Search Results (115)

Recent studies have highlighted the potential of urinary bladder matrix (UBM) derived from decellularized porcine urinary bladder as a bioactive hydrogel. Despite its complex composition of over 100 proteins, Type I collagen is the primary constituent of UBM. Caco-2 cells are widely used as an in vitro model of the intestinal epithelium; however, to date, no published study has evaluated the effects of UBM on Caco-2 cells. In this study, Electric Cell–Substrate Impedance Sensing (ECIS) was used to measure Caco-2 cell attachment and wound-healing migration on UBM-coated microelectrodes. Our results demonstrate that UBM hydrogel coating at 0.2 mg/mL significantly accelerates cell attachment and enhances migration rates compared to uncoated controls. These stimulatory effects were comparable to those observed with 0.2 mg/mL Type I collagen, suggesting that UBM can function as effectively as Type I collagen. We further monitored barrier formation in Caco-2 cells cultured on UBM-coated transwell membrane inserts using TEER measurements and scanning electron microscopy. The TEER values reached 300 Ω·cm² within three days, indicating the rapid establishment of mature tight junctions. Overall, these results show that UBM hydrogel coatings are effective substrates for Caco-2 cells, performing as well as Type I collagen in all our tests. Full article

Aberrant expression of multiple microRNAs has been reported in gastric cancer. In particular, microRNA-597 has been associated with poor survival rates but is not yet well characterized. Seventy-five clinical samples, four cell lines, and two patient-derived organoids were evaluated for the expression of microRNA-597 and its target genes. microRNA-597 was transiently transfected for analysis of cell migration, invasion, wound healing, colony formation, and cell viability, and its regulation by long non-coding RNAs was explored using the TCGA-STAD and LncBook tools. In clinical samples, low expression of microRNA-597 was associated with the intestinal subtype (p = 0.002) and stages III and IV (p = 0.048). All functional readouts were reduced after microRNA-597 transfection, including colony formation, in patient-derived organoids. Among target genes, RUNX1 was directly regulated by microRNA-597. Other cell invasion genes were dependent on RUNX1 as a hub for regulation. Analysis of the Intersection between long non-coding RNAs co-expressed with RUNX1 and those with the highest microRNA-597 prediction binding identified KCNQ1OT1 as the top transcript. Silencing of KCNQ1OT1 and co-expression in clinical samples suggest the existence of a KCNQ1OT1/microRNA-597/RUNX1 network. The results indicate that microRNA-597 directly suppresses RUNX1, while KCNQ1OT1 modulates this interaction. Our approach enabled the simultaneous analysis of dysregulation in three families of transcripts in gastric cancer progression. Full article

Anastomotic leakage (AL) is a significant complication associated with elevated morbidity and mortality rates following colorectal surgery. This complication primarily arises due to impaired wound healing. Anastomotic and intestinal wound healing is generally divided into three phases: inflammation, proliferation, and remodeling. The physiological transition between these phases is primarily orchestrated by macrophages, which are key regulators of inflammation and tissue repair. They undergo sequential phenotypic changes from pro-inflammatory to anti-inflammatory states and are involved in the phagocytosis of bacteria or debris, but also attract fibroblasts for collagen production and deposition. Importantly, they can promote local perfusion by secreting pro-angiogenic and growth factors. Failure of this transition from pro- to anti-inflammatory properties is associated with AL, scarring, and fibrosis. Intestinal macrophages represent the largest pool of resident myeloid cells and are promising cellular targets for therapeutic interventions. In this narrative review, we focus on intestinal and anastomotic wound healing, highlight the dichotomous role of macrophages, and discuss potential therapeutic strategies. A detailed understanding of macrophage polarization, recruitment, and targeted modulation may enhance wound healing and prevent complications such as AL. Full article

The fabrication of decellularized small intestinal submucosa (dSIS) requires a precise balance between effective cellular removal and the preservation of structural integrity. In this study, we compared four published dSIS protocols representing detergent-based, chaotropic-salt-based, and sequential ionic/alkaline–acidic strategies. Their performance was evaluated based on residual DNA, collagen preservation, surface ultrastructure, and mechanical properties. The best decellularization protocol demonstrated the lowest residual DNA levels, together with better collagen retention, scaffold architecture, and mechanical performance than the other methods tested. The selected decellularized scaffold was used in a murine acute wound model and showed good biocompatibility and integration with the surrounding tissue at 10 days after implantation. However, further extensive testing in murine models is essential before future scaling. Finally, this comparative study provides a practical framework for selecting dSIS preparation methods for skin repair applications. Full article

The escalating global burden of Ulcerative Colitis (UC) underscores the urgent need for novel therapeutic strategies. Although dietary modulation is known to influence UC progression, the specific molecular mediators remain largely undefined. Recently, the G protein coupled receptor 35 (GPR35) has emerged as a promising target for maintaining gut homeostasis and promoting intestinal epithelium repair. Yet, whether the therapeutic benefits of dietary polyphenols are mediated through the direct activation of GPR35 remains unexplored. Here, the NanoLuc Binary Technology (NanoBiT) assay was first used to identify the potential GPR35 agonist from a library of 30 natural polyphenolic compounds. We discovered Ellagic acid (EA), a natural polyphenol abundant in fruits and nuts, as the potent GPR35 agonist owing to its most potent agonistic effect. The dose-dependent effect was further confirmed by both NanoBiT and Bret assay. Then, the binding site of the ligand-receptor complex was predicted via molecular docking, and key interactions were validated by site-directed mutagenesis. The results indicated the key binding site of the complex was Gln93, Arg100, Arg151, Phe163 and Ser262. And the conformation of the complex was verified stable by the molecular dynamics simulation. The bioactivity of EA was then evaluated in vivo. And the in vivo experiment indicated that EA alleviated the symptoms of UC. In addition, complementary in vitro assays, including a wound healing (scratch) assay and an SRB proliferation assay, were employed to investigate its effect on intestinal epithelial repair. The in vitro experiment demonstrated that EA enhanced the migration and proliferation of human colonic epithelial cells, an effect that was specifically abolished by the GPR35 antagonist CID2745687, indicating the key role GPR35 played in the intestinal repair. Collectively, our study demonstrates that the natural polyphenolic compound EA promotes epithelial healing and ameliorates colitis by acting as a GPR35 agonist. Full article

Colorectal resection and subsequent anastomosis are the standard curative procedures for a variety of colorectal pathologies. However, anastomotic leakage (AL) is an early and frequent complication that can have life-threatening outcomes. The study aimed to evaluate the effect of silkworm fibroin sheets on colon anastomotic strength and wound healing early after intervention in Wistar rats. Male Wistar rats were randomized into two groups, control (N = 11) and fibroin (N = 11), and subjected to end-to-end colo-colic anastomosis. In the fibroin group, a single layer of fibroin membrane was applied externally around the anastomosis. The animals were sacrificed three days after the operation (POD3) and intestinal adhesions, anastomotic bursting pressure and histological parameters based on the eosin, hematoxylin, and Masson’s trichrome stains were compared between the groups. Fibroin-treated rats showed a significant increase in anastomotic bursting pressure compared to control animals (69 (18) vs. 41 (28) mmHg), whereas no differences in the intestinal adhesion scores were detected. No significant differences in the numbers of granulocytes, monocytes/macrophages and fibroblasts, nor the amount of collagen fibers, as measured by Masson’s trichrome stain, were found between the groups. These results indicate that fibroin sheets could represent a simple and promising tool to provide mechanical support and improve colonic anastomotic strength early after intervention. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with poor prognosis and limited targeted therapeutic options. Natural products, rich in bioactive phytochemicals, represent a potential source of novel anticancer agents. This study examined the phytochemical profile and anticancer activity of an ethanolic bulb extract of Cyclamen persicum (CPE), with a primary focus on TNBC. Methods: The phytochemical composition of CPE was analyzed by liquid chromatography–mass spectrometry (LC–MS). Antioxidant activity was evaluated using DPPH radical scavenging assay. The anticancer effects of CPE were assessed mainly in MDA-MB-231 TNBC cells using MTT cell viability assays, Ki-67 immunoblotting, Western blot analysis of signaling proteins, wound healing migration assays, Matrigel invasion assays, adhesion assays and cell–cell aggregation assays. Antiproliferative activity was also examined in 22RV1 (prostate), Capan-2 (pancreatic), and HCT116 (intestinal) cancer cell lines using MTT assays. Results: LC–MS analysis indicated that the extract contains multiple polyphenolic and organic acid constituents commonly associated with bioactivity. Consistent with this profile, CPE demonstrated strong antioxidant activity. In MDA-MB-231 cells, CPE significantly reduced cell viability and proliferation, accompanied by decreased Ki-67 expression. Treatment was associated with modulation of proteins involved in proliferative and survival signaling, induction of apoptosis-related markers, and reduced migratory and invasive capacities. CPE also promoted cell–cell homotypic aggregation, suggesting a shift toward a less aggressive phenotype. These effects were associated with reduced phosphorylation of p65, indicating possible modulation of NF-κB signaling. Additionally, CPE decreased proliferation in 22RV1, Capan-2, and HCT116 cancer cell lines. Conclusions: Collectively, these findings indicate that C. persicum bulb extract exerts multimodal anticancer effects in vitro, particularly in TNBC cells, and highlights its potential as a source of bioactive compounds warranting further mechanistic and translational investigation. Full article

Diabetes mellitus is one of the most common health problems worldwide; however, increased blood glucose alone cannot adequately explain its pathophysiology. Although high blood glucose is a defining feature, evidence increasingly proves that diabetes arises from systemic disturbances involving the gut microbiome, immune system, and metabolic control. From this perspective, diabetes can be viewed as a systemic condition shaped by the dynamic interactions between the gut microbiome, the immune system, and metabolic pathways. Alterations in gut microbiome composition and function can influence nutrient metabolism, microbial metabolite production, bile acid signaling, and intestinal barrier integrity. Any damage of the gut barrier allows movement of microbiome-derived molecules that activate innate immune pathways and provoke chronic low-grade inflammation. This inflammatory state interferes with insulin signaling, contributes to immune maladaptation, and exacerbates metabolic dysfunction. Over time, these processes contribute to the advance of multisystem complications, including cardiovascular disease, diabetic nephropathy, neuropathy with cognitive impairment, delayed wound healing, and increased susceptibility to infection. The review also integrates environmental and public health factors, demonstrating how diet, antibiotic exposure, circadian disruption, and social conditions shape the microbiome, immune function, metabolic regulation, and disease risk across the life course. By bringing together clinical, experimental, and population-based evidence, this review illustrates the limitations of care models that concentrate only on glucose. It also points out how integrated approaches targeting the microbiome, immune system, and metabolic pathways can improve diabetes prevention, management, and guide future research. Full article

Plant-derived nanovesicles (PDNVs) are increasingly recognized as mediators of intercellular communication in plants, where they play roles in defense, signaling, and cell wall remodeling. In addition, PDNVs are gaining increasing attention for their biomedical potential, both as natural delivery systems and as bioactive entities, with promising applications in inflammatory disorders and cancer. In this study, we isolated carob nanovesicles (CbNVs) from the apoplastic fluid of carob pods (Ceratonia siliqua L.) using vacuum infiltration centrifugation followed by tangential flow filtration and size-exclusion chromatography. Morphological and biophysical analyses revealed spherical vesicles, while proteomic profiling identified 197 proteins, including suggested PDNV markers such as annexin, HSP70, GAPDH, elongation factors, malate dehydrogenase, and TET-8. These proteins were enriched in metabolic processes, stress responses, and cell wall modification pathways. Protein–protein interaction analysis further linked HSP70 to pectinesterases, reinforcing their role in cell wall remodeling and stress adaptation. Functionally, CbNVs were non-cytotoxic to human macrophages, keratinocytes, and intestinal cells. Notably, CbNVs significantly reduced LPS-induced NF-κB expression in macrophages and promoted wound closure in keratinocytes, with superior efficacy compared to the carob bioactive compound D-pinitol. These findings suggest that CbNVs harbor a synergistic cargo of bioactive molecules with anti-inflammatory and wound-healing properties, highlighting their potential as natural nanotherapeutics. Full article

Oxidative stress is a state of imbalance between the process of producing and removing reactive oxygen species (ROS). With advancing age or in certain situations where oxidative stress cannot be combated, various pathologies such as inflammatory bowel diseases or neoplasia may occur. Over the past decade, a surge of intriguing discoveries has linked subtoxic levels of oxidative stress to key processes, including the maintenance of mucosal homeostasis, regulation of protective inflammation, and even the control of tissue wound healing. Given the complexity and limited understanding of oxidative mechanisms involved in human intestinal pathology, the relevance of experimental models becomes a critical consideration in efforts to elucidate these processes. Although diverse, none of these models fully replicate human digestive pathology; however, they remain valuable for developing new therapeutic strategies. This paper examines the main markers of oxidative stress and its mechanism and their impact on the intestinal tract, as well as the most widely used animal models that have contributed valuable insights into the pathogenesis of inflammatory bowel diseases (IBD). Full article

In the context of thermal injury, local tissue integrity and systemic homeostasis are compromised, often resulting in delayed healing, infections, and disturbances of the skin and intestinal microbial balance. Despite several reviews addressing probiotics in wound healing, none has specifically focused on their role in thermal injuries and burn-associated pathophysiology. This review uniquely integrates evidence on the gut–skin axis, postbiotic innovations, and regenerative perspectives tailored to burn care. We conducted a critical synthesis of recent preclinical and clinical trials evaluating the use of probiotics and their derivatives to promote tissue regeneration following burn injury. Previous reviews have addressed probiotics in general wound repair, but the present synthesis advances the field by bridging mechanistic insights (immune modulation, angiogenesis, microbiome restoration) with translational evidence in burn patients, offering a framework for personalized regenerative approaches. Based on a structured review of the literature—including in vitro models, animal experiments, and randomized trials with topical, enteral, and systemic administration of probiotic—we identified four main mechanisms of action: modulation of the immune response by balancing cytokines and polarization of T lymphocytes; stimulation of tissue repair by increasing the proliferation of keratinocytes and fibroblasts, increased collagen synthesis, and induction of angiogenesis; direct antimicrobial activity against biofilms and multiresistant pathogens; and the restoration of eubiosis with the improvement of the function of epithelial barriers. While these findings endorse the adjunctive use of probiotics in burn management, large multicenter trials are required to standardize strains, dosages, and formulations before their routine clinical adoption. Full article

Background: PTEN is a tumor suppressor that controls many pathophysiological pathways, including cell proliferation, differentiation, apoptosis and invasiveness. Although PTEN down-modulation is a critical event in neoplastic progression, it becomes apparent that transient and local inhibition of PTEN activity might be beneficial for the healing process. Methods: In the present study, we investigated the impact of PTEN invalidation in mouse intestinal epithelium under a physiological condition and after dextran sulfate sodium (DSS) treatment to induce experimental colitis. PTEN conditional knockout was induced in intestinal epithelial cells after crossing villin-Cre and PTEN^flox/flox mice. Results: PTEN invalidation alleviates experimental colitis induced by DSS, as evidenced by decreased weight loss during the acute phase, the lower expression of inflammation markers, including the proinflammatory cytokines IFN-γ, CXCL1 and CXCL2, reduced mucosal lesions, and faster recovery after resolution of inflammation. This protective effect might result in part from the sustained proliferation of colonic epithelium, leading to hyperplasia and increased colonic crypt depth under physiological conditions, which was further exacerbated in the vicinity of mucosal injury induced by DSS treatment. Furthermore, PTEN knockout decreased paracellular permeability, thereby enhancing the intestinal barrier function. This process was associated with the reinforcement of claudin-3 immunostaining, especially on the surface epithelium of villin-Cre PTEN^flox/flox mice. Conclusions: PTEN inactivation exerts a protective effect on the onset of colitis, and the transient and local down-modulation of PTEN might constitute an approach to drive recovery following acute intestinal inflammation. Full article

Porcine small intestinal submucosa (SIS) extracellular matrix (ECM) has emerged as a widely researched biological scaffold in regenerative medicine. This meta-analysis examines 205 peer-reviewed studies published from 1993 to 2025, emphasizing the biochemical composition, decellularization techniques, biomedical applications, and validation methods associated with SIS-ECM. Findings reveal a dominant focus on wound healing and cardiovascular repair, reflecting the scaffold’s mechanical adaptability and bioactivity. Research has evolved from basic compositional analyses to complex, application-specific investigations that incorporate in vivo models and functional outcome measures. Decellularization methods vary significantly, trending toward hybrid, multi-step protocols that preserve ECM integrity while ensuring cellular clearance. While the results are encouraging, a notable transparency issue persists, with only a third of studies providing full methodological details, which restricts reproducibility. Frequently utilized validation methods encompass mechanical testing, histology, DNA quantification, and growth factor retention. This review emphasizes the critical requirement for standardized guidelines in preparation and reporting to guarantee the safe and effective clinical application of SIS-ECM. Through continuous refinement and collaboration among various disciplines, SIS-ECM has the potential to serve as a next-generation scaffold for a range of regenerative uses. Full article

Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract that often leads to intestinal fibrosis, an irreversible complication associated with strictures and the need for surgical intervention. Fibrosis occurs due to prolonged inflammation and abnormal wound healing, involving complex interactions between immune cells, mesenchymal cells, cytokines, and the gut microbiota. Key fibrogenic mechanisms include the activation of fibroblasts and myofibroblasts, cytokine signaling, and disrupted turnover of the extracellular matrix. Advancements in imaging techniques, such as MRI and CT enterography, have improved the detection and monitoring of fibrosis. Additionally, molecular techniques targeting fibroblast activation proteins show promise as a new imaging method. However, there are currently no approved anti-fibrotic therapies for CD. Emerging strategies focus on key pathways and novel therapeutic targets, including growth factor modulators, intracellular enzyme and kinases modulators, and interventions targeting the modulation of inflammation and extracellular matrix, which are being evaluated in preclinical and clinical settings. This review discusses the pathophysiology, diagnostic advancements, and therapeutic perspectives related to intestinal fibrosis in CD, emphasizing the urgent need for targeted anti-fibrotic therapies to prevent long-term complications and improve the life quality of patients. Full article

Melanoma is one of the deathliest cancers worldwide and its incidence is reaching epidemic proportions. It is characterized by intrinsic chemo-resistance, low response rates to treatment and high metastatic potential. Because of this, new therapeutic options are permanently required. Tessaria absinthioides (Hook. & Arn.) DC. is a traditional medicinal plant, with antioxidant, selective cytotoxicity and anti-colorectal cancer evidence-based properties. This study aims to demonstrate the antitumoral and antimetastatic effects of T. absinthioides decoction (DETa), correlating in vitro and in vivo activities in a murine melanoma model. DETa was assayed on B16F0 murine non-metastatic cells to determine cytotoxicity and clonogenicity; while, in the B16F10 metastatic siblings, adhesion, wound healing migration and Boyden chamber invasion were studied. The ex vivo intestinal-sac model was used to quantify DETa bioavailability. Meanwhile, in C57BL6/wt mice, DETa was orally administered to evaluate its antitumoral and antimetastatic activities. DETa induced cytotoxicity in a dose- and time-dependent manner, affecting the long-term clonogenic survival, as well as the processes of adhesion and migration. Then, the intestinal absorption of DETa phenolics was proven, while the systemic anti-tumoral and anti-metastatic activities of DETa were confirmed. Results demonstrated that DETa has antimelanoma activity promoting this botanical compound as a relevant agent for cancer research and treatment. Full article