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Search Results (17,071)

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15 pages, 1622 KiB  
Article
Optimizing Transplanting Practices for Potted Tree Peony Based on Non-Structural Carbohydrates Accumulation
by Shuaiying Shi, Kun Hu, Shiqi Li, Tian Shi, Shuangcheng Gao, Muhammad Shaaban and Guoan Shi
Horticulturae 2025, 11(8), 995; https://doi.org/10.3390/horticulturae11080995 (registering DOI) - 21 Aug 2025
Abstract
Potted cultivation serves as a vital strategy for industrialized production of standardized tree peonies, engineering seedlings capable of year-round and off-site transplantation. However, the limited root zone in potted conditions restricts root development, resulting in suboptimal seedling quality and hindering commercial-scale production. This [...] Read more.
Potted cultivation serves as a vital strategy for industrialized production of standardized tree peonies, engineering seedlings capable of year-round and off-site transplantation. However, the limited root zone in potted conditions restricts root development, resulting in suboptimal seedling quality and hindering commercial-scale production. This study aimed to investigate the relationship between the accumulation characteristics of non-structural carbohydrates (NSCs) and growth performance in potted tree peonies, while also optimizing the transplantation technologies for potted cultivation. Using two-year-old grafted seedlings of ‘Luoyanghong’ as experimental material, the effects of root pruning, rooting agent, and Metarhizium anisopliae application on morphological development and NSCs accumulation in potted tree peony seedlings were investigated. The results showed that old roots serve as the primary storage organs for NSCs in the potted tree peony. Slight root pruning (25%) was beneficial for fibrous root growth, whereas excessive root pruning (50%) resulted in reduced biomass and NSCs accumulation. The application of a high concentration of rooting agents effectively promoted root growth and mitigated the adverse effects of root pruning. Furthermore, Metarhizium anisopliae significantly increased the stem number in potted tree peonies. The optimal protocol identified through range analysis involved 25% root pruning, followed by irrigation with a solution containing 750 mg·L−1 rooting agent and 20 million spores·mL−1 of Metarhizium anisopliae. The rational distribution of NSCs and coordinated growth across different organs enhanced NSCs accumulation in potted tree peonies. These results demonstrate that combining root pruning with the application of rooting agent and Metarhizium anisopliae can effectively increase NSCs accumulation, optimize plant morphology, and ultimately improve the quality of potted tree peony seedlings. Full article
(This article belongs to the Section Floriculture, Nursery and Landscape, and Turf)
21 pages, 1835 KiB  
Article
Biosynthetic Collagen-Analog Hydrogels Stimulate Endogenous Regrowth of Rabbit Corneas: A Pilot Study
by Iris Timmerman, Marie-Claude Robert, Claire Vergneau-Grosset, Tristan Juette, Javier Benito, Marta Garbin, Mostafa Zamani-Roudbaraki, Mona Moradi, Hamid Goodarzi, Christos Boutopoulos, Marie-Odile Benoit-Biancamano, May Griffith and Maria Vanore
Vet. Sci. 2025, 12(8), 785; https://doi.org/10.3390/vetsci12080785 (registering DOI) - 21 Aug 2025
Abstract
Pro-regenerative corneal implants are being developed to improve corneal healing for companion animals in clinical practice. This pilot study evaluated early corneal tissue and nerve regeneration using biosynthetic collagen-analog hydrogels (CAH) in liquid and solid forms. Their efficacy was compared to each other [...] Read more.
Pro-regenerative corneal implants are being developed to improve corneal healing for companion animals in clinical practice. This pilot study evaluated early corneal tissue and nerve regeneration using biosynthetic collagen-analog hydrogels (CAH) in liquid and solid forms. Their efficacy was compared to each other and to allografts on nine white New Zealand rabbits, divided in three groups of three. Each rabbit cornea underwent keratectomy followed by grafting with either a control allograft cornea, liquid injectable, or solid CAH implant. Corneal healing was assessed over 16 weeks using clinical exams, esthesiometry, in vivo confocal microscopy, and optical coherence tomography. One rabbit per group was euthanized at 3, 10, and 16 weeks for histopathological analysis. Both liquid and solid implants enabled corneal re-epithelialization and regeneration of stromal tissue and corneal nerves. Esthesiometric values indicated faster nerve regeneration in rabbits grafted with biosynthetic implants compared to allografts (p < 0.005). By 16 weeks, regenerated neocorneas achieved transparency comparable to allografts. Solid and liquid CAH implants supported complete corneal tissue and nerve regeneration in the studied rabbits. These results suggest that with further research and development, the current gold standard for corneal transplantation could be replaced by high-performing, easily produced biosynthetic alternatives. Full article
(This article belongs to the Special Issue Vision in Focus: Advances in Veterinary Ophthalmology)
29 pages, 2219 KiB  
Review
Fecal Microbiota Transplantation in Alzheimer’s Disease: Mechanistic Insights Through the Microbiota–Gut–Brain Axis and Therapeutic Prospects
by Jiayu Ren, Qinwen Wang, Hang Hong and Chunlan Tang
Microorganisms 2025, 13(8), 1956; https://doi.org/10.3390/microorganisms13081956 - 21 Aug 2025
Abstract
Alzheimer’s disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota–gut–brain axis (MGBA) have unveiled potential correlative mechanisms that [...] Read more.
Alzheimer’s disease (AD), a prevalent neurodegenerative disorder in the aging population, remains without definitive therapeutic solutions. Emerging insights into the gut microbiota (GM) and its bidirectional communication with the central nervous system(CNS) through the microbiota–gut–brain axis (MGBA) have unveiled potential correlative mechanisms that may contribute to AD pathogenesis, though causal evidence remains limited. Dysregulation of GM composition (dysbiosis) exacerbates AD progression via neuroinflammation, amyloid-β (Aβ) deposition, and tau hyperphosphorylation (p-tau), while restoring microbial homeostasis presents a promising therapeutic strategy. Fecal microbiota transplantation (FMT), a technique to reconstitute gut ecology by transferring processed fecal matter from healthy donors, has demonstrated efficacy in ameliorating cognitive deficits and neuropathology in AD animal models. Preclinical studies reveal that FMT reduces Aβ plaques, normalizes tau phosphorylation, suppresses inflammasome activation, and restores microglial homeostasis through modulation of microbial metabolites and immune pathways. Although clinical evidence remains limited to case reports and small-scale trials showing potential therapeutic effect, safety concerns regarding long-term effects and protocol standardization necessitate further investigation. This review synthesizes current knowledge on GM–AD interactions, evaluates FMT’s mechanistic potential, and discusses challenges in translating this ancient practice into a cutting-edge AD therapy. Rigorous randomized controlled trials and personalized microbiota-based interventions are imperative to advance FMT from bench to bedside. Full article
(This article belongs to the Special Issue Effects of Gut Microbiota on Human Health and Disease, 2nd Edition)
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17 pages, 1402 KiB  
Article
Once-Daily Versus Four-Times-Daily Intravenous Busulfan with Therapeutic Drug Monitoring as Conditioning for Hematopoietic Cell Transplantation in Children
by Safaa Bazbaz, Irina Zaidman, Ehud Even-Or, Polina Stepensky, Razan Sakran, Daniel Kurnik and Gefen Aldouby-Bier
Pharmaceutics 2025, 17(8), 1081; https://doi.org/10.3390/pharmaceutics17081081 - 21 Aug 2025
Abstract
Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing [...] Read more.
Background/Objectives: Busulfan is a key component of myeloablative conditioning regimens in hematopoietic stem cell transplantation (HSCT) for pediatric patients with acute myeloid leukemia, solid tumors, and certain non-malignant diseases. This study compares the clinical outcomes of once-daily (BU1) versus four-times-daily (BU4) busulfan dosing regimens in pediatric HSCT recipients. Methods: A retrospective analysis was conducted on 70 pediatric patients who underwent HSCT at Hadassah Medical Center between June 2018 and October 2023. Thirty-five patients received the BU4 regimen, and 35 received BU1. The primary endpoint was 100-day event-free survival (EFS). Results: There was no statistically significant difference in 100-day event-free survival between the BU1 group (88.6%) and the BU4 group (85.7%; p = 0.768). Similarly, no significant differences were found in time to neutrophil engraftment (p = 0.251) or platelet engraftment (p = 0.688). Sinusoidal obstruction syndrome (SOS) occurred in 17.1% of patients in each group. No significant differences were observed in the increase in liver enzyme levels (p = 1.0). The incidence of acute graft-versus-host disease was comparable between the groups (41.9% for BU1 vs. 40.0% for BU4; p = 0.878). Conclusions: Once-daily and four-times-daily busulfan regimens demonstrated comparable clinical outcomes in terms of efficacy and adverse events. Further prospective studies are needed to validate these findings. Full article
(This article belongs to the Section Clinical Pharmaceutics)
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15 pages, 1248 KiB  
Article
In Vitro Silencing of MHC-I in Keratinocytes by Herpesvirus US11 Protein to Model Alloreactive Suppression
by Frederik Schlottmann, Sarah Strauß, Peter Maria Vogt and Vesna Bucan
Eur. Burn J. 2025, 6(3), 47; https://doi.org/10.3390/ebj6030047 - 21 Aug 2025
Abstract
Background: Secondary rejection remains a major obstacle in skin allografting. Some viruses, such as human herpesvirus and cytomegalovirus, evade immune detection through proteins like the unique short glycoprotein 11 (US11), which down-regulates major histocompatibility complex (MHC) class I expression. This study explores the [...] Read more.
Background: Secondary rejection remains a major obstacle in skin allografting. Some viruses, such as human herpesvirus and cytomegalovirus, evade immune detection through proteins like the unique short glycoprotein 11 (US11), which down-regulates major histocompatibility complex (MHC) class I expression. This study explores the use of recombinant US11 protein as a biopharmaceutical approach to reduce MHC-I expression and thus decrease alloreactivity in human primary keratinocytes. Methods: Human keratinocytes were treated with recombinant US11 protein, and MHC-I expression was assessed via Western blot and flow cytometry. To evaluate immunomodulatory effects, US11-stimulated keratinocytes were co-cultured with peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-γ) levels were measured by ELISA. Additionally, ex vivo human skin tissue was stimulated with US11 to assess long-term MHC-I modulation. Results: US11 treatment significantly reduced MHC-I surface expression in keratinocytes. Co-cultures showed decreased IFN-γ secretion, indicating lower T cell activation. Human skin tissue stimulated with US11 exhibited reduced MHC-I expression after 7 days. Conclusions: This proof-of-concept study suggests that recombinant US11 protein may serve as an effective biopharmaceutical to reduce keratinocyte immunogenicity. Further in vitro and in vivo studies are warranted to validate its potential for clinical application in skin transplantation. Full article
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9 pages, 934 KiB  
Case Report
Pediatric Acute Megakaryoblastic Leukemia with a GATA2 Mutation and Monosomy 7: A Case Report and Clinical Management Challenges
by Gowri Joshi, Astil Jisho Anto, Md Maaz Mallick, Gwan Yong Lim and Łukasz Hutnik
Reports 2025, 8(3), 153; https://doi.org/10.3390/reports8030153 - 21 Aug 2025
Abstract
Background and Clinical Significance: Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive hematologic malignancy. The presence of genetic abnormalities often increases the complexity of AMKL. Among these, patients with monosomy 7 constitute a high-risk group associated with a poorer prognosis and [...] Read more.
Background and Clinical Significance: Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive hematologic malignancy. The presence of genetic abnormalities often increases the complexity of AMKL. Among these, patients with monosomy 7 constitute a high-risk group associated with a poorer prognosis and greater chemoresistance. We report the case of a 10-year-old boy who had AMKL along with monosomy 7 and familial GATA2 deficiency. The case highlights the diagnostic and therapeutic challenges faced, as well as the critical importance of early genetic screening and timely hematopoietic stem cell transplantation (HSCT). Case Presentation: A 10-year-old boy presented with easy bruising and pancytopenia. AMKL was diagnosed with the help of a bone marrow biopsy and immunophenotyping. Genetic testing showed a GATA2 mutation and monosomy 7. Two induction cycles with daunorubicin and cytarabine were administered but failed to eliminate residual disease. The patient also developed pneumonia of a fungal origin. HSCT was delayed due to liver toxicity and elevated minimal residual disease (MRD). Azacitidine and venetoclax stabilized the disease, thereby allowing for successful haploidentical HSCT. The patient achieved complete remission with full donor chimerism. Conclusions: This case emphasizes the importance of early molecular diagnostics in pediatric AMKL. Identifying GATA2 mutations and monosomy 7 early can help guide risk stratification and the timing of HSCT. Multimodal therapy, which includes the use of infection control and targeted agents, is important for improving the outcomes in high-risk patients. Full article
(This article belongs to the Section Haematology)
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12 pages, 960 KiB  
Article
Association Between Survival After Living Donor Liver Transplantation and Recipient Systemic Inflammation and Body Composition
by Jae Hwan Kim, Yeon Ju Kim, Hye-Mee Kwon, Kyung-Won Kim, Jin YanZhen, Sa-Jin Kang, In-Gu Jun, Jun-Gol Song and Gyu-Sam Hwang
J. Clin. Med. 2025, 14(16), 5889; https://doi.org/10.3390/jcm14165889 - 20 Aug 2025
Abstract
Background/Objectives: Preoperative sarcopenia in liver transplantation (LT) recipients is an important prognostic factor of LT outcomes. Systemic inflammatory status (SIS) has been proposed as a unifying mechanism for skeletal muscle loss; thus, considering SIS and sarcopenia together may enhance prognosis assessment in patients [...] Read more.
Background/Objectives: Preoperative sarcopenia in liver transplantation (LT) recipients is an important prognostic factor of LT outcomes. Systemic inflammatory status (SIS) has been proposed as a unifying mechanism for skeletal muscle loss; thus, considering SIS and sarcopenia together may enhance prognosis assessment in patients undergoing LT. Herein, we aimed to describe the relationship between the SIS and skeletal muscle index (SMI) with short-term and long-term mortality post-living donor LT (LDLT). Methods: In total, 3387 consecutive adult LDLT recipients were retrospectively evaluated. The neutrophil-to-lymphocyte ratio (NLR, using a cut-off of 3) was utilized as an SIS. SMI was calculated using computed tomography scans, measured at the third lumbar vertebra; sex-specific cut-offs were determined from contemporary donors. Univariate and multivariable Cox proportional hazard analyses were performed. Results: Decreasing SMI was associated with increasing NLR. Increasing NLR and decreasing SMI both showed dose-dependent relationships with a risk of 90-day mortality. Within sarcopenic patients, NLR > 3 (vs. NLR ≤ 3) was associated with higher 90-day (9.3% vs. 3.5%, p = 0.049) and overall mortality (28.4% vs. 19.1%, p = 0.045). Sarcopenia and NLR > 3 (vs. neither) were independent predictors of 90-day mortality (hazard ratio [HR] 2.48 [1.40–4.40], p = 0.002) and overall mortality (HR, 1.81 [1.37–2.38], p < 0.001) after multivariable adjustment. When stratified by age, sex, and MELD score, the association between sarcopenia and overall mortality persisted in all subgroups, with the highest risk observed in women (HR 3.43, 95% CI 1.83–6.43). Conclusions: Sarcopenia, with the systemic inflammatory response, nearly doubled the risk of 90-day and overall mortality post-LT, proposing that these readily available biomarkers are a practical index for predicting survival post-LT. Considering that these are potentially modifiable factors, our result may provide a new therapeutic target to improve survival post-LT. Full article
(This article belongs to the Section Anesthesiology)
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18 pages, 1803 KiB  
Article
One Shock, Not One Cure: Electroporation Reveals Disease-Specific Constraints in Hepatocyte Gene Editing Therapy
by Callie Clark, Menam Pokhrel, Benjamin Arthur, Pramita Suresh, Ilayda Ates, Justin Gibson, Abishek Dhungana, Ryan Mehlem, Andrew Boysia, Mugdha V. Padalkar, Achala Pokhrel, Jing Echesabal-Chen, Anne Vonada, Alexis Stamatikos, Olga V. Savinova, Markus Grompe and Renee N. Cottle
Biology 2025, 14(8), 1091; https://doi.org/10.3390/biology14081091 - 20 Aug 2025
Abstract
We previously demonstrated lipid nanoparticle-mediated CRISPR-Cas9 gene editing to disrupt the gene encoding cytochrome P450 oxidoreductase (Cypor), combined with transient administration of acetaminophen (APAP), to repopulate the liver with healthy hepatocytes and rescue a phenylketonuria mouse model. This study aimed to investigate electroporation-mediated [...] Read more.
We previously demonstrated lipid nanoparticle-mediated CRISPR-Cas9 gene editing to disrupt the gene encoding cytochrome P450 oxidoreductase (Cypor), combined with transient administration of acetaminophen (APAP), to repopulate the liver with healthy hepatocytes and rescue a phenylketonuria mouse model. This study aimed to investigate electroporation-mediated delivery of Cypor-targeting CRISPR-Cas9 ribonucleoproteins into wild-type hepatocytes, combined with liver engraftment under APAP treatment, as an in vivo selection approach in a mouse model of homozygous familial hypercholesterolemia (Ldlr−/−). Electroporation provides higher delivery efficiency compared to lipid nanoparticles. We observed engraftment levels up to 13% engraftment of electroporated Cypor-deficient hepatocytes with indels in the liver of Ldlr−/− mice after transient APAP administration, while negligible engraftment was observed in no-APAP controls (mean 9% and 2%, respectively, p = 0.0121). The engraftment of Cypor-deficient Ldlr+/+ hepatocytes was associated with reductions in LDL-cholesterol (18%) and triglycerides (52%) compared to the untransplanted control Ldlr−/− mice fed a Western diet for 5 weeks, but offered no protection from the development of diet-induced aortic root atherosclerosis or liver steatosis. While biochemical markers for liver damage normalized after discontinuation of APAP, we observed persistent lipid accumulation in the liver of Ldlr−/− mice grafted with Cypor-deficient Ldlr+/+ hepatocytes, likely stemming from the impact of Cypor deficiency on cholesterol clearance. Therefore, the combination of CRISPR-Cas9-mediated Cypor knockdown to induce clonal expansion of gene-edited hepatocytes using transient APAP administration is not a viable therapeutic strategy for familial hypercholesterolemia due to the essential role of Cypor in cholesterol metabolism. Unlike findings from phenylketonuria mouse model studies, the loss of Cypor function could not be compensated by unedited native hepatocytes in Ldlr−/− mice. Collectively, our results demonstrate that electroporation is a viable and informative approach for evaluating gene editing strategies for the treatment of inherited metabolic diseases that affect the liver. Our electroporation procedure revealed that a one-size-fits-all gene editing strategy may not be universally applicable for treating inherited metabolic liver disorders. Tailored gene editing and selection strategies may be needed for different liver disorders. Full article
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14 pages, 1900 KiB  
Article
Implementation of a Hybrid Cardiac Rehabilitation and Symptom Scoring System in Patients with Inappropriate or Postural Sinus Tachycardia Referred for Sinus Node Sparing Hybrid Ablation
by Marta Kornaszewska, Aleksandra Wilczek-Banc, Anna Ratajska, Ewa Piotrowicz, Bartosz Szkaradek, Mariusz Kowalewski, Piotr Suwalski, Natalia Ogorzelec, Antoni Wileczek, Magdalena Zając, Michał Pastyrzak and Sebastian Stec
J. Clin. Med. 2025, 14(16), 5879; https://doi.org/10.3390/jcm14165879 - 20 Aug 2025
Abstract
Background/Objectives: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure [...] Read more.
Background/Objectives: Patients with inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) exhibit complex clinical profiles due to autonomic dysfunction. While sinus node sparing (SNS) hybrid ablation is emerging as a promising therapy, there are no established guidelines worldwide for post-procedure patient management and care is mainly based on telemonitoring. In contrast, our hybrid cardiac rehabilitation (HCR) program integrates inpatient care and home-based telerehabilitation. We aim to evaluate the implementation of the HCR program, patient acceptance and adherence, and the effectiveness of the Malmö POTS scoring system in monitoring disease progression and rehabilitation outcomes. Methods: Patients underwent a personalized HCR program after SNS. The program included early mobilization, psychological support, respiratory therapy, and structured exercise. Clinical outcomes were assessed using symptom burden (Malmö POTS score), ECG parameters, exercise duration, perceived exertion, and rehabilitation adherence. Results: All patients completed the inpatient phase, and 87% completed the home-based phase. In the early postoperative period, pericarditis, anemia, and benign rhythm disturbances were mild and self-limiting. The Malmö POTS score decreased from 65.3 to 25.7. Lower perceived exertion early in the program correlated with clinical improvement. At the 2-month follow-up, 81% of patients no longer met the clinical criteria for IST/POTS without the use of medications. The program was evaluated as safe, feasible, and well-tolerated, with high patient satisfaction. Conclusions: A well-organized hybrid cardiac rehabilitation program after SNS is feasible, safe, and well-tolerated in IST/POTS patients. The Malmö POTS score may support outcome monitoring. The integration of individualized training and telemedicine represents a promising development for patients post-SNS ablation. While this study demonstrates feasibility and potential benefits, further controlled studies are needed to evaluate its impact on long-term recovery and symptom control. Full article
(This article belongs to the Special Issue Recent Clinical Advances in Cardiac Rehabilitation)
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11 pages, 377 KiB  
Article
Coronary Artery Disease in People Living with HIV May Reflect Their Sensitivity to Inflammation Associated with Cytomegalovirus
by Luna-faye Veld, Shelley Waters, Silvia Lee, Anna C. Hearps, Janine Trevillyan, Ari S. Mushin, Damien Foo, Jennifer Hoy and Patricia Price
Pathogens 2025, 14(8), 822; https://doi.org/10.3390/pathogens14080822 - 20 Aug 2025
Abstract
Cytomegalovirus (CMV) is implicated in cardiovascular disease in healthy adults and after transplantation, but analyses in people living with HIV (PLWH) are difficult as almost all have CMV co-infections. Here, we address whether coronary artery disease (CAD) is associated with levels of CMV-reactive [...] Read more.
Cytomegalovirus (CMV) is implicated in cardiovascular disease in healthy adults and after transplantation, but analyses in people living with HIV (PLWH) are difficult as almost all have CMV co-infections. Here, we address whether coronary artery disease (CAD) is associated with levels of CMV-reactive antibodies or with sensitivity to inflammation associated with CMV. PLWH stable on antiretroviral therapy (ART) with a recent diagnosis of CAD were matched with PLWH without CAD. Plasma samples stored at the time of the CAD event and 6, 12, 24 or 36 months earlier (n = 34–55 per group) were used for analyses. Antibodies reactive with a lysate from CMV infected cells were quantitated using an in-house ELISA, and inflammatory biomarkers were assessed using commercial kits. Bivariate analyses demonstrated similar levels of CMV antibodies in PLWH with and without CAD at all time points (p > 0.5). However, in PLWH with CAD, levels of CMV antibody correlated directly with plasma sCD14, LBP, CXCL10 and/or IL-6 at the earlier points. These correlations were not impacted by detectable plasma HIV RNA. Our findings suggest that individual differences in sensitivity to the inflammatory effects of CMV impact upon the development of CAD. Full article
(This article belongs to the Special Issue Immune Pathways and Mechanisms Involved in Viral Infections)
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23 pages, 3537 KiB  
Review
Therapeutic Potential of Stem Cell-Derived Exosomes in Skin Wound Healing
by ChanBee Jo, Yun Ji Choi and Tae-Jin Lee
Biomimetics 2025, 10(8), 546; https://doi.org/10.3390/biomimetics10080546 - 20 Aug 2025
Abstract
Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including [...] Read more.
Chronic skin wounds are difficult to heal or nonhealing. These wounds may become infected and progress to tissue necrosis, potentially leading to limb amputation, sepsis, reduced quality of life, depression, economic burden on the healthcare system, and social isolation. Several clinical strategies, including negative pressure wound therapy, antibiotic-based infection control, and wound debridement, have been developed to treat skin wounds. However, these approaches primarily target local wound conditions and offer only short-term relief, not achieving sustained functional regeneration. Stem cell-based therapy has emerged as an alternative therapeutic method for skin wound treatment owing to its ability to suppress inflammation, stimulate angiogenesis, and promote cellular proliferation. However, the low post-transplantation survival rate of stem cells remains a major limitation. Exosomes, nanosized extracellular vesicles, transport proteins, lipids, mRNAs, and miRNAs and mediate regenerative functions, including anti-inflammatory effects, angiogenesis promotion, and extracellular matrix remodeling. Stem cell-derived exosomes (SC-Exos) offer several advantages over their parent cells, including greater stability, lower immunogenicity, absence of tumorigenic risks, and ease of storage and distribution. These attributes render SC-Exos particularly attractive for cell-free regenerative therapies. In this review, we introduce exosomes derived from various types of stem cells and explore their therapeutic applications in skin wound regeneration. Full article
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10 pages, 2189 KiB  
Case Report
Challenging the Dogma: Reversal of End-Stage Liver Fibrosis with Tirzepatide in MASH Cirrhosis
by Thuy-Duyen Nguyen, Dora Lam-Himlin, Blanca Lizaola-Mayo and David Chascsa
Transplantology 2025, 6(3), 25; https://doi.org/10.3390/transplantology6030025 - 20 Aug 2025
Abstract
Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like [...] Read more.
Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression. Full article
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15 pages, 1243 KiB  
Article
Value of 18F-FDG PET/CT Scans in Staging and Follow-Up of Pediatric Langerhans Cell Histiocytosis: Comparison to CT and/or MRI
by Maria F. Dien Esquivel, Abdullah AlMutawa, Afsaneh Amirabadi, Sheila Weitzman, Ilia Buhtoiarov, Andrea S. Doria, Amer Shammas, Oussama Abla and Reza Vali
Children 2025, 12(8), 1089; https://doi.org/10.3390/children12081089 - 20 Aug 2025
Abstract
Background/Objectives: The purpose of this study is to determine the added value of 18F-FDG PET/CT scan in pediatric LCH compared to other imaging modalities (CT and MRI) at initial staging, during assessment of disease reactivation, and after treatment. Methods: This is a [...] Read more.
Background/Objectives: The purpose of this study is to determine the added value of 18F-FDG PET/CT scan in pediatric LCH compared to other imaging modalities (CT and MRI) at initial staging, during assessment of disease reactivation, and after treatment. Methods: This is a retrospective study of children diagnosed with LCH between 1 June 2007 and 8 December 2022 who met the inclusion criteria. 18F-FDG PET CT imaging was compared to CT and/or MRI when available. The interclass correlation coefficient (ICC) was used to assess the agreement between methods. p-Values of less than 0.05 were considered statistically significant. Results: A total of 39 children had undergone 18F-FDG PET/CT studies. Median (range) age at presentation was 10 years (1.3–17 y), with a female-to-male ratio of 0.7:1. Excellent concordance (ICC = 1; p < 0.0001) between 18F-FDG PET/CT and other imaging methods was found. Median SUVmax of the positive FDG-avid lesions at initial staging was 2.7 [range 1.3–16.7]. Conclusions: 18F-FDG PET/CT has been shown to be complementary to diagnostic CT and MRI, with the advantage of demonstrating additional metabolic information at initial staging, during assessment of disease reactivation, and to assess interval changes post therapy. These preliminary findings warrant further investigation. Full article
(This article belongs to the Section Pediatric Radiology)
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12 pages, 6157 KiB  
Case Report
Primary Hepatic Mucosa-Associated B-Cell Lymphoma in a Patient with Primary Sclerosing Cholangitis—A Case Ultimately Requiring Liver Transplantation
by Jerica Novak, Mihajlo Đokić, Miha Petrič, Diana Vozlič, Milanka Živanović, Branislava Ranković and Blaž Trotovšek
Diagnostics 2025, 15(16), 2082; https://doi.org/10.3390/diagnostics15162082 - 19 Aug 2025
Abstract
Background: Primary hepatic extranodal marginal zone lymphoma of mucosa-associated type (MALT) is an extremely rare liver neoplasm. The lesions are often misdiagnosed for the most common primary hepatic malignancy, such as hepatocellular carcinoma and cholangiocarcinoma. As the diagnosis is most often made after [...] Read more.
Background: Primary hepatic extranodal marginal zone lymphoma of mucosa-associated type (MALT) is an extremely rare liver neoplasm. The lesions are often misdiagnosed for the most common primary hepatic malignancy, such as hepatocellular carcinoma and cholangiocarcinoma. As the diagnosis is most often made after the resection, there are still no clear guidelines for the optimal treatment of these patients. Case Presentation: A 30-year-old male patient with known primary sclerosing cholangitis (PSC) was treated at the Department of Abdominal Surgery Ljubljana due to a mass in the right liver, believed to be an intrahepatic cholangiocarcinoma. Due to the extent of the disease, extended right hepatectomy with the resection of the hepatocholedochus, lymphadenectomy, and hepaticojejunal anastomosis were performed. After the surgery, the patient developed a small-for-size syndrome and therefore necessitated a liver transplantation (LT) that was afterwards successfully performed. Discussion: This case highlights the diagnostic challenges of differentiating primary hepatic MALT lymphoma from cholangiocarcinoma on imaging, especially in patients with underlying liver disease. Preoperative confirmation of the malignant disease could potentially change treatment course in our patient. Therefore, a serious surgical complication with development of small-for-size syndrome after major hepatectomy could potentially be prevented. Regarding the underlying liver disease, the patient could probably be a candidate for LT with the bridging chemotherapy. Conclusions: Primary hepatic MALT lymphoma is an extremely rare liver lesion but remains a valid option in a differential diagnosis of liver lesions in patients with chronic viral infection or autoimmune disease, especially in settings of cirrhosis. Moreover, a high level of suspicion must be raised in young patients with solitary liver mass and autoimmune liver disease. Surgical resection is the best way to achieve elimination of the disease. Full article
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11 pages, 1014 KiB  
Article
Clonal Hematopoiesis and Outcomes After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with AML, Myeloma, and Lymphoma
by Corinne Natalie Schmid, Katharina Sponagel, Ulrike Bacher, Katja Seipel, Naomi Porret, Gertrud Wiedemann, Michèle Hoffmann, Michael Daskalakis and Thomas Pabst
Int. J. Mol. Sci. 2025, 26(16), 8021; https://doi.org/10.3390/ijms26168021 - 19 Aug 2025
Abstract
Autologous stem cell transplantation (ASCT) after high-dose chemo-therapy (HDCT) is an option of consolidation therapy in patients with AML, lymphoma, or myeloma. Clonal hematopoiesis (CH) is a premalignant state, associated with an increased risk of hematological cancer. The incidence of CH in patients [...] Read more.
Autologous stem cell transplantation (ASCT) after high-dose chemo-therapy (HDCT) is an option of consolidation therapy in patients with AML, lymphoma, or myeloma. Clonal hematopoiesis (CH) is a premalignant state, associated with an increased risk of hematological cancer. The incidence of CH in patients with AML, myeloma, and lymphoma and its effect on the outcome after HDCT/ASCT remain poorly studied. Here we screened 142 patients treated with HDCT/ASCT between 2002 and 2021 at Bern University Hospital for somatic gene mutations in ASXL1, DNMT3A, JAK2, TET2, and TP53. CH-associated somatic gene mutations were detected in 14/31 AML patients (45%), 13/64 myeloma patients (20%), and 9/47 lymphoma patients (19%). Clinical characteristics, treatment modalities, and responses to treatment were similar in patients with and without CH. Patients with CH-associated gene mutations had higher relapse rates and reduced progression free survival, most evident in lymphoma patients (p = 0.007). Overall survival tended to be shorter in lymphoma patients with CH-associated mutations (p = 0.078), whereas this was not observed in AML and myeloma patients. Survival in lymphoma patients with CH was inferior, which may have an impact on post-transplant surveillance strategies in the future. In contrast, survival outcomes were not associated significantly with CH in AML and myeloma patients in our study. Longer follow-ups and larger cohorts will be needed to validate our observations. Full article
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