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Volume 15
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Life, Volume 15, Issue 6 (June 2025) – 157 articles

Cover Story (view full-size image): Clozapine remains the leading drug for treatment-resistant schizophrenia, yet its complex pharmacology, inconsistent efficacy, and adverse side effects hinder its adoption. In this review, we collate clinical, imaging, and molecular findings from 2013 to 2025 to address at least three factors: how clozapine’s rapid D2 drop-off but high affinity for D4, 5-HT2A/C, muscarinic, H1, and α1 receptors drives NMDA signaling, kynurenine turnover, mTOR-S6 translation, and cortical perfusion; when additional therapies such as paliperidone, amisulpride, memantine, minocycline, or rTMS rescue partial responders; and how plasma metabolite ratios, neurotrophins, brain morphometry, pharmacogenes, and polygenic risk scores can predict response and guide safer dosing. This article interweaves these strands to chart a path toward personalized, high-benefit, low-risk clozapine care. View this paper
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14 pages, 443 KiB  
Review
Platelet Transfusions: Current Practices and Emerging Alternatives in the United States
by Mark Friedman, Victoria Costa, Behnam Rafiee, Timothy Hilbert, Mansab Jafri and Ding Wen Wu
Life 2025, 15(6), 985; https://doi.org/10.3390/life15060985 - 19 Jun 2025
Viewed by 738
Abstract
Platelet transfusions are a cornerstone of hemorrhage management in patients with thrombocytopenia or platelet dysfunction, yet their indications and dosing are largely based on expert opinion and low-quality evidence. This review offers a timely and comprehensive analysis of platelet transfusion practices in the [...] Read more.
Platelet transfusions are a cornerstone of hemorrhage management in patients with thrombocytopenia or platelet dysfunction, yet their indications and dosing are largely based on expert opinion and low-quality evidence. This review offers a timely and comprehensive analysis of platelet transfusion practices in the United States (U.S.), uniquely integrating clinical evidence, such as the pivotal PLADO trial, with emerging technological advancements. Using a holistic approach, this manuscript addresses not only conventional practices (such as dosing standards and storage methods), but also cutting-edge alternatives like cold-stored and freeze-dried platelets, pathogen reduction technologies, and synthetic platelet substitutes. By juxtaposing U.S. practices with international standards, it highlights inefficiencies in dosing and supply management, proposing actionable solutions like lower-dose transfusions and diversified platelet inventories. Furthermore, the manuscript’s exploration of whole blood-derived platelets and the ethical debate surrounding paid donors adds a forward-looking perspective. By examining these innovations alongside strategies to optimize supply, this work aims to provide a comprehensive overview of how transfusion medicine is adapting to meet clinical and logistical demands. Full article
(This article belongs to the Section Medical Research)
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12 pages, 3540 KiB  
Article
Clinical Outcomes and Optical Bench Analysis of a Novel Enhanced Monofocal Intraocular Lens
by Giovanni Romualdi, Matilde Buzzi, Pier Giuseppe Ruggeri, Federico Tommasi, Alessio Giorgetti, Stefano Cavalieri and Rita Mencucci
Life 2025, 15(6), 984; https://doi.org/10.3390/life15060984 - 19 Jun 2025
Viewed by 468
Abstract
Purpose: A novel enhanced monofocal intraocular lens (IOL) has been developed to improve functional intermediate vision, maintaining a distance vision comparable to a standard monofocal lens and avoiding the drawbacks of multifocal IOLs. The aim of this study is to perform optical bench [...] Read more.
Purpose: A novel enhanced monofocal intraocular lens (IOL) has been developed to improve functional intermediate vision, maintaining a distance vision comparable to a standard monofocal lens and avoiding the drawbacks of multifocal IOLs. The aim of this study is to perform optical bench analysis and to evaluate refractive and visual outcomes and patient satisfaction. Methods: This prospective comparative single-center study was conducted in Careggi Hospital, University of Florence (Italy). We included 100 eyes from 50 patients who underwent bilateral cataract surgery. One group received the standard monofocal Tecnis GCB00 IOL, while the other group received the novel enhanced monofocal Evolux IOL. We evaluated binocular visual and refractive outcomes at 6 months after surgery. Binocular defocus curves and contrast sensitivity (CS) were also assessed. Optical quality was also analyzed in terms of higher-order aberrations (HOAs), modulation transfer function (MTF), objective scatter index (OSI), Strehl ratio, effective lens position (ELP), and halo analysis. A Patient-Reported Spectacle Independence Questionnaire (PRSIQ) was performed to assess spectacle independence outcomes. Finally, we analyzed the optical bench of both lenses. Results: All eyes implanted with Evolux achieved excellent distance vision, comparable to that achieved with GCB00. Evolux showed better intermediate and near vision, without any loss of visual quality, contrast sensitivity, or the presence of halos and photic phenomena. The optical bench analysis confirmed the different optical properties of the two lenses and supported the behavior obtained with the clinical defocus curve. Conclusions: These preliminary results show good refractive accuracy and visual outcomes for the enhanced monofocal IOL Evolux after cataract surgery. Further studies are needed to confirm our findings in terms of the number of patients and the period of follow-up. Full article
(This article belongs to the Special Issue Vision Science and Optometry)
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17 pages, 2399 KiB  
Article
In Vitro Antioxidant and Anti-Neuroinflammatory Effects of Elsholtzia blanda (Benth.) Benth.
by Yeo Dae Yoon, Krishna K. Shrestha and Seung-Hwa Baek
Life 2025, 15(6), 983; https://doi.org/10.3390/life15060983 - 19 Jun 2025
Viewed by 554
Abstract
Elsholtzia blanda (Benth.) Benth. (EBB) is a traditional plant in Nepal with bioactive properties, including antioxidant, cytotoxic, and antitumor activities. In this study, a methanol EBB extract was tested to evaluate the anti-inflammatory effect against lipopolysaccharide (LPS)-induced microglial (BV2) cells. EBB effectively suppressed [...] Read more.
Elsholtzia blanda (Benth.) Benth. (EBB) is a traditional plant in Nepal with bioactive properties, including antioxidant, cytotoxic, and antitumor activities. In this study, a methanol EBB extract was tested to evaluate the anti-inflammatory effect against lipopolysaccharide (LPS)-induced microglial (BV2) cells. EBB effectively suppressed LPS-induced nitric oxide production and inhibited the secretion of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6. In LPS-stimulated BV2 cells, EBB significantly inhibited inducible nitric oxide synthase (iNOS), TNF-α, IL-6, IL-1β, IL-8, IL-18, and IL-10 mRNA expression in a concentration-dependent manner. In particular, EBB significantly reduced the protein expression of iNOS and cyclooxygenase-2, which were upregulated by LPS. Further, EBB could alleviate the inflammatory response in microglia by suppressing the phosphorylation of mitogen-activated protein kinases. EBB also attenuated LPS-induced reactive oxygen species (ROS) in BV2 cells. In addition, EBB enhanced heme oxygenase-1 (HO-1) protein and mRNA expression. The present results show that an EBB extract could effectively suppress the neuroinflammatory response induced by LPS in BV2 cells. Accordingly, an EBB extract is a promising preventive agent against diseases involving neuroinflammatory responses. Full article
(This article belongs to the Section Pharmaceutical Science)
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23 pages, 2655 KiB  
Review
The Role of Nutrition in HIV-Associated Neurocognitive Disorders: Mechanisms, Risks, and Interventions
by Carlotta Siddi, Jihane Balla, Christy Agbey, Paola Fadda and Simona Dedoni
Life 2025, 15(6), 982; https://doi.org/10.3390/life15060982 - 19 Jun 2025
Viewed by 1376
Abstract
HIV-associated neurocognitive disorders (HANDs) refer to a range of cognitive deficits that afflict people living with the Human Immunodeficiency Virus (HIV). The fundamental processes of HAND include persistent inflammation, immunological activation, and direct viral impact on the central nervous system. Emerging research shows [...] Read more.
HIV-associated neurocognitive disorders (HANDs) refer to a range of cognitive deficits that afflict people living with the Human Immunodeficiency Virus (HIV). The fundamental processes of HAND include persistent inflammation, immunological activation, and direct viral impact on the central nervous system. Emerging research shows that nutritional status, especially food consumption and body weight, is critical in determining the course and severity of HAND. Malnutrition exacerbates neurocognitive impairment by increasing inflammation and oxidative stress, while obesity may contribute to HAND through the promotion of metabolic disruption, gut microbiota alterations, and systemic inflammation. Additionally, the introduction of antiretroviral treatment (ART) has substantially enhanced the prognosis of people living with HIV by lowering viral load and improving immune function. However, depending on the regimen, ART can cause changes in body weight, which may influence the progression of HAND. This emphasizes the intricate interplay between HIV, nutrition, body weight, and neurocognitive health. As a result, various dietary approaches are currently being investigated to improve the quality of life of individuals with HIV and possibly help prevent neurocognitive decline in this population. This review aims to elucidate the relationship between nutrition and neurocognitive function in individuals living with HIV, shedding light on aspects of HANDs related to diet, body weight fluctuations, and metabolic syndrome. It explores the shift from current pharmacological treatments to innovative non-pharmacological interventions, including specific dietary strategies, to support overall health and cognitive well being in HIV-positive people. Full article
(This article belongs to the Special Issue Novel Therapies for Chronic Inflammatory Diseases and Autoimmune Diseases)
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32 pages, 4906 KiB  
Article
Transcriptomic and miRNA Signatures of ChAdOx1 nCoV-19 Vaccine Response Using Machine Learning
by Jinting Lin, Qinglan Ma, Lei Chen, Wei Guo, Kaiyan Feng, Tao Huang and Yu-Dong Cai
Life 2025, 15(6), 981; https://doi.org/10.3390/life15060981 - 18 Jun 2025
Viewed by 471
Abstract
Vaccination with ChAdOx1 nCoV-19 is an important countermeasure to fight the COVID-19 pandemic. This vaccine enhances human immunoprotection against SARS-CoV-2 by inducing an immune response against the SARS-CoV-2 S protein. However, the immune-related genes induced by vaccination remain to be identified. This study [...] Read more.
Vaccination with ChAdOx1 nCoV-19 is an important countermeasure to fight the COVID-19 pandemic. This vaccine enhances human immunoprotection against SARS-CoV-2 by inducing an immune response against the SARS-CoV-2 S protein. However, the immune-related genes induced by vaccination remain to be identified. This study employs feature ranking algorithms, an incremental feature selection method, and classification algorithms to analyze transcriptomic data from an experimental group vaccinated with the ChAdOx1 nCoV-19 vaccine and a control group vaccinated with the MenACWY meningococcal vaccine. According to different time points, vaccination status, and SARS-CoV-2 infection status, the transcriptomic data was divided into five groups, including a pre-vaccination group, ChAdOx1-onset group, MenACWY-onset group, ChAdOx1-7D group, and MenACWY-7D group. Each group contained samples with 13,383 RNA features and 1662 small RNA features. The results identified key genes that could indicate the efficacy of the ChAdOx1 nCoV-19 vaccine, and a classifier was developed to classify samples into the above groups. Additionally, effective classification rules were established to distinguish between different vaccination statuses. It was found that subjects vaccinated with ChAdOx1 nCoV-19 vaccine and infected with SARS-CoV-2 were characterized by up-regulation of HIST1H3G expression and down-regulation of CASP10 expression. In addition, IGHG1, FOXM1, and CASP10 genes were strongly associated with ChAdOx1 nCoV-19 vaccine efficacy. Compared with previous omics-driven studies, the machine learning algorithms used in this study were able to analyze transcriptome data faster and more comprehensively to identify potential markers associated with vaccine effect and investigate ChAdOx1 nCoV-19 vaccine-induced gene expression changes. These observations contribute to an understanding of the immune protection and inflammatory responses induced by the ChAdOx1 nCoV-19 vaccine during symptomatic episodes and provide a rationale for improving vaccine efficacy. Full article
(This article belongs to the Section Biochemistry, Biophysics and Computational Biology)
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15 pages, 3402 KiB  
Article
Improvement on Ferrous Ion Accumulation and Mitochondrial Dysfunction in the COVID-19 Pseudovirus-Infected Cell Model Simulating the Long COVID Status by Nutritional Strategy
by Bo-Kai Chen, Chi-Ho Chan and Chin-Kun Wang
Life 2025, 15(6), 980; https://doi.org/10.3390/life15060980 - 18 Jun 2025
Viewed by 401
Abstract
The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID [...] Read more.
The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has plunged the world into a major crisis of overwhelming morbidity and mortality and emerged various mutant strains. Patients recovering from SARS-CoV-2 develop post-acute COVID syndrome, commonly known as long COVID (LC), lasting up to 12 weeks or even longer. The mechanism has yet to be clarified. COVID-19 pseudovirus is a suitable model to understand the infection of the COVID-19 virus to cells, which is suitable to see the acute change in cells owing to its one-time infection and inactivation. The ACE2-293T cell infected by COVID-19 pseudovirus was used in this study. After the infection and removal of the pseudovirus, high amounts of ferrous ions were accumulated in mitochondria and then released into the cytosol. Reactive oxygen species (ROS) accumulation was formed and caused mitochondrial dysfunction. To evaluate the effect of nutritional strategy on ferrous ion accumulation and mitochondrial dysfunction, lactoferrin, Q10 and Echinacea purpurea extract (EPE) were used in this study. Results showed that lactoferrin, Q10 and EPE could improve mitochondrial dysfunction by reducing the accumulation of ferrous ions and ROS in the mitochondria. HPLC analysis showed that EPE contained rich caffeic acid, and it also showed perfect improvement in mitochondrial dysfunction. In conclusion, cells infected with pseudovirus could increase the accumulation of ferrous ions and ROS in mitochondria and be released into the cytosol after removing pseudovirus, thereby causing mitochondrial dysfunction. Lactoferrin, Q10 and EPE were an effective nutritional strategy to suppress ferrous ion accumulation, ROS formation and advanced mitochondrial dysfunction. Full article
(This article belongs to the Topic New Insights of Natural Compounds in Antioxidant and Anti-Inflammatory Properties)
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19 pages, 2692 KiB  
Article
Low-Dose Quercetin Dephosphorylates AKT and Suppresses Proteins Related to Migration in Human Metastatic Uveal Melanoma Cells
by Petra Fodor, József Király, Zsuzsanna Szabó, Katalin Goda, Barbara Zsebik and Gábor Halmos
Life 2025, 15(6), 979; https://doi.org/10.3390/life15060979 - 18 Jun 2025
Viewed by 353
Abstract
Background: Uveal melanoma (UM) is the most common intraocular cancer of the eye, with high metastatic potential in adults. In 50% of patients, UM spreads to other tissues, causing a fatal outcome. Flavonoids are bioactive phenolic compounds found in fruits and plants, thus [...] Read more.
Background: Uveal melanoma (UM) is the most common intraocular cancer of the eye, with high metastatic potential in adults. In 50% of patients, UM spreads to other tissues, causing a fatal outcome. Flavonoids are bioactive phenolic compounds found in fruits and plants, thus commonly present in the natural diet. Quercetin is the most remarkable agent among flavonols proved to have an anticancer effect. Thus, we aimed to investigate the effect of quercetin on a metastatic UM cell line MM28. Methods: MM28 cells were treated with increasing concentrations of quercetin (0.1–10 µM). The changes of proliferation and migration markers were studied both in gene and protein expression level by qPCR, Western blotting, and Proteome Profiler Human XL Oncology Array. Results: Quercetin had only a slight anti-proliferative effect on MM28 cells. However, 1 µM of quercetin significantly elevated the mRNA expression of the Maspin gene and downregulated MMP2 gene expression. In addition, the protein expression levels of pAKT, NF-κB, and MMP8 were significantly decreased by the treatment. Conclusions: Our findings indicate that low-dose (1 µM) quercetin treatment is able to suppress the expression of certain migration markers, and therefore, it might be a useful adjuvant compound to reduce metastasis formation of UM. Full article
(This article belongs to the Special Issue Natural Bioactives: Exploring Their Therapeutic Potential—2nd Edition)
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9 pages, 198 KiB  
Article
Maternal and Clinical Outcomes of Placenta Accreta Spectrum: Insights from a Retrospective Study in Bahrain
by Kareeza Selby Chacko, Reem Satam AlSubeaei, Soumya Sunil Nair, Nusrat Khalil Kazi and Rafiea Jeddy
Life 2025, 15(6), 978; https://doi.org/10.3390/life15060978 - 18 Jun 2025
Viewed by 500
Abstract
Placenta accreta spectrum (PAS) refers to a group of abnormal placental attachments in which the placenta adheres too deeply to the uterine wall, with varying degrees of invasion classified as accreta, increta, or percreta. Increased rates of uterine surgeries, advanced maternal age, and [...] Read more.
Placenta accreta spectrum (PAS) refers to a group of abnormal placental attachments in which the placenta adheres too deeply to the uterine wall, with varying degrees of invasion classified as accreta, increta, or percreta. Increased rates of uterine surgeries, advanced maternal age, and cesarean deliveries have all contributed to an increase in the incidence of PAS. Complications associated with PAS can lead to severe intrapartum or postpartum hemorrhage, hysterectomy, and significant maternal morbidity, making early diagnosis and management crucial for improving outcomes. Understanding the epidemiology and risk factors of PAS is crucial for developing early detection protocols and preventive strategies. Localized data, particularly from Bahrain, can inform targeted care approaches and optimize resource allocation, ultimately leading to improved clinical guidelines, enhanced patient education, and better healthcare outcomes for affected women. There are growing concerns about the impact of PAS on maternal health and healthcare resources in Bahrain, similar to trends observed in other regions. To improve patient education and management strategies, it is essential to comprehend the regional patterns, characteristics, and outcomes associated with PAS. However, the absence of comprehensive data specific to Bahrain hinders effective clinical decision-making and policy development. Addressing this gap is imperative for advancing maternal healthcare in the region. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
15 pages, 1451 KiB  
Article
A Cross-Sectional Study on the Biomechanical Effects of Squat Depth and Movement Speed on Dynamic Postural Stability in Tai Chi
by Wenlong Li, Minjun Liang, Liangliang Xiang, Zsolt Radak and Yaodong Gu
Life 2025, 15(6), 977; https://doi.org/10.3390/life15060977 - 18 Jun 2025
Viewed by 894
Abstract
This study aimed to explore the independent and interactive effects of varying squat depths and movement speeds on dynamic postural stability during the Part the Wild Horse’s Mane (PWHM) movement. Thirteen male participants (age: 25.86 ± 1.35 years; height: 174.26 ± 6.09 cm; [...] Read more.
This study aimed to explore the independent and interactive effects of varying squat depths and movement speeds on dynamic postural stability during the Part the Wild Horse’s Mane (PWHM) movement. Thirteen male participants (age: 25.86 ± 1.35 years; height: 174.26 ± 6.09 cm; body mass: 68.64 ± 8.15 kg) performed the PWHM movement at three different squat heights, high squat (HS), middle squat (MS), low squat (LS), and two different speeds, fast and slow. Dynamic postural stability (DPSI) was assessed through the center-of-mass (CoM) trajectory and the center-of-pressure (CoP) trajectory. The analyses used two-factor repeated-measures ANOVA and statistical nonparametric mapping, with key metrics including anteroposterior stability (APSI), mediolateral stability (MLSI), vertical stability (VSI), DPSI indices, and the path lengths of the CoP and CoM. LS exhibited significantly greater CoP and CoM path lengths compared with MS and HS (p < 0.01). Furthermore, fast movements demonstrated higher VSI and DPSI than slow movements (p < 0.05). Tai Chi with different squat depths and speeds can affect postural stability. To reduce the fall risk, older adults and individuals with balance impairments should prioritize slower Tai Chi movements, particularly when using high squat postures. Full article
(This article belongs to the Section Physiology and Pathology)
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16 pages, 274 KiB  
Article
Risk Factors for Chronic Pain in Women: The Role of Violence Exposure in a Case–Control Study
by Allison Uvelli, Erica Pugliese and Fabio Ferretti
Life 2025, 15(6), 976; https://doi.org/10.3390/life15060976 - 18 Jun 2025
Viewed by 390
Abstract
Background: Chronic pain is an unpleasant sensory and emotional experience that greatly affects functioning and well-being. Studies link chronic pain and violence against women, with an odds ratio of 2.08 and a 26% prevalence rate. The bio-psycho-social consequences reduce quality of life and [...] Read more.
Background: Chronic pain is an unpleasant sensory and emotional experience that greatly affects functioning and well-being. Studies link chronic pain and violence against women, with an odds ratio of 2.08 and a 26% prevalence rate. The bio-psycho-social consequences reduce quality of life and cause disability. Despite extensive research, the etiology remains unclear. This study investigates the bio-psycho-social risk factors of chronic pain in women, both victims and non-victims of violence. Methods: A case–control study (December 2023–June 2024) used odds ratios and Fisher’s exact test to explore risk factors associated with chronic pain. Univariate logistic regressions identified significant predictors. Results: The study included 170 women (68 victims), half with chronic pain. Nine risk factors were specific to victims (three biological, six psycho-social), four to non-victims (two biological, two psycho-social), and twenty-three to all women (five biological, eighteen psycho-social). A four-factor model best explained risk in victims and all women, while a two-factor model fit non-victims. Conclusions: The bio-psycho-social model of chronic pain is supported, identifying specific risk factors. These findings can aid anti-violence and healthcare professionals in screening and early intervention. Full article
(This article belongs to the Special Issue Pain and Therapy: Historical Perspectives and Future Directions)
11 pages, 6334 KiB  
Article
Endoscopic-Assisted Transoral Approach (EATA) for Extracranial Tumors: A Multicentric Case Series
by Giovanni Motta, Arianna Di Stadio, Luca D’Ascanio, Luigi D’avino, Vincenzo della Peruta, Francesco Chiari, Carlo Magno, Giuseppe Tortoriello and Gaetano Motta
Life 2025, 15(6), 975; https://doi.org/10.3390/life15060975 - 18 Jun 2025
Viewed by 378
Abstract
Endoscopic surgery is useful and helpful especially to access areas with limited visibility. The combination of this technique with innovative approaches could be the solution to improve quality of surgery and patients’ outcome. This study aimed to illustrate how Endoscopic-Assisted Transoral Approach (EATA) [...] Read more.
Endoscopic surgery is useful and helpful especially to access areas with limited visibility. The combination of this technique with innovative approaches could be the solution to improve quality of surgery and patients’ outcome. This study aimed to illustrate how Endoscopic-Assisted Transoral Approach (EATA) can be used to successfully remove specific extracranial tumors with defined characteristics. Eleven patients with extracranial tumors underwent surgical resection using an EATA between 2003 and 2025. All patients underwent clinical examination and fiberoptic laryngoscopy. Preoperative CT and/or MRI was performed in all cases. All patients were successfully treated utilizing an EATA. Histological examination revealed nine parapharyngiomas, comprising five pleomorphic adenomas, two schwannomas, one ectopic thyroid gland, one lipoma, one masticator space schwannoma, and one nasopharyngeal pleomorphic adenoma. No intra-operative nor peri-operatory complications were observed. The only long-term sequela observed was Horner’s syndrome in the two schwannomas originating from the parapharyngeal-carotid space. The mean hospital stay was 2.6 days, while the mean follow-up duration was 9.8 years. The EATA represents a valid surgical technique for the treatment of benign, encapsulated, and non-vascular parapharyngeal space (PPS) tumors exhibiting posterior displacement of major vessels. This approach may also prove beneficial for the management of other benign, encapsulated, and non-vascular tumors located in the nasopharynx and masticator space. Full article
(This article belongs to the Section Medical Research)
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9 pages, 497 KiB  
Article
Efficacy and Safety of Selexipag Treatment in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension with Concomitant Interstitial Lung Disease
by Chebly Dagher, Maria Akiki, Kristen Swanson, Brett Carollo, Harrison W. Farber and Raj Parikh
Life 2025, 15(6), 974; https://doi.org/10.3390/life15060974 - 18 Jun 2025
Viewed by 450
Abstract
Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH [...] Read more.
Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH patients with concomitant ILD. Clinical, functional, and laboratory data were collected at baseline and after 16 weeks of treatment. After 16 weeks of treatment, the mean six-minute walk distance increased by 101.75 m (p < 0.05), and the mean estimated right ventricular systolic pressure decreased significantly (p < 0.05). Mean N-terminal pro b-type natriuretic peptide levels declined by 63%, though this reduction did not reach statistical significance. Importantly, supplemental oxygen requirements trended downward (p < 0.05) and pulmonary function tests remained stable. Pulmonary vasodilators have long been unsuccessfully studied in PH-ILD patients until the INCREASE trial. While other systemic agents used in PAH have not shown as much success as inhaled treprostinil in treating PH-ILD, our case series highlights the potential role of selexipag in patients with concomitant CTD-PAH and ILD. Further investigation of selexipag in pure Group 3 PH-ILD patients is warranted. Full article
(This article belongs to the Section Physiology and Pathology)
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12 pages, 859 KiB  
Systematic Review
Intravenous Magnesium Sulphate as an Adjuvant Therapy for Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis
by Taimur Farid, Abdousamad Said Omar, Sijah Varar Kandi, Soja Puthiyara Maliyekal, Tze Quan Tuen, Amrutha Thazhuthedath Vijayan, Lakshmi Sudhir Pillai, Ahmed Talaat Deiab, Muhammad Sajid, Ahmad Mesmar, Eman Ibrahim Elzain Hassan, Rijas Keethadath, Hasan Al Chalabi, Tallal Mushtaq Hashmi, Mushood Ahmed and Raheel Ahmed
Life 2025, 15(6), 973; https://doi.org/10.3390/life15060973 - 18 Jun 2025
Viewed by 529
Abstract
Background: Intravenous magnesium sulfate (IV MgSO4) may serve as an effective adjunct therapy to improve clinical outcomes in patients experiencing acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Methods: A comprehensive search was conducted on PubMed, Cochrane, and EMBASE [...] Read more.
Background: Intravenous magnesium sulfate (IV MgSO4) may serve as an effective adjunct therapy to improve clinical outcomes in patients experiencing acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). Methods: A comprehensive search was conducted on PubMed, Cochrane, and EMBASE from inception to April 2025 to find eligible studies comparing IV MgSO4 plus standard treatment versus standard treatment alone. A random-effects meta-analysis was conducted using RevMan. Results: Nine studies (seven RCTs and two observational studies) met the inclusion criteria. Pooled analysis demonstrated that adjunctive IV MgSO4 significantly improved peak expiratory flow rate at 45 min (MD = 18.50, 95% CI = 6.36 to 30.65) and significantly reduced hospital admission rates from the emergency department (OR = 0.45, 95% CI = 0.23 to 0.88). No significant differences were observed in the length of hospital stay (MD = −0.83, 95% CI = −2.99 to 1.33) and adverse events (OR = 0.79, 95% CI = 0.20 to 3.13; p = 0.73, I2 = 25%) between the two groups. Conclusions: Adjunct MgSO4 in AECOPD is associated with significant improvement in peak expiratory flow rate at 45 min and reduced hospitalization rates. Additional large-scale, multicenter randomized controlled trials are needed to validate and strengthen these findings. Full article
(This article belongs to the Special Issue Chronic Obstructive Pulmonary Disease: Clinical, Epidemiological, and Molecular Bases)
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21 pages, 2472 KiB  
Article
Integrating Soil Physicochemical Properties and Microbial Functional Prediction to Assess Land-Use Impacts in a Cold-Region Wetland Ecosystem
by Junnan Ding and Shaopeng Yu
Life 2025, 15(6), 972; https://doi.org/10.3390/life15060972 - 18 Jun 2025
Viewed by 428
Abstract
This study investigated the effects of land-use change and wetland restoration on soil microbial community diversity, structure, and function in a cold-region wetland ecosystem. Soil samples from six land-use types were analyzed for key physicochemical and biochemical properties, including soil water content, pH, [...] Read more.
This study investigated the effects of land-use change and wetland restoration on soil microbial community diversity, structure, and function in a cold-region wetland ecosystem. Soil samples from six land-use types were analyzed for key physicochemical and biochemical properties, including soil water content, pH, total nitrogen, soil organic carbon (SOC), and enzymatic activities. Significant differences in carbon and nitrogen availability were observed, with restored wetland soils showing higher SOC and moisture levels, while agricultural soils exhibited elevated nitrate concentrations. Bacterial community composition was estimated based on 16S ribosomal RNA gene sequencing, and microbial functional profiles were predicted using Functional Annotation of Prokaryotic Taxa (FAPROTAX) and BugBase. Bacterial communities were dominated by Proteobacteria, Actinobacteriota, and Acidobacteriota, with significant shifts among land-use types. Redundancy analysis revealed that SOC, SWC, total nitrogen (TN), and pH were key drivers of community differentiation. Functional prediction showed enrichment of fermentation and anaerobic metabolism in restored wetlands, while aerobic carbon metabolism dominated in agricultural and forest soils. These findings demonstrate that wetland restoration improves both taxonomic and functional diversity. While ecosystem multifunctionality and resilience were not directly quantified, the observed increases in microbial richness, functional group diversity, and enzymatic activity suggest enhanced ecological capacity and potential for system stability in cold-region wetlands. Full article
(This article belongs to the Section Microbiology)
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13 pages, 1130 KiB  
Article
The Platelet-to-Lymphocyte Ratio (PLR) as a Non-Invasive Biomarker for Cervical Malignancy in Conization Patients
by Noémi Kalas, Verita Szabó, Balázs Vida, Zsófia Tóth, Lotti Lőczi, Barbara Sebők, Petra Merkely, Balázs Lintner, Nándor Ács, Attila Keszthelyi, Szabolcs Várbíró, Richárd Tóth and Márton Keszthelyi
Life 2025, 15(6), 971; https://doi.org/10.3390/life15060971 - 18 Jun 2025
Viewed by 385
Abstract
Background: Cervical cancer continues to pose a significant global health challenge, particularly in low-resource regions with limited access to advanced diagnostics. Cervical conization can occasionally uncover invasive carcinoma in patients initially suspected of having only pre-invasive lesions. This study assessed the platelet-to-lymphocyte ratio [...] Read more.
Background: Cervical cancer continues to pose a significant global health challenge, particularly in low-resource regions with limited access to advanced diagnostics. Cervical conization can occasionally uncover invasive carcinoma in patients initially suspected of having only pre-invasive lesions. This study assessed the platelet-to-lymphocyte ratio (PLR) as a potential predictive biomarker for identifying invasive disease in patients undergoing a loop electrosurgical excision procedure (LEEP). Methods: A retrospective study was conducted on 371 patients who underwent LEEP conization for cervical dysplasia. Preoperative PLR values were collected and compared across final histopathological categories (negative, low-grade, high-grade, invasive carcinoma) using the Kruskal–Wallis test, followed by Mann–Whitney U tests for pairwise comparisons. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy. Results: PLR values above 7.7 were significantly associated with HPV positivity, increasing with histopathological severity. There were significant PLR differences across the outcome groups (p = 0.005), with notably higher values in cases of invasive carcinoma (p < 0.01). ROC analysis showed moderate diagnostic utility (AUC ≈ 0.72); at a PLR cutoff of ~11.9, sensitivity was 65% and specificity 81%. Conclusions: The PLR cutoff of 7.7 was associated with HPV positivity, while a higher cutoff of 11.93 was identified for predicting invasive cervical cancer. These findings support that preoperative PLR is a non-invasive, clinically relevant marker correlated with lesion severity, offering potential for preoperative risk stratification, particularly where advanced diagnostics are limited. Full article
(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: From Bench to Bedside—2nd Edition)
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12 pages, 719 KiB  
Article
Differential Analysis of Hemogram Parameters and Cellular Ratios in Severe Asthma Exacerbations: A Comparative Study of Eosinophilic and Non-Eosinophilic Phenotypes
by Nicolae Demenciuc, Corina Eugenia Budin, Corina Ureche, Mircea Stoian, Teodora Nicola-Varo, Dragos-Florin Baba, Dariana-Elena Pătrîntașu and Diana Deleanu
Life 2025, 15(6), 970; https://doi.org/10.3390/life15060970 - 18 Jun 2025
Cited by 1 | Viewed by 504
Abstract
Asthma exacerbations are acute worsening episodes in individuals with bronchial asthma, frequently necessitating emergency hospital care. Early differentiation between eosinophilic (≥150 eosinophils/mm3) and non-eosinophilic (<150 eosinophils/mm3) subtypes plays a crucial role in treatment decisions and identifying patients eligible for [...] Read more.
Asthma exacerbations are acute worsening episodes in individuals with bronchial asthma, frequently necessitating emergency hospital care. Early differentiation between eosinophilic (≥150 eosinophils/mm3) and non-eosinophilic (<150 eosinophils/mm3) subtypes plays a crucial role in treatment decisions and identifying patients eligible for biologic therapies. The ExBA Study explored variations in complete blood count (CBC) parameters and derived cellular ratios—namely the neutrophil-to-lymphocyte (NLR), thrombocyte-to-lymphocyte (TLR), and eosinophil-to-leukocyte ratios (ELR)—in adults hospitalized with severe asthma exacerbations. Ninety patients were enrolled and categorized into eosinophilic (n = 38) and non-eosinophilic (n = 52) groups. Significant statistical differences were observed in the neutrophil and lymphocyte levels, as well as in all three ratios. ROC analysis highlighted the ELR as the most specific indicator of the eosinophilic phenotype (specificity 100%, AUC 0.938, cut-off 0.003), whereas the NLR and TLR showed stronger associations with the non-eosinophilic group (AUC 0.733 and 0.676). No meaningful differences emerged regarding arterial blood gas levels, length of hospital stay, treatment costs, or mortality. A notable association was found between a personal or family history of atopy and the eosinophilic subtype (p = 0.0181). This study underscores the relevance of CBC-based ratios in asthma phenotyping during exacerbation events. Full article
(This article belongs to the Special Issue Advances in Pulmonology: Transforming Diagnosis and Treatment of Lung Diseases)
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14 pages, 240 KiB  
Article
Normalisation of AHI Under Positive Pressure Therapy Does Not Necessarily Mean Control of Symptoms: A Comparison of the Effectiveness of APAP and CPAP on Daytime Sleepiness and Nocturnal Urination
by Sorin Bivolaru and Ancuța Constantin
Life 2025, 15(6), 969; https://doi.org/10.3390/life15060969 - 18 Jun 2025
Viewed by 390
Abstract
In practice, many patients receive APAP treatment for the simple reason that it provides increased comfort and is easier for patients to accept and tolerate. Reality has proven that we have very many patients diagnosed with OSAS on APAP treatment, under which AHI [...] Read more.
In practice, many patients receive APAP treatment for the simple reason that it provides increased comfort and is easier for patients to accept and tolerate. Reality has proven that we have very many patients diagnosed with OSAS on APAP treatment, under which AHI has normalized, but patients continue to have remaining symptoms. Thus the question was born: is the persistence of remnant symptomatology under APAP related to the mode of ventilation in patients with normalized AHI? The target group was young obese men presenting to the urology service for nocturnal pollakiuria without urologic cause. After performing nocturnal ventilatory polygraphy, the patients were recommended APAP treatment for three months, subsequently, the patients were switched to CPAP treatment for another three months, thus comparing the results obtained. After 6 months of treatment, 71.4% of the subjects would opt to continue CPAP treatment. While a clear option for APAP treatment was expressed by 10.2%. Our research, suggests that we should not be misled by the normalization of AHI under APAP therapy, but to evaluate the patients also with the help of available and standardized questionnaires. Full article
(This article belongs to the Special Issue Current Trends in Obstructive Sleep Apnea)
15 pages, 390 KiB  
Article
Childhood Obesity and Overweight Are Associated with Higher Risk of Depression and Anxiety: A Cross-Sectional Study in Children Aged 6–9 Years
by Konstantinos Papadimitriou, Maria Mentzelou, Sousana K. Papadopoulou, Georgios Antasouras, Georgia-Eirini Deligiannidou, Olga Alexatou, Apostolia Ntovoli, Evmorfia Psara, Vasiliki G. Papadopoulou and Constantinos Giaginis
Life 2025, 15(6), 968; https://doi.org/10.3390/life15060968 - 18 Jun 2025
Viewed by 444
Abstract
Background/Objectives: The global prevalence of childhood obesity and overweight is steadily increasing, representing a pressing public health concern due to its persistence during adolescence and adulthood and its association with elevated morbidity and mortality risks. This cross-sectional study was designed to examine the [...] Read more.
Background/Objectives: The global prevalence of childhood obesity and overweight is steadily increasing, representing a pressing public health concern due to its persistence during adolescence and adulthood and its association with elevated morbidity and mortality risks. This cross-sectional study was designed to examine the potential association between overweight/obesity and the presence of depressive and anxiety symptoms in children aged 6 to 9 years. Methods: A total of 4098 children from various urban and rural regions in Greece were enrolled. Data was collected through maternal questionnaires capturing sociodemographic characteristics, perinatal outcomes, anthropometric measurements, breastfeeding practices, and physical activity levels. Children fulfilled the Children’s Depression Inventory (CDI) and the State-Trait Anxiety Inventory for Children—State form (STAIC-S) to evaluate symptoms of depression and anxiety, respectively. Results: Childhood overweight/obesity was independently and significantly associated with a more than two-fold increased likelihood of presenting depressive and anxiety symptoms. Childhood overweight/obesity was also significantly associated with maternal obesity, gestational weight gain, childbirth weight, mode of delivery, exclusive breastfeeding, and children’s physical activity. Conclusions: Overweight and obesity in children aged 6–9 years are significantly associated with an elevated risk of psychological distress, including depression and anxiety. These findings underscore the need for targeted public health policies and nutritional interventions aimed at promoting healthy lifestyle practices from early childhood. Educational efforts should also support new mothers in adopting and sustaining health-promoting behaviors to mitigate the long-term consequences of childhood obesity. Full article
(This article belongs to the Section Physiology and Pathology)
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23 pages, 7855 KiB  
Article
Novel Acylated Naringin Enhances Propionate Release and Stimulates the Growth of Flavanone-Metabolizing Bacteria in an In Vitro Batch Fermentation Model
by Blanca Elizabeth Ruiz-Álvarez, José Daniel Padilla-de la Rosa, Marisela González Avila, Georgina Sandoval and Yves Desjardins
Life 2025, 15(6), 967; https://doi.org/10.3390/life15060967 - 17 Jun 2025
Viewed by 649
Abstract
The increasing prevalence of non-communicable diseases (NCDs) is strongly associated with gut microbiota (GM) imbalances and reduced short-chain fatty acid (SCFA) production, primarily driven by poor diet and microbial dysbiosis. Since SCFAs are crucial for gut health, immune regulation, and inflammation control, restoring [...] Read more.
The increasing prevalence of non-communicable diseases (NCDs) is strongly associated with gut microbiota (GM) imbalances and reduced short-chain fatty acid (SCFA) production, primarily driven by poor diet and microbial dysbiosis. Since SCFAs are crucial for gut health, immune regulation, and inflammation control, restoring their levels is a key therapeutic target. SCFA-acylated naringin derivatives offer a novel approach by enhancing SCFA delivery and modulating GM composition. In this study, we investigated the effects of naringin acetate and naringin propionate on SCFA production using a 24 h short-term in vitro batch fecal fermentation model with microbiota from two donors. Naringin propionate and naringin plus free propionate significantly increased propionate levels by 0.74 mM and 0.75 mM, respectively (p < 0.0001), while naringin acetate induced a smaller increase of 0.26 mM. Donor-specific reflected differences in microbial communities, yet SCFA enhancement was observed across samples. Additionally, naringin treatments stimulated the growth of beneficial polyphenol-metabolizing bacteria, including Bacteroides, Streptococcus, and Eubacterium siraeum. The strong effect of naringin propionate suggests a sustained SCFA release mediated by microbial enzymes. These preliminary results highlight the potential of SCFA-acylated flavonoids as functional dietary components to increase SCFA bioavailability and support gut health, particularly from citrus-derived co-products. Full article
(This article belongs to the Special Issue Postbiotics—Bioactive Microbial Compounds as Health-Promoting Agents)
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14 pages, 1027 KiB  
Review
Seronegative Sicca Syndrome: Diagnostic Considerations and Management Strategies
by Yordanka M. Basheva-Kraeva, Krasimir I. Kraev, Petar A. Uchikov, Maria I. Kraeva, Bozhidar K. Hristov, Nina St. Stoyanova, Vesela T. Mitkova-Hristova, Borislav Ivanov, Stanislav S. Karamitev, Nina Koleva, Aleksandar Marinkov and Veselin A. Vassilev
Life 2025, 15(6), 966; https://doi.org/10.3390/life15060966 - 17 Jun 2025
Viewed by 494
Abstract
Seronegative sicca syndrome encompasses patients who present with xerostomia and/or keratoconjunctivitis sicca but lack anti-SSA/SSB antibodies and do not fulfill current classification criteria for primary Sjögren’s syndrome (pSS). Despite symptom overlap with pSS, these individuals remain diagnostically and therapeutically unclassified. This review studies [...] Read more.
Seronegative sicca syndrome encompasses patients who present with xerostomia and/or keratoconjunctivitis sicca but lack anti-SSA/SSB antibodies and do not fulfill current classification criteria for primary Sjögren’s syndrome (pSS). Despite symptom overlap with pSS, these individuals remain diagnostically and therapeutically unclassified. This review studies the clinical, immunological, and pathological spectrum of seronegative sicca, highlighting its heterogeneity and the limitations of antibody-centric diagnostic frameworks. Histopathologic findings in some seronegative patients—including focal lymphocytic sialadenitis—mirror those seen in pSS, suggesting underlying immune-mediated glandular damage. In others, nonspecific or normal biopsy findings suggest non-immune mechanisms. New evidence of immune activity, such as elevated cytokines (BAFF, IFN-α), and novel autoantibodies (SP-1, CA-VI), further supports the concept of subclinical autoimmunity in a subset of these patients. Clinically, they often face significant burden, including dryness, fatigue, and pain, yet remain excluded from most research cohorts, therapeutic trials, and clinical guidelines. Their management is often individualized, relying on symptomatic therapies rather than immunomodulatory agents. The lack of validated diagnostic criteria and prognostic markers compounds the uncertainty surrounding disease evolution, as some patients may later seroconvert or develop systemic features. To address these gaps, a paradigm shift is needed—one that embraces the spectrum of sicca syndromes, incorporates advanced immunophenotyping, and allows inclusion of seronegative patients in research and care algorithms. Full article
(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)
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20 pages, 1730 KiB  
Article
The Effects of Abdominal Draw-In Maneuvers Combined with Blood Flow Restriction on the Transverse Abdominis in University Students with Sedentary Lifestyles
by Yueh-Ling Hsieh, Tzu-Yu Weng, Nian-Pu Yang, Yu-Liang Lai and Andy Chien
Life 2025, 15(6), 965; https://doi.org/10.3390/life15060965 - 17 Jun 2025
Viewed by 501
Abstract
The abdominal drawing-in maneuver (ADIM) is one of the most valuable exercises for explicitly targeting and strengthening the transversus abdominis (TrA), a key muscle in the deep core. However, using the ADIM for the selective training of the transverse abdominis can be challenging [...] Read more.
The abdominal drawing-in maneuver (ADIM) is one of the most valuable exercises for explicitly targeting and strengthening the transversus abdominis (TrA), a key muscle in the deep core. However, using the ADIM for the selective training of the transverse abdominis can be challenging for certain individuals. This study investigated the effects of combining ADIM with blood flow restriction (BFR) training on TrA strengthening in sedentary university students. Forty university students with sedentary lifestyles (mean age: 23.28 ± 2.468 years; range 20–25 years) were randomly assigned to an ADIM+BFR group and a control group (ADIM only). Both groups underwent 25 min ADIM training sessions twice weekly for four weeks. Ultrasound measurements assessed TrA thickness, contraction ratio, and preferential activation. Core stability, strength, and endurance were evaluated using the double leg lowering, abdominal strength, and abdominal static endurance tests. The ADIM+BFR group showed significant improvements in TrA thickness, contraction ratio, and preferential activation compared to the control group following the four-week training intervention (p < 0.05). The ADIM+BFR group demonstrated improved core stability and enhanced abdominal strength and endurance compared to the control group (p < 0.05). The results support the effectiveness of ADIM+BFR training in enhancing TrA contraction and activation in sedentary university students. This approach also improves core stability, strength, and endurance. BFR provides a novel and readily applicable method for promoting TrA activation during ADIM training. Full article
(This article belongs to the Special Issue Innovative Perspectives in Physical Therapy and Health)
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16 pages, 778 KiB  
Review
The Junction of Allergic Inflammation and Atherosclerosis: Pathways and Clinical Implications—A Review
by Mihaela Valcovici, Mihai Sorin Iacob, Abhinav Sharma, Ana Maria Pah, Lucretia Marin-Bancila, Marcel Mihai Vaduva Berceanu, Milan Daniel Velimirovici, Anca-Raluca Dinu, Simona Ruxanda Drăgan and Nilima Rajpal Kundnani
Life 2025, 15(6), 964; https://doi.org/10.3390/life15060964 - 16 Jun 2025
Viewed by 688
Abstract
Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the [...] Read more.
Background: Cardiovascular disorders, especially atherosclerosis, have been associated with allergic inflammation. In addition to traditional inflammatory responses, there is evidence that the development and instability of coronary artery plaque may be influenced by effector cells of allergic inflammation. This review examines the phases of allergic pathology, the immunological mechanisms of atherosclerosis, and the clinical link between allergic diseases (asthma, atopic dermatitis, allergic rhinitis, and food allergy) and cardiovascular disease (CVD), along with future therapeutic perspectives. Material and Method: A literature search was conducted in PubMed, Google scholar; ScienceDirect, Scopus, and studies published between 2014–2024 were taken into consideration. Keywords included allergic inflammation, eosinophils, mast cells, reactive oxygen species, atherosclerosis, Th2 cells, and cytokines. Epidemiological studies and review articles were included. Results: Emerging evidence suggests that allergic inflammation contributes to atherosclerosis through interconnected mechanisms such as eosinophil activation, reactive oxygen species production, mast cell degranulation, and endothelial dysfunction. Th2-driven immune responses, which are mediated by cytokines such as IL-4, IL-5, and IL-13, as well as eosinophil activity and mast cell degranulation, play a crucial role in vascular inflammation and plaque progression. Additionally, changes in lipid metabolism contribute to this process. Epidemiological studies support this connection, indicating that patients with chronic allergic conditions such as asthma, allergic rhinitis, food allergy, and atopic dermatitis experience increased cardiovascular morbidity. However, most current data are observational, and our understanding of the underlying mechanisms in humans remains limited, often relying on insights gained from preclinical models. Conclusions: A potential mechanism for cardiovascular risk is suggested by the interaction between atherosclerosis and allergic inflammation. Promising alternatives for treating allergic inflammation and cardiovascular issues include novel treatments like cytokine inhibitors, mast cell stabilizers, and biologics that target certain pathways. Further research is necessary to see whether concentrating on allergy pathways could lead to innovative treatments for cardiovascular disorders or vice versa. Full article
(This article belongs to the Special Issue Interdisciplinarity in Cardiovascular Diseases: From Pathophysiology to Diagnosis and Treatment: 3rd Edition)
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16 pages, 715 KiB  
Article
HISLIS: Histology, Sarcopenia, and Lung Inflammation Score—A New Perspective for Lung Cancer Patients?
by Claudia Raluca Mariean, Oana Mirela Tiucă, Cristina Flavia Al-Akel and Ovidiu Simion Cotoi
Life 2025, 15(6), 963; https://doi.org/10.3390/life15060963 - 16 Jun 2025
Viewed by 420
Abstract
Background: Since lung cancer remains a health problem worldwide and is the leading cause of cancer death, finding new tools that can help in the early identification of high-risk patients remains a key target. Methods: A retrospective descriptive study of 70 patients diagnosed [...] Read more.
Background: Since lung cancer remains a health problem worldwide and is the leading cause of cancer death, finding new tools that can help in the early identification of high-risk patients remains a key target. Methods: A retrospective descriptive study of 70 patients diagnosed with lung cancer at the Clinical County Hospital Mureș was conducted. Information regarding the histopathological type of the tumor, the TNM stage at diagnosis, and the CBC-derived inflammatory status was obtained for all the included patients. Skeletal muscle area was measured at the level of the third lumbar vertebra (L3SMA), based on the patients’ native CT scans, to identify sarcopenia. These four primary characteristics (the histopathological type of the tumor, the TNM stage, the systemic inflammatory status, and the sarcopenic changes) were integrated into a new severity score: the histology, sarcopenia, and lung inflammation score (HISLIS). Subsequently, based on the HISLIS score, the patients were divided into three severity grades (high, medium, and low). Results: Our results showed that patients diagnosed in late advanced TNM stages (III or IV) had the highest severity grade. The severity grade strongly correlated with the systemic inflammatory biomarkers, with the highest severity grades being associated with an increased inflammatory status. In addition, sarcopenic patients were diagnosed in more advanced TNM stages, exhibited higher HISLIS levels, and had a higher degree of systemic inflammation than non-sarcopenic patients. Sarcopenic patients also showed an impaired hematological profile, with hemoglobin (Hb) and hematocrit (Ht) levels being significantly decreased in sarcopenic patients. Conclusions: Future prospective studies are needed to validate the HISLIS and integrate it into the routine clinical and paraclinical assessment of lung cancer patients, as it could represent a triage tool for the early identification of patients at higher risk of unfavorable outcomes. Combining critical information regarding the tumors’ characteristics, such as TNM stage and histological characteristics, together with biological and imaging-derived information like the CBC-derived inflammatory status and the associated degree of sarcopenia, could lead to a complex approach and a personalized therapeutic regimen for this highly deadly condition. Full article
(This article belongs to the Special Issue Enhancements in Screening Pathways for Early Detection of Lung Cancer)
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17 pages, 4596 KiB  
Article
OsMYBR1, a 1R-MYB Family Transcription Factor Regulates Starch Biosynthesis in Rice Endosperm
by Kunyong Huang, Long Chen, Guiai Jiao, Zheyan Ruan, Xinwei Li, Shaoqing Tang, Peisong Hu and Xiangjin Wei
Life 2025, 15(6), 962; https://doi.org/10.3390/life15060962 - 16 Jun 2025
Viewed by 463
Abstract
Starch is the primary component of the endosperm and plays a crucial role in rice quality. Although the enzymes involved in starch synthesis have been extensively studied, the transcription factors that regulate these enzymes remain largely unknown. Here, we identified a MYB family [...] Read more.
Starch is the primary component of the endosperm and plays a crucial role in rice quality. Although the enzymes involved in starch synthesis have been extensively studied, the transcription factors that regulate these enzymes remain largely unknown. Here, we identified a MYB family transcription factor, OsMYBR1, that regulates starch biosynthesis in rice. OsMYBR1 is highly expressed during endosperm development. Mutations of OsMYBR1 result in reduced grain thickness and a decrease in 1000-grain weight. The endosperm of osmybr1 mutants exhibit rounded and loosely packed starch granules, decreased amylose content, altered fine structure of amylopectin, and modified physicochemical properties. The analysis of RT-qPCR showed that the expression of several starch-synthesis enzyme-coding genes (SSEGs), including OsGBSSⅠ, OsAGPL1, OsAGPL2, OsBEⅡb, OsISA1, PHOL, and OsSSⅢa, is altered in osmybr1 mutants. Further experiments indicated that OsMYBR1 directly binds to the promoters of OsGBSSⅠ, OsAGPL1, OsAGPL2, OsISA1, OsBEⅡb, and PHOL, resulting in an increase in the expression of OsGBSSⅠ but a decrease in the expression of OsAGPL2, OsISA1, and OsSSⅢa. In contrast, OsMYBR1-overexpressing endosperm appears normal, with starch granule morphology, increased amylopectin content, and improved alkali spreading value, indicating enhanced rice eating and cooking quality (ECQ). These findings suggest that the overexpression of OsMYBR1 could be a promising strategy for improving rice ECQ. Full article
(This article belongs to the Special Issue Recent Advances in Crop Genetics and Breeding)
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14 pages, 616 KiB  
Article
Associations Between Shift Work, Sociodemographic and Lifestyle Characteristics, Body Measurements, and MASLD
by Javier Tosoratto, Pedro Juan Tárraga López, Ángel Arturo López-González, Carla Busquets-Cortes, Joan Obrador de Hevia and José Ignacio Ramirez-Manent
Life 2025, 15(6), 961; https://doi.org/10.3390/life15060961 - 16 Jun 2025
Viewed by 444
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide and is closely linked to the components of metabolic syndrome. Shift work, through its disruption of circadian rhythms and the promotion of adverse behavioral patterns, has been proposed [...] Read more.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide and is closely linked to the components of metabolic syndrome. Shift work, through its disruption of circadian rhythms and the promotion of adverse behavioral patterns, has been proposed as a potential contributor to metabolic dysfunction and liver disease, yet evidence on its association with MASLD remains limited in large, heterogeneous occupational populations. Objectives: To investigate the association between shift work and MASLD risk using multiple validated non-invasive indices in a large sample of Spanish workers, and to explore the influence of sociodemographic characteristics, lifestyle behaviors, and sex on these associations. Methods: This cross-sectional study analyzed data from 53,053 employed adults across diverse sectors in Spain, including 31,753 men and 21,300 women. The participants underwent standardized occupational health assessments between 2019 and 2020. The MASLD risk was evaluated using seven indices: fatty liver index (FLI), hepatic steatosis index (HSI), ZJU index, fatty liver disease (FLD) index, Framingham steatosis index (FSI), lipid accumulation product (LAP), and BARD score. Sociodemographic, anthropometric, clinical, biochemical, and lifestyle data were collected. Multinomial logistic regression models were used to assess independent associations between shift work and high-risk MASLD scores. Results: Shift workers exhibited significantly higher mean values and prevalence of elevated MASLD scores across all indices compared to non-shift workers, in both sexes. In men, the prevalence of high BARD scores increased from 43.5% (non-shift) to 71.5% (shift), while in women it rose from 49.9% to 85.7%. Multivariate analysis confirmed that shift work was independently associated with an increased MASLD risk, particularly for HSI (OR: 7.83; 95% CI: 7.40–8.26) and ZJU (OR: 5.91; 95% CI: 5.60–6.22). Male sex, older age, smoking, and blue-collar status were also consistently associated with elevated risk scores. Conclusions: Shift work is significantly associated with an increased MASLD risk, independent of sociodemographic and lifestyle factors. Women and blue-collar workers may be especially vulnerable to the hepatic consequences of circadian disruption. These findings support the inclusion of liver health screening in occupational health programs and highlight the need for targeted interventions to reduce the MASLD risk among shift-working populations. Cross-sectional design limits causality; longitudinal studies are needed to confirm temporal relationships. Full article
(This article belongs to the Section Physiology and Pathology)
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15 pages, 773 KiB  
Article
The Role of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Predicting Atrial Fibrillation and Its Comorbidities
by Evelina Maria Gosav, Daniela Maria Tanase, Anca Ouatu, Oana Nicoleta Buliga-Finis, Diana Popescu, Cristina Gena Dascalu, Nicoleta Dima, Minerva Codruta Badescu and Ciprian Rezus
Life 2025, 15(6), 960; https://doi.org/10.3390/life15060960 - 16 Jun 2025
Viewed by 484
Abstract
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias encountered globally, characterized by a pro-inflammatory pattern. This analysis evaluated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with AF alongside chronic kidney disease (CKD) and/or type 2 diabetes mellitus [...] Read more.
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias encountered globally, characterized by a pro-inflammatory pattern. This analysis evaluated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with AF alongside chronic kidney disease (CKD) and/or type 2 diabetes mellitus (T2DM). This retrospective cohort study included 6077 patients admitted to the Third Medical Clinic of Saint Spiridon Hospital in Iasi from 2018 to 2023, all diagnosed with AF, CKD, and T2DM. After applying the exclusion criteria, 1066 AF patients remained eligible. For a multivariate comparative analysis, the patients were divided into groups: I. control group (non-AF patients); II. AF patients; III. T2DM group; IV. CKD-only group; V. AF+CKD group; VI. AF+T2DM group; and VII. AF+T2DM+CKD group. The Mann–Whitney/Kruskal–Wallis test demonstrated a statistically significant difference in NLR and PLR values between the AF group and the non-AF group (H = 70.627, p < 0.001). The receiver operating characteristic (ROC) analysis identified statistical significance and predictive power for NLR (AUC = 0.722; sensitivity = 63.6%; specificity = 76.9%) and neutrophil count in diagnosing AF, T2DM, and CKD. In conclusion, this study illustrated the utility of NLR and PLR as readily available and predictive biomarkers of inflammation in patients with AF, with or without comorbidities. Full article
(This article belongs to the Special Issue Interdisciplinary Approach to Diabetes Mellitus: From Pathophysiology to Diagnosis and Therapeutic Challenges)
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15 pages, 1054 KiB  
Article
Alterations in the Morphology of the Testis and Epididymis Caused by the Consumption of Hyperlipidic Diets in Wistar Rats
by Rosario Tarragó Castellanos, Maria Mendoza Delgado, Lorena Ruiz Valderrama, Isabel Arrieta Cruz, Edith Cortés Barberena, Adriana Morales Otal, Ernesto Rodríguez Tobón, Ahiezer Rodríguez Tobón, Javier Olvera Ramírez and Edith Arenas Ríos
Life 2025, 15(6), 959; https://doi.org/10.3390/life15060959 - 14 Jun 2025
Viewed by 496
Abstract
Obesity is considered a metabolic disease, in which leptin is used as an indicator of energy in the body. This hormone, in turn, is related to the neuroendocrine regulation of the reproductive axis. However, leptin excess secretion due to obesity can have a [...] Read more.
Obesity is considered a metabolic disease, in which leptin is used as an indicator of energy in the body. This hormone, in turn, is related to the neuroendocrine regulation of the reproductive axis. However, leptin excess secretion due to obesity can have a negative effect on reproduction. Overweight and obesity were induced through high-calorie diets. Lee and gonadosomatic indices were determined to characterize the model and degree of reproductive development in the testis and epididymis. Sperm quality was analyzed using spermatobioscopy. Morphometry was analyzed through histological analysis. The changes described affect testicular function in hormone and sperm production. Exposure of 3-month-old male rats to diets with different fat contents (10% and 60%) induced both overweight and obesity. The animals showed morphological alterations, both testicular and epididymal, the latter being more sensitive to dietary changes by modifying the epididymal index, morphometric parameters (in both organs), and a decrease in cilia length. These changes induced a reduction in sperm viability, as well as an increase in malformed spermatozoa. In conclusion, both overweight and obesity have effects on male reproduction by modifying the morphology and physiology of reproductive organs. Full article
(This article belongs to the Section Reproductive and Developmental Biology)
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10 pages, 2054 KiB  
Article
Influence of Insert Brand and Culture Method on Ciliary Activity and Epithelial Cell Types in Human Nasal Air–Liquid Interface Cell Cultures
by Patricia Celkova, Emilie Seydoux, Susan De Groof and Loretta Müller
Life 2025, 15(6), 958; https://doi.org/10.3390/life15060958 - 14 Jun 2025
Viewed by 480
Abstract
Cultures of primary human nasal epithelial cells (hNECs) differentiated at the air–liquid interface (ALI) represent a sophisticated and widely used model of the human upper respiratory epithelium. Despite the availability of various cell culture insert types and the well-established understanding that different culture [...] Read more.
Cultures of primary human nasal epithelial cells (hNECs) differentiated at the air–liquid interface (ALI) represent a sophisticated and widely used model of the human upper respiratory epithelium. Despite the availability of various cell culture insert types and the well-established understanding that different culture media influence the cell culture characteristics, the possible impact of the insert brand remains rather underexplored. We cultured hNECs from nineteen healthy adult donors on three distinct brands of commercially available inserts—Corning® Transwell®, CELLTREAT®, and ThinCert®—and compared the ciliary activity and cellular composition of the cultures using high-speed video microscopy and flow cytometry, respectively. Additionally, we employed an alternative method of hNEC culture setup—the inverted condition—wherein the hNECs were seeded on the basal side of the insert with the idea to avoid mucus accumulation. Our results show that ciliary activity and cell type composition did not differ between insert types for both culture conditions. However, we found a higher ciliary beat frequency and a lower active (ciliated) area in the inverted setup compared to the conventional setup across all three insert brands. These findings indicate that all three mentioned insert types yield comparable cell cultures. Full article
(This article belongs to the Special Issue Updates on Respiratory Pathologies)
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19 pages, 3569 KiB  
Article
Bladder p75NTR-Mediated Anti-Inflammatory Response via the TLR4/TRAF6/NF-κB Axis
by Claudia Covarrubias, Abubakr H. Mossa, Laura R. Yan, Benjamin Desormeau, Philippe G. Cammisotto, H. Uri Saragovi and Lysanne Campeau
Life 2025, 15(6), 957; https://doi.org/10.3390/life15060957 - 14 Jun 2025
Viewed by 523
Abstract
Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75NTR. The aim of the presented study was to assess whether [...] Read more.
Recurrent bacterial cystitis in women can lead to interstitial cystitis or bladder pain syndrome (IC/BPS). Activation of Toll-like receptor 4 (TLR4) by LPS can upregulate signaling of the pro-inflammatory receptor p75NTR. The aim of the presented study was to assess whether p75NTR antagonist THX-B can modulate LPS-mediated inflammation in bladder cells. In vitro expression and LPS-activation of p75NTR were confirmed in urothelial (URO) and smooth muscle (SMC) cells. In UROs, p75NTR antagonism abolished the LPS-elicited rise in membrane-bound and soluble TNF-α. However, it could not prevent LPS-induced rise in phosphorylated ERK nor decrease in phosphorylated p38MAPK, nor the increase in iNOS and nitric oxide (NO) content. On the other hand, in SMCs, LPS increased phosphorylation of JNK, nuclear translocation of NF-κB, and association of TRAF6 to p75NTR, outcomes prevented by p75NTR antagonism. In UROs, LPS decreased the expression of tight junction proteins, ZO-1 and occludin, with the latter rescued by p75NTR antagonism. Intraurethral instillation of LPS increased inflammation in the lamina propria, activation of JNK, and contractile activity of bladder tissue. Alternatively, intraperitoneal THX-B injections prevented LPS-induced inflammation but not enhanced muscle contraction. Our results suggest that inhibition of p75NTR could help in reducing bladder symptoms during cystitis. Full article
(This article belongs to the Section Microbiology)
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Article
The Influence of Drinking Water Intake on Pollutant Levels in the Human Body: Evidence from NHANES Data
by Chenxu Dai, Ziyi Qian, Linjie Yang, Siyan Chen, Hongfei Hu and Xia Huo
Life 2025, 15(6), 956; https://doi.org/10.3390/life15060956 - 13 Jun 2025
Viewed by 398
Abstract
Most studies have focused on the levels of pollutants in drinking water and the health risks they pose. However, no studies have reported the effects of drinking water intake on pollutant levels in the human body. Therefore, this study collected data from National [...] Read more.
Most studies have focused on the levels of pollutants in drinking water and the health risks they pose. However, no studies have reported the effects of drinking water intake on pollutant levels in the human body. Therefore, this study collected data from National Health and Nutrition Examination Survey database to provide statistical evidence for the relationship between water intake and human pollutant levels. We analyzed 95 pollutants in human urine, blood, and serum. The study found that 82% (65/79) of urine pollutants unadjusted for creatinine showed a stable negative correlation with water intake, primarily due to the urine dilution effect caused by increased water consumption. Water intake was negatively correlated with cadmium, m-/p-xylene, and toluene in blood, but positively correlated with blood total mercury and methyl mercury. In summary, the habit of drinking more water may be beneficial to reduce levels of most pollutants in human urine (unadjusted for creatinine) and a small part in blood. Only a few pollutants, including total mercury and methyl mercury in blood, as well as benzophenone-3 in urine (both creatinine-adjusted and unadjusted), are positively related to water intake. The underlying mechanisms by which water intake influences pollutant levels in the human body require further investigation. Full article
(This article belongs to the Section Physiology and Pathology)
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