Life | June 2025 - Browse Articles

13 pages, 441 KiB

Open AccessArticle

The Influence of Drinking Water Intake on Pollutant Levels in the Human Body: Evidence from NHANES Data

by Chenxu Dai, Ziyi Qian, Linjie Yang, Siyan Chen, Hongfei Hu and Xia Huo

Life 2025, 15(6), 956; https://doi.org/10.3390/life15060956 (registering DOI) - 13 Jun 2025

Most studies have focused on the levels of pollutants in drinking water and the health risks they pose. However, no studies have reported the effects of drinking water intake on pollutant levels in the human body. Therefore, this study collected data from National [...] Read more.

Most studies have focused on the levels of pollutants in drinking water and the health risks they pose. However, no studies have reported the effects of drinking water intake on pollutant levels in the human body. Therefore, this study collected data from National Health and Nutrition Examination Survey database to provide statistical evidence for the relationship between water intake and human pollutant levels. We analyzed 95 pollutants in human urine, blood, and serum. The study found that 82% (65/79) of urine pollutants unadjusted for creatinine showed a stable negative correlation with water intake, primarily due to the urine dilution effect caused by increased water consumption. Water intake was negatively correlated with cadmium, m-/p-xylene, and toluene in blood, but positively correlated with blood total mercury and methyl mercury. In summary, the habit of drinking more water may be beneficial to reduce levels of most pollutants in human urine (unadjusted for creatinine) and a small part in blood. Only a few pollutants, including total mercury and methyl mercury in blood, as well as benzophenone-3 in urine (both creatinine-adjusted and unadjusted), are positively related to water intake. The underlying mechanisms by which water intake influences pollutant levels in the human body require further investigation. Full article

(This article belongs to the Section Physiology and Pathology)

21 pages, 552 KiB

Open AccessSystematic Review

Guidance on the Surgical Management of Rectal Cancer: An Umbrella Review

by Ionut Negoi

Life 2025, 15(6), 955; https://doi.org/10.3390/life15060955 (registering DOI) - 13 Jun 2025

Abstract

This umbrella review synthesizes international guidelines on the surgical management of rectal cancer to provide unified recommendations tailored to local healthcare organizations. This review emphasizes the importance of surgical centralization in high-volume centers, which maximizes outcomes, reduces morbidity, and increases survival rates. Minimally [...] Read more.

This umbrella review synthesizes international guidelines on the surgical management of rectal cancer to provide unified recommendations tailored to local healthcare organizations. This review emphasizes the importance of surgical centralization in high-volume centers, which maximizes outcomes, reduces morbidity, and increases survival rates. Minimally invasive approaches, such as laparoscopy and robotic surgery, are highlighted for their perioperative benefits, although careful patient selection and surgical expertise are required. Mechanical bowel preparation combined with oral antibiotics is recommended to effectively reduce complications, including surgical site infections and anastomotic leakage. Enhanced Recovery After Surgery protocols have been shown to significantly improve postoperative recovery and reduce hospital stay duration. Comprehensive perioperative care, including venous thromboembolism prophylaxis and infection control, is essential for optimal patient outcomes. This review underscores the need for structured training, certification, and regular audits for advanced techniques such as robotic surgery and transanal total mesorectal excision. Implementation of a national database is recommended to support ongoing improvements in rectal cancer surgery. This review centralizes evidence-based recommendations to guide surgical decision-making and harmonize the multidisciplinary care for patients with rectal cancer. Full article

(This article belongs to the Special Issue Gastrointestinal Diseases: Innovations in Diagnostics, Therapeutics, and Prognosis)

23 pages, 4522 KiB

Open AccessArticle

Betulinic Acid-Loaded Oleogel as a Novel Pharmaceutical Formulation for Potential Cutaneous Applications: Development, Characterization, and Biosafety Profile

by Andreea Smeu, Daliana Minda, Casiana Boru, Lavinia Vlaia, Vicențiu Vlaia, Cristina Adriana Dehelean, Sergio Liga, George Puenea and Daniela Lucia Muntean

Life 2025, 15(6), 954; https://doi.org/10.3390/life15060954 (registering DOI) - 13 Jun 2025

Abstract

Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due [...] Read more.

Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due to its lipophilic nature and low bioavailability, topical delivery systems are necessary for its proper administration. Oleogels are efficient carriers for the incorporation of hydrophobic biomolecules; however, their use for the delivery of BA remains scarce. Therefore, this study was designed to develop, characterize, and evaluate a BA-containing oleogel (BA-O) regarding its cutaneous safety profile as a potential pharmaceutical formulation targeting dermatologic issues. The findings illustrated the efficient formulation of BA as oleogel, the product presenting the specific conditions of topical semi-solid formulations in terms of physico-chemical characteristics and high biocompatibility in vitro and in ovo, as BA-O lacked a cytotoxic effect in HaCaT and JB6 Cl 41-5a skin cells (cell viability percentages being > 70%) and was categorized as non-irritant in EpiDerm™ tissues (viability > 80%) and on the chorioallantoic membrane (Irritation Score = 0.186). These results present the preclinical biosafety profile of BA-O with prospective potential for cutaneous applications that should be investigated in future studies. Full article

(This article belongs to the Special Issue Innovative Drug Development: Balancing Efficacy and Toxicity in Novel Pharmaceuticals)

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16 pages, 678 KiB

Open AccessArticle

5-Aminolevulinic Acid Phosphate as an Immune System Enhancer Along with Vaccination Against SARS-CoV-2 Virus Infection: An Open-Label, Randomized Pilot Study

by Norbert Berenzen, Riyadh Rehani, Andrea Ebeling, Marcus Stocker and Motowo Nakajima

Life 2025, 15(6), 953; https://doi.org/10.3390/life15060953 - 13 Jun 2025

Abstract

Previous studies have shown that 5-aminolevulinic acid phosphate together with sodium ferrous citrate, which is marketed as a food supplement, appears to be an important metabolic regulator in depleted T cell metabolism. Therefore, it was hypothesized that its administration in subjects vaccinated against [...] Read more.

Previous studies have shown that 5-aminolevulinic acid phosphate together with sodium ferrous citrate, which is marketed as a food supplement, appears to be an important metabolic regulator in depleted T cell metabolism. Therefore, it was hypothesized that its administration in subjects vaccinated against COVID-19 could enhance their immune system. Therefore, the aim of our proof-of-concept study was to determine the safety (by adverse events monitoring) and the tolerability (by subject questionnaires) and to investigate immune-boosting properties (by Immunoglobulins) in which 200 subjects were randomized in a ratio of 1:1 within 2 arms. In the intervention arm, the study product was administered together with the vaccines Covishield or Covaxin, and up to 21 days thereafter with a 150 mg daily dose, whereas in the control arm, the subjects were vaccinated only. No safety issues were detected, and the evaluation of the subject questionnaires showed no limitation of the well-being, which confirms the excellent tolerability of 5-aminolevulinic acid phosphate with sodium ferrous citrate. Moreover, the ‘Change in Immunoglobulin G levels’, although statistically insignificant, showed strong signals of its immune supportive potential. However, further studies are recommended to verify the results. Full article

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

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13 pages, 480 KiB

Open AccessArticle

Prodromal Parkinsonian Features in Carriers of Gaucher Disease Compared to Controls

by Michal Becker-Cohen, Ari Zimran, Tama Dinur, Maayan Tiomkin, Arndt Rolfs, David Arkadir, Peter Bauer, Elena Shulman, Gilad Yahalom, Mikhal E. Cohen, Orly Manor, Ora Paltiel and Shoshana Revel-Vilk

Life 2025, 15(6), 952; https://doi.org/10.3390/life15060952 - 13 Jun 2025

Abstract

Carriers of Gaucher disease have an increased risk of developing Parkinson’s disease (PD). Identifying PD in its prodromal stage is crucial, as early detection before motor symptoms appear allows for potential interventions to salvage neurons and slow or prevent disease progression. At the [...] Read more.

Carriers of Gaucher disease have an increased risk of developing Parkinson’s disease (PD). Identifying PD in its prodromal stage is crucial, as early detection before motor symptoms appear allows for potential interventions to salvage neurons and slow or prevent disease progression. At the Gaucher unit at Shaare Zedek Medical Center, we are following a large cohort of obligatory carriers of GBA1 variants (GBA1 carriers) and study ways to identify those at an increased risk for developing PD. In this study, we compared non-invasive prodromal PD tests in 164 GBA1 carriers and 49 participants with no genetic predisposition to PD (controls). The proportion of abnormal tests was compared between groups, and the risk factors for having abnormal tests (at least one or ≥20%) were studied. There were no differences between GBA1 carriers and controls in the frequency of abnormalities, having at least one abnormal test or having ≥20% abnormal tests. Having ≥20% of abnormal tests was associated mainly with age. Principal component analysis identified distinct cognitive, motor, and non-motor dysfunction patterns in GBA1 carriers compared to controls, with cognition in GBA1 carriers more closely linked to motor dysfunction and less influenced by mood and sleep, while in controls, executive function was tied to emotional state and fatigue. Younger carriers outperformed older ones in motor and some cognitive tasks. Those with a family history of PD showed worse cognitive scores than participants with no family history. Sex-based analysis revealed males obtained higher scores in most of the cognition subtests of the NeuroTrax test, whereas it was females in motor and other cognitive domains, mainly in the group of GBA1 carriers. A longitudinal follow-up of GBA1 carriers is ongoing to understand PD progression in GBA1 carriers with the aim of offering targeted intervention for those at higher risk. Full article

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16 pages, 1811 KiB

Open AccessArticle

Exceptional Heme Tolerance in Serratia plymuthica: Proteomic Insights into Oxidative Stress Adaptation in the Aedes aegypti Midgut

by Sâmella da Hora Machado, Rívea Cristina Custódio Rodrigues, Maria Aparecida Aride Bertonceli, Analiz de Oliveira Gaio, Gabriela Petroceli-Mota, Ricardo de Souza Reis, Marília Amorim Berbert-Molina, Vanildo Silveira and Francisco José Alves Lemos

Life 2025, 15(6), 950; https://doi.org/10.3390/life15060950 - 13 Jun 2025

Abstract

Serratia plymuthica, isolated from the midgut of Aedes aegypti, displays remarkable resilience to hemin, a toxic hemoglobin byproduct generated during blood digestion. This study explores its proteomic adaptations under oxidative stress induced by 5 mM hemin, mimicking midgut conditions. Growth assays [...] Read more.

Serratia plymuthica, isolated from the midgut of Aedes aegypti, displays remarkable resilience to hemin, a toxic hemoglobin byproduct generated during blood digestion. This study explores its proteomic adaptations under oxidative stress induced by 5 mM hemin, mimicking midgut conditions. Growth assays demonstrated that S. plymuthica tolerated hemin concentrations ranging from 5 µM to 1 mM, reaching the stationary phase within approximately 10 h. Colonies exhibited morphological changes—darkened peripheries and translucent halos—suggesting heme accumulation and detoxification. Label-free quantitative proteomics identified 436 proteins, among which 28 were significantly upregulated—including universal stress proteins (USPs), ABC transporters, and flavodoxin—while 54 were downregulated, including superoxide dismutase and several ribosomal proteins. Upregulated proteins were associated with antioxidant defense, heme transport, and redox regulation, whereas downregulated proteins suggested metabolic reprogramming to conserve energy under stress. Functional enrichment analysis revealed significant alterations in transmembrane transport, oxidative stress response, and central metabolism. These findings suggest that S. plymuthica contributes to redox homeostasis in the mosquito gut by mitigating reactive oxygen species (ROS) and detoxifying excess heme, supporting its role as a beneficial symbiont. The observed stress tolerance mechanisms may influence mosquito physiology and vector competence, offering novel insights into mosquito–microbiota interactions and potential microbiota-based strategies for vector control. Full article

(This article belongs to the Section Proteins and Proteomics)

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25 pages, 10529 KiB

Open AccessArticle

Comparison of Differentially Expressed Genes in Human and Canine Osteosarcoma

by Jorja Jackson-Oxley, Aziza A. Alibhai, Jack Guerin, Rachel Thompson, Rodhan Patke, Anna E. Harris, Corinne L. Woodcock, Dhruvika Varun, Maria Haque, Tinyiko K. Modikoane, Amber A. Kumari, Jennifer Lothion-Roy, Simone de Brot, Mark D. Dunning, Jennie N. Jeyapalan, Nigel P. Mongan and Catrin S. Rutland

Life 2025, 15(6), 951; https://doi.org/10.3390/life15060951 - 12 Jun 2025

Abstract

Osteosarcoma (OSA) is the most prevalent bone malignancy in people and dogs. Current survival rates show the need for advances in novel therapies to help overcome the growth, survival and metastatic progression of the cancer. Canine models are often used to advance prognostic [...] Read more.

Osteosarcoma (OSA) is the most prevalent bone malignancy in people and dogs. Current survival rates show the need for advances in novel therapies to help overcome the growth, survival and metastatic progression of the cancer. Canine models are often used to advance prognostic and treatment opportunities for OSA due to the similarities in the disease between species. This study focusses on the genetic and molecular similarities of OSA between human and canine specimens. Differentially expressed genes (DEGs) were compared and identified in canine and human OSA tumours, revealing 86 common genes, 36 having high and 50 having low expression. Further immunohistochemical analysis of the corresponding proteins of three identified DEGs (ASPN, STK3, BAMBI) allowed for the visualisation of protein expression in canine OSA tissues (n = 19). Overall nuclear and cytoplasmic H-scores were generated, and nuclear and cytoplasmic scores in males and females and in different anatomical locations (axial versus appendicular) were also investigated, presenting unique opportunities to understand the expression in this cancer type. This study contributes to a deeper knowledge of genetic pathways changes and identifies avenues for the diagnosis, prognosis and treatment of OSA in people and dogs, whilst encompassing the One Health concept in medicine. Full article

(This article belongs to the Section Genetics and Genomics)

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10 pages, 212 KiB

Open AccessArticle

Microbiota of Cervical Canal in Nine Patients Diagnosed with Ectopic Pregnancy: Case Series

by Kinga Bednarek, Katarzyna Wszołek, Monika Szewc, Mirosława Gałęcka, Adrian Mruczyński, Alan Bruszewski, Marcin Wierzchowski, Maciej Wilczak and Karolina Chmaj-Wierzchowska

Life 2025, 15(6), 949; https://doi.org/10.3390/life15060949 (registering DOI) - 12 Jun 2025

Abstract

Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses [...] Read more.

Dysbiosis, or an altered microbiota composition, has been implicated in chronic endometrial inflammation and recurrent implantation failure. Despite growing research on the relationship between the genital microbiome and reproductive health, few studies have examined its role in ectopic pregnancy. Therefore, our study focuses on the microbiota of the cervical canal in women diagnosed with an ectopic pregnancy. Material and methods: The study group consisted of nine women of a reproductive age who were hospitalized at the Department of Maternal and Child Health, Gynecology and Obstetrics, Clinical Hospital of the University of Poznań, between February and September 2023. In nine patients, an ectopic pregnancy was diagnosed based on a transvaginal ultrasound examination. The swabs were collected for quantitative microbiological culture (using Amies transport medium). The microbiological analyses involved quantitative culture on selected selective and differential media, following the Standard Operating Procedure developed by the Institute of Microecology. Results: A reduced Lactobacillus spp. count (≤5 × 10⁷ CFU/mL) was observed in 78% of the patients participating in the study, including those that produce H₂O₂, i.e., with strong protective properties for the environment of the female reproductive tract. The molecular analyses revealed Ureaplasma spp. (U. parvum and U. urealyticum) in 33% of the samples (three patients). However, Chlamydia trachomatis and Mycoplasma genitalium were not detected in any of the analyzed samples. Conclusions: The ease of obtaining material and the minimally invasive nature of lower reproductive tract examinations may allow for the evaluation of microbiota imbalances, helping to identify individuals at an increased risk of reproductive complications. Full article

(This article belongs to the Section Microbiology)

16 pages, 1162 KiB

Open AccessArticle

Putting Ethnobotany into Practice: In Vitro Antioxidant Potential and Impact on Rat Gastric Smooth Muscle Reactivity of Aqueous Extracts of Marrubium friwaldskyanum Boiss. and Marrubium peregrinum L.

by Mariya Choneva, Anelia Bivolarska, Donika Gyuzeleva, Valentin Turiyski, Plamen Stoyanov, Tsvetelina Mladenova, Krasimir Todorov, Rumen Mladenov, Natalia Prissadova, Raina Ardasheva, Viktor Yotov, Petko Denev, Aleksandrina Topalova-Shishmanova, Stoyan Bivolarski and Ivica Dimov

Life 2025, 15(6), 948; https://doi.org/10.3390/life15060948 (registering DOI) - 12 Jun 2025

Abstract

The genus Marrubium (Lamiaceae) is widely used in traditional medicine. While some representatives of the genus have been well investigated, the biological activity of others remains largely unknown. The aim of the current study was to assess the in vitro antioxidant potential and [...] Read more.

The genus Marrubium (Lamiaceae) is widely used in traditional medicine. While some representatives of the genus have been well investigated, the biological activity of others remains largely unknown. The aim of the current study was to assess the in vitro antioxidant potential and the effect on the reactivity of isolated rat gastric smooth muscles (SM) of aqueous extracts of Marrubium friwaldskyanum inflorescences, stems and leaves, and Marrubium peregrinum as a whole herb. The antioxidant activity was analyzed through multiple spectrophotometric and fluorometric assays. The effect on SM reactivity was determined by the treatment of excised gastric muscles of 10 male Whistar rats with the plant extracts alone or successive to 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide, ketanserin, verapamil, and acetylcholine. According to the obtained results, the M. friwaldskyanum leaf extract exhibited the greatest antioxidant potential, followed by the M. peregrinum one. The SM reactivity analysis revealed that the treatment with all four extracts induced a dose-dependent contractile response with predominant cholinergic character. However, activation of serotoninergic and/or dopaminergic pathways was also observed. Furthermore, when applied after verapamil, the extracts showed a SM relaxant effect. The discovered biological activity will serve as a basis for future analyses through which the therapeutic effect of the plants will be investigated. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds: Therapeutic Insights and Applications)

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21 pages, 7003 KiB

Open AccessArticle

Application of a New Device for Saccadic Training in Athletes

by Angelina Ganebnaya, Aiga Svede, Alina Kucika, Jekaterina Berkova, Alona Purmale, Liga Puhova, Mariya Misri, Svetlana Semjonova, Davids Davis Gailitis and Atis Kovalovs

Life 2025, 15(6), 947; https://doi.org/10.3390/life15060947 - 12 Jun 2025

Abstract

The aim of our study was to test the application of a new vision training device, the EYE ROLL, for home-based eye movement training in athletes. Sixty-seven participants were randomly divided into three groups: a control group (no training); an eye movement training [...] Read more.

The aim of our study was to test the application of a new vision training device, the EYE ROLL, for home-based eye movement training in athletes. Sixty-seven participants were randomly divided into three groups: a control group (no training); an eye movement training group with no device; and a group using the new EYE ROLL device. The results of 51 participants were used for statistical analyses after a 4-week period. Before and after the 4-week period, participants underwent the same assessment procedures: a comprehensive vision examination and saccadic eye movement recording. Before training, for both 10° and 5° stimuli, all subjects showed statistically significantly larger and faster rightward saccades compared to leftward saccades. After four weeks, the control group showed increased horizontal saccadic asymmetry and a decrease in leftward saccade amplitude. However, both velocities showed asymmetry in both visits. There were larger changes in saccadic parameters for leftward saccades, but no clear changes in saccadic response asymmetry after training. There were no consistent differences between the training groups. The EYE ROLL is a novel device that may serve as a substitute training tool for saccadic enhancement and may improve the symmetry of horizontal saccadic movements after four weeks of home-based training. Full article

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

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8 pages, 476 KiB

Open AccessArticle

Optimization of Isavuconazole Dosing in Patients with Invasive Fungal Infections Through Therapeutic Drug Monitoring: Real-World Clinical Practice Experience

by Diego Peña-Lorenzo, Noemí Rebollo, José Germán Sánchez-Hernández, Lourdes Vázquez-López, María José Otero and Aránzazu Zarzuelo-Castañeda

Life 2025, 15(6), 946; https://doi.org/10.3390/life15060946 - 12 Jun 2025

Abstract

Therapeutic drug monitoring (TDM) is routinely recommended for most antifungal triazoles to ensure efficacy and safety. Isavuconazole, however, was initially approved without this recommendation due to its predictable pharmacokinetic profile. Later clinical data have raised concerns about subtherapeutic exposures in certain populations. This [...] Read more.

Therapeutic drug monitoring (TDM) is routinely recommended for most antifungal triazoles to ensure efficacy and safety. Isavuconazole, however, was initially approved without this recommendation due to its predictable pharmacokinetic profile. Later clinical data have raised concerns about subtherapeutic exposures in certain populations. This prospective, single-center study aimed to assess the need for TDM of isavuconazole in critically ill and hematologic patients with invasive fungal infections. Between March 2022 and November 2023, patients receiving standard dosing of isavuconazole were enrolled, and plasma concentrations were measured to determine the proportion of patients with values outside the therapeutic range (1–4 µg/mL), particularly focusing on subtherapeutic levels. A total of 65 isavuconazole plasma concentrations from 24 patients (9 critically ill and 15 hematologic) were analyzed. Critically ill patients had lower initial concentrations than hematologic patients (median [range]: 0.75 [not detectable (ND)–5.18] vs. 3.03 [1.03–6.65] µg/mL), with 66.7% showing levels outside the therapeutic range and 55.5% having subtherapeutic concentrations. The coefficient of variation (CV%) of concentrations values at the first TDM was 124.7% in critically ill patients and 57.3% in hematologic patients. After dose adjustment in critically ill patients, the proportion with levels outside the therapeutic range decreased to 28.6%. These findings suggest that, despite initial assumptions, isavuconazole exhibits considerable pharmacokinetic variability in specific populations, particularly in critically ill patients, and the findings support the implementation of TDM to optimize antifungal therapy and improve patient outcomes in real-world clinical settings. Full article

(This article belongs to the Special Issue Pharmacokinetic and Pharmacogenetic Approaches in Personalized Medicine)

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14 pages, 696 KiB

Open AccessReview

The Effects of the Association Between a High-Fat Diet and Physical Exercise on BDNF Expression in the Hippocampus: A Comprehensive Review

by Francisca Tayná da Silva Gomes, Antônio Vicente Dias de Andrade, Paloma Katlheen Moura Melo, Roque Ribeiro da Silva Júnior, Débora Lopes Silva de Souza, Élyssa Adriolly Freitas Tavares, Ingrid Garcia de Sena, Thales Allyrio Araújo de Medeiros Fernandes, Paulo Leonardo Araújo de Góis Morais, Ivana Alice Teixeira Fonseca, Cibele dos Santos Borges and José Rodolfo Lopes de Paiva Cavalcanti

Life 2025, 15(6), 945; https://doi.org/10.3390/life15060945 - 12 Jun 2025

Abstract

High-fat diets, characterised by their high lipid content, have been associated with structural and functional alterations in the hippocampus of rodents, including a reduction in the expression of brain-derived neurotrophic factor (BDNF), which negatively impacts learning and memory. Evidence suggests that these impairments [...] Read more.

High-fat diets, characterised by their high lipid content, have been associated with structural and functional alterations in the hippocampus of rodents, including a reduction in the expression of brain-derived neurotrophic factor (BDNF), which negatively impacts learning and memory. Evidence suggests that these impairments may be attenuated by regular physical exercise. This review aimed to gather relevant scientific evidence available on the effects of the association between high-fat diets and physical exercise on BDNF expression levels in the hippocampus of rats. The studies analysed highlight a neuroprotective effect of exercise, capable of positively modulating BDNF levels and, consequently, improving the cognitive functions of these animals. Full article

(This article belongs to the Section Medical Research)

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27 pages, 4965 KiB

Open AccessSystematic Review

Association Between Lycopene and Metabolic Disease Risk and Mortality: Systematic Review and Meta-Analysis

by Isabel Viña, Alicia Robles and Juan R. Viña

Life 2025, 15(6), 944; https://doi.org/10.3390/life15060944 - 12 Jun 2025

Abstract

Background: Lycopene, a dietary carotenoid with antioxidant properties, protects against sun-induced skin damage, prostatic conditions such as chronic prostatitis, and cancer; however, its role in metabolic disorders, including metabolic syndrome and nonalcoholic fatty liver disease (MAFLD), remains unclear. This study aimed to systematically [...] Read more.

Background: Lycopene, a dietary carotenoid with antioxidant properties, protects against sun-induced skin damage, prostatic conditions such as chronic prostatitis, and cancer; however, its role in metabolic disorders, including metabolic syndrome and nonalcoholic fatty liver disease (MAFLD), remains unclear. This study aimed to systematically assess the association between lycopene levels (serum and dietary) and the risk of metabolic diseases. Methods: This study adhered to the PRISMA guidelines and was prospectively registered on the Open Science Framework (OSF). We searched PubMed, Scopus, Web of Science, and Medline via WoS. Pooled odds ratios (OR), hazard ratios (HR), and mean differences (MD) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models based on heterogeneity. Results: Twenty-nine studies were included, of which twenty-five were eligible for the meta-analysis. Pooled analysis showed that the individuals with the lowest serum lycopene levels had a significantly higher risk of MAFLD (OR = 1.39, 95%CI: 1.02–1.89, p = 0.0388). No significant associations were found between HbA1c levels, diabetes history, and weight status. Although not statistically significant, a clear trend of patients with DM having lower lycopene levels than the control group was observed (MD = −0.09, 95% CI: −0.19 to 0.00, p = 0.054). Comparisons based on weight status showed no significant differences. Conclusions: While lower serum lycopene levels are significantly associated with increased MAFLD risk, their impact on glycemic control remains inconclusive, underscoring the need for targeted clinical research. Full article

(This article belongs to the Special Issue Feature Papers in Medical Research: 3rd Edition)

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12 pages, 948 KiB

Open AccessArticle

Assessing Motor Performance and Ankle Mobility in Pre-Adolescent Male Fencers

by Yalcin Aydin, Gurkan Tokgoz, Nurkan Yilmaz, Ilgin Ali Coskun, Aysegul Beykumul, Enes Colak, Caner Aygoren, Samet Koc and Fahri Safa Cinarli

Life 2025, 15(6), 942; https://doi.org/10.3390/life15060942 - 12 Jun 2025

Abstract

Ankle mobility plays a critical role in dynamic stability and propulsion during fencing-specific actions. However, its relationship to performance metrics in young athletes remains unclear. This study aimed to investigate the relationship between ankle range of motion (ROM), acceleration, and jump height in [...] Read more.

Ankle mobility plays a critical role in dynamic stability and propulsion during fencing-specific actions. However, its relationship to performance metrics in young athletes remains unclear. This study aimed to investigate the relationship between ankle range of motion (ROM), acceleration, and jump height in pre-adolescent male fencers, as well as to examine bilateral differences in ankle mobility between the front and rear foot. Fifteen fencers (age 10.86 ± 0.91 years) were assessed for ankle ROM (dorsiflexion, plantar flexion, inversion, eversion) using a goniometer. Performance tests included a 7 m sprint lunge (acceleration) and countermovement jump. Significantly large correlations were observed between front and rear foot ankle plantar flexion range of motion and both acceleration (r = 0.625–0.628, p < 0.05) as well as vertical jump height (r = 0.579–0.647, p < 0.05). Rear foot ankle plantar flexion range of motion significantly predicted acceleration (r² = 0.335, p < 0.05) and jump height (r² = 0.418, p < 0.05). In contrast, no meaningful associations were found between dorsiflexion, inversion, or eversion range of motion and performance metrics. Additionally, bilateral comparisons revealed significantly greater dorsiflexion in the front foot ankle and greater eversion in the rear foot ankle (p < 0.05). Plantar flexion ROM is a key contributor to acceleration and jump capacity in youth fencers. Incorporating ankle mobility training may support physical development in this population. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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10 pages, 435 KiB

Open AccessArticle

Development of an Exercise Rehabilitation Functional Group for Individualized Exercise After Lumbar Spine Surgery

by Seong Son, Han Byeol Park, Chan Jong Yoo, Moon-Hee Kim, Byung Rhae Yoo and Jae Ang Sim

Life 2025, 15(6), 943; https://doi.org/10.3390/life15060943 - 11 Jun 2025

Abstract

Individualized exercise therapy is crucial for effective postoperative rehabilitation. However, a widely accepted, standardized framework for measuring individual exercise capabilities after lumbar spine surgery (LSS) is lacking. This study aimed to develop a novel Exercise Rehabilitation Functional Group (ERFG) classification system to enable [...] Read more.

Individualized exercise therapy is crucial for effective postoperative rehabilitation. However, a widely accepted, standardized framework for measuring individual exercise capabilities after lumbar spine surgery (LSS) is lacking. This study aimed to develop a novel Exercise Rehabilitation Functional Group (ERFG) classification system to enable systematic, individualized rehabilitation after LSS. Eight exercise parameters and two clinical factors were assessed in 428 volunteers within 12 weeks of single-segment LSS to establish reference data for the ERFG. The study cohort included 411 participants (mean age 67.10 ± 11.60; 128 males and 283 females) with an average postoperative interval of 42.96 ± 20.25 days. Key metrics included lumbar spine ROM (mean 74.24 ± 25.30°), trunk muscle strength (mean 15.71 ± 5.14 kg), trunk muscle endurance (mean 95.80 ± 35.66 s), whole-body flexibility (mean 3.30 ± 10.65 cm), cardiopulmonary capability (mean 433.91 ± 118.75 m), gait with affected single leg (mean 36.26 ± 5.98%), single-leg balance (median 13.60 s), coordination capability (mean 8.21 ± 3.23 s), EuroQol 5-Dimension 5-Level score (mean 9.39 ± 4.17), and visual analog scale for low back pain (mean 3.78 ± 2.55). Data were categorized into five grades using Cajori’s five-grade mathematical method. Significant correlations were observed between the eight exercise parameters and two clinical factors. This study established a foundational framework for standardizing baseline exercise capabilities after LSS. This ERFG system may provide a basis for individualized rehabilitation strategies to enhance patient outcomes. Full article

(This article belongs to the Special Issue Innovative Perspectives in Physical Therapy and Health)

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28 pages, 7654 KiB

Open AccessReview

Ultrasound of the Gallbladder—An Update on Measurements, Reference Values, Variants and Frequent Pathologies: A Scoping Review

by Claudia Lucius, Barbara Braden, Christian Jenssen, Kathleen Möller, Michael Sienz, Constantinos Zervides, Manfred Walter Essig and Christoph Frank Dietrich

Life 2025, 15(6), 941; https://doi.org/10.3390/life15060941 - 11 Jun 2025

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Abstract

Objective: We aimed to provide an update on ultrasound measurements of the gallbladder with studies focusing on measurement techniques, reference values, and influencing factors. Anatomical anomalies and common pathological findings are discussed together with their clinical impact. Methods: A literature search was [...] Read more.

Objective: We aimed to provide an update on ultrasound measurements of the gallbladder with studies focusing on measurement techniques, reference values, and influencing factors. Anatomical anomalies and common pathological findings are discussed together with their clinical impact. Methods: A literature search was performed for ultrasound studies in healthy subjects. Relevant data published between 2010 and March 2025 were extracted and evaluated. Possible clinical implications are discussed. Results: Many factors influence gallbladder size and wall thickness, as the gallbladder is a highly functional organ. Diabetes and obesity have been proven to increase gallbladder volume and wall thickness. A normal gallbladder wall should be echogenic with one layer and a thickness < 3 mm. Gallbladder size is variable and can achieve values above 10 × 4 × 4 cm, especially with increasing age. Gallbladders with maximal diameters below 3.5 cm are referred to as micro-gallbladders. Calculating gallbladder volume is reserved for special issues, achieving the best inter- and intra-observer variability with the ellipsoid formula. Clinical relevance and work-up of common pathological findings like wall thickening, gallbladder polyps, and stones are discussed. Full article

(This article belongs to the Section Medical Research)

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17 pages, 10068 KiB

Open AccessArticle

The Presence of Ejaculatory Bulbs in Vasa Deferentia: A Well-Preserved Trait Among Alpheoid Shrimps (Crustacea, Caridea, Alpheoidea)

by Lucas Rezende Penido Paschoal, Caio Santos Nogueira and Fernando José Zara

Life 2025, 15(6), 940; https://doi.org/10.3390/life15060940 - 11 Jun 2025

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Abstract

The superfamily Alpheoidea comprises eight families: Alpheidae, Barbouriidae, Bythocarididae, Hippolytidae, Lysmatidae, Merguiidae, Ogyrididae and Thoridae. Alpheoids are characterized by possessing two pairs of chelate pereopods, a multiarticulate carpus on pereopod 2, and a narrow strip as the last article on maxilliped 2. However, [...] Read more.

The superfamily Alpheoidea comprises eight families: Alpheidae, Barbouriidae, Bythocarididae, Hippolytidae, Lysmatidae, Merguiidae, Ogyrididae and Thoridae. Alpheoids are characterized by possessing two pairs of chelate pereopods, a multiarticulate carpus on pereopod 2, and a narrow strip as the last article on maxilliped 2. However, during the inspection of the reproductive system (RS) of several alpheoids, we consistently observed the presence of ejaculatory bulbs (EBs) in vasa deferentia (VDs) of these shrimps. To investigate whether the presence of EBs in the RS is a conserved trait among Alpheoidea representatives, we analyzed as many species as possible along the Brazilian coast: Alpheidae—5 genera, 19 spp., Hippolytidae—2 genera, 2 spp., Lysmatidae—2 genera, 10 spp., Merguiidae—1 genus, 1 sp., Ogyrididae—1 genus, 2 spp., and Thoridae—1 genus, 1 sp. In addition, we examined representatives of the superfamilies Atyoidea (1 family, 2 genera, 2 spp.), Nematocarcinoidea (1 family, 1 genus, 2 spp.), Palaemonoidea (2 families, 4 genera, 4 spp.) and Processoidea (1 family, 2 genera, 2 spp.) to determine whether EB are present in these groups. Among the groups analyzed, except for the family Alpheidae, most species of alpheoids exhibit an expansion on the ventral portion of the VD in continuity with the lumen of the vas deferens, i.e., the EB. This structure increases the surface area of the VD, consequently increasing the quantity of the seminal material to be ejaculated onto the female. We did not observe the presence of EB in any other of the analyzed superfamilies, suggesting that this structure is exclusive in Alpheoidea. In conclusion, the presence of EB in VD appears to be an exclusive trait in Alpheoidea, being considered a well-preserved synapomorphic trait in this group, except in the family Alpheidae that do not harbor EB, representing a plesiomorphic condition within this superfamily. Full article

(This article belongs to the Section Reproductive and Developmental Biology)

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13 pages, 7555 KiB

Open AccessArticle

Healed Perforated Corneal Ulcers in Human

by Yasser Helmy Mohamed, Masafumi Uematsu, Mao Kusano, Keiji Suzuki and Akio Oishi

Life 2025, 15(6), 939; https://doi.org/10.3390/life15060939 - 11 Jun 2025

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Abstract

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half [...] Read more.

This study investigates the pathophysiological process of healed perforated corneal ulcers (HPCUs) in humans. All subjects underwent keratoplasty due to opacities or leakage from HPCUs. Half of each specimen was fixed with 4% glutaraldehyde for transmission electron microscope (TEM) examination. The other half was fixed in 10% formaldehyde for immunofluorescence (IF) examination. TEM identified layered structures with two cell types (polygonal and elongated) connected by gap or adherent junctions during early stage of healing. Both apoptotic and mitotic changes were found in both types of cells. There were no endothelial cells or Descemet’s membrane (DM) present in early stage of healing. During the intermediate stage, the healed area comprised three layers: epithelium, Bowman’s layer, and stroma, with an increase in stromal collagen. Later, adjacent endothelial cells crept in, forming DM and completing the cornea’s 5-layer structure. IF examinations revealed that vimentin⁺ and α-smooth muscle actin (αSMA)⁺ myofibroblasts gathered around the damaged site. Proliferating cell nuclear antigen⁺ cells, which indicated cell proliferation, were found in both cells. Anti-phospho-histone H2AX antibodies were found in some epithelial cells. CK14-positive cells were only found in superficial polygonal cells. Corneal wound healing is a complex process that includes apoptosis, cell migration, mitosis, differentiation, and extracellular matrix remodeling. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

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18 pages, 545 KiB

Open AccessArticle

Biopsy-Proven Glomerulopathies in Romania: A 10-Year Nationwide Study

by Andreea Covic, Mihai Onofriescu, Flaviu R. Bob, Cristina Căpușă, Irina-Draga Căruntu, Otilia Ciurea, Adrian Covic, Simona Giusca, Ina Kacso, Adelina Mihăescu, Andreea Niculescu, Bogdan Obrișcă, Dacian Tirinescu, Adalbert Schiller, Alexandra Vrabie, Yuriy Maslyennikov and Gener Ismail

Life 2025, 15(6), 938; https://doi.org/10.3390/life15060938 - 11 Jun 2025

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Abstract

Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year [...] Read more.

Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year period. We retrospectively analyzed 4047 native kidney biopsies performed between 2014 and 2023 across four national nephrology reference centers. Patient demographics, clinical presentation, and histopathological diagnoses were collected and categorized into primary and secondary glomerular diseases, glomerulosclerosis, tubulointerstitial nephropathies, hereditary nephropathies, and vascular nephropathies. The mean patient age was 48 years, 54.8% were male, and 51.4% presented with nephrotic-range proteinuria. The most common primary glomerulopathies were membranous nephropathy (16.7%), immunoglobulin A nephropathy (15.6%), focal segmental glomerulosclerosis (8.8%), and membranoproliferative glomerulonephritis (10%). Among secondary glomerular diseases, lupus nephritis (9.3%), diabetic nephropathy (8.5%), and vasculitis (7.7%) were most frequent. Marked inter-center variability was observed, with a notably high prevalence of membranous nephropathy in Iași (31.1%). Over the study period, the incidence of focal segmental glomerulosclerosis increased while immunoglobulin A nephropathy declined. This study provides the first nationwide epidemiological assessment of biopsy-proven glomerular disease in Romania, revealing both similarities and distinctive differences compared to patterns reported in other European countries. Full article

(This article belongs to the Special Issue Recent Insights in the Pathogenesis, Diagnosis, Prognosis and Treatment of Glomerular Disorders)

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34 pages, 2583 KiB

Open AccessReview

Galectin-3 Release in the Bone Marrow Microenvironment Promotes Drug Resistance and Relapse in Acute Myeloid Leukemia

by Cansu Yıldırım

Life 2025, 15(6), 937; https://doi.org/10.3390/life15060937 - 10 Jun 2025

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Abstract

Reciprocal signaling between acute myeloid leukemia (AML) cells and the surrounding bone-marrow microenvironment (BMME) promotes AML progression through several mechanisms. One of the most important mechanisms is the induction of Galectin-3 (Gal-3) expression by AML cells and bone marrow mesenchymal stromal cells (BM-MSCs). [...] Read more.

Reciprocal signaling between acute myeloid leukemia (AML) cells and the surrounding bone-marrow microenvironment (BMME) promotes AML progression through several mechanisms. One of the most important mechanisms is the induction of Galectin-3 (Gal-3) expression by AML cells and bone marrow mesenchymal stromal cells (BM-MSCs). Emerging evidence indicates that Gal-3 upregulation in the BMME promotes AML cell adhesion and survival, leading to the development of chemotherapy resistance, relapse, and poor prognosis. Identifying the biological function and critical signaling pathways of Gal-3 may contribute to overcoming acquired drug resistance and preventing post-treatment relapse. Gal-3 is involved in several molecular signaling pathways, including PI3K/AKT/mTOR, Ras/Raf/MEK/ERK, JAK/STAT, JNK, Wnt/β-catenin, PLC/PKC and NF-κB, which are interconnected to promote AML cell survival and resistance to chemotherapy. This review focuses on the biological effects, molecular mechanisms of action and regulation of Gal-3 in the pathogenesis and progression of AML. The therapeutic potential of potent synthetic small-molecule Gal-3 inhibitors in high-risk patients with AML is also discussed based on preclinical and clinical evidence from several human diseases. Currently, the effect of these Gal-3 inhibitors in AML has not been investigated either in vitro or in vivo. The findings provide a rationale for targeting Gal-3 that may be a very promising therapeutic approach, especially for patients with relapsed/refractory AML, and may enhance the efficacy of conventional chemotherapeutic drugs and/or immune checkpoint inhibitors. Full article

(This article belongs to the Special Issue Bone Cancer: From Molecular Mechanism to Treatment)

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19 pages, 451 KiB

Open AccessArticle

Exploring the Role of Diabetes in ALS: A Population-Based Cohort Study

by Ilaria Martinelli, Giulia Gianferrari, Rebecca Santarelli, Elisabetta Zucchi, Cecilia Simonini, Nicola Fini, Andrea Ghezzi, Annalisa Gessani, Laura Ferri, Krzysztof Smolik, Diana Ferraro, Roberta Bedin, Matteo Gizzi, Elisabetta Sette, Veria Vacchiano, Luigi Bonan, Lucia Zinno, Patrizia De Massis, Elena Canali, Doriana Medici, Emilio Terlizzi, Simonetta Morresi, Mario Santangelo, Alberto Patuelli, Marco Currò Dossi, Marco Longoni, Maura Pugliatti, Tommaso Filippini, Salvatore Ferro, ERRALS Study Group and Jessica Mandrioli Show full author list Hide full author list

Life 2025, 15(6), 936; https://doi.org/10.3390/life15060936 - 10 Jun 2025

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Abstract

Type 2 diabetes mellitus (T2DM) as a comorbidity in amyotrophic lateral sclerosis (ALS) has sparked interest for its potential impact on disease expression and prognosis. In this retrospective cohort study, we investigated the prevalence and clinical correlates of T2DM in a large cohort [...] Read more.

Type 2 diabetes mellitus (T2DM) as a comorbidity in amyotrophic lateral sclerosis (ALS) has sparked interest for its potential impact on disease expression and prognosis. In this retrospective cohort study, we investigated the prevalence and clinical correlates of T2DM in a large cohort of patients from the ALS registry of a Northern Italy region, Emilia Romagna, established in 2009. Out of 1756 ALS patients enrolled up to 2021, 145 were affected by T2DM (diALS). Patients with diALS were older than those without T2DM (ndALS) (71.56 vs. 65.76 years, p < 0.001), had a higher body mass index (25.63 vs. 24.23, p < 0.001), but experienced greater weight loss at diagnosis (6.87% vs. 5.44%, p < 0.007). Respiratory onset (6.2% vs. 2.6%, p = 0.013) and respiratory phenotype (4.2% vs. 1.4%, p = 0.04) were more frequent among diALS. Coherently, diALS presented a lower forced vital capacity (74.9% vs. 87.9%, p ≤ 0.001) and more frequently adopted Non-Invasive Ventilation (NIV) (50.35% vs. 37.61%, p = 0.003), with significant influence on time to NIV (HR 1.71, 95% CI 1.07–2.74, p = 0.024). Exploring genetic background, among all the genes examined C9ORF72 emerged as underrepresented among diALS (7.64% in ndALS vs. 0% in diALS, p = 0.039). In conclusion, we confirmed a more severe respiratory dysfunction in diALS, suggesting a specific frailty in respiratory muscles, together with some peculiar clinical features consistent with the previous literature data, such as a later onset. The lower prevalence of C9ORF72 expansion in this population may hint towards a specific role of the gene in metabolism and inflammation, granting more space to non-genetic causes, warranting further studies for confirmation. Full article

(This article belongs to the Section Life Sciences)

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23 pages, 1127 KiB

Open AccessReview

The Genus Cordyceps Sensu Lato: Their Chemical Constituents, Biological Activities, and Therapeutic Effects on Air Pollutants Related to Lung and Vascular Diseases

by Hye-Jin Park

Life 2025, 15(6), 935; https://doi.org/10.3390/life15060935 - 10 Jun 2025

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Abstract

Air pollutants are significant environmental factors that contribute to the exacerbation of respiratory, cardiopulmonary, and skin diseases in East Asia, and their impact is based on particle size. Natural products represent a promising and sustainable strategy for reducing the adverse effects of air [...] Read more.

Air pollutants are significant environmental factors that contribute to the exacerbation of respiratory, cardiopulmonary, and skin diseases in East Asia, and their impact is based on particle size. Natural products represent a promising and sustainable strategy for reducing the adverse effects of air pollutants on health. Cordyceps spp. have been integral to traditional Chinese medicine. Recently, their fruiting bodies and related supplements have gained popularity. The physiological effects of Cordyceps species are well documented and attributed to their chemical constituents, such as cordycepin, polysaccharides, cordymin, glycoprotein, ergosterol, and other bioactive extracts. Cordyceps supplementation may support lung health and enhance respiratory function. Although further clinical data are necessary, many preclinical studies have found a connection between Cordyceps and improved lung health. In addition, preclinical and clinical studies have indicated that Cordyceps and its derivatives (e.g., Ningxinbao, Corbrin, and Jinshuibao capsules) protect against vascular diseases by modulating key molecular pathways. This review provides insights into the potential of Cordyceps for clinical application in the management of air pollutant-related respiratory and vascular diseases. Full article

(This article belongs to the Section Pharmaceutical Science)

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22 pages, 5301 KiB

Open AccessArticle

Protective Impacts of Chlorella vulgaris on Cisplatin-Induced Toxicity in Liver, Kidney, and Spleen of Rats: Role of Oxidative Stress, Inflammation, and Nrf2 Modulation

by Layla A. Almutairi, Ebtehal G. Abdelghaffar, Hany A. Hafney, Hala M. Ebaid, Sahar A. Alkhodair, Aly A. M. Shaalan and Heba N. Gad EL-Hak

Life 2025, 15(6), 934; https://doi.org/10.3390/life15060934 - 10 Jun 2025

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Abstract

Cisplatin is a widely utilized chemotherapy drug effective against various cancers, yet its use is often constrained by severe toxicity to healthy organs, including the liver, kidneys, and spleen. This study explored the protective role of Chlorella vulgaris, a microalga known for [...] Read more.

Cisplatin is a widely utilized chemotherapy drug effective against various cancers, yet its use is often constrained by severe toxicity to healthy organs, including the liver, kidneys, and spleen. This study explored the protective role of Chlorella vulgaris, a microalga known for its antioxidant and anti-inflammatory properties, against cisplatin-induced organ damage. The research focused on modulating oxidative stress, inflammation, and the Nrf2 signaling pathway. The experimental design included four groups: a control group receiving saline, a cisplatin group administered 1.34 mg/kg weekly for three months, a C. vulgaris group receiving 150 mg/kg daily, and a combined cisplatin/Chlorella vulgaris group. Cisplatin treatment significantly elevated oxidative stress markers, such as lipid peroxidation and nitric oxide, while increasing pro-inflammatory cytokines (TNF-α, IL-12, IL-6) and reducing antioxidant capacity. Additionally, liver and kidney function markers were markedly impaired, and histopathological analysis revealed structural damage in the liver, kidneys, and spleen. Conversely, C. vulgaris supplementation mitigated these effects, restoring oxidative stress markers, cytokine levels, and organ function to near-normal values. Microscopic examination confirmed that Chlorella vulgaris effectively prevented cisplatin-induced structural damage. Notably, while cisplatin increased Nrf2 expression as an adaptive response to oxidative stress, C. vulgaris attenuated this effect, reflecting its potent antioxidant capabilities. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

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15 pages, 1625 KiB

Open AccessReview

Navigating the Challenges of Acanthamoeba Keratitis: Current Trends and Future Directions

by Lanxing Fu, Joanna Wasielica-Poslednik, Gerd Geerling, Scott Robbie, Fabiana D’Esposito, Mutali Musa, Daniele Tognetto, Rosa Giglio, Caterina Gagliano and Marco Zeppieri

Life 2025, 15(6), 933; https://doi.org/10.3390/life15060933 - 10 Jun 2025

Viewed by 139

Abstract

Acanthamoeba keratitis (AK) is a vision-threatening eye infection induced by the free-living species of the amoeba genus Acanthamoeba, presenting considerable therapeutic difficulties due to its frequently delayed diagnosis, chronic nature, and resistance to standard treatments. This review examines the changing landscape of [...] Read more.

Acanthamoeba keratitis (AK) is a vision-threatening eye infection induced by the free-living species of the amoeba genus Acanthamoeba, presenting considerable therapeutic difficulties due to its frequently delayed diagnosis, chronic nature, and resistance to standard treatments. This review examines the changing landscape of AK, emphasizing recent developments in pathogenesis, diagnosis, and treatment. We examine the molecular pathways that enable Acanthamoeba invasion and persistence in the cornea, and how comprehending these processes can inform the creation of more effective treatment therapies. The review emphasizes current advancements in diagnostic methodologies, such as PCR-based tests and in vivo confocal imaging, which have enhanced early detection rates and diagnostic precision. Furthermore, we analyze contemporary treatment modalities, including antimicrobial therapy and surgical procedures, while recognizing the difficulties presented by antimicrobial resistance and the lack of standardized treatment protocols. This review seeks to deliver a thorough examination of AK, presenting insights into cutting-edge treatments and pinpointing essential areas for future research to address the persistent hurdles in controlling this potentially devastating ocular infection. Full article

(This article belongs to the Section Physiology and Pathology)

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20 pages, 1373 KiB

Open AccessArticle

Influence and Predictors of Anxiety on Health Status ≥ 5 Years Beyond Breast Cancer Diagnosis in Spain: A Cross-Sectional Study

by Francisco Álvarez-Salvago, Clara Pujol-Fuentes, Jose Medina-Luque, Maria Figueroa-Mayordomo, Carmen Boquete-Pumar and Sandra Atienzar-Aroca

Life 2025, 15(6), 932; https://doi.org/10.3390/life15060932 - 10 Jun 2025

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Abstract

Purpose: To explore the association between anxiety levels and health outcomes in long-term breast cancer survivors (LTBCSs) and to identify predictors of anxiety in this population. Methods: A multicenter cross-sectional study was conducted with 80 LTBCSs, categorized into two groups based on [...] Read more.

Purpose: To explore the association between anxiety levels and health outcomes in long-term breast cancer survivors (LTBCSs) and to identify predictors of anxiety in this population. Methods: A multicenter cross-sectional study was conducted with 80 LTBCSs, categorized into two groups based on their anxiety levels: low anxiety (≤3.4) and high anxiety (≥3.5). The analysis focused on variables assessed at least five years after diagnosis, including sociodemographic and clinical data, mood, cancer-related fatigue (CRF), pain, self-perceived physical fitness, physical activity (PA), and health-related quality of life (HRQoL). ANOVA, Mann–Whitney U, and chi-square tests were conducted, along with correlation and multiple regression analysis. Effect sizes were calculated using Cohen’s d. Results: Among the participants, 46.25% exhibited higher anxiety levels. This group showed significantly worse mood, self-perceived physical fitness, and HRQoL and elevated CRF and pain (p < 0.05). Regression analysis identified “total CRF” (β = 0.51; p < 0.01) and “cognitive functioning” (β = −0.24; p = 0.02) as significant predictors of higher levels of anxiety (r² adjusted = 0.470). Conclusions: Anxiety significantly impacts multiple dimensions of health in LTBCSs. Total CRF and cognitive functioning are key predictors of anxiety. These findings have direct clinical implications: routine psychological and physical assessments should be integrated into survivorship care to identify individuals at risk and inform targeted interventions to enhance long-term well-being and HRQoL. Full article

(This article belongs to the Section Physiology and Pathology)

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11 pages, 1001 KiB

Open AccessArticle

Extracellular Vesicles Mediate Epimastigogenesis in Trypanosoma cruzi: Strain-Specific Dynamics and Temperature-Dependent Differentiation

by Abel Sana, Izadora Volpato Rossi, Bruna Sabatke and Marcel Ivan Ramirez

Life 2025, 15(6), 931; https://doi.org/10.3390/life15060931 - 9 Jun 2025

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Abstract

Trypanosoma cruzi, the causative agent of Chagas disease, undergoes epimastigogenesis—a critical differentiation step in which trypomastigotes transform into epimastigotes. While this process is essential for the parasite’s survival in its insect vector, the molecular mechanisms regulating it remain poorly understood. Here, we [...] Read more.

Trypanosoma cruzi, the causative agent of Chagas disease, undergoes epimastigogenesis—a critical differentiation step in which trypomastigotes transform into epimastigotes. While this process is essential for the parasite’s survival in its insect vector, the molecular mechanisms regulating it remain poorly understood. Here, we present the first evidence implicating extracellular vesicles (EVs) as enhancing mediators of epimastigogenesis. Using in vitro models with T. cruzi strains CL Brener and Dm28c, we demonstrate that EVs, membrane-bound vesicles, were shown to enhance differentiation in a strain-specific and temperature-dependent manner. We observed strain-specific EV release patterns: Dm28c produced more EVs at 24 h, whereas CL Brener peaked at 72 h. Additionally, we confirm that epimastigogenesis occurs exclusively at 28 °C after 72 h. These findings establish EVs as novel regulators of T. cruzi differentiation and suggest new insight into parasite development, highlighting potential targets for therapeutic intervention. The observed enhancement of differentiation in the presence of EVs indicates a potential role for these vesicles in this developmental process, although the underlying mechanisms remain undefined. Full article

(This article belongs to the Special Issue Trends in Microbiology 2025)

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14 pages, 1837 KiB

Open AccessArticle

Synthesis and Evaluation of ¹²⁵I-IMPY: Application in Neuroblastoma Tracing and Treatment

by Tsung-Ming Wang, Shih-Chang Chuang, Kuo-Chen Hung, Chang-Ching Yu, Tzu-Chuan Ho, Kuo-Pin Chuang, Cheng-Hui Yuan, Ming-Hui Yang and Yu-Chang Tyan

Life 2025, 15(6), 930; https://doi.org/10.3390/life15060930 - 9 Jun 2025

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Abstract

Background: Radiolabeled compounds can serve as diagnostic or therapeutic agents depending on the characteristics of the isotopes used. IMPY (6-iodo-2-(4′-dimethylamino)-phenyl-imidazo[1,2-a]pyridine) is a lipophilic derivative of thioflavin-T, designed to function as a tracer when labeled with radioactive iodine. While it has been primarily studied [...] Read more.

Background: Radiolabeled compounds can serve as diagnostic or therapeutic agents depending on the characteristics of the isotopes used. IMPY (6-iodo-2-(4′-dimethylamino)-phenyl-imidazo[1,2-a]pyridine) is a lipophilic derivative of thioflavin-T, designed to function as a tracer when labeled with radioactive iodine. While it has been primarily studied for imaging applications, its potential therapeutic effects when labeled with iodine-125 (¹²⁵I) remain to be explored. Methods: In this study, IMPY was synthesized and labeled with ¹²⁵I for therapeutic purposes. Three different labeling methods were employed: isotope exchange reaction, redox reaction, and the Iodogen technique. The radiochemical yield of each method was determined to identify the most effective approach. Additionally, the effects of ¹²⁵I-IMPY on neuroblastoma cells were evaluated by assessing its toxicity and cellular uptake. Results: The radiochemical yields for the isotope exchange reaction, redox reaction, and Iodogen technique were found to be 0.96%, 10.74%, and 96.52%, respectively. The Iodogen technique exhibited the highest yield, exceeding 90% even after 48 h, making it the most efficient method. Furthermore, the impact of ¹²⁵I-IMPY on neuroblastoma cells was analyzed, revealing significant cellular uptake and potential therapeutic effects. Conclusions: This study demonstrated that the Iodogen technique is the most effective method for labeling IMPY with ¹²⁵I. The high labeling efficiency and observed cellular effects suggest that ¹²⁵I-IMPY could be considered not only as a tracer but also as a potential therapeutic agent for neuroblastoma. Further studies are needed to explore its full therapeutic potential and mechanism of action. Full article

(This article belongs to the Section Medical Research)

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13 pages, 1739 KiB

Open AccessArticle

CYTO-SV-ML: A Machine Learning Tool for Cytogenetic Structural Variant Analysis in Somatic Cell Type Using Genome Sequences

by Tao Zhang, Paul Auer, Stephen R. Spellman, Jing Dong, Wael Saber and Yung-Tsi Bolon

Life 2025, 15(6), 929; https://doi.org/10.3390/life15060929 - 9 Jun 2025

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Abstract

(1) Background: Although whole genome sequencing (WGS) has enabled the comprehensive analyses of structural variants (SVs), more accurate and efficient methods are needed to distinguish large somatic SVs (SV size ≥ 1 Mb) traditionally detected through cytogenetic testing from germline SVs. (2) Methods: [...] Read more.

(1) Background: Although whole genome sequencing (WGS) has enabled the comprehensive analyses of structural variants (SVs), more accurate and efficient methods are needed to distinguish large somatic SVs (SV size ≥ 1 Mb) traditionally detected through cytogenetic testing from germline SVs. (2) Methods: A customized machine learning pipeline (CYTO-SV-ML) under Snakemake automation workflow was developed with a user interface to identify somatic cytogenetic SVs in WGS data. And this tool was applied for characterizing structural variation profiles in the whole blood of patients with myelodysplastic syndromes (MDSs). Known SVs mapped from well-established open databases were split into training and validation subsets for an AUTO-ML machine learning model in a CYTO-SV-ML pipeline. (3) Results: The benchmarking performance of the CYTO-SV-ML pipeline on somatic cytogenetic SV classification displayed an area under the receiver operating characteristic curve (AUCROC) of 0.94 for translocations and 0.92 for non-translocations, a sensitivity of 0.83 for translocations and 0.85 for non-translocations, and a specificity of 0.96 for translocations and 0.82 for non-translocations. Our method (207 somatic cytogenetic SVs) outperformed a conventional SV calling pipeline (143 somatic cytogenetic SVs) in an independent validation of clinical cytogenetic records. In addition, the CYTO-SV-ML pipeline uncovered novel somatic cytogenetic SVs in 49 (89%) of 55 patients without successful clinical cytogenetic results. (4) Conclusions: Our study demonstrates the high-performance machine learning approach of CYTO-SV-ML on benchmarking SV classification from genomic sequencing data, and further validations of novel anomalies by orthogonal methods will be essential to unlock its full clinical potential of cytogenetic diagnostics. Full article

(This article belongs to the Special Issue Molecular and Cellular Biology of Transplantation)

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15 pages, 1570 KiB

Open AccessArticle

The Anti-Inflammatory Potential of Levosimendan in Sepsis: An Experimental Study Using a LPS-Induced Rat Model

by Elif Dedeler Ertanıdır, Ipek Duman, Duygu Onmaz Eryavuz, Ali Ünlü, Mehmet Ertanıdır and Ateş Duman

Life 2025, 15(6), 928; https://doi.org/10.3390/life15060928 - 9 Jun 2025

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Abstract

Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on [...] Read more.

Sepsis is a life-threatening condition driven by a dysregulated host immune response to infection, with cytokine overproduction contributing to organ dysfunction and high mortality. Levosimendan, a calcium sensitizer used in acute heart failure, has been proposed to exert anti-inflammatory effects, but information on its immunomodulatory effects in early sepsis remains scarce. This study aimed to investigate the dose- and time-dependent effects of levosimendan on cytokine profiles in a rat model of lipopolysaccharide (LPS)-induced sepsis. Thirty-two male Wistar albino rats were randomly assigned to four groups: sham, sepsis control, low-dose levosimendan (1 mg/kg), and high-dose levosimendan (2 mg/kg). Cytokine levels (TNF-α, IL-1β, IL-6, IL-8, IL-17, MCP-1) were measured at 5 and 10 h post-LPS administration. High-dose levosimendan significantly reduced TNF-α, IL-1β, IL-6, and MCP-1 levels by the 10th hour, accompanied by improved Murine Sepsis Scores. IL-17 and IL-6 showed biphasic responses, increasing initially and decreasing significantly later, particularly with high-dose treatment. IL-8 reduction was observed only in the high-dose group. These findings support levosimendan’s dose and time-dependent anti-inflammatory effects and suggest it may modulate both early and late-phase cytokines in sepsis. Further studies are warranted to clarify its potential role in clinical sepsis management. Full article

(This article belongs to the Section Pharmaceutical Science)

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17 pages, 1926 KiB

Open AccessArticle

Patterns of Variation and Coordination in Shoot Traits Across Four Branching Orders of Larix principis-rupprechtii

by Yang Yu, Huayong Zhang, Zhongyu Wang and Zhao Liu

Life 2025, 15(6), 927; https://doi.org/10.3390/life15060927 - 9 Jun 2025

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Abstract

Intraspecific variation in functional traits can more accurately quantify plant responses to environmental changes and resource competition, while the plant economic spectrum provides a fundamental framework for understanding trait variation along environmental gradients. As the structural units of the aboveground branching system in [...] Read more.

Intraspecific variation in functional traits can more accurately quantify plant responses to environmental changes and resource competition, while the plant economic spectrum provides a fundamental framework for understanding trait variation along environmental gradients. As the structural units of the aboveground branching system in woody plants, it remains unclear whether shoots exhibit a universal whole-plant economic spectrum and whether branch order significantly affects the patterns of trait variation and coordination. We collected 1551 shoots of Larix principis-rupprechtii to examine the patterns of trait variation and coordination from different branch orders to the whole-plant level. From the perspective of the plant economic spectrum, five functional traits were selected to represent the trade-off between structural and nutrient investment: the stem diameter (SD), stem length (SL), stem dry mass (SDM), specific stem length (SSL), and stem tissue density (STD). From different branch orders to the whole-plant level, allocation played a relatively more important role, and the patterns of pairwise trait correlations and trade-offs along the resource economic axis were consistent. Branch order did not strongly influence the correlations and degree of coordination within the shoot economic spectrum, as the whole-plant shoot economic spectrum was evident within each branch order. Our results support the hypothesis that the coordinated economic spectrum across branch orders forms an integrated whole-plant economic spectrum representing a “conservative–collaborative” resource management strategy. This strategy is robust to recent evolutionary changes (such as genotypic variation and even differences among shoots within the same species) as well as to variation across different branch orders. Full article

(This article belongs to the Section Plant Science)

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Life, Volume 15, Issue 6 (June 2025) – 128 articles

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