life16020320 - 12 Feb 2026

Viewed by 89

Abstract

Conventional measures such as maximal oxygen uptake (

\dot{V}

O₂max), although widely regarded as the gold standard, do not fully capture endurance performance. Therefore, this study investigated whether a 2.4 km Cooper test elicits measurable changes in blood-based biomarkers (decorin, [...] Read more.

Conventional measures such as maximal oxygen uptake (

\dot{V}

O₂max), although widely regarded as the gold standard, do not fully capture endurance performance. Therefore, this study investigated whether a 2.4 km Cooper test elicits measurable changes in blood-based biomarkers (decorin, hypoxanthine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), brain-derived neurotrophic factor (BDNF)) and whether integrating these markers may improve performance prediction in a heterogeneous sample of runners. In this cross-sectional observational proof-of-concept study, thirty-three participants completed the 2.4 km Cooper test, with venous blood samples collected at baseline and post-test. Non-parametric statistical tests were used to assess biomarker changes (α = 0.05), with exploratory correlations evaluated using Spearman’s ρ. To examine whether blood-based biomarkers provide information beyond conventional field-based predictors, Ridge regression with leave-one-out cross-validation (LOOCV) was applied to predict 10 km race time in a subsample of 24 participants who completed a 10 km race two weeks later. The Cooper test elicited significant post-test changes in decorin, hypoxanthine, and BDNF (all p < 0.001). Higher post-test decorin (ρ = −0.44, p = 0.010) and hypoxanthine (ρ = −0.37, p = 0.034) were associated with faster Cooper test performance. In Ridge regression analysis, adding post-test decorin to conventional predictors resulted in a minor reduction of 10 km race time prediction error. This study suggests that decorin may provide complementary information to a conventional field-based test in heterogeneous recreational runners. Post-test decorin marginally contributed to 10 km race performance prediction beyond established predictors, though external validation and comparison with directly measured

\dot{V}

O₂max are needed before practical application can be recommended. Full article

(This article belongs to the Special Issue Advances and Applications of Sport Physiology: 2nd Edition)

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13 pages, 345 KB

Open AccessArticle

Arrhythmias as Part of Long COVID Syndrome in Hospitalized Patients That Survived a Severe COVID-19 Infection and the Potential Protective Role of Metformin in These Patients

by Haydee Ninette Morales-Vazquez, David Cardona-Müller, Fernando Grover-Paez, Carlos Gerardo Ramos-Becerra, Ernesto Germán Cardona-Muñoz, Maria Guadalupe Ramos-Zavala, Jaime Carmona-Huerta, Jorge Eduardo Hernandez-del-Rio, Tomas Miranda-Aquino, Christian Gonzalez-Padilla and Christopher Josue Lopez-Gradilla

Life 2026, 16(2), 319; https://doi.org/10.3390/life16020319 - 12 Feb 2026

Viewed by 260

Abstract

Background: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined. Objectives: To assess the prevalence and types of arrhythmias in long COVID patients [...] Read more.

Background: Cardiac arrhythmias are a frequent complication of acute SARS-CoV-2 infection. However, their long-term prevalence and clinical determinants among patients with post-COVID-19 syndrome, especially those previously hospitalized, remain poorly defined. Objectives: To assess the prevalence and types of arrhythmias in long COVID patients following hospitalization and to identify associated clinical risk factors. Methods: In this cross-sectional study, 53 patients previously hospitalized with confirmed COVID-19 were evaluated ≥3 months post-infection. All participants underwent a standardized clinical assessment, 12-lead electrocardiography, and 24 h Holter monitoring. Logistic and Cox regression analyses were performed to identify predictors of arrhythmia. Results: Arrhythmias were identified in 41.5% (n = 22) of patients. Atrial fibrillation (32%) was the most frequent arrhythmia, followed by sinus bradycardia (27%) and sinus tachycardia (18%). Age (OR 1.06, 95% CI 1.01–1.10, p = 0.01) and length of hospital stay (OR 1.1, 95% CI 1.01–1.2, p = 0.04) were independently associated with arrhythmia. Biguanide (metformin) therapy was inversely associated with the occurrence of arrhythmia (Exp(B) = 0.017, p = 0.008). Dyspnea (82.4%) and palpitations (41.5%) were the most commonly reported symptoms. Conclusions: Arrhythmias are common in patients with long COVID following severe disease. Advanced age and prolonged hospitalization are significant risk factors, while biguanide use may offer a protective effect. These findings underscore the need for targeted cardiac surveillance in this population. Full article

(This article belongs to the Special Issue Advances in Cardiac Arrhythmias: Mechanisms, Diagnostics and Therapeutics)

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25 pages, 633 KB

Open AccessReview

5-Aminolevulinic Acid-Based Radiodynamic Therapy for Malignant Gliomas: A Conceptual Framework for Mitochondria-Centered Mechanisms, Target Cell States and Translational Perspectives

by Junkoh Yamamoto

Life 2026, 16(2), 318; https://doi.org/10.3390/life16020318 - 12 Feb 2026

Viewed by 246

Abstract

5-Aminolevulinic acid (5-ALA) is a naturally occurring heme precursor with a favorable safety profile and is widely used for fluorescence-guided resection of malignant gliomas. Exogenous administration of 5-ALA results in the selective intracellular accumulation of protoporphyrin IX (PpIX), predominantly within tumor cell mitochondria, [...] Read more.

5-Aminolevulinic acid (5-ALA) is a naturally occurring heme precursor with a favorable safety profile and is widely used for fluorescence-guided resection of malignant gliomas. Exogenous administration of 5-ALA results in the selective intracellular accumulation of protoporphyrin IX (PpIX), predominantly within tumor cell mitochondria, reflecting tumor-specific alterations in cellular metabolism and heme biosynthetic pathways. Historically, the radiosensitizing potential of 5-ALA was considered limited, as 5-ALA itself is not a porphyrin and intracellular PpIX levels are lower than those achieved with classical porphyrin-based agents, such as hematoporphyrin derivatives or porfimer sodium. Recent experimental and translational studies have challenged this view by demonstrating that the interactions between 5-ALA-induced PpIX and ionizing irradiation elicit biologically significant antitumor effects. This emerging concept has been termed radiodynamic therapy (RDT) and represents a therapeutic paradigm distinct from conventional DNA-centered radiosensitization. Accumulating evidence suggests that 5-ALA-based RDT induces mitochondria-centered oxidative stress through both immediate and delayed reactive oxygen species generation, thereby linking metabolic vulnerability to the radiation response. In this review, we summarize the current mechanistic insights into 5-ALA-based RDT, particularly mitochondrial dysfunction and oxidative stress amplification. We also discuss the translational implications and future perspectives for integrating 5-ALA-based RDT into multimodal treatment strategies for malignant gliomas. Full article

(This article belongs to the Special Issue Advances in 5-Aminolevulinic Acid Applications in Medical and Healthcare)

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15 pages, 1630 KB

Open AccessReview

Light-Controlled Membrane Fusion in Synthetic Cells

by Boying Xu, Adriano Caliari and Jian Xu

Life 2026, 16(2), 317; https://doi.org/10.3390/life16020317 - 12 Feb 2026

Viewed by 75

Abstract

Light-induced membrane fusion has become a pivotal technique for constructing and functionalizing synthetic cells by enabling precise control over membrane merging events. Traditional fusion approaches that rely on chemical, physical, and mechanical stimuli frequently lack both specificity and reversibility, limiting their utility in [...] Read more.

Light-induced membrane fusion has become a pivotal technique for constructing and functionalizing synthetic cells by enabling precise control over membrane merging events. Traditional fusion approaches that rely on chemical, physical, and mechanical stimuli frequently lack both specificity and reversibility, limiting their utility in mimicking dynamic cellular processes. Here, we review advances employing photosensitive molecules and optogenetic tools that facilitate spatiotemporally controlled fusion of lipid and polymer vesicles, enabling dynamic content exchange and membrane remodeling. These approaches have enhanced synthetic cell assembly, molecular transport, and signal transduction, with applications extending to drug delivery and biosensing. Despite challenges in efficiency and biocompatibility, ongoing innovations in photosensitizer design and light activation strategies promise to expand the capabilities of synthetic biology platforms. This work underscores the potential of light-induced fusion to advance the development of intelligent nanomaterials and functional synthetic cellular systems. Full article

(This article belongs to the Section Synthetic Biology and Systems Biology)

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9 pages, 6146 KB

Open AccessCase Report

Transcatheter Correction of Bilateral Partial Anomalous Pulmonary Venous Return with Intrapulmonary Dual Drainage: A Rare Entity

by Dusan Andric, Andrija Pavlovic, Igor Stefanovic, Marko Pavlovic, Maja Trkulja, Maja Bijelic, Milica Kuzmanovic, Jovan Petrovic, Mirko Topalovic, Vojislav Parezanovic and Milan Djukic

Life 2026, 16(2), 316; https://doi.org/10.3390/life16020316 - 12 Feb 2026

Viewed by 105

Abstract

Partial anomalous pulmonary venous return (PAPVR) with dual drainage is a very rare congenital heart anomaly. We report the case of a 6-year-old boy with PAPVR in whom both upper pulmonary veins (PVs) drain anomalously into the systemic venous circulation, while maintaining preserved [...] Read more.

Partial anomalous pulmonary venous return (PAPVR) with dual drainage is a very rare congenital heart anomaly. We report the case of a 6-year-old boy with PAPVR in whom both upper pulmonary veins (PVs) drain anomalously into the systemic venous circulation, while maintaining preserved intrapulmonary collateral venous connections with the remaining pulmonary veins draining into the left atrium. Careful balloon occlusion testing of the anomalous PVs was performed, simultaneously with measurements of pulmonary pressures and control angiography, proving the absence of venous congestion in the upper lung fields during the pulmonary venous phase. Transcatheter occlusion using vascular plugs was safely and successfully performed. Full article

(This article belongs to the Special Issue Pediatric Cardiology Frontiers: Innovations in Diagnosis and Treatment)

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22 pages, 992 KB

Open AccessArticle

Clozapine Mitigates Lipopolysaccharide-Induced Cognitive Dysfunction by Modulating Cholinergic Function, Oxidative Stress, and Apoptotic Signaling in Rats

by Vasudevan Mani and Mohammed A. Almatrafi

Life 2026, 16(2), 315; https://doi.org/10.3390/life16020315 - 12 Feb 2026

Viewed by 107

Abstract

Background: Clozapine (CLZ) is an atypical antipsychotic mainly prescribed for treatment-resistant schizophrenia. Beyond psychotic symptoms, patients often exhibit persistent cognitive impairments across domains such as attention, learning, and memory. The mechanisms by which CLZ may influence cognition and provide neuroprotection are not fully [...] Read more.

Background: Clozapine (CLZ) is an atypical antipsychotic mainly prescribed for treatment-resistant schizophrenia. Beyond psychotic symptoms, patients often exhibit persistent cognitive impairments across domains such as attention, learning, and memory. The mechanisms by which CLZ may influence cognition and provide neuroprotection are not fully elucidated. Accordingly, this study examined how CLZ modulates lipopolysaccharide (LPS)-induced neurotoxicity in rats. Method: Rats were administered LPS to induce cognitive impairment and subsequently treated with CLZ. Behavioral assessments were performed using maze tests (elevated plus-maze (EPM), novel object recognition (NOR), and Y-maze). Biochemical analyses included cholinergic function (acetylcholine (ACh)), neurodegeneration-associated enzymes (glycogen synthase kinase-3 beta (GSK-3β), β-site amyloid precursor protein cleaving enzyme-1 (BACE-1), and dipeptidyl peptidase-4 (DPP-4)), oxidative stress markers (lipid Peroxidation (LPO), catalase, and reduced glutathione (GSH)), and apoptotic proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved Caspase-3 (c-Caspase-3)). Results: CLZ treatment markedly improved performance in EPM, NOR, and Y-maze tasks, indicating recovery of cognitive function in LPS-exposed rats. At the molecular level, CLZ enhanced ACh levels, upregulated the anti-apoptotic protein Bcl-2, and restored antioxidant defenses (catalase and GSH). Conversely, CLZ reduced LPS-induced neurotoxicity by lowering GSK-3β activity, LPO, and pro-apoptotic markers (Bax and c-Caspase-3). Conclusion: The findings demonstrate that CLZ exerts neuroprotective effects in an LPS-induced rat model, improving cognition through modulation of cholinergic transmission, oxidative stress, and apoptosis pathways. These results clarify key mechanistic pathways through which CLZ may exert cognitive benefits and highlight its potential relevance for improving schizophrenia-related cognitive dysfunction. Further molecular studies are warranted to confirm and extend these observations toward clinical translation. Full article

(This article belongs to the Special Issue Transformative Frontiers in Mental Health Treatment: Advances in Neuropsychopharmacology)

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23 pages, 13369 KB

Open AccessHypothesis

Microvascular Genesis of Diseases: From Hypothesis to Theory

by Ruslan A. Nasyrov, Veronika A. Galichina, Anna O. Drobintseva, Daria V. Tonkonog, Elena Yu. Kalinina and Alexandra A. Agafonnikova

Life 2026, 16(2), 314; https://doi.org/10.3390/life16020314 - 11 Feb 2026

Viewed by 145

Abstract

Despite progress in understanding the molecular mechanisms of diseases, the dominant paradigm in explaining pathogenesis remains the concept of a pathogen’s direct damaging effect on parenchymal cells. Based on years of research, the authors of this article propose a revision of traditional views [...] Read more.

Despite progress in understanding the molecular mechanisms of diseases, the dominant paradigm in explaining pathogenesis remains the concept of a pathogen’s direct damaging effect on parenchymal cells. Based on years of research, the authors of this article propose a revision of traditional views on disease pathogenesis. We emphasize the pivotal role of the microvasculature. Existing morphological studies provide insufficient insight into the role of these structures in the development of the pathological process. We conducted a search in international databases to find literary sources current as of December 2025. As an evidence base for the presented concept, we used the results of our own studies published from 1989 to the present. Data from the literature on non-infectious diseases are also separately presented. Our novel data from investigation of infectious and non-infectious diseases demonstrate that even in the initial stages of a pathological process, the microvessels of organs become the primary target of damage. The cascade of pronounced changes in parenchymal cells triggered by this initial event determines the development of the disease. The work examines the cellular and molecular aspects of the interaction between microvessels, pathogens, and the surrounding tissue. The proposed concept provides an objective and fundamentally new explanation for known facts. An important contribution of this concept is its potential to reveal promising directions for further research and for developing innovative approaches to disease therapy. Full article

(This article belongs to the Section Physiology and Pathology)

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11 pages, 2813 KB

Open AccessCase Report

Severe HAPE in a Remote High-Altitude Research Station in Antarctica

by Fanny Larcher, Paul Laforet, Stephane Fraize, Mario Lecca, Riccardo Scipinotti, Gianluca Bianchi Fasani, Salvatore Vagnoni and Sascha Freigang

Life 2026, 16(2), 313; https://doi.org/10.3390/life16020313 - 11 Feb 2026

Viewed by 128

Abstract

Isolated, confined, and extreme environments hold the opportunity to collect unique biomedical data. These often-remote places present specific medical challenges for deployed expeditioners. Here we report a case of acute severe high altitude pulmonary oedema (HAPE) and its management at a remote research [...] Read more.

Isolated, confined, and extreme environments hold the opportunity to collect unique biomedical data. These often-remote places present specific medical challenges for deployed expeditioners. Here we report a case of acute severe high altitude pulmonary oedema (HAPE) and its management at a remote research station in Antarctica. At the beginning of the 2023 summer campaign at Concordia Station (3200 m AMSL), a technician presented with shortness of breath and compromised circulation three days after arrival on site. Immediate diagnostics and medical treatments with high-flow oxygen and the use of a mobile hyperbaric chamber after initial resuscitation were administered. Within a time window of 24 h, evacuation to sea level was organised via aircraft (flight duration 4 h, non-pressurised cabin) inside the mobile hyperbaric chamber. The patient was discharged from medical treatment 48 h later in Christchurch (NZ). We conclude that despite rigorous pre-deployment screening, even experienced expeditioners can develop critical medical conditions that require prompt reaction and rescue. Structured assessment tools can aid in their recognition and management. Full article

(This article belongs to the Section Medical Research)

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13 pages, 271 KB

Open AccessArticle

Concomitant Venous Disease in Patients with Advanced Peripheral Arterial Disease: A Patient- and Limb-Level Analysis

by Daniela Marinescu, Laurențiu Augustus Barbu, Tiberiu Stefăniță Țenea Cojan, Ștefan Pătrascu, Marius Bică, Răzvan Alexandru Marinescu, Sarmis Marian Săndulescu, Valeriu Șurlin and Ana-Maria Ciurea

Life 2026, 16(2), 312; https://doi.org/10.3390/life16020312 - 11 Feb 2026

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Abstract

Background: Advanced stages of peripheral arterial disease, particularly chronic limb-threatening ischemia, are characterized by unfavorable limb outcomes and a substantial risk of major amputation. Clinical evaluation traditionally focuses on arterial obstruction; however, venous dysfunction may coexist and contribute to local limb pathophysiology in [...] Read more.

Background: Advanced stages of peripheral arterial disease, particularly chronic limb-threatening ischemia, are characterized by unfavorable limb outcomes and a substantial risk of major amputation. Clinical evaluation traditionally focuses on arterial obstruction; however, venous dysfunction may coexist and contribute to local limb pathophysiology in advanced PAD, remaining insufficiently recognized in routine practice. Methods: We performed a retrospective cohort analysis of consecutive patients with advanced peripheral arterial disease managed at the First Surgical Clinic of the Emergency County Clinical Hospital of Craiova over a five-year period (January 2020 to December 2024). Venous disease was defined using a clinically oriented composite definition incorporating imaging-confirmed venous pathology, prior deep venous thrombosis, and persistent lower-limb edema attributable to venous dysfunction. Arterial disease severity was assessed using multimodal imaging. Analyses were performed at both patient and limb levels to evaluate associations between venous disease, arterial severity markers, and clinical outcomes. Results: Among 241 patients (482 limbs), concomitant venous disease was identified in 68.9% at the patient level and was predominantly unilateral. At the limb level, venous disease was significantly associated with markers of severe arterial involvement, including inflow disease, higher segment occlusion scores, impaired tibial runoff, and absence of a patent pedal arch. Despite greater arterial severity, patients with venous disease exhibited a lower unadjusted rate of major amputation compared with those without venous involvement. Conclusions: Concomitant venous disease is highly prevalent in patients with advanced PAD and is closely linked to arterial disease severity. These findings suggest that venous dysfunction represents an integral component of advanced limb-threatening ischemia rather than an isolated comorbidity. Incorporating clinically oriented venous assessment may improve understanding of limb pathophysiology and support a more integrated arterio-venous approach to advanced PAD management. Full article

(This article belongs to the Special Issue Advances in Vascular Health and Metabolism)

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Open AccessArticle

Increased Risk of Recurrent Ischemic Stroke in Male Patients Taking Medications for Benign Prostatic Hyperplasia

by Chun-Gu Cheng, Chun-Fang Chen, Wu-Chien Chien, Chia-Chao Wu, Hung-Wen Chiu, Fei-Hung Hung, Hung-Pin Peng, Chi-Hsiang Chung and Chun-An Cheng

Life 2026, 16(2), 311; https://doi.org/10.3390/life16020311 - 11 Feb 2026

Viewed by 195

Abstract

Background: Patients with benign prostatic hyperplasia (BPH) have an increased risk of developing cardiovascular disease. Taking alpha-1 blockers is associated with an increased risk of major adverse cardiovascular events. Patients suffering from ischemic stroke (IS) may develop baroreflex and parasympathetic dysfunction-induced cerebral autoregulation [...] Read more.

Background: Patients with benign prostatic hyperplasia (BPH) have an increased risk of developing cardiovascular disease. Taking alpha-1 blockers is associated with an increased risk of major adverse cardiovascular events. Patients suffering from ischemic stroke (IS) may develop baroreflex and parasympathetic dysfunction-induced cerebral autoregulation impairment. The relationship between pharmacotherapy for BPH and the risk of recurrent IS remains unclear. The purpose of this study was to determine whether medications for BPH increase the risk of recurrent IS. Methods: This is a retrospective cohort study. Data from patients diagnosed with IS between 2000 and 2015 was collected from Taiwan National Health Insurance Database. Newly diagnosed IS patients were identified (International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM): 433–437). BPH patients with an ICD-9-CM of 600 were identified. The event observed was recurrent IS after the firstever IS. The factors associated with recurrent IS were assessed via Cox proportional hazards regression. Results: Recurrent IS was associated with BPH with an adjusted hazard ratio (HR) of 1.505 and a 95% confidence interval (CI) of 1.112–1.829, p < 0.001), and a competing risk model showed an adjusted HR of 1.544 (95% CI: 1.128–1.896, p < 0.001). The adjusted HR for treatment with alpha-1 blockers was 1.581 (95% CI: 1.16–1.915, p < 0.001), and increased risk with adjusted HR for treatment with high doses of 5-alpha reductase inhibitors over a long period of time are also at risk of recurrent IS. Conclusions: These findings highlight the association between BPH incidence and the risk of recurrent IS. The pharmacotherapy for BPH in IS patients should take great care. Full article

(This article belongs to the Section Medical Research)

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Life, Volume 16, Issue 2 (February 2026) – 156 articles

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