Life

15 pages, 979 KiB

Open AccessArticle

Unveiling the Diagnostic Significance of Calprotectin in Serous Ovarian Carcinoma

by Alkis Matsas, Eleni Stamoula, Konstantinos Kontzoglou, Makarios Eleftheriades, Sophia Tsokkou, Panagiotis Christopoulos, Theodoros Panoskaltsis, Eleni Polydorou, Ioannis Sotiropoulos, Theodore Troupis and Dimitrios C. Iliopoulos

Life 2025, 15(7), 1080; https://doi.org/10.3390/life15071080 (registering DOI) - 8 Jul 2025

Abstract

Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of [...] Read more.

Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of great importance in order to improve survival rates. Emerging evidence reveals that tumor markers are valuable diagnostic and monitoring tools. In this study, we evaluated the aforementioned potential of three markers CA-125, CA 15-3, and serum Calprotectin. CA-125 is a protein that is found elevated in cases of ovarian, breast, and lung cancer. Cancer Antigen 15-3 (CA 15-3) is a protein detected in high levels in women with breast cancer and ovarian cancer and it is significantly elevated in patients with metastasis and recurrence of OC. Calprotectin is a protein released from activated neutrophils, related to inflammatory conditions and can be a potential immune-mediated marker in OC. Purpose: The purpose of this study was to explore the significance of serum calprotectin, CA-125, and CA 15-3 in women diagnosed with serous OC. Methodology: Thirty-eight (38) women with diagnosed OC were included in this research as the study group and twenty-seven (27) healthy women with no history or current diagnosis of OC were included in the control group. Women in both groups shared similar past histories to avoid any other parameters interfering with the study. Our study group was further subdivided into early stage and advanced stage patients. Blood samples were collected from all women of both groups and were examined using ELISA kits to evaluate the levels of the above markers. Results: When comparing patients versus control patients, those with OC exhibited higher levels of Calprotectin compared to healthy individuals. Additionally, Calprotectin showed a statistically significant elevation between the control group and advanced patients. CA-125 remains the current standard of care biomarker exhibiting 90% sensitivity, whereas sensitivities in Calprotectin and CA 15-3 were 60% and 50%, respectively. Conclusions: Serum CA-125 remains the single most valuable biomarker for ovarian cancer, having the highest statistical significance, correlation with disease stage, detecting both early or advanced patients, and sensitivity of 90%. It appears to be a promising inflammatory biomarker in the early diagnosis of ovarian cancer, showing an elevation in patients, while CA 15-3 provides moderate complementary information and exhibits inferior sensitivity when compared to both CA-125 and Calprotectin. The latter appears to be a promising marker and further studies could show if its addition to established protocols could improve early detection, disease progression, or risk stratification. Calprotectin enhances the detection range for ovarian cancer when used alongside CA-125, while this combined approach detected a greater proportion of patients than CA-125 alone, indicating improved diagnostic potential. Full article

(This article belongs to the Section Medical Research)

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4 pages, 152 KiB

Open AccessEditorial

Implications of Bioactive Compounds in Lifelong Disorders

by Francisco Les and Guillermo Cásedas

Life 2025, 15(7), 1079; https://doi.org/10.3390/life15071079 - 7 Jul 2025

Abstract

Over the past decade, there has been a remarkable surge in research focused on bioactive compounds, reflecting their growing importance in fields such as pharmacology, nutrition, and disease prevention [...] Full article

(This article belongs to the Special Issue Implications of Bioactive Compounds in Lifelong Disorders)

13 pages, 5262 KiB

Open AccessArticle

The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate

by Fevzi Bedir, Hüseyin Kocatürk, Mehmet Sefa Altay, Renad Mammadov, Bahadır Süleyman, Taha Abdulkadir Coban, Gülce Naz Yazici, Seval Bulut and Halis Süleyman

Life 2025, 15(7), 1078; https://doi.org/10.3390/life15071078 - 6 Jul 2025

Abstract

Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided [...] Read more.

Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility. Full article

(This article belongs to the Special Issue Testicular and Penile Disorders: Reproductive, Pathophysiological, Diagnostic and Therapeutic Insights)

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22 pages, 5021 KiB

Open AccessArticle

Luteolin-Rich Extract from Harrisonia perforata (Blanco) Merr. Root Alleviates SARS-CoV-2 Spike Protein-Stimulated Lung Inflammation via Inhibition of MAPK/NLRP3 Inflammasome Signaling Pathways

by Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Sonthaya Umsumarng and Pornngarm Dejkriengkraikul

Life 2025, 15(7), 1077; https://doi.org/10.3390/life15071077 - 5 Jul 2025

Abstract

The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need [...] Read more.

The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need for effective therapeutic strategies to mitigate spike protein-stimulated lung inflammation, we examined the anti-inflammatory properties of luteolin and ethanolic extract from Harrisonia perforata (Blanco) Merr. root. The ethanolic extract of H. perforata root (HPEE) contained a high concentration of luteolin flavonoid (143.53 ± 1.58 mg/g extract). Both HPEE (25–100 μg/mL) and luteolin (4.5–36 μM) significantly inhibited inflammation stimulated by the Wuhan (W) and Omicron (O) spike protein S1, as evidenced by a dose-dependent significant decrease in IL-6, IL-1β, and IL-18 secretion in A549 lung epithelial cells (p < 0.05). Furthermore, pretreatment with HPEE or luteolin prior to spike protein exposure (100 ng/mL) significantly, in a dose-dependent manner, repressed the inflammatory mRNA expression (p < 0.05). Mechanistic study revealed that HPEE and luteolin suppressed NLRP3 inflammasome signaling activation by reducing their machinery protein expressions. Additionally, they inhibited the ERK/JNK/p38 MAPK signaling activation, resulting in decreased inflammatory mRNA expression and cytokine release. These findings suggest that H. perforata root extract and its major flavonoid luteolin exert potent anti-inflammatory effects and may offer therapeutic potential against spike protein-induced lung inflammation. Full article

(This article belongs to the Special Issue Plant-Derived Natural Products and Their Biomedical Properties: 2nd Edition)

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15 pages, 3976 KiB

Open AccessArticle

Uncommon but Important: Tertiary Center Experience with Rare Cases of Breast Hamartoma

by Mihaela Camelia Tîrnovanu, Bogdan Florin Toma, Elena Cojocaru, Elena Țarcă, Ștefan Dragoș Tîrnovanu, Vlad Gabriel Tîrnovanu, Cristian Mârțu, Roxana Ana Covali, Anca Irina Gradinariu, Gabriela Ghiga and Ludmila Lozneanu

Life 2025, 15(7), 1076; https://doi.org/10.3390/life15071076 - 5 Jul 2025

Abstract

Background: A breast hamartoma or fibroadenolipoma is a rare, benign mass consisting of disorganized mature breast tissue elements. Surgical excision is recommended if the lesion exhibits rapid progressive growth. However, incomplete excision may result in recurrence. The objective of this study is to [...] Read more.

Background: A breast hamartoma or fibroadenolipoma is a rare, benign mass consisting of disorganized mature breast tissue elements. Surgical excision is recommended if the lesion exhibits rapid progressive growth. However, incomplete excision may result in recurrence. The objective of this study is to provide comprehensive insights into the characteristics of breast hamartomas and to conduct a thorough investigation into their clinical presentation, diagnostic procedures, and management strategies. Methods: We report on 13 cases of breast hamartomas treated surgically between January 2018 and June 2023 at the Obstetrics and Gynecology Hospital “Cuza Vodă” in Iași. We analyzed their histological images and immunohistochemical evaluations. Results: The mean age of the patients was 33.35 years, ranging from 22 to 57 years. Clinically, all patients presented with a painless mass. The diagnosis was confirmed through ultrasound examination, which revealed that hamartomas appeared as well-circumscribed, oval, and heterogeneous in echotexture. The tumor sizes ranged from 1 to 17 cm, with an average size of 6.75 cm. Surgical treatment involved lumpectomy with the excision of a small portion of normal tissue surrounding the tumor. The histological variability of these tumors poses diagnostic challenges for pathologists, potentially leading to underdiagnosis. Conclusions: Most hamartomas exhibit characteristic features on ultrasound attributable to their fibrous, glandular, and adipose tissue composition. Accurate identification of hamartomas is crucial due to the potential for recurrence. Notably, none of the women in our study experienced recurrence during the follow-up period. Full article

(This article belongs to the Section Medical Research)

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20 pages, 2843 KiB

Open AccessReview

Neural Mechanisms and Alterations of Sweet Sensing: Insights from Functional Magnetic Resonance Imaging Studies

by Tobias Long, Colette C. Milbourn, Alison Smith, Kyaw Linn Su Khin, Amanda J. Page, Iskandar Idris, Qian Yang, Richard L. Young and Sally Eldeghaidy

Life 2025, 15(7), 1075; https://doi.org/10.3390/life15071075 - 5 Jul 2025

Abstract

Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and [...] Read more.

Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and member 3 (T1R3), are now recognised as being widely distributed throughout the body, including the gastrointestinal tract. Preclinical studies suggest these receptors are central to nutrient and glucose sensing, detecting energy availability and triggering metabolic and behavioural responses to maintain energy balance. Both internal and external factors tightly regulate their signalling pathways, and dysfunction within these systems may contribute to the development of metabolic disorders such as obesity and type 2 diabetes (T2D). Functional magnetic resonance imaging (fMRI) has provided valuable insights into the neural mechanisms underlying sweet sensing by mapping brain responses to both lingual/oral and gastrointestinal sweet stimuli. This review highlights key findings from fMRI studies and explores how these neural responses are modulated by metabolic state and individual characteristics such as body mass index, habitual intake and metabolic health. By integrating current evidence, this review advances our understanding of the complex interplay between sweet sensing, brain responses, and health and identifies key gaps and directions for future research in nutritional neuroscience. Full article

(This article belongs to the Special Issue New Advances in Neuroimaging and Brain Functions: 2nd Edition)

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12 pages, 684 KiB

Open AccessArticle

Age-Related Effects on the Color Discrimination Threshold

by Ali Almustanyir, Mohammed Alhazmi, Amal Aldarwesh, Meznah S. Almutairi, Mohammed Almahubi, Ansam Alateeq, Tahani Alqahtani, Muteb Alanazi, Sultan Alotaibi, Mansour Alghamdi, Essam Almutleb, Basal H. Altoaimi, Balsam Alabdulkader and Mosaad Alhassan

Life 2025, 15(7), 1074; https://doi.org/10.3390/life15071074 - 5 Jul 2025

Abstract

Traditional color vision tests lack the sensitivity to detect subtle differences in individuals with normal color vision. The Konan ColorDx Cone Contrast Threshold (CCT) HD test allows the quantitative measurement of color discrimination thresholds for each cone type. This cross-sectional study established normative [...] Read more.

Traditional color vision tests lack the sensitivity to detect subtle differences in individuals with normal color vision. The Konan ColorDx Cone Contrast Threshold (CCT) HD test allows the quantitative measurement of color discrimination thresholds for each cone type. This cross-sectional study established normative values for L-, M-, and S-cone contrast sensitivities and evaluated the effects of age and sex on color discrimination thresholds. Participants aged 15–79 years with normal color vision were included (n = 216; 55% female). CCTs were measured monocularly using the Konan ColorDx CCT HD test under standardized conditions, and the influences of age and sex on L-, M-, and S-cone sensitivities were evaluated. In all groups, L-cone sensitivity was the highest, followed by the M- and S-cone sensitivities. Overall contrast sensitivity was significantly higher in females than in males (mean difference = −0.041), especially for adolescents and young adults (20–24 years). Young adults outperformed middle-aged and older adults, with age-related decline most pronounced for S-cone sensitivity in those over 60. The right and left eye sensitivities did not differ. This study provides age- and sex-stratified normative data for the Konan Color Dx CCT HD test, supporting its use for clinical and occupational assessments. Full article

(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)

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16 pages, 1785 KiB

Open AccessArticle

Effects of Betulinic Acid and Ursolic Acid on IL-17-Induced CCL20 Release in Normal Human Epidermal Keratinocytes

by Anna Arai, Takahiro Oyama, Toyoaki Nakajima, Michiru Usui, Ena Sato, Takanori Kamiya, Midori Oyama, Takashi Tanikawa, Tomoharu Takeuchi, Takehiko Abe and Tomomi Hatanaka

Life 2025, 15(7), 1073; https://doi.org/10.3390/life15071073 - 4 Jul 2025

Abstract

Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects [...] Read more.

Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that Morus alba extract (MAE) suppressed IL-17-induced CCL20 mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway. Full article

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

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10 pages, 240 KiB

Open AccessArticle

Which Classes of Antibiotics Are Associated with the Acquisition of Carbapenemase-Producing Enterobacterales?

by Lisa Sadou, Benoît Pilmis, Rasha Eid, Pierre Moenne Locoz, Sophie Lefèvre, Françoise Jauréguy, Vanessa Rathouin, Jean-Ralph Zahar and Laura Foucault-Fruchard

Life 2025, 15(7), 1072; https://doi.org/10.3390/life15071072 - 4 Jul 2025

Abstract

Background: Enterobacterales are among the most frequent causes of healthcare-associated infections and are increasingly affected by antimicrobial resistance. Antibiotic use disrupts the gut microbiota, facilitating colonization by multidrug-resistant organisms, including carbapenemase-producing Enterobacterales (CPE). While animal studies have suggested that certain antibiotic classes may [...] Read more.

Background: Enterobacterales are among the most frequent causes of healthcare-associated infections and are increasingly affected by antimicrobial resistance. Antibiotic use disrupts the gut microbiota, facilitating colonization by multidrug-resistant organisms, including carbapenemase-producing Enterobacterales (CPE). While animal studies have suggested that certain antibiotic classes may increase the risk of CPE acquisition, clinical data identifying which classes are most implicated remain limited. Methods: We conducted a single-center, retrospective case-control study (2021–2024) comparing antibiotic prescriptions in patients who acquired CPE with those in controls hospitalized in the same unit and during the same risk period but who did not acquire CPE. The objective of this study was to identify which antibiotic classes or pharmacological properties are associated with the acquisition of carbapenemase-producing Enterobacterales (CPE) in hospitalized patients. Results: During the study period, 35 cases and 70 controls were included. Most cases acquired NDM-type metalloenzymes. Before the risk period, 55 patients had received antibiotic therapy. Univariate analysis identified an association between CPE acquisition and the prescription of fluoroquinolones and antibiotics excreted in bile. During the risk period, only metronidazole prescription was significantly associated with CPE acquisition. Our study has several limitations, including the small sample size, the single-center retrospective design, and the lack of molecular typing (e.g., WGS) to confirm potential clonal transmission. Conclusions: In this preliminary study, metronidazole use was associated with an increased risk of CPE acquisition during risk periods. However, these results should be interpreted cautiously and need to be confirmed in larger, multicenter studies. The high exposure of patients to multiple antibiotic classes highlights the importance of strict antibiotic stewardship policies in the current era of global CPE dissemination. Full article

(This article belongs to the Collection Feature Papers in Microbiology)

19 pages, 1431 KiB

Open AccessArticle

Gastrointestinal Cancers with Consideration of DPD and UGT1A1 Plasma Levels: Chemotherapy-Related Toxicity

by Velko Minchev, Hristo Tsankov, Bozil Robev, Martin Takov, Stefan Federchev, Kalina Kamenova, Lozan Todorov, Liliya Atanasova, Nadya Hristova-Avakumova, Rumen Nikolov, Pavlina Gateva and Vanyo Mitev

Life 2025, 15(7), 1071; https://doi.org/10.3390/life15071071 - 4 Jul 2025

Abstract

Unpredictable, dose-limiting toxicity remains a challenge in cancer treatment. We evaluated dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) plasma levels in the context of chemotherapy-induced toxicity and disease progression. Seventy gastrointestinal cancer patients (30 FOLFOX; 40 FOLFIRI) were enrolled. DPD and UGT1A1 plasma [...] Read more.

Unpredictable, dose-limiting toxicity remains a challenge in cancer treatment. We evaluated dihydropyrimidine dehydrogenase (DPD) and UDP-glucuronosyltransferase 1A1 (UGT1A1) plasma levels in the context of chemotherapy-induced toxicity and disease progression. Seventy gastrointestinal cancer patients (30 FOLFOX; 40 FOLFIRI) were enrolled. DPD and UGT1A1 plasma levels were determined using ELISA. Univariable and bivariable analyses and a general linear model (GLM) framework were used. Post-infusional reductions in white blood cell and granulocyte counts were observed. For FOLFOX, the granulocyte counts decreased by 17% (r = 0.54; p = 0.0030), while FOLFIRI caused a 41% reduction (r = 0.43; p = 0.0063). DPD levels were lower in FOLFOX than in FOLFIRI (2.543 vs. 3.579; p = 0.0363; Cohen’s d = 0.52). The multiple linear regression models associated DPD levels with cancer progression (b* = 0.258, p = 0.034). The bivariate analysis and multiple linear regression indicated some trends of association between UGT1A1 levels and reduction in white blood cell (b* = 0.359, p = 0.042) and granulocyte counts (b* = 0.383, p = 0.030) among FOLFIRI-treated patients. These preliminary observations suggest that DPD and UGT1A1 might contribute to evaluating response assessment. Full article

(This article belongs to the Section Medical Research)

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16 pages, 570 KiB

Open AccessArticle

Comparison of Guided Exercise and Self-Paced Exercise After Lumbar Spine Surgery: A Randomized Controlled Trial

by Seong Son, Han Byeol Park, Kyeong Sik Kong, Byung Rhae Yoo, Woo Kyung Kim and Jae Ang Sim

Life 2025, 15(7), 1070; https://doi.org/10.3390/life15071070 - 4 Jul 2025

Abstract

Background: The efficacy of postoperative exercise rehabilitation after spine surgery is controversial, and a protocol for exercise treatment and detailed outcomes based on functional activity have not yet been established. This study aimed to determine the efficacy of exercise rehabilitation after lumbar spine [...] Read more.

Background: The efficacy of postoperative exercise rehabilitation after spine surgery is controversial, and a protocol for exercise treatment and detailed outcomes based on functional activity have not yet been established. This study aimed to determine the efficacy of exercise rehabilitation after lumbar spine surgery. Methods: A prospective, randomized controlled trial was conducted in 40 patients who underwent lumbar spine surgery (20 patients each in the exercise and control groups) for 12 weeks. Clinical outcomes were assessed using the visual analog scale (VAS) for pain and EuroQol-5 Dimensions 5-Level version (EQ-5D-5L). Body proportions, including body mass index, total muscle mass, and body fat percentage were analyzed. Functional activity was evaluated based on the range of motion of the lumbar spine, strength and endurance of lumbar flexion/extension, flexibility, 6 min walking test, single-leg stance, coordination, and gait pattern analysis. Results: The exercise group showed significantly greater improvement in VAS for pain (66.67% versus 20.00%, p < 0.001) and EQ-5D-5L (45.56% versus 20.00, p = 0.039) compared to the control group. Serial assessment revealed significant improvement in strength of lumbar flexion/extension, 6 min walking test, single-leg stance, coordination, and gait patterns in the exercise group compared to the control group. In particular, the single-leg stance time for the affected leg improved more markedly in the exercise group (280.9% versus 48.7%, p < 0.001). Conclusion: Tailored postoperative exercise after lumbar spine surgery is effective in reducing pain and enhancing functional recovery, including strength and balance. Full article

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

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13 pages, 680 KiB

Open AccessReview

Microbiome Against the Background of the Complex Aetiology in Sarcoidosis—What Do We Already Know?

by Maciej Szymański, Katarzyna Góralska and Ewa Brzeziańska-Lasota

Life 2025, 15(7), 1069; https://doi.org/10.3390/life15071069 - 4 Jul 2025

Abstract

Sarcoidosis is a multi-organ, systemic disease of immunological origin. While its aetiology is unknown, it is believed to be influenced by genetic susceptibility, environmental factors, and autoimmunity. Recent research on the development and progression of sarcoidosis has focused increasingly on the role of [...] Read more.

Sarcoidosis is a multi-organ, systemic disease of immunological origin. While its aetiology is unknown, it is believed to be influenced by genetic susceptibility, environmental factors, and autoimmunity. Recent research on the development and progression of sarcoidosis has focused increasingly on the role of microorganisms. Changes in the respiratory tract microbiome, and hence the physiology of the respiratory tract, are believed to influence the course of sarcoidosis; this is not unlikely, as research indicates that the state of the microbiota inhabiting individual ontocenoses, such as the intestines or blood, may be related to the health of the entire body. This review therefore discusses the microbiological factors that are believed to be involved in the development of the disease; however, as the aetiological factors of sarcoidosis are diverse and are based on highly complex mechanisms, our analysis is restricted to only the most likely factors. Full article

(This article belongs to the Special Issue The Emerging Role of Microbiota in Health and Diseases)

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11 pages, 6109 KiB

Open AccessCase Report

Severe ARDS Complicated by Active Pulmonary Tuberculosis and Recurrent Nosocomial Infections: Therapeutic Challenges and Clinical Outcomes

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

Life 2025, 15(7), 1068; https://doi.org/10.3390/life15071068 - 4 Jul 2025

Abstract

Background: Acute respiratory distress syndrome (ARDS) secondary to tuberculosis (TB) is rare and associated with high mortality. Management is further complicated by comorbidities and ICU-related complications. Methods: We report a 43-year-old woman with post-polio sequelae and uncontrolled diabetes who developed ARDS due to [...] Read more.

Background: Acute respiratory distress syndrome (ARDS) secondary to tuberculosis (TB) is rare and associated with high mortality. Management is further complicated by comorbidities and ICU-related complications. Methods: We report a 43-year-old woman with post-polio sequelae and uncontrolled diabetes who developed ARDS due to pulmonary TB, complicated by recurrent nosocomial infections and gastrointestinal bleeding. Early bronchoscopy and GeneXpert MTB/RIF PCR were performed on ICU Day 2, enabling anti-TB therapy initiation by ICU Day 3. The patient received lung-protective ventilation, prone positioning, tailored antibiotics, and multidisciplinary care. Results: The patient’s clinical course was complicated by two episodes of ventilator-associated pneumonia and gastrointestinal bleeding, but with individualized management, she achieved ventilator weaning and functional recovery. Conclusions: Early TB recognition in ARDS is crucial. Multidisciplinary ICU management, including prudent steroid use, improves outcomes. Full article

(This article belongs to the Special Issue Advances in Intensive Care Medicine)

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19 pages, 719 KiB

Open AccessArticle

Redefining Systemic Sclerosis Classification: Anti-Topoisomerase Antibody as a Superior Predictor of Interstitial Lung Disease and Skin Progression Compared to Limited Cutaneous Systemic Sclerosis Subset

by Chana Chaovanitkul, Tippawan Onchan, Patnarin Pongkulkiat, Ajanee Mahakkanukrauh, Siraphop Suwannaroj and Chingching Foocharoen

Life 2025, 15(7), 1067; https://doi.org/10.3390/life15071067 - 4 Jul 2025

Abstract

Background: Currently, no information exists on the clinical course of anti-topoisomerase I antibody (ATA)-positive limited cutaneous systemic sclerosis (lcSSc). We aimed to evaluate the incidence of and time to the development of interstitial lung disease (ILD), pulmonary hypertension (PHT), scleroderma renal crisis (SRC), [...] Read more.

Background: Currently, no information exists on the clinical course of anti-topoisomerase I antibody (ATA)-positive limited cutaneous systemic sclerosis (lcSSc). We aimed to evaluate the incidence of and time to the development of interstitial lung disease (ILD), pulmonary hypertension (PHT), scleroderma renal crisis (SRC), and maximal modified Rodnan skin score (max-mRSS) in patients with lcSSc and dcSSc, with and without ATA. Methods: This cohort study included 522 patients with systemic sclerosis (SSc). The incidence of and time to the development of ILD, PHT, SRC, and max-mRSS were assessed. Results: ATA-positive dcSSc (dcSSc-posATA) was the most common presentation among Thai patients (321 cases; 61.5%). The median time to the development of ILD was shorter than that in lcSSc-posATA, comparable to that in dcSSc-posATA (1.0 vs. 1.8 years, p = 0.21), and shorter than that in ATA-negative dcSSc (dcSSc-negATA) (1.0 vs. 4.8 years, p = 0.001). The time to max-mRSS in lcSSc-posATA was comparable to that in dcSSc-posATA (p = 0.17) but shorter than that in dcSSc-negATA (p < 0.001). Conclusions: Patients with lcSSc-posATA had a similar risk of ILD development and time to reach max-mRSS as those with dcSSc, regardless of the presence of ATA, but had earlier ILD development and max-mRSS compared to those with dcSSc-negATA. Their prognosis appeared to be better than that of dcSSc-posATA. Full article

(This article belongs to the Special Issue Clinical Manifestations and Treatment of Autoimmune Diseases: 2nd Edition)

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14 pages, 731 KiB

Open AccessArticle

Enhancing Bone–Cartilage Interface Healing in Osteochondral Autograft Transplantation: Effects of BMAC Augmentation and Rehabilitation Protocols

by Robert Gherghel, Ilie Onu, Ana Onu, Ioana-Irina Rezus, Ovidiu Alexa, Daniel Andrei Iordan, Luana Andreea Macovei and Elena Rezus

Life 2025, 15(7), 1066; https://doi.org/10.3390/life15071066 - 3 Jul 2025

Abstract

This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three [...] Read more.

This study aimed to evaluate the effectiveness of different rehabilitation protocols following osteochondral autograft transplantation (OAT) in patients with focal osteochondral defects of the femoral condyle, using the MOCART 2.0 knee score as a primary imaging outcome. Twenty-nine patients were divided into three groups: Group 1 (n = 9) received OAT with bone marrow aspirate concentrate (BMAC) and a 12-week two-phase rehabilitation program; Group 2 (n = 11) received OAT with a 12-week program without BMAC; and Group 3 (n = 9) received OAT with a shortened 6-week program. At the 12-month follow-up, Group 1 demonstrated a superior cartilage repair quality, with the highest mean MOCART 2.0 score (96.1), compared to Group 2 (80.2) and Group 3 (71.7). Notably, complete defect filling was observed in five patients in Group 1 versus four in Group 2 and only one in Group 3. The integration and surface integrity were also better preserved in Group 1. The addition of BMAC and an extended, progressive rehabilitation protocol significantly enhanced the morphological cartilage repair parameters. These results suggest that a biologically enhanced and prolonged recovery plan may offer a greater structural restoration of cartilage after OAT than conventional or accelerated protocols. Full article

(This article belongs to the Special Issue Recent Advances in Physiotherapy for Musculoskeletal)

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9 pages, 447 KiB

Open AccessArticle

Potential Clinical Use of CytoSorb^® for Ticagrelor and Rivaroxaban Elimination Prior to Emergency Orthopedic Surgery in Trauma Patients

by Gabriele Melegari, Fabio Gazzotti, Federica Arturi, Elisabetta Bertellini, Andrea Tognù, Domenico Pietro Santonastaso, Matteo Villani, Francesca Coppi, Fabrizio Fattorini, Fabio Catani and Alberto Barbieri

Life 2025, 15(7), 1065; https://doi.org/10.3390/life15071065 - 3 Jul 2025

Abstract

Background: Major orthopedic trauma in patients receiving anticoagulants such as ticagrelor or rivaroxaban poses a significant perioperative challenge, particularly in emergency contexts where bleeding risks are heightened and specific reversal agents may be unavailable. CytoSorb^®, a hemoadsorption device, has demonstrated efficacy [...] Read more.

Background: Major orthopedic trauma in patients receiving anticoagulants such as ticagrelor or rivaroxaban poses a significant perioperative challenge, particularly in emergency contexts where bleeding risks are heightened and specific reversal agents may be unavailable. CytoSorb^®, a hemoadsorption device, has demonstrated efficacy in cardiac surgery for drug removal. Its potential application in trauma surgery remains unexplored. Objective: This protocol describes a prospective clinical investigation assessing the feasibility and safety of CytoSorb^® hemoadsorption for the preoperative removal of ticagrelor and rivaroxaban in trauma patients requiring urgent orthopedic surgery. Methods: The proposed intervention involves integrating CytoSorb^® into a dedicated extracorporeal circuit under normothermic conditions (37 °C) with a blood flow of 150–200 mL/min for 300 min. Serial plasma samples will be collected at predefined intervals (0, 30, 60, 120, 240, 300 min) and drug concentrations. The primary outcome is the pharmacokinetic profile of drug clearance. Secondary endpoints include procedural safety, bleeding complications, and the feasibility of timely surgery. Expected Impact: The study aims to provide real-world data on the practical integration of CytoSorb^® for anticoagulant removal in orthopedic trauma care, potentially facilitating earlier surgery and improving perioperative safety. Findings may inform future randomized trials and protocol standardization. Full article

(This article belongs to the Special Issue Advances in Anesthesia and Critical Care)

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14 pages, 5332 KiB

Open AccessCase Report

Extramammary Paget’s Disease of the Scalp with an Underlying Atypical Meningioma—A Case Report and Review of the Literature

by Carolina Solomon, Adina Patricia Apostu, Ioana Irina Trufin, Salomea Ruth Halmagyi, Liliana Rogojan, Simona Corina Șenilă and Loredana Ungureanu

Life 2025, 15(7), 1064; https://doi.org/10.3390/life15071064 - 3 Jul 2025

Abstract

Extramammary Paget’s disease (EMPD) is a rare adenocarcinoma originating from apocrine glands, primarily affecting the anogenital and axillary regions. Ectopic EMPD, occurring in non-apocrine sites such as the scalp, is exceptionally uncommon. We report a case of ectopic EMPD of the scalp distinguished [...] Read more.

Extramammary Paget’s disease (EMPD) is a rare adenocarcinoma originating from apocrine glands, primarily affecting the anogenital and axillary regions. Ectopic EMPD, occurring in non-apocrine sites such as the scalp, is exceptionally uncommon. We report a case of ectopic EMPD of the scalp distinguished by its association with an intraosseous atypical meningioma, a previously unreported finding. A 70-year-old female presented with a persistent 15 cm erythematous, alopecic scalp lesion that had been misdiagnosed for a decade. Histopathological analysis confirmed ectopic EMPD, while imaging identified an adjacent intraosseous meningioma. Surgical resection was performed for the meningioma, and radiotherapy was selected as the treatment modality for EMPD. Due to its clinical resemblance to inflammatory dermatoses, ectopic EMPD is often underrecognized, underscoring the critical role of histopathology and immunohistochemical markers in diagnosis. Given its potential association with malignancies, comprehensive systemic evaluation is warranted. The high recurrence rate following surgical excision necessitates consideration of alternative therapeutic approaches, including radiotherapy, Mohs micrographic surgery, or photodynamic therapy. This case highlights the necessity for heightened clinical awareness of atypical scalp lesions and underscores the importance of thorough diagnostic assessment. Further research is needed to clarify the relationship between EMPD and other neoplasms and to optimize management strategies. Full article

(This article belongs to the Special Issue Skin Cancer: From Molecular Basis to Therapy: 2nd Edition)

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31 pages, 683 KiB

Open AccessReview

Risk Factors Associated with the Development of Immune-Checkpoint Inhibitor Diabetes Mellitus: An Integrative Review

by Vivian Crowder and Veronica Brady

Life 2025, 15(7), 1063; https://doi.org/10.3390/life15071063 - 3 Jul 2025

Abstract

Immune checkpoint inhibitor diabetes mellitus (ICI-DM) is an emerging phenomenon in the adult oncology population, with an increased incidence reflecting the increased use of immunotherapy; however, risk factors for ICI-DM have not been fully identified. The aim of this integrated literature review was [...] Read more.

Immune checkpoint inhibitor diabetes mellitus (ICI-DM) is an emerging phenomenon in the adult oncology population, with an increased incidence reflecting the increased use of immunotherapy; however, risk factors for ICI-DM have not been fully identified. The aim of this integrated literature review was to synthesize the published literature on ICI-DM and the factors associated with an increased risk for its development. The review was guided by Sanieszko’s Epidemiology Triad theoretical framework. We conducted a literature search using the Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed databases. The analysis included 2030 studies that met the search criteria, 23 of which were peer-reviewed articles that met the inclusion criteria. The results demonstrated a positive relationship between older age, medical history of diabetes, the presence of susceptible alleles, and exposure to immunotherapy, with an increased risk for ICI-DM. Future studies should include larger samples, more diverse populations, and a broad range of institutions to confirm the risk factors associated with ICI-DM. Full article

(This article belongs to the Special Issue Management of Patients with Diabetes)

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21 pages, 1475 KiB

Open AccessReview

The Role of Predictive Biomarkers in Modern Prostate Cancer Radiotherapy: A Literature Review on Personalised Treatment Strategies and the Prediction of Adverse Effects

by Jelena Stanić, Ivana Šović, Luka Jovanovic, Ivana Z. Matić, Predrag Nikić and Marina Nikitović

Life 2025, 15(7), 1062; https://doi.org/10.3390/life15071062 - 2 Jul 2025

Abstract

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements [...] Read more.

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy. Full article

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

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