Search Results (8,714)

Pelvic organ prolapse (POP) is a prevalent condition, affecting women all over the world, and is commonly treated through surgical interventions that present limitations such as recurrence or complications associated with synthetic meshes. In this study, biodegradable poly($ϵ$-caprolactone) (PCL) cog threads are proposed as a minimally invasive alternative for vaginal wall reinforcement. A custom cutting tool was developed to fabricate threads with varying barb angles (90°, 75°, 60°, and 45°), which were produced via Melt Electrowriting. Their mechanical behavior was assessed through uniaxial tensile tests and validated using finite element simulations. The results showed that barb orientation had minimal influence on tensile performance. In simulations of anterior vaginal wall deformation under cough pressure, all cog thread configurations significantly reduced displacement in the damaged tissue model, achieving values comparable to or even lower than those of healthy tissue. A ball burst simulation using an anatomically accurate model further demonstrated a 13% increase in reaction force with cog thread reinforcement. Despite fabrication limitations, this study supports the biomechanical potential of 3D-printed PCL cog threads for POP treatment, and lays the groundwork for future in vivo validation. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned meat rabbits (n = 450) were randomly assigned to five groups, Groups A, B, C, D, and E, and fed 0, 50, 100, 150, and 200 mg/kg CA diets, respectively, for 47 days. Biological samples including serum (antioxidants), duodenal/caecal content (enzymes), intestinal tissue (morphology), and caecal digesta (microbiota) were collected at day 47 postweaning for analysis. Groups C and D showed significantly higher final body weights than Group A, with Group D (150 mg/kg CA) demonstrating superior growth performance including 11.73% longer duodenal villi (p < 0.05), 28.6% higher microbial diversity (p < 0.01), and 62% lower diarrhoea rate versus controls. Digestive enzyme activity as well as serum antioxidant capacity increased with increasing CA dose, Microbiota analysis revealed CA increased fibre-fermenting Oscillospiraceae (+38%, p < 0.01) while reducing Ruminococcaceae (−27%, p < 0.05). Thus, dietary CA supplementation at 150 mg/kg was identified as the optimal CA dose for improving meat rabbit production. These findings highlight CA as a functional feed additive for promoting sustainable rabbit production. Full article

Background/Objectives: Low folate intake before and during pregnancy increases the risk of neural tube defects and other adverse outcomes. Gene variants such as MTHFR 677C>T (rs1801133) may increase risks associated with suboptimal folate intake. Our objective was to use BALB/cJ Mthfr^677C>T mice to evaluate the effects of the TT genotype and low folate diets on embryonic development and MTHFR protein expression in pregnant mice. Methods: Female 677CC (mCC) and 677TT (mTT) mice were fed control (2 mg folic acid/kg (2D)), 1 mg folic acid/kg (1D) and 0.3 mg folic acid/kg (0.3D) diets before and during pregnancy. Embryos and maternal tissues were collected at embryonic day 10.5. Embryos were examined for developmental delays and defects. Methyltetrahydrofolate (methylTHF) and total homocysteine (tHcy) were measured in maternal plasma, and MTHFR protein expression was evaluated in maternal liver. Results: MethylTHF decreased due to the experimental diets and mTT genotype. tHcy increased due to 0.3D and mTT genotype; mTT 0.3D mice had significantly higher tHcy than the other groups. MTHFR expression was lower in mTT liver than mCC. MTHFR protein expression increased due to low folate diets in mCC mice, whereas in mTT mice, MTHFR expression increased only due to 1D. Developmental delays were increased in the litters of mTT mice fed 1D and 0.3D. Conclusions: The Mthfr^677C>T mouse models the effects of the MTHFR 677TT genotype in humans and provides a folate-responsive model for examination of the effects of folate intake and the MTHFR 677C>T variant during gestation. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is widely used to manage prostate cancer (PC), but the emergence of treatment resistance remains a major clinical challenge. Although the GST family has been implicated in drug resistance, the specific role of GSTM5 remains poorly understood. This study investigates whether GSTM5, alone or in combination with clinical variables, can improve patient stratification based on the risk of early treatment resistance. Methods: In silico analyses were performed to examine GSTM5’s role in protein interactions, molecular pathways, and gene expression. The rs3768490 polymorphism was genotyped in 354 patients with PC, classified by ADT response. Descriptive analysis and logistic regression models were applied to evaluate associations between genotype, clinical variables, and ADT response. GSTM5 expression related to the rs3768490 genotype and ADT response was also analyzed in 129 prostate tissue samples. Results: The T/T genotype of rs3768490 was significantly associated with a lower likelihood of early ADT resistance in both individual (p = 0.0359, Odd Ratios (OR) = 0.18) and recessive models (p = 0.0491, OR = 0.21). High-risk classification according to D’Amico was strongly associated with early progression (p < 0.0004; OR > 5.4). Combining genotype and clinical risk improved predictive performance, highlighting their complementary value in stratifying patients by treatment response. Additionally, GSTM5 expression was slightly higher in T/T carriers, suggesting a potential protective role against ADT resistance. Conclusions: The T/T genotype of rs3768490 may protect against ADT resistance by modulating GSTM5 expression in PC. These preliminary findings highlight the potential of integrating genetic biomarkers into clinical models for personalized treatment strategies, although further studies are needed to validate these observations. Full article

Chronic kidney disease (CKD) is a heterogeneous condition with various etiologies, including type 2 diabetes mellitus (T2D), hypertension, and autoimmune disorders. Both diabetic CKD (CKD_T2D) and non-diabetic CKD (CKD_nonT2D) share overlapping clinical features, but understanding the molecular mechanisms underlying each subtype and distinguishing diabetic from non-diabetic forms remain poorly defined. To identify differentially expressed genes (DEGs) and enriched biological pathways between CKD_T2D and CKD_nonT2D cohorts, including autoimmune (CKD_nonT2D_AI) and hypertensive (CKD_nonT2D_HT) subtypes, through integrative transcriptomic analysis. Publicly available gene expression datasets from human glomerular and tubulointerstitial kidney tissues were curated and analyzed from GEO and ArrayExpress. Differential expression analysis and Gene Set Enrichment Analysis (GSEA) were conducted to assess cohort-specific molecular signatures. A considerable overlap in DEGs was observed between CKD_T2D and CKD_nonT2D, with CKD_T2D exhibiting more extensive gene expression changes. Hypertensive-CKD shared greater transcriptomic similarity with CKD_T2D than autoimmune-CKD. Key DEGs involved in fibrosis, inflammation, and complement activation—including Tgfb1, Timp1, Cxcl6, and C1qa/B—were differentially regulated in diabetic samples, where GSEA revealed immune pathway enrichment in glomeruli and metabolic pathway enrichment in tubulointerstitium. The transcriptomic landscape of CKD_T2D reveals stronger immune and metabolic dysregulation compared to non-diabetic CKD. These findings suggest divergent pathological mechanisms and support the need for tailored therapeutic approaches. Full article

Cyclodextrins (CDs), cyclic oligosaccharides formed by α-1,4-glycosidic-bonded D-glucopyranose units, feature unique hydrophobic cavities and hydrophilic exteriors that enable molecular encapsulation via host–guest interactions. CDs form supramolecular host–guest complexes with diverse molecular entities, establishing their fundamental role in supramolecular chemistry. This review examines fabrication strategies for CD-based supramolecular hydrogels and their applications in tissue engineering and regenerative medicine, with focused analysis on wound healing, corneal regeneration, and bone repair. We critically analyze CD–guest molecular interaction mechanisms and innovative therapeutic implementations, highlighting the significant potential of CD hydrogels for tissue regeneration while addressing clinical translation challenges and future directions. Full article

Pathologies of the heart (e.g., ischemic disease, valve fibrosis and calcification, progressive myocardial fibrosis, heart failure, and arrhythmogenic disorders) stem from the irreversible deterioration of cardiac tissues, leading to severe clinical consequences. The limited regenerative capacity of the adult myocardium and the architectural complexity of the heart present major challenges for tissue engineering. However, recent advances in biomaterials and biofabrication techniques have opened new avenues for recreating functional cardiac tissues. Particularly relevant in this context is the integration of biomimetic design principles, such as structural anisotropy, mechanical and electrical responsiveness, and tissue-specific composition, into 3D bioprinting platforms. This review aims to provide a comprehensive overview of current approaches in cardiac bioprinting, with a focus on how structural and functional biomimicry can be achieved using advanced hydrogels, bioprinting techniques, and post-fabrication stimulation. By critically evaluating materials, methods, and applications such as patches, vasculature, valves, and chamber models, we define the state of the art and highlight opportunities for developing next-generation bioengineered cardiac constructs. Full article

Cranial cruciate ligament (CrCL) rupture is a common orthopedic disorder in dogs, leading to stifle joint instability and progressive osteoarthritis. This study aimed to develop and biomechanically evaluate a novel intra-articular reconstruction system designed to mimic the natural ligament and restore joint stability following CrCL excision. The system consisted of a 3D-printed thermoplastic polyurethane (TPU) graft, cerclage wire, and H-button fixation. Fourteen pelvic limbs from mature mixed-breed cadaveric dogs were used. The inclination angle, dimensions, volume, tensile strength, and elongation of the native CrCL were measured. Seven CrCL-deficient stifles were reconstructed using the proposed system and tested biomechanically. The native CrCL showed a significantly higher tensile strength than the TPU graft; however, the TPU demonstrated a greater flexibility. The reconstruction system successfully stabilized the joint and provided repeatable fixation. Significant correlations were found between CrCL volume and both age and body weight. These findings support the mechanical suitability of the proposed system for ex vivo stifle stabilization and highlight the potential of 3D-printed TPU in ligament reconstruction. Further in vivo studies are recommended to assess long-term performance, including implant integration, tissue remodeling, and clinical outcomes. Full article

Background: Colorectal cancer (CRC) is strongly influenced by miRNAs as well as the circadian system. Methods: High-throughput sequencing of miRNAs expressed in the rat colon during 24 h light (L)/dark (D) cycle was performed to identify rhythmically expressed miRNAs. The role of miR-150-5p in CRC progression was analyzed in DLD1 cell line and human CRC tissues. Results: Nearly 10% of mature miRNAs showed a daily rhythm in expression. A peak of miRNAs’ levels was in most cases observed during the first half of the D phase of the LD cycle. The highest amplitude was detected in expression of miR-150-5p and miR-142-3p. In the L phase of the LD cycle, the maximum in miR-30d-5p expression was detected. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during the D phase influence apoptosis, angiogenesis, the immune system, and EGF and TGF-beta signaling. Rhythm in miR-150-5p, miR-142-3p, and miR-30d-5p expression was confirmed by real-time PCR. Oncogenes bcl2 and myb and clock gene cry1 were identified as miR-150-5p targets. miR-150-5p administration promoted camptothecin-induced apoptosis. Expression of myb showed a rhythmic profile in DLD1 cells with inverted acrophase with respect to miR-150-5p. miR-150-5p was decreased in cancer compared to adjacent tissue in CRC patients. Decrease in miR-150-5p was age dependent. Older patients with lower expression of miR-150-5p and higher expression of cry1 showed worse survival in comparison with younger patients. Conclusions: miRNA signaling differs between the L and D phases of the LD cycle. miR-150-5p, targeting myb, bcl2, and cry1, can influence CRC progression in a phase-dependent manner. Full article

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article

Scaffolds are widely used in bioengineering, both as 3D native tissue-mimicking models for investigating mechanisms under physiological and pathological conditions and also as implantable agents in regenerative medicine. Histological approaches, mainly formalin-fixed paraffin-embedded (FFPE) and frozen sample sectioning, are commonly applied to evaluate cell distribution and tissue-like properties of scaffolds. However, standard histological processing is not always compatible with the materials that scaffolds are made of. Thus, some adaptations to protocols are required to obtain intact sections. In this review we discuss challenges related to the histological processing of scaffolds and solutions to overcome them. We sequentially cover processing steps of the three main histological techniques for sample preparation—cryomicrotomy, FFPE samples microtomy and vibrating microtomy. Furthermore, we highlight the critical considerations in choosing the most appropriate method based on scaffold composition, mechanical properties and the specific research question. The goal of this review is to provide practical guidance on choosing reliable histological evaluation of complex scaffold-based systems in tissue engineering research. Full article

Gene therapy is a groundbreaking strategy in regenerative medicine, enabling precise cellular behavior modulation for tissue repair. In situ nucleic acid delivery systems aim to directly deliver nucleic acids to target cells or tissues to realize localized genetic reprogramming and avoid issues like donor cell dependency and immune rejection. The key to success relies on biomaterial-engineered delivery platforms that ensure tissue-specific targeting and efficient intracellular transport. Viral vectors and non-viral carriers are strategically modified to enhance nucleic acid stability and cellular uptake, and integrate them into injectable or 3D-printed scaffolds. These scaffolds not only control nucleic acid release but also mimic native extracellular microenvironments to support stem cell recruitment and tissue regeneration. This review explores three key aspects: the mechanisms of gene editing in tissue repair; advancements in viral and non-viral vector engineering; and innovations in biomaterial scaffolds, including stimuli-responsive hydrogels and 3D-printed matrices. We evaluate scaffold fabrication methodologies, nucleic acid loading–release kinetics, and their biological impacts. Despite progress in spatiotemporal gene delivery control, challenges remain in balancing vector biocompatibility, manufacturing scalability, and long-term safety. Future research should focus on multifunctional “smart” scaffolds with CRISPR-based editing tools, multi-stimuli responsiveness, and patient-specific designs. This work systematically integrates the latest methodological advances, outlines actionable strategies for future investigations and advances clinical translation perspectives beyond the existing literature. Full article

Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. While extensively characterized in breast MRI, the role of BPE in contrast-enhanced mammography (CEM) remains uncertain due to inconsistent findings regarding its correlation with breast density and cancer risk. Unlike breast density—standardized through the ACR BI-RADS lexicon—BPE lacks a uniform classification system in CEM, leading to variability in clinical interpretation and research outcomes. To address this gap, we introduce the BPE-CEM Standard Scale (BCSS), a structured four-tiered classification system specifically tailored to the two-dimensional characteristics of CEM, aiming to improve consistency and diagnostic alignment in BPE evaluation. Materials and Methods: In this retrospective single-center study, 213 patients who underwent mammography (MG), ultrasound (US), and contrast-enhanced mammography (CEM) between May 2022 and June 2023 at the “A. Perrino” Hospital in Brindisi were included. Breast density was classified according to ACR BI-RADS (categories A–D). BPE was categorized into four levels: Minimal (< 10% enhancement), Light (10–25%), Moderate (25–50%), and Marked (> 50%). Three radiologists independently assessed BPE in a subset of 50 randomly selected cases to evaluate inter-observer agreement using Cohen’s kappa. Correlations between BPE, breast density, and age were examined through regression analysis. Results: BPE was Minimal in 57% of patients, Light in 31%, Moderate in 10%, and Marked in 2%. A significant positive association was found between higher breast density (BI-RADS C–D) and increased BPE (p < 0.05), whereas lower-density breasts (A–B) were predominantly associated with minimal or light BPE. Regression analysis confirmed a modest but statistically significant association between breast density and BPE (R² = 0.144), while age showed no significant effect. Inter-observer agreement for BPE categorization using the BCSS was excellent (κ = 0.85; 95% CI: 0.78–0.92), supporting its reproducibility. Conclusions: Our findings indicate that breast density is a key determinant of BPE in CEM. The proposed BCSS offers a reproducible, four-level framework for standardized BPE assessment tailored to the imaging characteristics of CEM. By reducing variability in interpretation, the BCSS has the potential to improve diagnostic consistency and facilitate integration of BPE into personalized breast cancer risk models. Further prospective multicenter studies are needed to validate this classification and assess its clinical impact. Full article