Mesenchymal stromal cell therapy restores intestinal integrity and attentuates inflammation in a preterm piglet model of necrotizing enterocolitis

Pediatric Surgery International · 2026-03-09

PURPOSE: Necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of prematurity characterized by inflammation, necrosis, and high morbidity. Current therapies are limited, necessitating the development of novel treatments. Mesenchymal stromal cells (MSCs) have shown promise in murine NEC models. Given the anatomical and physiological similarities between premature piglets and human infants, we employed a preterm piglet model to evaluate MSC efficacy. We hypothesized that intraperitoneal MSC administration would reduce intestinal injury in NEC. METHODS: Preterm piglets were delivered via cesarean section. NEC was induced on day 3 through hypertonic enteral feeding. MSCs were administered intraperitoneally at low, medium, or high doses. Piglets were monitored and euthanized based on clinical criteria. Clinical scores, weight change, gross and histologic intestinal injuries were assessed. Cytokine levels in serum and ileum were quantified via ELISA, and intestinal tissue was analyzed by RNA sequencing. Statistical significance was set at p < 0.05. RESULTS: Medium-dose MSCs significantly improved clinical scores and reduced both gross and histologic intestinal injury (p < 0.05). A corresponding decrease in pro-inflammatory cytokines was observed. CONCLUSION: This is the first study to demonstrate therapeutic benefit of MSCs in a preterm piglet NEC model, supporting their potential use in translational NEC therapies.

Rumenomics: evaluation of rumen metabolites from healthy sheep identifies differentially produced metabolites across sex, age, and weight

PubMed Central · 2026-04-11

Comparison of Double-Loop Cerclage Wire Application using a Double Handle Wire Tightener versus a Single Handle Wire Tightener

Veterinary and Comparative Orthopaedics and Traumatology · 2025-07-01

A scalable methodology for optimizing hospital surgical schedules considering efficiency, flexibility, and improved patient outcomes

Healthcare Analytics · 2025-09-03

Hospitals face challenges in efficiently adapting treatment delivery to growing and changing demands. The main challenge arises from accommodating diverse patients requiring specific surgical resources and attention. Traditional scheduling methods often fail to address the dynamic nature of these environments, which are characterized by numerous uncertainties and stakeholders’ complex and changing needs. This study presents a novel methodology designed to enhance hospital operational efficiency while considering the interests of all stakeholders, including hospital administrators, medical staff (doctors, nurses, technicians), and patients. This requires a nuanced approach to effectively handle unpredictable treatment demands, resource availability, and patient requirements. The methodology systematically progresses from defining constraints and resources to modeling uncertainties generating and evaluating optimal schedules through iterative processes. This study develops and applies a 12-step method to optimize the surgery scheduling for the farm animal section of the Purdue Veterinary Hospital over a defined period. The application shows the practical benefits of the proposed approach by modeling dynamic surgical demands and exploring various scheduling possibilities within resource constraints. The results reveal that the proposed method effectively accommodates increased operational demands while managing delays, accidents, and illness costs. • Propose a method for optimizing surgical scheduling through systematic uncertainty modeling. • Enhance resource allocation by considering dynamic demands and stakeholder requirements. • Improve operational efficiency by minimizing delays and reducing treatment costs. • Demonstrate a scalable and flexible framework adaptable to diverse hospital environments. • Balance stakeholder needs while maintaining flexibility in resource management.

Rumenomics: Evaluation of rumen metabolites from healthy sheep identifies differentially produced metabolites across sex, age, and weight

bioRxiv (Cold Spring Harbor Laboratory) · 2025-02-08

Background: The rumen harbors a diverse and dynamic microbiome vital in digesting vegetation into metabolic byproducts for energy and general biological function. Although previous studies have reported connections between the rumen and the overall health of the sheep, the exact biological process by which this occurs is not well understood. Therefore, our study aimed to quantify sheep rumen metabolites to determine if enriched biological pathways are differentiable across phenotypic features of sex, age, and weight. Results: We collected and quantified metabolites of rumen samples from sixteen sheep using liquid chromatography-tandem mass spectrometry. We performed a series of univariate and multivariate statistical analyses to interpret the rumen metabolomics data. To identify metabolic pathways associated with the phenotypic features of sex, weight, and age, we used MetaboAnalyst, which identified amino acid metabolism as a distinguishing factor. Among the pathways, phenylalanine metabolism emerged as a key pathway differentiating sheep based on sex and age. Additionally, phenylalanine, tyrosine, and tryptophan biosynthesis were exclusively associated with age. In univariate linear models, we also discovered that these amino acid and protein pathways were associated with weight by age-corrected effect. Finally, we identified arginine and proline biosynthesis as a pathway linked to metabolites with weight. Conclusion: Our study identified differential pathways based on the sex, age, and weight features of sheep. Metabolites produced by the rumen may act as an indicator for sheep health and other ruminants. These findings encourage further investigation of the differentially produced metabolites to assess overall sheep health.

Mesenchymal Stromal Cell Therapy Restores Intestinal Integrity and Attentuates Inflammation in a Preterm Piglet Model of Necrotizing Enterocolitis

Research Square · 2025-08-18

Tibial Biomechanics and Adaptive Response to Mechanical Stimuli in the Green Iguana

Integrative Organismal Biology · 2025-01-01

Synopsis Mechanical loading models are used to study adaptive skeletal mechanobiology mechanisms. However, most studies have used mammal models, leaving a knowledge gap regarding how these mechanisms differ among vertebrate groups. To address this gap, we evaluated the in vivo bone strain environment of the left tibia in green iguanas during locomotion, axial compressive loading, and with finite element analysis. Our study involved examining male green iguanas (n = 7) over a range of speeds (0.45–1.34 m/s) and axial load magnitudes (–25 to –100 N) to determine peak strains. Bone strains were measured using single-element strain gauges and rosette strain gauges, surgically attached to the tibial anterior, posterior, and medial surfaces. At a speed of 1.34 m/s, peak strains ± standard deviation observed were 645 ± 699 µε, –448 ± 464 µε, and 206 ± 168 µε at the anterior, posterior, and medial surfaces, respectively. Peak principal tensile and compressive strains on the medial surface were 199 ± 113 µε and –153 ± 98 µε at 1.34 m/s. During –100 N compressive loading, peak strains were 403 ± 277 µε, –506 ± 460 µε, and –52 ± 177 µε at the anterior, posterior, and medial surfaces, respectively. Our finite element model demonstrated a close correlation with experimentally measured strain values at the gauge sites (slope = 1.07, R = 0.8381). Using these foundational in vivo strain results and a daily strain stimulus formula, our objective was to develop a novel noninvasive axial compressive tibial loading model to induce a cortical bone adaptive response in the green iguana tibia (n = 9). However, following 3 weeks of daily applied compressive loading, no significant difference was detected in critical bone parameters at 37 and 50% (midshaft) volume of interests from the proximal tibia (P &amp;lt; 0.05). While this study did not yield significant differences in critical bone parameters following the application of daily compressive loading, it provided new knowledge regarding the bone strain environment and the potential for inducing adaptive responses in the green iguana tibia. Further research may refine our understanding of skeletal mechanobiology mechanisms across vertebrate groups and develop more effective loading models for studying bone adaptation. Overall, the findings of this study, although limited, contribute to the broader field of musculoskeletal mechanobiology, giving insights that may inform bone health and adaptation in diverse species.

Multiscale correlations between joint and tissue-specific biomechanics and anatomy in postmortem ovine stifles

Scientific Reports · 2025-02-07

Abstract Joint stability depends on various properties that include the bone anatomy, joint capsule geometry and stiffness, and soft tissues within. The multiscale biomechanical relationships between the whole joint and individual tissues are useful in estimating the physiological condition of the knee. To better understand these relationships, we evaluated multiple structural and mechanical parameters in healthy ovine stifles, specifically joint laxity, joint morphology, individual tissue T 2 * relaxation and mechanical properties of ligaments (ACL, PCL, MCL, LCL), patellar tendon, menisci, and cartilage. By combining mechanical testing at two length scales and magnetic resonance imaging (MRI) scans, we quantify the strength of correlation coefficients between measured metrics, among joint size, whole joint and individual tissue properties. We observe positive correlations between joint laxity forces and the inter-epicondylar distance. Further, the viscoelastic properties of the tendons and ligaments correlate positively with joint laxity forces; however, no such correlations were observed for the cartilage and menisci. We also found weak inverse correlation between tissue viscoelasticity and T 2 * for MCL; and positive correlations for cartilage and menisci, LCL and PCL respectively. These results provide useful insights into the role of individual tissues that are crucial in measuring whole joint responses as key indicators of knee health.

Proteomic profiling of adipose-derived mesenchymal stromal cell response to novel compounds targeting the Laminin Receptor – PEDF interaction

Biochemistry and Biophysics Reports · 2025-11-25

This study characterizes the proteomic responses of adipose-derived mesenchymal stromal cells (ASC) to novel compounds that target the interaction between pigment epithelium-derived factor (PEDF) and the 37 KDa Laminin Receptor (LR). Building on previous research, we introduced the second-generation analog, 02–09, for comparative analysis with C3, the original compound. C3 was identified through in silico screening and experimental validation, showing anti-inflammatory activity. Analog 02–09 was synthesized by modifying C3's aromatic ring, resulting in similar binding affinities to LR. The distinct molecular effects of C3 and 02–09, along with their potential as anti-inflammatory therapies from prior work, suggested their multi-functional utility. Proteomic profiling of ASC, under both undifferentiated and chondrogenic differentiation conditions, was performed using LC-MS/MS, with controls including the PEDF-derived peptide p18 and the cartilage-regenerative compound Kartogenin (Krt). Both C3 and 02–09 induced significant proteomic modulation compared to controls, with enrichment in pathways related to integrin β1 signaling, extracellular matrix (ECM) organization , and TGF-β signaling . C3 uniquely activated the nuclear receptors meta-pathway, whereas 02–09 was associated with laminin interactions . Protein-protein interaction and transcription factor enrichment analyses revealed distinct and overlapping regulatory networks for LR-targeting compounds. During chondrogenic differentiation, C3 primarily enhanced proteins linked to a chondrogenic phenotype with minimal fibrogenic activity, while 02–09 showed an influence on both chondrogenic and fibrogenic pathways. Comparative analysis of the proteomic response to C3 or 02–09 with a single-cell RNA-sequencing dataset confirmed that C3's modulated proteins primarily correlated with a chondrogenic differentiation phenotype, with minimal fibrogenic influence. The proteins modulated by 02–09 correlated with a dual profile (both chondrogenic and fibrogenic potential). Our results suggest that C3 has potential as a targeted chondrogenic agent, while 02–09 may serve as a multifaceted modulator of both cartilage repair and ECM protection. These findings indicate the utility of these compounds for regenerative medicine and the development of disease-modifying therapies for inflammatory and immune-related conditions. • Proteomics showed ASC responses to LR–PEDF-targeting molecules. • Analog 02-09 and C3 displayed distinct differentiation profiles. • C3 promoted chondrogenic phenotype with minimal fibrogenic activity. • 02–09 induced chondrogenic and fibrogenic signatures. • LR-targeting modulated ECM, integrin, and TGF-β signaling pathways.

Review for "A case‐matched controlled retrospective performance indexed analysis of Thoroughbred racehorses that underwent surgical repair of proximal phalanx and third meta‐carpal/tarsal condylar fractures"

2025-06-01