Journal Description
Life
Life
is an international, peer-reviewed, open access journal of scientific studies related to fundamental themes in life sciences, from basic to applied research, published monthly online by MDPI. The Astrobiology Society of Britain (ASB) and Spanish Association for Cancer Research (ASEICA) are affiliated with Life and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Biology) / CiteScore - Q1 (Paleontology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 19.3 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Testimonials: See what our editors and authors say about Life.
- Companion journals for Life include: Physiologia and Hydrobiology.
Impact Factor:
3.4 (2024);
5-Year Impact Factor:
3.4 (2024)
Latest Articles
Refractory Neuropathic Pain in the Head and Neck: Neuroanatomical and Clinical Significance of the Cervicotrigeminal Complex
Life 2025, 15(9), 1457; https://doi.org/10.3390/life15091457 (registering DOI) - 17 Sep 2025
Abstract
Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide
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Refractory neuropathic pain of the head and neck remains a major clinical challenge, particularly when mediated through the cervicotrigeminal complex (CTC), a unique anatomical hub integrating trigeminal and upper cervical nociceptive inputs. This narrative review synthesizes neuroanatomical, pathophysiological, and clinical evidence to provide a unifying framework for diagnosis and management. A structured search of PubMed, Scopus, and Web of Science identified English-language clinical and mechanistic studies addressing CTC-mediated pain, with case reports excluded unless mechanistically informative. We propose multidimensional refractoriness criteria that integrate pharmacological non-response, failed interventional strategies, and objective functional impairment. Current treatments span pharmacotherapy, peripheral interventions (nerve blocks, radiofrequency ablation), and neuromodulation at multiple network levels (occipital nerve stimulation, spinal cord stimulation, motor cortex stimulation, deep brain stimulation). Non-invasive approaches such as rTMS, tDCS, and vagus nerve stimulation are emerging but remain investigational. Advances in imaging and neurophysiological biomarkers now permit greater precision in detecting CTC dysfunction and tailoring therapy. By combining anatomical precision, mechanistic insight, and multidisciplinary strategies, this review proposes a clinically actionable definition of refractoriness and supports a stepwise, mechanism-based approach to therapy. CTC emerges as a targetable hub for diagnostic and therapeutic strategies in refractory head and neck pain.
Full article
(This article belongs to the Special Issue Pain: New Insights into Mechanisms, Diagnosis, Therapy, and Management)
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Open AccessArticle
Lower ANXA3 Levels May Be Related to Major Depressive Disorder
by
Mine Büşra Bozkürk, Kadir Özdel, Bilge Ozan Çiçek, Özkan Önder, Selin Yıldız and Alpaslan Öztürk
Life 2025, 15(9), 1456; https://doi.org/10.3390/life15091456 - 17 Sep 2025
Abstract
Annexin A3 (ANXA3) is a calcium-binding protein that plays a role in membrane phospholipid metabolism and inflammation, and significant alterations have been shown in some psychotic disorders. Because its association with major depressive disorder (MDD) is unclear, we aimed to compare serum ANXA3
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Annexin A3 (ANXA3) is a calcium-binding protein that plays a role in membrane phospholipid metabolism and inflammation, and significant alterations have been shown in some psychotic disorders. Because its association with major depressive disorder (MDD) is unclear, we aimed to compare serum ANXA3 levels in patients with MDD and healthy controls and to investigate their relationship with depression severity. Serum ANXA3 concentrations in 90 patients diagnosed with MDD and 90 healthy controls were measured by ELISA. Depression severity was assessed using the Beck Depression Inventory (BDI). Serum ANXA3 levels were significantly lower in patients with MDD compared to controls (p < 0.001). ANXA3 showed negative correlations with neutrophil count, platelet count, neutrophil-to-lymphocyte ratio (NLR), glucose, creatinine, and ALT levels, and positive correlations with lymphocyte and red blood cell counts. We found that low ANXA3 levels, high NLR, and glucose dysregulation predicted greater depression severity. Using ROC analysis, we demonstrated that ANXA3 has high discriminatory power in distinguishing moderate to severe cases of MDD (AUC > 0.90). ANXA3 may serve as a biomarker of depression severity. Further studies are needed to clarify its clinical utility and confirm whether ANXA3 alterations represent state or trait markers of depression.
Full article
(This article belongs to the Section Physiology and Pathology)
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Open AccessArticle
Predicting Seizure Risk from Routine Electroencephalographs in Medical Intensive Care Units Using the 2HELPS2B Score
by
Cheng-Lun Hsiao, Wan-Ling Chang, Pei-Ya Chen, I-An Chen and Shinn-Kuang Lin
Life 2025, 15(9), 1455; https://doi.org/10.3390/life15091455 - 17 Sep 2025
Abstract
This study evaluated the utility of the 2HELPS2B score in predicting seizures from routine electroencephalographs (rEEGs). In total, 670 rEEGs obtained in a medical intensive care unit (MICU) between October 2018 and March 2023 were analyzed. More than 75% of these rEEGs were
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This study evaluated the utility of the 2HELPS2B score in predicting seizures from routine electroencephalographs (rEEGs). In total, 670 rEEGs obtained in a medical intensive care unit (MICU) between October 2018 and March 2023 were analyzed. More than 75% of these rEEGs were requested due to seizures and unexplained altered consciousness. Seizures occurred most frequently in patients with rEEGs characterized by brief, potentially ictal rhythmic discharges and electrographic seizures. A history of seizures was the most prevalent risk factor identified by the 2HELPS2B score. Seizures occurred in 28% of the cohort who experienced a seizure within 24 h of the rEEG and in 38% of the cohort who experienced a seizure before MICU discharge. Among the patients with suspected altered consciousness, the seizure incidence before MICU discharge (9.2%) was twice that within 24 h of the initial rEEG (4.7%). The seizure rate also increased from 12% for a 2HELPS2B score of 1 to 100% for scores ≥ 4. A score ≥ 2 was the optimal cutoff for predicting post-rEEG seizures and guiding antiseizure medication (ASM) treatment. Seizures occurred most frequently in patients whose ASMs were supplemented with new medications, and most new prescriptions for antiseizure medication were issued to patients with altered consciousness. These results demonstrate that the 2HELPS2B score can effectively predict seizures on the basis of rEEG results.
Full article
(This article belongs to the Special Issue Advances in Intensive Care Medicine)
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Open AccessArticle
The Effects of FemmeBalance Supplement on Symptoms of Premenstrual Syndrome: A Four-Cycle Single-Arm Observational Study of a Novel Nutritional Supplement
by
Isabel Viña and Juan R. Viña
Life 2025, 15(9), 1454; https://doi.org/10.3390/life15091454 - 17 Sep 2025
Abstract
Background: Premenstrual syndrome (PMS) affects 950 million women worldwide. However, conventional pharmacological treatments offer limited improvements. Objective: This study aimed to evaluate the effectiveness of the FemmeBalance supplement in relieving PMS symptoms. Methods: We conducted a single-group study of 38 women, aged 18–40,
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Background: Premenstrual syndrome (PMS) affects 950 million women worldwide. However, conventional pharmacological treatments offer limited improvements. Objective: This study aimed to evaluate the effectiveness of the FemmeBalance supplement in relieving PMS symptoms. Methods: We conducted a single-group study of 38 women, aged 18–40, with self-reported PMS symptoms. Participants received the FemmeBalance supplement (two capsules/day) for four menstrual cycles, completing the premenstrual symptoms screening tool (PSST) and study-specific questionnaires at baseline and on day 7 of each cycle. Skin changes were also assessed using dermatologist-graded facial photos. Results: By the first menstrual cycle, all PSST parameters showed significant improvement except insomnia. The greatest improvement was observed in interest in social activities, which improved by 40.13% in the fourth cycle. In addition, period heaviness was significantly decreased by the fourth cycle. Dermatologist skin grading showed improved overall skin health in 91.18% of participants. Moreover, 77.1% of the participants reported reduced PMS symptom severity, and 71.4% reported they would recommend the supplement. Conclusion: FemmeBalance was significantly effective in improving several PMS symptoms, including physical discomfort, mood disturbance, and skin health. The supplement also improved social functioning and overall menstrual health, suggesting that it could be an alternative to conventional PMS treatments.
Full article
(This article belongs to the Section Pharmaceutical Science)
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Open AccessReview
Cutaneous and Lymphangitic Infection Caused by Purpureocillium lilacinum in Immunocompromised Patients: A Case Report with a Narrative Review of the Literature
by
Tommaso Lupia, Cristina Sarda, Francesca Canta, Marco Casarotto, Guido Accardo, Gabriele Roccuzzo, Nicole Macagno, Federica Gelato, Rebecca Senetta, Antonio Ottobrelli, Francesco Giuseppe De Rosa, Silvia Corcione, Simone Ribero, Pietro Quaglino and Paolo Fava
Life 2025, 15(9), 1453; https://doi.org/10.3390/life15091453 - 17 Sep 2025
Abstract
Background: Purpureocillium lilacinum (P. lilacinum) is an emerging filamentous fungus known to cause opportunistic infections, particularly in immunocompromised patients. Formerly known as Paecilomyces lilacinus, this pathogen is widespread in the environment and can lead to a range of infections, from
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Background: Purpureocillium lilacinum (P. lilacinum) is an emerging filamentous fungus known to cause opportunistic infections, particularly in immunocompromised patients. Formerly known as Paecilomyces lilacinus, this pathogen is widespread in the environment and can lead to a range of infections, from superficial skin lesions to invasive diseases. This article presents a case of deep cutaneous hyalohyphomycosis caused by P. lilacinum in a liver transplant patient, followed by a review of the literature focusing on new antifungal agents. Methods: We reported a brief case description followed by a narrative review of the literature regarding P. lilacinum cutaneous and lymphangitic infections in immunocompromised patients. Results: We conducted a review of the literature over the past 20 years, focusing on the clinical features, diagnostic challenges, and therapeutic outcomes of cutaneous and lymphangitic P. lilacinum infections in immunocompromised hosts. Conclusions: This review highlights the critical importance of early diagnosis through the analysis of biopsy samples using standard microbiological and histological techniques, complemented by innovative molecular biology methods. We also emphasise the role of appropriate antifungal treatment, despite the absence of an established standard of care, particularly in high-risk patients. Furthermore, we review and discuss the current lack of a standardised therapeutic regimen and the potential of novel antifungal agents as promising treatment options for P. lilacinum infections.
Full article
(This article belongs to the Section Physiology and Pathology)
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Open AccessSystematic Review
Effect of Different Exercise Modalities on Inflammatory Markers in Individuals with Depressive Disorder: A Systematic Review and Meta-Analysis
by
Jie Song, Jinning Zhang, Xijin Wang, Jiaqi Liang and Yan Li
Life 2025, 15(9), 1452; https://doi.org/10.3390/life15091452 - 16 Sep 2025
Abstract
Background: One of the important mechanisms of depression is long-term high levels of inflammation. Exercise may help relieve depressive symptoms and is associated with anti-inflammatory effects. This research methodically assesses how various exercise modalities influence peripheral inflammatory markers in individuals with depression, so
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Background: One of the important mechanisms of depression is long-term high levels of inflammation. Exercise may help relieve depressive symptoms and is associated with anti-inflammatory effects. This research methodically assesses how various exercise modalities influence peripheral inflammatory markers in individuals with depression, so that more personalized and precise exercise schemes can be provided for people with depression to improve inflammation. Methods: Randomized controlled trials on depressive disorder, exercise, and inflammation published until May 2025 were screened in five databases. The Cochrane Risk of Bias tool (RoB2.0) was used to evaluate potential biases, with random effects meta-analyses gauging the impact of varying exercise regimens on peripheral inflammatory markers (CRP, IL-6 and TNF-α) involving exercise types, intensity, frequency, and length. Meta-regression analyses were employed to show the sources of heterogeneity and investigate potential moderator variables influencing CRP, IL-6, and TNF-α (PROSPERO CRD42024590612). Results: A total of 13 unique studies with 1004 participants were included. Overall, exercise training could alleviate depressive symptoms (SMD = −0.59, 95%CI: [−0.86, −0.32], I2 = 61.7%, p < 0.001), and subgroup analysis showed that exercise lasting 8–12 weeks could reduce the level of TNF-α (MD = −0.74, 95%CI: [−1.30, −0.17], I2 = 0, p < 0.05). Apparent discrepancies between subgroup and meta-regression findings were resolved by advanced modeling, which identified a significant non-linear relationship for TNF-α (quadratic term p = 0.003), characterized by a reduction peak at 8–12 weeks followed by a gradual increase, rather than a positive linear trend. Conclusions: Exercise could alleviate depressive symptoms in individuals with depression. However, the influence of exercise length on TNF-α levels has conflicting conclusions because of inconsistent evidence and substantial heterogeneity. Future high-quality trials with standardized biomarker measurements and better control of confounding factors are essential to determine whether the antidepressant effects of exercise are mediated by inflammation.
Full article
(This article belongs to the Topic Physical Exercise Impacts on Human Physical and Psychological Health)
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Open AccessArticle
Epilithic Algae from Seven Megaliths in the Vicinity of Topolovgrad (Haskovo District, Southeast Bulgaria)
by
Maya Petrova Stoyneva-Gärtner, Miroslav Ivov Androv, Blagoy Angelov Uzunov, Kristian Rosenov Ivanov and Georg Gärtner
Life 2025, 15(9), 1451; https://doi.org/10.3390/life15091451 - 16 Sep 2025
Abstract
The present work focuses on seven megaliths sampled for the first time as a continuation of our studies on the biodiversity of algae on megaliths in Bulgaria. A total of 55 species from four divisions were identified (Chlorophyta was the richest with 31
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The present work focuses on seven megaliths sampled for the first time as a continuation of our studies on the biodiversity of algae on megaliths in Bulgaria. A total of 55 species from four divisions were identified (Chlorophyta was the richest with 31 species), of which 14 species are new for Bulgaria. Two species were of conservation concern, but six were potential toxin producers that could affect the health of visitors to the megaliths. Despite the general granitic character and relatively close location of the studied sites, their floristic similarity was low, with most algae (51 species) being rarely distributed (except Stichococcus bacillaris and Mychonastes homosphaera). The largest cult complex Paleokastro, furthest from populated areas, had the highest species diversity (22 species), while the lowest (8 species) was found in the highly exposed Kalinkin Kamuk, located in a village. The NMDS analysis tool showed the existence of four distinct ecological groups and that temperature and light are the most important drivers for the distribution of the epilithic algae on the investigated megaliths. Correlations with temperatures estimated to identify potential indicators or future survivors under global warming conditions were low, except for the Streptophyta. It was represented by four species of the genus Klebsormidium, which is known for its high ecological tolerance and drought resistance. Extending the studies on lithophytic algae to megaliths is important for a better knowledge of their biodiversity and ecology, but also for the protection of megaliths and for understanding the impact of climate change on these fragile monuments.
Full article
(This article belongs to the Special Issue Advances in the Structure and Function of Microbial Communities)
Open AccessArticle
Inflammation, Autonomic Control, and Adiposity in Adolescents: Links to Early Cardiovascular Risk
by
Vladimir Micieta, Ingrid Tonhajzerova, Nikola Ferencova and Zuzana Visnovcova
Life 2025, 15(9), 1450; https://doi.org/10.3390/life15091450 - 16 Sep 2025
Abstract
Cardiovascular diseases (CVDs) are generally associated with adulthood, although the underlying processes may begin in childhood and adolescence. Thus, detecting increased cardiovascular risk in adolescence is essential for prevention. In this cross-sectional study, we comprehensively evaluated the inter-relationships between inflammatory markers, cardiac autonomic
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Cardiovascular diseases (CVDs) are generally associated with adulthood, although the underlying processes may begin in childhood and adolescence. Thus, detecting increased cardiovascular risk in adolescence is essential for prevention. In this cross-sectional study, we comprehensively evaluated the inter-relationships between inflammatory markers, cardiac autonomic control indexed by heart rate variability (HRV), and adiposity measures in healthy adolescents, with sex-stratified analyses. We examined 90 adolescents (55 females; age 15.8 ± 1.5 years; BMI 21.4 ± 3.3 kg/m2). We found mixed (positive and negative) associations between inflammatory markers and HRV indices among the entire adolescent group (absolute r range: 0.266–0.395, p < 0.05 for all), while only negative associations in the male group, and only positive associations in the female group (absolute r range: 0.373–0.404, p < 0.05 for all). Furthermore, predominantly positive associations between inflammatory markers and adiposity measures were found among the adolescent group (absolute r range: 0.298–0.338, p < 0.05 for all) and female group (absolute r range: 0.342–0.485, p < 0.05 for all), while contrasting negative associations were found in the male group (absolute r range: 0.421–0.497, p < 0.05 for all). These associations, representing early pathways to cardiovascular vulnerability, seem sex-dependent, but longitudinal confirmation is required.
Full article
(This article belongs to the Special Issue Cardiovascular Diseases: From Basic Research to Clinical Application—3rd Edition)
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Open AccessReview
Microplastics and Nanoplastics in Health Concerning Cellular Toxicity Mechanisms, Exposure Pathways, and Global Mitigation Strategies
by
Ruei-Hong Lin, Hao-Ting Chen, I-Ta Lee, Thi-Thuy-Tien Vo and Yung-Li Wang
Life 2025, 15(9), 1449; https://doi.org/10.3390/life15091449 - 16 Sep 2025
Abstract
Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants that pose significant threats to human health, with multiple exposure pathways (e.g., ingestion and inhalation) contributing to systemic exposure. Although growing evidence highlights their biological effects, the underlying mechanisms by which these
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Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants that pose significant threats to human health, with multiple exposure pathways (e.g., ingestion and inhalation) contributing to systemic exposure. Although growing evidence highlights their biological effects, the underlying mechanisms by which these particles induce cellular dysfunction remain incompletely understood. This review synthesizes current knowledge on the MPs/NPs-induced cellular toxicity mechanisms, including investigations into cellular uptake pathways, disruption of molecular signaling, oxidative stress, inflammatory responses, and genotoxic effects. MPs/NPs contamination can arise from consumer products and clinical procedures, with estimated Daily Microplastic Emission (DME)-based national totals (India) ranging from ~0.36 to 74 billion particles/day across oral-care product categories. At the cellular level, MPs and NPs trigger interconnected toxicological cascades, including impaired endocytosis, mitochondrial dysfunction, chronic inflammation, genotoxicity, endoplasmic reticulum (ER) stress, and accelerated cellular senescence. These mechanisms act in concert to compromise epithelial barrier integrity. Overall, MPs/NPs present substantial risks to health through multiple interconnected pathways. Local and systemic effects are plausible across exposed tissues which may also serve as a gateway for systemic distribution by these contaminants. These findings highlight the urgent need for coordinated global efforts, including restrictions on intentionally added MPs, improvements in product design, development of advanced removal technologies, and implementation of clinical prevention strategies.
Full article
(This article belongs to the Special Issue Exploring the Mechanisms of the Effects of Microplastics and Nanomaterials on Biological Physiological Functions)
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Open AccessArticle
Exploring Ochradenus baccatus: A Novel Source of Bioactive Compounds and Phytochemical Insights for Uncharted Therapeutic Applications
by
Salma Saddeek
Life 2025, 15(9), 1448; https://doi.org/10.3390/life15091448 - 16 Sep 2025
Abstract
Ochradenus baccatus (O. baccatus), a resilient medicinal plant native to arid regions, was systematically investigated for its neuroprotective potential against Alzheimer’s disease. Comprehensive phytochemical profiling of different plant parts revealed that the leaves possessed the highest levels of total phenolics (67.8
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Ochradenus baccatus (O. baccatus), a resilient medicinal plant native to arid regions, was systematically investigated for its neuroprotective potential against Alzheimer’s disease. Comprehensive phytochemical profiling of different plant parts revealed that the leaves possessed the highest levels of total phenolics (67.8 mg GAE/g) and flavonoids (49.2 mg QE/g), correlating with strong antioxidant activity (DPPH IC50 = 19.8 µg/mL, FRAP = 832 µmol Fe2+/g). HPLC and GC-MS analyses identified multiple bioactive flavonoids and fatty acids. The leaf extract demonstrated potent in vitro AChE inhibition (IC50 = 32.5 µg/mL) and significantly reduced amyloid-β aggregation (by 50%). In vivo, it ameliorated cognitive deficits in scopolamine-induced mice, as evidenced by improved performance in Morris Water Maze and Y-maze tests, and restored hippocampal neuronal density (CA3: +29.7%, DG: +30%). These findings highlight the therapeutic promise of O. baccatus leaves as a rich source of multifunctional anti-Alzheimer’s phytochemicals.
Full article
(This article belongs to the Special Issue Therapeutic Innovations from Plants and Their Bioactive Extracts)
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Open AccessReview
Indications and Mechanisms of Action of the Main Treatment Modalities for Non-Melanoma Skin Cancer
by
Marcio F. Chedid, Aline C. Tregnago, Floriano Riva, Lucas Prediger, Anisha Agarwal and Jane Mattei
Life 2025, 15(9), 1447; https://doi.org/10.3390/life15091447 - 16 Sep 2025
Abstract
Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or
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Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence.
Full article
(This article belongs to the Special Issue Advances in Novel Biomarkers and Emerging Immune/Targeted Therapies in Solid Tumors)
Open AccessReview
Mouflon and Domestic Sheep Phylogeny: Ancestry, Domestication, and Evolutionary Dynamics
by
Paolo Mereu, Monica Pirastru, Fabio Scarpa, Marco Zedda, Luisa Bogliolo, Salvatore Naitana and Giovanni Giuseppe Leoni
Life 2025, 15(9), 1446; https://doi.org/10.3390/life15091446 - 15 Sep 2025
Abstract
The ancestry of domestic species from their closest wild relatives is one of the most debated and intriguing topics in evolutionary genetics. This review synthesizes current scientific understanding of the phylogenetic relationships between wild mouflon populations and domestic sheep (Ovis aries).
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The ancestry of domestic species from their closest wild relatives is one of the most debated and intriguing topics in evolutionary genetics. This review synthesizes current scientific understanding of the phylogenetic relationships between wild mouflon populations and domestic sheep (Ovis aries). It delves into the complex ancestry, tracing the primary role of the Asiatic mouflon (Ovis gmelini) as the progenitor, while also addressing the debated contributions of other wild Ovis species. The report explores the insights gained from diverse genetic markers, including mitochondrial DNA haplogroups and comprehensive whole-genome sequencing, highlighting their strengths, limitations, and the resolution of phylogenetic discrepancies. The multi-faceted taming process is examined, discussing proposed evolutionary mechanisms such as the domestication syndrome and thyroid hormone hypotheses, alongside human-mediated selection for key phenotypic traits like horn morphology, coat type, and tail characteristics. Furthermore, the pervasive role of hybridization and introgression between wild and domestic populations is analyzed, detailing its impact on genetic distinctiveness, adaptive potential, and the critical implications for conservation strategies. Finally, the review addresses ongoing scientific debates, particularly concerning the taxonomic classification of European mouflon, and identifies crucial avenues for future research to further unravel the intricate evolutionary tapestry of Ovis species. To ensure taxonomic consistency and promote conservation, nomenclature should be updated across all public repositories. Following the widely accepted classification that recognizes its lineage from the Asian mouflon, the Corsican and Sardinian mouflon should be designated as Ovis gmelini musimon.
Full article
(This article belongs to the Special Issue Evolutionary and Conservation Genetics: 3rd Edition)
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Open AccessSystematic Review
Biomarkers in Pediatric Neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review
by
Evdoxia Sapountzi, Eleni P. Kotanidou, Vasiliki-Rengina Tsinopoulou, Paraskevi Tatsiopoulou, Vaios Dafoulis, Lilian Athanasopoulou, Lampros Fotis and Assimina Galli-Tsinopoulou
Life 2025, 15(9), 1445; https://doi.org/10.3390/life15091445 - 15 Sep 2025
Abstract
Diagnosis of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (pNPSLE) remains challenging due to NP symptom heterogeneity, lack of specific clinical criteria and validated diagnostic biomarkers, and invasiveness of common diagnostic methods for CNS disease. Although some biomarkers have been identified in
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Diagnosis of neuropsychiatric (NP) involvement in pediatric systemic lupus erythematosus (pNPSLE) remains challenging due to NP symptom heterogeneity, lack of specific clinical criteria and validated diagnostic biomarkers, and invasiveness of common diagnostic methods for CNS disease. Although some biomarkers have been identified in adults, their sensitivity, specificity, and clinical applicability in pNPSLE are uncertain. We performed a systematic review according to PRISMA guidelines to evaluate the current evidence on biomarkers associated with pNPSLE. We searched four databases using appropriate search terms for articles in English. After applying our selection criteria, we included 29 studies, from which we manually extracted relevant parameters, including study design, sample size, patient and disease characteristics, biomarker information, and effect sizes. The risk of bias, study quality, and quality of evidence were assessed with standard methods. Most studies had low quality, small samples, and were performed in single centers, which limited the quality of evidence of the biomarkers investigated. Biomarkers showing promising results, with high specificity and sensitivity or predictive value, included CSF neopterin, serum anti-ganglioside M1, a five-biomarker panel including neuronal proteins and anti-ribosomal P, and serum anti-neuronal. Our findings highlight the need for further replication and functional validation studies in pNPSLE.
Full article
(This article belongs to the Section Medical Research)
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Open AccessReview
The Predilection of Specific Diseases to Affect Different Sections of the Esophagus
by
Monjur Ahmed
Life 2025, 15(9), 1444; https://doi.org/10.3390/life15091444 - 15 Sep 2025
Abstract
Certain esophageal diseases have a predilection for affecting different parts of the esophagus. This predilection is noted in our clinical practice as we investigate various esophageal diseases using multiple imaging and motility studies, as well as endoscopic procedures with biopsies. Clinical presentations vary
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Certain esophageal diseases have a predilection for affecting different parts of the esophagus. This predilection is noted in our clinical practice as we investigate various esophageal diseases using multiple imaging and motility studies, as well as endoscopic procedures with biopsies. Clinical presentations vary with the stage and location of the disease. Clinicians can suspect certain diseases when a particular part of the esophagus is involved and then can perform appropriate investigations. Esophageal diseases with section involvement, with their symptomatology, diagnostic tests, and management, have been discussed in this narrative review. This review aims to revisit those diseases with a current update.
Full article
(This article belongs to the Special Issue Organ Predilection of Certain Gastrointestinal Diseases—Pathophysiology, Diagnosis and Management)
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Open AccessArticle
Proarrhythmogenic Echocardiographic Markers in Metabolic Syndrome: A Cross-Sectional Study
by
Spas Kitov, Maria-Florance Kitova, Boyan Nonchev, Mariya Tokmakova and Lyudmila Kitova
Life 2025, 15(9), 1443; https://doi.org/10.3390/life15091443 - 15 Sep 2025
Abstract
In metabolic syndrome, cardiomyocyte changes induced by metabolic and proinflammatory factors impair repolarization and exacerbate the heterogeneity of the transmural dispersion of repolarization, and this is proarrhythmogenic. Limited data in the literature on the capabilities of speckle tracking echocardiography for assessing proarrhythmogenicity in
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In metabolic syndrome, cardiomyocyte changes induced by metabolic and proinflammatory factors impair repolarization and exacerbate the heterogeneity of the transmural dispersion of repolarization, and this is proarrhythmogenic. Limited data in the literature on the capabilities of speckle tracking echocardiography for assessing proarrhythmogenicity in metabolic syndrome exists. 71 patients with newly diagnosed metabolic syndrome, aged 35–55 years, were studied. Ischemic heart disease was excluded in all patients with stress test cycle ergometry, CT-angiography or selective coronary angiography. All patients underwent a 48-h Holter ECG recording. Based on the latter, they were divided into two groups: 38 patients (53.5%) with a high arrhythmogenic load (supraventricular or ventricular tachycardia, atrial fibrillation/flutter, ventricular extrasystoles over 10%, frequent supraventricular extrasystoles > 500/24 h are included); and 33 patients (46.5%) with low arrhythmogenic load (no significant rhythm disturbances are included). Echocardiography was performed with a GE Vivid T9 emphasizing global longitudinal strain, mechanical dispersion index and left atrium strains. Statistically significant differences in the global longitudinal strain, mechanical dispersion index, and left atrium strain were found between the group with low arrhythmogenicity and the group with high arrhythmogenicity (p < 0.0001). The index of mechanical dispersion has the most optimal sensitivity and specificity of all investigated echocardiographic markers. These results support the mechanical dispersion index as an additional tool for assessing proarrhythmogenicity in metabolic syndrome.
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(This article belongs to the Special Issue Regulation of Cellular Signaling Pathways in the Metabolic Syndrome)
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Open AccessArticle
Finite Element Investigation of Patellofemoral Contact Mechanics: Influence of Tibial Tuberosity Lateralisation and Trochlear Dysplasia on Extensor Mechanism Stability
by
Georgian Iacobescu, Antonio-Daniel Corlatescu, Loredana Iacobescu, Bogdan Serban and Catalin Cirstoiu
Life 2025, 15(9), 1442; https://doi.org/10.3390/life15091442 - 15 Sep 2025
Abstract
Background: Patellofemoral instability arises from the interplay between trochlear morphology and malalignment of the extensor vector. Although each factor is individually well described, their combined mechanical effects have not been quantified within a single finite element framework. Objective: To investigate how lateral trochlear
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Background: Patellofemoral instability arises from the interplay between trochlear morphology and malalignment of the extensor vector. Although each factor is individually well described, their combined mechanical effects have not been quantified within a single finite element framework. Objective: To investigate how lateral trochlear inclination (LTI) and tibial tuberosity position interact to influence patellofemoral contact mechanics and stability across clinically relevant knee flexion angles. Methods: A subject-specific finite element model of the femur–patella–tibia complex was reconstructed from high-resolution CT data. Cortical and cancellous bone, patellar cartilage, the MPFL, and patellar tendon were included. Three trochlear morphologies were simulated (LTI = 15°, 10°, 5°) under native alignment (Case A) and after 10 mm lateral tibial tuberosity translation (Case B). Flexion at 30°, 60°, and 90° was imposed via solver-applied tibial displacement. Primary outcomes were contact pressure, contact area, MPFL stress, and lateral patellar translation. Instability was defined as >5 mm lateral translation or >50% reduction in contact area, consistent with the biomechanical literature. Model convergence (<5% variation) and validation against cadaveric pressure data were performed; a sensitivity analysis tested material property variation (±15%). Results: The native model reproduced peak pressures (3.6 MPa at 60°) within 9% of experimental benchmarks. Decreasing LTI enlarged the contact patch and lowered mean pressures (−18%) but increased MPFL stress (+37%). Tibial tuberosity lateralisation reduced mean pressures further (−25%), yet, when combined with shallow trochlear slopes (≤8°), produced >5 mm lateral patellar translation and near-complete loss of cartilage contact by 60°, simulating lateral dislocation. Sensitivity testing confirmed robustness to material property uncertainty. Conclusions: Shallow trochlear inclination dissipates articular load but destabilises the patella, an effect magnified by tibial tuberosity lateralisation. While these findings highlight thresholds at which stability may be compromised, they derive from a single-subject model and should be interpreted as hypothesis-generating rather than prescriptive. Broader validation across multiple geometries and loading conditions is required before clinical translation.
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(This article belongs to the Special Issue Orthopedic Disease Treatment and Management: Innovations, Challenges, and Future Directions)
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Sexual Dysfunction Is Common in Reproductive-Age Women with Systemic Sclerosis
by
Lingling Salang, Pranom Buppasiri, Arporn Jutiviboonsuk and Chingching Foocharoen
Life 2025, 15(9), 1441; https://doi.org/10.3390/life15091441 - 14 Sep 2025
Abstract
Background: Female sexual dysfunction (FSD) is an underrecognized issue in women with systemic sclerosis (SSc), influenced by physical and psychological factors. Data on FSD in reproductive-age SSc patients, especially those with diffuse cutaneous SSc (dcSSc), remain limited. Objectives: This study aimed to determine
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Background: Female sexual dysfunction (FSD) is an underrecognized issue in women with systemic sclerosis (SSc), influenced by physical and psychological factors. Data on FSD in reproductive-age SSc patients, especially those with diffuse cutaneous SSc (dcSSc), remain limited. Objectives: This study aimed to determine the prevalence of FSD and identify its associated factors among reproductive-age women with SSc. Methods: A cross-sectional study (May 2019–March 2020) included sexually active women with SSc aged 18–45. Patients with surgical amenorrhea, prior radiation, hormonal contraceptive use within 12 weeks, or pregnancy were excluded. Sexual function was assessed using the Female Sexual Function Index (FSFI). Results: Among 27 women of reproductive age, 66.7% had the dcSSc subset. The mean age was 39.4 ± 5.2 years (range: 22–45 years), with a mean disease duration of 9.9 ± 7.9 years. FSD was identified in 51.9% of patients (95%CI: 31.9–71.3), with a higher prevalence in the dcSSc subset (71.4%) compared to limited cutaneous SSc (28.6%). Patients with FSD were more likely to be older at disease onset, exhibit telangiectasia, and have longer exposure to cyclophosphamide (CYC), although these findings were not statistically significant. Women with FSD showed significantly lower FSFI scores in arousal, lubrication, orgasm, sexual satisfaction, and total sexual function (p < 0.01 for all). Conclusions: FSD is highly prevalent among SSc women of reproductive age, particularly in those with dcSSc. Disease severity, older age at onset, and prolonged CYC treatment may contribute to the risk of FSD. Early recognition and management of sexual health issues are essential in this patient population.
Full article
(This article belongs to the Special Issue Clinical Manifestations and Treatment of Autoimmune Diseases: 2nd Edition)
Open AccessArticle
Influence of Stride Length on Pelvic–Trunk Separation and Proximal Plyometrics in Baseball Pitching
by
Dan K. Ramsey and Ryan L. Crotin
Life 2025, 15(9), 1440; https://doi.org/10.3390/life15091440 - 14 Sep 2025
Abstract
Pelvis and trunk counter-rotation are key factors known to effect throwing arm kinematics in baseball pitching, where energy or momentum is transferred from the lower extremities through to the trunk during the pitching cycle. The purpose of this study was to retrospectively analyze
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Pelvis and trunk counter-rotation are key factors known to effect throwing arm kinematics in baseball pitching, where energy or momentum is transferred from the lower extremities through to the trunk during the pitching cycle. The purpose of this study was to retrospectively analyze previously recorded motion capture data of 19 skilled competitive pitchers to test the a priori hypothesis whether different stride lengths affect transverse pelvis and trunk biomechanics. A blinded randomized crossover design was used where pitchers threw two simulated games at ±25% from desired stride length (DSL), respective of overstride (OS) and under-stride (US). Variables of interest included pelvic–trunk separation (PTS) angle or degree of uncoupling and proximal plyometric effect (PPE) or ratio between trunk–pelvis angular velocities, as surrogate measures of rotational and elastic energy transfer. Paired t-tests were used to compare across stride conditions. A one-way ANOVA with a Bonferroni post hoc analysis demonstrated stride lengths differed statistically, (DSL vs. OS p = 0.006), (DSL vs. US, p < 0.001), and (US vs. OS, p < 0.001). Despite the statistically different stride lengths, fastball velocities tracked with radar were consistent. No significant differences within and across innings pitched between OS and OS conditions were found. The ±25% stride length changes influenced temporal parameters within the pitching cycle. Shorter stride elicited by early SFC reduced time during the Generation phase and extended the Brace-Transfer duration (p < 0.001). Statistically different transverse pelvis and trunk kinematics at hallmark events and phases consequently influenced pelvic–trunk separation and proximal plyometrics. During the Generation (PKH-SFC) and Brace-Transfer (SFC-MER) phases, the pelvis and trunk were significantly more externally rotated (p < 0.001) with shorter strides, concomitant with less separation at the instant of SFC and the Generation phase with greater peak proximal plyometrics effect ratios peak during throwing arm acceleration, indicative of greater contribution of trunk angular velocity (p < 0.05). Greater transverse trunk angular velocities relative to the pelvis late in double support necessitates the throwing arm to “catch up” from a position of greater arm lag, which compromises the dynamic and passive stabilizers. In conclusion, stride length alters pitching biomechanics and timing of peak pelvic–trunk separation and trunk angular velocity relative to the pelvis. Increased shoulder and elbow tensile stress is to be expected, consequently increasing risk for injury.
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(This article belongs to the Special Issue Advances and Applications of Sport Physiology: 2nd Edition)
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Pancreatic Injury in Severe SARS-CoV-2 Infection: A Retrospective Study Across Three Pandemic Waves
by
Mihai Lazar, Cristina Emilia Chitu and Ecaterina Constanta Barbu
Life 2025, 15(9), 1439; https://doi.org/10.3390/life15091439 - 14 Sep 2025
Abstract
Acute pancreatitis (AP) has emerged as a notable complication in patients with COVID-19, yet the interplay between viral infection, systemic inflammation, and pancreatic injury remains incompletely understood. This study aimed to evaluatethe characteristics and risk factors of APin patients with severe COVID-19 pneumonia.
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Acute pancreatitis (AP) has emerged as a notable complication in patients with COVID-19, yet the interplay between viral infection, systemic inflammation, and pancreatic injury remains incompletely understood. This study aimed to evaluatethe characteristics and risk factors of APin patients with severe COVID-19 pneumonia. We conducted a retrospective, single-center analysis of 405 hospitalized COVID-19 patients with and without AP. Laboratory markers, including CRP, ESR, fibrinogen, LDH, D-dimers, WBC, neutrophils, serum potassium, and serum glucose, alongside imaging and clinical parameters, were analyzed for associations with AP occurrence. Our results indicate that elevated inflammatory and coagulation markers, leukocytosis with neutrophilia, hyperglycemia, hypokalemia, and more severe pulmonary involvement were significantly associated with AP in COVID-19. LDH and inflammatory markers demonstrated particularly strong predictive value, while D-dimers and lung injury severity also contributed to risk stratification. These findings suggest that systemic inflammation, endothelial dysfunction, immunothrombosis, and metabolic impairments converge to increase pancreatic vulnerability in COVID-19 patients. Early recognition of these risk factors may guide monitoring and therapeutic interventions, although prospective validation is needed.
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(This article belongs to the Special Issue New Insights into Pneumonia Pathophysiology—from Lung Fibrosis to Coagulation Disorders)
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Investigating the Hemorheological, Metabolic, and Physical Performance Effect of a Core Muscle Strengthening Training Program
by
Tobias Mody, Zsuzsanna Nemethne Gyurcsik, Csaba Attila Bakos, Bela Horvath, Barbara Bedocs-Barath, Adam Varga, Adam Attila Matrai, Norbert Nemeth and Sandor Szanto
Life 2025, 15(9), 1438; https://doi.org/10.3390/life15091438 - 14 Sep 2025
Abstract
Physical activity influences red blood cell (RBC) deformability and aggregation, which affect oxygen transport and performance. While regular training may enhance RBC properties, adaptations depend on exercise intensity, duration, and recovery. This study aimed to assess the impact of a 12-week core muscle
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Physical activity influences red blood cell (RBC) deformability and aggregation, which affect oxygen transport and performance. While regular training may enhance RBC properties, adaptations depend on exercise intensity, duration, and recovery. This study aimed to assess the impact of a 12-week core muscle training program on RBC deformability, aggregation, and aerobic capacity in military trainees. A total of 35 male volunteers were divided into a Training group (n = 17) and a Control group (n = 18). The intervention included dynamic stretching, core stabilization, and functional movement exercises. Spiroergometry tests, blood gas analysis, and hemorheological measurements were conducted before and after the program. Results showed no significant changes in body composition or aerobic capacity. RBC deformability slightly decreased after exercise in both groups, while RBC aggregation increased. Blood viscosity changes were more moderate in the Training group, suggesting potential adaptation. However, the training intensity may have been insufficient for significant hemorheological improvements. While regular physical activity can enhance RBC function, adequate intensity, recovery, and nutrition are essential for optimal adaptation. Individualized training strategies should consider these factors to maximize performance and hemorheological benefits.
Full article
(This article belongs to the Special Issue Blood Rheology: Insights & Innovations)
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