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11 pages, 1293 KiB  
Article
RAB24 Missense Variant in Dogs with Cerebellar Ataxia
by Cleo Schwarz, Jan Wennemuth, Julien Guevar, Francesca Dörn, Vidhya Jagannathan and Tosso Leeb
Genes 2025, 16(8), 934; https://doi.org/10.3390/genes16080934 (registering DOI) - 4 Aug 2025
Abstract
Hereditary ataxias are a highly heterogenous group of diseases characterized by loss of coordination. In this study, we investigated a family of random-bred dogs, in which two siblings were affected by a slowly progressive ataxia. They presented with clinical signs of progressive cerebellar [...] Read more.
Hereditary ataxias are a highly heterogenous group of diseases characterized by loss of coordination. In this study, we investigated a family of random-bred dogs, in which two siblings were affected by a slowly progressive ataxia. They presented with clinical signs of progressive cerebellar ataxia, hypermetria, and absent menace response. The MRI revealed generalized brain atrophy, reduced cortical demarcation, hypoplastic corpus callosum, and cerebellar folia thinning, highly suggestive of a neurodegenerative disorder. We sequenced the genomes of the two affected dogs and their unaffected parents. Filtering for protein-changing variants that had homozygous alternate genotypes in the affected dogs, heterozygous genotypes in the parents, and homozygous reference genotypes in 1576 control genomes yielded a single missense variant in the RAB24 gene, XM_038534663.1:c.239G>T or XP_038390591.1:p.(Gly80Val). Genotypes at this variant showed the expected co-segregation with the ataxia phenotype in the investigated family. The predicted amino acid affects the conserved RabF4 motif. Glycine-80 resides at the protein surface and the introduction of a hydrophobic isopropyl side chain of the mutant valine might impede solvent accessibility. Another missense variant in RAB24, p.Glu38Pro, was previously reported to cause a clinically similar form of cerebellar ataxia in Gordon Setters and Old English Sheepdogs. Taken together, the available data suggest that RAB24:p.Gly80Val represents the causal variant in the studied dogs. To the best of our knowledge, this is only the second report of a potentially pathogenic RAB24 variant in any species and further supports that RAB24 should be considered a candidate gene in human ataxia patients with unclear molecular etiology. Full article
(This article belongs to the Special Issue Hereditary Traits and Diseases in Companion Animals)
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14 pages, 1169 KiB  
Article
Putting DOAC Doubts to Bed(Side): Preliminary Evidence of Comparable Functional Outcomes in Anticoagulated and Non-Anticoagulated Stroke Patients Using Point-of-Care ClotPro® Testing
by Jessica Seetge, Balázs Cséke, Zsófia Nozomi Karádi, Edit Bosnyák, Eszter Johanna Jozifek and László Szapáry
J. Clin. Med. 2025, 14(15), 5476; https://doi.org/10.3390/jcm14155476 (registering DOI) - 4 Aug 2025
Abstract
Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at [...] Read more.
Background/Objectives: Direct oral anticoagulants (DOACs) are now the guideline-recommended alternative to vitamin K antagonists (VKAs) for long-term anticoagulation in patients with non-valvular atrial fibrillation. However, accurately assessing their impact on ischemic stroke outcomes remains challenging, primarily due to uncertainty regarding anticoagulation status at the time of hospital admission. This preliminary study addresses this gap by using point-of-care testing (POCT) to confirm DOAC activity at bedside, allowing for a more accurate comparison of 90-day functional outcomes between anticoagulated and non-anticoagulated stroke patients. Methods: We conducted a retrospective cohort study of 786 ischemic stroke patients admitted to the University of Pécs between February 2023 and February 2025. Active DOAC therapy was confirmed using the ClotPro® viscoelastic testing platform, with ecarin Clotting Time (ECT) employed for thrombin inhibitors and Russell’s Viper Venom (RVV) assays for factor Xa inhibitors. Patients were categorized as non-anticoagulated (n = 767) or DOAC-treated with confirmed activity (n = 19). Mahalanobis distance-based matching was applied to account for confounding variables including age, sex, pre-stroke modified Rankin Scale (mRS), and National Institutes of Health Stroke Scale (NIHSS) scores at admission and 72 h post-stroke. The primary outcome was the change in mRS from baseline to 90 days. Statistical analysis included ordinary least squares (OLS) regression and principal component analysis (PCA). Results: After matching, 90-day functional outcomes were comparable between groups (mean mRS-shift: 2.00 in DOAC-treated vs. 1.78 in non-anticoagulated; p = 0.745). OLS regression showed no significant association between DOAC status and recovery (p = 0.599). In contrast, NIHSS score at 72 h (p = 0.004) and age (p = 0.015) were significant predictors of outcome. PCA supported these findings, identifying stroke severity as the primary driver of outcome. Conclusions: This preliminary analysis suggests that ischemic stroke patients with confirmed active DOAC therapy at admission may achieve 90-day functional outcomes comparable to those of non-anticoagulated patients. The integration of bedside POCT enhances the reliability of anticoagulation assessment and underscores its clinical value for real-time management in acute stroke care. Larger prospective studies are needed to validate these findings and to further refine treatment strategies. Full article
(This article belongs to the Section Clinical Neurology)
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20 pages, 968 KiB  
Article
Ten-Year Results of a Single-Center Trial Investigating Heart Rate Control with Ivabradine or Metoprolol Succinate in Patients After Heart Transplantation
by Fabrice F. Darche, Alexandra C. Alt, Rasmus Rivinius, Matthias Helmschrott, Philipp Ehlermann, Norbert Frey and Ann-Kathrin Rahm
J. Cardiovasc. Dev. Dis. 2025, 12(8), 297; https://doi.org/10.3390/jcdd12080297 - 1 Aug 2025
Viewed by 149
Abstract
Aims: Sinus tachycardia after heart transplantation (HTX) due to cardiac graft denervation is associated with reduced post-transplant survival and requires adequate treatment. We analyzed the long-term effects of heart rate control with ivabradine or metoprolol succinate in HTX recipients. Methods: This observational retrospective [...] Read more.
Aims: Sinus tachycardia after heart transplantation (HTX) due to cardiac graft denervation is associated with reduced post-transplant survival and requires adequate treatment. We analyzed the long-term effects of heart rate control with ivabradine or metoprolol succinate in HTX recipients. Methods: This observational retrospective single-center study analyzed the ten-year results of 110 patients receiving ivabradine (n = 54) or metoprolol succinate (n = 56) after HTX. Analysis included comparison of demographics, medications, heart rates, blood pressure values, echocardiographic features, cardiac catheterization data, cardiac biomarkers, and post-transplant survival including causes of death. Results: Both groups showed no significant differences concerning demographics or medications (except for ivabradine and metoprolol succinate). At 10-year follow-up, HTX recipients with ivabradine showed a significantly lower heart rate (72.7 ± 8.5 bpm) compared to baseline (88.8 ± 7.6 bpm; p < 0.001) and to metoprolol succinate (80.1 ± 8.1 bpm; p < 0.001), a significantly lower NT-proBNP level (588.4 ± 461.4 pg/mL) compared to baseline (3849.7 ± 1960.0 pg/mL; p < 0.001) and to metoprolol succinate (1229.0 ± 1098.6 pg/mL; p = 0.005), a significantly lower overall mortality (20.4% versus 46.4%; p = 0.004), and mortality due to graft failure (1.9% versus 21.4%; p = 0.001). Multivariate analysis showed a significantly decreased risk of death within 10 years after HTX in patients with post-transplant use of ivabradine (HR 0.374, CI 0.182–0.770; p = 0.008). Conclusions: In this single-center trial, patients with ivabradine revealed a significantly more pronounced heart rate reduction, a lower NT-proBNP level, and a superior 10-year survival after HTX. Full article
(This article belongs to the Collection Current Challenges in Heart Failure and Cardiac Transplantation)
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11 pages, 1521 KiB  
Article
Thermal Treatment Prevents Effects of Downward Loads on the Screw-In Force Generation and Canal-Centering Ability of Nickel–Titanium Rotary Instruments
by Keiichiro Maki, Arata Ebihara, Yanshan Luo, Yuka Kasuga, Hayate Unno, Satoshi Omori, Shunsuke Kimura and Takashi Okiji
Materials 2025, 18(15), 3610; https://doi.org/10.3390/ma18153610 (registering DOI) - 31 Jul 2025
Viewed by 177
Abstract
This study aimed to examine how downward load applied during instrumentation affects the stress generation and shaping properties in thermally treated and non-treated NiTi rotary instruments. ProTaper Universal (PTU; non-thermally treated) and ProTaper Gold (PTG; thermally treated) were used to prepare J-shaped canals [...] Read more.
This study aimed to examine how downward load applied during instrumentation affects the stress generation and shaping properties in thermally treated and non-treated NiTi rotary instruments. ProTaper Universal (PTU; non-thermally treated) and ProTaper Gold (PTG; thermally treated) were used to prepare J-shaped canals in resin blocks. Load-controlled automated instrumentation and torque/force sensing devices were employed with preset downward loads of 1, 2, or 3 N (n = 10 each). The torque/force, instrumentation time, and canal-centering ratio were measured and analyzed using two-way or one-way analysis of variance with Tukey’s test (α = 0.05). In the PTU-1N group, instrumentation was not completed because a ledge was formed in all canals. The PTU-3N group showed significantly greater upward force (screw-in force) and clockwise torque, along with a significantly smaller canal-centering ratio (less deviation) at the apical 0 mm level, than the PTU-2N group (p < 0.05). The downward load did not influence the instrumentation time (p > 0.05). In the PTG groups, these effects of downward load on the force generation and canal-centering ratio were not significant (p > 0.05). In the non-thermally treated PTU instruments, greater downward loads enhanced screw-in force while decreasing apical canal deviation; however, these effects were abolished in the thermally treated PTG instruments. This study highlights the importance of adapting the instrumentation technique with instrument characteristics: thermally treated flexible instruments facilitate smoother use, while stiffer, non-thermally treated ones may require precise control of downward loads. Full article
(This article belongs to the Topic Advances in Dental Materials)
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13 pages, 494 KiB  
Article
Clinicopathological Features and Risk Stratification of Multiple-Classifier Endometrial Cancers: A Multicenter Study from Poland
by Wiktor Szatkowski, Małgorzata Nowak-Jastrząb, Tomasz Kluz, Aleksandra Kmieć, Małgorzata Cieślak-Steć, Magdalena Śliwińska, Izabela Winkler, Jacek Tomaszewski, Jerzy Jakubowicz, Renata Pacholczak-Madej and Paweł Blecharz
Cancers 2025, 17(15), 2483; https://doi.org/10.3390/cancers17152483 - 28 Jul 2025
Viewed by 286
Abstract
Rationale: The ProMisE molecular classification improves risk assessment in endometrial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, complicating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study [...] Read more.
Rationale: The ProMisE molecular classification improves risk assessment in endometrial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, complicating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study (2022–2025), 1075 ECs from four institutions were classified by MMR and p53 immunohistochemistry and POLE exon sequencing. Tumors showing ≥2 molecular features (e.g., MMRd–p53abn, POLEmut–p53abn) were categorized as multiple-classifier ECs. Results: Multiple-classifier ECs comprised 6.9% (74/1075), with MMRd–p53abn (3.9%) being most common. These tumors exhibited more aggressive features vs. MMRd-only: G3 (28.57% vs. 11.79%, p = 0.002), non-endometrioid histology (11.9% vs. 2.85%, p = 0.018), and high–intermediate/high-risk (HIR/HR) groups (59.52% vs. 37.80%, p = 0.001). POLEmut–p53abn (N = 4) and POLEmut–MMRd–p53abn (N = 10) tumors showed advanced stages (75% and 40% FIGO III–IV, respectively), in contrast to classical POLEmut tumors (6.7% FIGO III–IV), and higher rates of nodal metastases. Conclusions: Co-occurrence of molecular classifiers, including triple-classifier tumors, correlates with more adverse profiles and may undermine current stratification paradigms. This study emphasizes the need to further investigate and refine molecular risk models to account for overlapping profiles. Full article
(This article belongs to the Special Issue Endometrial Cancer—from Diagnosis to Management)
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17 pages, 21259 KiB  
Article
Plumbagin Improves Cognitive Function via Attenuating Hippocampal Inflammation in Valproic Acid-Induced Autism Model
by Nasrin Nosratiyan, Maryam Ghasemi-Kasman, Mohsen Pourghasem, Farideh Feizi and Farzin Sadeghi
Brain Sci. 2025, 15(8), 798; https://doi.org/10.3390/brainsci15080798 - 27 Jul 2025
Viewed by 336
Abstract
Background/Objectives: The hippocampus is an essential part of the central nervous system (CNS); it plays a significant role in social–cognitive memory processing. Prenatal exposure to valproic acid (VPA) can lead to impaired hippocampal functions. In this study, we evaluated the effect of plumbagin [...] Read more.
Background/Objectives: The hippocampus is an essential part of the central nervous system (CNS); it plays a significant role in social–cognitive memory processing. Prenatal exposure to valproic acid (VPA) can lead to impaired hippocampal functions. In this study, we evaluated the effect of plumbagin (PLB) as a natural product on spatial learning and memory, neuro-morphological changes, and inflammation levels in a VPA-induced autism model during adolescence. Methods: Pregnant Wistar rats received a single intraperitoneal (i.p.) injection of VPA (600 mg/kg) or saline on gestational day 12.5. The male offspring were then categorized and assigned to five groups: Saline+DMSO-, VPA+DMSO-, and VPA+PLB-treated groups at doses of 0.25, 0.5, or 1 mg/kg. Spatial learning and memory were evaluated using the Morris water maze. Histopathological evaluations of the hippocampus were performed using Nissl and hematoxylin–eosin staining, as well as immunofluorescence. The pro-inflammatory cytokine levels were also quantified by quantitative real-time PCR. Results: The findings revealed that a VPA injection on gestational day 12.5 is associated with cognitive impairments in male pups, including a longer escape latency and traveled distance, as well as decreased time spent in the target quadrant. Treatment with PLB significantly enhanced the cognitive function, reduced dark cells, and ameliorated neuronal–morphological alterations in the hippocampus of VPA-exposed rats. Moreover, PLB was found to reduce astrocyte activation and the expression levels of pro-inflammatory cytokines. Conclusions: These findings suggest that PLB partly mitigates VPA-induced cognitive deficits by ameliorating hippocampal inflammation levels. Full article
(This article belongs to the Section Behavioral Neuroscience)
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21 pages, 5034 KiB  
Article
The Activation of the Microglial NLRP3 Inflammasome Is Involved in Tuberous Sclerosis Complex-Related Neuroinflammation
by Ran Ding, Shengxuan Zhang, Linxue Meng, Lingman Wang, Ziyao Han, Jianxiong Gui, Jiaxin Yang, Li Cheng, Lingling Xie and Li Jiang
Int. J. Mol. Sci. 2025, 26(15), 7244; https://doi.org/10.3390/ijms26157244 - 26 Jul 2025
Viewed by 348
Abstract
Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of [...] Read more.
Tuberous sclerosis complex (TSC) is a systemic disease caused by mutations in either the TSC1 (encoding hamartin) or TSC2 (encoding tuberin) gene, with mutations in the TSC2 gene potentially leading to more severe clinical symptoms. Neurological symptoms are a common clinical manifestation of TSC, and neuroinflammation is thought to play an important role. Glial cells are a major source of neuroinflammation, but whether microglia are involved in the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome and the expression of interleukin-1β (IL-1β) in TSC patients remains unclear. We used a transcriptome sequencing dataset for bioinformatics analysis to explore the differences in the expression of microglial inflammasome-associated hub genes. TSC2 knockdown (TSC2 KD) microglia (HMC3 cell line) were generated by lentivirus, and the expression of inflammasome-associated hub genes, microglial activation, and NLRP3 inflammasome activation were verified. In addition, experiments were performed to explore the regulatory effects of rapamycin. Bioinformatics analysis identified a total of eight inflammasome-associated hub genes. By detecting GFP fluorescence, TSC2 mRNA, TSC2 protein expression, and the phosphorylation of the mammalian target of rapamycin (p-mTOR)/mTOR, we confirmed that the TSC2 KD microglia model was successfully established. Compared with the control group, the TSC2 KD group presented higher mRNA levels and fluorescence intensities of microglia AIF1 and CD68, as well as greater reactive oxygen species (ROS) production. Eight inflammasome-associated hub gene mRNA assays revealed that the expression of the NLRP3 and IL1B genes was increased. Compared with the control group, the TSC2 KD group presented increased levels of NLRP3 and Pro-IL-1β proteins in cells and Cleaved-Caspase 1 and Cleaved-IL-1β proteins in the supernatant, suggesting NLRP3 inflammasome activation. Rapamycin intervention alleviated these changes, demonstrating that the TSC2 gene regulation of microglial activation and NLRP3 inflammasome activation are correlated with mTOR phosphorylation. In conclusion, microglia are activated in TSC patients and participate in the NLRP3 inflammasome-associated neuroinflammatory response, and rapamycin treatment can alleviate these changes. Full article
(This article belongs to the Section Molecular Neurobiology)
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16 pages, 1248 KiB  
Article
Coronary Artery Calcium Score as a Predictor of Anthracycline-Induced Cardiotoxicity: The ANTEC Study
by Anna Borowiec, Patrycja Ozdowska, Magdalena Rosinska, Agnieszka Maria Zebrowska, Sławomir Jasek, Beata Kotowicz, Joanna Waniewska, Hanna Kosela-Paterczyk, Elzbieta Lampka, Katarzyna Pogoda, Zbigniew Nowecki and Jan Walewski
Pharmaceuticals 2025, 18(8), 1102; https://doi.org/10.3390/ph18081102 - 25 Jul 2025
Viewed by 269
Abstract
Background: Many risk factors for cancer therapy-related cardiovascular toxicity overlap with risk factors for atherosclerosis. According to the ESC 2022 Cardio-Oncology Guidelines, coronary computed tomography angiography and coronary artery calcium score are not recommended as part of routine risk assessment prior to oncological [...] Read more.
Background: Many risk factors for cancer therapy-related cardiovascular toxicity overlap with risk factors for atherosclerosis. According to the ESC 2022 Cardio-Oncology Guidelines, coronary computed tomography angiography and coronary artery calcium score are not recommended as part of routine risk assessment prior to oncological treatment. The aim of this study was to prospectively assess the influence of coronary artery calcium score (CAC score) on cancer therapy-related cardiac dysfunction in patients with moderate and high risk of cardiovascular toxicity, qualified for anthracycline treatment. Methods: In all patients, risk factors were collected, laboratory tests, echocardiography with global longitudinal strain (GLS) assessment and coronary artery tomography with coronary artery calcium score were performed. A total of 80 patients were included in the study, of which 77 (96.25%) were followed for an average of 11.5 months. The mean age at baseline was 60.5 years and 72 (93.51%) were women. Results: During observation, five patients (6.49%) died, including two due to heart failure and three due to cancer progression. The majority of patients (59, 76.6%) had breast cancer, 11 (14.3%) were diagnosed with sarcoma and seven (9.1%) with lymphoma. According to the HFA-ICOS risk score, 40 patients (51.9%) were classified as moderate risk (MR), and 37 patients (48.1%) as high risk (HR) for cancer therapy-related cardiovascular toxicity. A CAC score greater than 100 was calculated in 17 (22.1%) patients and greater than 400 in three (3.9%) patients. The CAC score above zero was more common in older patients and in patients classified as high risk (p < 0.001). There was also a significant association between CAC score and hypertension, hyperlipidemia, chronic kidney disease, and the level of NT-proBNP. During 12-month follow-up, mild CTRCD occurred in 38 (49.4%) patients, moderate CTRCD was diagnosed in seven (9.1%), and severe in three (3.9%) patients. In the univariable analysis, CTRCD was more common in the high-risk group (p = 0.005) and in patients with a CAC score greater than zero (p = 0.036). In multivariable analysis, the incidence of CTRCD remains higher in the CAC score > 0 group, even after adjusting for age, hypertension, and hyperlipidemia. In this study group, the CTRCD rates increased with the HFA-ICOS risk score. Conclusions: In moderate and high-risk patients, a coronary artery calcium score greater than zero was identified as a significant risk factor for the development of cancer therapy-related cardiac dysfunction during anthracycline-based treatment. Furthermore, the HFA-ICOS risk score demonstrated good correlation with the incidence of CTRCD in this study, supporting its validity as a predictive tool in patients receiving anthracycline therapy. Full article
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11 pages, 764 KiB  
Article
Subscapularis CT-Scan Evaluation in Patients with Proximal Humerus Fracture: Reverse Total Shoulder Arthroplasty Versus Hemi-Arthroplasty
by Edoardo Gaj, Andrea Redler, Alessandro Maggiori, Susanna Pagnotta, Natale Criseo, Vikranth Mirle, Matthew Daggett and Angelo De Carli
J. Clin. Med. 2025, 14(15), 5257; https://doi.org/10.3390/jcm14155257 - 24 Jul 2025
Viewed by 336
Abstract
Background/Objectives: Hemiarthroplasty (HA) and Reverse Total Shoulder Arthroplasty (RTSA) are both reliable treatment options for complex proximal humerus fractures. The role of the subscapularis tendon is well-defined in HA, whereas it plays a controversial role in RTSA. The purpose of our study [...] Read more.
Background/Objectives: Hemiarthroplasty (HA) and Reverse Total Shoulder Arthroplasty (RTSA) are both reliable treatment options for complex proximal humerus fractures. The role of the subscapularis tendon is well-defined in HA, whereas it plays a controversial role in RTSA. The purpose of our study is to evaluate its role in patients with proximal humerus fractures treated with HA and RTSA and investigate its association with clinical outcomes. Methods: Sixty-eight consecutive patients with proximal humeral fracture were prospectively enrolled into the study from June 2015 to May 2020 (RTSA = 36; HA = 32). Pre- and postoperative shoulder CT scans were performed to measure the subscapularis muscle cross-sectional area (SMCSA) and the supraspinatus fossa cross-sectional area (SFCSA). The SMCSA/SFCSA ratio was employed to normalize measurements against individual patient anatomy. Patient reported outcomes (PROs) and range of motion (ROM) were evaluated at the final follow-up. Results: The RTSA group demonstrated superior patient-reported outcomes (PROs) and range of motion (ROM) compared to the HA group. Notably, the Constant Score was significantly higher in the RTSA group (58.00 vs. 38.50; p = 0.0001), as well as forward flexion (147.50° vs. 90.00°; p < 0.0001). A postoperative reduction in subscapularis size of >35% occurred more frequently in RTSA patients (55.6%) than in HA patients (25%) (p = 0.01). The loss of subscapularis surface was greater in the RTSA patients (p = 0.018). Conclusions: RTSA demonstrated better results compared to HA, providing better ROM and PROs. Postoperative reduction in subscapularis size was significantly higher in RTSA compared to HA. Subscapularis condition seems to show no correlation with functional outcome in RTSA. Full article
(This article belongs to the Section Orthopedics)
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21 pages, 1292 KiB  
Article
Polymorphism in IFNλ Can Impact the Immune/Inflammatory Response to COVID-19 Vaccination in Older CMV-Seropositive Adults
by Ariane Nardy, Fernanda Rodrigues Monteiro, Brenda Rodrigues Silva, Jônatas Bussador do Amaral, Danielle Bruna Leal Oliveira, Érika Donizetti de Oliveira Cândido, Edison Luiz Durigon, Andressa Simões Aguiar, Guilherme Pereira Scagion, Vanessa Nascimento Chalup, Guilherme Eustáquio Furtado, Marina Tiemi Shio, Carolina Nunes França, Luiz Henrique da Silva Nali and André Luis Lacerda Bachi
Vaccines 2025, 13(8), 785; https://doi.org/10.3390/vaccines13080785 - 24 Jul 2025
Viewed by 410
Abstract
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of [...] Read more.
Background: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article
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12 pages, 3204 KiB  
Systematic Review
Association Between ABO or Rh Blood Groups and Chikungunya Virus Infection: A Systematic Review and Meta-Analysis
by Yanisa Rattanapan, Wanatsanan Chulrik, Karunaithas Rasaratnam and Thitinat Duangchan
Medicina 2025, 61(8), 1316; https://doi.org/10.3390/medicina61081316 - 22 Jul 2025
Viewed by 316
Abstract
Background and Objectives: The relationship between ABO or Rh blood groups and susceptibility to Chikungunya virus (CHIKV) infection remains unclear. This systematic review and meta-analysis aimed to synthesize available evidence on this association. Materials and Methods: Studies reporting ABO and/or Rh [...] Read more.
Background and Objectives: The relationship between ABO or Rh blood groups and susceptibility to Chikungunya virus (CHIKV) infection remains unclear. This systematic review and meta-analysis aimed to synthesize available evidence on this association. Materials and Methods: Studies reporting ABO and/or Rh blood groups and CHIKV infection were searched through PubMed, Scopus, EMBASE, MEDLINE, Ovid, ProQuest, and Google Scholar up to 8 July 2025. A random-effects meta-analysis was conducted to calculate pooled odds ratios (Ors) with 95% CIs. Heterogeneity was assessed using I2 statistics. Subgroup analyses were performed based on study design and study quality. Sensitivity analysis was conducted using a leave-one-out method. Publication bias was evaluated via funnel plots and Egger’s test. Results: Seven studies, including 24,828 participants, were included. No significant associations were observed between blood groups A, B, AB, or Rh(D) and CHIKV infection. However, blood group O was significantly associated with an increased risk of CHIKV infection (OR: 1.52, 95% CI: 1.01–2.29, p = 0.043, I2 = 95.38%) compared to non-O blood groups. Subgroup analyses showed stable results. Nevertheless, the sensitivity analysis indicated that certain studies had a greater influence on the overall results. In addition, significant publication bias was also detected. Conclusions: Current evidence indicates that blood group O is significantly associated with an increased susceptibility to CHIKV infection. In contrast, no consistent associations were observed for other ABO or Rh blood groups. Due to substantial heterogeneity and methodological limitations, these findings should be interpreted with caution. Further well-designed, large-scale studies with standardized diagnostics are needed to clarify these associations and underlying mechanisms. Full article
(This article belongs to the Section Infectious Disease)
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11 pages, 892 KiB  
Article
Sotatercept for Connective Tissue Disease-Associated Pulmonary Arterial Hypertension with Concomitant Interstitial Lung Disease: Efficacy and Safety Insights
by Chebly Dagher, Maria Akiki, Kristin Swanson, Brett Carollo, Garett Fiscus, Harrison W. Farber and Raj Parikh
J. Clin. Med. 2025, 14(15), 5177; https://doi.org/10.3390/jcm14155177 - 22 Jul 2025
Viewed by 372
Abstract
Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited [...] Read more.
Background/Objectives: Sotatercept has demonstrated efficacy in pulmonary arterial hypertension (PAH), but its use has not been studied in patients with Group 3 pulmonary hypertension (PH). Additionally, patients with connective tissue disease-associated PAH (CTD-PAH) were underrepresented in the STELLAR trial. Given the limited treatment options for pulmonary hypertension in patients with interstitial lung disease (PH-ILD), this study aimed to evaluate the use of sotatercept in CTD-PAH patients with concomitant ILD. Methods: Eligible patients (n = 7) had a confirmed diagnosis of CTD-PAH with concomitant ILD. The patients were already receiving background PAH therapy. Baseline hemodynamic and clinical measurements were reassessed after 24 weeks of sotatercept therapy. The variables assessed included six-minute walk distance (6MWD), pulmonary vascular resistance (PVR), echocardiographic right ventricular systolic pressure (eRVSP), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, and supplemental oxygen requirements. Results: The study included seven patients with a mean age of 57 years (range: 39–73 years). After 24 weeks, the mean 6MWT distance increased from 211 m to 348 m (p < 0.01). Mean PVR decreased from 7.77 WU at baseline to 4.53 WU (p < 0.01). Mean eRVSP decreased from 79.43 mmHg to 54.14 mmHg (p < 0.01). NT-proBNP decreased from 3056.86 pg/mL to 1404.29 pg/mL (p < 0.01). The WHO functional class and supplemental oxygen requirements improved in all patients. Conclusions: Sotatercept was tolerated in patients with CTD-PAH and ILD, with no evidence of adverse respiratory effects. When added to foundational PAH therapy, sotatercept resulted in significant improvements across multiple parameters. These findings suggest that sotatercept may be a promising therapeutic option as an adjunctive treatment in this patient population. Full article
(This article belongs to the Section Respiratory Medicine)
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13 pages, 1910 KiB  
Article
Curcumin Ameliorates DSS-Induced Colitis in Mice Through Modulation of Gut Microbiota and Metabolites
by Chengxue Yi, Yuxuan Xia, Jiajing Yan, Wen Xia, Haoyu Wang, Fei Mao and Pan Huang
Life 2025, 15(7), 1153; https://doi.org/10.3390/life15071153 - 21 Jul 2025
Viewed by 217
Abstract
In this study, we established a mouse colitis model using DSS to investigate the impact of curcumin on gut injury, the intestinal microbiota, and fecal metabolites. The findings indicated that curcumin effectively mitigated weight loss and colon shortening caused by colitis, enhanced the [...] Read more.
In this study, we established a mouse colitis model using DSS to investigate the impact of curcumin on gut injury, the intestinal microbiota, and fecal metabolites. The findings indicated that curcumin effectively mitigated weight loss and colon shortening caused by colitis, enhanced the expression of anti-inflammatory factor IL-10 mRNA (p < 0.05), and suppressed the expression of pro-inflammatory factors (IL-1β, IL-6, and TNF-α mRNA; p < 0.05). 16S rDNA sequencing analysis showed that in the CUR group, compared to the NC and DSS groups, the abundances of Bacteroides, Lachnospiraceae NK4A136, and Ruminococcaceae UGC 014 significantly increased, while that of Lactobacillus markedly decreased. Additionally, compared with the DSS group, the CUR group demonstrated a significant decrease in levels of metabolites associated with nucleic acid and fat metabolism, including xanthosine, isocitric acid, and D-xylose. Conversely, levels of metabolites of curcumin, such as demethoxycurcumin and tetrahydrocurcumin, were significantly elevated in the CUR group. Curcumin appears to offer protection against mouse colitis by potentially enhancing the composition of the gut microbiota and regulating metabolic and inflammatory processes through its metabolites. Full article
(This article belongs to the Section Pharmaceutical Science)
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13 pages, 329 KiB  
Article
Postoperative Morbidity Is Not Associated with a Worse Mid-Term Quality of Life After Colorectal Surgery for Colorectal Carcinoma
by Maximilian Brunner, Theresa Jendrusch, Henriette Golcher, Klaus Weber, Axel Denz, Georg F. Weber, Robert Grützmann and Christian Krautz
J. Clin. Med. 2025, 14(14), 5167; https://doi.org/10.3390/jcm14145167 - 21 Jul 2025
Viewed by 307
Abstract
Objectives: The aim of the present study was to investigate the impact of postoperative morbidity on mid-term quality of life and patient-related outcome (PRO) parameters after colorectal surgery for colorectal carcinoma. Methods: Quality of life and perioperative data were prospectively collected [...] Read more.
Objectives: The aim of the present study was to investigate the impact of postoperative morbidity on mid-term quality of life and patient-related outcome (PRO) parameters after colorectal surgery for colorectal carcinoma. Methods: Quality of life and perioperative data were prospectively collected from 99 adult patients treated for colorectal carcinoma—56 patients with colonic carcinoma and 43 with rectal carcinoma, all of whom underwent R0 colorectal resection, at the University Hospital Erlangen between 2018 and 2021. Quality of life data (EQL C29 and C30) were assessed before the start of treatment and one year after. Patients were grouped based on the presence or absence of postoperative morbidity, and their quality of life was compared between the two groups. Results: In the colonic carcinoma cohort, global quality of life and emotional functioning showed significant improvement from pre-treatment to the one-year follow-up (63 vs. 72, p = 0.012 and 63 vs. 76, p = 0.009, respectively). Among the symptom scales, five items improved, while two worsened. Patients who experienced postoperative morbidity (32% in the colonic carcinoma group) did not exhibit worse outcomes in functioning or symptom scales compared to those without morbidity (4 items improved and 1 worsened in the morbidity group vs. 3 improved and 1 worsened in the no-morbidity group). The rectal carcinoma cohort demonstrated a decline in quality of life from pre-treatment to the one-year follow-up. Two functioning scales worsened significantly (physical function: 89 vs. 83, p < 0.001; role function: 81 vs. 68, p = 0.009), and twelve symptom scales showed deterioration, with only two symptom scales improving. Postoperative morbidity (33% in the rectal carcinoma group) did not result in more pronounced impairments compared to those without morbidity. The morbidity group experienced 2 worsened and 0 improved items, while the no-morbidity group had 10 worsened and 1 improved item. Conclusions: Postoperative morbidity was not significantly associated with a worse quality of life at one-year follow-up after treatment of colorectal carcinomas, including colorectal resections, compared to patients who did not develop postoperative morbidity. Full article
(This article belongs to the Section Oncology)
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17 pages, 2234 KiB  
Article
Impact of Live Ligilactobacillus salivarius CCFM1332 and Its Postbiotics on Porphyromonas gingivalis Colonization, Alveolar Bone Resorption and Inflammation in a Rat Model of Periodontitis
by Qing Hong, Yu Ren, Xin Tang, Bingyong Mao, Qiuxiang Zhang, Jianxin Zhao, Shumao Cui and Zhenmin Liu
Microorganisms 2025, 13(7), 1701; https://doi.org/10.3390/microorganisms13071701 - 20 Jul 2025
Viewed by 403
Abstract
Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and [...] Read more.
Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article
(This article belongs to the Section Medical Microbiology)
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