Search Results (197)

Cardiac fibrosis following myocardial infarction plays a critical role in the formation of scar tissue and contributes to ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. Current clinical diagnostics use electrical and structural markers, but lack precision due to low spatial resolution and absence of molecular information. In this paper, we employed line scan Raman microspectroscopy to classify sheep myocardial tissue into muscle, necrotic, granulated, and fibrotic tissue types, using collagen as a molecular biomarker. Three spectral regions were evaluated: region A (600–2960 cm⁻¹), region B (600–1399 cm⁻¹ and 1751–2960 cm⁻¹), and region C (1400–1750 cm⁻¹), which includes the prominent collagen-associated peaks at 1448 cm⁻¹ and 1652 cm⁻¹. Linear and nonlinear principal component analysis (PCA) and support vector machines (SVMs) were applied for dimensionality reduction and classification, with nonlinear models specifically addressing the nonlinearity of collagen formation during fibrogenesis. Histological validation was performed using Masson’s trichrome staining. Raman bands associated with collagen in region C consistently outperformed regions A and B, achieving the highest explained variance and best class separation in both binary and multiclass PCA models for both linear and nonlinear approaches. The ratio of collagen-related peaks enabled stage-dependent tissue characterization, confirming the nonlinear nature of fibrotic remodeling. Our findings highlight the diagnostic potential of collagen-associated Raman bands for characterizing myocardial fibrosis. The proposed PCA-SVM framework demonstrates robust performance even with limited sample size and has the potential to lay the foundation for real-time intraoperative diagnostics. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Background/Objectives: The aim of this study is to identify markers and develop a multifactorial model for characterizing extensive scar tissue after revascularization in patients with myocardial infarction (MI). Methods: A total of 123 patients with MI were examined. The patients underwent contrast-enhanced cardiac magnetic resonance imaging (MRI) with a 1.5 Tesla GE SIGNA Voyager (GE HealthCare, Chicago, IL, USA) on the 7th–10th days from the onset of the disease. At the first stage, we performed a comparative analysis and built a multifactorial model based on the examination results of 92 (75%) patients enrolled from April 2021 to October 2023. These patients formed the group used for model development, or the “modeling group”. The mass of the scar was calculated, including relative to the left ventricular (LV) myocardium mass (M_scar/LVMM, in %). Results: The first subgroup consisted of 36 (39%) patients with a large scar, denoted as “LS” (M_scar/LVMM > 20%). The second subgroup included 56 (61%) patients with a smaller scar, referred to as “SS” (M_scar/LVMM ≤ 20%). Logistic regression was used to identify independent factors affecting scar tissue size. A multifactorial model was created. This model predicts M_scar/LVMM > 20% on MRI. It uses readily available clinical parameters: high-sensitivity troponin I (HscTn I) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and LV relative wall thickness (RWT). We tested the multifactorial model on the “modeling group” (n = 31). The sensitivity was 63.6% and the specificity was 85.7%. Conclusions: These indicates the feasibility of its application in clinical practice. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

With alopecia affecting millions globally, recent advancements in the understanding of hair follicle biology have driven the development of novel therapies focused on hair regrowth. This review discusses two emerging therapeutic strategies: hair follicle neogenesis and the modulation of the Wnt/B-catenin signaling pathway. Hair follicle neogenesis, a frontier once considered impossible to achieve in adult humans, has recently gained traction due to advancements in stem cell biology and further understanding of the epithelial–mesenchymal interactions that are critical to hair follicle development. Such an approach shows significant potential for addressing conditions leading to hair loss, such as androgenetic and scarring alopecias. The Wnt/B-catenin signaling pathway, a critical intracellular pathway responsible for hair follicle cycles, has gained traction as a target for therapeutic interventions. Studies show that stimulating this pathway leads to hair follicle growth, while its inhibition prompts hair follicle regression. Investigations demonstrate clinical efficacy of small molecule inhibitors and peptides, such as PTD-DBM, which activates the Wnt/β-catenin pathway by interfering with CXXC5, a negative regulator that inhibits pathway activation. Such therapies show potential as more effective treatment options than existing solutions such as finasteride and minoxidil. Adjunctive therapies, such as low-level laser therapy, have also shown clinical efficacy, further highlighting how modulation of this pathway stimulates follicular regrowth. While these novel therapies require further research to validate their efficacy and to gain additional insight into their risk profile, it is clear that alopecia treatment is approaching a new frontier beyond traditional pharmacologic interviews, with regenerative medicine and pathway modulation paving the way forward. Full article

Background: The Profunda Artery Perforator (PAP) flap is a viable alternative to the Deep Inferior Epigastric Perforator (DIEP) flap, particularly for patients with low BMI and therefore insufficient abdominal tissue. To reduce the high complication rate, especially in our low BMI patient population, we have adapted the use of the vertical skin island design. This study compares complication rates and long-term outcomes of vertical versus horizontal skin island designs in PAP flap breast reconstruction. Methods: This prospective, single-center study included 20 patients who underwent PAP flap breast reconstruction. Quality of life and scar quality were assessed using the BREAST-Q and POSAS questionnaires. Additionally, the cosmetic outcomes were analyzed by four plastic surgeons. Results: Mean BMI in the vertical group was 23.9 kg/m² and 22.7 kg/m² in the horizontal group. Mean flap weight was 326 g for the vertical group and 355 g for the horizontal group. Fewer complications were observed at the donor site in the vertical group (Clavien–Dindo Classification 3b at donor site: p = 0.25). The BREAST-Q evaluation revealed significantly better results regarding the psycho-social well-being (p = 0.04) in patients with the horizontalskin island design. Scar evaluation using the POSAS revealed that the scar was perceived as thinner (p = 0.02), less pigmented (p = 0.03), and showed less relief (p = 0.02) in the vertical group. No significant difference was observed in the overall scar assessment by observers (p = 0.46). The aesthetic analysis by plastic surgeons showed significantly better results in the horizontal group. Conclusions: The vertical skin island design in PAP flap breast reconstruction was associated with lower complication rates and better scar quality compared to the horizontal design. Surgeons, however, rated the overall aesthetic outcome of the vertical design less favorably. These findings highlight the importance of balancing donor site morbidity with overall aesthetic results. Full article

Primary cutaneous lymphomas (PCLs) constitute a heterogeneous group of rare diseases. Previously, few studies have focused on the aspect of scalp involvement by PCLs. The objective of this study was to analyze the clinical presentation, diagnostic pathways, and treatment methods in patients diagnosed with scalp PCLs. A comprehensive literature review was conducted using the PubMed database, with the search terms “scalp” AND “cutaneous lymphoma”, “folliculotropic mycosis fungoides” AND “scalp”, “trichoscopy” AND “lymphoma”, and “dermoscopy” AND “scalp” AND “lymphoma.” The search was limited to articles published from database inception to May 2, 2024. Based on the title and abstract analysis, we included articles on PCLs involving the scalp. After a thorough review of the full manuscripts, several were excluded due to irrelevance, the absence of essential clinical data, discrepancies in patient age, gender, and diagnosis, and a lack of information pertinent to scalp PCLs. The literature search identified 1482 patients with scalp involvement in PCLs. Of the total number of cases, 1096 were diagnosed with B-cell PCLs, 384 with T-cell PCLs, and two cases lacked a precise PCL diagnosis. Primary cutaneous follicle center lymphoma was the most frequently reported B-cell PCL of the scalp, while mycosis fungoides was the most common T-cell PCL. Alopecia was observed in 69.0% of the patients analyzed, with the most prevalent form being non-scarring focal alopecia. It is imperative to consider the scalp in patients with PCLs, particularly in light of the knowledge that some lymphomas affecting the scalp exhibit a higher degree of aggressiveness. Full article

Prolonged healing time of acute burn wounds is associated with increased pain, infection, risk of scarring, poorer mobility and higher financial and emotional burden. Electrical stimulation (ES) reduces healing time in chronic wounds; however, its reported use on acute burn wounds is limited. This systematic review (SR) aimed to evaluate the relative benefit of ES compared to routine wound care on the healing time of acute burn wounds in adults. The online databases queried included Cochrane Database of SR’s, MEDLINE, EMBASE, PUBMED and CINAHL. The search criteria included RCTs involving the application of ES of varying voltage, duration and modality in acute burn patients aged ≥18 years. The primary outcome investigated was days to burn wound closure, while the secondary outcomes included edema and infection. Four RCTs were discovered, involving a total of 143 participants with a mean age 35.5 years. Two RCTs demonstrated (a) 36% (2.6 days) reduction in time to wound closure with ES (p < 0.001); and (b) significant reduction in wound area with ES (11.2 ± 3.2 cm², p < 0.001) compared to controls at 21 days. Two RCTs found ES promoted better wound-healing environments, reducing edema, bacterial infection, and biofilm. This review highlighted low-risk wound-healing benefits with ES as a feasible adjunct to routine burn care. Full article

Background/Objectives: Polysaccharides are complex molecules with a wide range of biological activities that can be used in various biomedical applications. In this work, the antiulcer effect and influence on the level of pro- and anti-inflammatory cytokines of Solanum tuberosum L. polysaccharide (STP) were studied. Methods: The antiulcer effect of STP was studied in the Okabe chronic peptic ulcer model by evaluating the influence of STP on the ulcer index in Wistar rats, comparing it to omeprazole and ranitidine. Dose-effect analysis was also carried out. The level of pro- and anti-inflammatory cytokines was studied using ELISA kits. Results: After treatment in the polysaccharide groups, ulcer healing is observed in 60–80% of cases, in the omeprazole group in 50%, and in the ranitidine group in 25%. STP intravenous injections lead to the formation of a more differentiated mucous membrane; no coarse scar tissue is formed, which is typical for control and comparison drugs. Glycan causes a significant acceleration of the healing of experimental peptic ulcers in rats. STP appears to modulate pro- and anti-inflammatory cytokines. On the fourth and tenth days, a significant decrease in the levels of pro-inflammatory cytokines IL-1b and IFN-γ was noted in the polysaccharide group compared to the control group, while the level of anti-inflammatory cytokine IL-4 significantly increased. Conclusions: Intravenous administration of STP leads to the restoration of functionality and effective tissue regeneration. The antiulcer activity of STP is based on the regulation of the pro- and anti-inflammatory balance. Full article

Body color is a key economic trait for Neocaridina denticulata sinensis, an important ornamental shrimp. Scarb1 may be an important mediator of astaxanthin uptake, changing the shrimp’s body color. To discover the relationship between scarb1 and the pigmentation of cherry shrimp, the expression profiles, RNAi, and SNP genotyping of scarb1 were studied. There were significant differences in four color populations and five development stages (p < 0.05). The highest expression level of scarb1 appeared in the red population and the pre-nauplius stage. Exposure to scarb1 dsRNA increased the number and development of chromatophores at the metanauplius stage, but almost no phenotypic changes were observed at the pre-zoea stage. There was a synonymous SNP (G1593A) with a significantly different genotype frequency between the red and yellow populations (p < 0.05). The above results suggested that scarb1 is involved in pigmentation by affecting the development of chromatophores. Full article

Background/Objectives: To assess the effectiveness of the levonorgestrel-releasing intrauterine device (LNG-IUD) compared to hysteroscopic resection for managing women with symptomatic cesarean scar defects (CSDs). Methods: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive search of four electronic databases was conducted to identify studies comparing LNG-IUD with hysteroscopic management for symptomatic CSDs. Studies reporting outcomes of bleeding and spotting days and effectiveness rates were included. Quality assessment was performed using the ROBINS-I and RoB-2 tools. Results: Three studies involving 344 patients met the inclusion criteria. At 6 months, LNG-IUD use significantly reduced total bleeding days (MD −4.13; 95% CI: −5.17 to −3.09; p < 0.00001) and spotting days (MD 1.90; 95% CI: 0.43 to 3.37; p = 0.01) compared to hysteroscopic treatment. By 12 months, LNG-IUD demonstrated superior effectiveness (OR 3.46; 95% CI: 1.53 to 7.80; p = 0.003), with fewer total bleeding days (MD −5.69; 95% CI: −6.55 to −4.83; p < 0.00001) and spotting days (MD 3.09; 95% CI: 1.49 to 4.69; p = 0.0002). Approximately 50% of LNG-IUD users experienced amenorrhea within 1 year. Conclusions: LNG-IUD offers a minimally invasive and effective alternative to hysteroscopic resection for women with symptomatic CSD and no desire for future pregnancies. Its role should be considered in clinical practice, but further research is needed to validate these findings and define its long-term benefits and limitations. Full article

Hand, Foot, and Mouth Disease (HFMD) is a viral illness caused by enterovirus infections. While the introduction of the enterovirus 71 (EV71) vaccine has significantly reduced the number of EV71-related cases, the continued spread of Coxsackievirus A16 (CVA16) remains a major public health threat. Previous studies have shown that human SCARB2 (hSCARB2) knock-in (KI) mice, generated using embryonic stem cell (ESC) technology, are susceptible to CVA16. However, these models have failed to reproduce the clinical pathology and neurotoxicity after CVA16 infection. Therefore, there is an urgent need for a more reliable and effective animal model to study CVA16. In this study, we successfully created a hSCARB2 KI mouse model targeting the ROSA26 locus using CRISPR/Cas9 gene editing technology. The application of CRISPR/Cas9 enabled stable and widespread expression of hSCARB2 in the model. After infection, the KI mice exhibited a clinical pathology that closely mimics human infection, with prominent limb weakness and paralysis. The virus was detectable in multiple major organs of the mice, with peak viral load observed on day 7 post-infection, gradually clearing thereafter. Further analysis revealed widespread neuronal necrosis and infiltration of inflammatory cells in the brain and spinal cord of the KI mice. Additionally, significant activation of astrocytes (GFAP-positive) and microglia (IBA1-positive) was observed in the brain, suggesting that CVA16 infection may induce limb paralysis by attacking neuronal cells. Overall, this model effectively replicates the neuropathological changes induced by CVA16 infection and provides a potential experimental platform for studying CVA16-associated pathogenesis and neurotoxicity. Full article

Cutaneous lupus erythematosus (CLE) is a chronic autoimmune skin disorder with limited therapeutic options, particularly for refractory discoid lupus (DLE), which often results in scarring and atrophy. Recent studies have identified miR-31, miR-485-3p, and miR-885-5p as key regulators of inflammation, apoptosis, and fibrosis in CLE skin lesions. This research investigates a novel topical miRNA therapy using DDC642 elastic liposomes to target these pathways in CLE. DDC642 liposomes were complexed with miRNAs (anti-miR-31, anti-miR-485-3p, pre-miR-885-5p) and characterized through dynamic light scattering and Cryo-TEM. Cytotoxicity, cellular penetration, and therapeutic efficacy were evaluated in primary keratinocytes, PBMCs, and immune 3D-skin organoids. miRNA lipoplexes were successfully synthesized with optimized particle size, surface charge, and encapsulation efficiency. These lipoplexes exhibited effective cellular penetration and low cytotoxicity. Anti-miR-31 lipoplexes reduced miR-31 and NF-κB levels while increasing STK40 and PPP6C expression. Pre-miR-885-5p lipoplexes elevated miR-885-5p levels and downregulated PSMB5 and NF-κB in keratinocytes. While anti-miR-485-3p lipoplexes reduced T-cell activation markers. Anti-miR-31 and pre-miR-885-5p lipoplexes successfully modulated inflammatory pathways in 3D-skin CLE models. miRNA lipoplexes represent promising candidates for pioneering topical genetic therapies for CLE. Further studies, including animal models, are necessary to validate and optimize these findings. Full article

Background: Gender-affirming surgery has become an integral part of the gender transition process that transgender and gender-diverse individuals undergo. Although ample literature exists on the short-term outcomes of gender-affirming surgery, very little is known about the long-term implications the surgery has on the psychological well-being of the patients. The purpose was to understand the long-term impact that gender-affirming surgery has on transgender and gender-diverse individuals and gain insight on potential contributors to improved psychological well-being and satisfaction. Methods: All patients who were operated on by a single surgeon during a 20-year period were invited to the clinic for a follow-up appointment. The patients were physically examined, their scars were graded, and NAC sensation was evaluated. BUT (A and B) and BREAST-Q questionnaires were filled out by them and evaluated by the research staff. Results: Satisfaction with pre-operative information provided to the patient was associated with satisfaction with the final appearance of the chest (R = 0.717, p < 0.001), the surgical outcome (R = 0.481, p = 0.037), psychosocial well-being at follow up (R = 0.489, p = 0.034), satisfaction with the surgeon (R = 0.486, p = 0.035), satisfaction with the medical team (R = 0.62, p = 0.005) and satisfaction with the office staff (R = 0.65, p = 0.003). Conclusions: Pre-operative communication between the medical staff and the patients improves the psychological outcomes and satisfaction of the patients over the years. Full article

Non-pathogenic natural and recombinant strains of human Enteroviruses are the subject of ongoing study with some strains having been approved for use as anticancer agents. The efficacy of oncolytic virotherapy depends upon identifying the receptor utilized by a specific strain for cell entry, and the presence of this receptor on the surface of cancer cells. Accordingly, a rapid and straightforward approach to determining the enteroviral receptors is necessary for developing an effective patient-specific, virus-based cancer therapy. To this end, we created a panel of seven lines with double knockouts on the background of the HEK293T cell line, which lacks the IFNAR1 gene. In these lines, the main viral receptor genes, including PVR, CXADR, CD55, ITGA2, SCARB2, ICAM1, and FCGRT, were knocked out using the CRISPR/Cas9 system. The panel of lines was validated on twelve different Enteroviruses types, providing a basis for studying the molecular mechanisms of enterovirus entry into cells, and for developing new therapeutic strains. Full article