Life

11 pages, 622 KB

Open AccessArticle

Preliminary Identification of Putative Terpene Synthase Genes in Caryocar brasiliense and Chemical Analysis of Major Components in the Fruit Exocarp

by Helena Trindade, Bruno Nevado, Raquel Linhares Bello de Araújo, Viviane Dias Medeiros Silva, Lara Louzada Aguiar, Ana Ribeiro, Julio Onesio-Ferreira Melo and Paula Batista-Santos

Life 2026, 16(1), 67; https://doi.org/10.3390/life16010067 (registering DOI) - 1 Jan 2026

Abstract

Background: Caryocar brasiliense Camb. Caryocaraceae is a typical tree from the Brazilian Cerrado with commercial importance due to its edible fruit, known as pequi. This native plant holds significant economic value and is a key candidate for cropping systems. Rich in phytochemicals, [...] Read more.

Background: Caryocar brasiliense Camb. Caryocaraceae is a typical tree from the Brazilian Cerrado with commercial importance due to its edible fruit, known as pequi. This native plant holds significant economic value and is a key candidate for cropping systems. Rich in phytochemicals, such as phenolics, flavonoids, and terpenoids, it has shown notable health benefits. Methods: Considering the importance of terpenes and their biological properties, and based on the first draft genome of C. brasiliense, this study aimed to identify putative terpene synthase genes and classify them into the phylogenetic subfamilies previously identified across all plant lineages. The presence of terpenes was also verified in samples of the outer portion of the fruit by solid-phase microextraction gas chromatography mass-spectrometry. Results: Analysis of genome completeness showed that over 90% of genes were identified despite a highly fragmented assembly, with 71% containing complete gene sequences. Twenty-two genes were retained as putative terpene synthase genes considering their homology with the terpene synthase Hidden Markov Model (HMM) profiles in the Pfam-A database. Ten sequences with a minimum length of 298 amino acids were used for phylogenetic inference. In the resulting phylogenetic tree, C. brasiliense terpene synthase genes clustered within the different previously identified Angiosperm clades and allowed us to classify each gene into different phylogenetic subfamilies: six genes belonged to the h/d/a/b/g, three to the c, and one to the e/f. The headspace solid-phase microextraction technique, in conjunction with gas chromatography mass-spectrometry, has allowed for the identification of eleven chemical compounds, including a terpene. Conclusions: This initial identification of putative terpene synthase genes in pequi, together with the chemical analysis of the outer fruits, lays the groundwork for future studies aimed at optimizing terpene biosynthesis for both biological and commercial applications. Full article

(This article belongs to the Section Plant Science)

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13 pages, 2469 KB

Open AccessArticle

Visual Large Language Models in Radiology: A Systematic Multimodel Evaluation of Diagnostic Accuracy and Hallucinations

by Marc Sebastian von der Stück, Roman Vuskov, Simon Westfechtel, Robert Siepmann, Christiane Kuhl, Daniel Truhn and Sven Nebelung

Life 2026, 16(1), 66; https://doi.org/10.3390/life16010066 (registering DOI) - 1 Jan 2026

Abstract

Visual large language models (VLLMs) are discussed as potential tools for assisting radiologists in image interpretation, yet their clinical value remains unclear. This study provides a systematic and comprehensive comparison of general-purpose and biomedical VLLMs in radiology. We evaluated 180 representative clinical images [...] Read more.

Visual large language models (VLLMs) are discussed as potential tools for assisting radiologists in image interpretation, yet their clinical value remains unclear. This study provides a systematic and comprehensive comparison of general-purpose and biomedical VLLMs in radiology. We evaluated 180 representative clinical images with validated reference diagnoses (radiography, CT, MRI; 60 each) using seven VLLMs (ChatGPT-4o, Gemini 2.0, Claude Sonnet 3.7, Perplexity AI, Google Vision AI, LLaVA-1.6, LLaVA-Med-v1.5). Each model interpreted the image without and with clinical context. Mixed-effects logistic regression models assessed the influence of model, modality, and context on diagnostic performance and hallucinations (fabricated findings or misidentifications). Diagnostic accuracy varied significantly across all dimensions (p ≤ 0.001), ranging from 8.1% to 29.2% across models, with Gemini 2.0 performing best and LLaVA performing weakest. CT achieved the best overall accuracy (20.7%), followed by radiography (17.3%) and MRI (13.9%). Clinical context improved accuracy from 10.6% to 24.0% (p < 0.001) but shifted the model to rely more on textual information. Hallucinations were frequent (74.4% overall) and model-dependent (51.7–82.8% across models; p ≤ 0.004). Current VLLMs remain diagnostically unreliable, heavily context-biased, and prone to generating false findings, which limits their clinical suitability. Domain-specific training and rigorous validation are required before clinical integration can be considered. Full article

(This article belongs to the Special Issue Current and Future Perspectives of Artificial Intelligence in Medicine)

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14 pages, 869 KB

Open AccessArticle

Gingival Thickness Improvement After Atelocollagen Injection—Retrospective Study

by Sylwia Klewin-Steinböck, Anna Duda-Sobczak and Marzena Liliana Wyganowska

Life 2026, 16(1), 65; https://doi.org/10.3390/life16010065 (registering DOI) - 1 Jan 2026

Abstract

Background: This study evaluates the increase in gingival thickness following the administration of injectable atelocollagen. Materials and Methods: A retrospective analysis was conducted using the medical records of 60 patients with a thin gingival phenotype at baseline, treated between 2017 and 2025. All [...] Read more.

Background: This study evaluates the increase in gingival thickness following the administration of injectable atelocollagen. Materials and Methods: A retrospective analysis was conducted using the medical records of 60 patients with a thin gingival phenotype at baseline, treated between 2017 and 2025. All patients received a standardised protocol for soft tissue thickness modification using atelocollagen injections. Based on the continuation of maintenance therapy, patients were divided into Group A (n = 30), consisting of patients who received booster doses at six-month intervals following completion of the full treatment protocol, and Group B (n = 30), consisting of patients who did not continue maintenance therapy. The observation period for all patients was five years. Gingival thickness was assessed by periodontal probe transparency using a standard WHO probe (WHO 621) and the Hu-Friedy Colorvue Biotype Probe. Longitudinal changes were analysed using linear mixed-effects models (LMMs) for continuous outcomes and generalised linear mixed-effects models (GLMMs) with a binomial distribution and logit link for binary outcomes, accounting for repeated measurements at the patient level. Results: Significant effects of Group and Time, as well as their interaction, were observed for the proportion of sites with a thick gingiva (Group effect: F (1,93.14) = 57.94, p < 0.001; Group × Time interaction: p < 0.001). GLMM analysis confirmed a significant Group × Time interaction (χ² = 23.11, p < 0.001), indicating sustained gingival thickness improvement in Group A and a gradual decrease in effectiveness in Group B. Conclusions: Injectable atelocollagen represents a reliable, effective, and user-friendly method for long-term modification of gingival thickness, particularly when supported by maintenance therapy. Full article

(This article belongs to the Section Medical Research)

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22 pages, 1218 KB

Open AccessSystematic Review

Systematic Review: Exploring Inter-Species Variability in Diabetes Mellitus for Translational Medicine

by Luminița Diana Hrițcu, Vasile Boghian, Geta Pavel, Teodor Daniel Hrițcu, Florin Nechifor, Alexandru Spataru, Alexandra Andreea Cherșunaru, Alexandru Munteanu, Manuela Ciocoiu and Mihaela-Claudia Spataru

Life 2026, 16(1), 64; https://doi.org/10.3390/life16010064 - 31 Dec 2025

Abstract

Interspecies variability in diabetes mellitus (DM) represents a critical challenge for translational medicine, as metabolic pathways, pancreatic architecture, and therapeutic responses differ substantially across animal models. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence from 86 eligible studies published between [...] Read more.

Interspecies variability in diabetes mellitus (DM) represents a critical challenge for translational medicine, as metabolic pathways, pancreatic architecture, and therapeutic responses differ substantially across animal models. This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence from 86 eligible studies published between 2001 and 2025. Comparative data from rodents, dogs, cats, pigs, non-human primates, and humans were analyzed to identify species-specific patterns in insulin secretion, insulin resistance (IR), β-cell dysfunction, microbiota–metabolism interactions, and susceptibility to diabetic complications. Results indicate that spontaneous diabetes in dogs closely mirrors human type 1 diabetes (T1DM), whereas feline obesity-associated diabetes reflects key features of human type 2 diabetes (T2DM). Rodent models remain essential for mechanistic and genetic studies but show limited chronicity and lower predictive fidelity for long-term outcomes. Non-human primates exhibit the highest physiological similarity to humans, especially regarding β-cell structure and incretin response, supporting their role in advanced translational studies. Major limitations included methodological heterogeneity and inconsistent molecular reporting. Integrating spontaneous models with standardized protocols and multi-omics approaches enhances translational relevance and supports more accurate model selection in diabetes research. Full article

(This article belongs to the Special Issue From Animal Models to Clinical Innovations: Translating Research into Medicine)

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20 pages, 957 KB

Open AccessReview

Paclitaxel- and Sirolimus-Coated Balloons Versus Drug-Eluting Stents in Coronary Artery Disease: A Comprehensive Narrative Review

by Flavius-Alexandru Gherasie, Al Hassan Ali, Ana Maria Corzanu, Eva Catalina Costescu and Sonia-Gabriela Cornea

Life 2026, 16(1), 63; https://doi.org/10.3390/life16010063 - 31 Dec 2025

Abstract

Drug-coated balloons (DCBs) have emerged as an alternative to drug-eluting stents (DESs) in percutaneous coronary intervention, delivering antiproliferative drugs without leaving a permanent implant. This review provides a comparative analysis of sirolimus-coated DCBs (DCB-S), paclitaxel-coated DCBs (DCB-P), and DESs across key scenarios: de [...] Read more.

Drug-coated balloons (DCBs) have emerged as an alternative to drug-eluting stents (DESs) in percutaneous coronary intervention, delivering antiproliferative drugs without leaving a permanent implant. This review provides a comparative analysis of sirolimus-coated DCBs (DCB-S), paclitaxel-coated DCBs (DCB-P), and DESs across key scenarios: de novo coronary lesions in chronic coronary syndrome (CCS), acute coronary syndromes (ACS), and in-stent restenosis (ISR). We discuss late lumen loss (LLL), target lesion/vessel revascularization (TLR/TVR), vessel patency, and major adverse cardiac events (MACE) outcomes, along with current guidelines and emerging indications for DCB-S. We also examine pharmacological differences between sirolimus and paclitaxel (mechanisms of action, tissue uptake, and healing profiles), trial methodologies, and recent innovations in DCB technology. Across stable de novo lesions (especially small vessels and high bleeding-risk patients), multiple trials show DCB-P can achieve non-inferior clinical outcomes to DES. Early data suggest newer DCB-S may likewise match DES outcomes in broader populations. In ACS, DCB-only strategies have demonstrated feasibility and safety in carefully selected lesions without heavy thrombus, with randomized studies like REVELATION (STEMI) showing non-inferior fractional flow reserve and low revascularization rates compared to DES. For ISR, DCB-P is an established Class I treatment in both BMS-ISR and DES-ISR, yielding similar or lower TLR rates than repeat stenting. DCB-S are now being evaluated as an alternative in ISR, aiming to avoid additional stent layers. Contemporary guidelines endorse DCB use in ISR and small vessels, and experts anticipate expanding indications as evidence grows. Sirolimus and paclitaxel differ in antiproliferative mechanisms and pharmacokinetics—sirolimus (cytostatic, mTOR inhibition) may offer faster endothelial recovery, whereas paclitaxel’s high lipophilicity ensures sustained arterial wall retention. Technological advances (e.g., phospholipid micro-reservoirs for sirolimus) are enhancing drug transfer and addressing prior limitations. In summary, DCB-P and DCB-S now represent viable alternatives to DES in specific scenarios, especially where “leaving nothing behind” could reduce long-term complications. Ongoing large randomized trials, such as SELUTION DeNovo, currently available as conference-presented data, together with longer-term follow-up will further clarify the optimal niches for DCB-S versus DCB-P and DES. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: From Basic Research to Clinical Application—3rd Edition)

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12 pages, 1308 KB

Open AccessArticle

Peak Lactate Within 24 h and Mortality in Septic Shock Patients Receiving Continuous Renal Replacement Therapy: A Real-World Cohort from an Asian ICU (2018–2020)

by Wei-Hung Chang, Ting-Yu Hu and Li-Kuo Kuo

Life 2026, 16(1), 62; https://doi.org/10.3390/life16010062 - 31 Dec 2025

Abstract

Background: Serum lactate is a key biomarker of tissue hypoperfusion and metabolic stress in sepsis. Although lactate clearance is widely recognized, many intensive care units record only a peak lactate within 24 h (pLac-24h). The prognostic value of pLac-24h among patients receiving blood [...] Read more.

Background: Serum lactate is a key biomarker of tissue hypoperfusion and metabolic stress in sepsis. Although lactate clearance is widely recognized, many intensive care units record only a peak lactate within 24 h (pLac-24h). The prognostic value of pLac-24h among patients receiving blood purification therapy remains unclear in Asian intensive care settings. Methods: We retrospectively analyzed the 2018–2020 ICU dataset from MacKay Memorial Hospital, Taiwan. Among 16,693 adult ICU admissions, 2506 patients received continuous renal replacement therapy (CRRT) as blood purification for severe sepsis or septic shock. Of these, 1264 (50.4%) had available pLac-24h data, and 27 (1.1%) also required extracorporeal membrane oxygenation (ECMO). The primary outcome was 28-day all-cause mortality. Multivariate logistic regression adjusted for age, sex, APACHE II score, infection source, and CRRT/ECMO use. Discrimination was evaluated by receiver operating characteristic (ROC) curves and decision-curve analysis. This analysis was conducted as a predefined sub-analysis of an institutional ICU database. Results: The mean age of the cohort was 65.7 ± 13.4 years, and 64.8% were male. Median pLac-24h was 5.1 mmol/L (IQR 3.2–8.6). The overall 28-day mortality among CRRT patients was 47.3%. Mortality rose progressively across pLac-24h quartiles (Q1–Q4: 28.9%, 39.4%, 54.7%, and 68.1%; p < 0.001). Each 1 mmol/L increase in pLac-24h independently predicted higher mortality (adjusted OR 1.18, 95% CI 1.10–1.26, p < 0.001). The area under the ROC curve for pLac-24h predicting 28-day mortality was 0.78 (95% CI 0.74–0.82), outperforming the APACHE II score (AUC 0.69, p = 0.02). Conclusions: In critically ill patients with septic shock undergoing CRRT, peak lactate within 24 h was a strong, independent predictor of 28-day mortality. pLac-24h offers a pragmatic, readily available prognostic indicator when serial lactate measurements are unavailable, supporting its integration into bedside risk assessment in real-world Asian ICU practice. Full article

(This article belongs to the Special Issue Acute Kidney Events in Intensive Care)

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35 pages, 2308 KB

Open AccessReview

Long-Term PM_2.5 Exposure and Clinical Skin Aging: A Systematic Review and Meta-Analysis of Pigmentary and Wrinkle Outcomes

by Jeng-Wei Tjiu and Chia-Fang Lu

Life 2026, 16(1), 61; https://doi.org/10.3390/life16010061 - 30 Dec 2025

Abstract

Background: Fine particulate matter (PM_2.5) is an established systemic toxicant, yet its association with clinical skin aging remains incompletely characterized. Although pigmentary changes and wrinkles are commonly attributed to ultraviolet exposure, experimental and epidemiologic evidence suggests that long-term PM_2.5 exposure [...] Read more.

Background: Fine particulate matter (PM_2.5) is an established systemic toxicant, yet its association with clinical skin aging remains incompletely characterized. Although pigmentary changes and wrinkles are commonly attributed to ultraviolet exposure, experimental and epidemiologic evidence suggests that long-term PM_2.5 exposure may contribute to extrinsic skin aging through oxidative, inflammatory, and aryl hydrocarbon receptor-mediated pathways. However, human studies specifically quantifying PM_2.5 exposure in relation to validated skin aging outcomes are sparse, and no prior meta-analysis has systematically synthesized this evidence. Objective: To conduct a systematic review and meta-analysis of epidemiologic studies reporting measured or modeled long-term PM_2.5 exposure and extractable quantitative associations with clinical skin aging outcomes. Methods: We performed a comprehensive PRISMA 2020-guided search of PubMed, Embase, Web of Science, and Scopus (inception to 18 November 2025). Eligible studies included human participants, quantified long-term PM_2.5 exposure, validated clinical or imaging-based skin aging outcomes, and extractable effect estimates. Ratio-type effect measures (arithmetic mean ratios, geometric mean ratios, and odds ratios) were transformed to the natural-log scale, standardized to a common exposure contrast of per 10 µg/m³ PM_2.5, and synthesized as generic relative association metrics. Random-effects models with DerSimonian–Laird estimation and Hartung–Knapp adjustment were applied for pigmentary outcomes. VISIA imaging β-coefficients were synthesized narratively. Results: Four epidemiologic cohorts met predefined eligibility criteria. From these, we extracted seven PM_2.5-specific pigmentary effect estimates, one clinically assessed wrinkle estimate, and two VISIA imaging outcomes. The pooled relative association for pigmentary aging corresponded to a ratio of 1.11 per 10 µg/m³ PM_2.5 (95% CI, 0.82–1.50), indicating a directionally positive but statistically imprecise association compatible with both increased and unchanged pigmentary aging. All individual pigmentary estimates were directionally positive. A single cohort reported a 3.2% increase in wrinkle severity per 10 µg/m³ PM_2.5 (ratio 1.032). VISIA imaging showed significant worsening of brown spot severity (+9.5 percentile per 10 µg/m³), while wrinkle percentiles showed a non-significant change. Conclusions: Based on a comprehensive PRISMA-guided search, the available epidemiologic evidence suggests a consistent directionally positive association between long-term PM_2.5 exposure and pigmentary skin aging outcomes, with limited and uncertain evidence for wrinkle-related phenotypes. The current evidence base remains small, heterogeneous, and of low certainty. Accordingly, these findings should be interpreted as hypothesis-generating and underscore the need for larger, longitudinal, and methodologically harmonized studies. (Registration: PROSPERO CRD420251231462) Full article

(This article belongs to the Section Medical Research)

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6 pages, 990 KB

Open AccessCase Report

Primary Colorectal Signet-Ring Cell Carcinoma with Synchronous Colonic Metastases in an Asymptomatic Patient: Case Presentation and Comprehensive Literature Review

by Oana-Bogdana Barboi, Radu-Alexandru Vulpoi, Diana-Elena Floria, Vadim Rosca, Constantin Simiras, Andriescu Elena-Corina, Amitoaie Iulia and Vasile-Liviu Drug

Life 2026, 16(1), 60; https://doi.org/10.3390/life16010060 - 30 Dec 2025

Abstract

Background: Less than 1% of all colorectal cancers (CRCs) are primary colorectal signet-ring cell carcinomas (SRCCs), which represent an uncommon and aggressive histological subtype. Given their subtle onset and rapid progression, these are often diagnosed in an advanced stage, and can be distinguished [...] Read more.

Background: Less than 1% of all colorectal cancers (CRCs) are primary colorectal signet-ring cell carcinomas (SRCCs), which represent an uncommon and aggressive histological subtype. Given their subtle onset and rapid progression, these are often diagnosed in an advanced stage, and can be distinguished by the presence of mucin-producing signet-ring cells. Synchronous colonic metastases at initial diagnosis are rather uncommon. Case presentation: We report the case of a 65-year-old male patient who underwent a routine colonoscopy following a positive fecal immunochemical test (FIT). The patient had no remarkable medical history and was asymptomatic. A 3 cm semi-pedunculated polyp and several smaller depressed lesions, 2 cm maximum in diameter, were observed in the descending colon during the colonoscopy. Multiple biopsies were obtained. The lesions were found to be SRCC according to histopathological examination. There was no sign of extra-colonic metastases on the computed tomography (CT). The patient was referred for extensive hemicolectomy, regional lymphadenectomy, and adjuvant chemotherapy. Conclusions: This article provides a thorough literature review on this uncommon presentation and discussion regarding the current understanding of the pathogenesis, clinical manifestations, and management strategies of SRCC. This case highlights the importance of routine screening in detecting aggressive malignancies like SRCC in asymptomatic individuals. Early identification through colonoscopy can lead to timely intervention, potentially improving prognosis. Full article

(This article belongs to the Section Medical Research)

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12 pages, 1713 KB

Open AccessArticle

Relationship Between Clinical Factors and the Risk of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: An Exploratory Analysis

by Máté Czabajszki, Attila Garami, Péter Csécsei, Béla Viskolcz, Csaba Oláh and Csaba Váradi

Life 2026, 16(1), 59; https://doi.org/10.3390/life16010059 - 30 Dec 2025

Abstract

Background/Objectives: Cerebral subarachnoid hemorrhage (SAH) from ruptured aneurysms poses significant morbidity and mortality risks. Among survivors, cerebral vasospasm can develop, increasing complications. This study investigates the relationship between blood parameters and the risk of vasospasm. Methods: We analyzed clinical data from patients with [...] Read more.

Background/Objectives: Cerebral subarachnoid hemorrhage (SAH) from ruptured aneurysms poses significant morbidity and mortality risks. Among survivors, cerebral vasospasm can develop, increasing complications. This study investigates the relationship between blood parameters and the risk of vasospasm. Methods: We analyzed clinical data from patients with SAH—both with and without vasospasm—and healthy controls. Statistical analyses, including Spearman’s rank correlation and univariate analysis, were conducted. Results: Significant differences were observed between patients with and without vasospasm. Elevated white blood cell counts, a higher neutrophil-to-lymphocyte ratio, and lower platelet counts showed a significant association with symptomatic vasospasm. Younger age and female gender were associated with a higher risk. Conclusions: These preliminary findings highlight the importance of specific blood parameters and demographic factors in assessing the risk of cerebral vasospasm in SAH patients, supporting early risk stratification and monitoring to improve outcomes; however, these results require validation in larger cohorts. Full article

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

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21 pages, 522 KB

Open AccessReview

PEDV Structural Proteins with Emphasis on M Protein as an Immunomodulatory Factor in Porcine Innate Immunity

by Jae-Yeon Park and Hye-Mi Lee

Life 2026, 16(1), 58; https://doi.org/10.3390/life16010058 - 30 Dec 2025

Abstract

Porcine epidemic diarrhea virus (PEDV) is an enteric alphacoronavirus that causes severe diarrhea and high mortality in neonatal pigs, leading to substantial economic loss in the porcine industry. Previous studies have primarily focused on the spike protein because of its role in viral [...] Read more.

Porcine epidemic diarrhea virus (PEDV) is an enteric alphacoronavirus that causes severe diarrhea and high mortality in neonatal pigs, leading to substantial economic loss in the porcine industry. Previous studies have primarily focused on the spike protein because of its role in viral entry and induction of neutralizing antibody responses. However, accumulating evidence indicates that other viral components also contribute to host immune modulation and pathogenesis. This review summarizes the current knowledge on PEDV structural proteins, with an emphasis on membrane proteins as regulators of porcine innate immune responses. The molecular characteristics and intracellular localization of membrane proteins were described, and the reported effects on interferon signaling, inflammatory pathways, and cellular stress responses were examined. Findings from related coronaviruses were incorporated to highlight the conserved features and virus-specific differences in membrane protein-mediated host modulation. Available evidence suggests that membrane protein-associated interference with innate immune signaling may contribute to intestinal immune dysregulation and disease severity in neonatal piglets. The implications of these observations on PEDV pathogenesis and intervention strategies are also discussed. By shifting attention from spike-centered frameworks to structural protein-driven host interactions, this review highlights membrane proteins as an underexplored but biologically relevant factor in porcine coronavirus research. Full article

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

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27 pages, 478 KB

Open AccessReview

Phage Therapy: Application and Related Problems—A Review

by Katharina Sippel and Branko Velimirov

Life 2026, 16(1), 57; https://doi.org/10.3390/life16010057 - 30 Dec 2025

Abstract

Bacteriophages, viruses that target bacteria, offer a promising alternative to antibiotics in the face of escalating bacterial resistance. Despite their discovery over a century ago, their widespread adoption has been impeded by regulatory challenges, limited funding, and the dominance of antibiotics. This review [...] Read more.

Bacteriophages, viruses that target bacteria, offer a promising alternative to antibiotics in the face of escalating bacterial resistance. Despite their discovery over a century ago, their widespread adoption has been impeded by regulatory challenges, limited funding, and the dominance of antibiotics. This review evaluates the current status of phage therapy by examining a comprehensive literature search, applying predefined inclusion and exclusion criteria. The review assesses selected scientific reports and clinical studies for their safety and efficacy profiles. Our findings indicate that advancements in phage therapy involve critical steps such as rapid bacterial detection, effective isolation, production, purification of phage preparations, and understanding their interactions with the host. Clinical studies generally show promising safety profiles with fewer adverse events compared to controls, and some trials suggest efficacy even at lower phage titers. Case reports further highlight phage therapy’s potential, demonstrating high success rates and minimal adverse events, although caution is advised due to potential biases. Despite promising results, significant research gaps remain, primarily due to the limited number of large-scale, well-designed clinical trials. Full article

(This article belongs to the Section Microbiology)

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1 pages, 123 KB

Open AccessCorrection

Correction: Solberg, A.; Reikvam, H. Iron Status and Physical Performance in Athletes. Life 2023, 13, 2007

by Andrea Solberg and Håkon Reikvam

Life 2026, 16(1), 56; https://doi.org/10.3390/life16010056 - 30 Dec 2025

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Sport Physiology and Physical Performance)

22 pages, 4237 KB

Open AccessReview

Multiple Basal Cell Carcinomas in a Long-Term Survivor of Childhood ALL and HSCT—A Call for Dermatologic Vigilance

by Elena Porumb-Andrese, Gabriela Stoleriu, Antonia Elena Huțanu, Cristian Mârţu, Mihaela-Paula Toader, Vlad Porumb, Cristina Colac-Boțoc, Ancuța Lupu, Gabriela Rusu-Zota, Emil Anton and Daciana Elena Brănișteanu

Life 2026, 16(1), 55; https://doi.org/10.3390/life16010055 - 30 Dec 2025

Abstract

(1) Background: Cutaneous secondary malignant neoplasms are a growing survivorship burden after pediatric cancers and hematopoietic stem cell transplantation (HSCT), yet skin-focused surveillance remains inconsistently implemented. (2) Objective: To synthesize current molecular dermatology insights relevant to prevention, early detection, and treatment of basal [...] Read more.

(1) Background: Cutaneous secondary malignant neoplasms are a growing survivorship burden after pediatric cancers and hematopoietic stem cell transplantation (HSCT), yet skin-focused surveillance remains inconsistently implemented. (2) Objective: To synthesize current molecular dermatology insights relevant to prevention, early detection, and treatment of basal cell carcinoma (BCC) in high-risk survivors, while anchoring the discussion in a detailed case of multiple BCCs after childhood acute lymphoblastic leukemia and HSCT. (3) Methods: Narrative review integrating clinical, dermoscopic, molecular, and translational data from recent high-impact studies; case retained in full. (4) Results: Radiation exposure (especially total body irradiation), prior immunosuppression, and persistent immune dysregulation synergize with ultraviolet mutagenesis to create a “field cancerization” state characterized by Hedgehog-pathway activation (Patched1/Smoothened), impaired Deoxyribonucleic Acid damage response, and stromal remodeling. Dermoscopy, when embedded in routine whole-body examinations, markedly improves accuracy for keratinocyte cancers. Chemoprevention (e.g., nicotinamide) and targeted therapies (hedgehog inhibitors; Programmed Death-1 blockade) represent key translational levers for care innovation. (5) Conclusions: Integrating structured dermatologic surveillance with molecularly informed prevention and therapy should be standard in survivorship pathways for hematopoietic stem cell transplantation/Radiotherapy-exposed patients. Full article

(This article belongs to the Section Physiology and Pathology)

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19 pages, 1115 KB

Open AccessArticle

Sex-Specific Patterns of Cortisol Fluctuation, Stress, and Academic Success in Quarantined Foreign Medical Students During the COVID-19 Lockdown

by Vedrana Ivić, Irena Labak, Oksana Shevchuk, Rudolf Scitovski, Viktoria Ivankiv, Kateryna Kozak, Mykhaylo Korda, Marija Heffer and Sandor G. Vari

Life 2026, 16(1), 54; https://doi.org/10.3390/life16010054 - 30 Dec 2025

Abstract

Cortisol is built into the circadian clock mechanism, but it is also the body’s natural response to stress. Insight into sex-specific cortisol fluctuations may elucidate individual differences in physiological and pathological patterns. This cross-sectional study examined sex-specific adaptation to stress induced by COVID-19 [...] Read more.

Cortisol is built into the circadian clock mechanism, but it is also the body’s natural response to stress. Insight into sex-specific cortisol fluctuations may elucidate individual differences in physiological and pathological patterns. This cross-sectional study examined sex-specific adaptation to stress induced by COVID-19 pandemic and lockdown in foreign medical students at I. Horbachevsky Ternopil National Medical University, Ukraine (TNMU). Salivary cortisol was analyzed using cluster-based mathematical modeling to identify natural groupings in the data. Perceived stress was measured using Perceived stress scale-10 (PSS-10). The academic success was accessed from the official records of the TNMU. Average value of area under the curve (AUC) of daily salivary cortisol from the whole sample showed that men had higher cortisol than women. Mathematical clustering explained shift of the cortisol peak, and divided sample into 5 clusters—two of which had predicted daily cortisol pattern and represented most participants (65.6% men and 73.6% women), while the rest had aberrant daily cortisol pattern. Females had higher total PSS-10 score than males. PSS-10 subscales correlated with aberrant daily cortisol pattern. Unexpectedly, COVID-related circumstances did not have impact on participants’ academic success. Full article

(This article belongs to the Section Physiology and Pathology)

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14 pages, 3198 KB

Open AccessArticle

The Role of Hemosiderin-Laden Macrophages (HLMs) in the Metastasis of Mammary Gland Cancers in Bitches

by Kacper Żebrowski, Małgorzata Kandefer-Gola, Izabela Janus-Ziółkowska, Rafał Ciaputa and Stanisław Dzimira

Life 2026, 16(1), 53; https://doi.org/10.3390/life16010053 - 29 Dec 2025

Abstract

Mammary gland tumors are among the most common neoplasms in female dogs. Macrophages are believed to play an important role in tumor progression and metastasis. The aim of this study was to determine whether hemosiderin-laden macrophages (HLMs) may be involved in the development [...] Read more.

Mammary gland tumors are among the most common neoplasms in female dogs. Macrophages are believed to play an important role in tumor progression and metastasis. The aim of this study was to determine whether hemosiderin-laden macrophages (HLMs) may be involved in the development of metastatic lesions in regional lymph nodes. Forty-two cases of mammary gland cancers in female dogs and their regional lymph nodes were included in the analysis. The samples were divided into two groups based on the presence or absence of metastases. The sections were stained with hematoxylin and eosin (HE) and Prussian blue and were additionally subjected to immunohistochemical labeling using antibodies against pan-cytokeratin (Pan-CK) and Ki-67. In 20 cases, no metastatic changes were detected in the regional lymph node, whereas metastases were identified in 22 cases. A positive correlation was observed between the number of HLMs in the tumor stroma and the number of HLMs in the regional lymph node. Furthermore, a positive correlation was found between Ki-67 nuclear immunoreactivity in the mammary tumor and the number of HLMs present within its stroma. HLMs may represent a component of the tumor microenvironment that promotes cancer cell proliferation and potentially contributes to the propensity for metastasis formation in mammary tumors of female dogs. Full article

(This article belongs to the Section Animal Science)

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25 pages, 1727 KB

Open AccessReview

Macrophage Plasticity and Regulatory Networks During the Transition from Inflammation to Fibrosis in the Kidney

by Yehun Moon, Jintaek Hong, Jinwoo Chung and Jea-Hyun Baek

Life 2026, 16(1), 52; https://doi.org/10.3390/life16010052 - 29 Dec 2025

Abstract

Kidney fibrosis represents the final common pathway of nearly all progressive renal diseases, linking acute kidney injury (AKI) and chronic kidney disease (CKD) through a maladaptive repair process. Regardless of etiology, persistent inflammation and excessive extracellular matrix (ECM) deposition drive irreversible structural distortion [...] Read more.

Kidney fibrosis represents the final common pathway of nearly all progressive renal diseases, linking acute kidney injury (AKI) and chronic kidney disease (CKD) through a maladaptive repair process. Regardless of etiology, persistent inflammation and excessive extracellular matrix (ECM) deposition drive irreversible structural distortion and functional decline in the kidney. Among cellular mediators, macrophages occupy a central role across the continuum from acute injury to fibrosis, orchestrating both tissue injury and repair through dynamic transitions between pro-inflammatory (M1) and pro-fibrotic (M2) states in response to local cues. Here, we synthesize macrophage-driven mechanisms of renal fibrosis, emphasizing recruitment, infiltration, and local proliferation mediated by chemokine–receptor networks and mechanosensitive ion channels. In addition, in this review paper, we provide an overview on the dual roles of macrophages in acute inflammation and chronic remodeling through key cytokine signaling pathways (TLR4/NF-κB, IL-4/STAT6, TGF-β/Smad, IL-10/STAT3), highlighting how metabolic reprogramming, mechanochemical feedback via Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling, and epigenetic modulators collectively stabilize the fibrotic macrophage phenotype. Also, emerging insights into mitochondrial dysfunction, succinate–succinate receptor 1 (SUCNR1) signaling, and autophagy dysregulation reveal the metabolic basis of macrophage persistence in fibrotic kidneys. Understanding these multilayered regulatory circuits offers a framework for therapeutic strategies that selectively target macrophage-dependent fibrogenesis to halt the transition from acute injury to chronic renal failure. Full article

(This article belongs to the Special Issue New Insights into Cellular Inflammation and Regeneration)

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8 pages, 518 KB

Open AccessArticle

Preliminary Experience with Oxygen-Enriched Oleic Matrix Breast-Shaped Dressings in Oncoplastic Breast Surgery

by Agostino Rodda, Stefano Bottosso, Andrea Lisa, Nadia Renzi, Elisa Bascialla, Giulia Benedetta Sidoti, Germana Lissidini and Giovanni Papa

Life 2026, 16(1), 51; https://doi.org/10.3390/life16010051 - 29 Dec 2025

Abstract

Wound-related issues such as delayed healing and patient discomfort remain common challenges in oncoplastic breast surgery and may negatively affect early postoperative recovery. This single-centre, retrospective, within-patient study explored the feasibility and safety of a breast-shaped polyurethane and polyester dressing impregnated with an [...] Read more.

Wound-related issues such as delayed healing and patient discomfort remain common challenges in oncoplastic breast surgery and may negatively affect early postoperative recovery. This single-centre, retrospective, within-patient study explored the feasibility and safety of a breast-shaped polyurethane and polyester dressing impregnated with an oxygen-enriched oleic matrix, designed to provide a controlled, low-level release of reactive oxygen species involved in physiological tissue repair. Sixty patients undergoing unilateral lumpectomy with contralateral breast remodelling were included. The advanced dressing was applied to the oncologic breast, while standard premedicated patches were used on the contralateral side, allowing each patient to serve as her own control. Early postoperative outcomes, including wound dehiscence, infection, delayed healing, and qualitative user experience, were assessed descriptively over the first postoperative month. The oxygen-enriched oleic matrix dressing was well tolerated and associated with good skin hydration, comfort, and ease of use. No infections, hematomas, or reoperations were observed, and no relevant differences in early complication patterns emerged between the treated and control sides. Both patients and healthcare personnel reported favourable handling characteristics and comfort, with no device-related adverse events. These preliminary, hypothesis-generating findings suggest that oxygen-enriched oleic matrix breast-shaped dressings are a feasible and safe option for early postoperative wound management in oncoplastic breast surgery. Prospective, adequately powered multicentre studies are warranted to further investigate their potential role within standardized postoperative care pathways. Full article

(This article belongs to the Section Medical Research)

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17 pages, 1441 KB

Open AccessReview

Clinical and Etiopathological Perspective of Vitamin B1 Hypersensitivity and an Example of a Desensitization Protocol

by Kinga Lis

Life 2026, 16(1), 50; https://doi.org/10.3390/life16010050 - 28 Dec 2025

Abstract

Vitamin B1 (thiamine) is a water-soluble B vitamin. As a cofactor of many enzymes, it is essential for the proper functioning of many body systems and organs, including metabolic and energy metabolism. In extreme cases, vitamin B1 deficiency causes neurodegenerative disorders, including beri-beri, [...] Read more.

Vitamin B1 (thiamine) is a water-soluble B vitamin. As a cofactor of many enzymes, it is essential for the proper functioning of many body systems and organs, including metabolic and energy metabolism. In extreme cases, vitamin B1 deficiency causes neurodegenerative disorders, including beri-beri, or cognitive impairment resulting from encephalopathy. B1 avitaminosis may result from increased demand, dietary errors, malabsorption, or excessive loss. Thiamine supplementation is used in cases of vitamin B1 deficiency or for preventative measures in situations of increased demand. Vitamin B1 can be administered enterally or parenterally (intravenously, intramuscularly, subcutaneously). The route and dose depend on the individual patient’s clinical situation. Hypersensitivity to vitamin B1 is rare and appears to be primarily associated with rapid intravenous infusion of large doses of thiamine hydrochloride over a short period (intravenous bolus). Hypersensitivity to thiamine administered by routes other than intravenous or intramuscular injection appears to be an incidental phenomenon. Thiamine should also be considered as an occupational allergen. The mechanism of thiamine hypersensitivity has not been clearly elucidated. However, considering the clinical nature and dynamics of the reaction, the most likely reaction seems to be an immediate type of hypersensitivity reaction (immunoglobulin E (IgE)-dependent), in which thiamine (but not its metabolites) acts as a hapten. Diagnosing hypersensitivity to vitamin B1 is difficult due to the lack of validated tests for additional testing. In individuals requiring thiamine supplementation who have experienced hypersensitivity to intramuscular or intravenous administration of this vitamin, switching to oral administration may be considered (provided this does not reduce treatment efficacy). This form of supplementation is usually well tolerated by individuals allergic to parenteral thiamine. However, if enteral supplementation does not guarantee the maintenance of therapeutic potential, thiamine desensitization may be considered, which seems to be an effective therapeutic method in such a clinical situation. Full article

(This article belongs to the Special Issue Allergies and Allergic Diseases—Perspectives in Diagnosis and Management: 2nd Edition)

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19 pages, 3708 KB

Open AccessArticle

Comparative Bioactivities and Fatty Acid Composition of Pinus koraiensis Leaf Oils Obtained Using Different Extraction Methods

by Jung-Eun Kim, Kyung Tae Jang, Leeseon An, Min-Ho Lee and Hyo-Jeong Lee

Life 2026, 16(1), 49; https://doi.org/10.3390/life16010049 - 27 Dec 2025

Abstract

Pinus koraiensis leaves are known for various bioactivities, including anti-cancer, anti-obesity, anti-diabetic, and anti-hyperlipidemic effects. This study aimed to compare the essential oil from P. koraiensis leaves (EPO) and the supercritical-CO₂-extracted oil (SPO) for physicochemical traits, antibacterial and anticancer activities, and [...] Read more.

Pinus koraiensis leaves are known for various bioactivities, including anti-cancer, anti-obesity, anti-diabetic, and anti-hyperlipidemic effects. This study aimed to compare the essential oil from P. koraiensis leaves (EPO) and the supercritical-CO₂-extracted oil (SPO) for physicochemical traits, antibacterial and anticancer activities, and anti-inflammatory/antioxidant effects, and profiled fatty acids by means of GC-MS. SPO showed stronger antimicrobial activity than EPO against Streptococcus mutans, whereas EPO was more active against Candida albicans. In HaCaT keratinocytes and THP-1 monocytic cell line, SPO more effectively suppressed LPS-induced ROS and attenuated TNF-α and IL-6 upregulation. Across a panel of human cancer cell lines, SPO exerted greater cytotoxicity, particularly in non–small cell lung, prostate, and colon cancers. GC–MS revealed greater compositional diversity in SPO (16 fatty acids, 10 unique), while linolelaidic acid was detected only in EPO; pentadecenoic acid was abundant in all oils. Collectively, SPO demonstrates broader bioactivity and richer fatty-acid diversity than EPO, supporting its potential as a functional food or medicinal ingredient. Full article

(This article belongs to the Special Issue New Advances in Natural Product Research for Drug Discovery and Therapeutics)

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