Search Results (2,190)

Background/Objectives: Liver fibrosis is a progressive consequence of chronic liver injury that can evolve into cirrhosis, liver failure, or hepatocellular carcinoma, representing a major global health burden. Fibrogenesis is driven by hepatic stellate cell (HSC) activation, excessive extracellular matrix deposition, and structural disruption of liver tissue, with transforming growth factor-β (TGF-β) signaling and inflammatory mediators as central pathways. Current therapies primarily target the underlying causes, which may halt disease progression but rarely reverse established fibrosis. This review aims to outline current and emerging therapeutic strategies for liver fibrosis, informing both clinical practice and future research directions. Methods: A narrative synthesis of preclinical and clinical evidence was conducted, focusing on pharmacological interventions, microbiota-directed strategies, and innovative modalities under investigation for antifibrotic activity. Results: Bile acids, including ursodeoxycholic acid and derivatives, modulate HSC activity and autophagy. Farnesoid X receptor (FXR) agonists, such as obeticholic acid, reduce fibrosis but are limited by adverse effects. Fatty acid synthase inhibitors, exemplified by denifanstat, show promise in metabolic dysfunction-associated steatohepatitis (MASH). Additional strategies include renin–angiotensin system inhibitors, omega-3 fatty acids, and agents targeting the gut–liver axis. Microbiota-directed interventions—probiotics, prebiotics, symbiotics, antibiotics (e.g., rifaximin), and fecal microbiota transplantation—are emerging as potential modulators of barrier integrity, inflammation, and fibrogenesis, though larger clinical trials are required. Reliable non-invasive biomarkers and innovative trial designs, including adaptive platforms, are essential to improve patient selection and efficiently evaluate multiple agents and combinations. Conclusions: Novel modalities such as immunotherapy, gene editing, and multi-targeted therapies hold additional potential for fibrosis reversal. Continued translational efforts are critical to establish safe, effective, and accessible treatments for patients with liver fibrosis. Full article

Background/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the factors that determine functional recovery remain uncertain. The primary objective of this study was to characterize patients who recover ventricular function. Secondary objectives included analyzing VA-ECMO-related complications and overall patient survival. Methods: This was a retrospective, single-center, observational study including all consecutive patients diagnosed with FM between 2008 and 2025 who were supported with VA-ECMO (n = 22). Clinical, biochemical, echocardiographic, and imaging variables were collected. Patients were classified based on their outcomes as either recovery or death/transplantation. Differential factors potentially affecting myocardial recovery, survival, and complications were analyzed. Results: The mean age was 49.7 ± 11 years, with 36% being male. Severe cardiogenic shock was the most common initial presentation (86%), and the average time from symptom onset to hospital admission was 5.7 days. Regarding mechanical support, the non-recovery group required longer ECMO support (328 ± 225 h vs. 188 ± 103 h; p = 0.03). The presence of fibrosis on cardiac magnetic resonance imaging (MRI) was associated with a lower probability of recovery (100% vs. 44.4%; p = 0.03). Renal failure and vascular complications were more frequent in the non-recovery group, with a significantly higher rate of surgical reintervention (50% vs. 10%; p = 0.04). Echocardiography performed before discharge (recovery group) vs. before death/transplant (non-recovery group) showed significant differences in left ventricular ejection fraction (51.1% vs. 29.5%; p = 0.04), along with better levels of creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), leukocytes, and C-reactive protein (CRP) in the recovery group. In-hospital survival for the entire cohort was 63.6%, significantly higher in the recovery group (100% vs. 33.3%; p < 0.01). One-year survival was 59%, which was also greater among those who recovered (90% vs. 33.3%; p = 0.02). Conclusions: FM is associated with an acceptable in-hospital survival rate. The presence of myocardial fibrosis on MRI and longer ECMO support duration were observed to be associated with a lower likelihood of cardiac recovery. Patients who recovered showed better ventricular function at discharge, as well as reduced systemic inflammation and renal dysfunction. These findings highlight the importance of early identification of predictors of myocardial recovery to optimize management and therapeutic decision making in this high-risk population. Full article

The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β₂-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability. Full article

Hemorrhagic stroke is a severe cerebrovascular disease with a high rate of disability and mortality. Its complex pathological mechanisms, such as blood–brain barrier damage, neuroinflammation, and oxidative stress, along with the restrictive nature of the blood–brain barrier, have restricted the clinical therapeutic effects of drugs. Nanotechnology, with its advantages of targeting ability, biocompatibility, and multifunctionality, has provided a new approach for the precise diagnosis and treatment of hemorrhagic stroke. In terms of diagnosis, imaging technology enhanced by magnetic nanoparticles can achieve real-time bedside monitoring of hematoma dynamics and cerebral perfusion, significantly improving the timeliness compared with traditional imaging methods. In the field of treatment, the nanodrug delivery system can remarkably improve the bioavailability and brain targeting of clinical drugs and herbal medicines by enhancing drug solubility, crossing the blood–brain barrier, and responsive and targeting drug release. Multifunctional inorganic nanomaterials, such as cerium oxide nanoparticles, graphene, and perfluorooctyl octyl ether nanoparticles, can alleviate brain edema and neuronal damage through antioxidant and anti-inflammatory effects, and the scavenging of free radicals. Moreover, gene delivery mediated by nanocarriers and stem cell transplantation protection strategies have provided innovative solutions for regulating molecular pathways and promoting nerve repair. Although nanotechnology has shown great potential in the diagnosis and treatment of hemorrhagic stroke, its clinical translation still faces challenges such as the evaluation of biosafety, standardization of formulations, and verification of long-term efficacy. In the future, it is necessary to further optimize material design and combine multimodal treatment strategies to promote a substantial breakthrough in this field from basic research to clinical application. Full article

Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment. Full article

Iris laevigata is an ornamental plant and so its wild genetic resources need to be protected. However, traditional inefficient propagation limits its landscape applications. In this study, we assessed the effects of phytohormones on growth of I. laevigata at various culture stages using roots and hypocotyls as explants and established an efficient micropropagation system. The highest callus induction of hypocotyl (75.0%) was obtained using Murashige and Skoog medium containing 6-benzylaminopurine (6-BA), 0.5 mg L⁻¹ + 2,4-dichlorophenoxyacetic acid (2,4-D), 1.0 mg L⁻¹ + 1-naphthylacetic acid (NAA), and 0.4 mg L⁻¹. Similarly, the highest callus induction (73.3%) of roots was achieved with 6-BA 0.5 mg L⁻¹ + 2,4-D 0.5 mg L⁻¹ + NAA 0.4 mg L⁻¹. The calli induced from hypocotyl and root tissues achieved 39.7% and 49.5% adventitious shoot induction on a medium containing indole-3-butyric acid (IBA) 0.5 mg L⁻¹ + 6-BA 1.5 mg L⁻¹ + NAA 1.0 mg L⁻¹ and 6-BA 2.0 mg L⁻¹ + NAA 0.4 mg L⁻¹ + kinetin (KT) 1.0 mg L⁻¹, respectively. The rooting of adventitious shoots reached 93.3% in the medium supplemented with NAA 0.2 mg L⁻¹. The survival of regenerated plants reached 90.0% after being transplanted into soil. This study provides an efficient and reliable propagation method for I. laevigata for landscape applications and the preservation of wild genetic material. Full article

Background: Autologous osteochondral transplantation (AOT)—the transfer of hyaline cartilage with its underlying subchondral bone—is well established for focal osteochondral lesions, yet evidence for larger (>200 mm²) defects is limited. We assessed clinical and functional outcomes of AOT in patients with osteochondral knee lesions exceeding 200 mm². Methods: In this retrospective cohort study, 52 patients underwent AOT for full-thickness osteochondral defects of the femoral condyles or patellofemoral joint. All lesions were ≥200 mm² and treated with a standardized press-fit technique using one to four overlapping cylindrical grafts. Pain and knee function were evaluated preoperatively and at 3, 6, and 12 months postoperatively with the Visual Analogue Scale (VAS), Tegner–Lysholm Knee Score (TLKS), and Knee Society Score (KSS). Results: Mean defect size was 224.4 ± 84.5 mm². The VAS improved from 6.32 ± 1.1 preoperatively to 0.72 ± 0.6 at 12 months (p < 0.001). The TLKS rose from 58.6 ± 11.4 to 95.0 ± 6.8 and the KSS from 63.8 ± 12.2 to 97.4 ± 4.9 during the same period (both p < 0.001). Most gains occurred within the first 3–6 months and were sustained at 12 months. No major surgical complications were observed, and outcomes were unaffected by age, sex, or graft number/size. Conclusions: AOT is a safe, effective option for large osteochondral knee defects (>200 mm²), offering rapid, durable pain relief and excellent functional recovery while preserving native joint structures. Accurate donor site reconstruction and precise graft placement in the weight-bearing zone appear critical for optimal results. Longer-term prospective studies are needed to confirm durability and refine patient-selection criteria. Full article

The human gut microbiota is a complex ecosystem that influences host metabolism, immune function, and cardiovascular health. Dysbiosis, defined as an imbalance in microbial composition or function, has been linked to the development and progression of atherosclerosis. This connection is mediated by microbial metabolites that enter the systemic circulation and interact with vascular and immune pathways. Among these, trimethylamine N-oxide (TMAO) has been most extensively studied and is consistently associated with cardiovascular events. Other metabolites, including lipopolysaccharides (LPS), short-chain fatty acids (SCFAs), and secondary bile acids, also contribute by modulating inflammation, endothelial function, and lipid metabolism. Recent research has expanded to emerging metabolites such as indoxyl sulfate, indole-3-propionic acid, and polyamines, which may provide additional mechanistic insights. These microbial products are increasingly explored as biomarkers of cardiovascular risk. TMAO has shown predictive value in large human cohorts, while microbiota composition and diversity measures remain less consistent across studies. However, interpretation of these biomarkers is limited by methodological variability, interindividual differences, and lack of standardization. Therapeutic interventions targeting the gut–heart axis are under investigation. Dietary strategies such as the Mediterranean diet and fiber-rich nutrition, probiotics and prebiotics, and fecal microbiota transplantation (FMT) show promise, while pharmacological approaches targeting TMAO or bile acid pathways are in early stages. This review summarizes current knowledge on the mechanistic, diagnostic, and therapeutic links between the gut microbiota and atherosclerosis, highlighting both established findings and emerging directions for future research. Full article

End-stage chronic kidney disease remains a global challenge, with dialysis and transplantation offering only partial or limited solutions. Recent advances in bioengineering have introduced modular strategies that aim to restore kidney function not by replicating the entire organ, but by rebuilding it one segment at a time. Platforms such as kidney organoids, implantable bioartificial kidneys, 3D-bioprinted tissues, and decellularized scaffolds each target specific nephron functions, from filtration to endocrine signaling. This Perspective examines how these technologies can be integrated into interoperable systems that reflect the nephron’s native structure and functional complexity. We assess translational readiness across key benchmarks, including vascular integration, hormonal responsiveness, immune compatibility, and implantability, and discuss the ethical, regulatory, and design considerations that will shape their clinical future. Collectively, these modular strategies offer a pathway toward more personalized, scalable, and physiologically relevant approaches to kidney replacement. Full article

Chronic kidney disease (CKD) is a fast-growing cause of death worldwide. Systemic hypertension and diabetes mellitus are the major causes of kidney damage leading to a reduction in glomerular filtration rate and to urinary protein loss. Sodium–glucose cotransporter 2 inhibitors (SGLT2is) are drugs able to address both of these deleterious effects, preventing kidney damage from progressing. Initially born as hypoglycemic agents, SGLT2is subsequently proved to have not only positive metabolic but also pleiotropic effects on the kidney and the cardiovascular system. Indeed, they improve the metabolic profile, reducing uric acid, blood sugar levels, and body weight. Moreover, they exert an anti-inflammatory and antifibrotic effect, reducing endothelial dysfunction and reactive oxygen species (ROS) production. Finally, they reduce renal hyperfiltration and control blood pressure, inducing osmotic diuresis and restoring tubulo-glomerular feedback. All these metabolic, anti-inflammatory, and hemodynamic effects contribute to significantly reducing the risk of cardiorenal events, as widely demonstrated in randomized clinical trials. The pleiotropic actions of SGLT2is together with their good tolerability make them a pillar treatment of CKD regardless of the presence of diabetes mellitus. Further studies will be needed in order to expand the indications to populations previously excluded from clinical trials such as transplant recipients or glomerulonephritis patients. This narrative review aims to summarize current knowledge regarding the nephroprotective mechanisms of SGLT2is which, after initial use as a hypoglycemic agent, have assumed a pivotal role in the actual and future management of patients with CKD. Full article

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment. Full article

Adipose-derived mesenchymal stem cells (ASCs) have great potential in regenerative medicine due to their abundance and innate multi-lineage differentiation potential. However, the therapeutic efficacy of ASCs is often compromised by poor microenvironmental conditions in the damaged tissues after transplantation. In this study, we generated and assessed genetically modified ASCs that expressed granulocyte chemotactic protein-2 (GCP-2) and platelet-derived growth factor-β (PDGF-β). The results revealed that three-dimensional (3D)-cultured ASCs overexpressing GCP-2 and PDGF-β (3D-A/GP) yielded a significant increase in proangiogenic gene expression, cell migration, and endothelial tube formation in vitro. Moreover, the Matrigel plug assay revealed that 3D-A/GP formed functional blood vessels, and 3D-A/GP injection in a hind limb ischemia (HLI) model revealed higher blood flow recovery, limb salvage, and capillary density and lower apoptosis in mice, compared to the controls. Notably, 3D-A/GP exhibited differentiation into endothelial-like cells and upregulated expression of angiogenic factors in ischemic limb tissue. Our results highlight the value of using a combination of genetic engineering and 3D culture systems to improve the therapeutic effect of ASCs in terms of angiogenesis-dependent tissue repair. The dual modulation of GCP-2 and PDGF-β, in combination with 3D culture, presents a new and synergistic opportunity to maximize the use of ASC-based therapies for ischemic diseases and other regenerative medicine applications. Full article

Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota–gut–brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota—dysbiosis—are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson’s and Alzheimer’s. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome—including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)—which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application. Full article

Background/Objectives: To evaluate the impact of the European–Mediterranean Postgraduate Program on Organ Donation and Transplantation (EMPODaT) on organ donation and transplantation (ODT) at 6 years. Methods: EMPODaT is a Trans-European Mobility Programme for University Studies (TEMPUS) project founded by the European Commission to address ODT professionals’ shortage in Middle East/North Africa (MENA) countries through structured postgraduate education. Leading universities from Spain, Germany, Sweden, and France, and key institutions in Egypt, Lebanon, and Morocco, developed a one-year blended training program incorporating e-learning, in-person courses, and hospital traineeships. The effect of the program at 6 years was analyzed by surveying the 90 healthcare participants. Results: A total of 73.9% of respondents remained actively engaged in the field, and some assumed leadership roles (local directors 14.4%, donor coordinators 13%). Also, 65.2% of participants reported improvements in policies and practices, with notable progress in donor screening (39.1%), brain death diagnosis (30.4%), and hospital policy reforms (69.7%). The study identified barriers, such as legal (34.4%), financial (34.8%), and public/social resistance (39.1%). Training alone, without strong hospital policies, support, and government involvement, was insufficient for introducing meaningful changes in ODT. Conclusions: Key aspects for successful implementation of training programs on ODT in MENA countries should consider hospital leadership engagement, strengthen institutional collaborations, and incorporate national health authorities to enhance sustainability and drive systemic changes. Prioritizing individuals in key decision-making positions could further enhance program effectiveness. Full article

Historically, colorectal liver metastases (CRLMs) have been considered a contraindication for liver transplantation (LT), primarily due to limited organ availability and concerns about oncologic efficacy. However, emerging evidence indicates that highly selected patients with unresectable CRLM can achieve long-term survival following LT—often with outcomes superior to those obtained through conventional systemic therapies. To evaluate the evolving role of LT in this setting, we conducted a scoping review of the literature. A comprehensive search was performed across PubMed, Embase, Web of Science, Scopus, and ClinicalTrials.gov, as well as ProQuest Dissertations & Theses and Google Scholar to capture gray literature. The search included English-language articles published between January 2015 and April 2025. Eligible studies included those reporting on the application of LT for patients with unresectable CRLM. This scoping review synthesizes current evidence on patient selection criteria, overall and disease-free survival, recurrence patterns, and emerging biomarkers that may guide transplant eligibility. In addition, we explore innovations in organ utilization—including living donor LT and machine perfusion technologies—that aim to expand access while addressing ethical concerns related to organ allocation. As LT for CRLM transitions from investigational use to clinical implementation, this review outlines the key challenges and future opportunities that will shape its role in the landscape of transplant oncology. Full article