Life

13 pages, 4849 KB

Open AccessCase Report

Acute Myocardial Infarction Complicated by Papillary Muscle Rupture and Cardiogenic Shock Requiring ECMO Support in a Patient with Bipolar Disorder and Chronic Cannabis Use

by Oana Elena Branea, Mihaly Veres, Oana Frandeș, Matild Keresztes, Mihai Claudiu Pui, Ciprian Fișcă, Radu Bălău and Leonard Azamfirei

Life 2026, 16(6), 879; https://doi.org/10.3390/life16060879 (registering DOI) - 24 May 2026

Abstract

Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with posterior papillary muscle rupture leading to severe mitral regurgitation, [...] Read more.

Cardiogenic shock secondary to acute myocardial infarction complicated by mechanical failure remains associated with high mortality despite advances in cardiac surgery and mechanical circulatory support. We report the case of a 42-year-old patient with posterior papillary muscle rupture leading to severe mitral regurgitation, managed with emergency surgical intervention and extracorporeal membrane oxygenation. The patient, with a history of Type I Bipolar Disorder under long-term lithium therapy and chronic Cannabis use, presented in critical condition with cardiogenic shock (Killip IV), acute pulmonary edema, and ST-segment elevation myocardial infarction in the infero-posterior territory. Coronary angiography revealed right coronary artery occlusion and involvement of an obtuse marginal branch. Emergency mitral valve replacement with a mechanical prosthesis and aortocoronary bypass were performed. Due to failure to wean from cardiopulmonary bypass, central veno-arterial ECMO was initiated. The postoperative course was complicated by hemodynamic instability and recurrent pericardial collections requiring repeated surgical interventions and conversion to peripheral ECMO. Multiorgan dysfunction developed, including hepato-renal failure requiring hemofiltration, neurological injury, respiratory impairment, and neuropsychiatric complications. Despite these challenges, progressive recovery was achieved under intensive multidisciplinary management. This case emphasizes the importance of early surgical correction and tailored ECMO support in managing post-infarction mechanical complications. Full article

(This article belongs to the Special Issue Critical Issues in Intensive Care Medicine—2nd Edition)

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20 pages, 2473 KB

Open AccessArticle

Pilot Study on the Effects of First-Line Antituberculosis Drugs and Their Combinations on Selected Reproductive Endpoints in Female Rats

by Elif Esra Uyar, Bulent Yavuzer, Mansura Babayeva, Nurinisa Yucel, Murat Gunay and Halis Suleyman

Life 2026, 16(6), 878; https://doi.org/10.3390/life16060878 (registering DOI) - 24 May 2026

Abstract

Background: The reproductive toxicity of first-line antituberculosis drugs remains poorly understood, particularly when used in combination. Rifampicin, isoniazid, pyrazinamide, and ethambutol are essential in tuberculosis therapy, but their potential influence on female fertility is uncertain. This pilot study evaluated their effects, given alone [...] Read more.

Background: The reproductive toxicity of first-line antituberculosis drugs remains poorly understood, particularly when used in combination. Rifampicin, isoniazid, pyrazinamide, and ethambutol are essential in tuberculosis therapy, but their potential influence on female fertility is uncertain. This pilot study evaluated their effects, given alone or in dual, triple, and quadruple combinations, on oxidative stress, endocrine markers, and reproductive outcomes in healthy female rats. Materials and Methods: Ninety-six albino Wistar-type female rats were divided into sixteen groups of six animals each and treated with single, dual, triple, or quadruple regimens of first-line antituberculosis drugs for 28 days. After treatment, two sexually mature males were introduced per group, and therapy continued for seven additional days. Serum malondialdehyde (MDA), total glutathione (tGSH), prolactin, and anti-Mullerian hormone (AMH) levels were measured, and fertility outcomes were evaluated. Results: In single-drug groups, MDA increased and tGSH decreased, but detectable infertility was not recorded. Prolactin remained stable except in the pyrazinamide group, where it declined. Dual-drug regimens increased oxidative imbalance; fertility failure occurred only in pyrazinamide-lacking groups and was accompanied by higher prolactin and lower AMH. Triple and quadruple combinations produced prominent oxidative imbalance. In triple-drug regimens, infertility was lower in pyrazinamide-containing groups than in the pyrazinamide-free group, but this pattern was not maintained in the quadruple regimen. Fertility impairment was not consistently aligned with the degree of oxidative stress and may involve prolactin and AMH alterations. Conclusions: These findings suggest that reproductive impairment under these experimental conditions may involve endocrine alterations and cannot be explained solely by serum oxidative imbalance. Pyrazinamide-associated fertility preservation appeared context-dependent and requires further confirmation in larger mechanistic studies with broader reproductive and endocrine assessment. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: From Bench to Bedside—3rd Edition)

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19 pages, 907 KB

Open AccessArticle

Epidemiological Analysis of Rabies Outbreaks in the European Union and Türkiye (2013–2023)

by Ralitsa Rankova, Dilek Muz, Koycho Koev and Gergana Balieva

Life 2026, 16(6), 877; https://doi.org/10.3390/life16060877 (registering DOI) - 24 May 2026

Abstract

Rabies is a fatal zoonotic viral disease that continues to pose a significant threat to both animal and public health worldwide. Despite considerable progress in its control across Europe, sporadic outbreaks still occur, particularly in regions where wildlife reservoirs and stray animal populations [...] Read more.

Rabies is a fatal zoonotic viral disease that continues to pose a significant threat to both animal and public health worldwide. Despite considerable progress in its control across Europe, sporadic outbreaks still occur, particularly in regions where wildlife reservoirs and stray animal populations sustain virus circulation. This study provides one of the first comparative longitudinal analyses integrating European countries and Turkiye rabies surveillance data over a decade (2013–2023). Information on reported outbreaks was obtained from the Animal Disease Information System (ADIS) and the World Animal Health Information System (WAHIS) database. The analysis focused on temporal trends, regional differences, and the distribution of affected animal species. During the study period, a total of 4865 outbreaks were reported in 16 countries. The number of detected outbreaks declined considerably over time, decreasing from 1022 cases in 2013 to 325 cases in 2023, representing an overall reduction of approximately 68%. The temporal trend was not uniform, with periods of decline followed by temporary increases. The highest number of outbreaks was registered in Türkiye, followed by Romania and Poland, indicating pronounced regional disparities. Domestic dogs represented the most frequently affected species, while cases were also recorded in wildlife and domestic cats, confirming the epidemiological importance of both domestic and wild reservoirs. The observed reduction in the number of outbreaks reflects the impact of vaccination programs and coordinated control measures, but may also be influenced by differences in surveillance systems and reporting practices. Nevertheless, the persistence of rabies in several regions indicates that the disease remains an epidemiological concern. Sustained vaccination of domestic animals, continued wildlife immunization, and strengthened surveillance and cross-border cooperation are essential for long-term control and prevention. Full article

(This article belongs to the Special Issue Molecular Epidemiology of Animal Viral Diseases)

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18 pages, 4899 KB

Open AccessArticle

Multimodal Functional Assessment of Asymmetries in Youth Soccer Players: Study Protocol

by Ada-Maria Codreanu, Dan-Andrei Korodi, Nicoleta-Alexandra Lupu, Anca-Valentina Onciulenco, Andreea-Ancuta Vataman, Adina-Octavia Duse, Marius-Zoltan Rezumes, Elena-Constanta Amaricai, Liliana Catan, Alexandru Caraba, Roxana-Ramona Onofrei and Claudia Borza

Life 2026, 16(6), 876; https://doi.org/10.3390/life16060876 (registering DOI) - 24 May 2026

Abstract

Background: Youth soccer players are exposed to repeated unilateral loading during a period of rapid growth and neuromuscular maturation. These demands may contribute to postural deviations and inter-limb functional asymmetries that can influence movement control and mechanical efficiency. This study protocol aims to [...] Read more.

Background: Youth soccer players are exposed to repeated unilateral loading during a period of rapid growth and neuromuscular maturation. These demands may contribute to postural deviations and inter-limb functional asymmetries that can influence movement control and mechanical efficiency. This study protocol aims to establish a standardized multimodal framework for assessing postural alignment, postural control, lower limb mechanical output, ankle dorsiflexion strength, support-limb neuromuscular activation, and contextual training and recovery variables in licensed youth soccer players aged 13 to 17 years. Methods: This prospective observational study will include 75 male youth soccer players recruited from S.C. Fotbal Club Ripensia Timișoara S.A. The primary outcome is the inter-limb asymmetry index derived from unilateral countermovement jump performance. Secondary outcomes include postural alignment, balance, bilateral jump performance, ankle dorsiflexion strength, and support limb electromyographic activity during the instep kick. Participants will complete a clinical evaluation questionnaire, including demographic, training, and recovery variables. Assessments will be conducted using the GaitON system, Kinvent K-Delta force platforms, K-Myo surface electromyography, and K-Pull dynamometry, before and after a regular training session. Biological maturation will be estimated using the Mirwald maturity offset method. Expected Results: The protocol will allow characterization of inter-limb asymmetries across postural, balance, jump, and electromyographic parameters. Conclusions: This protocol aims to provide a practical and standardized model for functional screening in youth soccer players. Full article

(This article belongs to the Special Issue Advanced Research in Exercise Medicine)

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29 pages, 1064 KB

Open AccessArticle

Cerebral Veins and Dural Sinuses Thrombosis: Data from a Monocentric Cohort Study of 55 Romanian Patients

by Dragos Catalin Jianu, Silviana Nina Jianu, Razvan Bertici, Nicoleta Iacob, Sergiu Florin Arnautu, Georgiana Munteanu, Traian Flavius Dan, Raphael Sadik, Tudor Nicolae Jianu, Any Axelerad, Cristina Tudoran, Andrei Gheorghe Marius Motoc, Stefan Strilciuc, Dafin Fior Muresanu and Ligia Petrica

Life 2026, 16(6), 875; https://doi.org/10.3390/life16060875 (registering DOI) - 23 May 2026

Abstract

Cerebral venous sinus thrombosis (CVST) is a rare form of stroke with heterogeneous clinical presentation and etiological profile. This study aimed to evaluate the demographic, clinical, imaging, etiological, treatment, and outcome characteristics of CVST in a Romanian population. We conducted a retrospective monocentric [...] Read more.

Cerebral venous sinus thrombosis (CVST) is a rare form of stroke with heterogeneous clinical presentation and etiological profile. This study aimed to evaluate the demographic, clinical, imaging, etiological, treatment, and outcome characteristics of CVST in a Romanian population. We conducted a retrospective monocentric cohort study including 55 patients diagnosed over a six-year period in a tertiary neurological center. CVST accounted for 1.2% of all stroke cases, with an incidence of 13.75 per million per year. Gender distribution was relatively balanced, differing from international cohorts, and traditional female-specific risk factors were less prominent. Thrombophilia (68.6%) and infections (38.2%) were the most frequent etiologies. Younger patients were more frequently associated with thrombophilia, while a higher inflammatory response was observed in older individuals; additionally, female patients showed a higher prevalence of the MTHFR C677T mutation. Transverse and sigmoid sinuses were the most affected, while cavernous sinus involvement was more frequent than typically reported and associated with infections. At discharge, long-term anticoagulation was recommended in 67.3% of patients, tailored to underlying etiology and risk profile. Outcomes were favorable, with 70–80% achieving a modified Rankin Scale score ≤2 at discharge and over 90% at 90-day follow-up, despite inconsistent correlation with imaging findings. These results highlight the heterogeneous nature of CVST and the need for comprehensive, individualized evaluation and management. Full article

(This article belongs to the Special Issue An Integrated Approach on Diagnosis and Treatment of Cerebral Veins and Intracranial Dural Sinuses Thrombosis (CVT))

16 pages, 3446 KB

Open AccessArticle

Resolving the Haplotype Complexity of Colorectal Cancer Genomes with Droplet Barcode Sequencing

by Humam Siga, Pontus Höjer, Parham Pourbozorgi, Hooman Aghelpasand, Max Käller, Johan Hartman, Cecilia Williams and Afshin Ahmadian

Life 2026, 16(6), 874; https://doi.org/10.3390/life16060874 (registering DOI) - 22 May 2026

Abstract

Precision medicine is increasingly applied in the cancer clinic, adapting treatment to genomic alterations of the tumor. However, whether alterations disrupt the function of a protein can depend on if both alleles of a gene are altered. While massively parallel sequencing technologies can [...] Read more.

Precision medicine is increasingly applied in the cancer clinic, adapting treatment to genomic alterations of the tumor. However, whether alterations disrupt the function of a protein can depend on if both alleles of a gene are altered. While massively parallel sequencing technologies can identify sequence aberrations, they are limited in resolving the corresponding haplotype information. In this proof-of-concept case study, we applied the linked-read droplet barcode sequencing (DBS) technology to resolve the haplotype complexity of colorectal cancer genomes on paired tumor and normal samples. Several cancer-related genes carried multiple mutations in either one or both haplotypes. Additionally, a number of haplotype-resolved large structural variants and copy number alterations were detected and phased with short somatic variants. Nearly all characterized oncogenic pathways harbored some of the identified short somatic variants. The study demonstrates that linked-read DBS technology can characterize complex genetic variations in a haplotype context and may provide essential information for personalized approaches. Full article

(This article belongs to the Special Issue Cancer Genomics and Transcriptomics: Uncovering New Frontiers in Tumor Biology)

38 pages, 1874 KB

Open AccessReview

Therapeutic Applications of Natural Products in Biomedicine and Pharmacotherapy

by Ashok Kumar Sah, Sakshi Patel, Rahul Kumar, Prem Shankar Mishra, Rakhi Mishra, Abdulkhakov Ikhtiyor Umarovich, Rabab H. Elshaikh, Shagun Agarwal, Ashwani Bhardwaj, Ranjay Kumar Choudhary and Ayman Hussein Alfeel

Life 2026, 16(6), 873; https://doi.org/10.3390/life16060873 (registering DOI) - 22 May 2026

Abstract

Natural products are the fundamentals of drug discovery due to their exceptional structural diversity and biological activity’s evolutionary optimization. The review provides a critical and integrative analysis of natural products in pharmaceutical chemistry, highlighting their significance for current biomedicine and pharmacotherapy. The review [...] Read more.

Natural products are the fundamentals of drug discovery due to their exceptional structural diversity and biological activity’s evolutionary optimization. The review provides a critical and integrative analysis of natural products in pharmaceutical chemistry, highlighting their significance for current biomedicine and pharmacotherapy. The review is organized around a system that connects structure, function, and translation, focusing on structural analysis, scaffold design, and mechanistic understanding in major disease-relevant therapeutic areas. Investigations on representative compounds like paclitaxel, artemisinin, and curcumin are presented to explain the way molecular architecture regulates pharmacological activity, drug selectivity, and clinical performance. The review evaluates significant medicinal chemistry strategies, including semisynthetic modification, prodrug design, and scaffold optimization, and their crucial roles in enhancing potency, pharmacokinetics, and safety. We critically examine the latest advancements in drug delivery technologies, particularly those based on nanotechnology and carrier-free methods, regarding their translational potential and regulatory concern. Current challenges pertaining to pharmacokinetics and ADMET properties, as well as the standardization of analysis, are also examined, emphasizing their impact on reproducibility in research. Researchers investigate the role and limitations of emerging fields such as genome mining, synthetic biology, and network pharmacology in enhancing discovery pipelines. Thus, this review integrates chemical, pharmacological, and translational approaches and suggests an effective strategy to overcome challenges in the development of natural products as the next generation of precision medicine therapeutic agents. Full article

(This article belongs to the Special Issue Green Medicine: Unraveling the Medicinal Effects of Plant Extracts and Functional Foods)

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18 pages, 6954 KB

Open AccessArticle

Comparative Proteomic Analysis Reveals That TaCAD-A1 Enhances Resistance of Wheat to Powdery Mildew (Blumeria graminis f. sp. tritici)

by NiNa Sun, Wei Liu, WeiHua Xu, LinZhi Li, TangYu Yuan and Lu Chen

Life 2026, 16(6), 872; https://doi.org/10.3390/life16060872 (registering DOI) - 22 May 2026

Abstract

Powdery mildew in wheat, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a major threat to global wheat production, yet the molecular mechanisms underlying differential cultivar resistance remain largely unresolved. In this study, tandem mass tag (TMT)-based [...] Read more.

Powdery mildew in wheat, caused by the biotrophic fungus Blumeria graminis f. sp. tritici (Bgt), is a major threat to global wheat production, yet the molecular mechanisms underlying differential cultivar resistance remain largely unresolved. In this study, tandem mass tag (TMT)-based quantitative proteomics was employed to investigate protein dynamics in resistant (Yannong37) and susceptible (Yannong1766) wheat cultivars at 0 and 24 h following Bgt inoculation. A total of 276 proteins exhibited significant changes in abundance after infection, with enrichment in cell wall and plasmodesmata-associated proteins. Comparative analysis further identified 456 differentially expressed proteins between the two cultivars at 24 h post-inoculation. Protein–protein interaction network analysis indicated that proteins involved in secondary metabolism and immune responses form coordinated regulatory networks contributing to disease resistance. RT–qPCR validation supported the reliability of the proteomic data. Notably, TaCAD-A1 displayed higher transcript abundance in the resistant cultivar and was associated with reduced fungal biomass accumulation. Silencing of TaCAD-A1 resulted in decreased expression of multiple defense-related genes. Collectively, these findings suggest that TaCAD-A1 may positively contribute to wheat resistance against Bgt infection and may be associated with defense responses and monolignol biosynthesis-related processes. Full article

(This article belongs to the Special Issue Advanced Research in Plant–Pathogen Interactions)

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21 pages, 745 KB

Open AccessArticle

Factors Associated with Live Birth After Placenta-Derived Mesenchymal Stromal Cell Therapy in Women with Recurrent Intrauterine Adhesions and Thin Endometrium

by Tabeeva Giuzial, Silachev Denis, Asaturova Aleksandra, Shevtsova Yulya, Yurin Alexander, Popov Konstantin, Pronin Stanislav, Korshunov Alexey, Dzhabiev Alan, Smetnik Antonina, Marсhenko Larisa, Chernukha Galina and Sukhikh Gennady

Life 2026, 16(6), 871; https://doi.org/10.3390/life16060871 (registering DOI) - 22 May 2026

Abstract

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, [...] Read more.

Recurrent intrauterine adhesions (IUA) and refractory thin endometrium are associated with impaired endometrial regeneration, reduced implantation, and poor live birth outcomes. Regenerative therapy using mesenchymal stromal cells (MSCs) has shown promising results; however, factors associated with reproductive success remain unclear. In this prospective, single-centre, single-arm uncontrolled observational study, 35 women with recurrent IUA and thin endometrium (<7 mm) unresponsive to standard surgical and hormonal therapy received combined subendometrial and systemic administration of placenta-derived MSCs. The primary endpoint was live birth. Secondary endpoints included clinical pregnancy rate, time to pregnancy, endometrial thickness changes, uterine blood flow (resistance index, RI), and anti-Müllerian hormone (AMH) levels. Univariable logistic regression was performed to identify factors associated with live birth. Clinical pregnancy occurred in 13/35 patients (37.1%), and live birth was achieved in 11/35 (31.4%). Median time to pregnancy was 7 (5–8) months. Shorter duration of infertility or prior pregnancy loss (OR 1.55 per year; 95% CI 1.10–2.57), AFS stage I adhesions (OR 6.8; 95% CI 1.1–42; p = 0.04), lower baseline RI in uterine, arcuate and radial arteries, and higher baseline AMH (OR 2.59 per doubling; 95% CI 1.15–6.89) were significantly associated with live birth. Endometrial thickness increased after therapy but was not significantly associated with live birth. No severe adverse events were observed. Placenta-derived MSC therapy was followed by live birth in 31.4% of women with recurrent IUA and refractory thin endometrium. A shorter duration of reproductive disorders, less severe adhesions, lower baseline RI in uterine, arcuate and radial arteries, and higher AMH levels were associated with live birth after treatment and may help identify patients with a more favourable reproductive prognosis in future controlled studies. Full article

(This article belongs to the Special Issue Stem Cell Biology, Tissue Formation, Cell Plasticity and Regenerative Medicine)

14 pages, 588 KB

Open AccessArticle

The Mediating Effect of Physical Fitness on the Relationship Between Developmental Coordination Disorder and Physical Activity in School-Aged Children—An Observational Study

by Huynh-Truc Tran, Wen-Chao Ho, Li-Wei Chou and Yao-Chuen Li

Life 2026, 16(6), 870; https://doi.org/10.3390/life16060870 (registering DOI) - 22 May 2026

Abstract

Evidence remains limited on the interconnections between developmental coordination disorder (DCD), health-related physical fitness—including body composition, flexibility, strength of lower body, and cardiorespiratory fitness—and objectively measured physical activity (PA) in school-aged children. This study aimed to (1) examine differences in physical fitness and [...] Read more.

Evidence remains limited on the interconnections between developmental coordination disorder (DCD), health-related physical fitness—including body composition, flexibility, strength of lower body, and cardiorespiratory fitness—and objectively measured physical activity (PA) in school-aged children. This study aimed to (1) examine differences in physical fitness and PA between children with and without DCD and (2) investigate whether physical fitness functions as a mediator in the association between DCD and PA in school-aged children. Sixty-three children aged 6.5–8 years (12 DCD, 19.05%) who provided valid data were enrolled. Mediation analysis was conducted using the PROCESS macro for SPSS. Flexibility significantly mediates the relationship of DCD to vigorous PA (VPA) (effect = 3.202, bootstrap SE = 1.682, 95% bootstrap CI = 0.463, 7.078), as well as DCD to moderate-to-vigorous (MVPA) (effect = 5.194, bootstrap SE = 2.903, 95% bootstrap CI = 0.434, 11.778). Additionally, there was a significant mediating effect of lower muscle strength on the relationship between DCD and VPA (effect = −1.943, bootstrap SE = 1.297, 95% bootstrap CI = −5.112, −0.021), and DCD and counts per minute (CPM) in axis 2 (effect = −34.388, bootstrap SE = 20.212, 95% bootstrap CI = −80.819, −1.353). The findings highlight flexibility and lower-body strength as potential mechanisms underlying the association between DCD and PA participation. These factors may represent candidate intervention targets; however, their roles require confirmation in larger samples and longitudinal designs. Full article

(This article belongs to the Special Issue Physical Medicine and Rehabilitation: Trends and Applications—5th Edition)

13 pages, 760 KB

Open AccessArticle

Time to Epidural Steroid Injection and Complete Remission in Zoster-Associated Pain: A Multicenter Retrospective Cohort Study

by Yongsoo Lee, Eun Hee Chun, Hee Yong Kang, Harin Hong, Yeji Yang, Hye Sun Lee and Jung Eun Kim

Life 2026, 16(6), 869; https://doi.org/10.3390/life16060869 (registering DOI) - 22 May 2026

Abstract

Background: In zoster-associated pain (ZAP), earlier epidural steroid injection (ESI) has been associated with better outcomes, but optimal timing remains unclear, and prior studies have largely relied on pain reduction alone. Methods: In this multicenter retrospective cohort, 215 patients with ZAP who completed [...] Read more.

Background: In zoster-associated pain (ZAP), earlier epidural steroid injection (ESI) has been associated with better outcomes, but optimal timing remains unclear, and prior studies have largely relied on pain reduction alone. Methods: In this multicenter retrospective cohort, 215 patients with ZAP who completed a three-session ESI course were classified into early (<30 days) and delayed (≥30–≤180 days) groups. The primary endpoint was complete remission at 12 weeks (≥50% visual analog scale [VAS] reduction, VAS ≤ 2, and sensory normalization); successful response (≥50% VAS reduction) served as the secondary endpoint. An ordered three-category framework and an exploratory generalized Youden index threshold analysis were applied. Results: Complete remission occurred in 82.1% versus 39.0% and successful response in 91.7% versus 67.8%. Each additional day of delay was associated with lower odds of complete remission (adjusted odds ratio [aOR], 0.957; p < 0.001) and higher odds of a worse outcome category (aOR, 1.030; p < 0.001). Exploratory candidate boundaries were 22 and 42 days. Conclusions: Earlier ESI initiation was associated with a higher likelihood of complete remission incorporating pain reduction, low residual pain intensity, and sensory normalization. These findings highlight the clinical relevance of treatment timing and recovery assessment beyond pain reduction alone in ZAP. Full article

(This article belongs to the Special Issue Feature Papers in Medical Research: 4th Edition)

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11 pages, 2090 KB

Open AccessArticle

Identification and Functional Characterization of a Novel POU3F4 Frameshift Mutation in a Chinese Family

by Shuwen Fan, Yaqiong Guan, Mengya Xiang, Hongzhe Yu, Tianyang Zhang, Jialei Fu, Jiahao Fei, Yongtao Xiao and Yunfeng Wang

Life 2026, 16(6), 868; https://doi.org/10.3390/life16060868 (registering DOI) - 22 May 2026

Abstract

Hereditary sensorineural hearing loss (SNHL) represents a significant global public health burden. DFNX2, an X-linked form of non-syndromic SNHL, is caused by pathogenic variants in the POU3F4 gene. This study aimed to identify a novel POU3F4 mutation and characterize its functional consequences to [...] Read more.

Hereditary sensorineural hearing loss (SNHL) represents a significant global public health burden. DFNX2, an X-linked form of non-syndromic SNHL, is caused by pathogenic variants in the POU3F4 gene. This study aimed to identify a novel POU3F4 mutation and characterize its functional consequences to elucidate the molecular pathogenesis of DFNX2. A three-generation Chinese family with X-linked deafness was recruited. Targeted next-generation sequencing was used to screen candidate variants, which were validated by Sanger sequencing for co-segregation analysis. Functional assays, including subcellular localization, dual-luciferase reporter assay, Western blotting, and homology modeling, were performed to assess the mutation’s effects. A novel frameshift mutation, c.670_673dupGGTA (p.(Asn225Argfs*2)), was identified and showed complete co-segregation with the deafness phenotype. The mutant protein exhibited cytoplasmic mislocalization, and dual-luciferase assays revealed a severe reduction in transcriptional activation capacity, whereas Western blot confirmed stable expression of the truncated protein. Structural modeling predicted the loss of both the POUS and POUH DNA-binding subdomains. Collectively, this study expands the mutational spectrum of POU3F4 and supports previously reported mechanisms underlying DFNX2 pathogenesis. Full article

(This article belongs to the Section Genetics and Genomics)

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11 pages, 1148 KB

Open AccessArticle

Reliability and Anatomical Agreement of High-Resolution Ultrasound for Measuring the Length and Thickness of the A1 Pulley: A Cadaveric Study

by Xeber Iruretagoiena, Marc Blasi, Ramón Balius, Xavier Sala, María Garralda and Javier De la Fuente

Life 2026, 16(6), 867; https://doi.org/10.3390/life16060867 (registering DOI) - 22 May 2026

Abstract

Accurate assessment of the A1 pulley is essential for the diagnosis and treatment of trigger finger, particularly in ultrasound-guided percutaneous release. Although high-resolution ultrasound is widely used to evaluate pulley morphology, the validity of sonographic measurements of A1 pulley length has not been [...] Read more.

Accurate assessment of the A1 pulley is essential for the diagnosis and treatment of trigger finger, particularly in ultrasound-guided percutaneous release. Although high-resolution ultrasound is widely used to evaluate pulley morphology, the validity of sonographic measurements of A1 pulley length has not been clearly established against anatomical reference standard. This study evaluated the reliability and validity of ultrasound for measuring A1 pulley length and thickness in human cadavers and assessed the reproducibility of A2 pulley length. Twenty fingers from five fresh-frozen cadaveric hands were examined. Two blinded expert musculoskeletal sonographers independently performed ultrasound acquisition and measurements of A1 and A2 pulley length and A1 pulley thickness, while a third blinded observer obtained anatomical measurements after meticulous dissection using a digital caliper. Ultrasound systematically overestimated A1 pulley length compared with anatomical measurements and showed very poor reliability (ICC = 0.05) with wide limits of agreement. In contrast, A2 pulley length showed high interobserver reliability (ICC = 0.83) and relatively better agreement with anatomical values, whereas A1 pulley thickness showed moderate reproducibility (ICC = 0.61). Overall, A1 length measurements showed substantial variability and limited agreement, while A2 length and A1 thickness appeared more consistent within this experimental setting. These findings should be interpreted within the limitations of a cadaveric model. Full article

(This article belongs to the Special Issue Ultrasound and Anatomical Studies)

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15 pages, 5938 KB

Open AccessCase Report

Phenotypic Variability of Kidney Involvement in Fabry Disease—Lessons from a Family Study

by Elena-Emanuela Rusu, Ruxandra-Oana Jurcut, Mihaela Gherghiceanu, Filip Muresan, Gheona Altarescu, Bogdan Stanciulescu, Robert Adam, Alexandru Procop, Cristina Stoica, Bogdan Marian Sorohan, Vlad Stefanescu and Gener Ismail

Life 2026, 16(6), 866; https://doi.org/10.3390/life16060866 (registering DOI) - 22 May 2026

Abstract

Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular accumulation of glycosphingolipids in many tissues and fluids, including the kidneys. We report a single family with Fabry disease that includes seven patients carrying the pathogenic variant c.797A>C in the [...] Read more.

Fabry disease is an X-linked lysosomal storage disease that leads to the intracellular accumulation of glycosphingolipids in many tissues and fluids, including the kidneys. We report a single family with Fabry disease that includes seven patients carrying the pathogenic variant c.797A>C in the GLA gene, with remarkable variability in kidney involvement, assessed based on clinical, biological, and histological data. The patients were monitored for 2–9 years, and all received enzyme replacement therapy. Kidney involvement was variable and included severely decreased GFR with significant proteinuria, mildly to moderately decreased GFR with proteinuria, mildly decreased GFR with microalbuminuria or normoalbuminuria, hyperfiltration with normoalbuminuria, and preserved kidney function. All patients who underwent kidney biopsy presented with Fabry-specific lesions and, in some cases, chronic histological damage. This study provides valuable insights into kidney involvement evaluated through kidney biopsy, personalized management strategies for family members according to their phenotype, and long-term follow-up of kidney function. We underscore the importance of molecular screening of the GLA gene in all family members for early identification of the disease and early initiation of specific treatments that can prevent or delay the progression of this disease. Full article

(This article belongs to the Special Issue Pathogenesis and Novel Treatment for Kidney Diseases)

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17 pages, 472 KB

Open AccessProtocol

Protocol for Developing and Validating a Multimarker-Clinical Prediction Model of SGLT2 Inhibitor-Induced Acute eGFR Dip in CKD Stages 3–4: A Three-Stage Urinary Proteomics Study

by Zhiyu Duan, Youhe Gao, Mengjie Huang, Yanjun Liang, Jing Hao, Jie Wang and Guangyan Cai

Life 2026, 16(6), 865; https://doi.org/10.3390/life16060865 (registering DOI) - 22 May 2026

Abstract

Introduction: SGLT2 inhibitors reduce renal composite endpoints and proteinuria, yet RCTs uniformly show an acute eGFR dip within 2 weeks to 2 months after initiation. However, demographic and clinical predictors of an acute eGFR dip demonstrate considerable heterogeneity across studies. This study aims [...] Read more.

Introduction: SGLT2 inhibitors reduce renal composite endpoints and proteinuria, yet RCTs uniformly show an acute eGFR dip within 2 weeks to 2 months after initiation. However, demographic and clinical predictors of an acute eGFR dip demonstrate considerable heterogeneity across studies. This study aims to identify urinary protein biomarkers of this early eGFR dip and integrate them with routine variables to build a clinically actionable prediction model. Methods and analysis: This three-stage proteomics study includes retrospective discovery, prospective internal validation, and external validation cohorts (total n ≈ 600–700). DIA mass spectrometry will screen for urinary proteins associated with ≥10% eGFR decline at 1 month post-SGLT2i initiation in CKD stages 3–4. Top candidates (FDR < 10%, FC > 1.5, ion intensity > 1 × 10⁴, unique gene families) will be validated by ELISA. A LASSO-logistic regression model will integrate the top three proteins with seven routinely available clinical variables: age, BMI, diabetes status, heart failure, systolic blood pressure, baseline eGFR, and diuretic use. Model performance will be assessed using the C-statistic, NRI, IDI, and calibration metrics. Adaptive stopping rules are pre-specified. Ethics and dissemination: Approved by the Ethics Review Committee at Chinese PLA General Hospital (S2025-859-02, 2025KY126-KS002), all participants will provide written informed consent prior to enrollment, and the study will adhere to the Declaration of Helsinki. Data will be pseudonymized and stored securely according to institutional regulations. Findings will be published in peer-reviewed journals and presented at international nephrology conferences. Trial Registration: Registered Report Identifier: ChiCTR2600119772. Date of registration: 3 March 2026. Full article

(This article belongs to the Special Issue Pathogenesis and Novel Treatment for Kidney Diseases)

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47 pages, 1720 KB

Open AccessReview

Trace Elements in the Pancreas: From Physiological Homeostasis to the Pathogenesis of Diabetes, Pancreatitis, and Cancer—A Review

by Łukasz Bryliński, Katarzyna Brylińska, Jolanta Sado, Kacper Kraśnik, Miłosz Smyk, Olga Komar, Filip Woliński, Alicja Forma, Katarzyna Rusek, Jolanta Flieger, Grzegorz Teresiński and Jacek Baj

Life 2026, 16(5), 864; https://doi.org/10.3390/life16050864 (registering DOI) - 21 May 2026

Abstract

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review [...] Read more.

The pancreas is an organ with two functions: endocrine and exocrine. The proper functioning of the pancreas depends on many factors. One of these is trace elements—precise control of trace element homeostasis is important for both the endocrine and exocrine parts. This review provides a comprehensive summary of current knowledge regarding the role of trace elements: iron (Fe), copper (Cu), cobalt (Co), iodine (I), manganese (Mn), zinc (Zn), silver (Ag), cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in pancreatic physiology and their influence on the pathogenesis of key diseases of this organ, such as diabetes (DM), acute (AP) and chronic pancreatitis (CP), autoimmune pancreatitis (AIP), and pancreatic cancer (PC). Trace elements, including Fe, Cu, Zn, Se, and Mn, play a fundamental role in maintaining endocrine and exocrine homeostasis, participating in insulin synthesis, stabilizing digestive enzymes, and the functioning of antioxidant systems. It has been demonstrated that disturbances in their concentrations lead to the activation of pathological molecular pathways, including oxidative stress, chronic inflammation, and beta-cell apoptosis. In the context of diabetes, excess Fe promotes ferroptosis, whilst exposure to heavy metals such as Cd, Pb, and Hg induces insulin resistance and pancreatic islet dysfunction. In the course of pancreatitis, elements such as Zn and Se exhibit protective potential by stabilizing tissue barriers, whereas toxic metals impair ion transport, exacerbating fibrotic processes. Furthermore, analysis of available data indicates a significant association between heavy metal accumulation and pancreatic carcinogenesis, driven by DNA damage and oncogene modulation. Understanding pancreatic metallomics opens new prospects for early diagnosis, environmental prevention, and the development of targeted therapeutic strategies that restore the body’s micronutrient balance. Full article

(This article belongs to the Section Medical Research)

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7 pages, 1022 KB

Open AccessCase Report

Topical Imiquimod for Lentigo Maligna in a Nonagenarian

by Sarah Hosseini, Georgios Kravvas and Sandra Jerkovic Gulin

Life 2026, 16(5), 863; https://doi.org/10.3390/life16050863 (registering DOI) - 21 May 2026

Abstract

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may [...] Read more.

Background: Lentigo maligna (LM) represents melanoma in situ and predominantly affects elderly individuals, typically arising on chronically sun-exposed skin of the head and neck. Although LM is characterized by slow horizontal growth and generally favourable prognosis, progression to invasive lentigo maligna melanoma may occur, making timely and effective treatment essential. Surgical excision remains the standard of care; however, advanced age, comorbidities, lesion size, and cosmetic or functional considerations may limit surgical feasibility. Case presentation: We report the case of a 93-year-old woman with no prior history of skin cancer who presented with a gradually enlarging pigmented lesion on the forehead. Clinical examination revealed an irregularly pigmented macule measuring 25 × 27 mm. Multiple mapping biopsies confirmed melanoma in situ of the lentigo maligna type, with adnexal extension and no evidence of dermal invasion. Given the patient’s advanced age and lesion location, a non-surgical approach was selected. Topical imiquimod 5% cream was applied five times per week for 12 weeks to the visible lesion and to a 20 mm margin around it. The patient was monitored closely throughout the treatment. Local inflammatory reactions were mild to moderate, consisting mainly of erythema, crusting, and superficial erosion, without systemic adverse effects. At treatment completion, marked clinical improvement with near-complete resolution of pigmentation was observed. Follow-up dermoscopic evaluation demonstrated only minimal residual granular pigmentation. Post-treatment mapping biopsies confirmed complete histological clearance of atypical melanocytic cells. Conclusions: This case illustrates that topical imiquimod may serve as a safe and effective alternative to surgery in carefully selected elderly patients with lentigo maligna. Close clinical follow-up and histological confirmation of clearance are essential to ensure treatment success and durable outcomes. Full article

(This article belongs to the Special Issue Skin Aging and Dermatosis)

13 pages, 252 KB

Open AccessReview

Infectious Complications in Metabolic and Bariatric Surgery: A Comprehensive Narrative Review of Pathophysiology, Prevention, and Management

by Marcello Agosta, Egle Augello, Carlo Maria Bellanca, Andrea Marino, Cristiana Rossitto, Giuseppe Nunnari, Maria Sofia and Saverio Latteri

Life 2026, 16(5), 862; https://doi.org/10.3390/life16050862 (registering DOI) - 21 May 2026

Abstract

Background: Metabolic and bariatric surgery is an established therapeutic option for severe obesity and obesity-related medical problems. Although minimally invasive techniques and enhanced recovery pathways have reduced postoperative morbidity, infectious complications remain clinically relevant because they may lead to readmission, reoperation, prolonged antimicrobial [...] Read more.

Background: Metabolic and bariatric surgery is an established therapeutic option for severe obesity and obesity-related medical problems. Although minimally invasive techniques and enhanced recovery pathways have reduced postoperative morbidity, infectious complications remain clinically relevant because they may lead to readmission, reoperation, prolonged antimicrobial therapy, and mortality. Methods: We conducted a narrative review of the literature on infectious complications after metabolic and bariatric surgery. Evidence was synthesized across five clinically relevant domains: host-related pathophysiology, microbial epidemiology, preoperative optimization, antimicrobial prophylaxis and pharmacokinetic considerations, and diagnosis and management of postoperative infectious complications. Results: Patients with obesity present specific infection-related vulnerabilities, including chronic low-grade inflammation, altered immune responses, impaired tissue oxygenation, obesity-related medical problems, and procedure-specific risks. Contemporary prevention relies on multidisciplinary preoperative optimization, appropriate skin antisepsis, weight-based antimicrobial prophylaxis, intraoperative redosing when indicated, and adherence to enhanced recovery principles. Anastomotic leaks and intra-abdominal abscesses represent the most severe organ/space infections and require early recognition, source control, antimicrobial therapy, nutritional support, and coordinated surgical, radiological, and endoscopic management. Conclusions: Infectious complications after metabolic and bariatric surgery result from the interaction between host physiology, microbial factors, pharmacological considerations, and surgical technique. A structured approach integrating prevention, early diagnosis, and multidisciplinary management may improve outcomes. Further bariatric-specific studies are needed to strengthen the evidence base for several preventive and therapeutic strategies. Full article

(This article belongs to the Special Issue Latest Updates on Clinical Microbiology and Antimicrobial Resistant Infection)

17 pages, 18840 KB

Open AccessArticle

Genome-Wide Characterization and Expression Profiling of the CCR Gene Family Associated with Stem Strength in Upland Cotton (Gossypium hirsutum L.)

by Cong-Hua Feng, Dan Li, Suen Liu, Linlin Liu, Cunpeng Zhao, Kaihui Wang, Di Liu, Haina Zhang, Jina Chi, Yuyuan Qian, Xinlong Gao, Yi Liu, Junyi Geng and Baosheng Guo

Life 2026, 16(5), 861; https://doi.org/10.3390/life16050861 (registering DOI) - 21 May 2026

Abstract

In this study, we performed the first genome-wide identification and characterization of the cinnamoyl-CoA reductase (CCR) gene family in upland cotton (Gossypium hirsutum), focusing on its potential association with stem strength. We identified 76 GhCCR genes and classified them [...] Read more.

In this study, we performed the first genome-wide identification and characterization of the cinnamoyl-CoA reductase (CCR) gene family in upland cotton (Gossypium hirsutum), focusing on its potential association with stem strength. We identified 76 GhCCR genes and classified them into four subfamilies. We then analyzed their evolutionary relationships, conserved domains, synteny, promoter cis-elements, and expression patterns. All GhCCR proteins possess the NADB_Rossmann superfamily domain, and family expansion appears to have been driven mainly by segmental and tandem duplications. A small number of GhCCR genes showed relatively high expression in leaf, pistil, and torus tissues, while genes such as GhCCR3/9/10 exhibited elevated transcript levels under abiotic stress conditions. RT-qPCR results indicated that three candidate GhCCR genes (GhCCR25, GhCCR52 and GhCCR64) were significantly more highly expressed in multiple tissues of the stiff-stem line JY-25 than in the soft-stem line JR-15. Together, these findings suggest that GhCCR genes may contribute to the regulation of growth, development, and stress adaptation in G. hirsutum. However, direct biochemical or genetic validation is required to confirm their functional roles in lignin biosynthesis and stem rigidity. Full article

(This article belongs to the Special Issue Plant Life: Integrating Multi-Omic Approaches from Molecules to Environment)

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